[Sensibility and specificity of cytology and colposcopy exams with the histological evaluation of cervical intraepithelial lesions].

PubMed

Tuon, Felipe Francisco Bondan; Bittencourt, Marcio Sommer; Panichi, Maria Alice; Pinto, Alvaro Piazetta

2002-01-01

To evaluate the correlation of cytopathological and colposcopycal diagnosis with the histopathological analysis from biopsy. 80 patients from the colposcopy ambulatory of the Hospital e Maternidade Santa Brígida de Curitiba, PR, were selected. Those patients were sent to colposcopy under the following criteria: 1) previous abnormal cytopathological exams, 2) Indicative clinical data or, 3) Suspected lesions on gynecological exam. The statistical significance analysis of the results was done using the chi-square test. Sensibility, specificity, positive predictive value (PPV) and negative predictive value (NPV) were also determined. The patients' mean age was 30.2 (+/-10.9). Cytopathological capability of identifying lesions was 50% when compared to histology. Its specificity was 77%, the sensibility 41%, the PPV 74%, and the NPV 45%. Colposcopy capability of identifying lesions was 50%. Its sensibility, specificity, PPV and NPV were 96%, 19%, 65% and 75% respectively. The two methods associated were capable of identifying 63% of the lesions. Cytopathology was a high specificity exam, while colposcopy from those selected patients had a high sensibility. Colposcopy association with cytopathological screening, on those selected patients, significantly raises the diagnostic accuracy of cervical cancer precursor lesions.

The effect of video information on anxiety levels in women attending colposcopy: a randomized controlled trial.

PubMed

Ketelaars, Pleun J W; Buskes, M H M; Bosgraaf, R P; van Hamont, D; Prins, Judith B; Massuger, L F A G; Melchers, Willem J G; Bekkers, Ruud L M

2017-12-01

The aim was to investigate whether additional information, in video form, reduces anxiety, depression and pain levels in women referred for colposcopy. Between September 2012 and March 2015, 136 patients referred for colposcopy were randomized into two study arms. Group A received video information in addition to the regular information leaflet, and group B (control group) received only the regular information leaflet. The patients were requested to complete standardized online questionnaires. The first online questionnaire (T1) was pre-randomization, and was completed at home, 5 days prior to the appointment. The second online questionnaire (T2) was completed directly before the colposcopy appointment, and the last online questionnaire (T3) was completed directly following colposcopy at the out-patient clinic. The questionnaires included the Spielberger State-Trait Anxiety Inventory (STAI), the Hospital Anxiety and Depression Scale (HADS), and the Numeric Rating Scale (NRS) to assess pain. The STAI state anxiety score was high (44.6), but there was no significant difference in STAI, HADS and NRS between the two groups at the three measuring points. A post hoc analysis showed that women with a generally higher baseline anxiety trait had significantly lower HADS anxiety levels following video information. Additional information (video) before colposcopy did not significantly reduce anxiety, depression, and expected or experienced pain, as measured by the STAI, HADS and NRS in patients attending their first colposcopy appointment. However, most patients positively appreciated the video information, which may reduce the anxiety of extremely anxious patients.

Discrepancy between colposcopy, punch biopsy and final histology of cone specimen: a prospective study.

PubMed

Petousis, Stamatios; Christidis, Panagiotis; Margioula-Siarkou, Chrysoula; Sparangis, Nikolaos; Athanasiadis, Apostolos; Kalogiannidis, Ioannis

2018-05-01

Τo estimate the discrepancy rate between colposcopy, punch biopsy histology and surgical specimen histology as well as the positive (PPV) and negative predictive value (NPV) of colposcopic diagnosis for high-grade squamous intraepithelial lesions (HGSIL). A prospective study was conducted during the period of 2012-2016. Αll cases in which surgical treatment had been applied and histopathological diagnosis of those surgical specimens was available were included. Cases in which ablation was performed and cases with incomplete data or conservative approach were excluded. Primary outcome was the agreement rate between histologic diagnosis of surgical specimen, histologic diagnosis of punch biopsy and colposcopic diagnosis according to REID Colposcopic Index. PPV and NPV of colposcopy and biopsy to diagnose HGSIL were also assessed. Τhere were 120 cases meeting our inclusion criteria, while biopsy was obtained in 104 cases. Mean age of women was 32.7 ± 9.0. Colposcopic diagnosis was CIN2 in 65 cases, CIN3 in 11 cases, CIN1 or less in 44 cases. Τhe level of agreement was fair between colposcopy-surgical specimen histology (κ value 0.443), fair between colposcopy-punch biopsy (κ value 0.34) and moderate between punch biopsy-cone specimen histology (κ value 0.443). PPV of colposcopy to detect HGSIL was 72.3%, while NPV was only 47.7%. Punch biopsy and surgical specimen histology present the highest agreement between the different diagnostic procedures. Colposcopy presented satisfying PPV for HGSIL cases, but its NPV was poor. In contrary, punch biopsy was characterized by both satisfying PPV and NPV for HGSIL cases.

Optimal Management Strategies for Primary HPV Testing for Cervical Screening: Cost-Effectiveness Evaluation for the National Cervical Screening Program in Australia.

PubMed

Simms, Kate T; Hall, Michaela; Smith, Megan A; Lew, Jie-Bin; Hughes, Suzanne; Yuill, Susan; Hammond, Ian; Saville, Marion; Canfell, Karen

2017-01-01

Several countries are implementing a transition to HPV testing for cervical screening in response to the introduction of HPV vaccination and evidence indicating that HPV screening is more effective than cytology. In Australia, a 2017 transition from 2-yearly conventional cytology in 18-20 to 69 years to 5-yearly primary HPV screening in 25 to 74 years will involve partial genotyping for HPV 16/18 with direct referral to colposcopy for this higher risk group. The objective of this study was to determine the optimal management of women positive for other high-risk HPV types (not 16/18) ('OHR HPV'). We used a dynamic model of HPV transmission, vaccination, natural history and cervical screening to determine the optimal management of women positive for OHR HPV. We assumed cytology triage testing was used to inform management in this group and that those with high-grade cytology would be referred to colposcopy and those with negative cytology would receive 12-month surveillance. For those with OHR HPV and low-grade cytology (considered to be a single low-grade category in Australia incorporating ASC-US and LSIL), we evaluated (1) the 20-year risk of invasive cervical cancer assuming this group are referred for 12-month follow-up vs. colposcopy, and compared this to the risk in women with low-grade cytology under the current program (i.e. an accepted benchmark risk for 12-month follow-up in Australia); (2) the population-level impact of the whole program, assuming this group are referred to 12-month surveillance vs. colposcopy; and (3) the cost-effectiveness of immediate colposcopy compared to 12-month follow-up. Evaluation was performed both for HPV-unvaccinated cohorts and cohorts offered vaccination (coverage ~72%). The estimated 20-year risk of cervical cancer is ≤1.0% at all ages if this group are referred to colposcopy vs. ≤1.2% if followed-up in 12 months, both of which are lower than the ≤2.6% benchmark risk in women with low-grade cytology in the current program (who are returned for 12-month follow-up). At the population level, immediate colposcopy referral provides an incremental 1-3% reduction in cervical cancer incidence and mortality compared with 12-month follow-up, but this is in the context of a predicted 24-36% reduction associated with the new HPV screening program compared to the current cytology-based program. Furthermore, immediate colposcopy substantially increases the predicted number of colposcopies, with >650 additional colposcopies required to avert each additional case of cervical cancer compared to 12-month follow-up. Compared to 12-month follow-up, immediate colposcopy has an incremental cost-effectiveness ratio (ICER) of A$104,600/LYS (95%CrI:A$100,100-109,100) in unvaccinated women and A$117,100/LYS (95%CrI:A$112,300-122,000) in cohorts offered vaccination [Indicative willingness-to-pay threshold: A$50,000/LYS]. In primary HPV screening programs, partial genotyping for HPV16/18 or high-grade triage cytology in OHR HPV positive women can be used to refer the highest risk group to colposcopy, but 12-month follow-up for women with OHR HPV and low-grade cytology is associated with a low risk of developing cervical cancer. Direct referral to colposcopy for this group would be associated with a substantial increase in colposcopy referrals and the associated harms, and is also cost-ineffective; thus, 12-month surveillance for women with OHR HPV and low-grade cytology provides the best balance between benefits, harms and cost-effectiveness.

Optimal Management Strategies for Primary HPV Testing for Cervical Screening: Cost-Effectiveness Evaluation for the National Cervical Screening Program in Australia

PubMed Central

Hall, Michaela; Lew, Jie-Bin; Hughes, Suzanne; Yuill, Susan; Hammond, Ian; Saville, Marion; Canfell, Karen

2017-01-01

Background Several countries are implementing a transition to HPV testing for cervical screening in response to the introduction of HPV vaccination and evidence indicating that HPV screening is more effective than cytology. In Australia, a 2017 transition from 2-yearly conventional cytology in 18–20 to 69 years to 5-yearly primary HPV screening in 25 to 74 years will involve partial genotyping for HPV 16/18 with direct referral to colposcopy for this higher risk group. The objective of this study was to determine the optimal management of women positive for other high-risk HPV types (not 16/18) ('OHR HPV'). Methods We used a dynamic model of HPV transmission, vaccination, natural history and cervical screening to determine the optimal management of women positive for OHR HPV. We assumed cytology triage testing was used to inform management in this group and that those with high-grade cytology would be referred to colposcopy and those with negative cytology would receive 12-month surveillance. For those with OHR HPV and low-grade cytology (considered to be a single low-grade category in Australia incorporating ASC-US and LSIL), we evaluated (1) the 20-year risk of invasive cervical cancer assuming this group are referred for 12-month follow-up vs. colposcopy, and compared this to the risk in women with low-grade cytology under the current program (i.e. an accepted benchmark risk for 12-month follow-up in Australia); (2) the population-level impact of the whole program, assuming this group are referred to 12-month surveillance vs. colposcopy; and (3) the cost-effectiveness of immediate colposcopy compared to 12-month follow-up. Evaluation was performed both for HPV-unvaccinated cohorts and cohorts offered vaccination (coverage ~72%). Findings The estimated 20-year risk of cervical cancer is ≤1.0% at all ages if this group are referred to colposcopy vs. ≤1.2% if followed-up in 12 months, both of which are lower than the ≤2.6% benchmark risk in women with low-grade cytology in the current program (who are returned for 12-month follow-up). At the population level, immediate colposcopy referral provides an incremental 1–3% reduction in cervical cancer incidence and mortality compared with 12-month follow-up, but this is in the context of a predicted 24–36% reduction associated with the new HPV screening program compared to the current cytology-based program. Furthermore, immediate colposcopy substantially increases the predicted number of colposcopies, with >650 additional colposcopies required to avert each additional case of cervical cancer compared to 12-month follow-up. Compared to 12-month follow-up, immediate colposcopy has an incremental cost-effectiveness ratio (ICER) of A$104,600/LYS (95%CrI:A$100,100–109,100) in unvaccinated women and A$117,100/LYS (95%CrI:A$112,300–122,000) in cohorts offered vaccination [Indicative willingness-to-pay threshold: A$50,000/LYS]. Conclusions In primary HPV screening programs, partial genotyping for HPV16/18 or high-grade triage cytology in OHR HPV positive women can be used to refer the highest risk group to colposcopy, but 12-month follow-up for women with OHR HPV and low-grade cytology is associated with a low risk of developing cervical cancer. Direct referral to colposcopy for this group would be associated with a substantial increase in colposcopy referrals and the associated harms, and is also cost-ineffective; thus, 12-month surveillance for women with OHR HPV and low-grade cytology provides the best balance between benefits, harms and cost-effectiveness. PMID:28095411

Detection of human papillomavirus DNA in patients referred to a family practice colposcopy clinic.

PubMed

Holman, J R

1996-01-01

Human papillomavirus (HPV) is strongly implicated in the pathogenesis of cervical neoplasia. The ability of a commercially available kit (Virapap/Viratype) to detect evidence of HPV is compared with cervical cytology, colposcopy, and directed biopsies. During a period of 16 months, cervical samples from 241 consecutive new patients referred for a colposcopy examination were obtained for HPV-DNA hybridization typing according to the kit instructions. Samples were sent to a reference laboratory for testing. The results were compared with results of the colposcopy examination, cervical cytology, and directed cervical biopsy samples processed and evaluated by our hospital laboratory. HPV DNA was detected in 27 of 107 patients who had abnormal colposcopy findings for a sensitivity of 25 +/- 7.5 percent at the 90 percent confidence interval. One of 134 patients with normal findings was positive for a specificity of 99 +/- 5 percent at the 95 percent confidence interval. Based on a 75 percent probability of HPV in the population, the positive predictive value was 99 percent and the negative predictive value 30 percent. With the low negative predictive value and sensitivity, HPV-DNA testing by this commercial kit is not an adequate tool for screening HPV in this population.

New technologies and advances in colposcopic assessment.

PubMed

Tan, Jeffrey H J; Wrede, C David H

2011-10-01

To have a good grasp of clinical colposcopy, it is necessary to understand the histopathologic structure of the normal and dysplastic cervical epithelium. Previous meta-analyses had indicated high overall sensitivity of colposcopy in detecting dysplastic lesions, but recent studies have suggested that the technique has much lower sensitivity in detecting high-grade intraepithelial neoplasia. The best practice in colposcopy relies on accurately taking a biopsy from the correct (i.e. most morphological abnormal) site, and by taking more than one biopsy, the sensitivity for detection of high-grade cervical intraepithelial neoplasia can be increased. Cytological screening programmes of proven and maintained high quality will enhance the predictive colposcopic accuracy for high-grade cervical intraepithelial neoplasia after referral. With the advent of computerised colposcopy and the Internet, digital imaging can be transmitted in real-time for instant viewing, facilitating distant consultation and education. This form of 'telemedicine' will allow family practice and remote areas to have access to colposcopy expertise. Of all the currently available technological adjuncts to colposcopy, spectroscopy devices have demonstrated relatively high sensitivities, and seem to have the best potential to become the technique of choice in future routine clinical practice in developed countries following the human papillomavirus vaccination. Other alternatives may need to be used in parts of the globe with high disease incidence and without organised screening or vaccination programmes. Opportunities remain for global collaboration in research, education and training to promote more effective and affordable cervical screening, and to enhance the skills of colposcopists worldwide. Copyright © 2011 Elsevier Ltd. All rights reserved.

Implementation of Canny and Isotropic Operator with Power Law Transformation to Identify Cervical Cancer

NASA Astrophysics Data System (ADS)

Amalia, A.; Rachmawati, D.; Lestari, I. A.; Mourisa, C.

2018-03-01

Colposcopy has been used primarily to diagnose pre-cancer and cancerous lesions because this procedure gives an exaggerated view of the tissues of the vagina and the cervix. But, the poor quality of colposcopy image sometimes makes physician challenging to recognize and analyze it. Generally, Implementation of image processing to identify cervical cancer have to implement a complex classification or clustering method. In this study, we wanted to prove that by only applying the identification of edge detection in the colposcopy image, identification of cervical cancer can be determined. In this study, we implement and comparing two edge detection operator which are isotropic and canny operator. Research methodology in this paper composed by image processing, training, and testing stages. In the image processing step, colposcopy image transformed by nth root power transformation to get better detection result and continued with edge detection process. Training is a process of labelling all dataset image with cervical cancer stage. This process involved pathology doctor as an expert in diagnosing the colposcopy image as a reference. Testing is a process of deciding cancer stage classification by comparing the similarity image of colposcopy results in the testing stage with the image of the results of the training process. We used 30 images as a dataset. The result gets same accuracy which is 80% for both Canny or Isotropic operator. Average running time for Canny operator implementation is 0.3619206 ms while Isotropic get 1.49136262 ms. The result showed that Canny operator is better than isotropic operator because Canny operator generates a more precise edge with a fast time instead.

HPV-DNA testing for patients with ASC-US helps identify the women who have a high risk for precancerous cervical lesions.

PubMed

Moarcăs, M; Georgescu, I C; Moarcăs, R; Badea, M; Cîrstoiu, M

2014-01-01

The cytological interpretation of ASC-US represents a category of morphologic uncertainty. For patients with this result, other tests are necessary in order to determine the risk for cervical lesions. 198 patients with ASC-US cytology have been analyzed between 2008 and 2013. All the patients included in the study have subsequently had a high oncogenic HPV testing and colposcopy risk. 103 (52%) patients tested positive for high risk HPV and 21 (10%) had associated colposcopy changes and precancerous and cancerous lesions identified through biopsy. 95 (48%) patients tested negative for HPV and none of these women had lesions at colposcopy. High oncogenic risk HPV testing was proven useful in identifying the patients with ASC-US cytology who are at high risk for cervical lesions (100% sensibility). In this study, the HPV testing had a negative predictive value of 100%, which uselessly renders a further colposcopy evaluation. HPV testing for women with ASC-US is not specific in identifying women with cervical lesions (Specificity 53%) and this results from a high prevalence of limited HPV infections in an age group which is less than 30 years old. High risk HPV testing for women with ASC-US cervical cytology is useful in determining the risk for precancerous and cancerous cervical lesions. A positive result is associated with a high risk for cervical lesions (20%) and for these patients colposcopy is necessary. For women with a negative result, the risk for cervical lesions is practically null so colposcopy is not required.

Direct booking colposcopy clinic -- the Portsmouth experience.

PubMed

Lukman, H; Bevan, J R; Greenwood, E

2004-08-01

We present 2 years data on direct booking in our colposcopy clinic. The new booking system has improved our efficiency and helped us to achieve the national quality standards on clinic waiting time. The non-attendance (DNA) rate has also improved.

A review of smoking cessation services in women attending colposcopy clinics in Scotland.

PubMed

Rumbles, A U; Nicholson, S C; Court, S J

2012-02-01

The most common reason for women being referred to colposcopy clinics is an abnormal smear suggesting pre-cancerous change within the cervix. It has been demonstrated that in women with low-grade lesions, smoking cessation led to a reduction in size of the cervical lesion over a 6-month period. Smoking is also recognised as an independent risk factor for treatment failure of cervical intraepithelial neoplasia. As 'stop smoking' services have become an integral part of the colposcopy clinic at St John's Hospital, Livingston, a national survey was undertaken. The aim of the survey was to establish what smoking cessation information, advice and support is available in colposcopy clinics throughout Scotland, and if staff had attended standardised training on raising the issue of smoking. The study demonstrated that 52% of colposcopy clinics in Scotland always establish smoking status but only 37% of clinics discuss the benefits of smoking cessation in relation to abnormal cervical smears. There was inaccurate and inconsistent written and verbal advice given on the benefits of cessation and whether women should cut down or stop smoking completely. The majority of staff had not attended standardised training on how to raise the issue of smoking and very few clinics have established referral pathways for smoking cessation support.

Long-Term Worries after Colposcopy: Which Women Are at Increased Risk?

PubMed

Sharp, Linda; Cotton, Seonaidh C; Cruickshank, Margaret E; Gray, Nicola M; Neal, Keith; Rothnie, Kieran; Thornton, Alison J; Walker, Leslie G; Little, Julian

2015-01-01

A colposcopy examination is the main management option for women with an abnormal cervical screening test result. Although some women experience adverse psychological effects after colposcopy, those at greatest risk are unknown. We investigated predictors of worries about cervical cancer, sex, future fertility and general health during 12 to 30 months after colposcopy. We invited 1,515 women, aged 20 to 59 years with low-grade cervical cytology who attended colposcopy to complete questionnaires at recruitment (∼8 weeks after cytology result) and after 12, 18, 24, and 30 months of follow up. Outcomes were worries about having cervical cancer, having sex, future fertility, and general health at any time during follow-up. Factors significantly associated with each outcome were identified using multiple logistic regression. At one or more time points during follow-up, 40% of women reported worries about having cervical cancer, 26% about having sex, 24% about future fertility, and 60% about general health. For all outcomes except sex, worries reported at recruitment were associated with significantly increased risk of worries during follow-up. Significant anxiety at recruitment was associated with all worries during follow-up. Women diagnosed with CIN2+ had significantly higher risks of worries about cervical cancer and future fertility. Management received was associated significantly with worries about cervical cancer and having sex. Younger women significantly more often reported worries about future fertility, whereas women who had children had reduced risk of future fertility worries but increased risk of cervical cancer worries. Clinical, sociodemographic, lifestyle, and psychological factors predicted risk of reporting worries after colposcopy. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

After-effects reported by women following colposcopy, cervical biopsies and LLETZ: results from the TOMBOLA trial.

PubMed

Sharp, Linda; Cotton, Seonaidh; Cochran, Claire; Gray, Nicola; Little, Julian; Neal, Keith; Cruickshank, Maggie

2009-10-01

Few studies have investigated physical after-effects of colposcopy. We compared post-colposcopy self-reported pain, bleeding, discharge and menstrual changes in women who underwent: colposcopic examination only; cervical punch biopsies; and large loop excision of the transformation zone (LLETZ). Observational study nested within a randomised controlled trial. Grampian, Tayside and Nottingham. Nine hundred-and-twenty-nine women, aged 20-59, with low-grade cytology, who had completed their initial colposcopic management. Women completed questionnaires on after-effects at approximately 6-weeks, and on menstruation at 4-months, post-colposcopy. Frequency of pain, bleeding, discharge; changes to first menstrual period post-colposcopy. Seven hundred-and-fifty-one women (80%) completed the 6-week questionnaire. Of women who had only a colposcopic examination, 14-18% reported pain, bleeding or discharge. Around half of women who had biopsies only and two-thirds treated by LLETZ reported pain or discharge (biopsies: 53% pain, 46% discharge; LLETZ: 67% pain, 63% discharge). The frequency of bleeding was similar in the biopsy (79%) and LLETZ groups (87%). Women treated by LLETZ reported bleeding and discharge of significantly longer duration than other women. The duration of pain was similar across management groups. Forty-three percent of women managed by biopsies and 71% managed by LLETZ reported some change to their first period post-colposcopy, as did 29% who only had a colposcopic examination. Cervical punch biopsies and, especially, LLETZ carry a substantial risk of after-effects. After-effects are also reported by women managed solely by colposcopic examination. Ensuring that women are fully informed about after-effects may help to alleviate anxiety and provide reassurance, thereby minimising the harms of screening.

Novel advancements in colposcopy: historical perspectives and a systematic review of future developments.

PubMed

Adelman, Marisa Rachel

2014-07-01

To describe novel innovations and techniques for the detection of high-grade dysplasia. Studies were identified through the PubMed database, spanning the last 10 years. The key words (["computerized colposcopy" or "digital colposcopy" or "spectroscopy" or "multispectral digital colposcopy" or "dynamic spectral imaging", or "electrical impedance spectroscopy" or "confocal endomicroscopy" or "confocal microscopy"or "optical coherence tomography"] and ["cervical dysplasia" or cervical precancer" or "cervix" or "cervical"]) were used. The inclusion criteria were published articles of original research referring to noncolposcopic evaluation of the cervix for the detection of cervical dysplasia. Only English-language articles from the past 10 years were included, in which the technologies were used in vivo, and sensitivities and specificities could be calculated. The single author reviewed the articles for inclusion. Primary search of the database yielded 59 articles, and secondary cross-reference yielded 12 articles. Thirty-two articles met the inclusion criteria. An instrument that globally assesses the cervix, such as computer-assisted colposcopy, optical spectroscopy, and dynamic spectral imaging, would provided the most comprehensive estimate of disease and is therefore best suited when treatment is preferred. Electrical impedance spectroscopy, confocal microscopy, and optical coherence tomography provide information at the cellular level to estimate histology and are therefore best suited when deferment of treatment is preferred. If a device is to eventually replace the colposcope, it will likely combine technologies to best meet the needs of the target population, and as such, no single instrument may prove to be universally appropriate. Analyses of false-positive rates, additional colposcopies and biopsies, cost, and absolute life-savings will be important when considering these technologies and are limited thus far.

American Society for Colposcopy and Cervical Pathology

MedlinePlus

... Colposcopy Standards Recommendations Patient Resources Journal Membership Member Benefits Join/Renew Member Resources Careers About History Bylaws ... MD, MS, Thomas C. Wright, Jr, MD ASCCP Mobile App Updated Consensus Guidelines for Managing Abnormal Cervical Cancer Screening Tests and Cancer ... * Email: * Enter code: * Message: Thank you Your ...

Colposcopic and histologic findings in women with a cytologic diagnosis of atypical squamous cells of undetermined significance.

PubMed

Yarandi, Fariba; Izadi Mood, Narges; Mirashrafi, Fatemeh; Eftekhar, Zahra

2004-12-01

The optimal method for managing a patient diagnosed with atypical squamous cells of undetermined significance (ASCUS) has not yet been established. The interim guidelines published by the National Cancer Institute suggest that a patient should be referred for colposcopy after the second ASCUS diagnosis within 2 years. To assess the significance of ASCUS in predicting the presence of underlying squamous intraepithelial lesion (SIL) of the uterine cervix. Women undergoing colposcopy for ASCUS cytology at a teaching hospital in Tehran University, in the years 1998-2001, considered eligible to enter this retrospective study. Of the 266 patients who underwent colposcopy, 28 (11%) had low-grade squamous intraepithelial lesion (LSIL), 16 (6.3%) had high-grade squamous intraepithelial lesion (HSIL) two (0.8%) had squamous cell carcinoma (SCC), and 48 (18.8%) had flat condyloma. Atypical squamous cells of undetermined significance (ASCUS) on a cervical smear is a good marker for detecting underlying SIL and condyloma. Thus, immediate colposcopy and directed biopsy are appropriate follow-up procedures.

Classification of images acquired with colposcopy using artificial neural networks.

PubMed

Simões, Priscyla W; Izumi, Narjara B; Casagrande, Ramon S; Venson, Ramon; Veronezi, Carlos D; Moretti, Gustavo P; da Rocha, Edroaldo L; Cechinel, Cristian; Ceretta, Luciane B; Comunello, Eros; Martins, Paulo J; Casagrande, Rogério A; Snoeyer, Maria L; Manenti, Sandra A

2014-01-01

To explore the advantages of using artificial neural networks (ANNs) to recognize patterns in colposcopy to classify images in colposcopy. Transversal, descriptive, and analytical study of a quantitative approach with an emphasis on diagnosis. The training test e validation set was composed of images collected from patients who underwent colposcopy. These images were provided by a gynecology clinic located in the city of Criciúma (Brazil). The image database (n = 170) was divided; 48 images were used for the training process, 58 images were used for the tests, and 64 images were used for the validation. A hybrid neural network based on Kohonen self-organizing maps and multilayer perceptron (MLP) networks was used. After 126 cycles, the validation was performed. The best results reached an accuracy of 72.15%, a sensibility of 69.78%, and a specificity of 68%. Although the preliminary results still exhibit an average efficiency, the present approach is an innovative and promising technique that should be deeply explored in the context of the present study.

Rationale and development of an on-line quality assurance programme for colposcopy in a population-based cervical screening setting in Italy.

PubMed

Bucchi, Lauro; Cristiani, Paolo; Costa, Silvano; Schincaglia, Patrizia; Garutti, Paola; Sassoli de Bianchi, Priscilla; Naldoni, Carlo; Olea, Oswaldo; Sideri, Mario

2013-06-28

Colposcopy, the key step in the management of women with abnormal Pap smear results, is a visual technique prone to observer variation, which implies the need for prolonged apprenticeship, continuous training, and quality assurance (QA) measures. Colposcopy QA programmes vary in level of responsibility of organizing subjects, geographic coverage, scope, model, and type of actions. The programmes addressing the clinical standards of colposcopy (quality of examination and appropriateness of clinical decisions) are more limited in space and less sustainable over time than those focused on the provision of the service (resources, accessibility, etc.). This article reports on the protocol of a QA programme targeting the clinical quality of colposcopy in a population-based cervical screening service in an administrative region of northern Italy. After a situation analysis of local colposcopy audit practices and previous QA initiatives, a permanent web-based QA programme was developed. The design places more emphasis on providing education and feedback to participants than on testing them. The technical core is a log-in web application accessible on the website of the regional Administration. The primary objectives are to provide (1) a practical opportunity for retraining of screening colposcopists, and (2) a platform for them to interact with colposcopists from other settings and regions through exchange and discussion of digital colposcopic images. The retraining function is based on repeated QA sessions in which the registered colposcopists log-in, classify a posted set of colpophotographs, and receive on line a set of personal feedback data. Each session ends with a plenary seminar featuring the presentation of overall results and an interactive review of the test set of colpophotographs. This is meant to be a forum for an open exchange of views that may lead to more knowledge and more diagnostic homogeneity. The protocol includes the criteria for selection of colpophotographs and the rationale for colposcopic gold standards. This programme is an ongoing initiative open to further developments, in particular in the area of basic training. It uses the infrastructure of the internet to give a novel solution to technical problems affecting colposcopy QA in population-based screening services.

Towards increase of diagnostic efficacy in gynecologic OCT

NASA Astrophysics Data System (ADS)

Kirillin, Mikhail; Panteleeva, Olga; Eliseeva, Darya; Kachalina, Olga; Sergeeva, Ekaterina; Dubasova, Lyubov; Agrba, Pavel; Mikailova, Gyular; Prudnikov, Maxim; Shakhova, Natalia

2013-06-01

Gynecologic applications of optical coherence tomography (OCT) are usually performed in combination with routine diagnostic procedures: laparoscopy and colposcopy. In combination with laparoscopy OCT is employed for inspection of fallopian tubes in cases of unrecognized infertility while in colposcopy it is used to identify cervix pathologies including cancer. In this paper we discuss methods for increasing diagnostic efficacy of OCT application in these procedures. For OCT-laparoscopy we demonstrate independent criteria for pathology recognition which allow to increase accuracy of diagnostics. For OCT-colposcopy we report on application of device for controlled compression allowing to sense the elasticity of the inspected cervix area and distinguish between neoplasia and inflammatory processes.

Who defaults from colposcopy? A multi-centre, population-based, prospective cohort study of predictors of non-attendance for follow-up among women with low-grade abnormal cervical cytology.

PubMed

Sharp, Linda; Cotton, Seonaidh; Thornton, Alison; Gray, Nicola; Cruickshank, Margaret; Whynes, David; Duncan, Ian; Hammond, Robert; Smart, Louise; Little, Julian

2012-12-01

The success of cervical screening relies on women with abnormal cervical cytology attending for follow-up by colposcopy and related procedures. Failure to attend for colposcopy, however, is a common problem in many countries. The objective of this study was to identify factors associated with non-attendance at an initial colposcopy examination among women with low-grade abnormal cervical cytology. A cohort study was conducted within one arm of a multi-centre population-based randomised controlled trial nested within the UK NHS Cervical Screening Programmes. The trial recruited women aged 20-59 years with recent low-grade cervical cytology; women randomised to immediate referral for colposcopy were included in the current analysis (n=2213). At trial recruitment, women completed a socio-demographic and lifestyle questionnaire; 1693 women in the colposcopy arm were also invited to complete a psychosocial questionnaire, including the Hospital Anxiety and Depression Scale. Women were sent up to two colposcopy appointments. A telephone number was provided to reschedule if necessary. Defaulters were defined as those who failed to attend after two appointments. Logistic regression methods were used to compute multivariate odds ratios (OR) to identify variables significantly associated with default. 148 women defaulted (6.7%, 95%CI 5.7-7.8%). In multivariate analysis, risk of default was significantly raised in those not in paid employment (OR=2.70, 95%CI 1.64-4.43) and current smokers (OR=1.62, 95%CI 1.12-2.34). Default risk deceased with increasing age and level of post-school education/training and was lower in women with children (OR=0.59, 95%CI 0.35-0.98). Among the sub-group invited to complete psychosocial questionnaires, women who were not worried about having cervical cancer were significantly more likely to default (multivariate OR=1.56, 95%CI 1.04-2.35). Anxiety and depression were not significantly associated with default. Women at highest risk of default from colposcopy are younger, not in paid employment, smoke, lack post-school education, have not had children and are not worried about having cervical cancer. Findings such as these could inform the development of tools to predict the likelihood that an individual woman will default from follow-up. Interventions to minimise default also deserve consideration, but a better understanding of reasons for default is needed to inform intervention development. Copyright © 2012. Published by Elsevier Ireland Ltd.

Impact of human papillomavirus vaccination on cervical cytology screening, colposcopy, and treatment.

PubMed

Rodríguez, Ana Cecilia; Solomon, Diane; Herrero, Rolando; Hildesheim, Allan; González, Paula; Wacholder, Sholom; Porras, Carolina; Jiménez, Silvia; Schiffman, Mark

2013-09-01

The impact of human papillomavirus (HPV) vaccination on cervical screening, colposcopy, and treatment is incompletely understood. In 2004-2005, investigators in the Costa Rica Vaccine Trial randomized 7,466 women aged 18-25 years, 1:1, to receive HPV vaccination or hepatitis A vaccination. The worst-ever cytology diagnosis and the 4-year cumulative proportions of colposcopy referral and treatment by vaccination arm were compared for 2 cohorts. The total vaccinated cohort included 6,844 women who provided cervical samples. The naive cohort included 2,284 women with no evidence of previous HPV exposure. In the total vaccinated cohort, HPV-vaccinated women had a significant (P = 0.01) reduction in cytological abnormalities: 12.4% for high-grade lesions and 5.9% for minor lesions. Colposcopy referral was reduced by 7.9% (P = 0.03) and treatment by 11.3% (P = 0.24). Greater relative reductions in abnormal cytology (P < 0.001) were observed for HPV-vaccinated women in the naive cohort: 49.2% for high-grade lesions and 18.1% for minor lesions. Colposcopy referral and treatment were reduced by 21.3% (P = 0.01) and 45.6% (P = 0.08), respectively, in the naive cohort. The overall impact on health services will be modest in the first years after vaccine introduction among young adult women, even in regions with high coverage.

Nature, frequency and duration of genital lesions after consensual sexual intercourse--implications for legal proceedings.

PubMed

Astrup, Birgitte Schmidt; Ravn, Pernille; Lauritsen, Jens; Thomsen, Jørgen Lange

2012-06-10

The purpose of this study was to make a normative description of the nature and duration of genital lesions sustained during consensual sexual intercourse, using the three most commonly used techniques; visualisation using the naked eye, colposcopy and toluidine blue dye followed by colposcopy. Ninety eight women were examined within 48 h of consensual sexual intercourse. Fifty of the women were examined twice again within the following 7 days of sexual abstinence after the first examination. The participants had a median age of 22.4 years and 88% were nulliparous. Lesions were frequent; 34% seen with the naked eye, 49% seen with colposcopy and 52% seen with toluidine blue dye and subsequent colposcopy. The lesions lasted for several days; the median survival times for lacerations were 24, 40 and 80 h, respectively. The legal implications of these findings are that genital lesions by themselves do not corroborate a rape complaint. Genital lesions may, however, corroborate specific details of a case and should be documented as carefully as any other lesion in rape complaints. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Economic analysis of human papillomavirus triage, repeat cytology, and immediate colposcopy in management of women with minor cytological abnormalities in Sweden.

PubMed

Ostensson, Ellinor; Fröberg, Maria; Hjerpe, Anders; Zethraeus, Niklas; Andersson, Sonia

2010-10-01

To assess the cost-effectiveness of using human papillomavirus testing (HPV triage) in the management of women with minor cytological abnormalities in Sweden. An economic analysis based on a clinical trial, complemented with data from published meta-analyses on accuracy of HPV triage. The study takes perspective of the Swedish healthcare system. The Swedish population-based cervical cancer screening program. A decision analytic model was constructed to evaluate cost-effectiveness of HPV triage compared to repeat cytology and immediate colposcopy with biopsy, stratifying by index cytology (ASCUS = atypical squamous cells of undetermined significance, and LSIL = low-grade squamous intraepithelial lesion) and age (23-60 years, <30 years and ≥30 years). Costs, incremental cost, incremental effectiveness and incremental cost per additional high-grade lesion (CIN2+) detected. For women with ASCUS ≥30 years, HPV triage is the least costly alternative, whereas immediate colposcopy with biopsy provides the most effective option at an incremental cost-effectiveness ratio (ICER) of SEK 2,056 per additional case of CIN2+ detected. For LSIL (all age groups) and ASCUS (23-60 years and <30 years), HPV triage is dominated by immediate colposcopy and biopsy. Model results were sensitive to HPV test cost changes. With improved HPV testing techniques at lower costs, HPV triage can become a cost-effective alternative for follow-up of minor cytological abnormalities. Today, immediate colposcopy with biopsy is a cost-effective alternative compared to HPV triage and repeat cytology.

Performance of Implementing Guideline Driven Cervical Cancer Screening Measures in an Inner City Hospital System

PubMed Central

Wieland, Daryl L.; Reimers, Laura L.; Wu, Eijean; Nathan, Lisa M.; Gruenberg, Tammy; Abadi, Maria; Einstein, Mark H.

2013-01-01

Objective In 2006, the American Society for Colposcopy and Cervical Pathology (ASCCP) updated evidence based guidelines recommending screening intervals for women with abnormal cervical cytology. In our low-income inner city population, we sought to improve performance by uniformly applying the guidelines to all patients. We report the prospective performance of a comprehensive tracking, evidence-based algorithmically driven call-back and appointment scheduling system for cervical cancer screening in a resource-limited inner city population. Materials and Methods Outreach efforts were formalized with algorithm-based protocols for triage to colposcopy, with universal adherence to evidence-based guidelines. During implementation from August 2006 through July 2008, we prospectively tracked performance using the electronic medical record with administrative and pathology reports to determine performance variables such as the total number of Pap tests, colposcopy visits, and the distribution of abnormal cytology and histology results, including all CIN 2,3 diagnoses. Results 86,257 gynecologic visits and 41,527 Pap tests were performed system-wide during this period of widespread and uniform implementation of standard cervical cancer screening guidelines. The number of Pap tests performed per month varied little. The incidence of CIN 1 significantly decreased from 117/171 (68.4%) the first tracked month to 52/95 (54.7%) the last tracked month (p=0.04). The monthly incidence rate of CIN 2,3, including incident cervical cancers did not change. The total number of colposcopy visits declined, resulting in a 50% decrease in costs related to colposcopy services and approximately a 12% decrease in costs related to excisional biopsies. Conclusions Adherence to cervical cancer screening guidelines reduced the number of unnecessary colposcopies without increasing numbers of potentially missed CIN 2,3 lesions, including cervical cancer. Uniform implementation of administrative-based performance initiatives for cervical cancer screening minimizes differences in provider practices and maximizes performance of screening while containing cervical cancer screening costs. PMID:21959573

HPV genotyping for triage of women with abnormal cervical cancer screening results: a multicenter prospective study.

PubMed

Nakamura, Yuko; Matsumoto, Koji; Satoh, Toyomi; Nishide, Ken; Nozue, Akiko; Shimabukuro, Koji; Endo, Seiichi; Nagai, Kimihiro; Oki, Akinori; Ochi, Hiroyuki; Morishita, Yukio; Noguchi, Masayuki; Yoshikawa, Hiroyuki

2015-10-01

In cervical cancer screening programs, women with abnormal cytology are referred for colposcopy for histological evaluation. We examined whether a human papillomavirus (HPV) genotyping assay could be used to identify women who do not need immediate colposcopy and biopsy because of low risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+). We prospectively evaluated test performance for 2 carcinogenic HPV genotypes (HPV16/18), for 8 types (HPV16/18/31/33/35/45/52/58), and for 13 types (HPV16/18/31/33/35/45/51/52/56/58/59/68) for prediction of histological CIN3+ results among 427 screen-positive women referred for colposcopy. The study subjects consisted of 214 women with low-grade squamous intraepithelial lesion (LSIL), 184 with high-grade squamous intraepithelial lesion (HSIL), and 29 with atypical squamous cells, cannot exclude HSIL (ASC-H). Among women with LSIL cytology, HPV16/18 positivity was 29.4 % and increased to 58.9 % for 8 types and to 74.8 % for 13 types (P < 0.001). The risk of CIN3+ biopsy results was still 7.9 % for women testing negative for HPV16/18, but decreased to 0.0 % for those testing negative for at least eight types of HPV (HPV16/18/31/33/35/45/52/58). Although HPV genotyping results enabled additional risk stratification among women with HSIL/ASC-H cytology, the risk of histological CIN3+ diagnosis among women testing negative for eight types or more was still sufficiently high (>35 %) to warrant immediate colposcopy referral. Of women with LSIL cytology, those testing negative for at least eight of the highest-risk types of HPV (HPV16/18/31/33/35/45/52/58) may not need immediate colposcopy and biopsy. This would reduce the number of colposcopy referrals by approximately 40 %. However, the HPV genotyping assay is not likely to alter the clinical management of women with HSIL/ASC-H.

History of colposcopy: a brief biography of Hinselmann

PubMed Central

Fusco, Eugenio; Padula, Francesco; Mancini, Emanuela; Cavaliere, Alessandro; Grubisic, Goran

2008-01-01

Objectives: To consider all the historical reasons for the slow growth of colposcopy through a brief biography of Hinselmann. The history of colposcopy is beginning in March 1924. In the first experiments, colposcopic examination was almost impossible to perform because of the distance from the focus, that was no more than 80 mm. Hinselmann tried to solve this problem by pulling out the uterine cervix. The examined part is anemised by this procedure, which can prejudice the final result and a small amount of blood might leak as well. Beside that, a patient can feel pain if the portio is held by a thin forceps. The colposcopy, established in Germany, had spread throughout slowly its motherland, probably thanks to the many mistakes caused by Hinselmann himself: a technique proposed and almost exclusively intended for early discovery of cervical carcinoma;very authoritative imposition of terms, especially histological, which caused resistance by hystopathologists possibly induced by the fear of loosing their prestige who considered them too complex;his stubbornness in considering leukoplakia as precancerous lesion imposed him a lot of opponents;until the 1950's there had not yet been any adequate didactic material at the disposal of numerous gynaecologists;Hinselmann’s temper, described by Wespi as a mixture of innocence and missionary eagerness, had not prepared him for dialogue and compromise. Conclusion: It might seem surprising that colposcopy, accurate in detecting all benign lesions and initial atypical transformations, and perfectly capable of pointing safe biopsy in cases of suspicious lesions, did not develop as it should have a method whose function is of great importance in the prevention and treatment of CIN. Despite the role and the importance of cytology in the realization of the population programme of cervical cancer detection, the colposcopy allows the precise diagnosis among women with abnormal pap smears. PMID:22439022

A normal colposcopy examination fails to provide psychological reassurance for women who have had low-grade abnormal cervical cytology.

PubMed

Cotton, S C; Sharp, L; Little, J; Gray, N M; Walker, L G; Whynes, D K; Cruickshank, M E

2015-06-01

Worldwide, each year, large numbers of women are referred for colposcopy following low-grade abnormal cervical cytology. Many have no visible abnormality on examination. The risk of cervical intra-epithelial neoplasia grade 2/3 (CIN2/3) in these women is low. It is unknown whether, for women, a normal colposcopy resolves the anxiety which often follows the receipt of an abnormal cytology result. We investigated the prevalence of adverse psychological outcomes over 30 months following a normal colposcopy. This cohort study was nested within the UK TOMBOLA randomized controlled trial. Women aged 20-59 years, with recent low-grade cytology, who had a satisfactory colposcopy examination and normal transformation zone, completed the Hospital Anxiety and Depression Scale (HADS) and Process Outcome Specific Measure (POSM) at recruitment and during follow-up (12, 18, 24 and 30 months post-recruitment). Outcomes included percentages reporting significant anxiety (HADS anxiety subscale score ≥11), significant depression (HADS depression subscale score ≥8) or worries about the result of the next cytology test, cervical cancer, having sex, future fertility and general health at each time point (point prevalence) and during follow-up (cumulative prevalence). The study included 727 women. All psychological measures (except depression) had high prevalence at recruitment, falling substantially by 12 months. During follow-up, the cumulative prevalence of significant anxiety was 27% and significant depression was 21%. The most frequently reported worry was that the next cytology test would be abnormal (cumulative prevalence of 71%; point prevalence of ≥50% at 12 and 18 months). The cumulative prevalence values of worries about cervical cancer, having sex and future fertility were 33%, 20% and 16%, respectively. For some women who have low-grade cytology, a normal colposcopy does not appear to provide psychological reassurance. © 2014 John Wiley & Sons Ltd.

Rationale and development of an on-line quality assurance programme for colposcopy in a population-based cervical screening setting in Italy

PubMed Central

2013-01-01

Background Colposcopy, the key step in the management of women with abnormal Pap smear results, is a visual technique prone to observer variation, which implies the need for prolonged apprenticeship, continuous training, and quality assurance (QA) measures. Colposcopy QA programmes vary in level of responsibility of organizing subjects, geographic coverage, scope, model, and type of actions. The programmes addressing the clinical standards of colposcopy (quality of examination and appropriateness of clinical decisions) are more limited in space and less sustainable over time than those focused on the provision of the service (resources, accessibility, etc.). This article reports on the protocol of a QA programme targeting the clinical quality of colposcopy in a population-based cervical screening service in an administrative region of northern Italy. Methods/design After a situation analysis of local colposcopy audit practices and previous QA initiatives, a permanent web-based QA programme was developed. The design places more emphasis on providing education and feedback to participants than on testing them. The technical core is a log-in web application accessible on the website of the regional Administration. The primary objectives are to provide (1) a practical opportunity for retraining of screening colposcopists, and (2) a platform for them to interact with colposcopists from other settings and regions through exchange and discussion of digital colposcopic images. The retraining function is based on repeated QA sessions in which the registered colposcopists log-in, classify a posted set of colpophotographs, and receive on line a set of personal feedback data. Each session ends with a plenary seminar featuring the presentation of overall results and an interactive review of the test set of colpophotographs. This is meant to be a forum for an open exchange of views that may lead to more knowledge and more diagnostic homogeneity. The protocol includes the criteria for selection of colpophotographs and the rationale for colposcopic gold standards. Discussion This programme is an ongoing initiative open to further developments, in particular in the area of basic training. It uses the infrastructure of the internet to give a novel solution to technical problems affecting colposcopy QA in population-based screening services. PMID:23809615

Cytological surveillance compared with immediate referral for colposcopy in management of women with low grade cervical abnormalities: multicentre randomised controlled trial.

PubMed

2009-07-28

To examine the effectiveness of cytological surveillance in primary care compared with immediate referral for colposcopic examination in women with low grade abnormal results on cervical cytology tests. Multicentre individually randomised controlled trial. NHS cervical screening programmes in Grampian, Tayside, and Nottingham. 4439 women, aged 20-59, with a cytology result showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002. Cytological screening every six months in primary care (n=2223) or referral for colposcopy and related interventions (n=2216). All women were followed for three years, concluding with an exit appointment at which colposcopic examination was undertaken. Colposcopists assessing outcome at this appointment were blinded to randomisation. Primary end point: cumulative incidence of cervical intraepithelial neoplasia grade II or more severe disease. Other end points: cervical intraepithelial neoplasia grade III or worse, clinically significant anxiety and depression, other self reported after effects, and rates of non-attendance. Analysis was by intention to treat; all those randomised were included. The cumulative incidence of cervical intraepithelial neoplasia grade II or worse was 79 per 1000 person years in the colposcopy arm and 58 per 1000 person years in the cytological surveillance arm (relative risk 1.37, 95% confidence interval 1.19 to 1.57). This difference was less marked for cervical intraepithelial neoplasia grade III or more severe disease, but the incidence was still higher in the colposcopy arm (relative risk 1.26, 1.04 to 1.53). Among women randomised to immediate colposcopy, 79% (74.9% to 82.5%) of cases of cervical intraepithelial neoplasia grade II or worse were diagnosed at the time of the immediate colposcopy, while among women randomised to cytological surveillance, 77% (72.1% to 81.2%) of cases were detected by surveillance cytology and related interventions. Similar proportions of women were anxious or depressed in the two arms. A higher proportion of women in the colposcopy arm reported after effects, and these were of longer duration and more severe. Non-attendance was low in both arms. The more marked difference between the arms in the occurrence of cervical intraepithelial neoplasia grade II or worse than in the occurrence of grade III or worse can probably be accounted for by the spontaneous regression of some cases of grade II neoplasia. Compared with cytological surveillance, a policy of immediate colposcopy detects more cervical intraepithelial neoplasia grade II or worse, and some more grade III or worse, but might lead to overtreatment. Such a policy is associated with a higher rate of reported after effects, which are more severe and of longer duration than those associated with cytological surveillance. ISRCTN 34841617.

Colposcopy audit for improving quality of service in areas with a high incidence of cervical cancer.

PubMed

Manopunya, Manatsawee; Suprasert, Prapaporn; Srisomboon, Jatupol; Kietpeerakool, Chumnan

2010-01-01

To audit routine colposcopy performance using 8 standard requirements of the National Health Service Cervical Screening Programme (NHSCSP). Records of women who underwent colposcopy for abnormal cervical cytology between January and December 2008 at Chiang Mai University Hospital, Thailand, were reviewed. The standard requirements were not achieved in 2 practices: (1) the proportion of women who had recordings of visibility of the transformation zone (96.6%) did not achieve the NHSCSP requirement of 100%; and (2) the rate of excisional biopsy (87.8%) was lower than the 95% minimum required. Colposcopic performance at Chiang Mai University Hospital was generally favorable. However, re-audit is necessary to ensure that unmet standards of performance are improved and achieved standards are maintained.

Using colposcopy in the rape exam: health care, forensic, and criminal justice issues.

PubMed

Sommers, Marilyn Sawyer; Fisher, Bonnie S; Karjane, Heather M

2005-01-01

In the setting of a forensic examination following rape, colposcopy allows practitioners to identify and photograph genital injury not readily visible to the unaided eye, thereby clarifying the location and extent of injury as well as providing evidence for court proceedings. Since the 1980s, the technique once reserved for victims of child abuse has been used across the lifespan and has been shown to identify genital injury in up to 87% of women who have been raped. The role of colposcopic findings as evidence in court testimony, however, remains controversial. This paper explores the history of colposcopy in the rape exam and describes the epidemiology of genital injury in consensual sex as well as rape.

Increased detection of precancerous cervical lesions with adjunctive dynamic spectral imaging.

PubMed

DeNardis, Sara A; Lavin, Philip T; Livingston, Jeff; Salter, William R; James-Patrick, Nanette; Papagiannakis, Emmanouil; Olson, Christopher G; Weinberg, Lori

2017-01-01

To validate, in US community-based colposcopy clinics, previous reports of increased detection of high-grade cervical intraepithelial neoplasia (CIN2+) with biopsies selected using dynamic spectral imaging (DSI) mapping after standard colposcopy. Cross-sectional observational study of 26 colposcopists across nine clinics recruiting consecutive colposcopy patients. Standard assessment with biopsy selections was completed before seeing the DSI map which was subsequently interpreted and used for additional biopsies per clinical judgment. Primary measure was the number of women with CIN2+ detected by DSI-assisted biopsies, over those detected by standard colposcopy biopsies. A total of 887 women were recruited. After exclusions, 881 women and 1,189 biopsies were analyzed. Standard biopsy detected 78 women with CIN2+ and DSI-assisted biopsies another 34, increasing the detection rate from 8.85% to 12.71% ( p =0.00016). This was achieved with 16.16% of DSI-assisted biopsies finding CIN2+ compared to 13.24% for the preceding standard biopsies. For secondary specificity analysis, 431 women had only

Increased detection of precancerous cervical lesions with adjunctive dynamic spectral imaging

PubMed Central

DeNardis, Sara A; Lavin, Philip T; Livingston, Jeff; Salter, William R; James-Patrick, Nanette; Papagiannakis, Emmanouil; Olson, Christopher G; Weinberg, Lori

2017-01-01

Objective To validate, in US community-based colposcopy clinics, previous reports of increased detection of high-grade cervical intraepithelial neoplasia (CIN2+) with biopsies selected using dynamic spectral imaging (DSI) mapping after standard colposcopy. Study design Cross-sectional observational study of 26 colposcopists across nine clinics recruiting consecutive colposcopy patients. Standard assessment with biopsy selections was completed before seeing the DSI map which was subsequently interpreted and used for additional biopsies per clinical judgment. Primary measure was the number of women with CIN2+ detected by DSI-assisted biopsies, over those detected by standard colposcopy biopsies. Results A total of 887 women were recruited. After exclusions, 881 women and 1,189 biopsies were analyzed. Standard biopsy detected 78 women with CIN2+ and DSI-assisted biopsies another 34, increasing the detection rate from 8.85% to 12.71% (p=0.00016). This was achieved with 16.16% of DSI-assisted biopsies finding CIN2+ compared to 13.24% for the preceding standard biopsies. For secondary specificity analysis, 431 women had only

Application of deep learning to the classification of images from colposcopy.

PubMed

Sato, Masakazu; Horie, Koji; Hara, Aki; Miyamoto, Yuichiro; Kurihara, Kazuko; Tomio, Kensuke; Yokota, Harushige

2018-03-01

The objective of the present study was to investigate whether deep learning could be applied successfully to the classification of images from colposcopy. For this purpose, a total of 158 patients who underwent conization were enrolled, and medical records and data from the gynecological oncology database were retrospectively reviewed. Deep learning was performed with the Keras neural network and TensorFlow libraries. Using preoperative images from colposcopy as the input data and deep learning technology, the patients were classified into three groups [severe dysplasia, carcinoma in situ (CIS) and invasive cancer (IC)]. A total of 485 images were obtained for the analysis, of which 142 images were of severe dysplasia (2.9 images/patient), 257 were of CIS (3.3 images/patient), and 86 were of IC (4.1 images/patient). Of these, 233 images were captured with a green filter, and the remaining 252 were captured without a green filter. Following the application of L2 regularization, L1 regularization, dropout and data augmentation, the accuracy of the validation dataset was ~50%. Although the present study is preliminary, the results indicated that deep learning may be applied to classify colposcopy images.

Application of deep learning to the classification of images from colposcopy

PubMed Central

Sato, Masakazu; Horie, Koji; Hara, Aki; Miyamoto, Yuichiro; Kurihara, Kazuko; Tomio, Kensuke; Yokota, Harushige

2018-01-01

The objective of the present study was to investigate whether deep learning could be applied successfully to the classification of images from colposcopy. For this purpose, a total of 158 patients who underwent conization were enrolled, and medical records and data from the gynecological oncology database were retrospectively reviewed. Deep learning was performed with the Keras neural network and TensorFlow libraries. Using preoperative images from colposcopy as the input data and deep learning technology, the patients were classified into three groups [severe dysplasia, carcinoma in situ (CIS) and invasive cancer (IC)]. A total of 485 images were obtained for the analysis, of which 142 images were of severe dysplasia (2.9 images/patient), 257 were of CIS (3.3 images/patient), and 86 were of IC (4.1 images/patient). Of these, 233 images were captured with a green filter, and the remaining 252 were captured without a green filter. Following the application of L2 regularization, L1 regularization, dropout and data augmentation, the accuracy of the validation dataset was ~50%. Although the present study is preliminary, the results indicated that deep learning may be applied to classify colposcopy images. PMID:29456725

Diagnostic accuracy of high-risk HPV DNA genotyping for primary cervical cancer screening and triage of HPV-positive women, compared to cytology: preliminary results of the PIPAVIR study.

PubMed

Chatzistamatiou, Kimon; Moysiadis, Theodoros; Angelis, Eleftherios; Kaufmann, Andreas; Skenderi, Alkmini; Jansen-Duerr, Pidder; Lekka, Irini; Kilintzis, Vasilis; Angelidou, Stamatia; Katsiki, Evangelia; Hagemann, Ingke; Tsertanidou, Athena; Koch, Isabel; Boecher, Oliver; Soutschek, Erwin; Maglaveras, Nikolaos; Agorastos, Theodoros

2017-05-01

The purpose of the presented PIPAVIR (persistent infections with human papillomaviruses; http://www.pipavir.com ) subanalysis is to assess the performance of high-risk (hr) HPV-DNA genotyping as a method of primary cervical cancer screening and triage of HPV positive women to colposcopy compared to liquid-based cytology (LBC) in an urban female population. Women, aged 30-60, provided cervicovaginal samples at the Family-Planning Centre, Hippokratio Hospital of Thessaloniki, Greece, and the Department of Gynecology and Obstetrics in Mare Klinikum, Kiel, Germany. Cytology and HPV genotyping was performed using LBC and HPV Multiplex Genotyping (MPG), respectively. Women positive for cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] or hrHPV were referred for colposcopy. Among 1723/1762 women included in the final analysis, hrHPV and HPV16/18 prevalence was 17.7 and 9.6%, respectively. Cytology was ASCUS or worse in 7.6%. Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+) was detected in 28 women (1.6%). Sensitivity of cytology (ASCUS or worse) and HPV DNA testing for the detection of CIN2+ was 50.0 and 100%, and specificity was 94.49 and 85.49%, respectively. The screening approach according to which only women positive for HPV16/18 and for hrHPV(non16/18) with ASCUS or worse were referred to colposcopy presented 78.57% sensitivity and 13.17% positive predictive value (PPV). HPV testing represents a more sensitive methodology for primary cervical cancer screening compared to cytology. For triage of HPV positive women to colposcopy, partial HPV genotyping offers better sensitivity than cytology, at the cost of higher number of colposcopies.

Multiple Biopsies and Detection of Cervical Cancer Precursors at Colposcopy

PubMed Central

Wentzensen, Nicolas; Walker, Joan L.; Gold, Michael A.; Smith, Katie M.; Zuna, Rosemary E.; Mathews, Cara; Dunn, S. Terence; Zhang, Roy; Moxley, Katherine; Bishop, Erin; Tenney, Meaghan; Nugent, Elizabeth; Graubard, Barry I.; Wacholder, Sholom; Schiffman, Mark

2015-01-01

Purpose Women with abnormal cervical cancer screening results are referred to colposcopy and biopsy for diagnosis of cervical cancer precursors (high-grade squamous intraepithelial lesions [HSILs]). Colposcopy with a single biopsy can miss identification of HSILs. No systematic study has quantified the improved detection of HSIL by taking multiple lesion-directed biopsies. Methods The Biopsy Study was an observational study of 690 women referred to colposcopy after abnormal cervical cancer screening results. Up to four directed biopsies were taken from distinct acetowhite lesions and ranked by colposcopic impression. A nondirected biopsy of a normal-appearing area was added if fewer than four directed biopsies were taken. HSIL identified by any biopsy was the reference standard of disease used to evaluate the incremental yield and sensitivity of multiple biopsies. Results In the overall population, sensitivities for detecting HSIL increased from 60.6% (95% CI, 54.8% to 66.6%) from a single biopsy to 85.6% (95% CI, 80.3% to 90.2%) after two biopsies and to 95.6% (95% CI, 91.3% to 99.2%) after three biopsies. A significant increase in sensitivity of multiple biopsies was observed in all subgroups. The highest increase in yield of HSIL was observed for women with a high-grade colposcopic impression, HSIL cytology, and human papillomavirus (HPV) type 16 positivity. Only 2% of all HSILs diagnosed in the participants were detected by biopsies of normal-appearing transformation zone. Conclusion Collection of additional lesion-directed biopsies during colposcopy increased detection of histologic HSIL, regardless of patient characteristics. Taking additional biopsies when multiple lesions are present should become the standard practice of colposcopic biopsy. PMID:25422481

Domestic violence is a leading risk factor in default from colposcopy services.

PubMed

Collier, Rachael; Quinlivan, Julie A

2014-06-01

Domestic violence is common in women and is associated with poorer health-care outcomes. However, no causal pathway has been identified to explain this observation. We have followed a cohort of women to determine whether poorer outcomes can be explained by high rates of default and loss to follow-up. A prospective cohort study was performed. Institutional ethics approval was obtained. Participants were consecutive patients attending colposcopy clinics at a major metropolitan hospital in Australia. Following ascertainment of domestic violence status, appointment outcomes for colposcopy services were tracked for a 3-year period. Multivariate analysis was undertaken to determine demographic factors associated with default from care and loss to follow-up. Of 581 women approached, consent was obtained from 574 women (99%). Domestic violence status was obtained from 566 women, of whom 187 (33%) had a recent history of exposure. Women exposed to violence were more likely to default from colposcopy once (26.2% vs 7.4%; P < 0.0001), twice (11.2% vs 3.2%, P = 0.0001), or thrice (10.7% vs 2.4%, P < 0.0001). They were more likely to be lost to follow-up (8.0% vs 1.1%, P < 0.0001). In multivariate analysis, exposure to domestic violence remained significantly associated with default and loss to follow-up. Domestic violence is a risk factor for default from attendance and loss to follow-up at colposcopy services. This may explain the mechanism behind adverse health-care outcomes seen. Screening and targeted appointment intervention programs may improve clinical compliance. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Fluorescence spectroscopy for diagnosis of squamous intraepithelial lesions of the cervix.

PubMed

Mitchell, M F; Cantor, S B; Ramanujam, N; Tortolero-Luna, G; Richards-Kortum, R

1999-03-01

To calculate receiver operating characteristic (ROC) curves for fluorescence spectroscopy in order to measure its performance in the diagnosis of squamous intraepithelial lesions (SILs) and to compare these curves with those for other diagnostic methods: colposcopy, cervicography, speculoscopy, Papanicolaou smear screening, and human papillomavirus (HPV) testing. Data from our previous clinical study were used to calculate ROC curves for fluorescence spectroscopy. Curves for other techniques were calculated from other investigators' reports. To identify these, a MEDLINE search for articles published from 1966 to 1996 was carried out, using the search terms "colposcopy," "cervicoscopy," "cervicography," "speculoscopy," "Papanicolaou smear," "HPV testing," "fluorescence spectroscopy," and "polar probe" in conjunction with the terms "diagnosis," "positive predictive value," "negative predictive value," and "receiver operating characteristic curve." We found 270 articles, from which articles were selected if they reported results of studies involving high-disease-prevalence populations, reported findings of studies in which colposcopically directed biopsy was the criterion standard, and included sufficient data for recalculation of the reported sensitivities and specificities. We calculated ROC curves for fluorescence spectroscopy using Bayesian and neural net algorithms. A meta-analytic approach was used to calculate ROC curves for the other techniques. Areas under the curves were calculated. Fluorescence spectroscopy using the neural net algorithm had the highest area under the ROC curve, followed by fluorescence spectroscopy using the Bayesian algorithm, followed by colposcopy, the standard diagnostic technique. Cervicography, Papanicolaou smear screening, and HPV testing performed comparably with each other but not as well as fluorescence spectroscopy and colposcopy. Fluorescence spectroscopy performs better than colposcopy and other techniques in the diagnosis of SILs. Because it also permits real-time diagnosis and has the potential of being used by inexperienced health care personnel, this technology holds bright promise.

Cervical human papilloma virus (HPV) DNA primary screening test: Results of a population-based screening programme in central Italy.

PubMed

Passamonti, Basilio; Gustinucci, Daniela; Giorgi Rossi, Paolo; Cesarini, Elena; Bulletti, Simonetta; Carlani, Angela; Martinelli, Nadia; Broccolini, Massimo; D'Angelo, Valentina; D'Amico, Maria Rosaria; Di Dato, Eugenio; Galeazzi, Paola; Malaspina, Morena; Spita, Nicoletta; Tintori, Beatrice; Giaimo, Maria Donata

2017-09-01

Objective To present the results of the first and second round human papilloma virus (HPV)-based screening programme in the Umbria region after three years. Methods From August 2010 to November 2011, the entire female population aged 35-64 in a local health district was invited for HPV testing (HPV-DNA cobas4800 on a liquid-based cytology sample). HPV-negative women were re-invited after three years. For HPV-positive women, a slide was prepared and interpreted. Positive cytologies were referred to colposcopy; negatives were referred to repeat HPV after one year. If HPV was persistently positive, women were referred to colposcopy; if negative, to normal screening. Indicators of the first and second round are compared with those of cytology screening in the same area in the preceding three years. Results Participation was 56.5%, the same as cytology (56.6%). HPV-positivity was 6.4% (396/6272), cytology triage positivity was 35.6%; 251 cytology negative women were referred to one-year HPV retesting, 84.1% complied, and 55.5% were positive. Total colposcopy referral was 4.1%, and for cytology 1%. The detection rate for cervical intraepithelial neoplasia grade 2 or more severe was 10‰, compared with 3.7‰ using cytology. After three years, HPV-positivity was 3.4% (129/3831), overall colposcopy referral was 2.3% (most at one-year follow-up), and detection rate was 0.5/1000. Conclusions The first round detection rate was more than twice that of cytology screening, while colposcopy referral increased fourfold. At the second round, the detection rate decreased dramatically, showing that longer interval and more conservative protocols are needed.

Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia: Testing a device as an adjunct to colposcopy.

PubMed

Cantor, Scott B; Yamal, Jose-Miguel; Guillaud, Martial; Cox, Dennis D; Atkinson, E Neely; Benedet, John L; Miller, Dianne; Ehlen, Thomas; Matisic, Jasenka; van Niekerk, Dirk; Bertrand, Monique; Milbourne, Andrea; Rhodes, Helen; Malpica, Anais; Staerkel, Gregg; Nader-Eftekhari, Shahla; Adler-Storthz, Karen; Scheurer, Michael E; Basen-Engquist, Karen; Shinn, Eileen; West, Loyd A; Vlastos, Anne-Therese; Tao, Xia; Beck, J Robert; Macaulay, Calum; Follen, Michele

2011-03-01

Testing emerging technologies involves the evaluation of biologic plausibility, technical efficacy, clinical effectiveness, patient satisfaction, and cost-effectiveness. The objective of this study was to select an effective classification algorithm for optical spectroscopy as an adjunct to colposcopy and obtain preliminary estimates of its accuracy for the detection of CIN 2 or worse. We recruited 1,000 patients from screening and prevention clinics and 850 patients from colposcopy clinics at two comprehensive cancer centers and a community hospital. Optical spectroscopy was performed, and 4,864 biopsies were obtained from the sites measured, including abnormal and normal colposcopic areas. The gold standard was the histologic report of biopsies, read 2 to 3 times by histopathologists blinded to the cytologic, histopathologic, and spectroscopic results. We calculated sensitivities, specificities, receiver operating characteristic (ROC) curves, and areas under the ROC curves. We identified a cutpoint for an algorithm based on optical spectroscopy that yielded an estimated sensitivity of 1.00 [95% confidence interval (CI) = 0.92-1.00] and an estimated specificity of 0.71 [95% CI = 0.62-0.79] in a combined screening and diagnostic population. The positive and negative predictive values were 0.58 and 1.00, respectively. The area under the ROC curve was 0.85 (95% CI = 0.81-0.89). The per-patient and per-site performance were similar in the diagnostic and poorer in the screening settings. Like colposcopy, the device performs best in a diagnostic population. Alternative statistical approaches demonstrate that the analysis is robust and that spectroscopy works as well as or slightly better than colposcopy for the detection of CIN 2 to cancer. Copyright © 2010 UICC.

[Colonic perforation during colonoscopy. 100 cases].

PubMed

Hureau, J; Avtan, L; Germain, M; Blanc, D; Chaussade, G

1992-01-01

The analysis of 100 cases of colon perforation during colposcopic examinations highly demonstrates such a statement. The perforation risk during colposcopies is generally of the order of 0.2% for a diagnosis coloscopy. According to the statistic data used, it can reach 0.5 to 3% in therapy coloscopy. This is a risk inherent to the technique used. It is thus required to analyse the causes and take the appropriate measures to reduce it to a minimum. Mortality due to such a complication remains high (14%), i.e about 0.015 to 0.1% (#2/10000) of all colposcopies. In 11% of the patients, serious sequelae are to be observed. This demonstrates the significance of the medico-legal problem set by these perforations during colposcopies. The whole personnel responsibility can be involved: colposcopist, surgeon, anesthetist and hospital unit.

Prevalence of High-Grade Intraepithelial Neoplasia in Patients with Cytology Presenting Atypical Squamous Cells of Undetermined Significance.

PubMed

Marcos Lopes, Ana Cristina; Campaner, Adriana Bittencourt; Henrique, Laílca Quirino

2016-01-01

To evaluate the prevalence of histological high-grade lesions and cervical cancer in patients with ASCUS cytology. This is a cross-sectional prospective study involving 703 women with a uterus and atypical squamous cells of undetermined significance (ASCUS). The patients were submitted to a colposcopy and underwent a guided biopsy when changes on the colposcopy were detected. The findings revealed 456 (64.9%) women with a normal colposcopy and 247 (35.1%) with colposcopic abnormalities. The biopsy results were: cervical intraepithelial neoplasia grade 1 (CIN 1) in 51 (20.6%) patients, CIN 2 in 11 (4.5%) patients, CIN 3 in 8 (3.2%) patients, and a negative result in 177 (71.7%) patients; no cases of cancer were detected. Tallying of 456 normal colposcopies and 177 negative biopsies yielded a total of 90.04% negative exams. Furthermore, around 7.2% (51/703) of the patients exhibited CIN 1, a lesion associated with a high potential for regression. The biopsy results were not associated with patient age or menopausal status. We conclude that cytological surveillance of patients with ASCUS is feasible and safe given the low risk of CIN 2/3 or cervical cancer. © 2016 S. Karger AG, Basel.

High risk HPV testing following treatment for cervical intraepithelial neoplasia.

PubMed

Molloy, M; Comer, R; Rogers, P; Dowling, M; Meskell, P; Asbury, K; O'Leary, M

2016-11-01

To determine the results of combined cytology and high-risk human papilloma virus (HR HPV) tests at 6 and 18 months postcolposcopy treatment at one Irish colposcopy centre. All women who attended the centre's colposcopy smear clinic for a co-test 6 months (initial test) posttreatment were included in the audit (n = 251). The results revealed negative HR HPV for 79 % (n = 198) of women tested 6 months after treatment and positive results for 21 % (n = 53). HR HPV testing was more sensitive than cytology and led to early detection of residual disease. No women with negative HR HPV had high-grade cytology. HR HPV is more sensitive than cytology for detection of persistent CIN. However, 19 women with positive HR HPV had normal colposcopy with no persistent CIN detected. A national cost-benefit analysis is recommended to determine the value of the second co-test.

Sensitivity, Specificity, and Clinical Value of Human Papillomavirus (HPV) E6/E7 mRNA Assay as a Triage Test for Cervical Cytology and HPV DNA Test ▿

PubMed Central

Benevolo, Maria; Vocaturo, Amina; Caraceni, Donatella; French, Deborah; Rosini, Sandra; Zappacosta, Roberta; Terrenato, Irene; Ciccocioppo, Lucia; Frega, Antonio; Rossi, Paolo Giorgi

2011-01-01

There is evidence that testing for human papillomavirus (HPV) E6/E7 mRNA is more specific than testing for HPV DNA. A retrospective study was carried out to evaluate the performance of the PreTect HPV-Proofer E6/E7 mRNA assay (Norchip) as a triage test for cytology and HPV DNA testing. This study analyzed 1,201 women, 688 of whom had a colposcopy follow-up and 195 of whom had histology-confirmed high-grade intraepithelial neoplasia or worse (CIN2+). The proportion of positive results and the sensitivity and specificity for CIN2+ were determined for HPV mRNA in comparison to HPV DNA and cytology. All data were adjusted for follow-up completeness. Stratified by cytological grades, the HPV mRNA sensitivity was 83% (95% confidence interval [CI] = 63 to 94%) in ASC-US (atypical squamous cells of undetermined significance), 62% (95% CI = 47 to 75%) in L-SIL (low-grade squamous intraepithelial lesion), and 67% (95% CI = 57 to 76%) in H-SIL (high-grade squamous intraepithelial lesion). The corresponding figures were 99, 91, and 96%, respectively, for HPV DNA. The specificities were 82, 76, and 45%, respectively, for HPV mRNA and 29, 13, and 4%, respectively, for HPV DNA. Used as a triage test for ASC-US and L-SIL, mRNA reduced colposcopies by 79% (95% CI = 74 to 83%) and 69% (95% CI = 65 to 74%), respectively, while HPV DNA reduced colposcopies by 38% (95% CI = 32 to 44%) and by 15% (95% CI = 12 to 19%), respectively. As a HPV DNA positivity triage test, mRNA reduced colposcopies by 63% (95% CI = 60 to 66%), having 68% sensitivity (95% CI = 61 to 75%), whereas cytology at the ASC-US+ threshold reduced colposcopies by 23% (95% CI = 20 to 26%), showing 92% sensitivity (95% CI = 87 to 95%). In conclusion, PreTect HPV-Proofer mRNA can serve as a better triage test than HPV DNA to reduce colposcopy referral in both ASC-US and L-SIL. It is also more efficient than cytology for the triage of HPV DNA-positive women. Nevertheless, its low sensitivity demands a strict follow-up of HPV DNA positive-mRNA negative cases. PMID:21525231

Psychosocial Impact of Alternative Management Policies for Low-Grade Cervical Abnormalities: Results from the TOMBOLA Randomised Controlled Trial

PubMed Central

Little, Julian; Gray, Nicola M.; Cruickshank, Margaret; Smart, Louise; Thornton, Alison; Waugh, Norman; Walker, Leslie

2013-01-01

Background Large numbers of women who participate in cervical screening require follow-up for minor cytological abnormalities. Little is known about the psychological consequences of alternative management policies for these women. We compared, over 30-months, psychosocial outcomes of two policies: cytological surveillance (repeat cervical cytology tests in primary care) and a hospital-based colposcopy examination. Methods Women attending for a routine cytology test within the UK NHS Cervical Screening Programmes were eligible to participate. 3399 women, aged 20–59 years, with low-grade abnormal cytology, were randomised to cytological surveillance (six-monthly tests; n = 1703) or initial colposcopy with biopsies and/or subsequent treatment based on colposcopic and histological findings (n = 1696). At 12, 18, 24 and 30-months post-recruitment, women completed the Hospital Anxiety and Depression Scale (HADS). A subgroup (n = 2354) completed the Impact of Event Scale (IES) six weeks after the colposcopy episode or first surveillance cytology test. Primary outcomes were percentages over the entire follow-up period of significant depression (≥8) and significant anxiety (≥11; “30-month percentages”). Secondary outcomes were point prevalences of significant depression, significant anxiety and procedure-related distress (≥9). Outcomes were compared between arms by calculating fully-adjusted odds ratios (ORs) for initial colposcopy versus cytological surveillance. Results There was no significant difference in 30-month percentages of significant depression (OR = 0.99, 95% CI 0.80–1.21) or anxiety (OR = 0.97, 95% CI 0.81–1.16) between arms. At the six-week assessment, anxiety and distress, but not depression, were significantly less common in the initial colposcopy arm (anxiety: 7.9% vs 13.4%; OR = 0.55, 95% CI 0.38–0.81; distress: 30.6% vs 39.3%, OR = 0.67 95% CI 0.54–0.84). Neither anxiety nor depression differed between arms at subsequent time-points. Conclusions There was no difference in the longer-term psychosocial impact of management policies based on cytological surveillance or initial colposcopy. Policy-makers, clinicians, and women themselves can be reassured that neither management policy has a significantly greater psychosocial cost. Trial Registration Controlled-Trials.com ISRCTN 34841617 PMID:24386076

Silent High Grade Cervical Intraepithelial Neoplasia in Atypical Smears from Liquid Based Cervical Cytology - Three Years Experience in Thammasat University Hospital.

PubMed

Lertvutivivat, Supapen; Chanthasenanont, Athita; Chanthasenanont, Athita; Muangto, Teerapat; Nanthakomon, Tongta; Pongrojpaw, Densak; Bhamarapravatana, Kornkarn; Suwannarurk, Komsun

2016-01-01

To study the prevalence of CIN2+ diagnosis in women with atypical Papaniculoau (Pap) smears to suggest appropriate management option for Thai health care. Data from all patients with liquid based cytology with human papillomavirus (HPV) testing between May 2013 - May 2016 were collected from medical records. Women with atypical cervical Pap smears were recruited. Results for age, HPV testing, HPV 16, 18, 45 and other genotypes tested, colposcopic examination and histopathological assessment were all collected. Atypical smears were defined as atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells cannot be exclude high grade squamous intraepithelial lesion (ASC-H). A total of 2,144 cases were recruited. Twenty six women with ASC-US on cytology had high risk (HR) HPV detection while eight cases with ASC-H had HR-HPV (40.0% VS 72.7%, p=0.005). Among the 26 women with ASC-US cytology and positive HR-HPV, HPV type 16 (n=8, 30.8%), type 18 (n=1, 3.8%), type 45 (n=1, 3.8%) and other HPV types (n=17, 65.4%) were found. Eight women with ASC-H and positive HR-HPV demonstrated type 16 (n=6, 75%) and other HPV types (n=2, 25%). Fifty seven women with ASC-US had normal colposcopy, CIN1 and CIN2+ at percentages of 80.7 (46/57), 14.0 (8/57) and 5.3 (3/57), respectively. In the ASC-H group, 7 out of 10 women had normal colposcopy and three (30%) had CIN2+ results. In women with ASC-US cytology, immediate colposcopy is highly recommended. HPV testing can be performed if colposcopy is not an available option because there was high prevalence (5.3%) of CIN2+ in our findings. ASCCP recommendations for ASC-H that colposcopy should be performed on all ASC-H cases regardless of HPV result are thereby supported by the findings of this investigation.

[Assessment of the treatment with imiquimod in persistent infection by human papillomavirus with the polimerase chain reaction method].

PubMed

Hernández Quijano, Tomás; Illanes Aguiar, Berenice; Salas Linares, Natividad; Alarcón Romero, Luz del Carmen; Hernández Valencia, Marcelino

2006-06-01

Molecular studies have shown that oncogenic genotypes of human papillomavirus (HPV) are the main risk factor for cervical cancer development. Sub-clinical wound does not cause symptoms and is diagnosed by colposcopy or histology, in addition the latent infection is associated with the presence of DNA of the HPV, but when clinical and histological abnormalities are not presented only molecular techniques can detect this infection. To determine if complementary processing with imiquimod, recent medicament with powerful antiviral activity in vitro as in vivo, reduces the cervical persistence of HPV. This study was carried out with 87 patients, who had antecedents of HPV cervical and intraepithelial wound with low degree. Patients were divided as follows: treated with cryotherapy, cervical loop electrosurgical and imiquimod, all with diagnosis by cervical cytology, colposcopy and polymerase chain reaction (PCR) for HPV. At 3, 6 and 12 months after the processing, PCR, cervical cytology and colposcopy control were carried out again. Out of the 87 patients studied, 11% (10) patients treated with cervical cytology were positive for VPH; with colposcopy 8% (7) of patients and with PCR 40% (34) of patients; decreased persistence with combined methods of loop and imiquimod was obtained in 29% (5) patients; however, when utilized imiquimod alone, there were 55% (11) patients with persistence determined by PCR method. Imiquimod appears to be beneficial in 45% of the patients, in contrast with efficacy reported until 85% in genitals and annals warts, in addition, the capacity of eliminating the viruses has been shown, therefore it is possible that its potential effect could be observed long-time. It is evident that the percentages of viral detection are improved for PCR method, compared with indirect methods as cervical cytology and colposcopy, which is favorable when virus serotypes are of high degree of transformation and ablative methods should be conservatives due to fertility motives.

HPV testing as a triage for borderline or mild dyskaryosis on cervical cytology: results from the Sentinel Sites study.

PubMed

Kelly, R S; Patnick, J; Kitchener, H C; Moss, S M

2011-09-27

Earlier pilot studies of human papillomavirus (HPV) triage concluded that HPV triage was feasible and cost-effective. The aim of the present study was to study the impact of wider rollout of HPV triage for women with low-grade cytology on colposcopy referral and outcomes. Human papillomavirus testing of liquid-based cytology (LBC) samples showing low-grade abnormalities was used to select women for colposcopy referral at six sites in England. Samples from 10,051 women aged 25-64 years with routine call or recall cytology reported as borderline or mild dyskaryosis were included. Human papillomavirus-positive rates were 53.7% in women with borderline cytology and 83.9% in those with mild dyskaryosis. The range between sites was 34.8-73.3% for borderline cytology, and 73.4-91.6% for mild dyskaryosis. In the single site using both LBC technologies there was no difference in rates between the two technologies. The positive predictive value of an HPV test was 16.3% for CIN2 or worse and 6.1% for CIN3 or worse, although there was considerable variation between sites. Triaging women with borderline cytological abnormalities and mild dyskaryosis with HPV testing would allow approximately a third of these women to be returned immediately to routine recall, and for a substantial proportion to be referred for colposcopy without repeat cytology. Variation in HPV-positive rates results in differing colposcopy workload.

Management of low-grade cervical abnormalities detected at screening: which method do women prefer?

PubMed

Whynes, D K; Woolley, C; Philips, Z

2008-12-01

To establish whether women with low-grade abnormalities detected during screening for cervical cancer prefer to be managed by cytological surveillance or by immediate colposcopy. TOMBOLA (Trial of Management of Borderline and Other Low-grade Abnormal smears) is a randomized controlled trial comparing alternative management strategies following the screen-detection of low-grade cytological abnormalities. At exit, a sample of TOMBOLA women completed a questionnaire eliciting opinions on their management, contingent valuations (CV) of the management methods and preferences. Within-trial quality of life (EQ-5D) data collected for a sample of TOMBOLA women throughout their follow-up enabled the comparison of self-reported health at various time points, by management method. Once management had been initiated, self-reported health in the colposcopy arm rose relative to that in the surveillance arm, although the effect was short-term only. For the majority of women, the satisfaction ratings and the CV indicated approval of the management method to which they had been randomized. Of the minority manifesting a preference for the method which they had not experienced, relatively more would have preferred colposcopy than would have preferred surveillance. The findings must be interpreted in the light of sample bias with respect to preferences, whereby enthusiasm for colposcopy was probably over-represented amongst trial participants. The study suggests that neither of the management methods is preferred unequivocally; rather, individual women have individual preferences, although many would be indifferent between methods.

[CIN and pregnancy. Apropos of 16 cases and review of the literature].

PubMed

Giraud, J R; Poulain, P; Renaud-Giono, A; Burtin, F; Burtin, J F; Proudhon, J F; Levêque, J

1997-01-01

To assess the means to diagnose grade 3 cervical intraepithelial neoplasia (CIN 3) during pregnancy, with special consideration to the risk of overlooking invasive lesions. a retrospective study on 16 cases of CIN 3 over 4 years and a literature review. Smear tests were indicative of low-grade lesions in 8 cases. Colposcopy always was suggestive and accompanied by biopsy. No conisations were performed during pregnancy but one was performed after delivery in 15 of 16 cases. After delivery, comparing conisation results with those of recent biopsies revealed that some lesions were less severe and others more severe than during pregnancy. So, a CIN 3 and a microinvasive carcinoma observed during pregnancy changed into CIN 2 and CIN 3, respectively, after delivery. In contrast, two pregnancy CIN 2 were seen as CIN 3 in post-partum and three CIN 3 as MIC. Such variations have been described in the literature and have several causes. In particular, improvements may sometimes reach "normalisation" in post partum although, recurrences remain possible. when the smear tests performed during pregnancy are indicative of cervical intra-epithalial lesions, whatever the severity, colposcopy with biopsies are mandatory. If a CIN 3 is detected, early MIC should be removed, which may require specific treatment according to the invasive degree. Colposcopy with guided biopsies is a safe and reliable diagnostic means. After delivery, the cervix should always be reexamined, preferably by conisation, even if smears or colposcopy were normal.

Detection of Human Papillomavirus among Women with Atypical Squamous Cells of Undetermined Significance Referred to Colposcopy: Implications for Clinical Management in Low and MiddleIncome Countries.

PubMed

de Abreu, Andre Lp; Gimenes, Fabricia; Malaguti, Natalia; Pereira, Monalisa W; Uchimura, Nelson S; Consolaro, Marcia El

2016-01-01

To determine the prevalence of human papillomavirus (HPV) among women with atypical squamous cells of undetermined significance (ASC-US) referred to colposcopy and the implications for clinical management in low- and middle-income countries (LMIC), the present study was conducted. We included 200 women living in Maringa÷Brazil referred to colposcopy service between August 2012 and March 2013 due to an abnormal cytology from ASC-US until high-grade intraepithelial lesion (HSIL). HPV was detected and genotyped by polymerase chain reaction (PCR). The mean age was 36.8±10.5 years, and women with and without ASC-US had similar mean ages (37.4±11.5 and 36.4±9.96 years, respectively). The highest prevalence of ASC-US occurred at 20-24 years (40%). HPV-DNA was positive in 164 (82.0%) women.Of the 57 women with ASC-US, 30 (52.6%) were HPV-DNA-positive and 21 (70%) were high-risk HPV-positive (HR-HPV); the latter was similar to women without ASC-US (76.9%) but with other abnormal cytological findings present. Our data demonstrated that performing tests for HR-HPV can be used for management of women with ASC-US to support the decision of which women should be referred for an immediate or later colposcopy. The same conclusions can be applied to other LMICs for which HPV testing for primary screening has not been adopted.

[Overuse of colposcopy service in Mexico].

PubMed

Madrigal de la Campa, María de los Angeles; Lazcano Ponce, Eduardo Cesar; Infante Castañeda, Claudia

2005-12-01

Cervicouterine cancer is one of the main public health problems in Mexico. Several problems related to the low effectiveness of the Program of Opportune Detection of Cervicouterine Cancer have been identified, among them: low cover of the disease detection and absence of quality control in the detection, diagnosis and treatment of it. In Mexico the quality control problem in cytology has been taken with success, but the opposite occurs with colposcopy practice. For that reason this service is overused by patients with low risk cancer and is not accessible for the high risk population. To evaluate the association between cervicouterine cancer knowledge and satisfaction with the service regarding the use and intention of adherence to it for the follow-up and treatment, as well as analyze the resources used for this attention. A transversal study was done from May to December, 2002. It included all the patients who went to the Colposcopy Service in three hospitals. 1,606 patients were interviewed, from them 443 cases were first-time visits and 1,163 were subsequent ones. In a multivariate model we observed that the real utility knowledge of cervicovaginal cytology increases the probability that women come back to the Colposcopy Service (OR 2.0, Cl 95%: 1.57, 2.54). Patients who know their diagnosis when it is dysplasia or cancer are more likely to become attached to their follow-up than those who do not know it. 91% of the users (1,463) had two or more cervicovaginal cytolgies done, and 49% (787) had eight or more. Patients who know the purpose and utility of the biopsy had a 4.4 fold probability of become subsequent than those that do not know such information (Cl 95%: 1.72 to 11.35). Nowadays colposcopy clinics treat 70% of the patients who are subsequent and that have normal reports of cytology. This shows us an overuse of the service, with the consequent service, monetary and opportunity costs for women. More studies should be done to reformulate the rule that controls the treatment of these patients, and incorporate follow-up guidelines according to the natural history of the disease in Mexican women.

Evaluation of the accuracy in detecting cervical lesions by nurses versus doctors using a stationary colposcope and Gynocular in a low-resource setting.

PubMed

Nessa, Ashrafun; Roy, Joya Shree; Chowdhury, Most Afroza; Khanam, Quayuma; Afroz, Romena; Wistrand, Charlotte; Thuresson, Marcus; Thorsell, Malin; Shemer, Isaac; Wikström Shemer, Elisabeth Andrea

2014-11-03

Evaluation of the performance of VIA (visual inspection with acetic acid) trained nurses to learn colposcopy and the Swede score method to detect cervical lesions by using stationary colposcope or a portable, hand-held colposcope; the Gynocular, as compared to doctors. A crossover randomised clinical trial. The Colposcopy Clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. 932 women attending the clinic as either screening naïve for VIA screening (404) or women referred as VIA positive (528) from other VIA screening centres in the Dhaka region. VIA trained nurses were trained on-site in colposcopy and in the Swede score systematic colposcopy method. The Swede score grade cervical acetowhiteness, margins plus surface. vessel pattern, lesion size and iodine staining. The women were randomised to start the examination by either a stationary colposcope or the Gynocular. Swede scores were first obtained by a nurse and the same patient was equally evaluated by a doctor. Agreement between nurses and doctors in Swede scores was evaluated using the weighted κ statistic for the Gynocular and standard colposcope. The ability to predict CIN 2+ (CIN 2, CIN 3 and invasive cervical cancer) using Swede scores was evaluated using receiver-operating characteristic curves. The Swede scores obtained by nurses and doctors using the Gynocular and stationary colposcope showed high agreement with a κ statistic of 0.858 and 0.859, respectively, and no difference in detecting cervical lesions in biopsy. Biopsy detected CIN 2+ in 39 (4.2%) women. Our study showed that VIA nurses can perform colposcopy. There was no significant differences compared to doctors in detecting cervical lesions by stationary colposcope or the Gynocular using the Swede score system. Swede scores obtained by nurses using the Gynocular could offer an accurate cervical diagnostic approach in low resource settings. ISRCTN53264564. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A comparison of techniques to assess cervicovaginal irritation and evaluation of the variability between two observers.

PubMed

Ballagh, Susan A; Mauck, Christine K; Henry, Deborah; Archer, David F; Abercrombie, Theresa; Callahan, Marianne M; Gabelnick, Henry L

2004-09-01

Colposcopy is used to evaluate effects of new vaginal products on cervicovaginal epithelium as part of the US Food and Drug Administration-mandated product approval process, yet few aspects of its use have been investigated. To determine the effect of the colposcopic examination itself on the number and type of findings seen, to compare colposcopy with the AviScope hand-held device and the naked eye and to compare the findings reported by two examiners during a single visit. Fourteen healthy women volunteered for five paired examinations in random order: (1) naked eye inspection plus colposcopy done twice by a single examiner; (2) naked eye inspection plus AviScope examination, then naked eye inspection plus colposcopy by a single examiner; (3) Examination 2 repeated with the order of device reversed; (4) naked eye inspection plus colposcopy done by two examiners; (5) Examination 4 repeated with the order of examiner reversed. The colposcopic examinations were done per published standards but were limited to the areas visible without manipulation of the speculum. Length of colposcopic examination averaged 7 min. The number of colposcopic findings found when the examination was done twice by the same clinician was not statistically different (p = 0.12), suggesting that the examination itself did not induce findings. More findings were seen using magnification than naked eye. A similar number of findings were seen by AviScope compared to the colposcope (p = 0.99), but clinically significant findings were "undercalled" or "overcalled" by the AviScope. A weighted kappa score of the "worst" colposcopic finding was 0.32 (SE 0.10, p = 0.00), indicating moderate agreement between examiners. The colposcopic examination is not burdensome nor does it induce findings. If naked eye observation were used alone in practice, these data suggest that half the colposcopically detected findings would be missed. Using the naked eye observation for screening would minimally reduce the number of magnified observations carried out. For detecting epithelial changes, the colposcope seems to be the most sensitive technique, followed by the AviScope.

Telemedical cervical cancer screening to bridge medicaid service care gap for rural women.

PubMed

Hitt, Wilbur C; Low, Gordon; Bird, Tommy Mac; Ott, Rachel

2013-05-01

The Arkansas Medicaid program for low-income women provides cervical cancer screening, in the form of Pap smears, and treatment but no diagnostic means of bridging the two, such as a procedure called "colposcopy." Telemedicine offers a viable means to bridging this gap. Previously telecolposcopy has been used in small demonstration projects as a means to deliver colposcopy services to at-risk rural populations at a comparable quality to in-person colposcopy. The University of Arkansas for Medical Sciences' Antenatal & Neonatal Guidelines, Education and Learning System Program and Center for Distance Health developed an innovative collaborative telemedicine pilot program with the Arkansas Department of Health that used both specialty physician oversight and nurse examiners. Underserved rural patients from the Department of Health were provided with colposcopy services via interactive telemedicine at four separate spoke sites. During each weekly 3-h clinic, an advanced practice nurse/nurse practitioner at each of the spoke sites performed the exams and collected biopsy specimens under the real-time, interactive supervision of an experienced faculty member at the hub site. Between January 1, 2010 and June 21, 2011, the program scheduled 1,812 visits, involving 1,504 unduplicated patient referrals from 68 of Arkansas's 75 counties, and performed 1,298 telecolposcopic exams. This project provides complex specialty gynecological services using telemedicine technology to overcome geographic barriers to care while producing results comparable to traditional examinations. It is cost-effective and well received by patients and can be used as a model for improving access to care among vulnerable populations.

Decision-making in the colposcopy clinic--a critical analysis.

PubMed

Bornstein, J; Yaakov, Z; Pascal, B; Faktor, J; Baram, A; Zarfati, D; Abramovici, H

1999-08-01

To consider the omission of several diagnostic steps from the management of patients with high-grade squamous intraepithelial lesion (SIL) by analyzing the role of each step on the choice of treatment. Each diagnostic procedure was correlated to the treatment and outcome in 87 women with high-grade SIL. Treatments considered were large loop excision of the transformation zone (LLETZ) cold knife conization, and CO2 laser vaporization. Unsatisfactory colposcopy (P< or =0.01) and positive endocervical curettage (ECC) specimen (P< or =0.01) were essential for choice of treatment. CIN2 diagnoses of the preoperative cervical biopsy were rediagnosed as CIN3 based on the surgical specimen in 57% of the cases. The margins of 33 and 23% of surgical specimens removed by LLETZ or knife conization, respectively, displayed CIN involvement. Forty and 47% of these patients, respectively, later developed recurrent CIN. Omission of colposcopy and ECC could have resulted in sub-optimal treatment in many cases. Excision by LLETZ or knife conization is recommended for cases of CIN2 and CIN3. Follow up is imperative for patients with involvement of the margins.

A systematic review of randomized trials assessing human papillomavirus testing in cervical cancer screening

PubMed Central

Patanwala, Insiyyah Y.; Bauer, Heidi M.; Miyamoto, Justin; Park, Ina U.; Huchko, Megan J.; Smith-McCune, Karen K.

2013-01-01

Our objective was to assess the sensitivity and specificity of human papillomavirus (HPV) testing for cervical cancer screening in randomized trials. We conducted a systematic literature search of the following databases: MEDLINE, CINAHL, EMBASE, and Cochrane. Eligible studies were randomized trials comparing HPV-based to cytology-based screening strategies, with disease status determined by colposcopy/biopsy for participants with positive results. Disease rates (cervical intraepithelial neoplasia [CIN]2 or greater and CIN3 or greater), sensitivity, and positive predictive value were abstracted or calculated from the articles. Six studies met inclusion criteria. Relative sensitivities for detecting CIN3 or greater of HPV testing-based strategies vs cytology ranged from 0.8 to 2.1. The main limitation of our study was that testing methodologies and screening/management protocols were highly variable across studies. Screening strategies in which a single initial HPV-positive test led to colposcopy were more sensitive than cytology but resulted in higher colposcopy rates. These results have implications for cotesting with HPV and cytology as recommended in the United States. PMID:23159693

Is atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesion clinically significant?

PubMed

McHale, Michael T; Souther, Jessica; Elkas, John C; Monk, Bradley J; Harrison, Terry A

2007-04-01

To determine the cumulative risk of cervical intraepithelial neoplasia (CIN) 2 or 3 in patients with atypical squamous cells, cannot exclude HSIL (ASC-H). A retrospective analysis was performed to identify patients referred to the dysplasia clinic with ASC-H. Initial evaluation included colposcopy, endocervical curettage, and an ectocervical biopsy, when indicated, in all the patients. A follow-up evaluation was performed at 6 and 12 months. Cumulative histological diagnosis of CIN 2 or 3 at 12 months served as the clinical end point. Two hundred twenty-nine patients with ASC-H and with a mean age of 32.8 years were evaluated. At the time of initial colposcopy, only 10.0% (23/229; 95% CI = 6.5%-15%) of the patients had histological evidence of CIN 2 or 3. The cumulative risk of CIN 2 or 3 was 12.2% (95% CI = 8%-17%). Evaluation of patients with ASC-H with colposcopy does lead to the detection of CIN 2 or 3 but perhaps at a rate lower than previously reported.

Cost-effective management of women with minor cervical lesions: Revisiting the application of HPV DNA testing.

PubMed

Pedersen, Kine; Burger, Emily A; Sy, Stephen; Kristiansen, Ivar S; Kim, Jane J

2016-11-01

Lack of consensus in management guidelines for women with minor cervical lesions, coupled with novel screening approaches, such as human papillomavirus (HPV) genotyping, necessitate revisiting prevention policies. We evaluated the cost-effectiveness and resource trade-offs of alternative triage strategies to inform cervical cancer prevention in Norway. We used a decision-analytic model to compare the lifetime health and economic consequences associated with ten novel candidate approaches to triage women with minor cervical lesions. Candidate strategies varied by: 1) the triage test(s): HPV testing in combination with cytology, HPV testing alone with or without genotyping for HPV-16 and -18, and immediate colposcopy, and 2) the length of time between index and triage testing (i.e., 6, 12 or 18months). Model outcomes included quality-adjusted life-years (QALYs), lifetime societal costs, and resource use (e.g., colposcopy referrals). The current Norwegian guidelines were less effective and more costly than candidate strategies. Given a commonly-cited willingness-to-pay threshold in Norway of $100,000 per QALY gained, the preferred strategy involved HPV genotyping with immediate colposcopy referral for HPV-16 or -18 positive and repeat HPV testing at 12months for non-HPV-16 or -18 positive ($78,010 per QALY gained). Differences in health benefits among candidate strategies were small, while resource use varied substantially. More effective strategies required a moderate increase in colposcopy referrals (e.g., a 9% increase for the preferred strategy) compared with current levels. New applications of HPV testing may improve management of women with minor cervical lesions, yet are accompanied by a trade-off of increased follow-up procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

Cost-effective management of women with minor cervical lesions: Revisiting the application of HPV DNA testing

PubMed Central

Pedersen, Kine; Burger, Emily A.; Sy, Stephen; Kristiansen, Ivar S.; Kim, Jane J.

2016-01-01

Background Lack of consensus in management guidelines for women with minor cervical lesions, coupled with novel screening approaches, such as human papillomavirus (HPV) genotyping, necessitate revisiting prevention policies. We evaluated the cost-effectiveness and resource trade-offs of alternative triage strategies to inform cervical cancer prevention in Norway. Methods We used a decision-analytic model to compare the lifetime health and economic consequences associated with ten novel candidate approaches to triage women with minor cervical lesions. Candidate strategies varied by: 1) the triage test(s): HPV testing in combination with cytology, HPV testing alone with or without genotyping for HPV-16 and-18, and immediate colposcopy, and 2) the length of time between index and triage testing (i.e., 6, 12 or 18 months). Model outcomes included quality-adjusted life-years (QALYs), lifetime societal costs, and resource use (e.g., colposcopy referrals). Results The current Norwegian guidelines were less effective and more costly than candidate strategies. Given a commonly-cited willingness-to-pay threshold in Norway of $100,000 per QALY gained, the preferred strategy involved HPV genotyping with immediate colposcopy referral for HPV-16 or -18 positive and repeat HPV testing at 12 months for non-HPV-16 or -18 positive ($78,010 per QALY gained). Differences in health benefits among candidate strategies were small, while resource use varied substantially. More effective strategies required a moderate increase in colposcopy referrals (e.g., a 9% increase for the preferred strategy) compared with current levels. Conclusion New applications of HPV testing may improve management for women with minor cervical lesions, yet are accompanied by a trade-off of increased follow-up procedures. PMID:27542966

The Ideal Strategy for Cervical Cancer Screening in Japan: Result from the Fukui Cervical Cancer Screening Study.

PubMed

Kurokawa, T; Onuma, T; Shinagawa, A; Chino, Y; Kobayashi, M; Yoshida, Y

2018-05-16

The aims of the Fukui Cervical Cancer Screening (FCCS) study are to determine the frequency of women with high-risk HPV (hrHPV), whether HPV16 or HPV18 (HPV16/18), in the Japanese cancer screening population for the first time and to identify the best strategy for cervical cancer screening in Japan. This study enrolled 7,584 women ≥25 years of age who were undergoing routine screening. All women underwent liquid-based cytology and cobas HPV tests. Women with abnormal cytology, whether hrHPV positive or negative; women with hrHPV positivity with either normal or abnormal cytology; and women randomly selected from women with normal cytology and negative hrHPV negative were referred for colposcopy. The prevalences of hrHPV positivity and HPV16/18 positivity were 6.8% and 1.7%, respectively. The baseline data from the FCCS study showed that the combination of HPV tests and cytology was more sensitive than cytology with respect to the detection of intraepithelial neoplasia grade 2 or worse. However, the specificity (94.1%) of the co-testing strategy that required all women with abnormal cytology or hrHPV positivity to be referred for colposcopy was much lower than that (97.8%) of cytology. The sensitivity and specificity of the co-testing strategy that required only women with abnormal cytology or HPV16/18 positivity to undergo colposcopy were 85.5% and 97.0%, respectively. The baseline data from the FCCS study suggest that a cervical cancer screening strategy in which only women with abnormal cytology or HPV16/18 positivity undergo colposcopy offers a more balanced sensitivity and specificity than other strategies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Impact of post-colposcopy management on women's long-term worries: results from the UK population-based TOMBOLA trial.

PubMed

Sharp, Linda; Cotton, Seonaidh; Cruickshank, Margaret; Gray, Nicola; Smart, Louise; Whynes, David; Little, Julian

2016-01-01

Effective cervical screening reduces cancer incidence and mortality. However, these benefits may be accompanied by some harms, potentially including, adverse psychological impacts. Studies suggest women may have concerns about various specific issues, such as cervical cancer. To compare worries about cervical cancer, future fertility, having sex, and general health between women managed by alternative policies at colposcopy. Multicentre individually-randomised controlled trial, nested within the National Health Service Cervical Screening Programmes. UK. 1515 women, aged 20-59 years, with low-grade cytology who attended colposcopy during February 2001-October 2002, were randomised to immediate loop excision or punch biopsies with recall for treatment if cervical intraepithelial neoplasia (CIN)2/3 was confirmed. Women completed questionnaires at recruitment and after 12, 18, 24 and 30 months. Outcomes were prevalence of worries at each time-point (point prevalence) and at any time-point during follow-up (12-30 months; cumulative prevalence). Primary analysis was by intention-to-treat (ITT); secondary per-protocol analysis compared groups according to management received among women with an abnormal transformation zone. Cumulative prevalence of worries was: cervical cancer 40%; having sex 26%, future fertility 24%, and general health 60%. In ITT analyses, there were no statistically significant differences between management arms in cumulative or point prevalence of any of the worries. In per-protocol analyses, between-group differences were significant only for future fertility; cumulative prevalence was highest in women who underwent punch biopsies and treatment. There is no difference in the prevalence of specific worries in women randomised to alternative post-colposcopy management policies. 34841617. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Psychosocial morbidity in women with abnormal cervical cytology managed by cytological surveillance or initial colposcopy: longitudinal analysis from the TOMBOLA randomised trial.

PubMed

Fielding, S; Rothnie, K; Gray, N M; Little, J; Cruickshank, M E; Neal, K; Walker, L G; Whynes, D; Cotton, S C; Sharp, L

2017-04-01

To compare psychosocial outcomes (follow-up related worries and satisfaction with follow-up related information and support) over 30 months of two alternative management policies for women with low-grade abnormal cervical cytology. Women aged 20-59 years with low-grade cytological abnormalities detected in the National Health Service Cervical Screening Programme were randomised to cytological surveillance or initial colposcopy. A total of 3399 women who completed psychosocial questionnaires at recruitment were invited to complete questionnaires at 12, 18, 24 and 30 months. Linear mixed models were used to investigate differences between arms in the two psychosocial outcomes. Each outcome had a maximum score of 100, and higher scores represented higher psychosocial morbidity. On average, over 30 months, women randomised to colposcopy scored 2.5 points (95%CI -3.6 to -1.3) lower for follow-up related worries than women randomised to cytological surveillance. Women in the colposcopy arm also scored significantly lower for follow-up related satisfaction with information and support (-2.4; -3.3 to -1.4) over 30 months. For both outcomes, the average difference between arms was greatest at 12th- and 18th-month time points. These differences remained when the analysis was stratified by post-school education. Women with low-grade cytology, irrespective of their management, have substantial initial psychosocial morbidity that reduces over time. Implementation of newer screening strategies, which include surveillance, such as primary HPV screening, need to consider the information and support provided to women. © 2016 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd. © 2016 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.

HPV E6/E7 mRNA Testing Is More Specific than Cytology in Post-Colposcopy Follow-Up of Women with Negative Cervical Biopsy

PubMed Central

Sørbye, Sveinung Wergeland; Arbyn, Marc; Fismen, Silje; Gutteberg, Tore Jarl; Mortensen, Elin Synnøve

2011-01-01

Background In Norway, women with negative or low-grade cervical biopsies (normal/CIN1) are followed up after six months in order to decide on further follow-up or recall for screening at three-year intervals. A high specificity and positive predictive value (PPV) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures whereas a low risk of high-grade disease among triage negative women assures safety. Materials and Methods At the University Hospital of North Norway, cytology and the HPV mRNA test PreTect HPV-Proofer, detecting E6/E7 mRNA from HPV types 16, 18, 31, 33 and 45, are used in post-colposcopy follow-up of women with negative or low-grade biopsy. In this study, women with negative biopsy after high grade cytology (ASC-H/HSIL) and/or positive HPV mRNA test in the period 2005–2009 were included (n = 520). Histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) was used as study endpoint. Results Of 520 women with negative or low-grade biopsy, 124 women (23.8%) had CIN2+ in follow-up biopsy. The sensitivity and specificity of the HPV mRNA test were 89.1% (95% CI, 80.1–98.1) and 92.5% (95% CI, 88.2–96.7), respectively. The ratios of sensitivity, specificity and PPV of HPV mRNA testing compared to repeat cytology for finding CIN2+ was 1.05 (95% CI: 0.92–1.21), 1.21 (95% CI: 1.12–1.32), and 1.49 (95% CI: 1.20–1.86), respectively. The PPV of mRNA was 77.3% (95% CI, 59.8–94.8) in women aged 40 or older. Conclusion Women with negative cervical biopsy require follow-up before resumption of routine screening. Post-colposcopy HPV mRNA testing was as sensitive but more specific than post-colposcopy cytology. In addition, the HPV mRNA test showed higher PPV. A positive mRNA test post-colposcopy could justify treatment in women above 40 years. PMID:21998748

Performance of ProEx C and PreTect HPV-Proofer E6/E7 mRNA tests in comparison with the hybrid capture 2 HPV DNA test for triaging ASCUS and LSIL cytology.

PubMed

Alaghehbandan, Reza; Fontaine, Daniel; Bentley, James; Escott, Nicholas; Ghatage, Prafull; Lear, Adrian; Coutlee, Francois; Ratnam, Samuel

2013-09-01

The clinical usefulness of the ProEx C (Becton Dickinson) and PreTect HPV-Proofer E6/E7 mRNA tests (Proofer; Norchip) for the triage of ASCUS and LSIL cytology was determined in comparison with the Hybrid Capture 2 HPV DNA test (HC2; Qiagen). The study population consisted of women with a history of abnormal cytology referred to colposcopy. Histology-confirmed CIN 2+ served as the disease endpoint. The study was based on 1,360 women (mean age 30.7 years), of whom 380 had CIN 2+. Among 315 with ASCUS (CIN 2+, n = 67), the sensitivities of ProEx C, Proofer, and HC2 to detect CIN 2+ were, 71.6, 71.6, and 95.5%, respectively, with a corresponding specificity of 74.6, 74.2, and 35.1%. Among 363 with LSIL (CIN 2+, n = 108), the sensitivities of ProEx C, Proofer, and HC2 were, 67.6, 74.1, and 96.3%, respectively, with a corresponding specificity of 60, 68.2, and 18.4%. Among 225 HC2-positive ASCUS (CIN 2+, n = 64), 105 tested positive by ProEx C, reducing colposcopy referral by 53.3% and detecting 71.9% of CIN 2+; Proofer was positive in 112/225, reducing colposcopy referral by 50.2% and detecting 75.0% of CIN 2+. Among 312 HC2-positive LSIL (CIN 2+, n = 104), 160 tested positive by ProEx C, reducing coloposcopy referral by 48.7% and detecting 66.3% of CIN 2+; Proofer was positive in 159/312, reducing colposcopy referral by 49.0% and detecting 75.0% of CIN 2+. In conclusion, both ProEx C and Proofer have a similar performance profile with a significantly higher specificity but lower sensitivity than HC2 for the detection of CIN 2+. Consequently, although they can reduce colposcopy referral, they will miss a proportion of CIN 2+ cases. This is a major limitation and should be taken into account if these tests are considered for ASCUS or LSIL triage. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy: multicentre randomised controlled trial.

PubMed

2009-07-28

To compare the effectiveness of punch biopsy and selective recall for treatment versus a policy of immediate treatment by large loop excision in the management of women with low grade abnormal cervical cytology referred for colposcopy. Multicentre individually randomised controlled trial, nested within the NHS cervical screening programmes. Grampian, Tayside, and Nottingham. 1983 women, aged 20-59, with cytology showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002. Immediate large loop excision or up to four targeted punch biopsies taken immediately with recall for treatment (by large loop excision) if these showed cervical intraepithelial neoplasia grade II or III or worse. Participants were followed for three years, concluding with an exit colposcopy. Clinical end points: cumulative incidence of cervical intraepithelial neoplasia grade II or worse and grade III or worse at three years. Clinically significant anxiety and depression and self reported after effects assessed six weeks after colposcopy, biopsies, or large loop excision. 879 women (44%) had a normal transformation zone at colposcopy and had no further procedures at that time. Colposcopists were less likely to classify the transformation zone as abnormal when the allocation was large loop excision (603 (60%) in the biopsy and selective recall group; 501 (51%) in the immediate large loop excision group). Of women randomised to biopsy and recall, 157 (16%) required a second clinic visit for treatment. Specimens from almost 60% (n=296) of women who underwent immediate large loop excision showed no cervical intraepithelial neoplasia (31%; n=156) or showed cervical intraepithelial neoplasia grade I (28%; n=140). The percentages of women diagnosed with grade II or worse up to and including the exit examination were 22% (n=216) in the biopsy and recall arm and 23% (n=228) in the immediate large loop excision arm. There was no significant difference between the arms in cumulative incidence of cervical intraepithelial neoplasia grade II or worse (adjusted relative for risk large loop excision v biopsy 1.04, 95% confidence interval 0.86 to 1.25) or grade III or worse (1.03, 0.79 to 1.34). A greater proportion of disease was detected at initial investigation and less during follow-up and at exit in the immediate large loop excision arm, but time of detection did not differ significantly between arms. Levels of anxiety and depression and reported pain did not differ between arms. Higher proportions of women randomised to large loop excision reported moderate or more severe bleeding and discharge. A policy of targeted punch biopsies with subsequent treatment for cervical intraepithelial neoplasia grade II or III and cytological surveillance for grade I or less provides the best balance between benefits and harms for the management of women with low grade abnormal cytology referred for colposcopy. Immediate large loop excision results in overtreatment and more after effects and should not be recommended. ISRCTN 34841617.

Median Filter Noise Reduction of Image and Backpropagation Neural Network Model for Cervical Cancer Classification

NASA Astrophysics Data System (ADS)

Wutsqa, D. U.; Marwah, M.

2017-06-01

In this paper, we consider spatial operation median filter to reduce the noise in the cervical images yielded by colposcopy tool. The backpropagation neural network (BPNN) model is applied to the colposcopy images to classify cervical cancer. The classification process requires an image extraction by using a gray level co-occurrence matrix (GLCM) method to obtain image features that are used as inputs of BPNN model. The advantage of noise reduction is evaluated by comparing the performances of BPNN models with and without spatial operation median filter. The experimental result shows that the spatial operation median filter can improve the accuracy of the BPNN model for cervical cancer classification.

Optimization of Classification Strategies of Acetowhite Temporal Patterns towards Improving Diagnostic Performance of Colposcopy

PubMed Central

Acosta-Mesa, Héctor Gabriel; Cruz-Ramírez, Nicandro; Hernández-Jiménez, Rodolfo

2017-01-01

Efforts have been being made to improve the diagnostic performance of colposcopy, trying to help better diagnose cervical cancer, particularly in developing countries. However, improvements in a number of areas are still necessary, such as the time it takes to process the full digital image of the cervix, the performance of the computing systems used to identify different kinds of tissues, and biopsy sampling. In this paper, we explore three different, well-known automatic classification methods (k-Nearest Neighbors, Naïve Bayes, and C4.5), in addition to different data models that take full advantage of this information and improve the diagnostic performance of colposcopy based on acetowhite temporal patterns. Based on the ROC and PRC area scores, the k-Nearest Neighbors and discrete PLA representation performed better than other methods. The values of sensitivity, specificity, and accuracy reached using this method were 60% (95% CI 50–70), 79% (95% CI 71–86), and 70% (95% CI 60–80), respectively. The acetowhitening phenomenon is not exclusive to high-grade lesions, and we have found acetowhite temporal patterns of epithelial changes that are not precancerous lesions but that are similar to positive ones. These findings need to be considered when developing more robust computing systems in the future. PMID:28744318

Diagnostic value of the 2011 International Federation for Cervical Pathology and Colposcopy Terminology in predicting cervical lesions.

PubMed

Fan, Aiping; Wang, Chen; Zhang, Liqin; Yan, Ye; Han, Cha; Xue, Fengxia

2018-02-06

To evaluate the diagnostic accuracy of the 2011 International Federation for Cervical Pathology and Colposcopy (IFCPC) colposcopic terminology. The clinicopathological data of 2262 patients who underwent colposcopy from September 2012 to September 2016 were reviewed. The colposcopic findings, colposcopic impression, and cervical histopathology of the patients were analyzed. Correlations between variables were evaluated using cervical histopathology as the gold standard. Colposcopic diagnosis matched biopsy histopathology in 1482 patients (65.5%), and the weighted kappa strength of agreement was 0.480 (P<0.01). Colposcopic diagnoses more often underestimated (22.1%) than overestimated (12.3%) cervical pathology. There was no significant difference between the colposcopic diagnosis and cervical pathology agreement among the various grades of lesions (P=0.282). The sensitivity, specificity for detecting high-grade lesions/carcinoma was 71.6% and 98.0%, respectively. Multivariate analysis showed that major changes were independent factors in predicting high-grade lesion/carcinoma, whereas transformation zone, lesion size, and non-stained were not statistically related to high-grade lesion/carcinoma. The 2011 IFCPC terminology can improve the diagnostic accuracy for all lesion severities. The categorization of major changes and minor changes is appropriate. However, colposcopic diagnosis remains unsatisfactory. Poor reproducibility of type 2 transformation zone and the significance of leukoplakia require further study.

Use of Cytology, E6/E7 mRNA, and p16INK4a-Ki-67 to Define the Management of Human Papillomavirus (HPV)-Positive Women in Cervical Cancer Screening.

PubMed

Gustinucci, Daniela; Giorgi Rossi, Paolo; Cesarini, Elena; Broccolini, Massimo; Bulletti, Simonetta; Carlani, Angela; D'angelo, Valentina; D'amico, Maria Rosaria; Di Dato, Eugenio; Galeazzi, Paola; Malaspina, Morena; Martinelli, Nadia; Spita, Nicoletta; Tintori, Beatrice; Giaimo, Maria Donata; Passamonti, Basilio

2016-01-01

We measured the accuracy of p16(INK4a)-Ki67 (CINtec PLUS, Roche, Mannheim, Germany), and E6/E7mRNA (types 16/18/31/33/45 NucliSENS easyQ, bioMérieux, Boxtel, The Netherlands) as triage test, alone and combined with cytology. Six thousand two hundred and seventy two women were recruited in a population-based screening using HPV DNA as primary test; 396 were positive and were tested for cytology and biomarkers. All tests were performed on the same sample. Cytology-positive women were referred to colposcopy; cytology-negative women were referred to one-year HPV re-testing. The endpoint was CIN2+ at baseline or follow up. Sensitivity was 77.6% (95% confidence interval (CI) 65.3-86.7) and 53.2% (95%CI: 40.3-65.4) for cytology at atypical squamous cells of undetermined significance (ASC-US) and high-grade threshold, and 87.6% (95%CI:75.7-93.6), and 80.8% (95%CI: 67.6-89.8) for p16INK4a-Ki67, and E6/E7mRNA, respectively. Colposcopy referral was 36% (95%CI: 31.2-40.9) and 11.2% (95%CI: 7.8-14.1) for cytology at ASC-US and high-grade threshold, respectively, and 36.0% (95%CI: 29.9-29.6), and 47.5% (95%CI: 32.5-42.4) for p16(INK4a)-Ki67, and E6/E7mRNA, respectively. Strategies referring high-grade cytology or biomarker positive women to colposcopy reached sensitivity close to 100%, with modest increase in colposcopy referral. The high sensitivity of combined strategies probably allows longer intervals in HPV-positive, triage-negative women. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Attendance at cervical cancer screening and use of diagnostic and therapeutic procedures on the uterine cervix assessed from individual health insurance data (Belgium, 2002-2006).

PubMed

Arbyn, Marc; Fabri, Valérie; Temmerman, Marleen; Simoens, Cindy

2014-01-01

To assess the coverage for cervical cancer screening as well as the use of cervical cytology, colposcopy and other diagnostic and therapeutic interventions on the uterine cervix in Belgium, using individual health insurance data. The Intermutualistic Agency compiled a database containing 14 million records from reimbursement claims for Pap smears, colposcopies, cervical biopsies and surgery, performed between 2002 and 2006. Cervical cancer screening coverage was defined as the proportion of women aged 25-64 that had a Pap smear within the last 3 years. Cervical cancer screening coverage was 61% at national level, for the target population of women between 25 and 64 years old, in the period 2004-2006. Differences between the 3 regions were small, but varied more substantially between provinces. Coverage was 70% for 25-34 year old women, 67% for those aged 35-39 years, and decreased to 44% in the age group of 60-64 years. The median screening interval was 13 months. The screening coverage varied substantially by social category: 40% and 64%, in women categorised as beneficiary or not-beneficiary of increased reimbursement from social insurance, respectively. In the 3-year period 2004-2006, 3.2 million screen tests were done in the target group consisting of 2.8 million women. However, only 1.7 million women got one or more smears and 1.1 million women had no smears, corresponding to an average of 1.88 smears per woman in three years of time. Colposcopy was excessively used (number of Pap smears over colposcopies = 3.2). The proportion of women with a history of conisation or hysterectomy, before the age of 65, was 7% and 19%, respectively. The screening coverage increased slightly from 59% in 2000 to 61% in 2006. The screening intensity remained at a high level, and the number of cytological examinations was theoretically sufficient to cover more than the whole target population.

Informed cytology for triaging HPV-positive women: substudy nested in the NTCC randomized controlled trial.

PubMed

Bergeron, Christine; Giorgi-Rossi, Paolo; Cas, Frederic; Schiboni, Maria Luisa; Ghiringhello, Bruno; Dalla Palma, Paolo; Minucci, Daria; Rosso, Stefano; Zorzi, Manuel; Naldoni, Carlo; Segnan, Nereo; Confortini, Massimo; Ronco, Guglielmo

2015-02-01

Human papillomavirus (HPV)-based screening needs triage. In most randomized controlled trials (RCTs) on HPV testing with cytological triage, cytology interpretation has been blind to HPV status. Women age 25 to 60 years enrolled in the New Technology in Cervical Cancer (NTCC) RCT comparing HPV testing with cytology were referred to colposcopy if HPV positive and, if no cervical intraepithelial neoplasia (CIN) was detected, followed up until HPV negativity. Cytological slides taken at the first colposcopy were retrieved and independently interpreted by an external laboratory, which was only aware of patients' HPV positivity. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were computed for histologically proven CIN2+ with HPV status-informed cytology for women with a determination of atypical squamous cells of undetermined significance (ASCUS) or more severe. All statistical tests were two-sided. Among HPV-positive women, informed cytology had cross-sectional sensitivity, specificity, PPV and 1-NPV for CIN2+ of 85.6% (95% confidence interval [CI] = 76.6 to 92.1), 65.9% (95% CI = 63.1 to 68.6), 16.2% (95% CI = 13.0 to 19.8), and 1.7 (95% CI = 0.9 to 2.8), respectively. Cytology was also associated with subsequent risk of newly diagnosed CIN2+ and CIN3+. The cross-sectional relative sensitivity for CIN2+ vs blind cytology obtained by referring to colposcopy and following up only HPV positive women who had HPV status-informed cytology greater than or equal to ASCUS was 1.58 (95% CI = 1.22 to 2.01), while the corresponding relative referral to colposcopy was 0.95 (95% CI = 0.86 to 1.04). Cytology informed of HPV positivity is more sensitive than blind cytology and could allow longer intervals before retesting HPV-positive, cytology-negative women. © The Author 2015. Published by Oxford University Press.

Informed Cytology for Triaging HPV-Positive Women: Substudy Nested in the NTCC Randomized Controlled Trial

PubMed Central

Bergeron, Christine; Giorgi-Rossi, Paolo; Cas, Frederic; Schiboni, Maria Luisa; Ghiringhello, Bruno; Dalla Palma, Paolo; Minucci, Daria; Rosso, Stefano; Zorzi, Manuel; Naldoni, Carlo; Segnan, Nereo; Confortini, Massimo

2015-01-01

Background: Human papillomavirus (HPV)–based screening needs triage. In most randomized controlled trials (RCTs) on HPV testing with cytological triage, cytology interpretation has been blind to HPV status. Methods: Women age 25 to 60 years enrolled in the New Technology in Cervical Cancer (NTCC) RCT comparing HPV testing with cytology were referred to colposcopy if HPV positive and, if no cervical intraepithelial neoplasia (CIN) was detected, followed up until HPV negativity. Cytological slides taken at the first colposcopy were retrieved and independently interpreted by an external laboratory, which was only aware of patients’ HPV positivity. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were computed for histologically proven CIN2+ with HPV status–informed cytology for women with a determination of atypical squamous cells of undetermined significance (ASCUS) or more severe. All statistical tests were two-sided. Results: Among HPV-positive women, informed cytology had cross-sectional sensitivity, specificity, PPV and 1-NPV for CIN2+ of 85.6% (95% confidence interval [CI] = 76.6 to 92.1), 65.9% (95% CI = 63.1 to 68.6), 16.2% (95% CI = 13.0 to 19.8), and 1.7 (95% CI = 0.9 to 2.8), respectively. Cytology was also associated with subsequent risk of newly diagnosed CIN2+ and CIN3+. The cross-sectional relative sensitivity for CIN2+ vs blind cytology obtained by referring to colposcopy and following up only HPV positive women who had HPV status–informed cytology greater than or equal to ASCUS was 1.58 (95% CI = 1.22 to 2.01), while the corresponding relative referral to colposcopy was 0.95 (95% CI = 0.86 to 1.04). Conclusions: Cytology informed of HPV positivity is more sensitive than blind cytology and could allow longer intervals before retesting HPV-positive, cytology-negative women. PMID:25568167

Guidelines for HPV-DNA Testing for Cervical Cancer Screening in Brazil.

PubMed

Zeferino, Luiz Carlos; Bastos, Joana Bragança; Vale, Diama Bhadra Andrade Peixoto do; Zanine, Rita Maria; Melo, Yara Lucia Mendes Furtado de; Primo, Walquíria Quida Salles Pereira; Corrêa, Flávia de Miranda; Val, Isabel Cristina Chulvis do; Russomano, Fábio

2018-06-06

Evidence-based clinical guidelines ensure best practice protocols are available in health care. There is a widespread use of human papillomavirus deoxyribonucleic acid (HPV-DNA) tests in Brazil, regardless of the lack of official guidelines. On behalf of the Brazilian Association for the Lower Genital Tract Pathology and Colposcopy (ABPTGIC, in the Portuguese acronym), a team of reviewers searched for published evidence and developed a set of recommendations for the use of HPV-DNA tests in cervical cancer screening in Brazil. The product of this process was debated and consensus was sought by the participants. One concern of the authors was the inclusion of these tests in the assessment of women with cytologic atypia and women treated for cervical intraepithelial neoplasia (CIN). Testing for HPV is recommended in an organized screening scenario to identify women with precursor lesions or asymptomatic cervical cancer older than 30 years of age, and it can be performed every 5 years. It also has value after the cytology showing atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSILs) as a triage test for colposcopy, in the investigation of other cytological alterations when no abnormal findings are observed at colposcopy, seeking to exclude disease, or, further, after treatment of high-grade cervical intraepithelial neoplasia, to rule out residual disease. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

Introducing a High-Risk HPV DNA Test Into a Public Sector Screening Program in El Salvador.

PubMed

Cremer, Miriam L; Maza, Mauricio; Alfaro, Karla M; Kim, Jane J; Ditzian, Lauren R; Villalta, Sofia; Alonzo, Todd A; Felix, Juan C; Castle, Philip E; Gage, Julia C

2016-04-01

In a primary human papillomavirus (HPV) screening program, we compared the 6-month follow-up among colposcopy and noncolposcopy-based management strategies for screen-positive women. Women aged 30 to 49 years were screened with HPV DNA tests using both self-collection and provider collection of samples. Women testing positive received either (1) colposcopy management (CM) consisting of colposcopy and management per local guidelines or (2) screen-and-treat (ST) management using visual inspection with acetic acid to determine cryotherapy eligibility, with eligible women undergoing immediate cryotherapy. One thousand women were recruited in each cohort. Of these, 368 (18.4%) of 2000 women were recruited using a more intensive outreach strategy. Demographics, HPV positivity, and treatment compliance were compared across recruitment and management strategies. More women in the ST cohort received treatment within 6 months compared with those in the CM cohort (117/119 [98.3%] vs 64/93 [68.8%]; p < .001). Women recruited through more intensive outreach were more likely to be HPV positive, lived in urban areas, were more educated, and had higher numbers of lifetime sexual partners and fewer children. Women in the CM arm were less likely to complete care than women in the ST arm. Targeted outreach to underscreened women successfully identified women with higher prevalence of HPV and possibly higher disease burden.

Diagnostic value of the 2011 International Federation for Cervical Pathology and Colposcopy Terminology in predicting cervical lesions

PubMed Central

Zhang, Liqin; Yan, Ye; Han, Cha; Xue, Fengxia

2018-01-01

Objective To evaluate the diagnostic accuracy of the 2011 International Federation for Cervical Pathology and Colposcopy (IFCPC) colposcopic terminology. Methods The clinicopathological data of 2262 patients who underwent colposcopy from September 2012 to September 2016 were reviewed. The colposcopic findings, colposcopic impression, and cervical histopathology of the patients were analyzed. Correlations between variables were evaluated using cervical histopathology as the gold standard. Results Colposcopic diagnosis matched biopsy histopathology in 1482 patients (65.5%), and the weighted kappa strength of agreement was 0.480 (P<0.01). Colposcopic diagnoses more often underestimated (22.1%) than overestimated (12.3%) cervical pathology. There was no significant difference between the colposcopic diagnosis and cervical pathology agreement among the various grades of lesions (P=0.282). The sensitivity, specificity for detecting high-grade lesions/carcinoma was 71.6% and 98.0%, respectively. Multivariate analysis showed that major changes were independent factors in predicting high-grade lesion/carcinoma, whereas transformation zone, lesion size, and non-stained were not statistically related to high-grade lesion/carcinoma. Conclusions The 2011 IFCPC terminology can improve the diagnostic accuracy for all lesion severities. The categorization of major changes and minor changes is appropriate. However, colposcopic diagnosis remains unsatisfactory. Poor reproducibility of type 2 transformation zone and the significance of leukoplakia require further study. PMID:29507681

Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings

PubMed Central

Zewdie, Getie A.; Cox, Dennis D.; Neely Atkinson, E.; Cantor, Scott B.; MacAulay, Calum; Davies, Kalatu; Adewole, Isaac; Buys, Timon P. H.; Follen, Michele

2012-01-01

Abstract. Optical spectroscopy has been proposed as an accurate and low-cost alternative for detection of cervical intraepithelial neoplasia. We previously published an algorithm using optical spectroscopy as an adjunct to colposcopy and found good accuracy (sensitivity=1.00 [95% confidence interval (CI)=0.92 to 1.00], specificity=0.71 [95% CI=0.62 to 0.79]). Those results used measurements taken by expert colposcopists as well as the colposcopy diagnosis. In this study, we trained and tested an algorithm for the detection of cervical intraepithelial neoplasia (i.e., identifying those patients who had histology reading CIN 2 or worse) that did not include the colposcopic diagnosis. Furthermore, we explored the interaction between spectroscopy and colposcopy, examining the importance of probe placement expertise. The colposcopic diagnosis-independent spectroscopy algorithm had a sensitivity of 0.98 (95% CI=0.89 to 1.00) and a specificity of 0.62 (95% CI=0.52 to 0.71). The difference in the partial area under the ROC curves between spectroscopy with and without the colposcopic diagnosis was statistically significant at the patient level (p=0.05) but not the site level (p=0.13). The results suggest that the device has high accuracy over a wide range of provider accuracy and hence could plausibly be implemented by providers with limited training. PMID:22559693

Colposcopy

MedlinePlus

... with friends and family. Consider bringing a portable music device, such as an MP3 player, to your ... doctor if it's OK if you listen to music quietly during the exam. Women may experience less ...

Colposcopy - directed biopsy

MedlinePlus

... changes that can come back after treatment. Normal Results A smooth, pink surface of the cervix is ... and no abnormal changes were seen. What Abnormal Results Mean Your provider should be able to tell ...

Benchmarking CIN3+ risk as the basis for incorporating HPV and Pap cotesting into cervical screening and management guidelines

PubMed Central

Katki, Hormuzd A.; Schiffman, Mark; Castle, Philip E.; Fetterman, Barbara; Poitras, Nancy E.; Lorey, Thomas; Cheung, Li C.; Raine-Bennett, Tina R.; Gage, Julia C.; Kinney, Walter K.

2013-01-01

Objective In 2012, the United States Preventive Services Task Force (USPSTF) and a consensus of 25 organizations endorsed concurrent cytology and HPV testing (“cotesting”) for cervical cancer screening. Past screening and management guidelines were implicitly based on risks defined by Pap-alone, without consideration of HPV test results. To promote management that is consistent with accepted practice, new guidelines incorporating cotesting should aim to achieve equal management of women at equal risk of cervical intraepithelial neoplasia grade 3 and cancer (CIN3+). Methods We estimated cumulative 5-year risks of CIN3+ for 965,360 women aged 30–64 undergoing cotesting at Kaiser Permanente Northern California 2003–2010. We calculated the implicit risk thresholds for Pap-alone and applied them for new management guidance on HPV and Pap cotesting, citing 2 examples: HPV-positive/ASC-US and HPV-negative/Pap-negative. We call this guidance process “benchmarking”. Results LSIL, for which immediate colposcopy is prescribed, carries 5-year CIN3+ risk of 5.2%, suggesting that test results with similar risks should be managed with colposcopy. Similarly, ASC-US (2.6% risk) is managed with 6–12 month follow-up and Pap-negative (0.26% risk) is managed with 3-year follow-up. The 5-year CIN3+ risk for women with HPV-positive/ASC-US was 6.8% (95%CI 6.2% to 7.6%). This is greater than the 5.2% risk implicitly leading to referral to colposcopy, consistent with current management recommendations that HPV-positive/ASC-US should be referred for immediate colposcopy. The 5-year CIN3+ risk for women with HPV-negative/Pap-negative was 0.08% (95%CI 0.07% to 0.09%), far below the 0.26% implicitly required for a 3-year return and justifying a longer (e.g., 5-year) return. Conclusions Using the principle of “equal management of equal risks,” benchmarking to implicit risk thresholds based on Pap-alone can be used to achieve safe and consistent incorporation of cotesting. PMID:23519302

Comparison of Triage Strategies for HPV-Positive Women: Canadian Cervical Cancer Screening Trial Results.

PubMed

Isidean, Sandra D; Mayrand, Marie-Hélène; Ramanakumar, Agnihotram V; Rodrigues, Isabel; Ferenczy, Alex; Ratnam, Sam; Coutlée, François; Franco, Eduardo L

2017-06-01

Background: High-risk human papillomavirus (HR-HPV) testing has become a preferred cervical cancer screening strategy in some countries due to its superior sensitivity over cytology-based methods for identifying cervical intraepithelial neoplasia of grade 2 or worse (CIN2 + ). Improved sensitivity has been accompanied by reductions in specificity and concerns regarding overscreening and overtreatment of women with transient or nonprogressing HR-HPV infections. Triage of HR-HPV + women to colposcopy is, thus, warranted for appropriate management and treatment. Methods: Using data from the Canadian Cervical Cancer Screening Trial (CCCaST), we compared the performance of cytology and HR-HPV strategies to detect CIN2 + among HR-HPV + women (age, 30-69 years). Colposcopy referral rates and performance gains from adding other HR-HPV genotypes to HPV16/18 + triage were also evaluated. Results: A strategy referring all women HPV16/18 + and HPV16/18 - , but with atypical squamous cells of undetermined significance or worse cytology (ASC-US + ) had the highest sensitivity [82.5%; 95% confidence interval (CI), 70.9%-91.0%] but yielded the highest colposcopy referral rate. HPV16/18 + triage was the next most sensitive strategy (64.1%; 95% CI, 51.1%-75.7%). Low-grade squamous intraepithelial lesion or worse cytology (LSIL + ) triage yielded a low sensitivity (32.8%; 95% CI, 21.9%-45.4%) but had the most favorable specificity (93.6%; 95% CI, 91.0%-95.6%), positive predictive value (41.5%; 95% CI, 28.1%-55.9%), and colposcopy referral rate of strategies examined. HPV viral load triage strategies did not perform optimally overall. Inclusion of HR-HPV genotypes 31 and 52 to HPV16/18 + triage provided the highest sensitivities. Conclusion: Concerns surrounding HPV-based screening can be effectively mitigated via triage. Impact: Balancing the benefits of HPV-based primary cervical screening with informed management recommendations for HR-HPV + women may decide the success of its widening utilization. Cancer Epidemiol Biomarkers Prev; 26(6); 923-9. ©2017 AACR . ©2017 American Association for Cancer Research.

HPV testing with cytology triage for cervical cancer screening in routine practice.

PubMed

Louvanto, Karolina; Chevarie-Davis, Myriam; Ramanakumar, Agnihotram Venkata; Franco, Eduardo Luis; Ferenczy, Alex

2014-05-01

The purpose of this study was to evaluate the feasibility and effectiveness of Viral Testing Alone with Pap (Papanicolaou) Triage for Screening Cervical Cancer in Routine Practice (VASCAR) in a publicly funded university-affiliated hospital in Montreal, Canada. Women who are 30-65 years old are screened with the Hybrid Capture-2 assay. Women with negative results are retested at 3-year intervals; women with positive results are triaged with conventional cytologic methods. Women with Papanicolaou positive test results (≥atypical squamous cells of undetermined significance) are referred to colposcopy; women with Papanicolaou negative test results are retested with Hybrid Capture-2 assay and a Papanicolaou test in 1 year. Results were compared with a historic era (annual cytology with ≥atypical squamous cells of undetermined significance threshold for colposcopy referral) in the 3 years before VASCAR. VASCAR included 23,739 eligible women, among whom 1646 women (6.9%) tested positive for the human papillomavirus (HPV). Because of the need for subsequent sampling for cytologic testing, follow-up evaluation for cytologic triage was relatively poor; only 46% and 24% of HPV-positive women were Papanicolaou-triaged and underwent biopsy, respectively. Protocol violations occurred mainly in the early phases of implementation (12%). Detection of high-grade cervical intraepithelial neoplasia increased nearly 3-fold (rate ratio, 2.78; 95% confidence interval [CI], 2.1-3.7) during VASCAR, mostly because of a doubling in the rate of high-grade cervical intraepithelial neoplasia (34.0%; 95% CI, 21.2-48.8) compared with the historic cytology-only era (16.3%; 95% CI, 13.2-19.8). VASCAR reduced the median time to colposcopy from a positive screen from 11 months (95% CI, 10.48-11.50) to 3 months (95% CI, 2.64-3.80). VASCAR is feasible; however, it requires cosampling for HPV and cytology and for continuous education of healthcare providers of the HPV-Papanicolaou triage protocol. Efficacy in disease detection and reduction in time to colposcopy referrals compared with the historic cytology era is encouraging but should be considered preliminary because of the small number of patients who were tested. Copyright © 2014 Mosby, Inc. All rights reserved.

Follow-up of women with cervical cytological abnormalities showing atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion: a nationwide cohort study.

PubMed

Sundström, Karin; Lu, Donghao; Elfström, K Miriam; Wang, Jiangrong; Andrae, Bengt; Dillner, Joakim; Sparén, Pär

2017-01-01

Atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion in abnormal cervical cytology among young women in cervical cancer screening is an increasing health burden, and comparative effectiveness studies of different management options for such diagnoses are needed. The objective of the study was to compare the incidence of invasive cervical cancer, following different management options pursued after an atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion index smear. In this nationwide cohort study, we included all women aged 22-50 years and resident in Sweden 1989-2011 and with at least 1 cervical smear registered during the study period (n = 2,466,671). Follow-up of a first atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion cytological diagnosis within 25 months was classified as repeat cytology, colposcopy/biopsy, or without further assessment. Incidence rate ratios and 95% confidence intervals of subsequent cervical cancer within 6.5 years following atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion were estimated using Poisson regression by age group and management strategy. Women managed with repeat cytology within 6 months after atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion cytology had a similar risk of cervical cancer compared with colposcopy/biopsy (incidence rate ratio, 1.1, 95% confidence interval, 0.5-2.5, and incidence rate ratio, 2.0, 95% confidence interval, 0.6-6.5, respectively) among women aged 22-27 years. For women aged 28 years and older, women managed with repeat cytology had a higher risk for cervical cancer than women managed with colposcopy/biopsy. Our findings suggest that women with a first cytological diagnosis of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion up to age 27 years may indeed be safely followed up with repeat cytology within 6 months. A large amount of colposcopies that are currently performed in this group, therefore, could safely be discontinued. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

MultipleColposcopyJCO

Cancer.gov

Performing multiple biopsies during a procedure known as colposcopy—visual inspection of the cervix—is more effective than performing only a single biopsy of the worst-appearing area for detecting cervical cancer precursors. This multiple biopsy approach

The comparative and cost-effectiveness of HPV-based cervical cancer screening algorithms in El Salvador.

PubMed

Campos, Nicole G; Maza, Mauricio; Alfaro, Karla; Gage, Julia C; Castle, Philip E; Felix, Juan C; Cremer, Miriam L; Kim, Jane J

2015-08-15

Cervical cancer is the leading cause of cancer death among women in El Salvador. Utilizing data from the Cervical Cancer Prevention in El Salvador (CAPE) demonstration project, we assessed the health and economic impact of HPV-based screening and two different algorithms for the management of women who test HPV-positive, relative to existing Pap-based screening. We calibrated a mathematical model of cervical cancer to epidemiologic data from El Salvador and compared three screening algorithms for women aged 30-65 years: (i) HPV screening every 5 years followed by referral to colposcopy for HPV-positive women (Colposcopy Management [CM]); (ii) HPV screening every 5 years followed by treatment with cryotherapy for eligible HPV-positive women (Screen and Treat [ST]); and (iii) Pap screening every 2 years followed by referral to colposcopy for Pap-positive women (Pap). Potential harms and complications associated with overtreatment were not assessed. Under base case assumptions of 65% screening coverage, HPV-based screening was more effective than Pap, reducing cancer risk by ∼ 60% (Pap: 50%). ST was the least costly strategy, and cost $2,040 per year of life saved. ST remained the most attractive strategy as visit compliance, costs, coverage, and test performance were varied. We conclude that a screen-and-treat algorithm within an HPV-based screening program is very cost-effective in El Salvador, with a cost-effectiveness ratio below per capita GDP. © 2015 UICC.

Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering

PubMed Central

Mourant, Judith R.; Bocklage, Thérese J.; Powers, Tamara M.; Greene, Heather M.; Dorin, Maxine H.; Waxman, Alan G.; Zsemlye, Meggan M.; Smith, Harriet O.

2009-01-01

Objective To examine the utility of in vivo elastic light scattering measurements to identify cervical intraepithelial neoplasias (CIN) 2/3 and cancers in women undergoing colposcopy and to determine the effects of patient characteristics such as menstrual status on the elastic light scattering spectroscopic measurements. Materials and Methods A fiber optic probe was used to measure light transport in the cervical epithelium of patients undergoing colposcopy. Spectroscopic results from 151 patients were compared with histopathology of the measured and biopsied sites. A method of classifying the measured sites into two clinically relevant categories was developed and tested using five-fold cross-validation. Results Statistically significant effects by age at diagnosis, menopausal status, timing of the menstrual cycle, and oral contraceptive use were identified, and adjustments based upon these measurements were incorporated in the classification algorithm. A sensitivity of 77±5% and a specificity of 62±2% were obtained for separating CIN 2/3 and cancer from other pathologies and normal tissue. Conclusions The effects of both menstrual status and age should be taken into account in the algorithm for classifying tissue sites based on elastic light scattering spectroscopy. When this is done, elastic light scattering spectroscopy shows good potential for real-time diagnosis of cervical tissue at colposcopy. Guiding biopsy location is one potential near-term clinical application area, while facilitating ”see and treat” protocols is a longer term goal. Improvements in accuracy are essential. PMID:20694193

Pooled analysis of the accuracy of five cervical cancer screening tests assessed in eleven studies in Africa and India.

PubMed

Arbyn, Marc; Sankaranarayanan, Rengaswamy; Muwonge, Richard; Keita, Namory; Dolo, Amadou; Mbalawa, Charles Gombe; Nouhou, Hassan; Sakande, Boblewende; Wesley, Ramani; Somanathan, Thara; Sharma, Anjali; Shastri, Surendra; Basu, Parthasarathy

2008-07-01

Cervical cancer is the main cancer among women in sub-Saharan Africa, India and other parts of the developing world. Evaluation of screening performance of effective, feasible and affordable early detection and management methods is a public health priority. Five screening methods, naked eye visual inspection of the cervix uteri after application of diluted acetic acid (VIA), or Lugol's iodine (VILI) or with a magnifying device (VIAM), the Pap smear and human papillomavirus testing with the high-risk probe of the Hybrid Capture-2 assay (HC2), were evaluated in 11 studies in India and Africa. More than 58,000 women, aged 25-64 years, were tested with 2-5 screening tests and outcome verification was done on all women independent of the screen test results. The outcome was presence or absence of cervical intraepithelial neoplasia (CIN) of different degrees or invasive cervical cancer. Verification was based on colposcopy and histological interpretation of colposcopy-directed biopsies. Negative colposcopy was accepted as a truly negative outcome. VIA showed a sensitivity of 79% (95% CI 73-85%) and 83% (95% CI 77-89%), and a specificity of 85% (95% CI 81-89%) and 84% (95% CI 80-88%) for the outcomes CIN2+ or CIN3+, respectively. VILI was on average 10% more sensitive and equally specific. VIAM showed similar results as VIA. The Pap smear showed lowest sensitivity, even at the lowest cutoff of atypical squamous cells of undetermined significance (57%; 95% CI 38-76%) for CIN2+ but the specificity was rather high (93%; 95% CI 89-97%). The HC2-assay showed a sensitivity for CIN2+ of 62% (95% CI 56-68%) and a specificity of 94% (95% CI 92-95%). Substantial interstudy variation was observed in the accuracy of the visual screening methods. Accuracy of visual methods and cytology increased over time, whereas performance of HC2 was constant. Results of visual tests and colposcopy were highly correlated. This study was the largest ever done that evaluates the cross-sectional accuracy of screening tests for cervical cancer precursors in developing countries. The merit of the study was that all screened subjects were submitted to confirmatory investigations avoiding to verification bias. A major finding was the consistently higher sensitivity but equal specificity of VILI compared with VIA. Nevertheless, some caution is warranted in the interpretation of observed accuracy measures, since a certain degree of gold standard misclassification cannot be excluded. Because of the correlation between visual screening tests and colposcopy and a certain degree of over-diagnosis of apparent CIN2+ by study pathologists, it is possible that both sensitivity and specificity of VIA and VILI were overestimated. Gold standard verification error could also explain the surprisingly low sensitivity of HC2, which contrasts with findings from other studies. (c) 2008 Wiley-Liss, Inc.

Carbon dioxide laser management cervical intraepithelial neoplasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bellina, J.H.; Wright, V.C.; Voros, J.I.

1981-12-01

In this report we describe the use of the carbon dioxide laser for the outpatient management of cervical intraepithelial neoplasia (CIN). A comparison of treatment effectiveness for different grades of CIN is also included. Two hundred fifty-six cases were evaluated by colposcopy, cytology, and histopathology, treated by at least 5 to 6 mm of laser vaporization, and followed up for an average of 10.7 months. Follow-up examinations included cytology, colposcopy, and directed biopsy if a suspicious lesion was discovered. During the follow-up, 18 cases of persistent CIN were identified (7.0%). Most of these were successfully managed with repeat laser treatment.more » Overall success of laser surgery for CIN, one or two applications, was 97.6%. Few complications were encountered. Laser surgery appears to offer acceptable treatment effectiveness, early identification of persistent disease, and easy retreatment when required. (Am. J. Obstet. Gynecol. 141:828, 1981.)« less

Cervical endometriosis: a diagnostic and management dilemma.

PubMed

Phadnis, Saurabh V; Doshi, Jagruti S; Ogunnaike, Oluyemisi; Coady, Andrew; Padwick, Malcolm; Sanusi, F A

2005-10-01

Cervical endometriosis is usually a retrospective finding on histology. We describe the diverse symptomatology of the disease, wherein a suspicion of diagnosis may be raised. A series of five patients with cervical endometriosis confirmed on histology was identified. One patient was asymptomatic but examination revealed a mass arising from the cervix. Two patients presented with persistent postcoital bleeding, one patient with intermenstrual bleeding and one patient with both intermenstrual and postcoital bleeding. All patients were followed up with colposcopy and cervical biopsy. Persistence of symptoms determined the mode of treatment which included surgical management in the form of large loop excision of the transformation zone (LLETZ) biopsy in four patients. Cervical endometriosis is a benign condition which may present with symptoms such as persistent post-coital bleeding or intermenstrual bleeding. Colposcopy and cervical biopsy are pivotal to the diagnosis. This condition can be managed expectantly in asymptomatic patients and persistent symptoms may warrant surgery.

American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology Screening Guidelines for the Prevention and Early Detection of Cervical Cancer

PubMed Central

Saslow, Debbie; Solomon, Diane; Lawson, Herschel W.; Killackey, Maureen; Kulasingam, Shalini; Cain, Joanna; Garcia, Francisco A. R.; Moriarty, Ann; Waxman, Alan; Wilbur, David; Wentzensen, Nicolas; Downs, Levi; Spitzer, Mark; Moscicki, Anna-Barbara; Saraiya, Mona; Franco, Eduardo L.; Stoler, Mark H.; Schiffman, Mark; Castle, Philip E.; Myers, Evan R.

2013-01-01

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from six working groups, and a recent symposium co-sponsored by the ACS, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP), which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (e.g., management of screen positives and screening interval for screen negatives) of women after screening, age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. PMID:22418039

American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology Screening Guidelines for the Prevention and Early Detection of Cervical Cancer

PubMed Central

Saslow, Debbie; Solomon, Diane; Lawson, Herschel W.; Killackey, Maureen; Kulasingam, Shalini; Cain, Joanna; Garcia, Francisco A. R.; Moriarty, Ann; Waxman, Alan; Wilbur, David; Wentzensen, Nicolas; Downs, Levi; Spitzer, Mark; Moscicki, Anna-Barbara; Franco, Eduardo L.; Stoler, Mark H.; Schiffman, Mark; Castle, Philip E.; Myers, Evan R.

2013-01-01

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from six working groups, and a recent symposium cosponsored by the ACS, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP), which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (e.g., management of screen positives and screening interval for screen negatives) of women after screening, age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. PMID:22422631

Conservative approach to preneoplastic cervical lesions in postmenopause.

PubMed

Vetrano, Giuseppe; Aleandri, Vincenzo; Ciolli, Paola; Scardamaglia, Paola; Pacchiarotti, Arianna; Verrico, Monica; Carboni, Simona; Corosu, Roberto

2008-01-01

To evaluate the recurrence rate of high-grade squamous intraepithelial lesions in postmenopausal women previously submitted to laser CO2 conization and the role of persistent oncogenic HPV types. Fifty-five patients with a cytological diagnosis of high-grade squamous intraepithelial lesions were triaged with a standard colposcopy. Hormonal replacement therapy was considered as significative in influencing cervical trophism. Vaginal smears for microbiological examination were obtained. H-R HPV test was performed by PCR. The follow-up checks including cytology, colposcopy and HVP test were performed for a minimum of 5 years. Histological analysis revealed 19 CIN2 (cervical intraepithelial lesions) and 36 CIN3 lesions. The cumulative failure rate at first treatment was 14%. HPV test was positive for HPV 16 type in all patients. Forty-two patients during the follow up checks resulted negative to cytology, colposcopy and HR HPV test. At the one-year follow-up check, 7 patients revealed normal cytological and abnormal colposcopical findings and persistent positive HR HPV test. At the five-year follow-up check, 14 patients with a normal cytological smear had a recurrence of CIN2/3 and positive HR HPV test. In postmenopause, the correct management of H-R squamous intraepithelial lesions is still debated. However, a satisfactory follow-up is the main requirement for the conservative management. HPV typing in the follow-up is important to detect persistent types to identify women at risk of developing cervical abnormalities. The incidence of cervical neoplasia does not decrease with increasing age. Since HPV positivity predicted subsequent infection, testing postmenopausal patients for the virus may be a cost-effective method of disease prevention.

Understanding Cervical Changes: A Health Guide for Women

Cancer.gov

Explains abnormal Pap test, HPV test, and Pap/HPV cotest results. Treatment and follow-up care for abnormal cervical cancer screening results including ASC-US, AGC, LSIL, ASC-H, HSIL, AIS. Learn about colposcopy, types of biopsies, CIN, and HPV vaccine.

Diagnosing Cervical Neoplasia in Rural Brazil Using a Mobile Van Equipped with In Vivo Microscopy: A Cluster-Randomized Community Trial.

PubMed

Hunt, Brady; Fregnani, José Humberto Tavares Guerreiro; Schwarz, Richard A; Pantano, Naitielle; Tesoni, Suelen; Possati-Resende, Júlio César; Antoniazzi, Marcio; de Oliveira Fonseca, Bruno; de Macêdo Matsushita, Graziela; Scapulatempo-Neto, Cristovam; Kerr, Ligia; Castle, Philip E; Schmeler, Kathleen; Richards-Kortum, Rebecca

2018-06-01

Cervical cancer is a leading cause of death in underserved areas of Brazil. This prospective randomized trial involved 200 women in southern/central Brazil with abnormal Papanicolaou tests. Participants were randomized by geographic cluster and referred for diagnostic evaluation either at a mobile van upon its scheduled visit to their local community, or at a central hospital. Participants in both arms underwent colposcopy, in vivo microscopy, and cervical biopsies. We compared rates of diagnostic follow-up completion between study arms, and also evaluated the diagnostic performance of in vivo microscopy compared with colposcopy. There was a 23% absolute and 37% relative increase in diagnostic follow-up completion rates for patients referred to the mobile van (102/117, 87%) compared with the central hospital (53/83, 64%; P = 0.0001; risk ratio = 1.37, 95% CI, 1.14-1.63). In 229 cervical sites in 144 patients, colposcopic examination identified sites diagnosed as cervical intraepithelial neoplasia grade 2 or more severe (CIN2+; 85 sites) with a sensitivity of 94% (95% CI, 87%-98%) and specificity of 50% (95% CI, 42%-58%). In vivo microscopy with real-time automated image analysis identified CIN2+ with a sensitivity of 92% (95% CI, 84%-97%) and specificity of 48% (95% CI, 40%-56%). Women referred to the mobile van were more likely to complete their diagnostic follow-up compared with those referred to a central hospital, without compromise in clinical care. In vivo microscopy in a mobile van provides automated diagnostic imaging with sensitivity and specificity similar to colposcopy. Cancer Prev Res; 11(6); 359-70. ©2018 AACR . ©2018 American Association for Cancer Research.

Comparison of cytology, HPV DNA testing and HPV 16/18 genotyping alone or combined targeting to the more balanced methodology for cervical cancer screening.

PubMed

Chatzistamatiou, Kimon; Moysiadis, Theodoros; Moschaki, Viktoria; Panteleris, Nikolaos; Agorastos, Theodoros

2016-07-01

The objective of the present study was to identify the most effective cervical cancer screening algorithm incorporating different combinations of cytology, HPV testing and genotyping. Women 25-55years old recruited for the "HERMES" (HEllenic Real life Multicentric cErvical Screening) study were screened in terms of cytology and high-risk (hr) HPV testing with HPV 16/18 genotyping. Women positive for cytology or/and hrHPV were referred for colposcopy, biopsy and treatment. Ten screening algorithms based on different combinations of cytology, HPV testing and HPV 16/18 genotyping were investigated in terms of diagnostic accuracy. Three clusters of algorithms were formed according to the balance between effectiveness and harm caused by screening. The cluster showing the best balance included two algorithms based on co-testing and two based on HPV primary screening with HPV 16/18 genotyping. Among these, hrHPV testing with HPV 16/18 genotyping and reflex cytology (atypical squamous cells of undetermined significance - ASCUS threshold) presented the optimal combination of sensitivity (82.9%) and specificity relative to cytology alone (0.99) with 1.26 false positive rate relative to cytology alone. HPV testing with HPV 16/18 genotyping, referring HPV 16/18 positive women directly to colposcopy, and hrHPV (non 16/18) positive women to reflex cytology (ASCUS threshold), as a triage method to colposcopy, reflects the best equilibrium between screening effectiveness and harm. Algorithms, based on cytology as initial screening method, on co-testing or HPV primary without genotyping, and on HPV primary with genotyping but without cytology triage, are not supported according to the present analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

Scale-Up of an Human Papillomavirus Testing Implementation Program in El Salvador.

PubMed

Cremer, Miriam; Maza, Mauricio; Alfaro, Karla; Morales Velado, Mario; Felix, Juan; Castle, Philip E; Kim, Jane; Gage, Julia C

2017-01-01

The Cervical Cancer Prevention in El Salvador is a demonstration project to introduce a lower-cost human papillomavirus (HPV)-DNA test into a public sector project. Started in October 2012, The Cervical Cancer Prevention in El Salvador consists of 3 phases and will ultimately screen 30,000 women. Results of phase 2 of the project are presented. The objective of this project was to compare colposcopy and noncolposcopy-based management for HPV-positive women. In phase 2, a total of 8,050 women, aged 30 to 49 years, were screened; 6,761 provided both self- and provider-collected specimens and 1,289 provided only provider-testing specimens. HPV results from self-collected specimens were not used in clinical management decisions. Women with provider-collected HPV-positive results were treated based on the strategy assigned to their community; the strategy was colposcopy management (CM) or screen-and-treat (ST) management if they were cryotherapy eligible or colposcopy if not eligible. Outcomes were assessed 6 months after screening. Overall, 489 (12.3%) of 3,963 women receiving CM and 465 (11.4%) of 4,087 women receiving ST tested HPV positive. In the CM cohort, 216 (44.2%) of 489 completed their intervention (203 treated, 11 diagnosed negative, 2 pregnant). In the ST cohort, 411 (88.4%) of 465 completed their intervention (407 treated, 2 diagnosed negative, 1 pregnant). Overall agreement between HPV test results from self-collected and provider-collected specimens was 93.7%, with a κ value of 0.70 (95% CI = 0.68-0.73). Human papillomavirus testing with ST management resulted in an approximately twice completion rate compared with CM management. Agreement between self- and provider-based sampling was good and might be used to extend screening to women in areas that are more difficult to reach.

Reliability of unaided naked-eye examination as a screening test for cervical lesions in a developing country setup.

PubMed

Darwish, Atef M; Abdulla, Sayed A; Zahran, Kamal M; Abdel-Fattah, Nermat A

2013-04-01

This study aimed to test the reliability of unaided naked-eye examination (UNEE) of the cervix as a sole cervical cancer screening test in a developing country setup compared with the standard cervical cytology. A total of 3,500 nonpregnant women aged between 25 and 55 years were included. An unlubricated bivalve speculum was inserted into the vagina under good light to visualize the cervix. A thorough UNEE of the cervix was done to detect any apparent lesions. Cervical smears were obtained using the long tip of an Ayre spatula. An additional endocervical sample was obtained by cytobrush. Women with abnormal Pap smears or visible cervical lesions by UNEE were scheduled for colposcopic examination. A biopsy specimen was obtained in every abnormal colposcopic examination. Of 3,500 cases, there were 9 (2.57%) preinvasive cervical lesions (cervical intraepithelial neoplasia 1-3) diagnosed with various diagnostic tools used in the study and confirmed by histopathologic examination. Of 3,500 cases, invasive cervical lesions were diagnosed in 6 (1.71%). The sensitivity of UNEE is much better than that of Pap smear (80% vs 60%) but less than that of colposcopy (86.7%). However, the specificity of UNEE (100%) is lower than that of Pap smear (91.16%) and better than that colposcopy (83.12%). The UNEE has a poor positive predictive value (3.75%) when compared with Pap smear (100%) and colposcopy (20%). The negative predictive values of the 3 tests were nearly comparable. Whenever access to Pap smear is limited, UNEE performed by general gynecologists and well-trained nurses is an acceptable alternative for detecting cervical premalignant or malignant lesions especially in low-resource settings.

The role of low-level magnification in visual inspection with acetic acid for the early detection of cervical neoplasia.

PubMed

Sankaranarayanan, Rengaswamy; Shastri, Surendra S; Basu, Parthasarathi; Mahé, Cédric; Mandal, Ranajit; Amin, Geethanjali; Roy, Chinmayi; Muwonge, Richard; Goswami, Smriti; Das, Pradip; Chinoy, Roshini; Frappart, Lucien; Patil, Sharmila; Choudhury, Devjani; Mukherjee, Titha; Dinshaw, Ketayun

2004-01-01

Several studies have investigated the accuracy of naked eye visual inspection with acetic acid (VIA) in the early detection of cervical neoplasia. It is not clear whether low-level (2-4x) magnification (VIAM) can improve the sensitivity and specificity of VIA. The accuracy of both VIA and VIAM, provided by independent health workers, were evaluated in three cross-sectional studies involving 18,675 women aged 25-65 years in Kolkata and Mumbai in India. All screened women were investigated with colposcopy and biopsies were obtained based on colposcopy findings. The final disease status was based on the reference standard of histology (if biopsies had been taken) or colposcopy. Data from the studies were pooled to calculate the test characteristics for the detection of high-grade squamous intraepithelial lesions (HSIL). 14.1% and 14.2% were positive on testing with VIA and VIAM respectively. Two hundred twenty-nine were diagnosed with HSIL and 68 with invasive cancer. The pooled sensitivity, specificity, positive and negative predictive values for VIA in detecting high-grade squamous intraepithelial lesions (HSIL) were 60.3% (95% CI: 53.6-66.7), 86.8% (95% CI: 86.3-87.3), 5.9% (95% CI: 5.0-7.0), and 99.4% (95% CI: 99.2-99.5), respectively. The values were 64.2% (95% CI: 57.6-70.4), 86.8% (95% CI: 86.2-87.3), 6.3% (95% CI: 5.3-7.3) and 99.4% (95% CI: 99.3-99.6), respectively, for VIAM. Low-level magnification did not improve the test performance of naked eye visualization of acetic acid impregnated uterine cervix.

Using Decision-Analytic Modeling to Isolate Interventions That Are Feasible, Efficient and Optimal: An Application from the Norwegian Cervical Cancer Screening Program.

PubMed

Pedersen, Kine; Sørbye, Sveinung Wergeland; Burger, Emily Annika; Lönnberg, Stefan; Kristiansen, Ivar Sønbø

2015-12-01

Decision makers often need to simultaneously consider multiple criteria or outcomes when deciding whether to adopt new health interventions. Using decision analysis within the context of cervical cancer screening in Norway, we aimed to aid decision makers in identifying a subset of relevant strategies that are simultaneously efficient, feasible, and optimal. We developed an age-stratified probabilistic decision tree model following a cohort of women attending primary screening through one screening round. We enumerated detected precancers (i.e., cervical intraepithelial neoplasia of grade 2 or more severe (CIN2+)), colposcopies performed, and monetary costs associated with 10 alternative triage algorithms for women with abnormal cytology results. As efficiency metrics, we calculated incremental cost-effectiveness, and harm-benefit, ratios, defined as the additional costs, or the additional number of colposcopies, per additional CIN2+ detected. We estimated capacity requirements and uncertainty surrounding which strategy is optimal according to the decision rule, involving willingness to pay (monetary or resources consumed per added benefit). For ages 25 to 33 years, we eliminated four strategies that did not fall on either efficiency frontier, while one strategy was efficient with respect to both efficiency metrics. Compared with current practice in Norway, two strategies detected more precancers at lower monetary costs, but some required more colposcopies. Similar results were found for women aged 34 to 69 years. Improving the effectiveness and efficiency of cervical cancer screening may necessitate additional resources. Although efficient and feasible, both society and individuals must specify their willingness to accept the additional resources and perceived harms required to increase effectiveness before a strategy can be considered optimal. Copyright © 2015. Published by Elsevier Inc.

Colpocytological abnormalities in HIV infected and uninfected pregnant women: prevalence, persistence and progression.

PubMed

Carriero, Carmine; Fascilla, Fabiana Divina; Cramarossa, Paola; Lepera, Achiropita; Bettocchi, Stefano; Vimercati, Antonella

2018-02-01

In this retrospective case-control study, we analyse data of 48 HIV-positive pregnant patients, versus a control group of 99 HIV-negative pregnant women, followed as outpatients by our department from 2009 to 2014. The aims of the study were to investigate the prevalence, persistence and progression of cervical squamous intraepithelial lesions (SIL) in each group and to correlate colpo-cytological lesions to the socio-demographic and clinical-laboratory findings in the HIV + pregnant women. In our study we observed that immunosuppression, HPV infection and vaginal coinfections were predictive of cervical lesions. Pap smear and colposcopy should be part of routine care for HIV-infected pregnant women because these lesions behave aggressively in these patients. Success of prevention depends on massive access of patients to screening. HAART reduces viral load and maintains CD4 count and can affect progression of SIL. Multidisciplinary services on the same site appear to be one promising strategy to improve compliance in patients. Impact Statement What is already known on this subject: Our study provided novel information on a highly vulnerable population of young HIV + pregnant women. What the results of this study add: We observed that immunosuppression, HPV infection and vaginal coinfections were predictive of cervical lesions remarkable with colposcopy. We could consider these important risk factors to evaluate to establish an appropriate strategy of management for these patients. What the implications are of these findings for clinical practice and/or further research: Association of the risk between SIL presence and HIV and HPV infection also deserves additional investigation. We believe that Pap smears and colposcopies should be part of the routine care for HIV-infected women because these lesions behave particularly aggressively in these patients.

The effectiveness of conization treatment for post-menopausal women with high-grade cervical intraepithelial neoplasia

PubMed Central

CHENG, XIAODONG; FENG, YAN; WANG, XINYU; WAN, XIAOYUN; XIE, XING; LU, WEIGUO

2013-01-01

The aim of this study was to evaluate the effectiveness of conization in the diagnosis and treatment of high-grade cervical intraepithelial neoplasia (CIN) in post-menopausal women. A total of 101 post-menopausal patients who were diagnosed with high-grade lesion CIN by biopsy and in whom conization was used as the primary treatment were examined and 202 pre-menopausal patients were studied as the controls. Clinical and pathological data including symptoms, cytological examination and HPV DNA test results before and after conization treatment were analyzed. Both the cytological abnormalities (57.9 vs. 58.5%, P=0.260) and the positive rate of the HPV DNA test (89.5 vs. 86.4%, P=0.812) did not show a significant difference between the post- and pre-menopausal group. The rate of satisfactory colposcopy was significantly lower in post-menopausal patients compared with pre-menosausal patients (23.2 vs. 68.9%, P<0.001). Post-menopausal patients presented a significantly lower diagnostic consistency between colpscopy-directed biopsy and conization (46.4 vs. 68.9%, P=0.004), and a significantly higher positive margin rate of conization (20.8 vs. 10.9%, P=0.020). A total of 10 of the 101 post-menopausal and 2 of the 202 pre-menopausal women were diagnosed with invasive cancer by conization and underwent further treatment. In conclusion, these data suggest that conization, as a conservative primary treatment, is not suitable for post-menopausal women with high-grade lesion CIN due to the lower rate of satisfactory colposcopy, lower consistency of diagnosis between colposcopy-directed biopsy and conization, and a higher positive margin of conization. PMID:23251264

Triage of women with atypical squamous cells of undetermined significance (ASC-US): results of an Italian multicentric study.

PubMed

Del Mistro, Annarosa; Frayle-Salamanca, Helena; Trevisan, Rossana; Matteucci, Mario; Pinarello, Antonella; Zambenedetti, Pamela; Buoso, Rita; Fantin, Gian Piero; Zorzi, Manuel; Minucci, Daria

2010-04-01

To compare the performance of immediate colposcopy, repeat Pap test and HPV test as triage options for women diagnosed as having atypical squamous cells of undetermined significance (ASC-US) while attending organised screening for cervical carcinoma in five centres of the Veneto region. Women consecutively diagnosed as having ASC-US were included in a prospective study, and underwent colposcopy and collection of cervico-vaginal cells for conventional Pap test and HPV test (Hybrid Capture 2, High-risk probe set, Digene). Repetition of all three tests was scheduled for 12 months later. DNA was subsequently extracted from residual cells of positive samples, and analysed by polymerase chain reaction with several primers for typing of HPV sequences. Sensitivity, specificity and positive predictive value (PPV) of the different triage options for histology-confirmed cervical intraepithelial neoplasia, grade 2 or worse (CIN2+) were calculated among all women and by age (under and above 35 years). Seven hundred forty-nine women 25-64 years old (median age 42 years) were enrolled in the study. Pap smears at enrolment were read as ASC-US or more severe in 211 (29.4%) cases, colposcopy disclosed an atypical transformation zone in 254 (34.2%) women, and HPV test was positive in 181 (24.2%). High-grade cervical lesions developed in 29/749 (3.9%) women. HPV typing was possible in 163 (90%) of the samples, and carcinogenic types were present in 123. HPV test showed the best performance; overall, it had the highest sensitivity (92.3%), specificity (78.6%) and PPV (14.9%). Copyright 2009 Elsevier Inc. All rights reserved.

Results of delayed triage by HPV testing and cytology in the Norwegian Cervical Cancer Screening Programme.

PubMed

Haldorsen, Tor; Skare, Gry Baadstrand; Ursin, Giske; Bjørge, Tone

2015-02-01

High-risk human papilloma virus (hrHPV) testing was added to the cytology triage of women with equivocal screening smears in the Norwegian programme for cervical cancer screening in 2005. In this population-based observational before and after study we assessed the effect of changing the screening algorithm. In periods before and after the change 75 852 and 66 616 women, respectively, were eligible for triage, i.e. they had smear results of unsatisfactory, atypical squamous cells of undetermined significance (ASC-US), or low-grade squamous intraepithelial lesion (LSIL) at routine screening. The triage was delayed as supplementary testing started six months after the initial screening. The groups were compared with respect to results of triage and later three-year cumulative incidence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Before and after the change in the screening algorithm 5.2% (3964/75 852) and 8.1% (5417/66 616) of women, respectively, were referred to colposcopy. Among women referred to colposcopy cumulative incidence of CIN2+ (positive predictive value of referral) increased from 42.0% [95% confidence interval (CI): 40.3 - 43.7%] in the period with cytology only to 48.0% (95% CI 46.6 - 49.4%) after the start of HPV testing. For women recalled to ordinary screening the three-year cumulative incidence decreased from 2.7% (95% CI 2.5 - 2.9%) to 1.0% (95% CI 0.9 - 1.2%) during the same period. Among women with LSIL at routine screening and HPV testing in triage, 52.5% (1976/3766) were HPV positive. The new algorithm with HPV testing implemented in 2005 resulted in an increased rate of referral to colposcopy, but in a better risk stratification with respect to precancerous disease.

[Detection of human papillomavirus (HVP) 16/18 infections of the vaginal uterine cervix in females before and following conisation].

PubMed

Götze, W; Jantschak, J; Kohls, A; Elling, D; Schildhaus, I

1990-01-01

280 women have been tested by FISH to detect an HPV 16/18-infection of the portio uteri. In a group of 133 women treated by conisation (all with a history of abnormal smear and colposcopy) 67 (50%) were positive for HPV 16/18 DNA before the operation. Follow up examinations of 20 cases with positive HPV 16/18 test before conisation, showed 6 and 12 months after operation only in 3 cases a persistence of HPV 16/18 infection. Only 5 (6.4%) of 78 women with a history of conisation and diagnosis CIN III some years ago were positive for HPV 16/18. In another group of 47 elderly women, treated by abrasio and with normal cervical histology, only 5 (10.6%) had a positive result in the HPV 16/18 FISH-test. 2 (10.6%) of 22 women with normal smear and colposcopy (control group) were positive for HPV 16/18.

Epidemiological, clinical, and virological characteristics of women with genital warts in Greece.

PubMed

Loumpardia, P; Bourmpos, K; Loumpardias, G A; Kalampoki, V; Valasoulis, G; Valari, O; Vythoulkasl, D; Deligeoroglou, E; Koliopoulos, G

2015-01-01

This is a prospective study of the epidemiological, clinical, and virological characteristics of cases of genital warts in a Greek University Hospital. The women completed a questionnaire regarding their medical and sexual history and underwent cervical cytology, HPV DNA typing, mRNA testing, colposcopy, Chlamydia testing, and proctoscopy. Univariate and multivariate analyses were performed. The most commonly detected types were type 6 (36.1%) and 16 (24.3%). E6/E7 mRNA testing was positive in 21.5%. Concurrent cervical intraepithelial neoplasia grade 2 or worse was found in 11.1% and intra-anal warts in 10.4%. For chlamydial infection the number of sexual partners was a significant predictor. Women with warts infected with types 6 and 11 constituted only 37.5% of the total. This could have a negative effect on the efficacy of vaccination in reducing the incidence of the disease. Based on the present findings the authors recommend cytology and colposcopy for all women with genital warts.

[Behavior of cervical intraepithelial neoplasia in pregnant adolescents and its persistence after an obstetric event].

PubMed

Machain-Loera, Alfredo; Jiménez-Rodríguez, Antonio; Huerta-Casillas, Félix Rafael; Barajas-Serrano, Tanya Lizbeth; Barrera-de León, Juan Carlos

2014-12-01

To observe the behavior of cervical intraepithelial neoplasia in pregnant adolescents and the persistence before the delivery. A cross-sectional study including 47 pregnant adolescents with NIC-positive results diagnosed by colposcopy during pregnancy with subsequent evaluation before the delivery. Nonrandom sampling of consecutive cases. Descriptive statistics with central and dispersal measures. In total, 156 pregnant adolescents were studied, of which 30% (n = 47) had positive results to NIC with subsequent evaluation. Ages 18 ± 1.5 years, primiparous 77%, sexual activity initiation 15.6 ± 1.6 years old, sexual partners 1 (1-6), smoking and alcoholism 21%. At the beginning of pregnancy, 98% had NIC I results and 2% had NIC II by colposcopy. After delivery, 13% had normal results and 87% remained in NIC I. The findings suggest that in pregnant adolescents there exists a natural dysplasia history as in pregnant women. Most of the lesions are NIC I and don't modify the evolution, with some regressing after the delivery.

Reflex Human Papillomavirus Test Results as an Option for the Management of Korean Women With Atypical Squamous Cells Cannot Exclude High-Grade Squamous Intraepithelial Lesion

PubMed Central

Ryu, Ki-Jin; Lee, Sanghoon; Min, Kyung-Jin; Kim, Jae Won; Hong, Jin Hwa; Song, Jae Yun; Lee, Jae Kwan

2015-01-01

Background. Current guidelines recommend initial colposcopy with biopsy regardless of human papillomavirus (HPV) test results in women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). The purpose of this study was to evaluate the value of HPV testing in women with ASC-H based on colposcopic pathology results. Materials and Methods. A multicenter cross-sectional study was carried out at three academic hospitals and involved 40,847 Korean women who underwent cervical cancer screening with cytology and HPV tests with or without subsequent colposcopic biopsies between January 2007 and December 2013. Results. ASC-H was diagnosed in 276 women (0.7%). Only 6 of 68 (8.8%) women with ASC-H who were HPV negative had cervical intraepithelial neoplasia grade ≥2 (CIN ≥2) lesions, whereas 47.4% of the women with ASC-H who were HPV positive had CIN ≥2 lesions. No cases of invasive cervical cancer were diagnosed among women with ASC-H who were HPV negative. Logistic regression analysis was performed using the group with normal Papanicolaou test results and HPV-negative status as the reference group. Women with ASC-H who were HPV positive had a significantly increased risk of CIN ≥2 lesions, whereas no significant increase was observed in patients with ASC-H and HPV-negative status. Conclusion. If the result of the HPV test was negative, the risk of CIN ≥2 lesions in Korean women with ASC-H cytology was low. Reflex HPV testing should be an option for the management of women with cytology showing ASC-H to decrease unnecessary colposcopic biopsies, which are expensive and invasive. Implications for Practice: Current American Society for Colposcopy and Cervical Pathology guidelines recommend universal colposcopy for the management of women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) on cytology, regardless of human papillomavirus (HPV) test results. The present study suggested that HPV cotesting in patients with ASC-H cytology can provide more detailed and useful information regarding the risk of high-grade cervical intraepithelial neoplasia (CIN) lesions and the need for further treatment. When the result of the HPV test was negative, the risk of CIN lesions of grade ≥2 in women with ASC-H cytology was low. Consequently, reflex HPV testing, rather than immediately performance of invasive and expensive colposcopy with biopsy, should be an option for the management of women with ASC-H. PMID:25964305

Factors Associated with Adherence to Follow-up Colposcopy

ERIC Educational Resources Information Center

Fish, Laura J.; Moorman, Patricia G.; Wordlaw-Stintson, Lashawn; Vidal, Adriana; Smith, Jennifer S.; Hoyo, Cathrine

2013-01-01

Background: Understanding the gaps in knowledge about human papilloma virus (HPV) infection, transmission, and health consequences and factors associated with the knowledge gap is an essential first step for the development of interventions to improve adherence to follow-up among women with abnormal Pap smears. Purpose: To examine the relationship…

Cervical Cancer Screening - Multiple Languages

MedlinePlus

... français) Haitian Creole (Kreyol ayisyen) Hindi (हिन्दी) Japanese (日本語) Korean (한국어) Polish (polski) Portuguese (português) Russian ( ... Screening - हिन्दी (Hindi) PDF American Cancer Society Japanese (日本語) Expand Section Colposcopy - 日本語 (Japanese) Bilingual PDF ...

In vivo and in vitro hyperspectral imaging of cervical neoplasia

NASA Astrophysics Data System (ADS)

Wang, Chaojian; Zheng, Wenli; Bu, Yanggao; Chang, Shufang; Tong, Qingping; Zhang, Shiwu; Xu, Ronald X.

2014-02-01

Cervical cancer is a prevalent disease in many developing countries. Colposcopy is the most common approach for screening cervical intraepithelial neoplasia (CIN). However, its clinical efficacy heavily relies on the examiner's experience. Spectroscopy is a potentially effective method for noninvasive diagnosis of cervical neoplasia. In this paper, we introduce a hyperspectral imaging technique for noninvasive detection and quantitative analysis of cervical neoplasia. A hyperspectral camera is used to collect the reflectance images of the entire cervix under xenon lamp illumination, followed by standard colposcopy examination and cervical tissue biopsy at both normal and abnormal sites in different quadrants. The collected reflectance data are calibrated and the hyperspectral signals are extracted. Further spectral analysis and image processing works are carried out to classify tissue into different types based on the spectral characteristics at different stages of cervical intraepithelial neoplasia. The hyperspectral camera is also coupled with a lab microscope to acquire the hyperspectral transmittance images of the pathological slides. The in vivo and the in vitro imaging results are compared with clinical findings to assess the accuracy and efficacy of the method.

High prevalence of human papillomavirus type 58 in Mexican colposcopy patients.

PubMed

González-Losa, Maria del Refugio; Rosado-Lopez, Iván; Valdez-González, Nina; Puerto-Solís, Marylín

2004-03-01

Cervical cancer is the second most common cancer of the women worldwide. Infection with some genotypes of human papillomavirus is the most important risk factor associated to cervical cancer. To determine the prevalence and genotypes of papillomavirus in biopsies of women with squamous intraepithelial lesion and cervical cancer. Two hundred sequential patients of colposcopy clinic were studied. HPV diagnosis was done by polymerase chain reaction using MY09/MY11 primers, for genotyping line blot hybridization was used. A total of 186 women were beta globin positive; 104 (55.9%) had histology diagnosis of low-grade squamous intraepitelial lesions (LSIL), 67 (36.0%) high-grade squamous intraepitelial lesions (HSIL) and 15 (8.1%) invasive cervical cancer (IC). The prevalence of HPV was 56.4% (104/185); HPV 58 was founded in 28.5% of all positive women, HPV 16 in 25.7%, HPV 18 in 13.3%, HPV 33 in 11.4% and 31 in 8.5%. In all grades of the lesions HPV 58 was the most frequently. The high prevalence of HPV 58 among Mexican women with HSIL and IC, has important implications in prophylaxis.

Trade-offs in Cervical Cancer Prevention: Balancing Benefits and Risks

PubMed Central

Stout, Natasha K.; Goldhaber-Fiebert, Jeremy D.; Ortendahl, Jesse D.; Goldie, Sue J.

2009-01-01

Background New screening and vaccination technologies will provide women with more options for cervical cancer prevention. Because the risk of cervical cancer diminishes with effective routine screening, women may wish to consider additional attributes, such as the likelihood of false-positive results and diagnostic procedures for mild abnormalities likely to resolve without intervention in their screening choices. Methods We used an empirically calibrated simulation model of cervical cancer in the United States to assess the benefits and potential risks associated with prevention strategies differing by primary screening test, triage test for abnormal results (cytologic testing, human papillomavirus [HPV] DNA test), and screening frequency. Outcomes included colposcopy referrals, cervical intraepithelial neoplasia (CIN) types 1 and 2 or 3, lifetime cancer risk, and quality-adjusted life expectancy. Results Across strategies, colposcopy referrals and diagnostic workups varied 3-fold, although diagnostic rates of CIN 2 or 3 were similar and 95% of positive screening test results were for mild abnormalities likely to resolve on their own. For a representative group of a thousand 20-year-old women undergoing triennial screening for 10 years, we expect 1038 colposcopy referrals (7 CIN 2 or 3 diagnoses) from combined cytologic and HPV DNA testing and fewer than 200 referrals (6–7 CIN 2 or 3 diagnoses) for strategies that use triage testing. Similarly, for a thousand 40-year-old women, combined cytologic and HPV DNA testing led to 489 referrals (9 CIN 2 or 3), whereas alternative strategies resulted in fewer than 150 referrals (7–8 CIN 2 or 3). Using cytologic testing followed by triage testing in younger women minimizes both diagnostic workups and positive HPV test results, whereas in older women diagnostic workups are minimized with HPV DNA testing followed by cytologic triage testing. Conclusions Clinically relevant information highlighting trade-offs among cervical cancer prevention strategies allows for inclusion of personal preferences into women’s decision making about screening and provides additional dimensions to the construction of clinical guidelines. PMID:18809815

Effectiveness of see-and-treat for approaching pre-invasive lesions of uterine cervix.

PubMed

Monteiro, Aparecida Cristina Sampaio; Russomano, Fábio; Reis, Aldo; Camargo, Maria José de; Fialho, Susana Aidé; Tristão, Maria Aparecida; Soares, Thiers

2009-10-01

To compare the effectiveness between the see-and-treat (S&T) approach and the conventional one (with prior biopsy) for squamous intraepithelial lesions of uterine cervix. A cross-sectional study was conducted with 900 nonpregnant women with cytology suggestive of high grade squamous intraepithelial lesions in the city of Rio de Janeiro, Southeastern Brazil, between 1998 and 2004. The S&T approach consists of a large loop excision of the transformation zone procedure and is recommended when cytology is suggestive of high grade squamous intraepithelial lesion, satisfactory colposcopy with abnormalities compatible with the suspected cytological results, and the lesion is limited to the ectocervix or extends up to one centimeter of the endocervical canal. A subgroup of 336 patients whose colposcopy was considered satisfactory was analyzed, and they were divided into two groups for comparison: patients treated without prior biopsy (n = 288) and patients treated after a biopsy showing high grade squamous intraepithelial lesions (n = 48). Patients who were not treated or only treated more than a year later after recruitment at the colposcopy unit were considered dropouts. Of patients recruited during the study period, 71 were not treated or were only treated for at least a year. The overall dropout rate was 7.9% (95% CI: 6.1;9.7). Mean time elapsed between patient recruitment and treatment was 17.5 days in the S&T group and 102.5 days in the prior biopsy group. Dropout rates were 1.4% (95% CI: 0.04;2.7) and 5.% (95% CI: 0;12.3), respectively (p=0.07). The proportion of overtreated cases (negative histology) in the S&T group was 2.0% (95% CI: 0.4;3.6). The difference in the mean time elapsed between patient recruitment and treatment indicates that S&T is a time-saving approach The proportion of negative cases from using the S&T approach can be regarded as low.

Scale-Up of an Human Papillomavirus Testing Implementation Program in El Salvador

PubMed Central

Cremer, Miriam; Maza, Mauricio; Alfaro, Karla; Morales Velado, Mario; Felix, Juan; Castle, Philip E.; Kim, Jane; Gage, Julia C.

2017-01-01

Objective The Cervical Cancer Prevention in El Salvador is a demonstration project to introduce a lower-cost human papillomavirus (HPV)-DNA test into a public sector project. Started in October 2012, The Cervical Cancer Prevention in El Salvador consists of 3 phases and will ultimately screen 30,000 women. Results of phase 2 of the project are presented. The objective of this project was to compare colposcopy and noncolposcopy-based management for HPV-positive women. Material and Methods In phase 2, a total of 8,050 women, aged 30 to 49 years, were screened; 6,761 provided both self- and provider-collected specimens and 1,289 provided only provider-testing specimens. HPV results from self-collected specimens were not used in clinical management decisions. Women with provider-collected HPV-positive results were treated based on the strategy assigned to their community; the strategy was colposcopy management (CM) or screen-and-treat (ST) management if they were cryotherapy eligible or colposcopy if not eligible. Outcomes were assessed 6 months after screening. Results Overall, 489 (12.3%) of 3,963 women receiving CM and 465 (11.4%) of 4,087 women receiving ST tested HPV positive. In the CM cohort, 216 (44.2%) of 489 completed their intervention (203 treated, 11 diagnosed negative, 2 pregnant). In the ST cohort, 411 (88.4%) of 465 completed their intervention (407 treated, 2 diagnosed negative, 1 pregnant). Overall agreement between HPV test results from self-collected and provider-collected specimens was 93.7%, with a κ value of 0.70 (95% CI = 0.68–0.73). Conclusions Human papillomavirus testing with ST management resulted in an approximately twice completion rate compared with CM management. Agreement between self- and provider-based sampling was good and might be used to extend screening to women in areas that are more difficult to reach. PMID:27922905

Microarray detection of human papilloma virus genotypes among Turkish women with abnormal cytology at a colposcopy unit

PubMed Central

Uzun Çilingir, Işıl; Bengisu, Ergin; Ağaçfidan, Ali; Koksal, Muammer Osman; Topuz, Samet; Berkman, Sinan; İyibozkurt, Ahmet Cem

2013-01-01

Objective: There is a well-known association between human papilloma virus (HPV) and cervical neoplasia. The aim of this study was to investigate the types of HPV DNA and to compare the results with colposcopic findings among women with abnormal cytology. Material and Methods: A series of 76 consecutive women attending the clinic with the usual referral indications (ASC-US or higher in Pap) were examined by the conventional diagnostic tools (PAP smear, colposcopy,punch biopsy) and subjected to HPV testing. For HPV genotyping, we used a commercially avaliable HPV DNA chip (Genomica-CLART) which is a PCR based microarray system.The HPV test detected 35types of HPV (HPV-6/-11/-16/-18/-26/-31/-33/-35/-39/-40/-42/-43/-44/-45/-51/-52/-53/-54/-56/-58/-59/-61/-62/-66/-70/-71/-72/-73/-81/-83/84/-85/-89). Results: Overall, 44.7% of all patients were HPV positive. HPV was positive in 35%, 51.9%, 77.7% of the ASCUS, LSIL and HSIL groups respectively and HPV 16 was the most prevalent type in all groups. 6 %of patients had mutiple infections. 57.8% of biopsy proven SIL’s were HPV positive. The most prevalent HPV type was HPV 16 (54.5%).Colposcopic assessment revealed pathologic findings in 94.7% of biopsy proven SIL cases. Conclusion: Although it has been reported that the prevalence of HPV in the general population is lower than Western countries, and the prevalence and distribution of genotypes are smilar in patients with abnormal cytology. Further population based studies are needed to determine the prevalance and type distribution of HPV with normal and abnormal cytology in Turkish women. Despite the new technological progress in HPV virion, colposcopy is still very important diagnostic tool in the management of abnormal smears. PMID:24592066

Computer-aided-diagnosis (CAD) for colposcopy

NASA Astrophysics Data System (ADS)

Lange, Holger; Ferris, Daron G.

2005-04-01

Uterine cervical cancer is the second most common cancer among women worldwide. Colposcopy is a diagnostic method, whereby a physician (colposcopist) visually inspects the lower genital tract (cervix, vulva and vagina), with special emphasis on the subjective appearance of metaplastic epithelium comprising the transformation zone on the cervix. Cervical cancer precursor lesions and invasive cancer exhibit certain distinctly abnormal morphologic features. Lesion characteristics such as margin; color or opacity; blood vessel caliber, intercapillary spacing and distribution; and contour are considered by colposcopists to derive a clinical diagnosis. Clinicians and academia have suggested and shown proof of concept that automated image analysis of cervical imagery can be used for cervical cancer screening and diagnosis, having the potential to have a direct impact on improving women"s health care and reducing associated costs. STI Medical Systems is developing a Computer-Aided-Diagnosis (CAD) system for colposcopy -- ColpoCAD. At the heart of ColpoCAD is a complex multi-sensor, multi-data and multi-feature image analysis system. A functional description is presented of the envisioned ColpoCAD system, broken down into: Modality Data Management System, Image Enhancement, Feature Extraction, Reference Database, and Diagnosis and directed Biopsies. The system design and development process of the image analysis system is outlined. The system design provides a modular and open architecture built on feature based processing. The core feature set includes the visual features used by colposcopists. This feature set can be extended to include new features introduced by new instrument technologies, like fluorescence and impedance, and any other plausible feature that can be extracted from the cervical data. Preliminary results of our research on detecting the three most important features: blood vessel structures, acetowhite regions and lesion margins are shown. As this is a new and very complex field in medical image processing, the hope is that this paper can provide a framework and basis to encourage and facilitate collaboration and discussion between industry, academia, and medical practitioners.

Prevalence and predicting factors for anxiety in thai women with abnormal cervical cytology undergoing colposcopy.

PubMed

Jerachotechueantaveechai, Tanut; Charoenkwan, Kittipat; Wongpakaran, Nahathai

2015-01-01

To compare prevalence of anxiety in women with abnormal cervical cytology (Pap) undergoing colposcopy to that of women attending the outpatient clinic for check-up and to examine predicting factors. In this cross-sectional analytical study, 100 women with abnormal cervical cytology (abnormal Pap group) and 100 women who attended our outpatient clinic for check-up (control group) were recruited from June 2013 to January 2014. The Hospital Anxiety and Depression Scale (HADS) was employed to determine anxiety in the participants with the score of ≥ 11 suggestive of clinically significant anxiety. The prevalence of anxiety and the mean HADS scores for anxiety were compared between the groups. For those with abnormal Pap, association between clinical factors and anxiety was assessed. A p-value of < 0.05 was considered significant. Median age was different between the groups, 44.0 years in the abnormal Pap group and 50.0 years in the control group (p=0.01). The proportion of participants who had more than one sexual partner was higher in the abnormal Pap group, 39.2% vs. 24.7% (p=0.03) and the prevalence of anxiety was significantly higher 14/100 (14.0%) vs. 3/100 (3.0%) (p < 0.01). The prevalence of depression was comparable between the groups. The mean HADS scores for anxiety and depression subscales were significantly higher in the abnormal Pap group, 6.6 vs. 4.8 (P < 0.01) and 3.9 vs. 3.1 (p=0.05), respectively. For the abnormal Pap group, no definite association between clinical factors and anxiety was demonstrated. The prevalence of anxiety in women with abnormal Pap awaiting colposcopy was significantly higher than that of normal controls. Special attention including thorough counselling, with use of information leaflets and psychological support, should be directed to these women.

A Study of HPV Typing for the Management of HPV-Positive ASC-US Cervical Cytologic Results

PubMed Central

Schiffman, Mark; Vaughan, Laurence; Raine-Bennett, Tina R.; Castle, Philip E.; Katki, Hormuzd A.; Gage, Julia C.; Fetterman, Barbara; Befano, Brian; Wentzensen, Nicolas

2015-01-01

Background In US cervical screening, immediate colposcopy is recommended for women with HPV-positive ASC-US (equivocal) cytology. We evaluated whether partial typing by Onclarity™ (BD) might identify HPV-positive women with low enough CIN3+ risk to permit 1-year follow-up instead. Methods The NCI-Kaiser Permanente Northern California Persistence and Progression Cohort includes a subset of 13,890 women aged 21+ with HC2 (Qiagen)-positive ASC-US at enrollment; current median follow-up is 3.0 years. Using stratified random sampling, we typed 2,079 archived enrollment specimens including 329 women subsequently diagnosed with CIN3+, 563 with CIN2, and 1,187 with

A study of HPV typing for the management of HPV-positive ASC-US cervical cytologic results.

PubMed

Schiffman, Mark; Vaughan, Laurence M; Raine-Bennett, Tina R; Castle, Philip E; Katki, Hormuzd A; Gage, Julia C; Fetterman, Barbara; Befano, Brian; Wentzensen, Nicolas

2015-09-01

In US cervical screening, immediate colposcopy is recommended for women with HPV-positive ASC-US (equivocal) cytology. We evaluated whether partial typing by Onclarity™ (BD) might identify HPV-positive women with low enough CIN3+ risk to permit 1-year follow-up instead. The NCI-Kaiser Permanente Northern California Persistence and Progression cohort includes a subset of 13,890 women aged 21+ with HC2 (Qiagen)-positive ASC-US at enrollment; current median follow-up is 3.0years. Using stratified random sampling, we typed 2079 archived enrollment specimens including 329 women subsequently diagnosed with CIN3+, 563 with CIN2, and 1187 with

A cohort study of cervical screening using partial HPV typing and cytology triage.

PubMed

Schiffman, Mark; Hyun, Noorie; Raine-Bennett, Tina R; Katki, Hormuzd; Fetterman, Barbara; Gage, Julia C; Cheung, Li C; Befano, Brian; Poitras, Nancy; Lorey, Thomas; Castle, Philip E; Wentzensen, Nicolas

2016-12-01

HPV testing is more sensitive than cytology for cervical screening. However, to incorporate HPV tests into screening, risk-stratification ("triage") of HPV-positive women is needed to avoid excessive colposcopy and overtreatment. We prospectively evaluated combinations of partial HPV typing (Onclarity, BD) and cytology triage, and explored whether management could be simplified, based on grouping combinations yielding similar 3-year or 18-month CIN3+ risks. We typed ∼9,000 archived specimens, taken at enrollment (2007-2011) into the NCI-Kaiser Permanente Northern California (KPNC) HPV Persistence and Progression (PaP) cohort. Stratified sampling, with reweighting in the statistical analysis, permitted risk estimation of HPV/cytology combinations for the 700,000+-woman KPNC screening population. Based on 3-year CIN3+ risks, Onclarity results could be combined into five groups (HPV16, else HPV18/45, else HPV31/33/58/52, else HPV51/35/39/68/56/66/68, else HPV negative); cytology results fell into three risk groups ("high-grade," ASC-US/LSIL, NILM). For the resultant 15 HPV group-cytology combinations, 3-year CIN3+ risks ranged 1,000-fold from 60.6% to 0.06%. To guide management, we compared the risks to established "benchmark" risk/management thresholds in this same population (e.g., LSIL predicted 3-year CIN3+ risk of 5.8% in the screening population, providing the benchmark for colposcopic referral). By benchmarking to 3-year risk thresholds (supplemented by 18-month estimates), the widely varying risk strata could be condensed into four action bands (very high risk of CIN3+ mandating consideration of cone biopsy if colposcopy did not find precancer; moderate risk justifying colposcopy; low risk managed by intensified follow-up to permit HPV "clearance"; and very low risk permitting routine screening.) Overall, the results support primary HPV testing, with management of HPV-positive women using partial HPV typing and cytology. © 2016 UICC.

The population impact of HPV/cytology cervical cotesting at 3-year intervals: reduced cervical cancer risk and decreased yield of precancer per screen

PubMed Central

Silver, Michelle I.; Schiffman, Mark; Fetterman, Barbara; Poitras, Nancy; Gage, Julia C.; Wentzensen, Nicolas; Lorey, Thomas; Kinney, Walter; Castle, Philip E.

2016-01-01

Background Cervical screening aims to detect and treat precancer to prevent cervical cancer mortality and morbidity, while minimizing overtreatment of benign human papillomavirus (HPV) infections and related minor abnormalities. HPV/cytology cotesting at extended 5-year intervals is now a recommended screening strategy in the US, but the interval extension is controversial. We studied the impact of a decade of an alternative, 3-year cotesting, on rates of precancer and cancer at Kaiser Permanente Northern California. We also considered the effect on screening efficiency, defined as numbers of cotests/colposcopy visits needed to detect a precancer. Methods Two cohorts were defined. The “open cohort” included all women screened at least once during the study period; >1 million cotests were performed. In a fixed “long-term screening cohort”, we considered the cumulative impact of repeated screening at 3-year intervals by restricting to women first cotested in 2003–4 (i.e., no women entering screening later were added to this group). Results Detection of CIN3/AIS increased in the open cohort (2004–6, 82.0/100,000 women screened; 2007–9, 140.6/100,000; and 2010–12, 126.0/100,000); cancer diagnoses were unchanged. In the long-term screening cohort, detection of CIN3/AIS increased then decreased to the original level (2004–6, 80.5/100,000; 2007–9, 118.6/100,000; and 2010–2, 84.9/100,000). Cancer diagnoses decreased. Seen in terms of screening efficiency, the number of colposcopies performed todetect a single CIN3/AIS increased in the cohort with repeat screening. Conclusion Repeated cotesting at a 3-year interval eventually lowers population rates of precancer and cancer; however, a greater number of colposcopies is required to detect a single precancer. PMID:27657992

Enhancing colposcopy with polarized light.

PubMed

Ferris, Daron G; Li, Wenjing; Gustafsson, Ulf; Lieberman, Richard W; Galdos, Oscar; Santos, Carlos

2010-07-01

To determine the potential utility of polarized light used during colposcopic examinations. Matched, polarized, and unpolarized colposcopic images and diagnostic annotations from 31 subjects receiving excisional treatment of cervical neoplasia were compared. Sensitivity, specificity, and mean Euclidean distances between the centroids of the gaussian ellipsoids for the different epithelial types were calculated for unpolarized and polarized images. The sensitivities of polarized colposcopic annotations for discriminating cervical intraepithelial neoplasia (CIN) 2 or higher were greater for all 3 acetowhite categories when compared with unpolarized annotations (58% [44/76] vs 45% [34/76], 68% [50/74] vs 59% [45/76], and 68% [49/72] vs 66% [50/76], respectively). The average percent differences in Euclidean distances between the epithelial types for unpolarized and polarized cervical images were as follows: CIN 2/3 versus CIN 1 = 33% (10/30, p =.03), CIN 2/3 versus columnar epithelium = 22% (p =.004), CIN 2/3 versus immature metaplasia = 29% (14/47, p =.11), and CIN 1 versus immature metaplasia = 27% (4.4/16, p =.16). Because of its ability to interrogate at a deeper plane and eliminate obscuring glare, polarized light colposcopy may enhance the evaluation and detection of cervical neoplasias.

Organization and evolution of organized cervical cytology screening in Thailand.

PubMed

Khuhaprema, Thiravud; Attasara, Pattarawin; Srivatanakul, Petcharin; Sangrajrang, Suleeporn; Muwonge, Richard; Sauvaget, Catherine; Sankaranarayanan, Rengaswamy

2012-08-01

To describe phase 1 of an organized cytology screening project initiated in Thailand by the Ministry of Public Health and the National Health Security Office. Women aged 35-60 years were encouraged to undergo cervical screening in primary care units and hospitals through awareness programs. Papanicolaou smears were processed and reported at district or provincial cytology laboratories. Women with normal test results were advised to undergo repeat screening after 5 years, while those with precancerous and cancerous lesions were referred for colposcopy, biopsy, and treatment. Information on screening, referral, investigations, and therapy were logged in a computer database. Between 2005 and 2009, 69.2% of the 4030833 targeted women were screened. In all, 20991 women had inadequate smears; 27253 had low-grade squamous intraepithelial lesions; 15706 had high-grade squamous intraepithelial lesions; and 2920 had invasive cancers. Information on the management of precancerous lesions was available for only 17.4% of women referred for colposcopy. Although follow-up data on women with positive test results were inadequately documented, the present findings indicate that provision of cytology services through the existing healthcare system is feasible. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Reliability of the Xpert HPV assay to detect high-risk human papillomavirus DNA in a colposcopy referral population.

PubMed

Castle, Philip E; Smith, Katherine M; Davis, Thomas E; Schmeler, Kathleen M; Ferris, Daron G; Savage, Ashlyn H; Gray, Jermaine E; Stoler, Mark H; Wright, Thomas C; Ferenczy, Alex; Einstein, Mark H

2015-01-01

The Xpert HPV Assay (Xpert; Cepheid, Sunnyvale, CA) was developed for the multianalytic GeneXpert platform. In a colposcopy referral population of 708 women living in the United States, two cervical specimens, A and B, were collected, and both were tested by the Xpert assay for high-risk human papillomavirus (hrHPV) DNA, permitting an evaluation of its test reliability. Specimen B was also tested by Hybrid Capture 2 (hc2; Qiagen, Germantown, MD) and the cobas HPV Test (cobas; Roche Molecular Systems, Pleasanton, CA). The κ and percent agreement for any hrHPV for the two Xpert results were 0.88 and 94.5%, respectively. There was no statistical difference in testing positive on both specimens by Xpert (P = .62). The sensitivity for detection of cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) was 89.0% using specimen A and 90.4% using specimen B for Xpert, 90.4% for cobas, and 81.6% for hc2. The Xpert assay was sensitive and reliable for the detection of hrHPV and the identification of women with CIN2+. Copyright© by the American Society for Clinical Pathology.

Results at recruitment from a randomized controlled trial comparing human papillomavirus testing alone with conventional cytology as the primary cervical cancer screening test.

PubMed

Ronco, Guglielmo; Giorgi-Rossi, Paolo; Carozzi, Francesca; Confortini, Massimo; Dalla Palma, Paolo; Del Mistro, Annarosa; Gillio-Tos, Anna; Minucci, Daria; Naldoni, Carlo; Rizzolo, Raffaella; Schincaglia, Patrizia; Volante, Renza; Zappa, Marco; Zorzi, Manuel; Cuzick, Jack; Segnan, Nereo

2008-04-02

In the first recruitment phase of a randomized trial of cervical cancer screening methods (New Technologies for Cervical Cancer Screening [NTCC] study), we compared screening with conventional cytology with screening by human papillomavirus (HPV) testing in combination with liquid-based cytology. HPV-positive women were directly referred to colposcopy if aged 35 or older; if younger, they were retested after 1 year. In the second recruitment phase of NTCC, we randomly assigned women to conventional cytology (n = 24,661) with referral to colposcopy if cytology indicated atypical squamous cells of undetermined significance or more severe abnormality or to testing for high-risk HPV DNA alone by Hybrid Capture 2 (n = 24,535) with referral to colposcopy if the test was positive at a concentration of HPV DNA 1 pg/mL or greater. For the main endpoint of the study, histologic detection of cervical intraepithelial neoplasia of grade 2 or more (CIN2+), we calculated and compared sensitivity and positive predictive value (PPV) of the two screening methods using HPV DNA cutoffs of 1 pg/mL and 2 pg/mL. All statistical tests were two-sided. For women aged 35-60 years, the relative sensitivity of HPV testing for detection of CIN2+ at a cutoff of 1 pg/mL vs conventional cytology was 1.92 (95% CI = 1.28 to 2.87) and the relative PPV was 0.80 (95% CI = 0.55 to 1.18). At a cutoff of 2 pg/mL HPV DNA, the relative sensitivity was 1.81 (95% CI = 1.20 to 2.72) and the relative PPV was 0.99 (95% CI = 0.67 to 1.46). In this age group, there was no evidence of heterogeneity between study phases. Among women aged 25-34 years, the relative sensitivity for detection of CIN2+ of HPV testing at a cutoff of 1 pg/mL vs cytology was 3.50 (95% CI = 2.11 to 5.82), statistically significantly larger (P = .019) than that observed in phase 1 at this age (1.58; 95% CI = 1.03 to 2.44). For women aged 35-60 years, HPV testing with a cutoff of 2 pg/mL achieves a substantial gain in sensitivity over cytology with only a small reduction in PPV. Among women aged 25-34 years, the large relative sensitivity of HPV testing compared with conventional cytology and the difference between relative sensitivity during phases 1 and 2 suggests that there is frequent regression of CIN2+ that are detected by direct referral of younger HPV-positive women to colposcopy. Thus, triage test or repeat testing is needed if HPV is to be used for primary testing in this context.

Human papillomavirus (HPV) DNA triage of women with atypical squamous cells of undetermined significance with Amplicor HPV and Hybrid Capture 2 assays for detection of high-grade lesions of the uterine cervix.

PubMed

Dufresne, Simon; Sauthier, Philippe; Mayrand, Marie-Hélène; Petignat, Patrick; Provencher, Diane; Drouin, Pierre; Gauthier, Philippe; Dupuis, Marie-Josée; Michon, Bertrand; Ouellet, Stéphan; Hadjeres, Rachid; Ferenczy, Alex; Franco, Eduardo L; Coutlée, François

2011-01-01

Up to 20% of women having a cytology smear showing atypical squamous cells of undetermined significance (ASC-US) and infected with high-risk human papillomavirus (HR HPV) have high-grade cervical intraepithelial neoplasia (CIN 2/3). Results obtained with the Amplicor HPV and Hybrid Capture 2 (HC-2) assays for HR HPV DNA detection in women referred to colposcopy for an ASC-US smear were compared. Cervical samples in PreservCyt were tested for the presence of 13 HR HPV types with HC-2, with Amplicor at three cutoffs for positivity (0.2, 1.0, and 1.5 optical density units), and for 36 genotypes with the Linear Array (LA). Of 396 eligible women, 316 did not have CIN, 47 had CIN 1, 29 had CIN 2/3, and 4 had CIN of unknown grade. HR HPV was detected in 129 (32.6%) and 164 (41.4%) samples with HC-2 and Amplicor HPV (cutoff, 0.2), respectively (P = 0.01). Overall, 112 specimens were positive and 215 were negative with the HC-2 and Amplicor HPV assays (agreement of 82.6%; 95% confidence interval [CI], 78.5 to 86.0). The clinical sensitivity and specificity of Amplicor HPV at cutoffs of 0.2, 1.0 and 1.5 and of HC-2 for detection of CIN 2/3 were 89.7% (95% CI, 72.8 to 97.2) and 62.5% (95% CI, 57.5 to 52.4), 89.7% (95% CI, 72.8 to 97.2) and 64.5% (95% CI, 59.4 to 69.2), 89.7% (95% CI, 72.8 to 97.2) and 64.7% (95% CI, 59.7 to 69.5), and 93.1% (95% CI, 77.0 to 99.2) and 72.2% (95% CI, 67.4 to 76.5), respectively. Both HR HPV detection tests identified women with ASC-US who would benefit the most from colposcopy. Women with persistent HR HPV infection need further investigation despite a first normal colposcopy.

Genotyping for Human Papillomavirus (HPV) 16/18/52/58 Has a Higher Performance than HPV16/18 Genotyping in Triaging Women with Positive High-risk HPV Test in Northern Thailand

PubMed Central

Khunamornpong, Surapan; Settakorn, Jongkolnee; Sukpan, Kornkanok; Suprasert, Prapaporn; Srisomboon, Jatupol; Intaraphet, Suthida; Siriaunkgul, Sumalee

2016-01-01

Background Testing for high-risk human papillomavirus DNA (HPV test) has gained increasing acceptance as an alternative method to cytology in cervical cancer screening. Compared to cytology, HPV test has a higher sensitivity for the detection of histologic high-grade squamous intraepithelial lesion or worse (HSIL+), but this could lead to a large colposcopy burden. Genotyping for HPV16/18 has been recommended in triaging HPV-positive women. This study was aimed to evaluate the screening performance of HPV testing and the role of genotyping triage in Northern Thailand. Methods A population-based cervical screening program was performed in Chiang Mai (Northern Thailand) using cytology (conventional Pap test) and HPV test (Hybrid Capture 2). Women who had abnormal cytology or were HPV-positive were referred for colposcopy. Cervical samples from these women were genotyped using the Linear Array assay. Results Of 5,456 women, 2.0% had abnormal Pap test results and 6.5% tested positive with Hybrid Capture 2. Of 5,433 women eligible for analysis, 355 with any positive test had histologic confirmation and 57 of these had histologic HSIL+. The sensitivity for histologic HSIL+ detection was 64.9% for Pap test and 100% for Hybrid Capture 2, but the ratio of colposcopy per detection of each HSIL+ was more than two-fold higher with Hybrid Capture 2 than Pap test (5.9 versus 2.8). Genotyping results were available in 316 samples. HPV52, HPV16, and HPV58 were the three most common genotypes among women with histologic HSIL+. Performance of genotyping triage using HPV16/18/52/58 was superior to that of HPV16/18, with a higher sensitivity (85.7% versus 28.6%) and negative predictive value (94.2% versus 83.9%). Conclusions In Northern Thailand, HPV testing with genotyping triage shows better screening performance than cervical cytology alone. In this region, the addition of genotyping for HPV52/58 to HPV16/18 is deemed necessary in triaging women with positive HPV test. PMID:27336913

Primary screening for cervical cancer based on high-risk human papillomavirus (HPV) detection and HPV 16 and HPV 18 genotyping, in comparison to cytology.

PubMed

Agorastos, Theodoros; Chatzistamatiou, Kimon; Katsamagkas, Taxiarchis; Koliopoulos, George; Daponte, Alexandros; Constantinidis, Theocharis; Constantinidis, Theodoros C

2015-01-01

The objective of the present study is to assess the performance of a high-risk human papillomavirus (HR-HPV) DNA test with individual HPV-16/HPV-18 genotyping as a method for primary cervical cancer screening compared with liquid-based cytology (LBC) in a population of Greek women taking part in routine cervical cancer screening. The study, conducted by the "HEllenic Real life Multicentric cErvical Screening" (HERMES) study group, involved the recruitment of 4,009 women, aged 25-55, who took part in routine cervical screening at nine Gynecology Departments in Greece. At first visit cervical specimens were collected for LBC and HPV testing using the Roche Cobas 4800 system. Women found positive for either cytology or HPV were referred for colposcopy, whereas women negative for both tests will be retested after three years. The study is ongoing and the results of the first screening round are reported herein. Valid results for cytology and HPV testing were obtained for 3,993 women. The overall prevalence of HR-HPV was 12.7%, of HPV-16 2.7% and of HPV-18 1.4%. Of those referred for colposcopy, cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was detected in 41 women (1.07%). At the threshold of CIN2+, cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] and HPV testing showed a sensitivity of 53.7% and 100% respectively, without change between age groups. Cytology and HPV testing showed specificity of 96.8% and 90.3% respectively, which was increased in older women (≥30) in comparison to younger ones (25-29). Genotyping for HPV16/18 had similar accuracy to cytology for the detection of CIN2+ (sensitivity: 58.5%; specificity 97.5%) as well as for triage to colposcopy (sensitivity: 58.5% vs 53.7% for cytology). HPV testing has much better sensitivity than cytology to identify high-grade cervical lesions with slightly lower specificity. HPV testing with individual HPV-16/HPV-18 genotyping could represent a more accurate methodology for primary cervical cancer screening in comparison to liquid-based cytology, especially in older women.

Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test.

PubMed

Wright, Thomas C; Stoler, Mark H; Behrens, Catherine M; Sharma, Abha; Zhang, Guili; Wright, Teresa L

2015-02-01

ATHENA evaluated the cobas HPV Test as the primary screen for cervical cancer in women ≥25years. This reports the 3-year end-of-study results comparing the performance of HPV primary screening to different screening and triage combinations. 42,209 women ≥25years were enrolled and had cytology and hrHPV testing. Women with abnormal cytology (≥atypical squamous cells of undetermined significance) and those HPV positive were referred to colposcopy. Women not reaching the study endpoint of CIN2+ entered the 3-year follow-up phase. 3-year CIR of CIN3+ in cytology-negative women was 0.8% (95% CI; 0.5-1.1%), 0.3% (95% CI 0.1-0.7%) in HPV-negative women, and 0.3% (95% CI; 0.1-0.6%) in cytology and HPV negative women. The sensitivity for CIN3+ of cytology was 47.8% (95% CI; 41.6-54.1%) compared to 61.7% (95% CI; 56.0-67.5%) for the hybrid strategy (cytology if 25-29years and cotesting with cytology and HPV if ≥30years) and 76.1% (95% CI; 70.3-81.8%) for HPV primary. The specificity for CIN3+ was 97.1% (95% CI; 96.9-97.2%), 94.6% (95% CI; 94.4-94.8%), and 93.5% (95% CI; 93.3-93.8%) for cytology, hybrid strategy, and HPV primary, respectively. Although HPV primary detects significantly more cases of CIN3+ in women ≥25years than either cytology or hybrid strategy, it requires significantly more colposcopies. However, the number of colposcopies required to detect a single CIN3+ is the same as for the hybrid strategy. HPV primary screening in women ≥25years is as effective as a hybrid screening strategy that uses cytology if 25-29years and cotesting if ≥30years. However, HPV primary screening requires less screening tests. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

HPV16/18 genotyping for the triage of HPV positive women in primary cervical cancer screening in Chile.

PubMed

Lagos, Marcela; Van De Wyngard, Vanessa; Poggi, Helena; Cook, Paz; Viviani, Paola; Barriga, María Isabel; Pruyas, Martha; Ferreccio, Catterina

2015-01-01

We previously conducted a population-based screening trial of high-risk human papillomavirus (hrHPV) testing and conventional cytology, demonstrating higher sensitivity (92.7 % vs 22.1 % for CIN2+) but lower positive predictive value (10.5 % vs 23.9 %) of hrHPV testing. Here we report the performance of HPV16/18 genotyping to triage the hrHPV positive participants. Women aged 25 years and older received hrHPV (Hybrid Capture 2) and Papanicolaou testing; positives by either test underwent colposcopy and directed biopsy, as did a sample of double-negatives. hrHPV positive women were reflex-tested with HPV16/18 genotyping (Digene HPV Genotyping PS Test). Among the 8,265 participants, 10.7 % were hrHPV positive, 1.7 % had ASCUS+ cytology, 1.2 % had CIN2+; 776 (88 %) hrHPV positive women had complete results, of whom 38.8 % were positive for HPV16 (24.0 %), HPV18 (9.7 %) or both (5.1 %). CIN2+ prevalence in HPV16/18 positive women (16.3 %, 95 % CI 12.3-20.9) was twice that of HPV16/18 negative women (8.0 %, 95 % CI 5.7-10.8). HPV16/18 genotyping identified 40.5 % of CIN2, 66.7 % of CIN3 and 75.0 % of cancers. Compared to hrHPV screening alone, HPV16/18 triage significantly reduced the referral rate (10.7 % vs 3.7 %) and the number of colposcopies required to detect one CIN2+ (9 vs 6). When HPV16/18 negative women with baseline ASCUS+ cytology were also colposcopied, an additional 14 % of CIN2+ was identified; referral increased slightly to 4.2 %. HPV16/18 triage effectively stratified hrHPV positive women by their risk of high-grade lesions. HPV16/18 positive women must be referred immediately; referral could be deferred in HPV16/18 negative women given the slower progression of non-HPV16/18 lesions, however, they will require active follow-up.

Attendance at Cervical Cancer Screening and Use of Diagnostic and Therapeutic Procedures on the Uterine Cervix Assessed from Individual Health Insurance Data (Belgium, 2002-2006)

PubMed Central

Arbyn, Marc; Fabri, Valérie; Temmerman, Marleen; Simoens, Cindy

2014-01-01

Objective To assess the coverage for cervical cancer screening as well as the use of cervical cytology, colposcopy and other diagnostic and therapeutic interventions on the uterine cervix in Belgium, using individual health insurance data. Methods The Intermutualistic Agency compiled a database containing 14 million records from reimbursement claims for Pap smears, colposcopies, cervical biopsies and surgery, performed between 2002 and 2006. Cervical cancer screening coverage was defined as the proportion of women aged 25–64 that had a Pap smear within the last 3 years. Results Cervical cancer screening coverage was 61% at national level, for the target population of women between 25 and 64 years old, in the period 2004–2006. Differences between the 3 regions were small, but varied more substantially between provinces. Coverage was 70% for 25–34 year old women, 67% for those aged 35–39 years, and decreased to 44% in the age group of 60–64 years. The median screening interval was 13 months. The screening coverage varied substantially by social category: 40% and 64%, in women categorised as beneficiary or not-beneficiary of increased reimbursement from social insurance, respectively. In the 3-year period 2004–2006, 3.2 million screen tests were done in the target group consisting of 2.8 million women. However, only 1.7 million women got one or more smears and 1.1 million women had no smears, corresponding to an average of 1.88 smears per woman in three years of time. Colposcopy was excessively used (number of Pap smears over colposcopies = 3.2). The proportion of women with a history of conisation or hysterectomy, before the age of 65, was 7% and 19%, respectively. Conclusion The screening coverage increased slightly from 59% in 2000 to 61% in 2006. The screening intensity remained at a high level, and the number of cytological examinations was theoretically sufficient to cover more than the whole target population. PMID:24690620

Conservative management of CIN2: National Audit of British Society for Colposcopy and Cervical Pathology members' opinion.

PubMed

Macdonald, Madeleine; Smith, John H F; Tidy, John A; Palmer, Julia E

2018-04-01

There is no doubt that organised cervical screening programmes have significantly reduced the rates of cervical cancer by detection and treatment of high-grade cervical intraepithelial neoplasia (CIN2, CIN3). National UK guidelines do not differentiate between CIN2 and CIN3 as separate entities and recommend treatment for both, although a degree of uncertainty exists regarding the natural history of CIN2. This national survey of British Society for Colposcopy and Cervical Pathology members aimed to assess attitudes towards conservative management (CM) of CIN2 in the UK and identify potential selection criteria. In total, 511 members responded (response rate 32%); 55.6% offered CM for selective cases; 12.4% for all cases; 16.4% had formal guidelines. Most agreed age group was >40yrs (83%), HPV 16/18 positive (51.4%), smoking (60%), immuno-compromise (74.2%), and large lesion size (80.8%) were relative contraindications for CM. 75.9% favoured six-monthly monitoring, with 80.2% preferring excisional treatment for persistent high-grade disease. Many UK colposcopists manage CIN2 conservatively without formal guidelines. Potential selection criteria should be investigated by a multicentre study. Impact statement Although anecdotally some colposcopists manage many women with CIN2 conservatively, this National Audit of British Society for Colposcopy and Cytopathology members, we believe, is the first time this has been formally recorded. The survey assesses current attitudes towards conservative management (CM) of CIN2 and seeks to identify potential selection criteria that could be used to identify suitable women. It received over 500 responses and significantly, identified many colposcopists recommending CM of CIN2 for patients despite the lack of any formal guidance regarding this approach. The greater majority of respondents were keen to consider participating in a multicentre trial on CM of CIN2 targeting the UK screening population (25-64 years). The paper has international relevance as ACOG and ASCCP have recently changed their guidance for the management of CIN2 in younger women and now recommend CM with monitoring rather than first line ablative or excisional treatment due to concerns regarding overtreatment, especially in women who have not yet completed their family.

Balancing uncertainty and acceptance: understanding Chinese women's responses to an abnormal cervical smear result.

PubMed

Twinn, Sheila

2006-09-01

The aims of this study were to examine the responses of Hong Kong Chinese women receiving an abnormal smear result and to compare any differences in responses depending on the diagnosis of the abnormal smear. The implementation of cervical screening programmes has resulted in an increasing number of women receiving an abnormal smear result requiring cytological surveillance or referral for colposcopy. Evidence suggests that women frequently misunderstood such results, believing that they already have cancer. However, little is known about the responses of Chinese women in this situation. An exploratory qualitative study. Face-to-face semi-structured tape-recorded interviews were undertaken with 66 women sampled opportunistically from an urban centre of a major non-governmental service provider. Amongst this sample, 22 women required cytological surveillance, 20 required treatment for vaginitis and 24 were referred for colposcopy. Thematic analysis was undertaken of the translated interviews within and across groups to identify categories and themes illustrating women's responses to an abnormal smear result. An important difference in the comparison of the data sets was that of women's understanding of the cause of the abnormal result. Women with vaginitis understood the cause of their abnormality, whereas those in the other groups remained unclear about their abnormality, generating feelings of fear and uncertainty. Trust in practitioners influenced women's acceptance of the result. Although responses of Chinese women are similar to those in other population groups, with those referred for colposcopy experiencing greater anxiety than those undergoing cytological surveillance, balancing feelings of uncertainty and acceptance influenced Chinese women's responses to their abnormal results and allowed them to make sense of their result in their everyday life. Trust in the practitioner was essential to the acceptance of their result. Such findings highlight implications for nursing practice, in particular developing information-giving strategies and targeted information to help women manage feelings of uncertainty. The importance of trusting professional relationships in determining women's acceptance of an abnormal result is also highlighted. The findings suggest nurses working with Chinese women should consider the underlying influence of culture on women's beliefs and actions.

ACCISS study rationale and design: activating collaborative cancer information service support for cervical cancer screening.

PubMed

Cofta-Woerpel, Ludmila; Randhawa, Veenu; McFadden, H Gene; Fought, Angela; Bullard, Emily; Spring, Bonnie

2009-12-02

High-quality cancer information resources are available but underutilized by the public. Despite greater awareness of the National Cancer Institute's Cancer Information Service among low-income African Americans and Hispanics compared with Caucasians, actual Cancer Information Service usage is lower than expected, paralleling excess cancer-related morbidity and mortality for these subgroups. The proposed research examines how to connect the Cancer Information Service to low-income African-American and Hispanic women and their health care providers. The study will examine whether targeted physician mailing to women scheduled for colposcopy to follow up an abnormal Pap test can increase calls to the Cancer Information Service, enhance appropriate medical follow-up, and improve satisfaction with provider-patient communication. The study will be conducted in two clinics in ethnically diverse low-income communities in Chicago. During the formative phase, patients and providers will provide input regarding materials planned for use in the experimental phase of the study. The experimental phase will use a two-group prospective randomized controlled trial design. African American and Hispanic women with an abnormal Pap test will be randomized to Usual Care (routine colposcopy reminder letter) or Intervention (reminder plus provider recommendation to call the Cancer Information Service and sample questions to ask). Primary outcomes will be: 1) calls to the Cancer Information Service; 2) timely medical follow-up, operationalized by whether the patient keeps her colposcopy appointment within six months of the abnormal Pap; and 3) patient satisfaction with provider-patient communication at follow-up. The study examines the effectiveness of a feasible, sustainable, and culturally sensitive strategy to increase awareness and use of the Cancer Information Service among an underserved population. The goal of linking a public service (the Cancer Information Service) with real-life settings of practice (the clinics), and considering input from patients, providers, and Cancer Information Service staff, is to ensure that the intervention, if proven effective, can be incorporated into existing care systems and sustained. The approach to study design and planning is aimed at bridging the gap between research and practice/service. NCT00873288.

The population impact of human papillomavirus/cytology cervical cotesting at 3-year intervals: Reduced cervical cancer risk and decreased yield of precancer per screen.

PubMed

Silver, Michelle I; Schiffman, Mark; Fetterman, Barbara; Poitras, Nancy E; Gage, Julia C; Wentzensen, Nicolas; Lorey, Thomas; Kinney, Walter K; Castle, Philip E

2016-12-01

The objective of cervical screening is to detect and treat precancer to prevent cervical cancer mortality and morbidity while minimizing overtreatment of benign human papillomavirus (HPV) infections and related minor abnormalities. HPV/cytology cotesting at extended 5-year intervals currently is a recommended screening strategy in the United States, but the interval extension is controversial. In the current study, the authors examined the impact of a decade of an alternative, 3-year cotesting, on rates of precancer and cancer at Kaiser Permanente Northern California. The effect on screening efficiency, defined as numbers of cotests/colposcopy visits needed to detect a precancer, also was considered. Two cohorts were defined. The "open cohort" included all women screened at least once during the study period; > 1 million cotests were performed. In a fixed "long-term screening cohort," the authors considered the cumulative impact of repeated screening at 3-year intervals by restricting the cohort to women first cotested in 2003 through 2004 (ie, no women entering screening later were added to this group). Detection of cervical intraepithelial neoplasia 3/adenocarcinoma in situ (CIN3/AIS) increased in the open cohort (2004-2006: 82.0/100,000 women screened; 2007-2009: 140.6/100,000 women screened; and 2010-2012: 126.0/100,000 women screened); cancer diagnoses were unchanged. In the long-term screening cohort, the detection of CIN3/AIS increased and then decreased to the original level (2004-2006: 80.5/100,000 women screened; 2007-2009: 118.6/100,000 women screened; and 2010-2012: 84.9./100,000 women screened). The number of cancer diagnoses was found to decrease. When viewed in terms of screening efficiency, the number of colposcopies performed to detect a single case of CIN3/AIS increased in the cohort with repeat screening. Repeated cotesting at a 3-year interval eventually lowers population rates of precancer and cancer. However, a greater number of colposcopies are required to detect a single precancer. Cancer 2016;122:3682-6. © 2016 American Cancer Society. © 2016 American Cancer Society.

Application of Computer Assisted Colposcopy Education

DTIC Science & Technology

2001-05-01

design allowed for less generalizability of findings when compared with a randomized, controlled study. Language, age , and a literacy level of seventh...participants (Bensen et al., 1999; Lewis, 1999). Lewis (1999) noted CAI to be effective for persons across the age continuum. Even patients with low literacy...years of age or older and eligible for military medical care. Additionally, participants had to read at least at a seventh grade level, speak English

Application of Computer Assisted Colposcopy Education

DTIC Science & Technology

2001-05-29

Language, age , and a literacy level of seventh grade also limited the study. The comfort level of the participant with computer utilization was another...across the age continuum. Even patients with low literacy skills also benefited from the self- paced instruction and non-threatening learning environment...Inclusion criteria were that women had to be 18 years of age or older and eligible for military medical care. Additionally, participants had to read

Cost-effectiveness of liquid-based cytology with or without hybrid-capture II HPV test compared with conventional Pap smears: a study by the French Society of Clinical Cytology.

PubMed

Cochand-Priollet, Béatrix; Cartier, Isabelle; de Cremoux, Patricia; Le Galès, Catherine; Ziol, Marianne; Molinié, Vincent; Petitjean, Alain; Dosda, Anne; Merea, Estelle; Biaggi, Annonciade; Gouget, Isabelle; Arkwright, Sylviane; Vacher-Lavenu, Marie-Cécile; Vielh, Philippe; Coste, Joël

2005-11-01

Many articles concerning conventional Pap smears, ThinPrep liquid-based cytology (LBC) and Hybrid-Capture II HPV test (HC II) have been published. This study, carried out by the French Society of Clinical Cytology, may be conspicuous for several reasons: it was financially independent; it compared the efficiency of the conventional Pap smear and LBC, of the conventional Pap smear and HC II, and included an economic study based on real costs; for all the women, a "gold standard" reference method, colposcopy, was available and biopsies were performed whenever a lesion was detected; The conventional Pap smear, the LBC (split-sample technique), the colposcopy, and the biopsies were done at the same time. This study included 2,585 women shared into two groups: a group A of a high-risk population, a group B of a screening population. The statistical analysis of the results showed that conventional Pap smears consistently had superior or equivalent sensitivity and specificity than LBC for the lesions at threshold CIN-I (Cervical Intraepithelial Neoplasia) or CIN-II or higher. It underlined the low specificity of the HC II. Finally, the LBC mean cost was never covered by the Social Security tariff.

Automatic classification of acetowhite temporal patterns to identify precursor lesions of cervical cancer

NASA Astrophysics Data System (ADS)

Gutiérrez-Fragoso, K.; Acosta-Mesa, H. G.; Cruz-Ramírez, N.; Hernández-Jiménez, R.

2013-12-01

Cervical cancer has remained, until now, as a serious public health problem in developing countries. The most common method of screening is the Pap test or cytology. When abnormalities are reported in the result, the patient is referred to a dysplasia clinic for colposcopy. During this test, a solution of acetic acid is applied, which produces a color change in the tissue and is known as acetowhitening phenomenon. This reaction aims to obtaining a sample of tissue and its histological analysis let to establish a final diagnosis. During the colposcopy test, digital images can be acquired to analyze the behavior of the acetowhitening reaction from a temporal approach. In this way, we try to identify precursor lesions of cervical cancer through a process of automatic classification of acetowhite temporal patterns. In this paper, we present the performance analysis of three classification methods: kNN, Naïve Bayes and C4.5. The results showed that there is similarity between some acetowhite temporal patterns of normal and abnormal tissues. Therefore we conclude that it is not sufficient to only consider the temporal dynamic of the acetowhitening reaction to establish a diagnosis by an automatic method. Information from cytologic, colposcopic and histopathologic disciplines should be integrated as well.

The performance of multimodal hyperspectral spectroscopy in the detection of precancerous cervical lesions

NASA Astrophysics Data System (ADS)

Trahmono; Lusiana, N.; Indarti, J.

2017-08-01

The aim of this study was to compare the performance of multimodal hyperspectral spectroscopy (MHS), which combines fluorescence and reflectance spectroscopy, with that of conventional laboratory-based screening tests, such as the Papanicolaou (Pap) smear test and human papilloma virus (HPV) DNA test, for detecting precancerous lesions of the cervix. The study utilized a cross-sectional design, and the kappa test was used in the analytical assessment. MHS scans were obtained from a sample of 70 consecutive patients, followed by sample collection for Pap and HPV DNA analysis and colposcopy referral, if indicated. Of the 70 patients evaluated, the results of cervical spectroscopy were normal in 38 (54.3%) patients, and they were abnormal in 32 (45.7%) patients. Based on the cytology results, 45 (64.3%) samples were normal, and 25 (35.7%) samples were abnormal. According to the results of the HPV DNA test, 47 (67.14%) samples were normal, and 17 (24.28%) samples were abnormal. Based on the results of the kappa test, the agreement between MHS and cytology was 0.793 (p < 0.001). The agreement between MHS and the HPV DNA test was 0.195 (p = 0.086), and the agreement between MHS and colposcopy was 0.479 (p < 0.001).

[Early detection of cervical cancer in Chile: time for change].

PubMed

Léniz Martelli, Javiera; Van De Wyngard, Vanessa; Lagos, Marcela; Barriga, María Isabel; Puschel Illanes, Klaus; Ferreccio Readi, Catterina

2014-08-01

Mortality rates for cervical cancer (CC) in Chile are higher than those of developed countries and it has an unequal socioeconomic distribution. The recognition of human papilloma virus (HPV) as the causal agent of cervical cancer in the early 80's changed the prevention paradigms. Current goals are to prevent HPV infection by vaccination before the onset of sexual activity and to detect HPV infection in women older than 30 years. This article reviews CC prevention and early detection methods, discusses relevant evidence to support a change in Chile and presents an innovation proposal. A strategy of primary screening based on HPV detection followed by triage of HPV-positive women by colposcopy in primary care or by cytological or molecular reflex testing is proposed. Due to the existence in Chile of a well-organized nationwide CC prevention program, the replacement of a low-sensitivity screening test such as the Papanicolau test with a highly sensitive one such as HPV detection, could quickly improve the effectiveness of the program. The program also has a network of personnel qualified to conduct naked-eye inspections of the cervix, who could easily be trained to perform triage colposcopy. The incorporation of new prevention strategies could reduce the deaths of Chilean women and correct inequities.

[New colposcopic terminology: Rio de Janeiro--2011].

PubMed

Zlatkov, V; Kostova, P

2014-01-01

The purpose of this work is to review the new colposcopic classification of the International Federation for Cervical Pathology and Colposcopy (IFCPC) from 2011 and the possibilities for its application in diagnostic and treatment processes and research. It fulfills the necessity for a modern and widely applicable nomenclature of the findings and it is based on the latest knowledge in this area. Colposcopic terminology of the vagina, as part of the pathology of the lower genital tract, is included as well, while the vulva and perineum terminology is not yet finally adopted. Furthermore, the various cervical excisional techniques are evaluated and described. According to experts, the popularity of colposcopy will not diminish and it will continue to be used as a routine technique in daily practice. In a critical sense, despite its descriptive and punctual character, the accepted terminology classification does not give a new interpretation of the severity of changes, and as such, it does not significantly modify the diagnostic and therapeutic approach. The lack of a scoring system that would allow the dynamic comparison of the severity of symptoms and the categories over time is a serious weakness. This limits the new colposcopic classification as no more than a working sheet that descriptively assesses the findings of the lower genital tract.

Reduction of low- and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland.

PubMed

Pollock, K G J; Kavanagh, K; Potts, A; Love, J; Cuschieri, K; Cubie, H; Robertson, C; Cruickshank, M; Palmer, T J; Nicoll, S; Donaghy, M

2014-10-28

In Scotland, a national HPV immunisation programme began in 2008 for 12- to 13-year olds, with a catch-up campaign from 2008 to 2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established. We analysed colposcopy data from a cohort of women born between 1988 and 1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20-21 in 2008-2012. By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1; RR 0.71, 95% CI 0.58 to 0.87; P=0.0008), CIN 2 (RR 0.5, 95% CI 0.4 to 0.63; P<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58; P<0.0001) for women who received three doses of vaccine compared with unvaccinated women. To our knowledge, this is one of the first studies to show a reduction of low- and high-grade CIN associated with high uptake of the HPV bivalent vaccine at the population level. These data are very encouraging for countries that have achieved high HPV vaccine uptake.

An intelligent clinical decision support system for patient-specific predictions to improve cervical intraepithelial neoplasia detection.

PubMed

Bountris, Panagiotis; Haritou, Maria; Pouliakis, Abraham; Margari, Niki; Kyrgiou, Maria; Spathis, Aris; Pappas, Asimakis; Panayiotides, Ioannis; Paraskevaidis, Evangelos A; Karakitsos, Petros; Koutsouris, Dimitrios-Dionyssios

2014-01-01

Nowadays, there are molecular biology techniques providing information related to cervical cancer and its cause: the human Papillomavirus (HPV), including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS), composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%), high specificity (97.1%), high positive predictive value (89.4%), and high negative predictive value (97.1%), for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions.

An Intelligent Clinical Decision Support System for Patient-Specific Predictions to Improve Cervical Intraepithelial Neoplasia Detection

PubMed Central

Bountris, Panagiotis; Haritou, Maria; Pouliakis, Abraham; Margari, Niki; Kyrgiou, Maria; Spathis, Aris; Pappas, Asimakis; Panayiotides, Ioannis; Paraskevaidis, Evangelos A.; Karakitsos, Petros; Koutsouris, Dimitrios-Dionyssios

2014-01-01

Nowadays, there are molecular biology techniques providing information related to cervical cancer and its cause: the human Papillomavirus (HPV), including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS), composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%), high specificity (97.1%), high positive predictive value (89.4%), and high negative predictive value (97.1%), for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions. PMID:24812614

[Pap smear for mass screening: Results of an African experiment].

PubMed

Somé, O-R; Zongo, N; Ka, S; Wardini, R; Dem, A

2016-06-01

To assess the impact of smear test in the fight against cervix uteri cancer in Senegal. This was a descriptive cross-sectional study of 1836 Pap smears performed in patients over 15 years during several screening campaigns in Senegal conducted between June 2010 and June 2012. We analyzed epidemiological data, pathological smears, and the proposed management. In 69% of cases, the women were less than 45 years old. They were mostly multiparous and did not use contraceptive methods before. The smears were interpreted in 91.4% (n=1661) and were pathological in 5.2% of cases. They revealed mainly atypical squamous cells of undetermined significance, squamous intraepithelial low-grade lesions, and squamous intraepithelial high-grade lesions, respectively in 2.5% (n=46), 1.7% (n=30) and 1% (n=19) of cases. Multiparity, early marriages were the main risk factors. Patients with pathological smars had colposcopy with cryotherapy (23 cases), and colposcopy and biopsy (13 cases). A hysterectomy was performed in 4 cases. The pathological smear rate found in this study confirms the interest to continue cervical cancer screening with this practice. Strengthening of its geographical and financial access through a national prevention program will effectively help to lower cases of cervical cancer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

HPV DNA testing in population-based cervical screening (VUSA-Screen study): results and implications

PubMed Central

Rijkaart, D C; Berkhof, J; van Kemenade, F J; Coupe, V M H; Rozendaal, L; Heideman, D A M; Verheijen, R H M; Bulk, S; Verweij, W; Snijders, P J F; Meijer, C J L M

2012-01-01

Background: Human papillomavirus (HPV) testing is more sensitive than cytology for detecting high-grade cervical intraepithelial neoplasia (CIN). We evaluated the performance of high-risk HPV (hrHPV) testing in routine screening. Methods: In all, 25 871 women (29–61) enrolled in our population-based cohort study were offered both cytology and hrHPV testing. High-risk HPV-positive women with normal cytology and an age-matched subcohort of hrHPV-negative women with normal cytology were invited for repeat testing after 1 and/or 2 years and were referred for colposcopy if they presented with abnormal cytology and/or a positive hrHPV test. The hrHPV-positive women with borderline or mild dyskaryosis (BMD) and all women with moderate dyskaryosis or worse (>BMD) were directly referred for colposcopy. Women with BMD and an hrHPV-negative test were advised to repeat cytology at 6 and 18 months and were referred for colposcopy if the repeat cytology test was abnormal. The main outcome measure was CIN grade 3 or worse (CIN3+). Results were adjusted for non-attendance at repeat testing. Results: The hrHPV-positive women with abnormal cytology had a CIN3+ risk of 42.2% (95% confidence interval (CI): 36.4–48.2), whereas the hrHPV-positive women with normal cytology had a much lower risk of 5.22% (95% CI: 3.72–7.91). In hrHPV-positive women with normal cytology, an additional cytology step after 1 year reduced the CIN3+ risk to only 1.6% (95% CI: 0.6–4.9) if the repeat test was normal. The CIN3+ risk in women with hrHPV-positive normal cytology was higher among women invited for the first time (29–33 years of age) (9.1% 95% CI: 5.6–14.3) than among older women (3.0% 95% CI: 1.5–5.5). Conclusion: Primary hrHPV screening with cytology triage in women aged ⩾30 years is an effective way to stratify women on CIN3+ risk and seems a feasible alternative to cytological screening. Repeat cytology after 1 year for hrHPV-positive women with normal cytology is however necessary before returning women to routine screening. PMID:22251922

Cervical cancer screening intervals and management for women living with HIV: a risk benchmarking approach.

PubMed

Robbins, Hilary A; Strickler, Howard D; Massad, L Stewart; Pierce, Christopher B; Darragh, Teresa M; Minkoff, Howard; Keller, Marla J; Fischl, Margaret; Palefsky, Joel; Flowers, Lisa; Rahangdale, Lisa; Milam, Joel; Shrestha, Sadeep; Colie, Christine; DʼSouza, Gypsyamber

2017-04-24

We suggested cervical cancer screening strategies for women living with HIV (WLHIV) by comparing their precancer risks to general population women, and then compared our suggestions with current Centers for Disease Control and Prevention (CDC) guidelines. We compared risks of biopsy-confirmed cervical high-grade squamous intraepithelial neoplasia or worse (bHSIL+), calculated among WLHIV in the Women's Interagency HIV Study, to 'risk benchmarks' for specific management strategies in the general population. We applied parametric survival models among 2423 WLHIV with negative or atypical squamous cell of undetermined significance (ASC-US) cytology during 2000-2015. Separately, we synthesized published general population bHSIL+ risks to generate 3-year risk benchmarks for a 3-year return (after negative cytology, i.e. 'rescreening threshold'), a 6-12-month return (after ASC-US), and immediate colposcopy [after low-grade squamous intraepithelial lesion (LSIL)]. Average 3-year bHSIL+ risks among general population women ('risk benchmarks') were 0.69% for a 3-year return (after negative cytology), 8.8% for a 6-12-month return (after ASC-US), and 14.4% for colposcopy (after LSIL). Most CDC guidelines for WLHIV were supported by comparing risks in WLHIV to these benchmarks, including a 3-year return with CD4 greater than 500 cells/μl and after either three negative cytology tests or a negative cytology/oncogenic human papillomavirus cotest (all 3-year risks≤1.3%); a 1-year return after negative cytology with either positive oncogenic human papillomavirus cotest (1-year risk = 1.0%) or CD4 cell count less than 500 cells/μl (1-year risk = 1.1%); and a 6-12-month return after ASC-US (3-year risk = 8.2% if CD4 cell count at least 500 cells/μl; 10.4% if CD4 cell count = 350-499 cells/μl). Other suggestions differed modestly from current guidelines, including colposcopy (vs. 6-12 month return) for WLHIV with ASC-US and CD4 cell count less than 350 cells/μl (3-year risk = 16.4%) and a lengthened 2-year (vs. 1-year) interval after negative cytology with CD4 cell count at least 500 cells/μl (2-year risk = 0.98%). Current cervical cancer screening guidelines for WLHIV are largely appropriate. CD4 cell count may inform risk-tailored strategies.

The clinical application of HPV E6/E7 mRNA testing in triaging women with atypical squamous cells of undetermined significance or low-grade squamous intra-epithelial lesion Pap smear: A meta-analysis.

PubMed

Yang, Li; Zhu, Yuanhang; Bai, Yang; Zhang, Xiaoan; Ren, Chenchen

2017-01-01

The aim is to evaluate the clinical application value and correlation with cervical lesions' progression of human papillomavirus (HPV) E6/E7 mRNA test in women with atypical squamous cells of undetermined significance (ASCUS/borderline) or low-grade squamous intraepithelial lesions (LSILs/mild dyskaryosis) cytological abnormalities. A meta-analysis was conduct by searching China National Knowledge Infrastructure (1979-2016), Wanfang Date (1998-2016), VIP (1989-2016), PubMed (1950-2016), Web of Science (1950-2016) and Elsevier Science Direct (1998-2016), for studies on effect of HPV E6/E7 mRNA detection in women with ASCUS/LSIL/dyskaryosis. Study selection and appraisal were conducted independently by three authors, according to inclusive and exclusive criteria. Then, a meta-analysis was performed using the RevMan4.2 software. The subgroups analysis was conducted according to women's initial HPV DNA test results. Six articles with a total of 1024 subjects were included in the study. It was concluded that a positive HPV E6/E7 mRNA tested result have a higher risk of progressing to CIN2+ in future 2 years than a negative result. The pooled relative risk (RR) is 3.08, (95% confidence interval [CI] = 1.57-6.07, P < 0.05). The same situation was also observed in the subgroup of HPV DNA tested positive group and HPV DNA tested unlimited group. The pooled RR value of the two subgroups was, respectively, 1.98, (95% CI = 1.19-1.19, P < 0.05) and 7.58, (95% CI = 3.64-3.64, P < 0.05). A positive HPV E6/E7 mRNA testing result suggested the women with ASCUS, or LSIL Pap smear was in a truly dangerous position, which is an adverse prognostic factor. It suggested that cervical lesions stay in a progressing status and these women should be referred for colposcopy and strengthen follow-up promptly. Whereas, women with a negative HPV E6/E7 mRNA testing result can increase follow-up interval, by comprehensively considering their situation, thus, avoiding unnecessary colposcopy and reducing the rate of colposcopy and biopsy.

[Comparison of screening performance between primary high-risk HPV screening and high-risk HPV screening plus liquid-based cytology cotesting in diagnosis of cervical precancerous or cancerous lesions].

PubMed

Zhao, X L; Remila, Rezhake; Hu, S Y; Zhang, L; Xu, X Q; Chen, F; Pan, Q J; Zhang, X; Zhao, F H

2018-05-06

Objective: To evaluate and compare the screening performance of primary high-risk HPV(HR-HPV) screening and HR-HPV screening plus liquid-based cytology (LBC) cotesting in diagnosis of cervical cancer and precancerous lesions (CIN2+). Methods: We pooled 17 population-based cross-sectional studies which were conducted across China from 1999 to 2008. After obtaining informed consent, all women received liquid-based cytology(LBC)testing, HR-HPV DNA testing. Totally 28 777 women with complete LBC, HPV and biopsy results were included in the final analysis. Screening performance of primary HR-HPV DNA screening and HPV screening plus LBC co-testing in diagnosis of CIN2+ were calculated and compared among different age groups. Results: Among the whole population, the detection rates of primary HR-HPV screening and HR-HPV screening plus LBC co-testing are 3.05% (879 CIN2+) and 3.13%(900 CIN2+), respectively. The sensitivity were 96.4% and 98.7% (χ(2)=19.00, P< 0.001), and the specificity were 86.2% and 78.8% (χ(2)=2 067.00, P< 0.001), respectively. Areas under the receiver operating characteristic (ROC) curve (AUC) showed that the primary HR-HPV screening performed better than co-testing (AUC were 0.913 and 0.888; Z= 6.16, P< 0.001). Compared with primary HR-HPV screening, co-testing showed significantly higher colposcopy referral rates (16.5% and 23.6%, respectively, χ(2)=132.00, P< 0.001) and the number of colposcopy examination for detecting per CIN2+ (5.4 and 7.6, respectively).In the group aged 25-29, the colposcopy referral rates was 8.7 (10.9%(199 cases) vs 1.3%(23 cases)) times as much as the detection rate of primary HR-HPV screening in diagnosis of CIN2+, and was 12.5 (15.7%(288 cases) vs 1.3%(23 cases)) times as much as the detection rate of HR-HPV screening plus cytology contesting. Conclusion: Compared with primary HR-HPV screening, HR-HPV screening plus cytology co-testing does not show better results in the screening performance for CIN2+ detection, and the cost-effectiveness is not good enough, especially in younger age group.

Quality Improvement to Demonstrate the Lack of Reliability of the Human Papillomavirus mRNA Assay to Identify Women With Latent Human Papillomavirus Infections.

PubMed

Cotton, Sarah; Brown, Robert E; Nugent, Elizabeth K; Robazetti, Sonia C; Berens, Pamela D; Smith, Judith A

2018-04-01

To assess the consistency between human papillomavirus (HPV) mRNA testing in women with a history of previous HPV infections diagnosed by HPV DNA assay and the potential effects on follow-up HPV screening. This was a quality improvement study that used data from a pathology laboratory software database reviewed from November 2014 to June 2016 to identify female patients aged 30 years or older with greater than one HPV-positive result, including one or more HPV mRNA assay results and one or more documented HPV DNA assay results for comparison. Previous correlative cytology and colposcopic histopathology were also documented. American College of Obstetricians and Gynecologists' cervical cancer screening guidelines were used to compare potential differences in follow-up recommendations. Four hundred twenty-five charts for female patients 30 years of age or older were identified with one or more prior high-risk HPV infections by DNA assay. There was a 69.3% difference in HPV mRNA results compared with previous HPV DNA-positive results. There was a potential change in follow-up for 71.7% of patients with one prior high-risk-HPV-positive result and 60.0% of patients with two or more prior high-risk HPV-positive results. There were 231 colposcopy reports evaluated in this study. Of these, 62 (26.8%) were abnormal colposcopy reports, including 45 low-grade squamous intraepithelial lesions, 15 high-grade squamous intraepithelial lesions, and two cancers. Twenty-five (40.3%) abnormal colposcopy findings were in patients with a history of at least than two prior HPV DNA-positive results and a report of currently being HPV-negative with the mRNA assay. The HPV mRNA assays are less sensitive for detection of latent HPV infections compared with HPV DNA assays. Based on these data and the potential change in follow-up care, the HPV mRNA assay should not be used for a primary screening tool for cervical cancer. Many pathology laboratories have shifted to using the HPV mRNA assay without clear discussion with gynecologists about the effects on patient follow-up. The type of HPV assay being used should be documented and any HPV mRNA result confirmed by HPV DNA assay.

Management of ASCUS findings in Papanicolaou smears. A retrospective study.

PubMed

Iavazzo, C; Boutas, I; Grigoriadis, C; Vrachnis, N; Salakos, N

2012-01-01

Atypical squamous cells of undetermined significance (ASCUS) are a cervical cytologic finding category suggestive but not definitive of squamous intraepithelial lesions. ASCUS remains an incompletely described entity and accounts for even 5%-10% of reported Papanicolaou (Pap) smears. The management of women with such cytologic findings remains controversial. The aim of this study was to evaluate the cytology laboratory findings with regards to ASCUS diagnosis, using cervical Pap smears, and colposcopic biopsies, as well as their management. This is a retrospective study of patients with ASCUS Pap smears taken during the period January 2010 - December 2010 in the Second Department of Obstetrics and Gynecology, Aretaieion Hospital. During the study period, 657 Pap smears were examined at the Aretaieion Hospital; moreover, seven patients, whose Pap smears were cytologically diagnosed with ASCUS, were referred from other clinics, providing a total of 42 cases with a descriptive diagnosis of ASCUS for review. Of the 42 cases, eight were not studied because they were either lost in follow-up or they did not have available data. The remaining 34/42 patients were evaluated by colposcopic examination and directed biopsies where necessary. The ratio of ASCUS to low-grade squamous intraepithelial lesion (LGSIL), high-grade squamous cell intraepithelial lesion (HGSIL) or squamous cell carcinoma (SCC) was 5/34, 1/34, and 0/34, respectively. In the 34 ASCUS cases evaluated by colposcopy, the age distribution varied from 22 to 54 years. Eight of 34 cases did not have a child, 7/34 were primigravida, 18/34 were secondi-gravida, and 1/34 had four children. Four out of 34 cases were postmenopausal, 3/34 referred no history of abnormal bleeding, 21/34 were smokers, 6/34 used oral contraceptives, 2/34 used intrauterine devices, 1/34 took replacement of hormones, 4/34 had prior abnormal Pap smears human papillomavirus (HPV), or 1/34 had previous cancer (breast cancer). Colposcopy was inconclusive in 4/34 patients, while 8/34 cases were negative for Schiller and acetic acid tests and also had normal colposcopy. Infectious organisms were found in 8/34 patients with ASCUS, including actinomyces (1/8), trichomonas (5/8), and candida albicans (2/8). Histologic tests revealed 16/34 koilocytosis cases, 5/34 LGSIL, 1/34 HGSIL, and 0/34 SCC. The dilemma in the management of patients with an ASCUS diagnosis still exists as a significant problem for clinicians.

Primary Screening for Cervical Cancer Based on High-Risk Human Papillomavirus (HPV) Detection and HPV 16 and HPV 18 Genotyping, in Comparison to Cytology

PubMed Central

Constantinidis, Theocharis; Constantinidis, Theodoros C.

2015-01-01

Objectives The objective of the present study is to assess the performance of a high-risk human papillomavirus (HR-HPV) DNA test with individual HPV-16/HPV-18 genotyping as a method for primary cervical cancer screening compared with liquid-based cytology (LBC) in a population of Greek women taking part in routine cervical cancer screening. Methods The study, conducted by the “HEllenic Real life Multicentric cErvical Screening” (HERMES) study group, involved the recruitment of 4,009 women, aged 25–55, who took part in routine cervical screening at nine Gynecology Departments in Greece. At first visit cervical specimens were collected for LBC and HPV testing using the Roche Cobas 4800 system. Women found positive for either cytology or HPV were referred for colposcopy, whereas women negative for both tests will be retested after three years. The study is ongoing and the results of the first screening round are reported herein. Results Valid results for cytology and HPV testing were obtained for 3,993 women. The overall prevalence of HR-HPV was 12.7%, of HPV-16 2.7% and of HPV-18 1.4%. Of those referred for colposcopy, cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was detected in 41 women (1.07%). At the threshold of CIN2+, cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] and HPV testing showed a sensitivity of 53.7% and 100% respectively, without change between age groups. Cytology and HPV testing showed specificity of 96.8% and 90.3% respectively, which was increased in older women (≥30) in comparison to younger ones (25–29). Genotyping for HPV16/18 had similar accuracy to cytology for the detection of CIN2+ (sensitivity: 58.5%; specificity 97.5%) as well as for triage to colposcopy (sensitivity: 58.5% vs 53.7% for cytology). Conclusion HPV testing has much better sensitivity than cytology to identify high-grade cervical lesions with slightly lower specificity. HPV testing with individual HPV-16/HPV-18 genotyping could represent a more accurate methodology for primary cervical cancer screening in comparison to liquid-based cytology, especially in older women. PMID:25793281

A Study of Factors Influencing Productivity in the Obstetrics and Gynecology Outpatient Clinic at Walter Reed Army Medical Center.

DTIC Science & Technology

1992-08-01

area of infertility or GYN cancer . Patients for preoperative evaluation and post operative follow up are also seen in this clinic. This clinic is held...physicians can examine the cervix and surrounding tissue. In some cases, biopsies are performed to check for cancer . This clinic is held on Wednesday and...for fourteen physicians conducting various clinics (i.e., post-partum, oncology, infertility, colposcopy, cryotherapy , and sterilization), (d) three

What Resources are Required to Provide Full Service Obstetric and Gynecologic Care to DoD Employees and their Families on the Korean Peninsula?

DTIC Science & Technology

2007-06-10

limited high risk OB care Pelvic Pain Routine anatomy scan Polycystic Ovarian Syndrome (PCOS) Screening for cystic fibrosis/triple screen Incontinence...Amniocentesis Abnormal Uterine Bleeding Gestational diabetes Dysplasia (colposcopy/LEEP/cone biopsy) Preeclampsia Endometriosis Fetal anomalies (some...Analysis and Reporting Tool is a powerful ad-hoc query tool used to obtain summary and detailed views of population, clinical, and financial data from all

[Reliability of endocervical curettage after conservative treatment of intraepithelial neoplasia of the cervix].

PubMed

Lecointre, L; Akladios, C-Y; Averous, G; Lefebvre, F; Baulon, E; Thoma, V; Fender, M; Baldauf, J-J

2015-02-01

To evaluate the reliability of endocervical curettage (ECC) in patients previously treated for CIN. Retrospective analysis of data from 85 patients between January 1985 and December 2011 who received an ECC during monitoring after treatment of CIN. The reliability of the ECC was evaluated by comparison with the final histological analysis of the surgical specimen or the data for subsequent cyto-colpo-histological follow-up. Patients were referred to colposcopy either within the immediate post-treatment monitoring (n=42), meanly 9.7±5.3 months after treatment, or if cytological abnormalities were detected during long-term monitoring, meanly 78.6±52.4 months after treatment. Colposcopy was unsatisfactory in 75.3% of patients and normal colposcopic findings were found in 80% of patients. A perfect agreement between the ECC and the endocervical final diagnosis was noted in 68 patients (80%). For the diagnosis of severe cervical lesions (CIN 2+) ECC had a sensitivity of 86.2% (68.3-96.1), a specificity of 94.6% (85.1-98.9) and positive and negative predictive values of 61.4% (47.6-74.0) and 93% (83.0-98.1), respectively. The high sensitivity and negative predictive value of ECC for the diagnosis of severe post-therapeutic endocervical lesions avoid iterative treatment without increasing the risk of progression of a lesion to cancer. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Laser conization for the treatment of cervical intraepithelial neoplasia: the experience of the Colposcopy and Laser Surgery Unit, Department of Obstetrics and Gynecology, Conegliano Hospital

NASA Astrophysics Data System (ADS)

Fantin, Gian P.; Grasso, Alessandra; Tasinazzo, Raffaella; Bortolozzi, Giorgio

1998-01-01

From November 1990 to December 1995 eighty patients were treated with laser conization. They were high grade CIN extending to the endocervical canal and/or with purely ectocervical lesions and patients with low grade endocervical CIN persisting more than one year or cyto- histological discrepancy. Before surgery all the patients had colposcopy, cytology and guided cervical biopsies. Seventy-six out of eighty underwent local anaesthesia and in three cases a general anaesthetic was required although one case was treated without any anaesthesia. Complementary vaporization of the cone bed was performed in every single case. All specimens were judged fully evaluable by the pathologist. The accuracy of the preconization histology as evaluated in 79 patients. Exact agreement or a one degree discrepancy between punch biopsies and cone specimens was found in 96.25%. We did not find any unexpected invasive carcinoma. The apex of the specimen was free of disease in 93.75% of cases. A high grade lesion on the endocervical margin was found in 4 out of 5 cases with an apex involvement. Stenosis of the external cervical os occurred in 7 cases, 3 of which were symptomatic. In our experience laser conization is an effective and safe treatment of CIN with the results comparable to the literature.

Diagnostic performance of dual-staining cytology for cervical cancer screening: A systematic literature review.

PubMed

Tjalma, Wiebren A A

2017-03-01

Cervical cancer screening saves lives. Secondary prevention in cervical cancer screening relies on the results of primary cytology and/or HPV testing. However, primary screening with cytology has a low sensitivity, and HPV screening has a low specificity. This means that either cancers are missed, or women are over-treated. To improve performance outcomes, the concept of dual-stain cytology (CINtec ® PLUS Cytology test) has been introduced. In this approach, additional staining with p16/Ki-67 is performed in cases where cytology results are abnormal (LSIL or ASCUS) and/or HPV-positive. Another way to describe this approach might be "diagnostic" cytology. In order to assess the value of this "diagnostic cytology", a systematic literature review was conducted of dual-stain cytology performance across multiple studies until May 2016. In a Belgian screening population (women age 25-65 years), dual-stain cytology was significantly more sensitive (66%) and slightly less specific (-1.0%) than cytology. In the population referred to colposcopy or with abnormal cytology (ASCUS, LSIL), dual-staining showed a significantly higher increase in specificity, and a slightly lower sensitivity than HPV testing. Specificity gains resulted in fewer false positives and an increase in the number of correct referrals to colposcopy. Dual-staining with p16/Ki-67 cytology is an attractive biomarker approach for triage in cervical cancer screening. Copyright © 2017 Elsevier B.V. All rights reserved.

[Evaluation of practices of excisional therapies for CIN: An audit of surgery rooms from Marseilles' area].

PubMed

Einaudi, L; Boubli, L; Carcopino, X

2015-11-01

To evaluate what is the proportion of surgery rooms from Marseilles' area that do perform excisional therapies for CIN without any use of colposcopic guidance. From November 2012 to January 2013, a survey was conducted among all surgery rooms from Marseilles' area practicing excisional therapies for CIN. In addition, answers from gynecologists from Marseilles' area who participated to a national survey that evaluated practices of excisional therapies in France were specifically analyzed. Among the 55 surgery rooms from Marseilles' area practicing excisional therapies, 52 (94.1%) participated to the current survey. A colposcope was available in only 19 (36.5%) surgery rooms and was systematically used for the guidance of excisional therapies in only 4 (21%) of these surgery rooms. Finally, 36 (69.2%) surgery rooms answered performing excisional therapies without any use of colposcopic guidance. Colposcopy was occasionally and systematically used in 12 (23.1%) and 4 (7.7%) surgery rooms, respectively. Among the 116 gynecologists from Marseilles' area who answered to the national survey, 88 (75.9%) answered not using colposcopy when performing excision for CIN. Only 6% answered performing excision systematically under direct colposcopic vision and 18.1% occasionally. No colposcopic guidance is used when performing excision for CIN in the majority of surgery rooms from Marseilles' area. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Atypical Squamous Cells of Undetermined Significance: Bethesda Classification and Association with Human Papillomavirus

PubMed Central

Barcelos, Ana Cristina Macêdo; Michelin, Márcia Antoniazi; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

2011-01-01

Introduction. To analyze patients with atypical squamous cells of undetermined significance (ASCUS) through a cytology review and the presence of microbiological agents, with consideration of colposcopy and semiannual tracking. Methods. 103 women with ASCUS were reviewed and reclassified: normal/inflammatory, ASCUS, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). If ASCUS confirmed, it was subclassified in reactive or neoplastic ASCUS, ASC-US, or ASC-H; and Regione Emilia Romagna Screening Protocol. Patients underwent a colposcopic examination, and test for Candida sp., bacterial vaginosis, Trichomonas vaginalis, and human papillomavirus (HPV) were performed. Results. Upon review, ASCUS was diagnosis in 70/103 (67.9%), being 38 (54.2%) reactive ASCUS and 32 (45.71%) neoplastic ASCUS; 62 (88.5%) ASC-US and 8 (11.41%) ASC-H. ASCUS (Regione Protocol), respectively 1-5: 15 (21.4%), 19 (27.1%), 3 (27.1%), 16 (22.8%), and 1 (1.4%). A higher number of cases of cervical intraepithelial neoplasia (CIN) II/III in the biopsies of patients with ASC-H compared to ASC-US (P = .0021). High-risk HPV test and presence of CIN II/III are more frequent in ASC-H than ASC-US (P = .031). Conclusions. ASC-H is associated with clinically significant disease. High-risk HPV-positive status in the triage for colposcopy of patients with ASC-US is associated with increased of CIN. PMID:21760701

Andriod Device-Based Cervical Cancer Screening for Resource-Poor Settings.

PubMed

Kudva, Vidya; Prasad, Keerthana; Guruvare, Shyamala

2018-05-18

Visual inspection with acetic acid (VIA) is an effective, affordable and simple test for cervical cancer screening in resource-poor settings. But considerable expertise is needed to differentiate cancerous lesions from normal lesions, which is lacking in developing countries. Many studies have attempted automation of cervical cancer detection from cervix images acquired during the VIA process. These studies used images acquired through colposcopy or cervicography. However, colposcopy is expensive and hence is not feasible as a screening tool in resource-poor settings. Cervicography uses a digital camera to acquire cervix images which are subsequently sent to experts for evaluation. Hence, cervicography does not provide a real-time decision of whether the cervix is normal or not, during the VIA examination. In case the cervix is found to be abnormal, the patient may be referred to a hospital for further evaluation using Pap smear and/or biopsy. An android device with an inbuilt app to acquire images and provide instant results would be an obvious choice in resource-poor settings. In this paper, we propose an algorithm for analysis of cervix images acquired using an android device, which can be used for the development of decision support system to provide instant decision during cervical cancer screening. This algorithm offers an accuracy of 97.94%, a sensitivity of 99.05% and specificity of 97.16%.

Amplification of human papillomavirus early genes for detection of nine genotypes in Venezuelan women.

PubMed

Michelli, Elvia; Téllez, Luis; Mendoza, José-Andrés; Noguera, María-Eugenia; Milano, Melisse; Vera, Reauben; Callejas, Diana

2013-12-01

Genotyping of human papillomavirus (HPV) by molecular methods may enhance assessment information for screening and following of cervical infection. In this study, cervical samples were obtained from 250 women, along with colposcopic and cytological evaluations. A Nested-PCR-Multiplex assay was used for HPV detection and genotyping for HPV E6/E7 early regions. Infection with HPV was detected in 26.0% of the samples, with 98.46% positive for at least one genotype. High-risk HPVs were identified in 98.44%. HPV18 infection was detected in 76.92% of samples and HPV16 in 36.92%, whether as individual or as multiple infections. These infections were seen more frequently in women under 35 years of age (64.7%). The Pap-smear examination showed that 16.92% (11/65) of the samples had cervical changes suggesting HPV infection, whereas the colposcopic evaluation was suggestive of HPV infection in 47.69% (31/65) of DNA-HPV positive samples. There was a high frequency of high-risk HPV genotypes, particularly HPV18, alone or in multiple-type infections. Colposcopy findings showed to have a high predictive value for the diagnosis of HPV infection. The results reflect that over 50% of HPV-positive patients had a normal colposcopy and/or cytology, highlighting the importance of including HPV testing along with genotype identification in routine gynecological evaluations.

An audit of the cervical cancer screening histories of 246 women with carcinoma.

PubMed

Duggan, Máire A; Nation, Jill

2012-07-01

Women with cervical carcinoma and residing in the Calgary Health Region between 1996 and 2001 were audited to characterize factors in the opportunistic cervical cancer screening pathway contributing to screening failures. The cohort consisted of 246 women. Information on their Pap tests and colposcopic/gynecologic examinations was obtained from the files of Calgary Laboratory Services and their colposcopic/cancer center treatment charts. Screening failure factors were defined, and frequencies were calculated. Screening failure factors were as follows: (1) 41 (16.7%) were not screened, that is, no Pap test screening; (2) 29 (11.8%) were underscreened, that is, no Pap test within 12 months of diagnosis; (3) 28 (13.7%) were undersampled, that is, the Pap test result was negative; (4) 34 (13.8%) had no referral for a colposcopy/gynecology examination, and/or it was delayed for more than 3 months; (5) 18 (13.2%) had delayed referral for examination of an atypical glandular cell-high-grade squamous intraepithelial lesion and higher Pap test for more than 3 months; and (6) 73 (55.3%) were underdiagnosed, that is, the diagnosis in colposcopy examination was less than malignant. Underreported Pap tests and delayed Pap test reporting could not be fully investigated, but limited evidence suggested that underreporting contributed to some failures. Factors other than recruitment to cytological screening need targeted improvement if the region's cervical cancer prevention program is to be more effective.

Value of PAX1 Methylation Analysis by MS-HRM in the Triage of Atypical Squamous Cells of Undetermined Significance.

PubMed

Li, Shi-Rong; Wang, Zhen-Ming; Wang, Yu-Hui; Wang, Xi-Bo; Zhao, Jian-Qiang; Xue, Hai-Bin; Jiang, Fu-Guo

2015-01-01

Detection of cervical high grade lesions in patients with atypical squamous cells of undetermined significance (ASCUS) is still a challenge. Our study tested the efficacy of the paired boxed gene 1 (PAX1) methylation analysis by methylation-sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in ASCUS and compared performance with the hybrid capture 2 (HC2) human papillomavirus (HPV) test. A total of 463 consecutive ASCUS women from primary screening were selected. Their cervical scrapings were collected and assessed by PAX1 methylation analysis (MS-HRM) and high-risk HPV-DNA test (HC2). All patients with ASCUS were admitted to colposcopy and cervical biopsies. The Chi- square test was used to test the differences of PAX1 methylation or HPV infection between groups. The specificity, sensitivity, and accuracy for detecting CIN2 + lesions were: 95.6%, 82.4%, and 94.6%, respectively, for the PAX1 MS-HRM test; and 59.7%, 64.7%, and 60.0% for the HC2 HPV test. The PAX1 methylation analysis by MS-HRM demonstrated a better performance than the high-risk HPV-DNA test for the detection of high grade lesions (CIN2 +) in ASCUS cases. This approach could screen out the majority of low grade cases of ASCUS, and thus reduce the referral rate to colposcopy.

[Treatment of human papilloma virus of the cervix using cryosurgery].

PubMed

González Sánchez, J L; Celis, C; Rodríguez de Santiago, J D; Peña Sandoval, M; Menéndez Velásquez, J

1991-05-01

The causal lesions by VPH in the cervix, are associated to cancer. Currently 56 different subtypes have been isolated, from which, the 16, 18, 31, 33, 35 and 39 are more frequently related with the cervical intraepithelial neoplasia; from here derives the importance of opportune treatment. The objective of this paper is to evaluate VPH of the cervix opportune treatment with cryosurgery. Seventy five patients were analyzed, from April 1988 to May 1990 with diagnosis of cervical VPH, by cytology, colposcopy and histopathology; in whom cryosurgery with double freezing technique, was practiced; and were evaluated ever six months, during two years with cytology and colposcopy. Whenever there was persistence or recurrence, cryosurgery was used again; doing this even three times, previously discarding intraepithelial cancer. Seventy seven per cent of the patients received only one session; 16% two, and 7% three. At the six months review, it was found that 92% of the cases were negative, and 8% with persistence; at 12 months, 89% negative and 11% with recurrences; at 18 months, 93% negative, 3% with persistence and 4% with recurrence; at 24 months, 96% negative and 4% with recurrence. It is concluded that cryosurgery is efficacious in the treatment of these lesions, easy to use, well tolerated, with minimal side effects, it does not require anesthesia and is of a low cost.

Cervical cancer prevention in El Salvador (CAPE)-An HPV testing-based demonstration project: Changing the secondary prevention paradigm in a lower middle-income country.

PubMed

Maza, Mauricio; Alfaro, Karla; Garai, Jillian; Velado, Mario Morales; Gage, Julia C; Castle, Philip E; Felix, Juan; Luciani, Silvana; Campos, Nicole; Kim, Jane; Masch, Rachel; Cremer, Miriam

2017-05-01

•CareHPV tests were used to compare screen-and-treat and colposcopy management.•Screen-and-treat strategy with HPV testing was found to be very cost-effective.•CAPE has screened > 25,000 women in the Paracentral region.•Over 70% of screen-positive women received recommended treatment within six months.•CAPE is an example of public-private partnership resulting in paradigm change.

Pain Management for Gynecologic Procedures in the Office.

PubMed

Ireland, Luu Doan; Allen, Rebecca H

2016-02-01

Satisfactory pain control for women undergoing office gynecologic procedures is critical for both patient comfort and procedure success. Therefore, it is important for clinicians to be aware of the safety and efficacy of different pain control regimens. This article aimed to review the literature regarding pain control regimens for procedures such as endometrial biopsy, intrauterine device insertion, colposcopy and loop electrosurgical excisional procedure, uterine aspiration, and hysteroscopy. A search of published literature using PubMed was conducted using the following keywords: "pain" or "anesthesia." These terms were paired with the following keywords: "intrauterine device" or "IUD," "endometrial biopsy," "uterine aspiration" or "abortion," "colposcopy" or "loop electrosurgical excisional procedure" or "LEEP," "hysteroscopy" or "hysteroscopic sterilization." The search was conducted through July 2015. Articles were hand reviewed and selected by the authors for study quality. Meta-analyses and randomized controlled trials were prioritized. Although local anesthesia is commonly used for gynecologic procedures, a multimodal approach may be more effective including oral medication, a dedicated emotional support person, and visual or auditory distraction. Women who are nulliparous, are postmenopausal, have a history of dysmenorrhea, or suffer from anxiety are more likely to experience greater pain with gynecologic procedures. Evidence for some interventions exists; however, the interpretation of intervention comparisons is limited by the use of different regimens, pain measurement scales, patient populations, and procedure techniques. There are many options for pain management for office gynecologic procedures, and depending on the procedure, different modalities may work best. The importance of patient counseling and selection cannot be overstated.

PAX1 methylation analysis by MS-HRM is useful in triage of high-grade squamous intraepithelial lesions.

PubMed

Wang, Zhen-Ming

2014-01-01

This study is aimed to investigate the role of paired boxed gene 1 (PAX1) methylation analysis by methylation- sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and compared its performance with the Hybrid Capture 2 (HC2) human papillomavirus (HPV) test. In our study, 130 cases with a diagnosis of ASC-H from the cervical cytological screening by Thinprep cytologic test (TCT) technique were selected for triage. Their cervical scrapings were collected and evaluated by using PAX1 methylation analysis (MS-HRM) and high-risk HPV DNA test (HC2), followed by colposcopy and cervical biopsy. Chi-square test were used to test the differences of PAX1 methylation or HPV infection between groups. In the detection of CIN2+, the sensitivity, specificity, the PPV, NPV and the accuracy of PAX1 MS-HRM assay and high-risk HPV (HR-HPV) tests were respectively 80.6% vs 67.7%, 94.9% vs 54.5%, 83.3%, vs 31.8%, 94.0% vs 84.4%, and 91.5% vs 57.7%. The PAX1 MS-HRM assay proved superior to HR-HPV testing in the detection of high grade lesions (CIN2+) in ASC-H. This approach could screen out the majority of high grade lesion cases of ASC-H, and thus could reduce the referral rate to colposcopy.

Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

PubMed

Huh, Warner K; Ault, Kevin A; Chelmow, David; Davey, Diane D; Goulart, Robert A; Garcia, Francisco A R; Kinney, Walter K; Massad, L Stewart; Mayeaux, Edward J; Saslow, Debbie; Schiffman, Mark; Wentzensen, Nicolas; Lawson, Herschel W; Einstein, Mark H

2015-02-01

In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology and cotesting (cytology in combination with hrHPV testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective US-based registration study. Thirteen experts including representatives from the Society of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology, American College of Obstetricians and Gynecologists, American Cancer Society, American Society of Cytopathology, College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the FDA for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for healthcare providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

Cervical screening with primary HPV testing or cytology in a population of women in which those aged 33 years or younger had previously been offered HPV vaccination: Results of the Compass pilot randomised trial

PubMed Central

Canfell, Karen; Gebski, Val; Heley, Stella; Brotherton, Julia; Gertig, Dorota; Jennett, Chloe J.; Farnsworth, Annabelle; Castle, Philip E.; Saville, Marion

2017-01-01

Background Using primary human papillomavirus (HPV) testing for cervical screening increases detection of high-grade cervical intraepithelial neoplastic lesions and invasive cancer (cervical intraepithelial neoplasia grade 2+ [CIN2+]) compared to cytology, but no evaluation has been conducted in a population previously offered HPV vaccination. We aimed to assess colposcopy referral and CIN2+ detection rates for HPV-screened versus cytology-screened women in Australia’s HPV-vaccinated population (by 2014, resident women ≤33 years had been age-eligible for HPV vaccination, with 3-dose uptake across age cohorts being about 50%–77%). Methods and findings Compass is an open-label randomised trial of 5-yearly HPV screening versus 2.5-yearly liquid-based cytology (LBC) screening. In the first phase, consenting women aged 25–64 years presenting for routine screening at 47 primary practices in Victoria, Australia, provided a cervical sample and were randomised at a central laboratory at a 1:2:2 allocation to (i) image-read LBC screening with HPV triage of low-grade cytology (‘LBC screening’), (ii) HPV screening with those HPV16/18 positive referred to colposcopy and with LBC triage for other oncogenic (OHR) types (‘HPV+LBC triage’), or (iii) HPV screening with those HPV16/18 positive referred to colposcopy and with dual-stained cytology triage for OHR types (‘HPV+DS triage’). A total of 5,006 eligible women were recruited from 29 October 2013 to 7 November 2014 (recruitment rate 58%); of these, 22% were in the group age-eligible for vaccination. Data on 4,995 participants were analysed after 11 withdrawals; 998 were assigned to, and 995 analysed (99.7%) in, the LBC-screened group; 1,996 assigned to and 1,992 analysed (99.8%) in the HPV+LBC triage group; and 2,012 assigned to and 2,008 analysed (99.8%) in the HPV+DS triage group. No serious trial-related adverse events were reported. The main outcomes were colposcopy referral and detected CIN2+ rates at baseline screening, assessed on an intention-to-treat basis after follow-up of the subgroup of triage-negative women in each arm referred to 12 months of surveillance, and after a further 6 months of follow-up for histological outcomes (dataset closed 31 August 2016). Analysis was adjusted for whether women had been age-eligible for HPV vaccination or not. For the LBC-screened group, the overall referral and detected CIN2+ rates were 27/995 (2.7% [95% CI 1.8%–3.9%]) and 1/995 (0.1% [95% CI 0.0%–0.6%]), respectively; for HPV+LBC triage, these were 75/1,992 (3.8% [95% CI 3.0%–4.7%]) and 20/1,992 (1.0% [95% CI 0.6%–1.5%]); and for HPV+DS triage, these were 79/2,008 (3.9% [95% CI 3.1%–4.9%]) and 24/2,008 (1.2% [95% CI 0.8%–1.6%]) (p = 0.09 for difference in referral rate in LBC versus all HPV-screened women; p = 0.003 for difference in CIN2+ detection rate in LBC versus all HPV-screened women, with p = 0.62 between HPV screening groups). Limitations include that the study population involved a relatively low risk group in a previously well-screened and treated population, that individual women’s vaccination status was unknown, and that long-term follow-up data on disease detection in screen-negative women are not yet available. Conclusions In this study, primary HPV screening was associated with significantly increased detection of high-grade precancerous cervical lesions compared to cytology, in a population where high vaccine uptake was reported in women aged 33 years or younger who were offered vaccination. It had been predicted that increased disease detection might be associated with a transient increase in colposcopy referral rates in the first round of HPV screening, possibly dampened by HPV vaccine effect; in this study, although the point estimates for referral rates in women in each HPV-screened group were 41%–44% higher than in cytology-screened women, the difference in referral rate between cytology- and HPV-screened women was not significant. These findings provide initial support for the implementation of primary HPV screening in vaccinated populations. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12613001207707 PMID:28926579

Cervical screening with primary HPV testing or cytology in a population of women in which those aged 33 years or younger had previously been offered HPV vaccination: Results of the Compass pilot randomised trial.

PubMed

Canfell, Karen; Caruana, Michael; Gebski, Val; Darlington-Brown, Jessica; Heley, Stella; Brotherton, Julia; Gertig, Dorota; Jennett, Chloe J; Farnsworth, Annabelle; Tan, Jeffrey; Wrede, C David; Castle, Philip E; Saville, Marion

2017-09-01

Using primary human papillomavirus (HPV) testing for cervical screening increases detection of high-grade cervical intraepithelial neoplastic lesions and invasive cancer (cervical intraepithelial neoplasia grade 2+ [CIN2+]) compared to cytology, but no evaluation has been conducted in a population previously offered HPV vaccination. We aimed to assess colposcopy referral and CIN2+ detection rates for HPV-screened versus cytology-screened women in Australia's HPV-vaccinated population (by 2014, resident women ≤33 years had been age-eligible for HPV vaccination, with 3-dose uptake across age cohorts being about 50%-77%). Compass is an open-label randomised trial of 5-yearly HPV screening versus 2.5-yearly liquid-based cytology (LBC) screening. In the first phase, consenting women aged 25-64 years presenting for routine screening at 47 primary practices in Victoria, Australia, provided a cervical sample and were randomised at a central laboratory at a 1:2:2 allocation to (i) image-read LBC screening with HPV triage of low-grade cytology ('LBC screening'), (ii) HPV screening with those HPV16/18 positive referred to colposcopy and with LBC triage for other oncogenic (OHR) types ('HPV+LBC triage'), or (iii) HPV screening with those HPV16/18 positive referred to colposcopy and with dual-stained cytology triage for OHR types ('HPV+DS triage'). A total of 5,006 eligible women were recruited from 29 October 2013 to 7 November 2014 (recruitment rate 58%); of these, 22% were in the group age-eligible for vaccination. Data on 4,995 participants were analysed after 11 withdrawals; 998 were assigned to, and 995 analysed (99.7%) in, the LBC-screened group; 1,996 assigned to and 1,992 analysed (99.8%) in the HPV+LBC triage group; and 2,012 assigned to and 2,008 analysed (99.8%) in the HPV+DS triage group. No serious trial-related adverse events were reported. The main outcomes were colposcopy referral and detected CIN2+ rates at baseline screening, assessed on an intention-to-treat basis after follow-up of the subgroup of triage-negative women in each arm referred to 12 months of surveillance, and after a further 6 months of follow-up for histological outcomes (dataset closed 31 August 2016). Analysis was adjusted for whether women had been age-eligible for HPV vaccination or not. For the LBC-screened group, the overall referral and detected CIN2+ rates were 27/995 (2.7% [95% CI 1.8%-3.9%]) and 1/995 (0.1% [95% CI 0.0%-0.6%]), respectively; for HPV+LBC triage, these were 75/1,992 (3.8% [95% CI 3.0%-4.7%]) and 20/1,992 (1.0% [95% CI 0.6%-1.5%]); and for HPV+DS triage, these were 79/2,008 (3.9% [95% CI 3.1%-4.9%]) and 24/2,008 (1.2% [95% CI 0.8%-1.6%]) (p = 0.09 for difference in referral rate in LBC versus all HPV-screened women; p = 0.003 for difference in CIN2+ detection rate in LBC versus all HPV-screened women, with p = 0.62 between HPV screening groups). Limitations include that the study population involved a relatively low risk group in a previously well-screened and treated population, that individual women's vaccination status was unknown, and that long-term follow-up data on disease detection in screen-negative women are not yet available. In this study, primary HPV screening was associated with significantly increased detection of high-grade precancerous cervical lesions compared to cytology, in a population where high vaccine uptake was reported in women aged 33 years or younger who were offered vaccination. It had been predicted that increased disease detection might be associated with a transient increase in colposcopy referral rates in the first round of HPV screening, possibly dampened by HPV vaccine effect; in this study, although the point estimates for referral rates in women in each HPV-screened group were 41%-44% higher than in cytology-screened women, the difference in referral rate between cytology- and HPV-screened women was not significant. These findings provide initial support for the implementation of primary HPV screening in vaccinated populations. Australian New Zealand Clinical Trials Registry ACTRN12613001207707.

Clinical scoring system to detect malignant and premalignant vulval lesions.

PubMed

Tyagi, Shakun; Tripathi, Reva; Batra, Swaraj

2014-02-01

To construct a simple clinical scoring system for evaluation of vulval lesions that will be helpful in clinically detecting the premalignant or malignant lesions of vulva. Seventy women referred for vulval examination at a tertiary care centre in north India were examined over a period of 2 years. Biopsy was performed in 66 consenting women. Association of high-grade vulval lesion with various clinical parameters such as age, duration of symptoms, presenting complaints, the presence of depigmentation, ulceration, hyperkeratosis, acetowhite changes on acetic acid application, asymmetrical distribution of the lesion, surface elevation on naked eye or colposcopy, induration on palpation and toluidine blue stain retention was studied. The significantly associated factors were assigned a value of 0 or 1 depending on whether they were present or absent. Score was then formulated for detection of high-grade lesion defined as moderate to severe dysplasia and early malignancy. Histopathology. Out of the various parameters that were studied, duration of symptoms more than 6 months, hyperkeratosis, asymmetrical distribution of the lesion, surface elevation on naked eye or colposcopy, induration on palpation and positive toluidine blue stain retention of the lesion were found to be significantly associated with a malignant or premalignant lesion. It was found that a score of equal to or greater than 3/6 was significantly associated with a malignant or premalignant lesion. This simple scoring system has a potential to identify the high-grade lesions and can be used to identify the vulval lesion requiring a biopsy or further referral to higher centre.

Identification of potential missed opportunities for human papillomavirus (HPV) vaccination in women referred to an academic colposcopy clinic for evaluation of abnormal cervical cytology.

PubMed

Dorton, Benjamin J; Vitonis, Allison F; Feldman, Sarah

2016-06-02

To identify possible predictors of missed opportunities for human papillomavirus (HPV) counseling and vaccination prior to presentation at an academic colposcopy clinic. We examined the characteristics of 638 vaccinated and 1,024 unvaccinated age-eligible patients using data from a patient registry of women presenting for colposcopic evaluation between 2/26/2007 and 3/10/2014 who were aged 26 or less at presentation. Demographics, smoking history, pregnancy history, sexually transmitted infections (STIs), sexual history, contraception use, immunosuppression, and medical problems were compared between HPV vaccinated and unvaccinated women. Multivariable logistic regression models included age, race, language, marital status, insurance type, lifetime number of sexual partners, other medical illnesses, number of pregnancies, contraception use, history of STIs, and smoking history to determine predictors of HPV vaccination. In multivariable analysis, race, marital status, and language were not significantly associated with HPV vaccination. Women with fewer pregnancies were more likely to be vaccinated (p-trend <0 .0001). Vaccinated women were more likely to have other medical illnesses (OR=1.44, 95% CI=1.13-1.83) and be aware of their HPV status (OR=1.75, 95% CI= 1.40-2.18). In this study, greater number of pregnancies was associated with lower vaccination rates as compared to women who had never been pregnant. Reproductive health visits, such as postpartum and family planning visits, represent an ideal opportunity to educate women about HPV and the importance of vaccination, and should be an area of focus to improve current HPV vaccination rates.

Long-term psychosocial impact of alternative management policies in women with low-grade abnormal cervical cytology referred for colposcopy: a randomised controlled trial.

PubMed

Sharp, L; Cotton, S; Gray, N; Avis, M; Russell, I; Walker, L; Waugh, N; Whynes, D; Woolley, C; Thornton, A; Smart, L; Cruickshank, M; Little, J

2011-01-18

The debate continues regarding the best management for women with low-grade abnormal cervical cytology attending colposcopy. We compared psychosocial outcomes of alternative management policies in these women. In all, 989 women, aged 20-59 years, with low-grade abnormal cytology, were randomised to immediate large loop excision (LLETZ) or two to four targeted punch biopsies taken immediately with recall for LLETZ if these showed cervical intra-epithelial neoplasia 2/3. At 6 weeks after the last procedure, women completed the hospital anxiety and depression scale (HADS) and the impact of event scale (IES). At 12, 18, 24 and 30 months post recruitment, women completed the HADS and process outcome specific measure (POSM). Prevalence of significant depression (≥ 8), significant anxiety (≥ 11) and distress (≥ 9) and median POSM scores were compared between arms. Multivariate odds ratios (ORs) for immediate LLETZ vs biopsy and recall were computed. Over the entire follow-up, there was no significant difference between arms in cumulative prevalence or risk of significant depression (OR=0.78, 95% CI 0.52-1.17) or significant anxiety (OR=0.83, 95% CI 0.57-1.19). At 6 weeks post procedure, distress did not differ significantly between arms. At later time points, 8-11% had significant depression and 14-16% had significant anxiety but with no differences between arms. The POSM scores did not differ between the arms. There is no difference in long- or short-term psychosocial outcomes of immediate LLETZ and punch biopsies with selective recall.

Naked-eye inspection of the cervix after acetic acid application may improve the predictive value of negative cytologic screening.

PubMed

Frisch, L E; Milner, F H; Ferris, D G

1994-11-01

The purpose of this study was to assess the predictive value of naked-eye inspection of the cervix (NIC) after acetic acid application as an adjunct to Papanicolaou (Pap) testing for cervical cancer screening. Study subjects were women attending a medical college student health clinic either for cervical cytologic screening (67%) or because of a recent atypical cytologic screening result (33%). All study participants received cytologic screening, cervicography, and NIC. Of the 95 patients, 71 (75%) had abnormal findings on NIC. Fifty-one patients underwent colposcopy with biopsy, including 48 of the 71 with an abnormal finding on NIC. The results of 40 of the biopsies were abnormal: 36 showed human papillomavirus or low-grade squamous intraepithelial lesions, 3 showed high-grade squamous intraepithelial lesions, and 1 showed invasive cervical cancer. Sixty-five percent (26) of the abnormal biopsy findings occurred in women with normal cytologic test results. NIC and cervicography both were effective in identifying patients with abnormalities, but the combination of NIC followed by cervicography referred fewer women for colposcopy than did a positive result on NIC alone (52% vs 75%). The combination of a negative Pap smear and a negative NIC result had a 91% predictive value for the absence of cervical intraepithelial neoplasia. This was a significant improvement over cytologic screening alone. In this study, the combination of cytologic screening (Pap smear) and NIC increased the screening yield as compared with a Pap smear alone but with some loss of positive predictive value. NIC significantly improved the predictive value of negative cytologic screening results.

Analysis of 13 million individual patient records pertaining to Pap smears, colposcopies, biopsies and surgery on the uterine cervix (Belgium, 1996-2000).

PubMed

Arbyn, Marc; Simoens, Cindy; Van Oyen, Herman; Foidart, Jean-Michel; Goffin, Frédéric; Simon, Philippe; Fabri, Valérie

2009-05-01

Cervical cancer screening by surveys overestimate coverage because of selection and reporting biases. The prepared Inter-Mutualistic Agency dataset has about 13 million records from Pap smears, colposcopies, cervical biopsies and surgery, performed in Belgium between 1996 and 2000. Cervical cancer screening coverage was defined as the proportion of the target population (women of 25-64 years) that has had a Pap smear taken within the last 3 years. Proportions and incidence rates were computed using official population data of the corresponding age group, area and calendar year. Cervical cancer screening coverage, in the period 1998-2000, was 59% at national level, for the target age group 25-64 years. Differences were small between the 3 regions. Variation ranged from 39% to 71%. Coverage was 64% for 25-29 year old women, 67% for those aged 30-39 years, 56% for those aged 50-54. The modal screening interval was 1 year. In the 3-year period 1998-2000, 3 million smears were taken from the 2.7 million women in the age group 25-64. Only 1.6 million women of the target group got one or more smears in that period and 1.1 million women had no smears, corresponding to an average of 1.88 smears per woman. Coverage reached only 59%, but the number of smears used was sufficient to cover more than 100% of the target population. Structural reduction of overuse and extension of coverage is warranted.

Information and cervical screening: a qualitative study of women's awareness, understanding and information needs about HPV.

PubMed

Goldsmith, Megan R; Bankhead, Clare R; Kehoe, Sean T; Marsh, Gill; Austoker, Joan

2007-01-01

To explore women's attitudes towards the information about human papilloma virus (HPV) provided during cervical screening and to describe women's HPV information needs. Women with a range of screening results (normal, inadequate, borderline and abnormal) were identified by three screening centres in England. Two consecutive samples of women attending for colposcopy for the first time following screening were also approached. Seven focus groups were conducted between May 2005 and April 2006 with 38 women who had recently been for cervical screening or had attended a colposcopy appointment. Most women had no prior awareness of HPV. Many women queried the importance of being informed about HPV as no preventive advice or treatment is available. The HPV information included in the UK national screening programme abnormal result leaflet left women with more questions than answers (a list of unanswered questions is included with the results). Further information was requested about HPV detection, infection and transmission as well as the natural history and progression of cervical cancer. No consensus was reached regarding the best time to provide HPV information. Clear communication of the complicated issues surrounding HPV infection and the natural history of cervical cancer is a considerable educational challenge for screening providers. As awareness of HPV becomes more widespread and HPV testing is explored as a triage during cervical screening, women are likely to require more information about the virus and the implications of infection. Consideration should be given to the production of a separate national screening programme HPV leaflet.

Final results of a phase 2 study using continuous 5% Imiquimod cream application in the primary treatment of high-grade vulva intraepithelial neoplasia.

PubMed

Le, Tien; Menard, Chantal; Hicks-Boucher, Wendy; Hopkins, Laura; Weberpals, Johanne; Fung-Kee-Fung, Michael

2007-09-01

To investigate the activity of 5% Imiquimod cream in the primary treatment of vulva intraepithelial neoplasia (VIN) grade 2/3. Patients with histologically confirmed VIN 2/3 were recruited from regional colposcopy units. A Simon two-stage phase 2 study design was used. Imiquimod cream was applied over the abnormal VIN areas by the patients, using an escalating dose regimen for a total treatment duration of 16 weeks. Colposcopy assessments were performed every 2 weeks to evaluate for response. A historical cohort of VIN 2/3 patients treated with primary surgical ablation was used to compare recurrence patterns. Thirty-nine patients enrolled in the study. Six patients dropped out due to side effects and non-compliance with study protocol. Thirty-six patients (92%) had VIN 3. Therapy was well tolerated with the most common observed side effects being only minor skin irritation at the application site. Histologic complete response was observed in 21 patients with partial response in another nine patients. The overall response rate was 77% using intention to treat principle. No VIN progression or cancer was diagnosed. At a median follow-up of 16 months in the whole study cohort, eight recurrences (20.5%) were observed. In comparison, the recurrence rate for primary surgically treated patients was 53.5% (p=0.013). Imiquimod cream was well tolerated and resulted in the regression in a majority of high-grade VIN lesions. The recurrence rate appeared to be comparable to primary surgical ablation.

Semi-quantitative HPV viral load in patients with ASC-US cytology: viral load correlates strongly with the presence of CIN but only weakly with its severity.

PubMed

Lee, S J; Kim, W Y; Shim, S-H; Cho, S-H; Oh, I K; Hwang, T S; Kim, S-N; Kang, S-B

2015-02-01

This study was performed to evaluate the prognostic significance of human papillomavirus (HPV) viral load, expressed in relative light units (RLUs), in patients with atypical squamous cells of undetermined significance (ASC-US) cytology. A total of 349 ASC-US cases with HPV infection, detected using Hybrid Capture 2, were diagnosed histologically. A colposcopically directed punch biopsy was performed on acetowhite areas. Endocervical curettage biopsy and random cervical punch biopsy in four quadrants were performed in unsatisfactory colposcopy cases. In negative colposcopy cases, random cervical punch biopsy in four quadrants was performed. Case with no cervical intraepithelial neoplasia (CIN), CIN1 and CIN2+ (CIN2/CIN3) accounted for 162, 135 and 52 cases, respectively. The mean age showed no difference among the three groups (P = 0.510). There was a significant correlation between RLU values and the presence of CIN (P < 0.001), but less so with its severity: the median RLU values for negative, CIN1 and CIN2+ cases were 42.68, 146.45 and 156.43, respectively, with widely overlapping confidence intervals. The cut-off values of RLU to detect CIN1+ and CIN2+ were 6.73 and 45.64, respectively. The HPV viral load in ASC-US cases showed a significant correlation with the presence of CIN and less so with its severity, and showed large overlap of viral loads between grades of CIN. In ASC-US cases, RLU was not an accurate predictor of immediate high-grade CIN. © 2014 John Wiley & Sons Ltd.

Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

PubMed

Huh, Warner K; Ault, Kevin A; Chelmow, David; Davey, Diane D; Goulart, Robert A; Garcia, Francisco A R; Kinney, Walter K; Massad, L Stewart; Mayeaux, Edward J; Saslow, Debbie; Schiffman, Mark; Wentzensen, Nicolas; Lawson, Herschel W; Einstein, Mark H

2015-02-01

In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk human papillomavirus [hrHPV] testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective U.S.-based registration study. Thirteen experts, including representatives from the Society of Gynecologic Oncology, the American Society for Colposcopy and Cervical Pathology, the American College of Obstetricians and Gynecologists, the American Cancer Society, the American Society of Cytopathology, the College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the U.S. Food and Drug Administration (FDA) for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

MAVARIC - a comparison of automation-assisted and manual cervical screening: a randomised controlled trial.

PubMed

Kitchener, H C; Blanks, R; Cubie, H; Desai, M; Dunn, G; Legood, R; Gray, A; Sadique, Z; Moss, S

2011-01-01

The principal objective was to compare automation-assisted reading of cervical cytology with manual reading using the histological end point of cervical intraepithelial neoplasia grade II (CIN2) or worse (CIN2+). Secondary objectives included (i) an assessment of the slide ranking facility of the Becton Dickinson (BD) FocalPoint™ Slide Profiler (Becton Dickinson, Franklin Lakes, NJ, USA), especially 'No Further Review', (ii) a comparison of the two approved automated systems, the ThinPrep® Imaging System (Hologic, Bedford, MA, USA) and the BD FocalPoint Guided Screener Imaging System, and (iii) automated versus manual in terms of productivity and cost-effectiveness. A 1 : 2 randomised allocation of slides to either manual reading or automation-assisted paired with manual reading. Cytoscreeners were blinded to whether samples would be read only manually or manually paired with automated. Slide reading procedures followed real-life laboratory protocol to produce a final result and, for paired readings, the worse result determined the management. Costs per event were estimated and combined with productivity to produce a cost per slide, per woman and per CIN2+ and cervical intraepithelial neoplasia grade III (CIN3) or worse (CIN3+) lesion detected. Cost-effectiveness was estimated using cost per CIN2+ detected. Lifetime cost-effectiveness in terms of life-years and quality-adjusted life-years was estimated using a mathematical model. Liquid-based cytology samples were obtained in primary care, and a small number of abnormal samples were obtained from local colposcopy clinics, from different women, in order to enrich the proportion of abnormals. All of the samples were read in a single large service laboratory. Liquid residues used for human papillomavirus (HPV) triage were tested (with Hybrid Capture 2, Qiagen, Crawley, UK) in a specialist virology laboratory in Edinburgh, UK. Histopathology was read by a specialist gynaecological pathology team blinded to HPV results and type of reading. Samples were obtained from women aged 25-64 years undergoing primary cervical screening in Greater Manchester, UK, with small proportions from women outside this age range and from women undergoing colposcopy. The principal intervention was automation-assisted reading of cervical cytology slides which was paired with a manual reading of the same slide. Low-grade cytological abnormalities (borderline and mild dyskaryosis) were triaged with HPV testing to direct colposcopy referral. Women with high-grade cytology were referred for colposcopy and those with negative cytology were returned to recall. The principal outcome measure was the sensitivity of automation-assisted reading relative to manual for the detection of CIN2+. A secondary outcome measure was cost-effectiveness of each type of reading to detect CIN2+. The study was powered to detect a relative sensitivity difference equivalent to an absolute difference of 5%. The principal finding was that automated reading was 8% less sensitive relative to manual, 6.3% in absolute terms. 'No further review' was very reliable and, if restricted to routine screening samples, < 1% of CIN2+ would have been missed. Automated and manual were very similar in terms of cost-effectiveness despite a 60%-80% increase in productivity for automation-assisted reading. The significantly reduced sensitivity of automated reading, combined with uncertainty over cost-effectiveness, suggests no justification at present to recommend its introduction. The reliability of 'no further review' warrants further consideration as a means of saving staff time. Current Controlled Trials ISRCTN66377374. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 3. See the HTA programme website for further project information.

Clinical performance of RNA and DNA based HPV testing in a colposcopy setting: Influence of assay target, cut off and age.

PubMed

Cuschieri, Kate; Cubie, Heather; Graham, Catriona; Rowan, Jennifer; Hardie, Alison; Horne, Andrew; Earle, Camille Busby; Bailey, Andrew; Crosbie, Emma J; Kitchener, Henry

2014-02-01

As HPV testing is used increasingly for cervical disease management, there is a demand to optimise the performance of HPV tests, particularly with respect to specificity. To compare the clinical performance of an HPV DNA and a RNA based test in women with cytological abnormalities. The influence of age and assay cut off on test performance was also assessed. A prospective comparison of the Hybrid Capture 2 test (HC2) and the Aptima HPV assay (AHPV) was performed within a colposcopy setting. Clinical sensitivity and specificity were determined for the detection of cervical intraepithelial neoplasia (CIN) grade 2 or worse. Both assays were >90% sensitive for the detection of CIN2+. AHPV was slightly more specific than HC2 [49.9% (46.8-53.1) vs 45.9% (42.8, 49.1), p<0.0001]. Raising HC2 cut off to 2 RLU did not improve specificity. A cut-off of 10 RLU increased specificity by approximately 10% - although this led to a reduction in sensitivity of 6.3% which equated to 24 missed cases of CIN2+. Both assays were more specific in women over 30 years of age, compared to women under 30 (p<0.001). Although AHPV was more specific than HC2 in the total cohort (p<0.001), we found this difference to be smaller than other studies. This could be attributed to different indications for colposcopic referral across different settings. This study also confirms the relatively poor specificity of commercial HPV assays in women under 30. Copyright © 2013 Elsevier B.V. All rights reserved.

Remote quality assurance in cervical cancer screening in low resource settings using a handheld smartphone-based colposcope

NASA Astrophysics Data System (ADS)

Millien, Christophe; Jean-Baptiste, Meredith C.; Manite, Garçon; Levitz, David

2015-03-01

Cervical cancer is a leading cause of cancer death for women all across the developing world, where much of the infrastructure required for effective cervical cancer screening is unavailable because of limited resources. One of the most common method to screen for cervical cancer is by visual inspection with acetic acid (VIA), in which the cervix is imaged with the naked eye. Given inherent challenges in analysis and documentation when characterizing cervical tissue with the naked eye, an optical solution is needed. To address this challenge, a smartphone was modified and transformed into a mobile colposcope (a device used to image the cervix from outside) by adding a custom-fit light source and optics. The mobile smartphone colposcope was designed such that it augments VIA and easily integrates within the standard of care. The mobile smartphone colposcope is controlled by an app, which, stores cervical images captured on the mobile smartphone colposcope on a portal, enabling remote doctors to evaluate images and the treatment chosen by the health worker. Images from patients undergoing cervical cancer screening by a nurse using VIA in the University Hospital of Mirebalais (HUM) GYN outpatient clinic in Haiti were captured on the mobile smartphone colposcope. These images were later analyzed by an experienced OB/GYN at HUM, who determined whether or not the patient should be treated with cryoablation; more complicated cases were also shared with a consulting doctor in the US. The opinions of the experienced OB/GYN doctors at HUM, as well as the experts from the US, were used to educate nurses and midwives performing mobile colposcopy. These results suggest that remote assessment offered by mobile colposcopy can improve training of health workers performing VIA, and ultimately affect the therapy administered to patients.

Health Service Accessibility and Risk in Cervical Cancer Prevention: Comparing Rural Versus Nonrural Residence in New Mexico.

PubMed

McDonald, Yolanda J; Goldberg, Daniel W; Scarinci, Isabel C; Castle, Philip E; Cuzick, Jack; Robertson, Michael; Wheeler, Cosette M

2017-09-01

Multiple intrapersonal and structural barriers, including geography, may prevent women from engaging in cervical cancer preventive care such as screening, diagnostic colposcopy, and excisional precancer treatment procedures. Geographic accessibility, stratified by rural and nonrural areas, to necessary services across the cervical cancer continuum of preventive care is largely unknown. Health care facility data for New Mexico (2010-2012) was provided by the New Mexico Human Papillomavirus Pap Registry (NMHPVPR), the first population-based statewide cervical cancer screening registry in the United States. Travel distance and time between the population-weighted census tract centroid to the nearest facility providing screening, diagnostic, and excisional treatment services were examined using proximity analysis by rural and nonrural census tracts. Mann-Whitney test (P < .05) was used to determine if differences were significant and Cohen's r to measure effect. Across all cervical cancer preventive health care services and years, women who resided in rural areas had a significantly greater geographic accessibility burden when compared to nonrural areas (4.4 km vs 2.5 km and 4.9 minutes vs 3.0 minutes for screening; 9.9 km vs 4.2 km and 10.4 minutes vs 4.9 minutes for colposcopy; and 14.8 km vs 6.6 km and 14.4 minutes vs 7.4 minutes for precancer treatment services, all P < .001). Improvements in cervical cancer prevention should address the potential benefits of providing the full spectrum of screening, diagnostic and precancer treatment services within individual facilities. Accessibility, assessments distinguishing rural and nonrural areas are essential when monitoring and recommending changes to service infrastructures (eg, mobile versus brick and mortar). © 2016 National Rural Health Association.

Performance of the cobas HPV Test for the Triage of Atypical Squamous Cells of Undetermined Significance Cytology in Cervical Specimens Collected in SurePath.

PubMed

Tewari, Devansu; Novak-Weekley, Susan; Hong, Christina; Aslam, Shagufta; Behrens, Catherine M

2017-11-02

Determine performance of the cobas human papillomavirus (HPV) test for triage of atypical squamous cells of undetermined significance (ASC-US) in SurePath. Women presenting for routine screening had cervical specimens collected in SurePath and specimen transport medium (STM); those with ASC-US cytology underwent colposcopy. Performance of cobas HPV in SurePath specimens that had undergone a preanalytic procedure to reverse possible cross-linking of HPV DNA was compared with Hybrid Capture 2 (hc2) specimens in STM. Among 856 women, HPV prevalence was 45.8%; HPV 16 and HPV 18 prevalences were lower than expected in the 21- to 29-year-old group in this highly vaccinated population. cobas HPV performance in SurePath was comparable to hc2 in STM. Sensitivity and specificity for detection of cervical intraepithelial neoplasia grade 3 or worse were 87.5% (95% confidence interval [CI], 71.9%-95.2%) and 55.5% (95% CI, 52.1%-58.9%) for cobas and 85.3% (95% CI, 69.9%-93.6%) and 54.7% (95% CI, 51.4%-57.9%) for hc2. Sensitivity was negatively affected by random biopsies performed at colposcopy; comparable sensitivities were achieved in the nonvaccinated and vaccinated populations with disease determined by directed biopsy only. Performance of cobas HPV for ASC-US triage in pretreated SurePath specimens meets criteria for validation. Preliminary data indicate reliable performance of HPV testing in a highly vaccinated population. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Concurrent evaluation of visual, cytological and HPV testing as screening methods for the early detection of cervical neoplasia in Mumbai, India.

PubMed

Shastri, Surendra S; Dinshaw, Ketayun; Amin, Geetanjali; Goswami, Smriti; Patil, Sharmila; Chinoy, Roshini; Kane, S; Kelkar, Rohini; Muwonge, Richard; Mahé, Cédric; Ajit, Dulhan; Sankaranarayanan, R

2005-03-01

Naked eye visual inspection with acetic acid (VIA), magnified VIA (VIAM), visual inspection with Lugol's iodine (VILI), cytology and human papillomavirus (HPV) testing were evaluated as screening methods for the detection of high-grade squamous intraepithelial lesions (HSIL) of the uterine cervix in a cross-sectional study in Mumbai, India. Cytology, HPV testing, VIA, VIAM and VILI were carried out concurrently for 4039 women aged 30-65 years. All women were investigated with colposcopy and biopsies were taken from 939 women who had colposcopic abnormalities. The reference standard for final disease status was histology or negative colposcopy. The presence of HSIL was confirmed in 57 women (1.4%). The test characteristics for each method were calculated using standard formulae. The sensitivities of cytology, HPV testing, VIA, VIAM and VILI were 57.4%, 62.0%, 59.7%, 64.9%, and 75.4%, respectively (differences were not statistically significant). The specificities were 98.6%, 93.5%, 88.4%, 86.3%, and 84.3%, respectively. Adding a visual test to cytology or HPV testing in parallel combination resulted in a substantial increase in sensitivity, with a moderate decrease in specificity. The parallel combination of VILI and HPV testing resulted in a sensitivity of 92.0% and a specificity of 79.9%. As a single test, cytology had the best balance of sensitivity and specificity. Visual tests are promising in low-resource settings, such as India. The use of both VIA and VILI may be considered where good quality cytology or HPV testing are not feasible. The sensitivity of cytology and HPV testing increased significantly when combined with VIA or VILI.

Cervical cancer screening among HIV infected women in an urban, U.S. safety-net healthcare system.

PubMed

Barnes, Arti; Betts, Andrea C; Borton, Eric K; Sanders, Joanne M; Pruitt, Sandi L; Werner, Claudia; Bran, Andres; Estelle, Carolee D; Balasubramanian, Bijal A; Inrig, Stephen J; Halm, Ethan A; Skinner, Celette Sugg; Tiro, Jasmin A

2018-05-11

Little is known about cervical cancer screening and results patterns among HIV infected (HIV+) women in real-world healthcare settings. We characterized two periods of screening opportunity. Retrospective cohort. U.S. safety-net healthcare system in Dallas County, Texas. We analyzed data from electronic medical records (EMR) of 1,490 HIV+ women receiving care 2010-2014. At baseline, we categorized a woman's Pap status 15 months prior to index date as under-screened (vs. screened), and cytology result (normal vs. abnormal). Then, we examined screening completion and results, and colposcopy uptake and results after an abnormal screen, in the subsequent 15-month period. More than half of women (56%) had no evidence of a Pap test (i.e., under-screened) at baseline. Under-screened women were more likely to be older (50-64 years), have diabetes, and unknown viral load; they were less likely to be Black, Hispanic, have Medicaid, recently pregnant, have a HIV clinic visit, or a CD4 count ≥200 cells/mm. Nearly half of under-screened women (46%, n = 383) remained under-screened in the subsequent 15 months. Among women under-screened at baseline who later completed screening and follow-up during the study period, 21 high-grade dysplasia and 3 cancers were diagnosed. Overall, 40% of women did not receive colposcopy when needed, with most failures to follow-up occurring in women who were under-screened at baseline. Most HIV+ women receiving care in a safety-net system did not receive sufficient screening for cervical cancer and remained at exceptionally high risk of developing high-grade dysplasia.

Evaluation of anogenital injuries using white and UV-light among adult volunteers following consensual sexual intercourse.

PubMed

Joki-Erkkilä, Minna; Rainio, Juha; Huhtala, Heini; Salonen, Aki; Karhunen, Pekka J

2014-09-01

New clinical forensic examination techniques for sexual assaults have not been introduced over the last few decades. We evaluated the benefit of ultraviolet light compared to white light for detecting minor anogenital injuries and scars, following consensual sexual intercourse among adult volunteers. A prospective study comparing female genital findings utilising white and ultraviolet light. A colposcopy with photographic documentation was used. Personal invitation to healthcare students, hospital employees or acquaintances to volunteer for a gynecological examination, with a focus on clinical forensic aspects. Eighty-eight adult female volunteers were recruited for the study. The examination was performed after consensual intercourse. Age ranged from 20 to 52 years (median 26.5 years). Presence of acute findings and scars in the genital area using white and UV-light. Acute genital injury rate was 14.8% under white light colposcopy and 23.0% using UV light. Submucosal hemorrhages in the genital area were documented significantly better under UV-light than white light (14.9% vs. 6.8%; p=0.016), whereas petechiaes (4.5%) and abrasions (2.3%) were detected using either method. UV-light revealed significantly more often delivery-associated genital scars compared to white light (39.8% vs. 31.8%; p=0.016). Furthermore, 10 out of 31 (33.3%) women had no residual anogenital skin or mucosal surface findings, despite a prior episiotomy or rupture of the vaginal outlet wall during delivery, supporting its enormous ability to heal even after major trauma. UV-light may provide additional value for the evaluation of physical findings in clinical forensic examinations after sexual assault, and is especially useful in detecting otherwise invisible early submucosal hemorrhages and scars. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Automatic detection of multi-level acetowhite regions in RGB color images of the uterine cervix

NASA Astrophysics Data System (ADS)

Lange, Holger

2005-04-01

Uterine cervical cancer is the second most common cancer among women worldwide. Colposcopy is a diagnostic method used to detect cancer precursors and cancer of the uterine cervix, whereby a physician (colposcopist) visually inspects the metaplastic epithelium on the cervix for certain distinctly abnormal morphologic features. A contrast agent, a 3-5% acetic acid solution, is used, causing abnormal and metaplastic epithelia to turn white. The colposcopist considers diagnostic features such as the acetowhite, blood vessel structure, and lesion margin to derive a clinical diagnosis. STI Medical Systems is developing a Computer-Aided-Diagnosis (CAD) system for colposcopy -- ColpoCAD, a complex image analysis system that at its core assesses the same visual features as used by colposcopists. The acetowhite feature has been identified as one of the most important individual predictors of lesion severity. Here, we present the details and preliminary results of a multi-level acetowhite region detection algorithm for RGB color images of the cervix, including the detection of the anatomic features: cervix, os and columnar region, which are used for the acetowhite region detection. The RGB images are assumed to be glare free, either obtained by cross-polarized image acquisition or glare removal pre-processing. The basic approach of the algorithm is to extract a feature image from the RGB image that provides a good acetowhite to cervix background ratio, to segment the feature image using novel pixel grouping and multi-stage region-growing algorithms that provide region segmentations with different levels of detail, to extract the acetowhite regions from the region segmentations using a novel region selection algorithm, and then finally to extract the multi-levels from the acetowhite regions using multiple thresholds. The performance of the algorithm is demonstrated using human subject data.

Health Service Accessibility and Risk in Cervical Cancer Prevention: Comparing Rural Versus Nonrural Residence in New Mexico

PubMed Central

McDonald, Yolanda J.; Goldberg, Daniel W.; Scarinci, Isabel C.; Castle, Philip E.; Cuzick, Jack; Robertson, Michael; Wheeler, Cosette M.

2018-01-01

Purpose Multiple intrapersonal and structural barriers, including geography, may prevent women from engaging in cervical cancer preventive care such as screening, diagnostic colposcopy, and excisional precancer treatment procedures. Geographic accessibility, stratified by rural and nonrural areas, to necessary services across the cervical cancer continuum of preventive care is largely unknown. Methods Health care facility data for New Mexico (2010-2012) was provided by the New Mexico Human Papillomavirus Pap Registry (NMHPVPR), the first population-based statewide cervical cancer screening registry in the United States. Travel distance and time between the population-weighted census tract centroid to the nearest facility providing screening, diagnostic, and excisional treatment services were examined using proximity analysis by rural and nonrural census tracts. Mann-Whitney test (P < .05) was used to determine if differences were significant and Cohen's r to measure effect. Findings Across all cervical cancer preventive health care services and years, women who resided in rural areas had a significantly greater geographic accessibility burden when compared to nonrural areas (4.4 km vs 2.5 km and 4.9 minutes vs 3.0 minutes for screening; 9.9 km vs 4.2 km and 10.4 minutes vs 4.9 minutes for colposcopy; and 14.8 km vs 6.6 km and 14.4 minutes vs 7.4 minutes for precancer treatment services, all P < .001). Conclusion Improvements in cervical cancer prevention should address the potential benefits of providing the full spectrum of screening, diagnostic and precancer treatment services within individual facilities. Accessibility, assessments distinguishing rural and nonrural areas are essential when monitoring and recommending changes to service infrastructures (eg, mobile versus brick and mortar). PMID:27557124

A model to evaluate the costs and clinical effectiveness of human papilloma virus screening compared with annual papanicolaou cytology in Germany.

PubMed

Petry, Karl Ulrich; Barth, Cordula; Wasem, Jürgen; Neumann, Anja

2017-05-01

We modelled human papilloma virus (HPV) primary screening scenarios compared with Pap cytology to evaluate clinical effectiveness and projected annual costs in Germany. A Markov cohort model was built to compare the budget impact of annual Pap cytology with different 5-yearly HPV screening scenarios: (1) a positive HPV test followed by Pap cytology; (2) a positive HPV test followed by p16/Ki-67 dual-stained cytology; (3) a positive HPV test followed by colposcopy if HPV-16/18-positive or p16/Ki-67 dual-stained cytology if positive for other subtypes; (4) co-testing with HPV and Pap. Screening scenarios were based on a 10-year horizon. All HPV screening scenarios in the model were associated with fewer deaths from missed diagnosis of cervical cancer compared with Pap screening; 10-year totals n=172-344 (1.5-3 per 100,000) versus n=477 (4.1 per 100,000), respectively. Total annual costs were lower with HPV screening than Pap cytology. The projected average annual cost for HPV screening ranged from €117 million to €136 million compared with €177 million for Pap screening, representing annual savings of €41-60 million. The greatest clinical impact was achieved with primary HPV screening (with genotyping) followed by colposcopy for HPV 16/18-positive women or p16/Ki-67 dual-stained cytology for women positive for other HPV subtypes. Screening strategies including primary HPV testing for high-risk subtypes (HPV-16/18) in conjunction with p16/Ki-67 dual-stained cytology can improve the detection of cervical cancer at a lower total annual cost than conventional Pap cytology screening. Copyright © 2017. Published by Elsevier B.V.

Initial results of population based cervical cancer screening program using HPV testing in one million Turkish women.

PubMed

Gultekin, Murat; Zayifoglu Karaca, Mujdegul; Kucukyildiz, Irem; Dundar, Selin; Boztas, Guledal; Semra Turan, Hatice; Hacikamiloglu, Ezgi; Murtuza, Kamil; Keskinkilic, Bekir; Sencan, Irfan

2018-05-01

To evaluate the Turkey's nationwide HPV DNA screening program on the basis of first 1 million screened women. Women over age 30 were invited for population based screening via HPV DNA and conventional cytology. Samples were collected by family physicians and the evaluations and reports had been performed in the National Central HPV laboratories. The acceptance rate for HPV based cervical cancer screening after first invitation was nearly 36.5%. Since HPV DNA tests have been implemented, cervical cancer screening rates have shown 4-5-fold increase in primary level. Through the evaluation of all, HPV positivity was seen in 3.5%. The commonest HPV genotypes were 16, followed by 51, 31, 52 and 18. Among the 37.515 HPV positive cases, cytological abnormality rate was 19.1%. Among HPV positive cases, 16.962 cases had HPV 16 or 18 or other oncogenic HPV types with abnormal cytology (>ASC-US). These patients were referred to colposcopy. The colposcopy referral rate was 1.6%. Among these, final clinico-pathological data of 3.499 patients were normal in 1.985 patients, CIN1 in 708, CIN2 in 285, CIN3 in 436 and cancer in 85 patients and only pap-smear program could miss 45.9% of ≥CIN3 cases. The results of 1 million women including the evaluation of 13 HPV genotypes with respect to prevalence, geographic distribution and abnormal cytology results shows that HPV DNA can be used in primary level settings to have a high coverage rated screening program and is very effective compared to conventional pap-smear. © 2017 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Determinants of Viral Oncogene E6-E7 mRNA Overexpression in a Population-Based Large Sample of Women Infected by High-Risk Human Papillomavirus Types

PubMed Central

Bisanzi, Simonetta; Allia, Elena; Mongia, Alessandra; Carozzi, Francesca; Gillio-Tos, Anna; De Marco, Laura; Ronco, Guglielmo; Gustinucci, Daniela; Del Mistro, Annarosa; Frayle, Helena; Iossa, Anna; Fantacci, Giulia; Pompeo, Giampaolo; Cesarini, Elena; Bulletti, Simonetta; Passamonti, Basilio; Rizzi, Martina; Penon, Maria Gabriella; Barca, Alessandra; Benevolo, Maria

2017-01-01

ABSTRACT Cervical cancer screening by human papillomavirus (HPV) DNA testing with cytology triage is more effective than cytology testing. Compared to cytology, the HPV DNA test's higher sensitivity, which allows better protection with longer intervals, makes it necessary to triage the women with a positive result to compensate its lower specificity. We are conducting a large randomized clinical trial (New Technologies for Cervical Cancer 2 [NTCC2]) within organized population-based screening programs in Italy using HPV DNA as the primary screening test to evaluate, by the Aptima HPV assay (Hologic), the use of HPV E6-E7 mRNA in a triage test in comparison to cytology. By the end of June 2016, data were available for 35,877 of 38,535 enrolled women, 2,651 (7.4%) of whom were HPV DNA positive. Among the samples obtained, 2,453 samples were tested also by Aptima, and 1,649 (67.2%) gave a positive result. The proportion of mRNA positivity was slightly higher among samples tested for HPV DNA by the Cobas 4800 HPV assay (Roche) than by the Hybrid Capture 2 (HC2) assay (Qiagen). In our setting, the observed E6-E7 mRNA positivity rate, if used as a triage test, would bring a rate of immediate referral to colposcopy of about 4 to 5%. This value is higher than that observed with cytology triage for both immediate and delayed referrals to colposcopy. By showing only a very high sensitivity and thus allowing a longer interval for HPV DNA-positive/HPV mRNA-negative women, a triage by this test might be more efficient than by cytology. PMID:28100595

One-year follow-up of single-visit approach to cervical cancer prevention based on visual inspection with acetic acid wash and immediate cryotherapy in rural Thailand.

PubMed

Chumworathayi, B; Srisupundit, S; Lumbiganon, P; Limpaphayom, K K

2008-01-01

The aim is to evaluate 1) the visibility of cervical squamocolumnar junction (SCJ) after cryotherapy treatment and 2) to evaluate the effectiveness of cryotherapy treatment originally performed as part of a safety, acceptability, and feasibility (SAFE) demonstration project evaluating the SAFE of visual inspection with acetic acid (VIA) followed by immediate offer of cryotherapy among those who were tested positive and eligible for treatment. A total of 704 women presented at 1-year follow-up exam during which VIA was performed again by nurses. Six hundred and forty eight (92.0%) women received colposcopy and any kind of biopsy, if indicated, by trained physician colposcopists at a referral hospital. At 1 year, VIA nurses assessed 42 of 648 referred women (6.5%) as abnormal (test positive or suspected cancer). The SCJ was visible to the colposcopists in 91.7% (594/648) of the women. Among 42 women assessed as abnormal by the nurses, colposcopic findings were abnormal in 83.3% (35/42), with one low-grade squamous intraepithelial lesion, two high-grade squamous intraepithelial lesion (HSIL), and one adenocarcinoma confirmed later by biopsy. Among 606 VIA negative women, colposcopy was abnormal in only 23.4% (142/606), with two cases of HSIL confirmed later. Given that the SCJ was visible in the vast majority of women (91.7%) after cryotherapy, VIA could be used to provide follow-up for women previously treated. The disease negative rate after cryotherapy (no human papillomavirus infection, no cervical intraepithelial neoplasia, and no cancer) at 1 year after treatment was 85.5% (554/648).

A comparison of human papillomavirus testing of clinician-collected and self-collected samples during follow-up after screen-and-treat.

PubMed

Taylor, Sylvia; Wang, Chunhui; Wright, Thomas C; Denny, Lynette; Kuhn, Louise

2011-08-15

Screen-and-treat cervical cancer prevention programs based on high-risk human papillomavirus (HPV) testing and cryotherapy have been shown to be effective in resource-limited settings. However, because cryotherapy is not 100% effective, follow-up is needed after treatment to detect post-treatment failures. We compared the test performances of high-risk HPV testing (Hybrid Capture 2) using self-collected and clinician-collected samples as well as cervical cytology for identifying cervical intraepithelial neoplasia grades 2 or 3 or invasive cervical cancer (CIN2+) among women who did (n=812) and did not (n=1858) undergo cryotherapy in a South African screen-and-treat trial. At 6 months after enrolment (and after cryotherapy, if performed), women were tested using all three screening methods and then underwent colposcopy/biopsy. A predefined subset of women (n=1,455) had extended follow-up with colposcopy/biopsy at 12 months. A total of 33 and 91 cases of CIN2+ were detected among treated and untreated women, respectively. The sensitivity of HPV testing using clinician-collected samples and cervical cytology did not differ by treatment status. HPV testing of clinician-collected samples detected the most cases of CIN2+ among both treated (85%) and untreated (91%) women (p=0.31). Cytology (at a cutoff of atypical squamous cells of undetermined significance or greater) detected 76% of cases among both treated and untreated women. However, the sensitivity of HPV testing using self-collected samples was significantly lower among treated versus untreated women (55% vs. 78%, p=0.01). HPV testing using self-collected vaginal specimens may be useful in primary screening but performs poorly for detecting post-treatment failures. Copyright © 2010 UICC.

Near-infrared-excited confocal Raman spectroscopy advances in vivo diagnosis of cervical precancer.

PubMed

Duraipandian, Shiyamala; Zheng, Wei; Ng, Joseph; Low, Jeffrey J H; Ilancheran, Arunachalam; Huang, Zhiwei

2013-06-01

Raman spectroscopy is a unique optical technique that can probe the changes of vibrational modes of biomolecules associated with tissue premalignant transformation. This study evaluates the clinical utility of confocal Raman spectroscopy over near-infrared (NIR) autofluorescence (AF) spectroscopy and composite NIR AF/Raman spectroscopy for improving early diagnosis of cervical precancer in vivo at colposcopy. A rapid NIR Raman system coupled with a ball-lens fiber-optic confocal Raman probe was utilized for in vivo NIR AF/Raman spectral measurements of the cervix. A total of 1240 in vivo Raman spectra [normal (n=993), dysplasia (n=247)] were acquired from 84 cervical patients. Principal components analysis (PCA) and linear discriminant analysis (LDA) together with a leave-one-patient-out, cross-validation method were used to extract the diagnostic information associated with distinctive spectroscopic modalities. The diagnostic ability of confocal Raman spectroscopy was evaluated using the PCA-LDA model developed from the significant principal components (PCs) [i.e., PC4, 0.0023%; PC5, 0.00095%; PC8, 0.00022%, (p<0.05)], representing the primary tissue Raman features (e.g., 854, 937, 1095, 1253, 1311, 1445, and 1654 cm(-1)). Confocal Raman spectroscopy coupled with PCA-LDA modeling yielded the diagnostic accuracy of 84.1% (a sensitivity of 81.0% and a specificity of 87.1%) for in vivo discrimination of dysplastic cervix. The receiver operating characteristic curves further confirmed that the best classification was achieved using confocal Raman spectroscopy compared to the composite NIR AF/Raman spectroscopy or NIR AF spectroscopy alone. This study illustrates that confocal Raman spectroscopy has great potential to improve early diagnosis of cervical precancer in vivo during clinical colposcopy.

Human papillomavirus cervical infection and associated risk factors in a region of Argentina with a high incidence of cervical carcinoma.

PubMed Central

Tonon, S A; Picconi, M A; Zinovich, J B; Liotta, D J; Bos, P D; Galuppo, J A; Alonio, L V; Ferreras, J A; Teyssié, A R

1999-01-01

OBJECTIVE: To assess the prevalence and potential risk factors associated with human papillomavirus (HPV) cervical infection among women residing in a region of northeastern Argentina with a high incidence of cervical cancer. METHODS: A case-control study of 330 women participating in a cervical cytological screening program conducted in Posadas city, Misiones, Argentina, from February 1997 to November 1998 was carried out. Standardized questionnaires were administered, and clinical examination including colposcopy was performed. Fresh endocervical specimens for HPV DNA detection by generic polymerase chain reaction were collected and the products typed by dot-blot hybridization. RESULTS: Human papillomavirus DNA was found in 61% of samples analyzed (185/301). Samples with normal cytology had a 43% infection rate (85/199), while those classified as low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, and invasive cervical carcinoma had an infection rate of 96% (53/55), 100% (29/29), and 100% (18/18), respectively. Human papillomavirus typing showed a 64% (118/185) prevalence of type 16 among all the infected population analyzed; type 16 was detected among 49% (42/85) of infected samples with normal cytology and in an average of 74% (74/100) with abnormal cytology. Sexual behavior, residence in southern Paraguay, and history of a previous sexually transmitted diseases were the main risk factors associated with high-grade cervical lesions. CONCLUSIONS: An elevated prevalence of HPV infection was detected in this population, which also has a high incidence of cervical cancer. The broad distribution of high-risk HPV type 16 in women with normal cytology and colposcopy suggests that viral infection is an important determinant of regional cancer incidence. PMID:10524669

Psychosocial barriers to follow-up adherence after an abnormal cervical cytology test result among low-income, inner-city women.

PubMed

Hui, Siu-Kuen Azor; Miller, Suzanne M; Wen, Kuang-Yi; Fang, Zhu; Li, Tianyu; Buzaglo, Joanne; Hernandez, Enrique

2014-10-01

Low-income, inner-city women bear a disproportionate burden of cervical cancer in both incidence and mortality rates in the United States, largely because of low adherence to follow-up recommendations after an abnormal cervical cytology result in the primary care setting. The goals of the present study were to delineate the theory-based psychosocial barriers underlying these persistent low follow-up rates and their sociodemographic correlates. Guided by a well-validated psychosocial theory of health behaviors, this cross-sectional, correlational study assessed the barriers to follow-up adherence among underserved women (N = 210) who received an abnormal cervical cytology result. Participants were recruited through an inner-city hospital colposcopy clinic, and were assessed by telephone prior to the colposcopy appointment. Participants were largely of African American race (82.2%), lower than high school completion education (58.7%), single, never married (67.3%), and without full-time employment (64.1%). Knowledge barriers were most often endorsed (68%, M = 3.22), followed by distress barriers (64%, M = 3.09), and coping barriers (36%, M = 2.36). Forty-six percent reported more than one barrier category. Less education and being unemployed were correlated with higher knowledge barriers (P < .0001 and P < .01, respectively) and more coping barriers (P < .05 and P < .05, respectively). Women who were younger than 30 years displayed greater distress barriers (P < .05). In the primary care setting, assessing and addressing knowledge and distress barriers after feedback of an abnormal cervical cytology result may improve adherence to follow-up recommendations. The use of structured counseling protocols and referral to navigational and other resources may facilitate this process and thereby reduce disparities in cervical cancer. © The Author(s) 2014.

Initial results of population based cervical cancer screening program using HPV testing in one million Turkish women

PubMed Central

Zayifoglu Karaca, Mujdegul; Kucukyildiz, Irem; Dundar, Selin; Boztas, Guledal; Semra Turan, Hatice; Hacikamiloglu, Ezgi; Murtuza, Kamil; Keskinkilic, Bekir; Sencan, Irfan

2017-01-01

To evaluate the Turkey's nationwide HPV DNA screening program on the basis of first 1 million screened women. Women over age 30 were invited for population based screening via HPV DNA and conventional cytology. Samples were collected by family physicians and the evaluations and reports had been performed in the National Central HPV laboratories. The acceptance rate for HPV based cervical cancer screening after first invitation was nearly 36.5%. Since HPV DNA tests have been implemented, cervical cancer screening rates have shown 4–5‐fold increase in primary level. Through the evaluation of all, HPV positivity was seen in 3.5%. The commonest HPV genotypes were 16, followed by 51, 31, 52 and 18. Among the 37.515 HPV positive cases, cytological abnormality rate was 19.1%. Among HPV positive cases, 16.962 cases had HPV 16 or 18 or other oncogenic HPV types with abnormal cytology (>ASC‐US). These patients were referred to colposcopy. The colposcopy referral rate was 1.6%. Among these, final clinico‐pathological data of 3.499 patients were normal in 1.985 patients, CIN1 in 708, CIN2 in 285, CIN3 in 436 and cancer in 85 patients and only pap‐smear program could miss 45.9% of ≥CIN3 cases. The results of 1 million women including the evaluation of 13 HPV genotypes with respect to prevalence, geographic distribution and abnormal cytology results shows that HPV DNA can be used in primary level settings to have a high coverage rated screening program and is very effective compared to conventional pap‐smear. PMID:29235108

Integrated fingerprint and high wavenumber confocal Raman spectroscopy for in vivo diagnosis of cervical precancer

NASA Astrophysics Data System (ADS)

Duraipandian, Shiyamala; Zheng, Wei; Ng, Joseph; Low, Jeffrey J. H.; Ilancheran, A.; Huang, Zhiwei

2013-03-01

Raman spectroscopy is a vibrational spectroscopic technique capable of optically probing the compositional, conformational, and structural changes in the tissue associated with disease progression. The main goal of this work is to develop an integrated fingerprint (FP) and high wavenumber (HW) in vivo confocal Raman spectroscopy for simultaneous FP/HW tissue Raman spectral measurements. This work further explores the potential of integrated FP/HW Raman spectroscopy developed as a diagnostic tool for in vivo detection of cervical precancer. A total of 473 in vivo integrated FP/HW Raman spectra (340 normal and 133 precancer) were acquired from 35 patients within 1 s during clinical colposcopy. The major tissue Raman peaks are noticed around 854, 937, 1001, 1095, 1253, 1313, 1445, 1654, 2946 and 3400 cm-1, related to the molecular changes (e.g., proteins, lipids, glycogen, nucleic acids, water, etc.) that accompany the dysplastic transformation of tissue. The FP (800 - 1800 cm-1), HW (2800 - 3800 cm-1) and the integrated FP/HW Raman spectra were analyzed using partial least squares-discriminant analysis (PLS-DA) together with the leave-one patient-out, cross-validation. The developed PLS-DA classification models and receiver operating characteristics (ROC) curves for the FP, HW and integrated FP/HW spectroscopy further discloses that the performance of integrated FP/HW Raman spectroscopy is superior to that of all others in discriminating the dysplastic cervix. The results of this work indicate that the co-contributions of underlying rich biochemical information revealed by the complementary spectral modalities (FP and HW Raman) can improve the in vivo early diagnosis of cervical precancer at clinical colposcopy

Triage of ASC-H: a meta-analysis of the accuracy of hrHPV testing and other markers to detect cervical precancer

PubMed Central

Xu, Lan; Verdoodt, Freija; Wentzensen, Nicolas; Bergeron, Christine; Arbyn, Marc

2015-01-01

Background Women with a cytological diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) are usually immediately referred to colposcopy. However, triage may reduce the burden of diagnostic work-up and avoid over-treatment. Methods A meta-analysis was conducted to assess the accuracy of hrHPV testing, and testing for other molecular markers to detect CIN of grade II or III or worse (CIN2+ or CIN3+) in women with ASC-H. An additional question assessed was whether triage is useful given the relatively high pre-triage probability of underlying precancer. Results The pooled absolute sensitivity and specificity for CIN2+ of HC2 (derived from 19 studies) was 93% (95% CI: 89–95%) and 45% (95% CI: 41–50%), respectively. The p16INK4a staining (only 3 studies) has similar sensitivity (93%, 95% CI:75–100%) but superior specificity (specificity ratio: 1.69) to HC2 for CIN2+. Testing for PAX1 gene methylation (only 1 study) showed a superior specificity of 95% (specificity ratio: 2.08). The average pre-test risk was 34% for CIN2+ and 20% for CIN3+. A negative HC2 result decreased this to 8% and 5%, whereas a positive result upgraded the risk to 47% and 28%. Conclusions Due to the high probability of precancer in ASC-H, the utility of triage is limited. The usual recommendation to refer women with ASC-H to colposcopy is not altered by a positive triage test, whatever the test used. A negative hrHPV DNA or p16INK4a test may allow for repeat testing but this recommendation will depend on local decision thresholds for referral. PMID:26618614

Hierarchical clustering of HPV genotype patterns in the ASCUS-LSIL triage study

PubMed Central

Wentzensen, Nicolas; Wilson, Lauren E.; Wheeler, Cosette M.; Carreon, Joseph D.; Gravitt, Patti E.; Schiffman, Mark; Castle, Philip E.

2010-01-01

Anogenital cancers are associated with about 13 carcinogenic HPV types in a broader group that cause cervical intraepithelial neoplasia (CIN). Multiple concurrent cervical HPV infections are common which complicate the attribution of HPV types to different grades of CIN. Here we report the analysis of HPV genotype patterns in the ASCUS-LSIL triage study using unsupervised hierarchical clustering. Women who underwent colposcopy at baseline (n = 2780) were grouped into 20 disease categories based on histology and cytology. Disease groups and HPV genotypes were clustered using complete linkage. Risk of 2-year cumulative CIN3+, viral load, colposcopic impression, and age were compared between disease groups and major clusters. Hierarchical clustering yielded four major disease clusters: Cluster 1 included all CIN3 histology with abnormal cytology; Cluster 2 included CIN3 histology with normal cytology and combinations with either CIN2 or high-grade squamous intraepithelial lesion (HSIL) cytology; Cluster 3 included older women with normal or low grade histology/cytology and low viral load; Cluster 4 included younger women with low grade histology/cytology, multiple infections, and the highest viral load. Three major groups of HPV genotypes were identified: Group 1 included only HPV16; Group 2 included nine carcinogenic types plus non-carcinogenic HPV53 and HPV66; and Group 3 included non-carcinogenic types plus carcinogenic HPV33 and HPV45. Clustering results suggested that colposcopy missed a prevalent precancer in many women with no biopsy/normal histology and HSIL. This result was confirmed by an elevated 2-year risk of CIN3+ in these groups. Our novel approach to study multiple genotype infections in cervical disease using unsupervised hierarchical clustering can address complex genotype distributions on a population level. PMID:20959485

Reflex high-risk human papilloma virus DNA test is useful in the triage of women with atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion.

PubMed

Wu, Howard Her-Juing; Allen, Susan L; Kirkpatrick, Joseph L; Elsheikh, Tarik M

2006-10-01

This study is aimed to investigate the role of reflex high-risk human papilloma virus (HPV) DNA testing as an alternative triage method to colposcopy for women with atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) on Papanicolaou (Pap) tests. Reflex HPV DNA testing using Hybrid Capture II method was carried out on 88 women with ASC-H diagnosed by Thin Prep Pap test. Correlation with follow-up biopsies was available on 42 of these patients. The reflex HPV DNA test showed an overall positive rate of 67% and negative rate of 33% in 88 patients with ASC-H. Using age 30 as the cut off point, the positive rate had increased to 83.3% (35/42) in patients 30 yr or younger, while the positive rate for patients older than 30 yr had decreased to 52.2% (24/46). Follow-up colposcopic biopsy results were available in 35 of 59 HPV-positive women, which revealed 15 (43%) high-grade squamous intraepithelial lesions (HSIL), 12 low-grade squamous intraepithelial lesions (LSIL), and 8 negative for dysplasia. In 7 HPV-negative patients, the follow-up biopsies showed no evidence of HSIL or LSIL. Correlation between clinical risk factors and the HPV results demonstrated no significant differences in HPV positivity between the high-risk and low-risk patients. The high sensitivity (100%) and negative predictive rate (100%) in detecting HSIL in our study provide strong evidence that, instead of automatic referral to colposcopy, reflex HPV DNA testing may be used as an alternative triage method for women diagnosed with ASC-H on Thin Prep Pap test, especially for women older than 30 yr of age.

Provider management of equivocal cervical cancer screening results among underserved women, 2009–2011: follow-up of atypical squamous cells of undetermined significance

PubMed Central

Watson, Meg; Benard, Vicki; Lin, Lavinia; Rockwell, Tanner; Royalty, Janet

2015-01-01

Purpose Reflex human papillomavirus (HPV) testing is the preferred triage option for most women diagnosed with atypical squamous cells of undetermined significance (ASC-US). This study was conducted to describe follow-up results of women with ASC-US Pap test results in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), focusing on HPV test use. Methods We examined the follow-up of 45,049 women in the NBCCEDP with ASC-US Pap tests during 2009–2011. Data on demographic characteristics, diagnostic procedures, and clinical outcomes were analyzed. Results NBCCEDP providers diagnosed 45,049 women (4.5 % of all Pap tests) with an ASC-US result. Of those, 28,271 (62.8 %) were followed with an HPV test, 3,883 (8.6 %) with a repeat Pap test, 6,592 (14.6 %) with colposcopy, and 6,303 were lost to follow-up (14.0 %). Women aged 40 and older were followed more often with an HPV test. White, black, and Asian/Pacific Islander women were followed more often with an HPV test after an ASC-US Pap compared to Hispanic and American Indian/Alaska Native (AI/AN) women. Among women with a positive HPV test on follow-up, almost 90 % continued with colposcopy as recommended. AI/AN women had the highest rates of HPV positivity (55.2 %) and of no follow-up (25.0 %). Conclusion This is the first analysis describing follow-up of ASC-US Pap test results in the NBCCEDP, providing a window into current management of ASC-US results. Findings raise concerns about persistent disparities among AI/AN women. During 2009–2011, nearly two-thirds of women with an ASC-US Pap test result were followed with an HPV reflex test. PMID:25794897

Celebrities and screening: a measurable impact on high-grade cervical neoplasia diagnosis from the ‘Jade Goody effect' in the UK

PubMed Central

Casey, G M; Morris, B; Burnell, M; Parberry, A; Singh, N; Rosenthal, A N

2013-01-01

Background: The celebrity Jade Goody's cervical cancer diagnosis was associated with increased UK cervical screening attendance. We wanted to establish if there was an increase in high-grade (HG) cervical neoplasia diagnoses, and if so, what the characteristics of the women with HG disease were. Methods: We analysed prospective data on 3233 consecutive colposcopy referrals in North East London, UK, from 01 April 2005 to 30 June 2010. Characteristics and outcomes of pre- and post-Goody cohorts were compared. Results: Goody's diagnosis was associated with an increased incidence of colposcopy referrals in all subsequent annual quarters (incidence rate ratio (IRR) 1.3–1.9, P<0.002–P<0.0005) and increased HG disease diagnoses in the fourth quarter 2008/2009 (IRR 1.3, P=0.05) and first quarter 2009/2010 (IRR 1.3, P=0.07). We observed 1.90-fold (CI: 1.06–3.39), 2.06 (CI: 1.13–3.76) and 2.13-fold (CI: 1.07–4.25) respective increases in the odds of HG disease women being screening-naive in the first and second quarter 2009/2010, and the first quarter 2010/2011 (P<0.04, P<0.02 and P<0.04, respectively). There was a 2.23-fold increase in the odds of screening-naive HG disease women being symptomatic post-Goody's diagnosis (P=0.023). The age distributions of the pre- and post-Goody cohorts did not differ in any study group. Conclusion: Continued publicity about celebrities' diagnoses might encourage screening in at-risk populations. PMID:23963142

Human papillomavirus genotypes and clinical management of genital warts in women attending a colposcopy clinic in Cape Town, South Africa.

PubMed

Tayib, Shahila; Allan, Bruce; Williamson, Anna-Lise; Denny, Lynette

2015-09-21

Genital human papillomavirus (HPV) infection is the most common sexually transmitted viral disease in the world. HPV infection of the genital epithelium is associated with genital warts and malignancies of the lower genital tract. To describe the distribution, phenotypic appearance and HPV type associated with genital warts in women. This was a prospective observational study of all women with genital warts who attended the Colposcopy Clinic, Groote Schuur Hospital, Cape Town, South Africa, during 2010 and fulfilled the inclusion and exclusion criteria. One hundred and thirteen women were tested for HPV using the Roche Linear Array HPV genotyping kit to determine the HPV genotypes causing genital warts. The median age of the women was 27 years (range 15 - 53); 90 (79.6%) were HIV-positive, and two-thirds were on antiretroviral treatment. Treatment involved ablation with topical agents, cauterisation or carbon dioxide laser. At 3 months' follow-up after treatment, 56.6% of the women, the majority of whom were HIV-positive, had recurrent/persistent disease. In both HIV-positive and HIV-negative women, HPV was detected in over 90% of cases. However, over half the HIV-positive women as opposed to 2/18 of the HIV-negative women were infected with multiple HPV genotypes. The commonest HPV genotypes in HIV-positive and HIV-negative women were types 11, 6, 89, 61, 55 and 62 and types 11 and 6, respectively. The majority of the patients were HIV-positive and had multiple HPV infections. While this did not alter the phenotypic appearance of the warts, recurrence/persistence after treatment was more common.

Automated Cervical Screening and Triage, Based on HPV Testing and Computer-Interpreted Cytology.

PubMed

Yu, Kai; Hyun, Noorie; Fetterman, Barbara; Lorey, Thomas; Raine-Bennett, Tina R; Zhang, Han; Stamps, Robin E; Poitras, Nancy E; Wheeler, William; Befano, Brian; Gage, Julia C; Castle, Philip E; Wentzensen, Nicolas; Schiffman, Mark

2018-04-11

State-of-the-art cervical cancer prevention includes human papillomavirus (HPV) vaccination among adolescents and screening/treatment of cervical precancer (CIN3/AIS and, less strictly, CIN2) among adults. HPV testing provides sensitive detection of precancer but, to reduce overtreatment, secondary "triage" is needed to predict women at highest risk. Those with the highest-risk HPV types or abnormal cytology are commonly referred to colposcopy; however, expert cytology services are critically lacking in many regions. To permit completely automatable cervical screening/triage, we designed and validated a novel triage method, a cytologic risk score algorithm based on computer-scanned liquid-based slide features (FocalPoint, BD, Burlington, NC). We compared it with abnormal cytology in predicting precancer among 1839 women testing HPV positive (HC2, Qiagen, Germantown, MD) in 2010 at Kaiser Permanente Northern California (KPNC). Precancer outcomes were ascertained by record linkage. As additional validation, we compared the algorithm prospectively with cytology results among 243 807 women screened at KPNC (2016-2017). All statistical tests were two-sided. Among HPV-positive women, the algorithm matched the triage performance of abnormal cytology. Combined with HPV16/18/45 typing (Onclarity, BD, Sparks, MD), the automatable strategy referred 91.7% of HPV-positive CIN3/AIS cases to immediate colposcopy while deferring 38.4% of all HPV-positive women to one-year retesting (compared with 89.1% and 37.4%, respectively, for typing and cytology triage). In the 2016-2017 validation, the predicted risk scores strongly correlated with cytology (P < .001). High-quality cervical screening and triage performance is achievable using this completely automated approach. Automated technology could permit extension of high-quality cervical screening/triage coverage to currently underserved regions.

The New Technologies for Cervical Cancer Screening randomised controlled trial. An overview of results during the first phase of recruitment.

PubMed

Ronco, Guglielmo; Brezzi, Silvia; Carozzi, Francesca; Dalla Palma, Paolo; Giorgi-Rossi, Paolo; Minucci, Daria; Naldoni, Carlo; Segnan, Nereo; Zappa, Marco; Zorzi, Manuel; Cuzick, Jack

2007-10-01

To study the impact of different cervical cancer screening strategies including HPV testing. A randomised controlled trial with a conventional arm (conventional cytology) and an experimental arm following two phases (first HPV testing+conventional cytology, second HPV testing alone). In phase one, different protocols were applied to different age groups (25-34 and 35-60). Published data on test accuracy during the phase one of recruitment are summarised. 45,307 women were recruited in phase one (about 95,000 overall). In the age group 35-60, HPV testing (by Hybrid Capture 2) alone at 2 RLU cut-off increased sensitivity vs. conventional cytology (relative sensitivity 1.41; 95% CI: 0.98-1.02) with a small loss in Positive Predictive Value (PPV; relative PPV 0.75; 95% CI: 0.45-1.25). Adding liquid-based cytology as screening test and referring to colposcopy women positive to either only marginally increased sensitivity but strongly reduced PPV. In the age group 25-34, similar results (relative sensitivity vs. conventional cytology 1.58; 95% CI: 1.032.44; relative PPV 0.78; 95% CI: 0.72-1.16) were obtained, despite 14% of women were HPV positive, with a strategy based on HPV alone as screening test, triaging HPV positive women by cytology, directly referring those ASCUS+ to colposcopy and repeating both tests after 1 year in those with normal cytology. HPV testing, if used as screening test, should be applied alone, with cytology triage essential in younger women but preferable at all ages. Follow-up data will allow analysis of the safety of prolonging screening intervals and the relative persistence of lesions detected with different methods.

Integrative approach to diagnosis of genital human papillomaviruses (HPV) infection of female.

PubMed

Dunjic, Momir; Stanisic, Slavisa; Krstic, Dejan; Stanisic, Miodrag; Ignjatic, Z Jovanovic; Dunjic, Marija

2014-01-01

Human papillomavirus (HPV) is a virus from the papillomavirus family that is capable of infecting humans. Some types of HPVs cause warts, while others can lead to cancers of the cervix, vulva, vagina, penis, oropharynx and anus. High-risk human papillomavirus (hr HPV) has been detected in almost all cervical squamous cell carcinomas and adenocarcinomas. All patients examined by colposcopy. Cervical swab is routinely done and patients are screened with both HPV DNA by Real Time Polimerase Chain Reaction (RT PCR) testing and Pap testing. Pictures obtained by colposcopy were examined by indirect Bi-Digital O-Ring Test (BDORT) by using reference control substance (RCS): HPV 16, HPV 18, and Integrin α5 β1. BDORT was developed by Prof. Omura Y. of New York and received U.S. patent in 1993. For detection of HPV DNA we used RT PCR and standard Qiagen method which detect 18 types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 6, 11, 42, 43, 44) of HPV from smear. From 63 patients where is BDORT indicated presence of HPV, in 49 patients (77.8%) RT PCR confirmed presence of HPV. From 63 patients in 54 patients (85.7%), we detected, by colposcopic exam, some kind of lesions associated with HPV infection. Results obtained by RT PCR: one type (1/18) of DNA HPV in 25 patients (51.02%), 2 types (2/18) in 15 patients (30.61%) and 3 types (3/18) in 9 patients (18.37%). Although BDORT results usually have higher sensitivity and detection rate is much higher, it can be used together with RT PCR in detection of HPV and cervical lesions associated with HPV infection.

Joint Healthcare Manpower Standards (JHMS)

DTIC Science & Technology

1989-11-01

I ’I I I I I I I I6 I 0 9 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I Ilhticl Sport 1 2 3 1 21 21 21 21 3 31 I I I I I I...TREATMENT. Performs minor surgical treatment or biopsy in the clinic, to include cryotherapy for warts and colposcopy examinations on obstetrical patients...Supports Community/ Sports Activities. (4) Clinic Initiated Research. (5) Performs Data Collection in PT Clinic in Support S of Research Sponsored by

Cervical deciduosis imitating dysplasia

PubMed Central

van Diepen, Diederik Anthony; Hellebrekers, Bart; van Haaften, Anne-Marie; Natté, Remco

2015-01-01

Ectopic cervical deciduosis is generally an accidental finding during pregnancy, and usually presents without any symptoms or need for therapeutic intervention. However, it can sometimes imitate dysplasia or carcinoma. We report a case of a 34-year-old G2P0, with a history of cervical dysplasia, presenting at 11 weeks of gestation, with vaginal blood loss. During examination, lesions mimicking dysplasia were found on the cervix. Histological examination reported cervical deciduosis. Deciduosis is a benign change during pregnancy and will resolve spontaneously. With the increasing use of cytology and colposcopy, the reported incidence is growing. When it is hard to differentiate between dysplasia and deciduosis, histological confirmation should be considered. PMID:26396123

The clinical value of HPV E6/E7 and STAT3 mRNA detection in cervical cancer screening.

PubMed

Fan, Yibing; Shen, Zongji

2018-05-01

To explore the value of human papillomavirus (HPV) E6/E7 and signal transducer and activator of transcription 3 (STAT3) mRNA detection in the screening of cervical lesions. 192 patients with abnormal ThinPrep cytology test (TCT) results and/or high-risk HPV infection were screened to identify possible cervical lesions in cases. Diagnoses were confirmed by histopathology. Fluorescence in situ hybridization (FISH) was performed to detect and qualify the mRNAs of HPV E6/E7, STAT3, and Survivin in cervical exfoliated cells. In addition, the performance of separate and combined mRNA detection methods were compared with TCT, HR-HPV DNA schemes respectively. 1. Compared with HPVE6/E7 and STAT3 mRNA methods, Survivin mRNA assay had poor specificity (Sp), Youden index (YI) and concordance rate. 2. HPV E6/E7, STAT3, and STAT3 + HR-HPV methods had the best Sp, concordance rate and positive predictive value (PPV) for cervical lesions screening and atypical squamous cells of undetermined significance (ASCUS) triage. For screening of high grade squamous intraepithelial lesions or greater (HSILs+), no difference was observed in the Se of mRNA detection methods in comparison with that of TCT, HR-HPV and TCT + HR-HPV, whereas the false positive rate (FPR) decreased by 41.48%/55.99%/17.19% and the colposcopy referral rate reduced by about 20.00%/25.00%/11.17%. For triage of women with ASCUS, no difference was observed in the Se of mRNA detection methods as compared to that of HR-HPV (χ 2  = 1.05, P > 0.75), while the FPR decreased by 45.83%/37.50%/41.66% and the colposcopy referral rate reduced by 32.42%/22.60%/25.28%, respectively. The Se, YI, and PPV of the combined methods increased in comparison to each method alone. 3. Compared with the TCT + HR-HPV method, HPV E6/E7 + STAT3 method had perfect Sp (95.92%) and PPV (95.40%) for screening HSILs+, the FPR and colposcopy referral rate decreased by 31.06% and 22.48% respectively. 1. The expression of HPV E6/E7 and STAT3 mRNA confirmed using FISH assay is expected to be a new method and molecular marker for cervical lesions screening. Survivin mRNA was excluded due to its poor performance. 2. HPV E6/E7, STAT3, and STAT3 +HR-HPV assays could be new approaches for cervical cancer screening and ASCUS triage, and the efficiency of combined screening program was better than that of a separate one. 3. HPV E6/E7 + STAT3 regimen is expected to be a diagnostic strategy for cervical lesions. Copyright © 2018 Elsevier GmbH. All rights reserved.

Disease-free and overall survival of patients diagnosed with HPV-associated or HPV-negative cervical cancer

NASA Astrophysics Data System (ADS)

Ibragimova, M. K.; Tsyganov, M. M.; Karabut, I. V.; Kolomiets, L. A.; Choynzonov, E. L.; Litviakov, N. V.

2015-11-01

The real-time PCR method is used to study scrapings of cervical epithelium and outer portion of the cervix in 116 patients aged 24-79 years with stage I-IV primary cervical cancer. The comprehensive survey included colposcopy, cytological and histological analysis, detection and genotyping of high-risk human papillomavirus. In 84 patients (72.4%) the presence of human papillomavirus (HPV) of high carcinogenic risk (HCR) is found, in 32 patients (27.6%) the presence of the virus has not been inspected in the tumor. A significant decrease in the survival rate as well as the prevalence of the worst prognosis for patients with HPV-negative cervical cancer are shown.

Cervical deciduosis imitating dysplasia.

PubMed

van Diepen, Diederik Anthony; Hellebrekers, Bart; van Haaften, Anne-Marie; Natté, Remco

2015-09-22

Ectopic cervical deciduosis is generally an accidental finding during pregnancy, and usually presents without any symptoms or need for therapeutic intervention. However, it can sometimes imitate dysplasia or carcinoma. We report a case of a 34-year-old G2P0, with a history of cervical dysplasia, presenting at 11 weeks of gestation, with vaginal blood loss. During examination, lesions mimicking dysplasia were found on the cervix. Histological examination reported cervical deciduosis. Deciduosis is a benign change during pregnancy and will resolve spontaneously. With the increasing use of cytology and colposcopy, the reported incidence is growing. When it is hard to differentiate between dysplasia and deciduosis, histological confirmation should be considered. 2015 BMJ Publishing Group Ltd.

[Precancerous lesions of the uterine cervix: morphology and molecular pathology].

PubMed

Horn, L-C; Klostermann, K

2011-11-01

HPV-induced alterations of the uterine cervix are frequently biopsied because of suspicious findings on a Pap smear and/or colposcopy. Precancerous lesions occur at the so called transformation zone. For those representing squamous differentiation, the traditional three-tier grading system in CIN 1 to 3 is used. CIN 1 and CIN 2 represent (spontaneous) regression in 60-90% and 50%, respectively. In CIN 3 lesions progression is seen in 20-50%. For appropriate grading, improvement of inter- and intraobserver correlation as well as the exclusion of non-precancerous lesions, p16 immunohistochemistry might be helpful. The terms endocervical glandular dysplasia and low-grade glandular intraepithelial neoplasia have been suggested for glandular lesions less than adenocarcinoma in situ (AIS). Until now reproducible histological criteria have not been established. Additional studies using HPV analysis, p16 and Ki-67 immunohistochemistry have not been proved for these lesions. In accordance with international consensus meetings, these diagnostic terms are not recommended for use in practice. AIS, characterised by the replacement of glandular epithelium by cytologically malignant cells, has been established as the precancerous lesion of the endocervix. AIS is much less common than CIN 3 with a reported range of 1:50-100. But, AIS is found in association with CIN 3 with 25-75%. The differential diagnosis between AIS and non-neoplastic glandular lesion may be aided by immunohistochemistry (e.g. p16, Ki-67, bcl-2, vimentin). All specimens obtained after the clinical diagnosis of cervical precancerous lesions should be examined using step sectioning to rule out microinvasive growth. Important information for clinicians includes the quality of the specimen (cautery artefacts, transformation zone enclosed within the probe), exact grading of CIN lesions, identification of other lesions responsible for suspicious findings of a Pap smear or at colposcopy, and in the case of conisation the distance of the lesion from the resection margins (endo- and ectocervical and circumferential margin).

Risks of CIN 2+, CIN 3+, and Cancer by Cytology and Human Papillomavirus Status: The Foundation of Risk-Based Cervical Screening Guidelines.

PubMed

Demarco, Maria; Lorey, Thomas S; Fetterman, Barbara; Cheung, Li C; Guido, Richard S; Wentzensen, Nicolas; Kinney, Walter K; Poitras, Nancy E; Befano, Brian; Castle, Philip E; Schiffman, Mark

2017-10-01

The next round of the American Society for Colposcopy and Cervical Pathology (ASCCP)-sponsored cervical cancer screening and management guidelines will recommend clinical actions based on risk, rather than test-based algorithms. This article gives preliminary risk estimates for the screening setting, showing combinations of the 2 most important predictors, human papillomavirus (HPV) status and cytology result. Among 1,262,713 women aged 25 to 77 years co-tested with HC2 (Qiagen) and cytology at Kaiser Permanente Northern California, we estimated 0-5-year cumulative risk of cervical intraepithelial neoplasia (CIN) 2+, CIN 3+, and cancer for combinations of cytology (negative for intraepithelial lesion or malignancy [NILM], atypical squamous cells of undetermined significance [ASC-US], low-grade squamous intraepithelial lesion [LSIL], atypical squamous cells cannot exclude HSIL [ASC-H], high-grade squamous intraepithelial lesion [HSIL], atypical glandular cells [AGC]) and HPV status. Ninety percent of screened women had HPV-negative NILM and an extremely low risk of subsequent cancer. Five-year risks of CIN 3+ were lower after HPV negativity (0.12%) than after NILM (0.25%). Among HPV-negative women, 5-year risks for CIN 3+ were 0.10% for NILM, 0.44% for ASC-US, 1.8% for LSIL, 3.0% for ASC-H, 1.2% for AGC, and 29% for HSIL+ cytology (which was very rare). Among HPV-positive women, 5-year risks were 4.0% for NILM, 6.8% for ASC-US, 6.1% for LSIL, 28% for ASC-H, 30% for AGC, and 50% for HSIL+ cytology. As a foundation for the next guidelines revision, we confirmed with additional precision the risk estimates previously reported for combinations of HPV and cytology. Future analyses will estimate risks for women being followed in colposcopy clinic and posttreatment and will consider the role of risk modifiers such as age, HPV vaccine status, HPV type, and screening and treatment history.

Cost-Effectiveness of Primary HPV Testing, Cytology and Co-testing as Cervical Cancer Screening for Women Above Age 30 Years.

PubMed

Jin, Xian Wen; Lipold, Laura; Foucher, Julie; Sikon, Andrea; Brainard, Jennifer; Belinson, Jerome; Schramm, Sarah; Nottingham, Kelly; Hu, Bo; Rothberg, Michael B

2016-11-01

Cervical cancer screening guidelines for women aged ≥30 years allow for co-testing or primary cytology testing. Our objective was to determine the test characteristics and costs associated with Cytology, HPV and Co-testing screening strategies. Retrospective cohort study of women undergoing cervical cancer screening with both cytology and HPV (Hybrid Capture 2) testing from 2004 to 2010 in an integrated health system. The electronic health record was used to identify women aged ≥30 years who had co-testing. Unsatisfactory or unavailable test results and incorrectly ordered tests were excluded. The main outcome was biopsy-proven cervical intraepithelial neoplasia grade 3 or higher (CIN3+). The final cohort consisted of 99,549 women. Subjects were mostly white (78.4 %), married (70.7 %), never smokers (61.3 %) and with private insurance (86.1 %). Overall, 5121 (5.1 %) tested positive for HPV and 6115 (6.1 %) had cytology ≥ ASCUS; 1681 had both and underwent colposcopy and 310 (0.3 %) had CIN3+. Sensitivity for CIN3+ was 91.9 % for Primary Cytology, 99.4 % for Co-testing, and 94.8 % for Primary HPV; specificity was 97.3 % for Co-testing and Primary Cytology and 97.9 % for Primary HPV. Over a 3-year screening interval, Primary HPV detected more cases of CIN3+ and was less expensive than Primary Cytology. Co-testing detected 14 more cases of CIN3+ than Primary HPV, but required an additional 100,277 cytology tests and 566 colposcopies at an added cost of $2.38 million, or $170,096 per additional case detected. Primary HPV was more effective and less expensive than Primary Cytology. Primary HPV screening appears to represent a cost-effective alternative to Co-testing.

Diagnostic performance of HPV E6/E7 mRNA assay for detection of cervical high-grade intraepithelial neoplasia and cancer among women with ASCUS Papanicolaou smears.

PubMed

Ren, Chenchen; Zhu, Yuanhang; Yang, Li; Zhang, Xiaoan; Liu, Ling; Ren, Chunying

2018-02-01

The aim of this study was to investigate the clinical performance of high risk (HR) HPV E6/E7 mRNA assay in detecting cervical high-grade intraepithelial neoplasia and cancer among women with atypical squamous cells of undetermined significance (ASCUS) Papanicolaou (Pap) smears. A total of 160 patients with ASCUS who underwent HR-HPV DNA assay, HR-HPV E6/E7 mRNA assay and colposcopy biopsy at Third Affiliated Hospital of Zhengzhou University, China, from December 2015 to March 2017, were enrolled. Logistic regression analysis was used to evaluate the relationship between pathological results with clinical biologic factors. Univariate analysis showed that the qualitative results of HR-HPV DNA, qualitative results of HR-HPV E6/E7 mRNA and expression levels of HR-HPV E6/E7 mRNA were risk factors of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer (all P < 0.05). Multivariable analysis found that only the expression levels of HR-HPV E6/E7 mRNA was associated with high-grade CIN and cervical cancer (OR = 8.971, 95% CI = 2.572-31.289, P = 0.001). An optimal cut-off value of ≥ 558.26 copies/ml was determined using receiver operating characteristic curve, and specificity of cut-off value were higher than E6/E7 mRNA qualitative assay and DNA qualitative assay. HPV E6/E7 mRNA quantitative assay may be a valuable tool in triage of ASCUS pap smears. A high specificity of E6/E7 mRNA quantitative assay as a triage test in women with ASCUS can be translated into a low referral for colposcopy.

Uptake of community-based, self-collected HPV testing vs. visual inspection with acetic acid for cervical cancer screening in Kampala, Uganda: preliminary results of a randomised controlled trial.

PubMed

Moses, Erin; Pedersen, Heather N; Mitchell, Sheona M; Sekikubo, Musa; Mwesigwa, David; Singer, Joel; Biryabarema, Christine; Byamugisha, Josaphat K; Money, Deborah M; Ogilvie, Gina S

2015-10-01

To compare two cervical cancer screening methods: community-based self-collection of high-risk human papillomavirus (HR-HPV) testing and visual inspection with acetic acid (VIA). Pilot randomised controlled trial of 500 women aged 30-65 in the community of Kisenyi, Uganda. Women randomised to self-collection-based HR-HPV testing provided a cervico-vaginal swab for HR-HPV, and results were provided by phone after laboratory testing. Women who tested HPV positive were referred for VIA at the local health unit. Women randomised to VIA underwent screening at the local health unit, where women who tested positive with VIA were provided cryotherapy at time of screening, as per local standard of care. Women were referred for colposcopy when indicated. Outcome measures were uptake of screening, HR-HPV prevalence, VIA result and treatment rates. In the HR-HPV arm, 248 of 250 (p < 0.01) women provided samples, while in the VIA arm, 121 of 250 (48.4%) women attended screening. Among the 73 of 248 HR-HPV-positive women, 45.2% (N = 33) attended VIA screening for follow-up, 21.2% (N = 7) of whom screened positive; five received treatment and two were missing clinical follow-up records. Of the 121 women in the VIA arm who attended screening, 13.2% (N = 16) screened positive; seven received cryotherapy, three refused treatment, five were referred to colposcopy; and one woman had suspected cervical cancer and received treatment after confirmatory testing. This pilot study demonstrated trial feasibility and willingness of the women to participate and be randomised successfully into the two arms. Self-collection-based cervical cancer screening had a higher uptake than VIA. © 2015 John Wiley & Sons Ltd.

Effectiveness of VIA, Pap, and HPV DNA Testing in a Cervical Cancer Screening Program in a Peri-Urban Community in Andhra Pradesh, India

PubMed Central

Gravitt, Patti E.; Paul, Proma; Katki, Hormuzd A.; Vendantham, Haripriya; Ramakrishna, Gayatri; Sudula, Mrudula; Kalpana, Basany; Ronnett, Brigitte M.; Vijayaraghavan, K.; Shah, Keerti V.

2010-01-01

Background While many studies have compared the efficacy of Pap cytology, visual inspection with acetic acid (VIA) and human papillomavirus (HPV) DNA assays for the detection cervical intraepithelial neoplasia and cancer, few have evaluated the program effectiveness. Methods and Findings A population-based sample of 5603 women from Medchal Mandal in Andhra Pradesh, India were invited to participate in a study comparing Pap cytology, VIA, and HPV DNA screening for the detection of CIN3+. Participation in primary screening and all subsequent follow-up visits was rigorously tracked. A 20% random sample of all women screened, in addition to all women with a positive screening test result underwent colposcopy with directed biopsy for final diagnosis. Sensitivity, specificity, positive and negative predictive values were adjusted for verification bias. HPV testing had a higher sensitivity (100%) and specificity (90.6%) compared to Pap cytology (sensitivity  =  78.2%; specificity = 86.0%) and VIA (sensitivity = 31.6%; specificity = 87.5%). Since 58% of the sample refused involvement and another 28% refused colposcopy or biopsy, we estimated that potentially 87.6% of the total underlying cases of CIN3 and cancer may have been missed due to program failures. Conclusions We conclude that despite our use of available resources, infrastructure, and guidelines for cervical cancer screening implementation in resource limited areas, community participation and non-compliance remain the major obstacles to successful reduction in cervical cancer mortality in this Indian population. HPV DNA testing was both more sensitive and specific than Pap cytology and VIA. The use of a less invasive and more user-friendly primary screening strategy (such as self-collected swabs for HPV DNA testing) may be required to achieve the coverage necessary for effective reduction in cervical cancer mortality. PMID:21060889

Comparison of Human Papillomavirus Detection by Aptima HPV and cobas HPV Tests in a Population of Women Referred for Colposcopy following Detection of Atypical Squamous Cells of Undetermined Significance by Pap Cytology

PubMed Central

Castle, Philip E.; Eaton, Barbara; Reid, Jennifer; Dockter, Janel

2015-01-01

Few studies have compared the cobas HPV test to the Aptima HPV assay (AHPV) and the Aptima HPV 16 18/45 genotype assay (AHPV GT) for high-risk human papillomavirus (hrHPV) detection, clinical performance in detecting cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+) diagnoses, and risk stratification by partial HPV genotyping. The cobas HPV test is a DNA test that separately and concurrently detects HPV16, HPV18, and a pool of 12 other hrHPV types. AHPV is an RNA test for a pool of 14 hrHPV genotypes, and AHPV GT is an RNA test run on AHPV-positive results to detect HPV16 separately from HPV18 and HPV45, which are detected together. In a population of patients (n = 988) referred for colposcopy because of a cervical Pap cytology result of atypical squamous cells of undetermined significance (ASC-US), a cervical scrape specimen was taken, placed into a ThinPrep Pap test vial containing PreservCyt liquid cytology medium, and tested in a blinded fashion with cobas and AHPV and with AHPV GT for AHPV-positive results. The final diagnoses were based on a consensus panel review of the biopsy specimen histology. AHPV and cobas were equally sensitive for CIN2+ diagnoses (89.4% each; P = 1.000), and AHPV was more specific than cobas (63.1% versus 59.3%; P ≤ 0.001). The percent total agreement, percent positive agreement, and kappa value were 90.9%, 81.1%, and 0.815, respectively. Risk stratification using partial HPV genotyping was similar for the two assays. AHPV and AHPV GT had similar sensitivity and risk stratification to cobas HPV, but they were more specific than cobas HPV. PMID:25653409

Should all women with cervical atypia be referred for colposcopy: a HARNET study. Harrisburgh Area Research Network.

PubMed

Slawson, D C; Bennett, J H; Simon, L J; Herman, J M

1994-04-01

Clinicians who manage women with Papanicolaou (Pap) smears showing atypical squamous cells of undetermined significance (ASCUS) may miss clinically significant cervical disease by repeating the cytology alone. We evaluated the ability of the human papillomavirus (HPV) screen and the naked-eye examination after a cervical acetic acid wash to enhance the follow-up Pap smear in predicting an abnormal colposcopic biopsy. Pap smears were performed on all women (N = 7458) attending six family practice offices for a health maintenance examination from August 1989 through February 1991. Consenting subjects with ASCUS underwent repeat cytological testing, an HPV screen, and a cervical acetic acid wash examination immediately before colposcopy after a 4- to 6-month waiting period. Of the 122 consenting women identified with ASCUS, 67 (55%) demonstrated abnormalities on biopsy, including 26 with condyloma, 26 with cervical intraepithelial neoplasia I (CIN I), and 15 with CIN II to III. The false-negative rate, 58%, of the follow-up Pap smear alone for detecting these cases of condyloma and CIN was significantly decreased (false-negative rate, 27%) with the use of the cervical acetic acid wash as an adjunctive test. There was no additional reduction in the false-negative rate with the use of the HPV screen. Of the 15 subjects with high-grade cervical lesions (CIN II to III), 14 had either an abnormal follow-up Pap smear or an abnormal cervical acetic acid wash examination. Among women with cervical atypia, a single follow-up Pap smear alone failed to detect one third of the cases of high-grade disease. Ninety-three percent of these cases were detected, however, with a follow-up Pap smear and an acetic acid wash. Our one subject with a high-grade lesion missed with this combination of tests had an unsatisfactory Pap smear. Use of both tests together may reliably guide clinical decisions regarding the management of cervical atypia.

Options for managing low grade cervical abnormalities detected at screening: cost effectiveness study.

PubMed

2009-07-28

To estimate the cost effectiveness of alternative methods of managing low grade cervical cytological abnormalities detected at routine screening. Design Cost analysis within multicentre individually randomised controlled trial. Grampian, Tayside, and Nottingham. 4201 women with low grade abnormalities. Cytological surveillance or referral to colposcopy for biopsy and recall if necessary or referral to colposcopy with immediate treatment based on colposcopic appearance. Data on resource use collected from participants throughout the duration of the trial (36 months), enabling the estimation of both the direct (health care) and indirect (time and travel) costs of management. Quality of life assessed at recruitment and at 12, 18, 24, and 30 months, using the EQ-5D instrument. Economic outcomes expressed as costs per case of cervical intraepithelial neoplasia (grade II or worse) detected, by trial arm, as confirmed at exit, and cost utility ratios (cost per quality adjusted life year (QALY) gained) for the three pairwise comparisons of trial arms. The mean three year discounted costs of surveillance, immediate treatment, and biopsy and recall were pound150.20 (euro177, $249), pound240.30 (euro283, $415), and pound241.10 (euro284, $4000), respectively, viewed from the health service perspective. From the social perspective, mean discounted costs were pound204.40 (euro241, $339), pound339.90 (euro440, $563), and pound327.50 (euro386, $543), respectively. Estimated at the means, the incremental cost effectiveness ratios indicated that immediate treatment was dominated by the other two management methods, although it did offer the lowest cost per case of cervical intraepithelial neoplasia detected and treated. The pronounced skews in the distributions indicated that probabilistic uncertainty analysis would offer more meaningful estimates of cost effectiveness. The observed differences in the cost effectiveness ratios between trial arms were not significant. Judged within the time frame of the TOMBOLA evaluation, there is no compelling economic reason to favour any one follow-up method over either of the others. ISRCTN 34841617.

Periodic health examination, 1995 update: 1. Screening for human papillomavirus infection in asymptomatic women. Canadian Task Force on the Periodic Health Examination.

PubMed

Johnson, K

1995-02-15

To develop recommendations for practising physicians on the advisability of screening for human papillomavirus (HPV) infection in asymptomatic women. Visual inspection, Papanicolaou testing, colposcopy or cervicography, use of HPV group-specific antigen, DNA hybridization, dot blot technique, Southern blot technique or polymerase chain reaction followed by physical or chemical therapeutic intervention. Evidence for a link between HPV infection and cervical cancer, sensitivity and specificity of HPV screening techniques, effectiveness of treatments for HPV infection, and the social and economic costs incurred by screening. MEDLINE was searched for articles published between January 1966 to June 1993 with the use of the key words "papillomavirus," "cervix neoplasms," "mass screening," "prospective studies," "prevalence," "sensitivity," "specificity," "human" and "female." Proven cost-effective screening techniques that could lead to decreased morbidity or mortality were given a high value. The evidence-based methods and values of the Canadian Task Force on the Periodic Health Examination were used. Potential benefits are to prevent cervical cancer and eliminate HPV infection. Potential harmful effects include the creation of an unnecessary burden on the health care system and the labelling of otherwise healthy people as patients with a sexually transmitted disease for which therapy is generally ineffective. Potential costs would include expense of testing, increased use of colposcopy and treatment. There is fair evidence to exclude HPV screening (beyond Papanicolaou testing for cervical cancer) in asymptomatic women (grade D recommendation). The report was reviewed by members of the task force and three external reviewers who were selected to represent different areas of expertise. These guidelines were developed and endorsed by the task force, which is funded by Health Canada and the National Health Research and Development Program. The principal author (K.J.) was supported in part by the National Health Research and Development Program through a National Health Fellowship (AIDS).

Comparison of Human Papillomavirus Detections in Urine, Vulvar, and Cervical Samples from Women Attending a Colposcopy Clinic

PubMed Central

Gravitt, Patti E.; Dunn, S. Terence; Brown, David; Allen, Richard A.; Eby, Yolanda J.; Smith, Katie; Zuna, Rosemary E.; Zhang, Roy R.; Gold, Michael A.; Schiffman, Mark; Walker, Joan L.; Castle, Philip E.; Wentzensen, Nicolas

2014-01-01

While urine-based sampling for human papillomavirus (HPV) is being explored as a simple and noninvasive approach for cervical cancer screening, data comparing HPV genotyping in urine and those in cellular sampling of the cervix and vulva, and their correlation with rigorously confirmed cervical disease status, are sparse. We performed HPV genotyping on voided-urine and clinician-collected vulvar and cervical samples from 72 women undergoing colposcopy. Although urine-based HPV carcinogenic HPV detection was lower (58.3%) than cervical (73.6%) and vulvar (72.1%) detection (P = 0.05 and 0.07, respectively), the agreement of urine HPV with cervical and vulvar HPV was moderate (kappa = 0.55) and substantial (kappa = 0.62), respectively. Urine-based carcinogenic HPV detection had a clinical sensitivity of 80.8% (95% confidence interval [CI] = 60.7 to 93.5) and a specificity of 53.3% (95% CI = 37.9 to 68.3) for diagnosing cervical intraepithelial neoplasia grades 2/3 (CIN2/3) on histology; 90.0% of CIN3 was positive for urine HPV. The corresponding sensitivity and specificity values for vulvar sampling were 92% (95% CI = 74 to 99) and 40.5% (95% CI = 25.6 to 56.7), and those for cervical sampling were 96.2% (95% CI = 80.4 to 99.9) and 40% (95% CI = 25.7 to 55.7), respectively. HPV16 was the most common carcinogenic genotype detectable in 25% of urine, 33.8% of vulvar, and 31.9% of cervical samples overall, with prevalence increasing with cervical disease grade, regardless of the sampling method. Stronger cervical HPV PCR signal strengths were associated with increased frequency of urine HPV detection. In summary, the relatively lower detection rates but comparable clinical performance of urine-based HPV sampling underscore the need for larger studies to evaluate urine-based sampling for cervical cancer screening, epidemiologic studies, and postvaccination HPV disease surveillance. PMID:24197879

Comparison of urine specimen collection times and testing fractions for the detection of high-risk human papillomavirus and high-grade cervical precancer.

PubMed

Senkomago, V; Des Marais, A C; Rahangdale, L; Vibat, C R T; Erlander, M G; Smith, J S

2016-01-01

Urine testing for high-risk human papillomavirus (HR-HPV) detection could provide a non-invasive, simple method for cervical cancer screening. We examined whether HR-HPV detection is affected by urine collection time, portion of urine stream, or urine fraction tested, and assessed the performance of HR-HPV testing in urine for detection of cervical intraepithelial neoplasia grade II or worse (CIN2+). A total of 37 female colposcopy clinic attendees, ≥ 30 years, provided three urine samples: "first void" urine collected at home, and "initial stream" and "mid-stream" urine samples collected at the clinic later in the day. Self- and physician-collected brush specimens were obtained at the same clinic visit. Colposcopy was performed and directed biopsies obtained if clinically indicated. For each urine sample, HR-HPV DNA testing was conducted for unfractionated, pellet, and supernatant fractions using the Trovagene test. HR-HPV mRNA testing was performed on brush specimens using the Aptima HPV assay. HR-HPV prevalence was similar in unfractionated and pellet fractions of all urine samples. For supernatant urine fractions, HR-HPV prevalence appeared lower in mid-stream urine (56.8%[40.8-72.7%]) than in initial stream urine (75.7%[61.9-89.5%]). Sensitivity of CIN2+ detection was identical for initial stream urine and physician-collected cervical specimen (89.9%[95%CI=62.7-99.6%]), and similar to self-collected vaginal specimen (79.1%[48.1-96.6%]). This is among the first studies to compare methodologies for collection and processing of urine for HR-HPV detection. HR-HPV prevalence was similar in first void and initial stream urine, and was highly sensitive for CIN2+ detection. Additional research in a larger and general screening population is needed. Copyright © 2015 Elsevier B.V. All rights reserved.

Clinical Practice Guidelines on the Screening and Treatment of Precancerous Lesions for Cervical Cancer Prevention in Saudi Arabia.

PubMed

Al-Mandeel, Hazem Mahmoud; Sagr, Emad; Sait, Khalid; Latifah, Hassan Mohamed; Al-Obaid, Abdulaziz; Al-Badawi, Ismail A; Alkushi, Abdulmohsen O; Salem, Hany; Massoudi, Nada S; Schunemann, Holger; Mustafa, Reem A; Brignardello-Petersen, Romina

2016-01-01

Cervical cancer is the third most common gynecological malignancy in Saudi women with an estimated incidence rate of 1.9 cases per 100 000 women-years. More than 40% of cervical cancer cases are diagnosed at advanced stages due to lack of a routine screening program in Saudi Arabia. Thus, national guidelines for routine screening and treatment of precancerous cervical lesions are needed. The Saudi Centre for Evidence-Based Healthcare invited a panel of local experts and partnered them with a team from McMaster University in Canada for methodological support, to develop national clinical practice guidelines on the screening and treatment of precancerous lesions for cervical cancer. After the panel identified key clinical questions, the McMaster University working group updated existing systematic reviews that had been used for the 2013 WHO Guidelines for screening and treatment of precancerous lesions for cervical cancer prevention. Recommendations were based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. Those recommendations took into account the available evidence, patient values and preferences, and resource use in the Saudi context. The panel provided recommendations on two major issues: screening for precancerous lesions (cervical intraepithelial neoplasia 2 & 3) and treatment of those lesions to prevent cervical cancer in women who tested positive after screening. The Saudi expert panel recommends using the HPV DNA test followed by colposcopy or cytology (Pap test) followed by colposcopy to screen for CIN2+ in women at risk of cervical cancer. The panel recommends cryotherapy or loop excision electrosurgery procedure (LEEP) over cold knife cone biopsy to treat women at risk of cervical cancer that tests positive for CIN2+. Universal screening for precancerous cervical dysplasia in women in Saudi Arabia is recommended using HPV testing and or cytology. Either cryotherapy or LEEP are preferred for treatment. National studies on cervical cancer screening modalities and treatment of precancerous cervical lesions, including HPV prevalence and its association with cervical cancer, are scarce.

p16/Ki-67 Dual Stain Cytology for Detection of Cervical Precancer in HPV-Positive Women

PubMed Central

Fetterman, Barbara; Castle, Philip E.; Schiffman, Mark; Wood, Shannon N.; Stiemerling, Eric; Tokugawa, Diane; Bodelon, Clara; Poitras, Nancy; Lorey, Thomas; Kinney, Walter

2015-01-01

Background: Human papillomavirus (HPV)–based cervical cancer screening requires triage markers to decide who should be referred to colposcopy. p16/Ki-67 dual stain cytology has been proposed as a biomarker for cervical precancers. We evaluated the dual stain in a large population of HPV-positive women. Methods: One thousand five hundred and nine HPV-positive women screened with HPV/cytology cotesting at Kaiser Permanente California were enrolled into a prospective observational study in 2012. Dual stain cytology was performed on residual Surepath material, and slides were evaluated for dual stain–positive cells. Disease endpoints were ascertained from the clinical database at KPNC. We evaluated the clinical performance of the assay among all HPV-positive women and among HPV-positive, cytology-negative women. We used internal benchmarks for clinical management to evaluate the clinical relevance of the dual stain assay. We evaluated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the dual stain compared with Pap cytology. All statistical tests were two-sided. Results: The dual stain had lower positivity (45.9%) compared with cytology at an ASC-US threshold (53.4%). For detection of CIN2+, the dual stain had similar sensitivity (83.4% vs 76.6%, P = .1), and statistically higher specificity (58.9% vs 49.6%, P < .001), PPV (21.0% vs 16.6%, P < .001), and NPV (96.4% vs 94.2%, P = .01) compared with cytology. Similar patterns were observed for CIN3+. Women with a positive test had high enough risk for referral to colposcopy, while the risk for women with negative tests was below a one-year return threshold based on current US management guidelines. Conclusion: Dual stain cytology showed good risk stratification for all HPV-positive women and for HPV-positive women with normal cytology. Additional follow-up is needed to determine how long dual stain negative women remain at low risk of precancer. PMID:26376685

Risks of CIN 2+, CIN 3+, and Cancer by Cytology and Human Papillomavirus Status: The Foundation of Risk-Based Cervical Screening Guidelines

PubMed Central

Demarco, Maria; Lorey, Thomas S.; Fetterman, Barbara; Cheung, Li C.; Guido, Richard S.; Wentzensen, Nicolas; Kinney, Walter K.; Poitras, Nancy E.; Befano, Brian; Castle, Philip E.; Schiffman, Mark

2017-01-01

Objectives The next round of the American Society for Colposcopy and Cervical Pathology (ASCCP)-sponsored cervical cancer screening and management guidelines will recommend clinical actions based on risk, rather than test-based algorithms. This article gives preliminary risk estimates for the screening setting, showing combinations of the 2 most important predictors, human papillomavirus (HPV) status and cytology result. Materials and Methods Among 1,262,713 women aged 25 to 77 years co-tested with HC2 (Qiagen) and cytology at Kaiser Permanente Northern California, we estimated 0–5-year cumulative risk of cervical intraepithelial neoplasia (CIN) 2+, CIN 3+, and cancer for combinations of cytology (negative for intraepithelial lesion or malignancy [NILM], atypical squamous cells of undetermined significance [ASC-US], low-grade squamous intraepithelial lesion [LSIL], atypical squamous cells cannot exclude HSIL [ASC-H], high-grade squamous intraepithelial lesion [HSIL], atypical glandular cells [AGC]) and HPV status. Results Ninety percent of screened women had HPV-negative NILM and an extremely low risk of subsequent cancer. Five-year risks of CIN 3+ were lower after HPV negativity (0.12%) than after NILM (0.25%). Among HPV-negative women, 5-year risks for CIN 3+ were 0.10% for NILM, 0.44% for ASC-US, 1.8% for LSIL, 3.0% for ASC-H, 1.2% for AGC, and 29% for HSIL+ cytology (which was very rare). Among HPV-positive women, 5-year risks were 4.0% for NILM, 6.8% for ASC-US, 6.1% for LSIL, 28% for ASC-H, 30% for AGC, and 50% for HSIL+ cytology. Conclusions As a foundation for the next guidelines revision, we confirmed with additional precision the risk estimates previously reported for combinations of HPV and cytology. Future analyses will estimate risks for women being followed in colposcopy clinic and posttreatment and will consider the role of risk modifiers such as age, HPV vaccine status, HPV type, and screening and treatment history. PMID:28953116

Estimation of the costs of cervical cancer screening, diagnosis and treatment in rural Shanxi Province, China: a micro-costing study

PubMed Central

2012-01-01

Background Cost estimation is a central feature of health economic analyses. The aim of this study was to use a micro-costing approach and a societal perspective to estimate aggregated costs associated with cervical cancer screening, diagnosis and treatment in rural China. Methods We assumed that future screening programs will be organized at a county level (population ~250,000), and related treatments will be performed at county or prefecture hospitals; therefore, this study was conducted in a county and a prefecture hospital in Shanxi during 2008–9. Direct medical costs were estimated by gathering information on quantities and prices of drugs, supplies, equipment and labour. Direct non-medical costs were estimated via structured patient interviews and expert opinion. Results Under the base case assumption of a high-volume screening initiative (11,475 women screened annually per county), the aggregated direct medical costs of visual inspection, self-sampled careHPV (Qiagen USA) screening, clinician-sampled careHPV, colposcopy and biopsy were estimated as US$2.64,$7.49,$7.95,$3.90 and $5.76, respectively. Screening costs were robust to screening volume (<5% variation if 2,000 women screened annually), but costs of colposcopy/biopsy tripled at the lower volume. Direct medical costs of Loop Excision, Cold-Knife Conization and Simple and Radical Hysterectomy varied from $61–544, depending on the procedure and whether conducted at county or prefecture level. Direct non-medical expenditure varied from $0.68–$3.09 for screening/diagnosis and $83–$494 for pre-cancer/cancer treatment. Conclusions Diagnostic costs were comparable to screening costs for high-volume screening but were greatly increased in lower-volume situations, which is a key consideration for the scale-up phase of new programs. The study’s findings will facilitate cost-effectiveness evaluation and budget planning for cervical cancer prevention initiatives in China. PMID:22624619

Clinical evaluation of the cartridge-based GeneXpert human papillomavirus assay in women referred for colposcopy.

PubMed

Einstein, Mark H; Smith, Katherine M; Davis, Thomas E; Schmeler, Kathleen M; Ferris, Daron G; Savage, Ashlyn H; Gray, Jermaine E; Stoler, Mark H; Wright, Thomas C; Ferenczy, Alex; Castle, Philip E

2014-06-01

High-risk human papillomavirus (hrHPV) testing is now being introduced as a potential primary screening test for improved detection of cervical precancer and cancer. Current U.S. Food and Drug Administration-approved tests are batch tests that take several hours to complete. A rapid, non-batch test might permit point-of-care (POC) testing, which can facilitate same-day screen and management strategies. For a non-batch, random-access platform (GeneXpert; Cepheid, Sunnyvale, CA), a prototype hrHPV assay (Xpert) has been developed where testing for 14 hrHPV types can be completed in 1 h. In the first clinical evaluation, Xpert was compared to two validated hrHPV tests, the cobas HPV test (cobas, Roche Molecular Systems) and Hybrid Capture 2 (hc2, Qiagen), and to histologic outcomes using specimens from colposcopy referral populations at 7 clinical sites in the United States (n = 697). The sensitivity of Xpert for cervical intraepithelial neoplasia grade 2 or more severe diagnoses (CIN2+) (n = 141) was equal to that of cobas (90.8% versus 90.8%, P = 1) and greater than that of hc2 (90.8% versus 81.6%, P = 0.004). Xpert was more specific than cobas (42.6% versus 39.6%, P = 0.02) and less specific than hc2 (42.6% versus 47.7%, P < 0.001). Similar results were observed for cervical intraepithelial neoplasia grade 3 or higher (CIN3+) (n = 91). HPV16 detection by Xpert identified 41.8% of the CIN2+ specimens with a positive predictive value (PPV) of 54.6%. By comparison, HPV16 detection by cobas identified 42.6% of the CIN2+ specimens with a PPV of 55.0%. hrHPV detection by the Xpert demonstrated excellent clinical performance for identifying women with CIN2+ and CIN3+ that was comparable to that of currently available clinically validated tests. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Cervical Dysplasia

PubMed Central

Carmichael, John A.

1983-01-01

Invasive squamous carcinoma of the cervix is preceded by a series of premalignant changes described as mild, moderate, or severe dysplasia, and carcinoma in situ. These premalignant states are identified by cervical cytology, diagnosed by colposcopy and if effectively treated, can prevent invasive squamous carcinoma of the cervix. Because of the apparent biological variation of the premalignant states, even the most aggressive cervical screening program cannot be expected to eliminate all invasive squamous cancer of the cervix. Optimal results of a cervical screening program will be achieved when all women under 35 years of age and sexually active have an annual cytological smear; the cytology is screened by a laboratory with high quality control; the patient's positive cytology is accurately assessed by an experienced colposcopist, and the premalignant lesion is effectively treated. PMID:21283455

Use of Mueller matrix colposcopy in the characterization of cervical collagen anisotropy

NASA Astrophysics Data System (ADS)

Montejo, Karla A.; Chue-Sang, Joseph; Bai, Yuqiang; Stoff, Susan; Holness, Nola; Gonzalez, Mariacarla; Gomes, Jefferson; Gandjbakhche, Amir; Chernomordik, Viktor V.; Ramella-Roman, Jessica C.

2017-02-01

Preterm birth (PTB) presents a serious medical heath concern in both economically developed and developing nations, with incidence rate from 15%-11% respectively. Changes in cervical collagen bundle orientation and distribution may prove to be a predictor of PTB. Polarization imaging is an effective means to measure optical anisotropy in birefringent biological tissue such as those rich in collagen. Non-invasive, full-field Mueller Matrix polarimetry (MMP) imaging methodologies, optical coherence tomography (OCT), and second harmonic generation (SHG) microscopy were used to assess cervical collagen content and structure in non-pregnant cervices. In vivo studies using a Mueller Matrix colposcope are underway. Further studies of cervical collagen orientation throughout pregnancy are needed to understand if Mueller matrix polarimetry can effectively identify at-risk conditions for PTB.

A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease.

PubMed

Hampson, Lynne; Maranga, Innocent O; Masinde, Millicent S; Oliver, Anthony W; Batman, Gavin; He, Xiaotong; Desai, Minaxi; Okemwa, Parmenas M; Stringfellow, Helen; Martin-Hirsch, Pierre; Mwaniki, Alex M; Gichangi, Peter; Hampson, Ian N

2016-01-01

Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings. Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC-ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration. A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions. These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy. ISRCTN Registry 48776874.

A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease

PubMed Central

Masinde, Millicent S.; Oliver, Anthony W.; Batman, Gavin; He, Xiaotong; Desai, Minaxi; Okemwa, Parmenas M.; Stringfellow, Helen; Martin-Hirsch, Pierre; Mwaniki, Alex M.; Gichangi, Peter; Hampson, Ian N.

2016-01-01

Background Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings. Methods Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC -ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration. Results A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6–73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6–82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9–65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions. Conclusions These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy. Trial Registration ISRCTN Registry 48776874 PMID:26824902

Validation of a new HPV self-sampling device for cervical cancer screening: The Cervical and Self-Sample In Screening (CASSIS) study.

PubMed

El-Zein, Mariam; Bouten, Sheila; Louvanto, Karolina; Gilbert, Lucy; Gotlieb, Walter; Hemmings, Robert; Behr, Marcel A; Franco, Eduardo L

2018-04-17

We compared the self-sampling performance of the newly designed HerSwab™ device with a physician-collected cervical sample and another self-sample using the cobas® PCR Female swab for the detection of cervical intraepithelial neoplasia (CIN) and cancer. Women referred for colposcopy at McGill University affiliated hospital clinics collected two consecutive self-samples, one with HerSwab™ and one with cobas® swab, after receiving instructions. The order of sampling was randomized. The colposcopist then collected a cervical sample and conducted a colposcopic examination. Samples were tested for human papillomavirus (HPV) DNA. Sensitivity and specificity to detect CIN2+ and respective 95% confidence intervals (CI) were calculated to compare sampling approaches. The HPV testing agreement between samples was measured using the Kappa statistic. Of 1217 women enrolled, 1076 had complete results for HPV and cytology; 148 (13.8%) had CIN1, 147 (13.7%) had CIN2/3, and 5 (0.5%) had cancer. There was very good agreement between methods for HPV detection (HerSwab™ versus physician: kappa=0.84; cobas® swabs versus physician: kappa=0.81; HerSwab™ versus cobas® swabs: kappa=0.87). The sensitivity of HPV detection for CIN2+ was 87.6% (95%CI: 79.8-93.2) with self-sampling using HerSwab™, 88.6% (95%CI: 80.9-94.0) with self-sampling using the cobas® swab, and 92.4% (95%CI: 85.5-96.7) with physician sampling. Corresponding estimates of specificity were 58.1% (95%CI: 54.1-62.1), 55.0% (95%CI: 50.9-59.0) and 58.7% (95%CI: 54.6-62.6). Cytology (ASC-US or more severe) done on the physician-collected specimen was 80.2% (95%CI: 70.8-87.6) sensitive and 61.4% (95%CI: 57.2-65.5) specific for CIN2+. The HerSwab™ had good agreement with physician sampling in detecting HPV, and adequate performance in detecting high-grade lesions among women referred to colposcopy for abnormal cytology. Copyright © 2018 Elsevier Inc. All rights reserved.

Triage strategies in cervical cancer detection in Mexico: methods of the FRIDA Study.

PubMed

Torres-Ibarra, Leticia; Lazcano-Ponce, Eduardo; Franco, Eduardo L; Cuzick, Jack; Hernández-Ávila, Mauricio; Lorincz, Attila; Rivera, Berenice; Ramírez, Paula; Mendiola-Pastrana, Indira; Rudolph, Samantha E; León-Maldonado, Leith; Hernández, Rubí; Barrios, Elizabeth; Gravitt, Patti; Moscicki, Anna Barbara; Schmeler, Kathleen M; Flores, Yvonne N; Méndez-Hernández, Pablo; Salmerón, Jorge

2016-04-01

This paper describes the study design and baseline characteristics of the study population, including the first 30 829 women who enrolled in the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA Study). This is a large population based study that is evaluating the performance and cost-effectiveness of different triage strategies for high-risk HPV (hrHPV) positive women in Mexico. The target population is more than 100 000 women aged 30 to 64 years who attend the Cervical Cancer Screening Program in 100 health centers in the state of Tlaxcala, Mexico. Since August 2013, all women in the region have been invited to enroll in the study. The study participants are evaluated to determine hrHPV infection using the Cobas 4800 HPV test. The HPV-16/18 genotyping and cytology triage strategies are performed as reflex tests in all hrHPV-positive participants. Women with a positive HPV-16/18 test and/or abnormal cytology (atypical squamous cells of undetermined significance or worse, ASCUS+) are referred for colposcopy evaluation, where a minimum of four biopsies and an endocervical sample are systematically collected. Histologic confirmation is performed by a standardized panel of pathologists. Among the 30 829 women who have been screened, the overall prevalence of hrHPV is 11.0%. The overall prevalence of HPV16 and HPV18 are 1.5% and 0.7%, respectively. Cytological abnormalities (ASCUS+) were detected in 11.8% of the hrHPV-positive women. A total of 27.0% (920/3,401) of the hrHPV-positive women were referred to colposcopy because of a positive HPV16/18 test and/or abnormal reflex cytology, (31.6% had only ASCUS+, 53.6% were HPV16/18 positive with a normal cytology result, and 9.5% were positive to both triage tests). The results of this study will help policy makers and health service providers establish the best practices for triage in cervical cancer screening in Mexico and other countries.

Significance of atypical squamous cells of undetermined significance on ThinPrep papanicolaou smears.

PubMed

Eltabbakh, G H; Lipman, J N; Mount, S L; Morgan, A

2000-10-01

The aim of this study was to assess the prevalence and risk factors predictive of dysplasia among women seen in a gynecologic oncology service with the cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) on Papanicolaou smears obtained by the ThinPrep method. Patients with ASCUS ThinPrep Papanicolaou smears seen at the Division of Gynecologic Oncology, University of Vermont, between 1997 and 1999 were identified. The cytologic smears were reviewed and subtyped into reactive or suggestive of squamous intraepithelial lesion (SIL). The charts of these patients were reviewed and the following information was abstracted: age, gravidity, parity, menopausal status, use of hormonal replacement therapy, smoking, history of pelvic cancer, history of radiation therapy, history of abnormal Papanicolaou smear and its treatment, history of human papillomavirus (HPV) infection, and follow-up information including results of repeat Papanicolaou smears, colposcopy, and biopsies. The prevalence of dysplasia was calculated. The demographic features of women with ASCUS, reactive, were compared with those with ASCUS, SIL, using a two-sample t test, chi(2), and Fisher's exact test. Risk factors predictive of dysplasia were calculated using the odds ratio and the 95% confidence interval. P < 0.05 was considered significant. One hundred twenty-six patients with ASCUS on ThinPrep Papanicolaou smear were identified; 63 patients had ASCUS, reactive, and 63 patients had ASCUS, SIL. The demographic features of both groups were similar. The overall prevalence of dysplasia was 15.9% and was significantly higher among women with ASCUS, SIL, than among women with ASCUS, reactive (25.4% versus 6.4%, P = 0.003). The type of ASCUS cytology (reactive versus SIL), smoking, and history of HPV were significant risk factors for dysplasia (P = 0.003, 0.037, and 0. 042, respectively). The prevalence of dysplasia among women seen in a gynecologic oncology service with ASCUS cytology on ThinPrep Papanicolaou smears is 15.9%. Women with ASCUS favor SIL, those who smoke, and those with a history of HPV are at higher risk for dysplasia and should be offered colposcopy. Copyright 2000 Academic Press.

p16/Ki-67 Dual Stain Cytology for Detection of Cervical Precancer in HPV-Positive Women.

PubMed

Wentzensen, Nicolas; Fetterman, Barbara; Castle, Philip E; Schiffman, Mark; Wood, Shannon N; Stiemerling, Eric; Tokugawa, Diane; Bodelon, Clara; Poitras, Nancy; Lorey, Thomas; Kinney, Walter

2015-12-01

Human papillomavirus (HPV)-based cervical cancer screening requires triage markers to decide who should be referred to colposcopy. p16/Ki-67 dual stain cytology has been proposed as a biomarker for cervical precancers. We evaluated the dual stain in a large population of HPV-positive women. One thousand five hundred and nine HPV-positive women screened with HPV/cytology cotesting at Kaiser Permanente California were enrolled into a prospective observational study in 2012. Dual stain cytology was performed on residual Surepath material, and slides were evaluated for dual stain-positive cells. Disease endpoints were ascertained from the clinical database at KPNC. We evaluated the clinical performance of the assay among all HPV-positive women and among HPV-positive, cytology-negative women. We used internal benchmarks for clinical management to evaluate the clinical relevance of the dual stain assay. We evaluated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the dual stain compared with Pap cytology. All statistical tests were two-sided. The dual stain had lower positivity (45.9%) compared with cytology at an ASC-US threshold (53.4%). For detection of CIN2+, the dual stain had similar sensitivity (83.4% vs 76.6%, P = .1), and statistically higher specificity (58.9% vs 49.6%, P < .001), PPV (21.0% vs 16.6%, P < .001), and NPV (96.4% vs 94.2%, P = .01) compared with cytology. Similar patterns were observed for CIN3+. Women with a positive test had high enough risk for referral to colposcopy, while the risk for women with negative tests was below a one-year return threshold based on current US management guidelines. Dual stain cytology showed good risk stratification for all HPV-positive women and for HPV-positive women with normal cytology. Additional follow-up is needed to determine how long dual stain negative women remain at low risk of precancer. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Clinical Outcomes after Conservative Management of Cervical Intraepithelial Neoplasia Grade 2 (CIN2) in Women Ages 21-39 Years.

PubMed

Silver, Michelle I; Gage, Julia C; Schiffman, Mark; Fetterman, Barbara; Poitras, Nancy E; Lorey, Thomas; Cheung, Li C; Katki, Hormuzd A; Locke, Alexander; Kinney, Walter K; Castle, Philip E

2018-03-01

Cervical intraepithelial neoplasia grade 2 (CIN2) frequently regresses, is typically slow-growing, and rarely progresses to cancer. Some women forgo immediate treatment, opting for conservative management (heightened surveillance with cytology and colposcopy), to minimize overtreatment and increased risk of obstetric complications; however, there are limited data examining clinical outcomes in these women. We performed a retrospective cohort analysis of younger women diagnosed with initially untreated CIN1/2, CIN2 and CIN2/3 lesions at Kaiser Permanente Northern California between 2003 and 2015. Clinical outcomes were categorized into five mutually exclusive hierarchical groups: cancer, treated, returned to routine screening, persistent high-grade lesion, or persistent low-grade lesion. Median follow-up for the 2,417 women was 48 months. Six women were diagnosed with cancer (0.2%), all with history of high-grade cytology, and none after a negative cotest. Thirty percent of women were treated, and only 20% returned to routine screening; 50% remained in continued intensive follow-up, of which 86% had either low-grade cytology/histology or high-risk human papillomavirus (HPV) positivity, but not necessarily persistence of a single HPV type. No cancers were detected after a single negative cotest in follow-up. Almost half of initially untreated women did not undergo treatment, but remained by protocol in colposcopy clinic for 2 or more years in the absence of persisting CIN2 + Their incomplete return to total negativity was possibly due to sequential new and unrelated low-grade abnormalities. The prolonged colposcopic surveillance currently required to return to routine screening in the absence of persisting CIN2 + might not be necessary after a negative cotest. Significance: Many younger women under conservative management following an initial CIN2 result remain in a clinical protocol of prolonged intensified surveillance without a subsequent diagnosis of CIN2 or more severe diagnoses. More research is needed to determine whether such prolonged management might be unnecessary following a negative cotest for those women with an initial CIN2 but otherwise only low-grade findings. Cancer Prev Res; 11(3); 165-70. ©2018 AACR . ©2018 American Association for Cancer Research.

Point-Counterpoint: Cervical Cancer Screening Should Be Done by Primary Human Papillomavirus Testing with Genotyping and Reflex Cytology for Women over the Age of 25 Years

PubMed Central

Zhao, Chengquan

2015-01-01

Screening for cervical cancer with cytology testing has been very effective in reducing cervical cancer in the United States. For decades, the approach was an annual Pap test. In 2000, the Hybrid Capture 2 human papillomavirus (HPV) test was approved by the U.S. Food and Drug Administration (FDA) for screening women who have atypical squamous cells of underdetermined significance (ASCUS) detected by Pap test to determine the need for colposcopy. In 2003, the FDA approved expanding the use of the test to include screening performed in conjunction with a Pap test for women over the age of 30 years, referred to as “cotesting.” Cotesting allows women to extend the testing interval to 3 years if both tests have negative results. In April of 2014, the FDA approved the use of an HPV test (the cobas HPV test) for primary cervical cancer screening for women over the age of 25 years, without the need for a concomitant Pap test. The approval recommended either colposcopy or a Pap test for patients with specific high-risk HPV types detected by the HPV test. This was based on the results of the ATHENA trial, which included more than 40,000 women. Reaction to this decision has been mixed. Supporters point to the fact that the primary-screening algorithm found more disease (cervical intraepithelial neoplasia 3 or worse [CIN3+]) and also found it earlier than did cytology or cotesting. Moreover, the positive predictive value and positive-likelihood ratio of the primary-screening algorithm were higher than those of cytology. Opponents of the decision prefer cotesting, as this approach detects more disease than the HPV test alone. In addition, the performance of this new algorithm has not been assessed in routine clinical use. Professional organizations will need to develop guidelines that incorporate this testing algorithm. In this Point-Counterpoint, Dr. Stoler explains why he favors the primary-screening algorithm, while Drs. Austin and Zhao explain why they prefer the cotesting approach to screening for cervical cancer. PMID:25948606

Raman spectroscopic characterization of urine of normal and cervical cancer subjects

NASA Astrophysics Data System (ADS)

Pappu, Raja; Prakasarao, Aruna; Dornadula, Koteeswaran; Singaravelu, Ganesan

2017-02-01

Cervical cancer is the fourth most common malignancy in female worldwide; the present method for diagnosis is the biopsy, Pap smear, colposcopy etc. To overcome the drawbacks of diagnosis an alternative technique is required, optical spectroscopy is a new technique where the discrimination of normal and cancer subjects provides valuable potential information in the diagnostic oncology at an early stage. Raman peaks in the spectra suggest interesting differences in various bio molecules. In this regard, non invasive optical detection of cervical cancer using urine samples by Raman Spectroscopy combined with LDA diagnostic algorithm yields an accuracy of 100% for original and cross validated group respectively. As the results were appreciable it is necessary to carry out the analysis for more number of samples to explore the facts hidden at different stages during the development of cervical cancer.

Intermediate-grade squamous intraepithelial lesion may be a valid diagnostic/interpretive category.

PubMed

Ravinsky, Esther; Baker, Patricia

2009-02-01

We undertook this study to assess the characteristics of smears with features intermediate between high-grade squamous intraepithelial lesion (HSIL) and low-grade squamous intraepithelial lesion (ISIL). We also wanted to determine how these smears correlate with high risk biopsy diagnosis and to compare this with the biopsy correlation of LSIL and HSIL. Seventy-four squamous intraepithelial lesion (SIL) smears were identified as intermediate-grade SIL smears taken at colposcopy in a 1 year period. They were correlated with concurrent colposcopically guided biopsies. Thirty-five percent of cases with intermediate-grade SIL smears had a biopsy diagnosis of moderate dysplasia or higher as compared with 12% for LSIL 74% for HSIL. This confirmed our hypothesis that intermediate-grade SIL smears have a rate of biopsy diagnosis of moderate dysplasia or higher intermediate to that of LSIL and HSIL.

[Expression of gamma interferon during HPV and Chlamydia trachomatis infection in cervical samples].

PubMed

Colín-Ferreyra, María Del Carmen; Mendieta-Zerón, Hugo; Romero-Figueroa, María Del Socorro; Martínez-Madrigal, Migdania; Martínez-Pérez, Sergio; Domínguez-García, María Victoria

2015-02-01

The aim of this study was to mesure the expression of gamma interferon in HPV and Chlamydia trachomatis infection in squamous intraepithelial lesions. Samples from 100 patients diagnosed by colposcopy with or without squamous intraepithelial lesions were used in the present study. Each patient was found to be infected by HPV and C.trachomatis. Relative gamma interferon mRNA expression was assessed using a real-time reverse transcriptase PCR assay (RT-PCR). The relative units of expression of gamma interferon mRNA were 13, 1.8 and 0.3, for HPV and C.trachomatis co-infection, or HPV or C.trachomatis infection, respectively. HPV and C.trachomatis could overstimulate the expression of gamma interferon. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Detection of CIN by naked eye visualization after application of acetic acid.

PubMed

Londhe, M; George, S S; Seshadri, L

1997-06-01

A prospective study was undertaken to determine the sensitivity and specificity of acetic application to the cervix followed by naked eye visualization as a screening test for detection of cervical intraepithelial neoplasia. Three hundred and seventy two sexually active woman in the reproductive age group were studied. All the women underwent Papanicolaou test, acetic acid test and colposcopy. One hundred and seventy five woman were acetic acid test negative, 197 women were acetic acid test positive. The sensitivity of acetic acid test was 72.4%, specificity 54% and false negative rate 15.2%, as compared to papanicolaou test which had a sensitivity of 13.2%, specificity of 96.3% and false negative rate of 24.4%. The advantage of the acetic acid test lies in its easy technique, low cost and high sensitivity which are important factors for determining the efficacy of any screening programme in developing countries.

Effectiveness of cryotherapy treatment for cervical intraepithelial neoplasia.

PubMed

Luciani, Silvana; Gonzales, Miguel; Munoz, Sergio; Jeronimo, Jose; Robles, Sylvia

2008-05-01

To assess the effectiveness of cryotherapy treatment delivered by general practitioners in primary care settings, as part of a screen-and-treat approach for cervical cancer prevention. Women aged between 25 and 49 years residing in San Martin, Peru, who were positive on visual inspection screening were treated, if eligible, with cryotherapy following biopsy. At 12 months post cryotherapy treatment the participants were evaluated for treatment effectiveness and examined by visual inspection and Papanicolaou test and, if positive, referred to a gynecologist for colposcopy and biopsy. Cryotherapy treatment was performed for 1398 women; of these, 531 (38%) had a histology result of cervical intraepithelial neoplasia (CIN). Cryotherapy effectively cured CIN in 418 (88%) women, including 49 (70%) women with a baseline diagnosis of CIN 3. Cryotherapy is an effective treatment for cervical precancerous lesions; it can easily be administered by general practitioners in primary care settings following visual inspection screening.

[Possibilities of the TruScreen for screening of precancer and cancer of the uterine cervix].

PubMed

Zlatkov, V

2009-01-01

The classic approach of detection of pre-cancer and cancer of uterine cervix includes cytological examination, followed by colposcopy assessment of the detected cytological abnormalities. Real-time devices use in-vivo techniques for the measurement, computerized analysis and classifying of different types of cervical tissues. The aim of the present review is to present the technical characteristics and to discus the diagnostic possibilities of TruScreen-automated optical-electron system for cervical screening. The analysis of the presented in the literature diagnostic value of the method at different grades intraepithelial lesions shows that it has higher sensitivity (67-70%) and lower specificity (81%) in comparison to the Pap test with the following results (45-69% sensitivity and 95% specificity). This makes the method suitable for independent primary screening, as well as for adding the diagnostic assurance of the cytological method.

A pilot analytic study of a research-level, lower-cost human papillomavirus 16, 18, and 45 test.

PubMed

Yang, Hannah P; Walmer, David K; Merisier, Delson; Gage, Julia C; Bell, Laura; Rangwala, Sameera; Shrestha, Niwashin; Kobayashi, Lori; Eder, Paul S; Castle, Philip E

2011-09-01

The analytic performance of a low-cost, research-stage DNA test for the most carcinogenic human papillomavirus (HPV) genotypes (HPV16, HPV18, and HPV45) in aggregate was evaluated among carcinogenic HPV-positive women, which might be used to decide who needs immediate colposcopy in low-resource settings ("triage test"). We found that HPV16/18/45 test agreed well with two DNA tests, a GP5+/6+ genotyping assay (Kappa = 0.77) and a quantitative PCR assay (at a cutpoint of 5000 viral copies) (Kappa = 0.87). DNA sequencing on a subset of 16 HPV16/18/45 positive and 16 HPV16/18/45 negative verified the analytic specificity of the research test. It is concluded that the HPV16/18/45 assay is a promising triage test with a minimum detection of approximately 5000 viral copies, the clinically relevant threshold. Published by Elsevier B.V.

p16 staining has limited value in predicting the outcome of histological low-grade squamous intraepithelial lesions of the cervix.

PubMed

Sagasta, Amaia; Castillo, Paola; Saco, Adela; Torné, Aureli; Esteve, Roser; Marimon, Lorena; Ordi, Jaume; Del Pino, Marta

2016-01-01

In order to evaluate the usefulness of p16 staining in predicting the outcome of histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) we prospectively recruited all the patients referred to colposcopy from 2003 to 2011 due to abnormal screening test results and diagnosed with LSIL/CIN1 at biopsy (n=507). All biopsies were stained for p16 and re-evaluated after three years by the same gynecological pathologist using the LAST criteria. Follow-up was conducted every 6 months and included a Pap test (liquid-based cytology), high-risk human papillomavirus testing (Hybrid Capture 2 test), and colposcopy. The mean follow-up was 28 months. An outcome diagnosis of HSIL was defined as a histological diagnosis of high-grade SIL/CIN (HSIL/CIN2-3). The diagnosis of LSIL/CIN1 was confirmed in 416 out of 507 biopsies (82%), whereas 58 (11%) were reclassified as negative and 33 (6%) as HSIL/CIN2-3. During follow-up, 86/507 women initially diagnosed with LSIL/CIN1 (17%) showed an outcome diagnosis of HSIL/CIN2-3, with the rate of HSIL final diagnosis of 3% (2/58) in the women with biopsies reclassified as negative, 17% (70/416) in the group with confirmed LSIL and 42% (14/33) in the women with biopsies reclassified as HSIL (P<0.001). p16 was positive in 245/507 patients (48%) and in 210/416 patients (50%) with confirmed LSIL/CIN1 at re-evaluation. Although positive p16 immunostaining was associated with risk of HSIL/CIN2-3 outcome in the multivariate analysis (Hazard ratio (HR) 1.9; 95% confidence interval (CI): 1.2-3.1; P=0.009) in the overall group of patients with LSIL/CIN1, this association was not verified in the subset of patients with confirmed LSIL/CIN1 after re-evaluation (HR: 1.6; 95% CI: 0.9-2.6; P=0.095). In conclusion, in LSIL/CIN1 lesions p16 should be limited to equivocal cases in which HSIL/CIN2 is included in the differential diagnosis since it has low value in clinical practice as a marker of progression of LSIL/CIN1.

Recommendations for cervical cancer screening programs in developing countries. The need for equity and technological development.

PubMed

Lazcano-Ponce, Eduardo; Alonso, Patricia; Ruiz-Moreno, José Antonio; Hernández-Avila, Mauricio

2003-01-01

The cervical cancer screening programs (CCSP) have not been very efficient in the developing countries. This explains the need to foster changes on policies, standards, quality control mechanisms, evaluation and integration of new screening alternatives considered as low and high cost, as well as to regulate colposcopy practices and the foundation of HPV laboratories. Cervical cancer (CC) is a disease most frequently found in poverty-stricken communities and reflecting a problem of equity at both levels gender and regional, and this, is not only due to social and economic development inequalities, but to the infrastructure and human resources necessary for primary care. For this reason, the CCSP program must be restructured, a) to primarily address unprivileged rural and urban areas; b) to foster actions aimed at ensuring extensive coverage as well as a similar quality of that coverage in every region; c) to use screening strategies in keeping with the availability of health care services. In countries with a great regional heterogeneity, a variety of screening procedures must be regulated and standardized, including a combination of assisted visual inspection, cervical cytology and HPV detection; d) regional community intervention must be set up to assess the effectiveness of using HPV detection as an strategy in addition to cervical cytology (pap smear); e) the practice of colposcopy must be regulated to prevent the use of it in healthy women at a population level, thus preventing unnecessary diagnosis and treatment which not only are expensive but also causes unnecessary anxiety to women at risk; f) the operation of those clinical laboratories using HPV as a detection strategy must likewise be accredited and regulated and g) the CCSP program for assuring health care quality should meet the expectations of its beneficiaries, and increase the knowledge in cervical cancer related matters. Finally, though a variety of clinical tests on prophylactic and therapeutic vaccines against HPV are recently being developed worldwide; it will take at least from 5 to 10-years time to have them available in the market. For this reason, it will be necessary to intensify the CCSP programs. All these reasons lay emphasis on the need to reinforce actions for CCSP programs. This paper is available too at: http://www.insp.mx/salud/index.html.

Human papillomavirus-based cervical cancer prevention: long-term results of a randomized screening trial.

PubMed

Denny, Lynette; Kuhn, Louise; Hu, Chih-Chi; Tsai, Wei-Yann; Wright, Thomas C

2010-10-20

Screen-and-treat approaches to cervical cancer prevention are an attractive option for low-resource settings, but data on their long-term efficacy are lacking. We evaluated the efficacy of two screen-and-treat approaches through 36 months of follow-up in a randomized trial. A total of 6637 unscreened South African women aged 35-65 years who were tested for the presence of high-risk human papillomavirus (HPV) DNA in cervical samples underwent visual inspection of the cervix using acetic acid staining and HIV serotesting. Of these, 6555 were randomly assigned to three study arms: 1) HPV-and-treat, in which all women with a positive HPV DNA test result underwent cryotherapy; 2) visual inspection-and-treat, in which all women with a positive visual inspection test result underwent cryotherapy; or 3) control, in which further evaluation or treatment was delayed for 6 months. All women underwent colposcopy with biopsy at 6 months. All women who were HPV DNA- or visual inspection-positive at enrollment, and a subset of all other women had extended follow-up to 36 months (n = 3639) with yearly colposcopy. The endpoint-cervical intraepithelial neoplasia grade 2 or worse (CIN2+)-was analyzed using actuarial life-table methods. All statistical tests were two-sided. After 36 months, there was a sustained statistically significant decrease in the cumulative detection of CIN2+ in the HPV-and-treat arm compared with the control arm (1.5% vs 5.6%, difference = 4.1%, 95% confidence interval [CI] = 2.8% to 5.3%, P < .001). The difference in the cumulative detection of CIN2+ in the visual inspection-and-treat arm compared with the control was less (3.8% vs 5.6%, difference = 1.8%, 95% CI = 0.4% to 3.2%, P = .002). Incident cases of CIN2+ (identified more than 12 months after enrollment) were less common in the HPV-and-treat arm (0.3%, 95% CI = 0.05% to 1.02%) than in the control (1.0%, 95% CI = 0.5% to 1.7%) or visual inspection-and-treat (1.3%, 95% CI = 0.8% to 2.1%) arms. In this trial, a screen-and-treat approach using HPV DNA testing identified and treated prevalent cases of CIN2+ and appeared to reduce the number of incident cases of CIN2+ that developed more than 12 months after cryotherapy.

"Low-grade squamous intraepithelial lesion, cannot exclude high-grade:" TBS says "Don't Use It!" should I really stop it?

PubMed

Chiaffarano, Jeanine M; Alexander, Melissa; Rogers, Robert; Zhou, Fang; Cangiarella, Joan; Yee-Chang, Melissa; Elgert, Paul; Simsir, Aylin

2017-01-01

The Bethesda System uses a two-tiered approach in the diagnosis of cervical squamous intraepithelial lesions (SILs). Occasionally, Papanicolaou (Pap) tests with evident low-grade SIL (LSIL) also have some features suggestive but not diagnostic of high-grade SIL (HSIL). This study reviews our experience with "Low-grade Squamous Intraepithelial Lesion, Cannot Exclude High-grade" (LSIL-H) and discusses the best approach to report such Paps if the LSIL-H interpretation is abandoned. Abnormal Paps were identified between January and December 2014 that had surgical follow-up within 6 months. Their biopsy outcomes were compared. Statistical analysis was performed using Pearson's Chi-square and McNemar tests in SPSS software version 23. Statistical significance was defined as P ≤ 0.05. There were a total of 1049 abnormal Paps with follow-up. High-grade dysplasia/carcinoma (HGD+) was found in 8% of LSIL, 30% of LSIL-H, 52% of atypical squamous cells (ASCs), cannot rule out HSIL (ASC-H), and 77% of HSIL Paps. The detection rate of HGD+ for LSIL-H was between that of LSIL (Pearson's Chi-square test, P = 0.000) and ASC-H ( P = 0.04). If LSIL-H cases are reported as ASC-H, the rate of HGD+ for the ASC-H category would decrease from 51.5% to 37.4% (McNemar test, P = 0.000). Alternatively, if LSIL-H cases are downgraded to LSIL, the rate of HGD+ for the LSIL category would rise from 7.7% to 10.4% (McNemar test, P = 0.000). Nearly 86.7% of LSIL-H cases were positive for high-risk HPV (HR-HPV) in comparison to 77.5% of LSILs, 100% of ASC-Hs, and 75% of HSILs. The sample size for HR-HPV and LSIL-H was too small for meaningful statistical analysis. "LSIL-H" category detects more HGD+ than LSIL, and fewer than ASC-H and HSIL. If LSIL-H is eliminated, Paps with this finding are best reported as ASC-H to ensure that women with potential HGD+ undergo colposcopy in a timely manner. Reporting LSIL-H as LSIL may delay colposcopy since management of LSIL Paps depends on multiple factors (age, HPV status, etc.).

Vaginal microbicides: detecting toxicities in vivo that paradoxically increase pathogen transmission

PubMed Central

Cone, Richard A; Hoen, Timothy; Wong, XiXi; Abusuwwa, Raed; Anderson, Deborah J; Moench, Thomas R

2006-01-01

Background Microbicides must protect against STD pathogens without causing unacceptable toxic effects. Microbicides based on nonoxynol-9 (N9) and other detergents disrupt sperm, HSV and HIV membranes, and these agents are effective contraceptives. But paradoxically N9 fails to protect women against HIV and other STD pathogens, most likely because it causes toxic effects that increase susceptibility. The mouse HSV-2 vaginal transmission model reported here: (a) Directly tests for toxic effects that increase susceptibility to HSV-2, (b) Determines in vivo whether a microbicide can protect against HSV-2 transmission without causing toxicities that increase susceptibility, and (c) Identifies those toxic effects that best correlate with the increased HSV susceptibility. Methods Susceptibility was evaluated in progestin-treated mice by delivering a low-dose viral inoculum (0.1 ID50) at various times after delivering the candidate microbicide to detect whether the candidate increased the fraction of mice infected. Ten agents were tested – five detergents: nonionic (N9), cationic (benzalkonium chloride, BZK), anionic (sodium dodecylsulfate, SDS), the pair of detergents in C31G (C14AO and C16B); one surface active agent (chlorhexidine); two non-detergents (BufferGel®, and sulfonated polystyrene, SPS); and HEC placebo gel (hydroxyethylcellulose). Toxic effects were evaluated by histology, uptake of a 'dead cell' dye, colposcopy, enumeration of vaginal macrophages, and measurement of inflammatory cytokines. Results A single dose of N9 protected against HSV-2 for a few minutes but then rapidly increased susceptibility, which reached maximum at 12 hours. When applied at the minimal concentration needed for brief partial protection, all five detergents caused a subsequent increase in susceptibility at 12 hours of ~20–30-fold. Surprisingly, colposcopy failed to detect visible signs of the N9 toxic effect that increased susceptibility at 12 hours. Toxic effects that occurred contemporaneously with increased susceptibility were rapid exfoliation and re-growth of epithelial cell layers, entry of macrophages into the vaginal lumen, and release of one or more inflammatory cytokines (Il-1β, KC, MIP 1α, RANTES). The non-detergent microbicides and HEC placebo caused no significant increase in susceptibility or toxic effects. Conclusion This mouse HSV-2 model provides a sensitive method to detect microbicide-induced toxicities that increase susceptibility to infection. In this model, there was no concentration at which detergents provided protection without significantly increasing susceptibility. PMID:16740164

Screening women for cervical cancer carcinoma with a HPV mRNA test: first results from the Venice pilot program.

PubMed

Maggino, Tiziano; Sciarrone, Rocco; Murer, Bruno; Dei Rossi, Maria Rosa; Fedato, Chiara; Maran, Michela; Lorio, Melania; Soldà, Marika; Zago, Fiorella; Giorgi Rossi, Paolo; Zorzi, Manuel

2016-08-23

HPV DNA-based screening is more effective than a Pap test in preventing cervical cancer, but the test is less specific. New HPV tests have been proposed for primary screening. The HPV mRNA test showed a similar or slightly lower sensitivity than the HPV DNA tests but with a higher specificity. We report the results of an organised HPV mRNA-based screening pilot program in Venice, Italy. From October 2011 to May 2014, women aged 25-64 years were invited to undergo a HPV mRNA test (Aptima). Those testing positive underwent cytological triage. Women with positive cytology were referred to colposcopy, whereas those with negative cytology were referred to repeat the HPV mRNA test 1 year later. The results of the HPV mRNA test program were compared with both the local historical cytology-based program and with four neighbouring DNA HPV-based pilot projects. Overall, 23 211 women underwent a HPV mRNA test. The age-standardised positivity rate was 7.0%, higher than in HPV DNA programs (6.8%; relative rate (RR) 1.11, 95% confidence interval (CI) 1.05-1.17). The total colposcopy referral was 5.1%, double than with cytology (2.6%; RR 2.02, 95% CI 1.82-2.25) but similar to the HPV DNA programs (4.8%; RR 1.02; 95% CI 0.96-1.08). The cervical intraepithelial neoplasia grade 2+ detection rate with HPV mRNA was greater than in the HPV DNA programs at baseline (RR 1.50; 95% CI 1.19-1.88) and not significantly lower at the 1-year repeat (RR 0.70; 95% CI 0.40-1.16). The overall RR was 1.29 (95% CI 1.05-1.59), which was much higher than with cytology (detection rate 5.5‰ vs 2.1‰; RR 2.50, 95% CI 1.76-3.62). A screening programme based on the HPV mRNA obtained results similar to those observed with the HPV DNA test. In routine screening programmes, even a limited increase in HPV prevalence may conceal the advantage represented by the higher specificity of HPV mRNA.

Human papillomavirus testing and liquid-based cytology in primary screening of women younger than 35 years: results at recruitment for a randomised controlled trial.

PubMed

Ronco, Guglielmo; Giorgi-Rossi, Paolo; Carozzi, Francesca; Dalla Palma, Paolo; Del Mistro, Annarosa; De Marco, Laura; De Lillo, Margherita; Naldoni, Carlo; Pierotti, Paola; Rizzolo, Raffaella; Segnan, Nereo; Schincaglia, Patrizia; Zorzi, Manuel; Confortini, Massimo; Cuzick, Jack

2006-07-01

Testing for human papillomavirus (HPV) DNA is more sensitive but less specific than cytological analysis. Loss in specificity is most relevant in women younger than 35 years because of increased HPV prevalence. We aimed to compare conventional screening with an experimental strategy in women aged 25-34 years, and investigate the effect of different criteria of referral to define the best methods of HPV screening. Women were randomly assigned to the conventional procedure (standard cytology, with referral to colposcopy if cytology showed atypical squamous cells of undetermined significance or more [ASCUS+]) or an experimental procedure (liquid-based cytology and testing for high-risk HPV types, with referral to colposcopy with ASCUS+ cytology). Women positive for HPV (cutoff > or = 1 pg/mL) but with normal cytology were retested after 1 year. The main endpoint was the presence of cervical intraepithelial neoplasia at grade 2 or more (CIN2+) in reviewed histology. The main analysis was by intention to screen. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN81678807. We randomly assigned 5808 women aged 25-34 years to the conventional group and 6002 to the experimental group. The experimental procedure was significantly more sensitive than the conventional procedure (55 vs 33 CIN2+ lesions detected; relative sensitivity 1.61 [95% CI 1.05-2.48]), but had a lower positive predictive value (PPV; relative PPV 0.55 [0.37-0.82]). HPV testing (> or = 1 pg/mL) with cytology triage was also more sensitive than conventional cytology (relative sensitivity 1.58 [1.03-2.44], relative PPV 0.78 [0.52-1.16]). Relative PPV could be improved, with minimum loss in sensitivity, by use of a 2 pg/mL cutoff for HPV testing. Compared with conventional cytology, liquid-based cytology had a relative sensitivity of 1.32 (0.84-2.06), relative PPV 0.58 [0.38-0.89]). HPV testing alone with cytology triage could be a feasible alternative to conventional cytology for screening women younger than 35 years. Follow-up will provide data on possible overdiagnosis and on the feasibility of extended intervals.

Expenditure and resource utilisation for cervical screening in Australia

PubMed Central

2012-01-01

Background The National Cervical Screening Program in Australia currently recommends that women aged 18–69 years are screened with conventional cytology every 2 years. Publicly funded HPV vaccination was introduced in 2007, and partly as a consequence, a renewal of the screening program that includes a review of screening recommendations has recently been announced. This study aimed to provide a baseline for such a review by quantifying screening program resource utilisation and costs in 2010. Methods A detailed model of current cervical screening practice in Australia was constructed and we used data from the Victorian Cervical Cytology Registry to model age-specific compliance with screening and follow-up. We applied model-derived rate estimates to the 2010 Australian female population to calculate costs and numbers of colposcopies, biopsies, treatments for precancer and cervical cancers in that year, assuming that the numbers of these procedures were not yet substantially impacted by vaccination. Results The total cost of the screening program in 2010 (excluding administrative program overheads) was estimated to be A$194.8M. We estimated that a total of 1.7 million primary screening smears costing $96.7M were conducted, a further 188,900 smears costing $10.9M were conducted to follow-up low grade abnormalities, 70,900 colposcopy and 34,100 histological evaluations together costing $21.2M were conducted, and about 18,900 treatments for precancerous lesions were performed (including retreatments), associated with a cost of $45.5M for treatment and post-treatment follow-up. We also estimated that $20.5M was spent on work-up and treatment for approximately 761 women diagnosed with invasive cervical cancer. Overall, an estimated $23 was spent in 2010 for each adult woman in Australia on cervical screening program-related activities. Conclusions Approximately half of the total cost of the screening program is spent on delivery of primary screening tests; but the introduction of HPV vaccination, new technologies, increasing the interval and changing the age range of screening is expected to have a substantial impact on this expenditure, as well as having some impact on follow-up and management costs. These estimates provide a benchmark for future assessment of the impact of changes to screening program recommendations to the costs of cervical screening in Australia. PMID:23216968

Young women, cervical intraepithelial neoplasia and human papillomavirus: risk factors for persistence and recurrence.

PubMed

Frega, Antonio; Stentella, Patrizia; De Ioris, Andrea; Piazze, Juan Josè; Fambrini, Massimiliano; Marchionni, Mauro; Cosmi, Ermelando Vinicio

2003-07-10

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections (STIs) in young women. They can occur in one or multiple areas of the female genitalia. Usually, the vulva is the initial site of implantation for HPV. The purpose of our study is to evaluate the epidemiological aspects, incidence of single or multiple lesions in the lower genital tract, correlation between sexual behaviour and their localization and behaviour risk factors for persistence and recurrence of HPV lesions and cervical intraepithelial lesion (CIN) in a long-term follow-up among young women. We recruited 268 patients aged 11-21 years who previously had cytology and/or physical examination suspicious for HPV infection. The women were interviewed and asked information about lifestyle, sexual behaviour, work, personal or family history of genital warts and school attendance. We considered individuals to be 'smokers' if they smoked more than five cigarettes/day. No specific data were recorded about oral contraception, nevertheless, no woman had used oral contraceptives (OCs) for more than 2 years. Young women included in the study were between the age of 12 and 21 years who had HVP lesions after entry examinations and had undergone no treatment for HPV lesions prior to entry. Other exclusion criteria relevant to this study included cervical excisional treatment prior to entry or later. Two hundred and thirty-four young women were included in our study group. Our diagnostic schedule for a complete evaluation included exo- and endocervical cytology, colposcopy, directed biopsy and microcolpohysteroscopy. The treatment was performed with a LASER CO2 Coherent 400, model 451, with Zeiss photocolposcopy attachment. The finding that, among 126/234 (53.8%) adolescents using contraceptives, only 85 (36.3%) have used condom, the only barrier form of contraceptive effectively protecting against virus, shows a low awareness of the high risk for contracting HPV infection among young sexually active women. The sites most frequently affected in our study were vulva, perianus and perineum (194/234), 82.9% and the cervix (125/234), 53.4%. Vaginal lesions were detected only in 29/234 patients (12.3%). According to our data, in 161 patients, sexual habits, age at the first intercourse (P=0.68), frequency of intercourses (P=0.49) and number of lifetime partners (P=0.27) as well as age (P=0.26) play a role in transmission and incidence of HPV infection but not on the location of the lesions. This can be due to a coexistent clinical and subclinical multiple infection as well as a transmission via intercourse or from other sources, including tampons. Abnormal Pap test was related to HPV infection, but the low correlation with colposcopic and histological findings in this study justify the support of other examinations such as colposcopy and punch biopsy for diagnosis. Moreover, according to our data, cytology alone shows to be not suitable to exclude CIN (seven underestimated cases of CIN) and a closer correspondence were found between colposcopy and the result of histological sample after punch biopsy in CIN detection. More attention must be paid to psychological aspect of diagnoses and treatment among adolescents, more than older women as the high rate of patients lost shows in our study: 75/234 (32.05%) before LASER surgery and 55/159 (34.59%) during follow-up. International data shows that only 12-45% of sexually active adolescent girls have obtained Pap smear screening. In our study, we found no correlation between treatment failure and cigarette smoking or between the use of oral contraceptives and persistence/recurrence after LASER CO2 surgery. Because the small sample of our study group, further analyses were required.

Pain relief for women with cervical intraepithelial neoplasia undergoing colposcopy treatment.

PubMed

Gajjar, Ketan; Martin-Hirsch, Pierre P L; Bryant, Andrew; Owens, Gemma L

2016-07-18

Pre-cancerous lesions of cervix (cervical intraepithelial neoplasia (CIN)) are usually treated with excisional or ablative procedures. In the UK, the National Health Service (NHS) cervical screening guidelines suggest that over 80% of treatments should be performed in an outpatient setting (colposcopy clinics). Furthermore, these guidelines suggest that analgesia should always be given prior to laser or excisional treatments. Currently various pain relief strategies are employed that may reduce pain during these procedures. To assess whether the administration of pain relief (analgesia) reduces pain during colposcopy treatment and in the postoperative period. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2), MEDLINE (1950 to March week 3, 2016) and Embase (1980 to week 12, 2016) for studies of any design relating to analgesia for colposcopic management. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Randomised controlled trials (RCTs) that compared all types of pain relief before, during or after outpatient treatment to the cervix, in women with CIN undergoing loop excision, laser ablation, laser excision or cryosurgery in an outpatient colposcopy clinic setting. We independently assessed study eligibility, extracted data and assessed risk of bias. We entered data into Review Manager 5 and double checked it for accuracy. Where possible, we expressed results as mean pain score and standard error of the mean with 95% confidence intervals (CI) and synthesised data in a meta-analysis. We included 19 RCTs (1720 women) of varying methodological quality in the review. These trials compared a variety of interventions aimed at reducing pain in women who underwent treatment for CIN, including cervical injection with lignocaine alone, lignocaine with adrenaline, buffered lignocaine with adrenaline, prilocaine with felypressin, oral analgesics (non-steroidal anti-inflammatory drugs (NSAIDs)), inhalation analgesia (gas mixture of isoflurane and desflurane), lignocaine spray, cocaine spray, local application of benzocaine gel, lignocaine-prilocaine cream (EMLA cream) and transcutaneous electrical nerve stimulation (TENS).Most comparisons were restricted to single trial analyses and were under-powered to detect differences in pain scores between treatments that may or may not have been present. There was no difference in pain relief between women who received local anaesthetic infiltration (lignocaine 2%; administered as a paracervical or direct cervical injection) and a saline placebo (mean difference (MD) -13.74; 95% CI -34.32 to 6.83; 2 trials; 130 women; low quality evidence). However, when local anaesthetic was combined with a vasoconstrictor agent (one trial used lignocaine plus adrenaline while the second trial used prilocaine plus felypressin), there was less pain (on visual analogue scale (VAS)) compared with no treatment (MD -23.73; 95% CI -37.53 to -9.93; 2 trials; 95 women; low quality evidence). Comparing two preparations of local anaesthetic combined with vasoconstrictor, prilocaine plus felypressin did not differ from lignocaine plus adrenaline for its effect on pain control (MD -0.05; 95% CI -0.26 to 0.16; 1 trial; 200 women). Although the mean (± standard deviation (SD)) observed blood loss score was less with lignocaine plus adrenaline (1.33 ± 1.05) compared with prilocaine plus felypressin (1.74 ± 0.98), the difference was not clinically as the overall scores in both groups were low (MD 0.41; 95% CI 0.13 to 0.69; 1 trial; 200 women). Inhalation of gas mixture (isoflurane and desflurane) in addition to standard cervical injection with prilocaine plus felypressin resulted in less pain during the LLETZ (loop excision of the transformation zone) procedure (MD -7.20; 95% CI -12.45 to -1.95; 1 trial; 389 women). Lignocaine plus ornipressin resulted in less measured blood loss (MD -8.75 ml; 95% CI -10.43 to -7.07; 1 trial; 100 women) and a shorter duration of treatment (MD -7.72 minutes; 95% CI -8.49 to -6.95; 1 trial; 100 women) than cervical infiltration with lignocaine alone. Buffered solution (sodium bicarbonate buffer mixed with lignocaine plus adrenaline) was not superior to non-buffered solution of lignocaine plus adrenaline in relieving pain during the procedure (MD -8.00; 95% CI -17.57 to 1.57; 1 trial; 52 women).One meta-analysis found no difference in pain using VAS between women who received oral analgesic and women who received placebo (MD -3.51; 95% CI -10.03 to 3.01; 2 trials; 129 women; low quality evidence).Cocaine spray was associated with less pain (MD -28.00; 95% CI -37.86 to -18.14; 1 trial; 50 women) and blood loss (MD 0.04; 95% CI 0 to 0.70; 1 trial; 50 women) than placebo.None of the trials reported serious adverse events and majority of trials were at moderate or high risk of bias (13 trials). Based on two small trials, there was no difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (MD -3.51; 95% CI -10.03 to 3.01; 129 women). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.

Investigation of the sensitivity of a cross-polarized light visualization system to detect subclinical erythema and dryness in women with vulvovaginitis.

PubMed

Farage, Miranda A; Singh, Mukul; Ledger, William J

2009-07-01

An enhanced visualization technique using polarized light (Syris v600 enhanced visualization system; Syris Scientific LLC, Gray, ME) detects surface and subsurface ( approximately 1 mm depth) inflammation. We sought to compare the Syris v600 system with unaided visual inspection and colposcopy of the female genitalia. Erythema and dryness of the vulva, introitus, vagina, and cervix were visualized and scored by each method in patients with and without vulvitis. Subsurface visualization was more sensitive in detecting genital erythema and dryness at all sites whether or not symptoms were present. Subsurface inflammation of the introitus, vagina, and cervix only was detected uniquely in women with vulvar vestibulitis syndrome (VVS). A subset of women presenting with VVS exhibited subclinical inflammation of the vulva vestibule and vagina (designated VVS/lichen sclerosus subgroup). Enhanced visualization of the genital epithelial subsurface with cross-polarized light may assist in diagnosing subclinical inflammation in vulvar conditions heretofore characterized as sensory syndromes.

Capabilities of OCT in diagnosing pathological processes, functional states, and treatment adequacy in gynecology

NASA Astrophysics Data System (ADS)

Shakhova, Natalia M.; Kachalina, Tatiana S.; Kuznetzova, Irina N.; Chumakov, Yuri; Feldchtein, Felix I.; Gelikonov, Valentin M.; Gelikonov, Grigory V.; Gladkova, Natalia D.; Kamensky, Vladislav A.; Kuranov, Roman V.; Sergeev, Alexander M.

1999-01-01

We report on the results of using the optical coherence tomography (OCT) as one of the diagnostic methods at the Department of Gynecology of the Nizhny Novgorod Regional Hospital. An endoscopic OCT device adjusted for gynecological examinations with colposcopy, hysteroscopy and laparoscopy has been developed at the Institute of Applied Physics. It provides clinicians with sharp (up to 15 - 20 micron resolution) images of 1.5 mm thick superficial mucosa layers in the female genital tract, that are recorded at the 0.83 micron wavelength with approximately 1 frame/second rate for a 200 X 200 pixel image. Data obtained during examination of more than 100 patients demonstrate the capability of OCT in estimation of structural alterations in organs, connected with different types of pathologies and functional states of the female genital system. We present first results of OCT application to assess the adequacy of cervical pathologies treatment (electro-, laser surgery and cryotherapy) and to control the healing process.

[S3 guidelines on diagnostics and treatment of cervical cancer: Demands on pathology].

PubMed

Horn, L-C; Beckmann, M W; Follmann, M; Koch, M C; Mallmann, P; Marnitz, S; Schmidt, D

2015-11-01

Between 2011 and the end of 2014 the former consensus S2k guidelines for the diagnostics and treatment of cervical cancer were updated and upgraded to S3 level, methodologically based on the regulations of the German Cancer Society (DKG). The present article summarizes the relevant aspects for the sectioning, histopathological workup, diagnostics and reporting for the pathology of invasive cancer of the uterine cervix. The recommendations are based on the most recent World Health Organization (WHO) and TNM classification systems and consider the needs of the clinician for appropriate surgical and radiotherapeutic treatment of patients. Detailed processing rules of colposcopy-guided diagnostic biopsies, conization and trachelectomy as well as for radical hysterectomy specimens and lymph node resection (including sentinel lymph node resection) are given. In the guidelines deep stromal invasion in macroinvasive cervical cancer is defined for the first time as tumor infiltration of > 66% of the cervical stromal wall. Furthermore, morphological prognostic factors for microinvasive and macroinvasive cervical cancer are summarized.

Large loop excision of the transformation zone for treating cervical intraepithelial neoplasia: a 12-year experience.

PubMed

Paraskevaidis, E; Koliopoulos, G; Malamou-Mitsi, V; Zikopoulos, K; Paschopoulos, M; Pappa, L; Agnantis, N J; Loli, D E

2001-01-01

Although the existing evidence suggests that there is no obviously superior conservative method for treating cervical intraepithelial neoplasia (CIN), one of the most widely used is the large loop excision of the transformation zone (LLETZ). A total of 897 women who were treated with LLETZ at our colposcopy clinic from 1989 to 2000 were retrospectively studied. Forty women did not have significant cervical pathology (4.5% over-treatment rate). Clear margins of excision were obtained in 748 (88.5%) of the 845 cases of CIN or microinvasive cancers. Treatment failure rates were 4.7% for clear margins and 26.8% for involved or uncertain. LLETZ is a fast and reliable method of treating CIN and microinvasive carcinoma. Generalized cauterization of the resulting crater should be avoided and satellite HPV lesions ablated. Involved margins have a higher treatmentfailure rate, therefore a larger excision is recommended as cervical craters regenerate. Treatment in pregnant women can be delayed until postpartum provided they have adequate surveillance during pregnancy.

[Local treatment of cervical intraepithelial neoplasia with a 5 percent fluorouracil ointment].

PubMed

Barten, G

1987-01-01

The results of treatment of histologically proven cervical intraepithelial neoplasia (CIN) in 10 women are described. Two of them had CIN I and 8 CIN III. All patients had a application of 5 g 5 per cent 5-fluorouracil cream in a cervical cup daily over a period of 12 hours for one week. All 10 patients have been examined colposcopically, cytological and by biopsy following therapy. In 8 women cone biopsie were done 6-12 months afterwards for having a final diagnosis 2 patients having CIN I pretherapeutically were follow up for 16 months with cytology, colposcopy and punch biopsy. In 6 cases we found better findings (Twice complete healing, twice only CIN I and twice CIN II as residues). In 4 cases severe dysplasia and carcinoma in situ could be found in endocervix. Based on these results were recommended more (not only one) treatment cycles for local efficient chemotherapy using 5 per cent 5-fluorouracil cream.

Primary HPV testing versus cytology-based cervical screening in women in Australia vaccinated for HPV and unvaccinated: effectiveness and economic assessment for the National Cervical Screening Program.

PubMed

Lew, Jie-Bin; Simms, Kate T; Smith, Megan A; Hall, Michaela; Kang, Yoon-Jung; Xu, Xiang Ming; Caruana, Michael; Velentzis, Louiza Sofia; Bessell, Tracey; Saville, Marion; Hammond, Ian; Canfell, Karen

2017-02-01

Australia's National Cervical Screening Program currently recommends cytological screening every 2 years for women aged 18-69 years. Human papillomavirus (HPV) vaccination was implemented in 2007 with high population coverage, and falls in high-grade lesions in young women have been reported extensively. This decline prompted a major review of the National Cervical Screening Program and new clinical management guidelines, for which we undertook this analysis. We did effectiveness modelling and an economic assessment of potential new screening strategies, using a model of HPV transmission, vaccination, natural history, and cervical screening. First, we evaluated 132 screening strategies, including those based on cytology and primary HPV testing. Second, after a recommendation was made to adopt primary HPV screening with partial genotyping and direct referral to colposcopy of women positive for HPV16/18, we evaluated the final effect of HPV screening after incorporating new clinical guidelines for women positive for HPV. Both evaluations considered both unvaccinated and vaccinated cohorts. Strategies entailing HPV testing every 5 years and either partial genotyping for HPV16/18 or cytological co-testing were the most effective. One of the most effective and cost-effective strategies comprised primary HPV screening with referral of women positive for oncogenic HPV16/18 direct to colposcopy, with reflex cytological triage for women with other oncogenic types and direct referral for those in this group with high-grade cytological findings. After incorporating detailed clinical guidelines recommendations, this strategy is predicted to reduce cervical cancer incidence and mortality by 31% and 36%, respectively, in unvaccinated cohorts, and by 24% and 29%, respectively, in cohorts offered vaccination. Furthermore, this strategy is predicted to reduce costs by up to 19% for unvaccinated cohorts and 26% for cohorts offered vaccination, compared with the current programme. Primary HPV screening every 5 years with partial genotyping is predicted to be substantially more effective and potentially cost-saving compared with the current cytology-based screening programme undertaken every 2 years. These findings underpin the decision to transition to primary HPV screening with partial genotyping in the Australian National Cervical Screening Program, which will occur in May, 2017. Department of Health, Australia. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.

Persistent infection with high-risk human papilloma viruses: cohort study, Mérida, Venezuela

PubMed Central

Téllez, Luis; Michelli, Elvia; Mendoza, José Andrés; Vielma, Silvana; Noguera, María-Eugenia; Callejas, Diana; Cavazza, María; Correnti, María

2015-01-01

Cervical lesions have been associated with infection by high-risk human papilloma virus (high-risk HPV). In 409 women aged >15 years high-risk HPV lesions were identified. In a cohort of this population persistent infection was compared with cytological, colposcopic, and histological lesions. Cervical scrapes were taken and DNA was isolated. HPV was detected by PCR in the E6/E7 region. Genotyping was performed by PCR nested multiple E6/E7. HPV was detected in a 37.40% (153/409), high-risk HPV in 86% (153/178), HPV18 46.64% (83/178), HPV16 34.28% (61/178). Among these 53.93% (96/178) were multiple infections, and HPV18/16 (30/96) was the most frequent 31.25%. The cytology showed changes in 15% of positive patients. A 49.67% in women positive for HPV infection showed abnormalities in the colposcopic study, a relationship that turned out to be statistically significant ( p < 0.0019 test χ2). Among all 85% of the women were younger than 45 years of age. Fifty-seven patients were evaluated 15 months after the base study, with initial prevalence of morbidity 49.12% (28/57) and at the end 10.53% (6/57), showing in 89.29% (25/28) negative for HR-HPV infection, 10.34% (3/28) showed persistence of infection, 17.54% (10/57) presented cytological alterations, with 80% of positivity for HPV, and a regression of 100% (10/10) of the previously identified lesions. With colposcopy, 50% (14/28) presented alterations related to HPV, of these 85.71% (12/14) showed regression of such an alteration. The cumulative incidence for HPV was 10.34% (3/29). The incidence rate was 4.23% (3/71), which is equal to 4.23 new cases of HPV infection per 100 people, per year of follow-up. In conclusion, the present work shows a high frequency of infection by high-risk HPV, with predominance of HPV18 and 16 and in general for multiple infections. Colposcopy was better predictor than the Pap smear for infection. The follow-up study revealed a low percentage of persistent infection, and a high frequency of negativity for viral infection, high regression of cytological and colposcopic lesions, a low cumulative and incidence rate similar to that reported by other Latin American countries and higher than the European countries. PMID:26557877

Performance of p16INK4a ELISA as a primary cervical cancer screening test among a large cohort of HIV-infected women in western Kenya: a 2-year cross-sectional study.

PubMed

Wu, Tara J; Smith-McCune, Karen; Reuschenbach, Miriam; von Knebel Doeberitz, Magnus; Maloba, May; Huchko, Megan J

2016-09-13

A biomarker with increased specificity for cervical dysplasia compared with human papillomavirus (HPV) testing would be an attractive option for cervical cancer screening among HIV-infected women in resource-limited settings. p16(INK4a) has been explored as a biomarker for screening in general populations. A 2-year cross-sectional study. 2 large HIV primary care clinics in western Kenya. 1054 HIV-infected women in western Kenya undergoing cervical cancer screening as part of routine HIV care from October 2010 to November 2012. Participants underwent p16(INK4a) specimen collection and colposcopy. Lesions with unsatisfactory colposcopy or suspicious for cervical intraepithelial neoplasia 2+ (CIN2+; including CIN2/3 or invasive cervical cancer) were biopsied. Following biopsy, disease status was determined by histopathological diagnosis. We measured the sensitivity, specificity and predictive values of p16(INK4a) ELISA for CIN2+ detection among HIV-infected women and compared them to the test characteristics of current screening methods used in general as well as HIV-infected populations. Average p16(INK4a) concentration in cervical samples was 37.4 U/mL. After colposcopically directed biopsy, 127 (12%) women were determined to have CIN2+. Receiver operating characteristic analysis showed an area under the curve of 0.664 for p16(INK4a) to detect biopsy-proven CIN2+. At a p16(INK4a) cut-off level of 9 U/mL, sensitivity, specificity, positive and negative predictive values were 89.0%, 22.9%, 13.6% and 93.8%, respectively. The overall p16(INK4a) positivity at a cut-off level of 9 U/mL was 828 (78.6%) women. There were 325 (30.8%) cases of correct p16(INK4a) prediction to detect or rule out CIN2+, and 729 (69.2%) cases of incorrect p16(INK4a) prediction. p16(INK4a) ELISA did not perform well as a screening test for CIN2+ detection among HIV-infected women due to low specificity. Our study contributes to the ongoing search for a more specific alternative to HPV testing for CIN2+ detection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Performance of p16INK4a ELISA as a primary cervical cancer screening test among a large cohort of HIV-infected women in western Kenya: a 2-year cross-sectional study

PubMed Central

Wu, Tara J; Smith-McCune, Karen; Reuschenbach, Miriam; von Knebel Doeberitz, Magnus; Maloba, May; Huchko, Megan J

2016-01-01

Objective A biomarker with increased specificity for cervical dysplasia compared with human papillomavirus (HPV) testing would be an attractive option for cervical cancer screening among HIV-infected women in resource-limited settings. p16INK4a has been explored as a biomarker for screening in general populations. Design A 2-year cross-sectional study. Setting 2 large HIV primary care clinics in western Kenya. Participants 1054 HIV-infected women in western Kenya undergoing cervical cancer screening as part of routine HIV care from October 2010 to November 2012. Interventions Participants underwent p16INK4a specimen collection and colposcopy. Lesions with unsatisfactory colposcopy or suspicious for cervical intraepithelial neoplasia 2+ (CIN2+; including CIN2/3 or invasive cervical cancer) were biopsied. Following biopsy, disease status was determined by histopathological diagnosis. Primary and secondary outcome measures We measured the sensitivity, specificity and predictive values of p16INK4a ELISA for CIN2+ detection among HIV-infected women and compared them to the test characteristics of current screening methods used in general as well as HIV-infected populations. Results Average p16INK4a concentration in cervical samples was 37.4 U/mL. After colposcopically directed biopsy, 127 (12%) women were determined to have CIN2+. Receiver operating characteristic analysis showed an area under the curve of 0.664 for p16INK4a to detect biopsy-proven CIN2+. At a p16INK4a cut-off level of 9 U/mL, sensitivity, specificity, positive and negative predictive values were 89.0%, 22.9%, 13.6% and 93.8%, respectively. The overall p16INK4a positivity at a cut-off level of 9 U/mL was 828 (78.6%) women. There were 325 (30.8%) cases of correct p16INK4a prediction to detect or rule out CIN2+, and 729 (69.2%) cases of incorrect p16INK4a prediction. Conclusions p16INK4a ELISA did not perform well as a screening test for CIN2+ detection among HIV-infected women due to low specificity. Our study contributes to the ongoing search for a more specific alternative to HPV testing for CIN2+ detection. PMID:27625065

An interesting finding in the uterine cervix: Schistosoma hematobium calcified eggs.

PubMed

Toller, Alexia; Scopin, Ana Carolina; Apfel, Vanessa; Prigenzi, Karla Calaça Kabbach; Tso, Fernanda Kesselring; Focchi, Gustavo Rubino de Azevedo; Speck, Neila; Ribalta, Julisa

2015-01-01

Schistosoma hematobium infection is an endemic parasitic disease in Africa, which is frequently associated with urinary schistosomiasis. The parasite infection causes epithelial changes and disruption, facilitating the infection by the human papilloma virus and human immunodeficiency virus (HIV). The authors report the case of a 44-year-old African HIV-positive woman who presented an abnormal routine Pap smear. Colposcopy examination revealed dense acetowhite micropapillary epithelium covering the ectocervix, iodine-negative, an erosion area in endocervical canal, and atypical vessels. Histologic examination of the surgical specimens showed numerous calcified schistosome eggs (probably S. hematobium) and a high-grade cervical intraepithelial neoplasia. The relation between S. hematobium infection and bladder cancer is well known; however, this relationship with cervical cancer remains controversial. The symptoms of schistosomiasis of the female genital tract are rather non-specific, and are often misdiagnosed with other pelvic diseases. The familiarity of health professionals with schistosomiasis of the female genital tract is less than expected, even in endemic regions. Therefore, great awareness of this differential diagnosis in routine gynecological practice is of paramount importance.

Voiding dysfunction: another etiology of vulvovaginitis in young girls.

PubMed

Romero, P; Rodríguez, E; Muñoz, M; Delucchi, A; Guerrero, J L; Lillo, A M; Cano, F; Matilde Osses, Sra; Romero, M I; Gonzalez Roca, C

2011-08-01

To determine the prevalence of voiding dysfunction (VD) in patients with persistent vulvovaginitis (PVV), and to evaluate the clinical response of PVV in the treatment of VD. Girls four years or older who consulted for PVV for at least one month and who did not respond to general measures. A physical examination was performed with visual inspection and colposcopy; vaginal samples for culture and vaginoscopy were carried out. On every patient urodynamic studies were performed. Girls who were diagnosed with VD were treated. A pediatric gynecologist did the follow-up; a successful response was considered when inflammatory symptoms and vaginal discharge ceased. Twenty patients were included, mean age 8.6 years (range: 4.6-14 years); 75% prepubertal symptoms lasted for 1.8 years; 19 (95%) had urodynamia, 10 (52.6%) had an overactive bladder, 8 (42.1%) external bladder sphincter dyssynergia, 1 (5.2%) hypotonic bladder, and 13 (65%) showed improvement. VD is an important cause when considering the etiology of PVV. 2011 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Safety and tolerability of BufferGel, a novel vaginal microbicide, in women in the United States.

PubMed

Mayer, K H; Peipert, J; Fleming, T; Fullem, A; Moench, T; Cu-Uvin, S; Bentley, M; Chesney, M; Rosenberg, Z

2001-02-01

BufferGel (ReProtect, LLC) is a vaginal gel with an acidic buffering action that was designed to prevent vaginal neutralization by semen. The purpose of this study was to evaluate the safety and tolerability of BufferGel (ReProtect, Limited Liability Company) applied vaginally either once or twice daily by 27 women who were at low risk for acquisition of human immunodeficiency virus (HIV). Participants initially used the product once daily for 14 days and then twice daily for 14 days; they underwent colposcopy before and after product exposure. BufferGel was well tolerated, although two-thirds of the participants reported at least 1 mild or moderate adverse experience. The most common adverse events were irritative genitourinary symptoms. Product use was discontinued after 3 adverse events. BufferGel was well tolerated in women at low risk for acquisition of HIV; toxicity was limited and occurred at frequencies similar to those in women who did not use any vaginal product and at levels lower than in women who used detergent-based microbicides.

Frequent use of menfegol spermicidal vaginal foaming tablets associated with a high incidence of genital lesions.

PubMed

Goeman, J; Ndoye, I; Sakho, L M; Mboup, S; Piot, P; Karam, M; Belsey, E; Lange, J M; Laga, M; Perriëns, J H

1995-06-01

Menfegol is a spermicide with in vitro activity against human immunodeficiency virus (HIV). A randomized placebo-controlled safety study covered the use of menfegol foaming tablets for 14 days at increasing frequencies of insertion by 125 prostitutes in Dakar, Senegal. The frequencies of colposcopically diagnosed genital lesions were 5.0%, 11.8%, 27.8%, 49.7%, and 29.4% among menfegol recipients when tablets were used once every other day or 1, 2, 4, or 8 times a day, respectively (P < .05). Among placebo recipients, frequencies were 11.1% and 23.5% when tablets were used < 8 times daily and 8 times daily, respectively. There was no association between subjective genital symptoms and the incidence of colposcopically detected lesions. The high incidence of genital lesions when menfegol foaming tablets were used more than once daily suggests that their frequent use should not be recommended to prevent HIV transmission. In use at low frequency, the tablets' toxicity might be balanced by anti-HIV properties. Safety studies on vaginal microbicides should use objective methods, such as colposcopy, to assess the incidence of lesions.

DNA Methylation of Cellular Retinoic Acid-Binding Proteins in Cervical Cancer.

PubMed

Arellano-Ortiz, Ana L; Salcedo-Vargas, Mauricio; Vargas-Requena, Claudia L; López-Díaz, José A; De la Mora-Covarrubias, Antonio; Silva-Espinoza, Juan C; Jiménez-Vega, Florinda

2016-01-01

This study determined the methylation status of cellular retinoic acid-binding protein ( CRABP ) gene promoters and associated them with demographic characteristics, habits, and the presence of human papilloma virus (HPV) in patients with cervical cancer (CC), low and high squamous intraepithelial lesions, and no intraepithelial lesion. Women (n = 158) were selected from the Colposcopy Clinic of Sanitary Jurisdiction II in Ciudad Juarez, Chihuahua, Mexico. Demographic characteristics and habit information were collected. Cervical biopsy and endocervical scraping were used to determine methylation in promoter regions by methylation-specific polymerase chain reaction technique. We found hemi-methylation patterns in the promoter regions of CRABP1 and CRABP2 ; there was 28.5% hemi-methylation in CRABP1 and 7.0% in that of CRABP2 . Methylation in CRABP1 was associated with age (≥35 years, P = 0.002), family history of cancer ( P = 0.032), the presence of HPV-16 ( P = 0.013), and no alcohol intake ( P = 0.035). These epigenetic changes could be involved in the CC process, and CRABP1 has the potential to be a predictive molecular marker of retinoid therapy response.

DNA Methylation of Cellular Retinoic Acid-Binding Proteins in Cervical Cancer

PubMed Central

Arellano-Ortiz, Ana L.; Salcedo-Vargas, Mauricio; Vargas-Requena, Claudia L.; López-Díaz, José A.; De la Mora-Covarrubias, Antonio; Silva-Espinoza, Juan C.; Jiménez-Vega, Florinda

2016-01-01

This study determined the methylation status of cellular retinoic acid-binding protein (CRABP) gene promoters and associated them with demographic characteristics, habits, and the presence of human papilloma virus (HPV) in patients with cervical cancer (CC), low and high squamous intraepithelial lesions, and no intraepithelial lesion. Women (n = 158) were selected from the Colposcopy Clinic of Sanitary Jurisdiction II in Ciudad Juarez, Chihuahua, Mexico. Demographic characteristics and habit information were collected. Cervical biopsy and endocervical scraping were used to determine methylation in promoter regions by methylation-specific polymerase chain reaction technique. We found hemi-methylation patterns in the promoter regions of CRABP1 and CRABP2; there was 28.5% hemi-methylation in CRABP1 and 7.0% in that of CRABP2. Methylation in CRABP1 was associated with age (≥35 years, P = 0.002), family history of cancer (P = 0.032), the presence of HPV-16 (P = 0.013), and no alcohol intake (P = 0.035). These epigenetic changes could be involved in the CC process, and CRABP1 has the potential to be a predictive molecular marker of retinoid therapy response. PMID:27867303

Comparison of Keyes Punch Biopsy Instrument with Cervical Punch Biopsy Forceps for Diagnosing Cervical Lesions.

PubMed

Tyagi, Natasha; Suneja, Amita; Mishra, Kiran; Jain, Sandhya; Vaid, Neelam Bala; Guleria, Kiran

2017-01-01

To assess the feasibility and efficacy of Keyes punch biopsy instrument (KP) in diagnosing cervical lesions and compare it with cervical punch biopsy forceps (CP). 75 women having satisfactory colposcopy with abnormal transformation zone were included and paired colposcopic directed biopsies were taken using KP followed by CP from the same target area. It was feasible in all cases to take cervical biopsy with KP after increasing its effective length. The volume of gross specimen obtained by KP was less than CP (0.076 ± 0.097 vs. 0.101 ± 0.156 cm3, p = 0.061), however on microscopic examination, mean length and mean depth of tissue in KP was greater than CP by 0.06 mm (p = 0.810) and 0.14 mm (p = 0.634) respectively. Exact agreement was found with the final surgical specimen in 42% of cases in both the biopsy forceps. KP is almost at par with CP for diagnosing preinvasive cervical lesions and is a useful adjunct to the existing armamentarium of biopsy forceps. © 2016 S. Karger AG, Basel.

Mucosal integrity and inflammatory markers in the female lower genital tract as potential screening tools for vaginal microbicides.

PubMed

Su, H Irene; Schreiber, Courtney A; Fay, Courtney; Parry, Sam; Elovitz, Michal A; Zhang, Jian; Shaunik, Alka; Barnhart, Kurt

2011-11-01

In the female genital tract, vaginal colposcopy, endometrial mucosal integrity and inflammatory mediators are potential in vivo biomarkers of microbicide and contraceptive safety. A randomized, blinded crossover trial of 18 subjects comparing effects of nonoxynol-9 vaginal gel (Gynol II; putative inflammatory gel), hydroxyethyl cellulose gel (HEC; putative inert gel) and no gel exposure on endometrial and vaginal epithelial integrity and endometrial and vaginal inflammatory markers [interleukin (IL) 1β, IL-6, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, tumor necrosis factor α, IL-1RA, IL-10, SLPI). Gynol II was associated with more vaginal lesions. No endometrial disruptions were observed across conditions. In the vagina, RANTES (p=.055) and IL-6 (p=.04) were higher after HEC exposure than at baseline. In the endometrium, IL-1β (p=.003) and IL-8 (p=.025) were lower after Gynol II cycles than after no gel. Gynol II and HEC may modulate inflammatory markers in the vagina and endometrium. How these changes relate to infection susceptibility warrants further study. Copyright © 2011 Elsevier Inc. All rights reserved.

Ensembles of radial basis function networks for spectroscopic detection of cervical precancer

NASA Technical Reports Server (NTRS)

Tumer, K.; Ramanujam, N.; Ghosh, J.; Richards-Kortum, R.

1998-01-01

The mortality related to cervical cancer can be substantially reduced through early detection and treatment. However, current detection techniques, such as Pap smear and colposcopy, fail to achieve a concurrently high sensitivity and specificity. In vivo fluorescence spectroscopy is a technique which quickly, noninvasively and quantitatively probes the biochemical and morphological changes that occur in precancerous tissue. A multivariate statistical algorithm was used to extract clinically useful information from tissue spectra acquired from 361 cervical sites from 95 patients at 337-, 380-, and 460-nm excitation wavelengths. The multivariate statistical analysis was also employed to reduce the number of fluorescence excitation-emission wavelength pairs required to discriminate healthy tissue samples from precancerous tissue samples. The use of connectionist methods such as multilayered perceptrons, radial basis function (RBF) networks, and ensembles of such networks was investigated. RBF ensemble algorithms based on fluorescence spectra potentially provide automated and near real-time implementation of precancer detection in the hands of nonexperts. The results are more reliable, direct, and accurate than those achieved by either human experts or multivariate statistical algorithms.

[Health technology assessment report: HPV DNA based primary screening for cervical cancer precursors].

PubMed

Ronco, Guglielmo; Biggeri, Annibale; Confortini, Massimo; Naldoni, Carlo; Segnan, Nereo; Sideri, Mario; Zappa, Marco; Zorzi, Manuel; Calvia, Maria; Accetta, Gabriele; Giordano, Livia; Cogo, Carla; Carozzi, Francesca; Gillio Tos, Anna; Arbyn, Marc; Mejier, Chris J L M; Snijders, Peter J F; Cuzick, Jack; Giorgi Rossi, Paolo

2012-01-01

OBJECTIVE OF THE PROJECT: The introduction of the HPV test as a primary screening test will cause important changes in the screening system based on cytology. The purposes of this report are: to define the best screening policies with HPV-based screening on the basis of the resulting efficacy and of undesired effects; comparing them to cytology-based screening; to identify their best conditions of application; to evaluate economic cost, feasibility and impact on the organisation of services of such policy in the Italian situation. This report contains a section on efficacy and undesired effects based on a systematic review of literature conducted in strict coordination with the preparation of a supplement to the European Guidelines for quality assurance in cervical cancer screening. This chapter corresponds to a preliminary version of the chapter of the European Guidelines on primary screening with HPV. The sections on costs, impact on organisation, and social, ethical and legal impact reflect the Italian situation; they are based on a review of the available Italian data (including unpublished data, mainly from on-going pilot projects) and on a structured analysis of what will result if the proposed protocol is applied to the Italian situation. Efficacy and undesired effects. There is clear scientific evidence that a screening based on validated tests for the DNA of oncogenic HPV as primary test and applying an appropriate protocol is more effective than screening based on cytology in preventing invasive cancers of the uterine cervix. In addition, it entails a limited--if any--increase of the undesired effects both in terms of unneeded referral to diagnostic work-up and in terms of over-diagnosis and consequent overtreatment of spontaneously regressive lesions. The crucial elements of such protocol are the followings: HPV-positive women are not to be directly referred to colposcopy, but the use of triage systems is essential. The currently recommendable method is based on performing cytology in HPV positive women. If the result of this test is abnormal, the woman is immediately referred to colposcopy; if cytology is normal, the woman is invited to repeat a new HPV test after one year. In case such a test is still positive, the woman is referred to colposcopy; in case of negative result, the woman will be re-invited for a new screening round at the regular interval. In organised population-based screening programmes the interval after a negative primary HPV test should be at least 5 years. There is evidence that the 5-year cumulative risk of high-grade CIN after a negative HPV test is lower than the 3-year risk after a normal cytology. On the other hand, the probability of unneeded colposcopies and treatments would plausibly be relevant with 3-year intervals after a negative HPV test. HPV-based screening should not start before 30-35 years. There is evidence that below 30 years HPV-based screening leads to an increased overdiagnosis of CIN2 that would regress spontaneously, with consequent overtreatment. Some increase in overdiagnosis is plausible also between 30 and 34 years. Below such ages, cytological screening is the recommended test. Only tests for the DNA of oncogenic HPV, validated according to the European guidelines as for sensitivity and specificity for high-grade lesions, should be applied. There is no evidence that double testing with cytology and HPV is more protective than stand-alone HPV as primary test, although it entails a small and not relevant increase in sensitivity vs stand-alone HPV. On the contrary, there is evidence that double testing causes a substantial increase in referral to colposcopy and a decrease in its PPV. For this reason, if HPV is used as primary screening test, it is recommended not to add cytology in parallel. Cost and economic evaluation. It is estimated that, if the protocol described is applied, in the current Italian situation the overall costs of HPV-based screening are lower than those of conventional cytological screening applied at the current 3-year intervals, although the cost of each screening round is higher. Impact on organization. For reasons of quality and cost, both the interpretation of cytology and HPV testing require a centralisation. This need is particularly strong, in terms of costs, for HPV test execution. It is therefore recommended to perform the HPV test in a limited number of reference laboratories of large size. This also makes monitoring and evaluating the spontaneous activity easier. HPV-based screening entails problems of organisation related to the need of triage, to complex protocols and to reconversion of the activities of cytological interpretation. Social, ethical and legal impact. The communication of the result of the HPV test to women, particularly if positive, is a further crucial aspect in order to reduce not only the emotional impact, but also the possible risks that women are inappropriately managed or lost to follow-up. Great efforts must be put in the education of healthcare professionals, both directly involved in organised programmes or not, particularly private gynaecologists and general practitioners. In conclusion, the crucial requirement to introduce HPV-based screening programmes is the capacity to guarantee the application of appropriate screening protocols. If protocols do not respect the criteria described above they can cause relevant increase of undesired effects and costs compared to cytology-based screening. Therefore they should be avoided, except in studies able to provide clear evidence about human and economic costs. For this purpose, correct education and information both to healthcare professionals and to the population is needed. In the Italian situation, where organised screening and a relevant spontaneous activity coexist, their interaction is crucial. Actions directed to integrate them and to guarantee as more uniformity of interventions as possible are needed, in particular through the integration of registries and thorough monitoring and a progressive homogenization of protocols. In order to grant the safety of transition, it is needed that the HPV-based organised screening activities are strictly monitored and that the National Centre for Screening Monitoring (ONS) ensures coordination. Knowledge about HPV based screening is still rapidly evolving. It is possible that currently on-going researches suggest changes to the optimal protocols in the next few years, particularly as for the management of HPV positive women. In addition, studies on the validation of new assays were recently published and others are expected. It is suggested to exploit the organised screening activity to produce scientific evidence, in order to clarify the still uncertain aspects of optimal protocols. Different protocols in terms of screening intervals, age of application and management of HPV positive women should be studied in the frame of controlled implementation, through multicentre projects coordinated by ONS. Finally, it is suggested the creation of a National working group to promptly update the recommendations for screening and the list of assays to be considered as validated. On the bases of the results obtained in the first vaccinated cohorts reaching the screening age, for the future, it will be crucial to deliver specific recommendations to the population vaccinated against HPV during adolescence.

Cervical specimens collected in liquid buffer are suitable for both cytologic screening and ancillary human papillomavirus testing.

PubMed

Sherman, M E; Schiffman, M H; Lorincz, A T; Herrero, R; Hutchinson, M L; Bratti, C; Zahniser, D; Morales, J; Hildesheim, A; Helgesen, K; Kelly, D; Alfaro, M; Mena, F; Balmaceda, I; Mango, L; Greenberg, M

1997-04-25

Several new techniques have been developed to improve the sensitivity of cervical carcinoma screening and reduce equivocal cytologic diagnoses referred to as atypical squamous cells of undetermined significance (ASCUS). This study evaluates the effectiveness of combining two newly introduced diagnostic techniques: preparation of thin-layer cytologic slides from ThinPrep liquid buffer and selected Hybrid Capture testing for human papillomavirus (HPV) DNA. Because HPV DNA detection has been strongly associated with the presence of a cervical carcinoma precursor ("squamous intraepithelial lesion," or SIL), HPV testing might be useful for identifying women with ASCUS who have an underlying SIL. Two hundred specimens demonstrating diverse cervical abnormalities were selected from a prospective population-based study of 9174 women conducted in Costa Rica. The entire cohort had been screened with conventional cervical smears; ThinPrep slides made from liquid buffer, PAPNET, a computerized slide reading system; and Cervicography. Patients with any abnormal screening test were referred for colposcopy, punch biopsy, and loop excision of cases with high grade cytologic abnormalities not explained by punch biopsy. For this investigation, the results of ThinPrep cytology and HPV testing alone and in combination were compared with the final diagnoses, with an emphasis on the detection of carcinoma and high grade SIL. The 200 subjects studied included 7 women with a final diagnosis of carcinoma, 44 with high grade SIL, 34 with low grade SIL, 51 with a variety of equivocal diagnoses, and 64 with normal diagnoses. A ThinPrep cytologic diagnosis of SIL or carcinoma was made in 39 (76%) of the 51 women with final diagnoses of high grade SIL or carcinoma. Hybrid Capture testing detected carcinoma-associated types of HPV DNA in 100% of women with carcinoma, 75% with high grade SIL, 62% with low grade SIL, 20% with equivocal final diagnoses, and 12% of normal women. If colposcopy referral had been limited to women with a ThinPrep diagnosis of SIL or a diagnosis of ASCUS associated with the detection of carcinoma-associated HPV DNA from the same vial, 100% of women with carcinoma and 80% with high grade SIL would have been examined. To achieve this high sensitivity in the entire population of 9174 women would have required the referral of about 7% of the population. The combined screening strategy would have performed marginally better than optimized conventional screening with referral of any abnormal cytology (ASCUS and above). A cervical carcinoma screening technique which uses a single sample for cytopathology and HPV testing to triage equivocal diagnoses may be promising if it proves to be cost-effective.

HPV genotype distribution and anomalous association of HPV33 to cervical neoplastic lesions in San Luis Potosí, Mexico.

PubMed

DelaRosa-Martínez, Raúl; Sánchez-Garza, Mireya; López-Revilla, Rubén

2016-01-01

The association of human papillomavirus (HPV) types to neoplastic lesions increase as a function of their oncogenicity and the duration of the infection since lesion severity progresses from low-grade to high-grade and cancer. In an outbreak, the prevalence of the HPV type involved would increase and the proportion of the associated low-grade lesions would predominate over severe lesions. In this study, the prevalence of HPV types and their association to neoplastic lesions was determined in women subjected to colposcopy in San Luis Potosí, Mexico. DNA from high-risk (HR) and low-risk (LR) HPV types was identified by E6 nested multiplex PCR in cervical scrapes from 700 women with normal cytology, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL) or invasive cervical cancer (CC). Overall HPV-DNA prevalence was 67.7 %, that of HR-HPV was 63.1 %, and that of LR-HPV was 21.3 %. The highest prevalence (78.2 %) occurred in the 15-24 year group, whereas that of single infections was 52 % and that of multiple infections (i.e., by 2-6 HPV types) was 48 %. The most prevalent HR types were HPV33 (33.1 %), HPV16 (16.6 %), HPV18 and HPV51 (6.7 % each). HR-HPV prevalence was 29.6 % in normal cytology, 26.7 % in ASCUS, 63.3 % in LSIL, 68.2 % in HSIL, and 90.5 % in CC. Three prevalence trends for HR-HPV types were found in neoplastic lesions of increasing severity: increasing (LSIL < HSIL < CC) for HPV16, HPV39, HPV18, HPV58, HPV31 and HPV35; asymptotic (LSIL < HSIL ≈ CC) for HPV51 and HPV68; U-shaped (LSIL < HSIL > CC) for HPV33. Two-thirds of the women subjected to colposcopy from 2007 to 2010 in San Luis Potosí have HPV infections which predominate in the 15-24 years group. Around half of the infections are by one viral type and the rest by 2-6 types. HPV33 is the most prevalent type, followed by HPV16. Overall HR-HPV prevalence increases with the severity of neoplastic lesions. HPV33 prevalence is highest in LSIL and its U-shaped trend with progressing neoplastic lesions differs from the growing/asymptotic trends of other HR-HPV types. An ongoing or recent HPV33 outbreak is consistent with its high prevalence and anomalous association to LSIL.

A novel use of a statewide telecolposcopy network for recruitment of participants in a Phase I clinical trial of a human papillomavirus therapeutic vaccine.

PubMed

Stratton, Shawna L; Spencer, Horace J; Greenfield, William W; Low, Gordon; Hitt, Wilbur C; Quick, Charles M; Jeffus, Susanne K; Blackmon, Victoria; Nakagawa, Mayumi

2015-06-01

Historically, recruitment and retention of young women in intervention-based clinical trials have been challenging. In August 2012, enrollment for a clinical trial testing of an investigational human papillomavirus therapeutic vaccine called PepCan was opened at our institution. This study was an open-label, single-arm, single-institution, dose-escalation Phase I clinical trial. Women with recent Papanicolaou smear results showing high-grade squamous intraepithelial lesions or results that could not rule out high-grade squamous intraepithelial lesion were eligible to enroll. Patients with biopsy-confirmed high-grade squamous intraepithelial lesion were also eligible. Colposcopy was performed at the screening visit, and participants became eligible for vaccination when the diagnosis of high-grade squamous intraepithelial lesion was confirmed with biopsy and other inclusion criteria were met. The aim of this study was to identify strategies and factors effective in recruitment and retention of study participants. Potential vaccine candidates were recruited through direct advertisement as well as referrals, including referrals through the Arkansas telecolposcopy network. The network is a federally funded program, administered by physicians and advanced practice nurses. The network telemedically links rural health sites and allows physician-guided colposcopy and biopsies to be conducted by advanced practice nurses. A variety of strategies were employed to assure good retention, including face-to-face contact with the study coordinator at the time of consent and most of study visits; frequent contact using text messaging, phone calls, and e-mails; and creation of a private Facebook page to improve communication among research staff and study participants. A questionnaire, inquiring about motivation for joining the study, occupation, education, household income, number of children, and number of sexual partners, was administered at the screening visit with the intent of identifying factor(s) associated with recruitment and retention. A total of 37 participants were enrolled between September 2012 and March 2014. The largest proportion of participants (46%) was enrolled from the telecolposcopy network. Others were enrolled through outside institutions (43%), in-house referrals (8%), or direct advertisement (3%). Most participants were motivated to join the study to take care of their health issues. Only two participants joined the Facebook private page. Of the 24 participants who qualified for vaccination, only 1 terminated early due to an unanticipated move. The availability of a large number of potential participants from the telecolposcopy network increased recruitment to this clinical trial by 85% over other traditional means of recruitment. The telecolposcopy network is not only a means of providing a gynecological service to women who otherwise would forego care but also a novel and valuable resource in recruiting participants for a clinical trial. © The Author(s) 2015.

Epidemiology, prevention and treatment of cervical cancer in the Philippines.

PubMed

Domingo, Efren J; Dy Echo, Ana Victoria V

2009-03-01

Cervical cancer remains to be one of the leading malignancies among Filipino women. High-risk human papillomavirus (HPV) types, such as 16 and 18, are consistently identified in Filipino women with cervical cancer. Factors identified to increase the likelihood of HPV infection and subsequent development of cervical cancer include young age at first intercourse, low socioeconomic status, high parity, smoking, use of oral contraception and risky sexual behaviors. Cancer screening programs presently available in the Philippines include Pap smears, single visit approach utilizing visual inspection with acetic acid followed by cryotherapy, as well as colposcopy. However, the uptake of screening remains low and is further compounded by the lack of basic knowledge women have regarding screening as an opportunity for prevention of cervical cancer. Prophylactic HPV vaccination of both quadrivalent and bivalent vaccines has already been approved in the Philippines and is gaining popularity among the Filipinos. However, there has been no national or government vaccination policy implemented as of yet. The standard of treatment of cervical cancer is radiotherapy concurrent with chemotherapy. Current researches are directed towards improving availability of both preventive and curative measures of cervical cancer management.

Comparative study of the results from conventional cervico-vaginal oncotic cytology and liquid-based cytology.

PubMed

Stabile, Sueli Aparecida Batista; Evangelista, Dilson Henrique Ramos; Talamonte, Valdely Helena; Lippi, Umberto Gazi; Lopes, Reginaldo Guedes Coelho

2012-01-01

To compare two oncotic cervical cytology techniques, the conventional and the liquid-based cytology, in low risk patients for uterine cervical cancer. Comparative prospective study with 100 patients who came to their annual gynecological exam, and were submitted simultaneously to both techniques. We used the McNemar test, with a significance level of p < 0.05 to compare the results obtained related to adequacy of the smear quality, descriptive diagnosis prevalence, guided biopsy confirmation and histology. Adequacy of the smear was similar for both methods. The quality with squamocolumnar junction in 93% of conventional cytology and in 84% of the liquid-based cytology had statistical significance. As for the diagnosis of atypical cells they were detected in 3% of conventional cytology and in 10% of liquid-based cytology (p = 0.06). Atypical squamous cells of undetermined significance were the most prevalent abnormality. The liquid-based cytology performance was better when compared with colposcopy (guided biopsy), presenting sensitivity of 66.7% and specificity of 100%. There was no cytological and histological concordance for the conventional cytology. Liquid-based cytology had a better performance to diagnose atypical cells and the cytohistological concordance was higher than in the conventional cytology.

OCT in Gynecology

NASA Astrophysics Data System (ADS)

Kuznetsova, Irina A.; Gladkova, Natalia D.; Gelikonov, Valentin M.; Belinson, Jerome L.; Shakhova, Natalia M.; Feldchtein, Felix I.

Timely and efficient diagnosis of diseases of the female reproductivesystem is very important from the social viewpoint [1, 2]. Diagnosticefficacy of the existing techniques still needs improvement sincemalignant neoplasms of the female reproductive system organs are stableleaders among causes of death (over 35.9 %) [3]. Each year, 851.9 thousand genital cancer cases are recorded worldwide [1, 2]. However, the diagnostic efficacy of the visual examination with biopsy is limited. Correct interpretation of colposcopic features requires high skills and long-term clinical experience, which makes colposcopy very subjective and limits interobserver agreement [8-10]. OCT is known to visualize in vivo and noninvasively tissue microstructure with spatial resolution approaching the histologic level and therefore can be expected to guide biopsies and to provide real-time tissue structure information when biopsies are contraindicated or impractical. Although thorough clinical studies are required to determine if OCT can be suitable for this purpose in gynecology in general and for cervical cancer in particular, the early results look encouraging. In this chapter, we present a wide spectrum of the OCT studies of different partsof the female reproductive system and demonstrate the potential of the clinical use of this new visualization method in gynecological practice.

Mobile colposcopy in urban and underserved suburban areas in Baja California

NASA Astrophysics Data System (ADS)

Madiedo, Marta; Contreras, Sonia; Villalobos, Octavio; Kahn, Bruce S.; Safir, Amit; Levitz, David

2016-03-01

Cervical cancer is the leading cause of cancer death for women in low resource settings, often affecting the most economically disenfranchised segment of the population. The key challenge with cervical cancer is the lack of an effective screening program for many of the at-risk, difficult-to-reach women. Outreach programs that utilize mobile clinics to increase access to screening and care in Baja California have been developed. However, many barriers such as quality assurance, efficient referral remained a challenge in this region. Visualization-based co-tests together with cytology (Pap smears) as a primary screen have been proposed. Here, the mobile colposcope of the enhanced visual assessment (EVA) is used to capture an image immediately following a Pap smear. EVA images were reviewed by expert colposcopists. Initial or preliminary data from pilot services showed that Pap false positives and Pap false negatives maybe reduced by expert review of EVA images. This suggests that reviewing of EVA images may be instrumental in catching inaccurate Pap results, thereby improving care. Thus, there is a need to further explore the benefits of using EVA as additional information when conducting Pap smear screenings.

Human Papillomavirus Laboratory Testing: the Changing Paradigm

PubMed Central

2016-01-01

SUMMARY High-risk human papillomaviruses (HPVs) cause essentially all cervical cancers, most anal and oropharyngeal cancers, and some vaginal, vulvar, and penile cancers. Improved understanding of the pathogenesis of infection and the availability of newer tests are changing the approach to screening and diagnosis. Molecular tests to detect DNA from the most common high-risk HPVs are FDA approved for use in conjunction with cytology in cervical cancer screening programs. More-specific tests that detect RNA from high-risk HPV types are now also available. The use of molecular tests as the primary screening tests is being adopted in some areas. Genotyping to identify HPV16 and -18 has a recommended role in triaging patients for colposcopy who are high-risk HPV positive but have normal cytology. There are currently no recommended screening methods for anal, vulvar, vaginal, penile, or oropharyngeal HPV infections. HPV testing has limited utility in patients at high risk for anal cancer, but p16 immunohistochemistry is recommended to clarify lesions in tissue biopsy specimens that show moderate dysplasia or precancer mimics. HPV testing is recommended for oropharyngeal squamous cell tumors as a prognostic indicator. Ongoing research will help to improve the content of future guidelines for screening and diagnostic testing. PMID:26912568

Six-day randomized safety trial of intravaginal lime juice.

PubMed

Mauck, Christine K; Ballagh, Susan A; Creinin, Mitchell D; Weiner, Debra H; Doncel, Gustavo F; Fichorova, Raina N; Schwartz, Jill L; Chandra, Neelima; Callahan, Marianne M

2008-11-01

Nigerian women reportedly apply lime juice intravaginally to protect themselves against HIV. In vitro data suggest that lime juice is virucidal, but only at cytotoxic concentrations. This is the first controlled, randomized safety trial of lime juice applied to the human vagina. Forty-seven women were randomized to apply water or lime juice (25%, 50%, or undiluted) intravaginally twice daily for two 6-day intervals, separated by a 3-week washout period. Product application also was randomized: during 1 interval, product was applied using a saturated tampon and in the other by douche. Vaginal pH, symptoms, signs of irritation observed via naked eye examination and colposcopy, microflora, and markers of inflammation in cervicovaginal lavages were evaluated after 1 hour and on days 3 and 7. The largest reduction in pH was about one-half a pH unit, seen 1 hour after douching with 100% lime juice. We observed a dose-dependent pattern of symptoms and clinical and laboratory findings that were consistent with a compromised vaginal barrier function. The brief reduction in pH after vaginal lime juice application is unlikely to be virucidal in the presence of semen. Lime juice is unlikely to protect against HIV and may actually be harmful.

[History of the development of screening tests for cervical cancer].

PubMed

Herrera, Yelda A; Piña-Sánchez, Patricia

2015-01-01

Cervical cancer (CC) is one of the best known malignancies. Currently, it is accepted that the etiological factor is persistent infection with high-risk human papillomavirus (HPV). Even before the identification of its etiological factors, methods such as Pap cytology and colposcopy were developed as tools for early diagnosis on CC and its precursor lesions. At the time when such tests were being developed, they were not fully accepted by the scientific community of the time; however, as time went by, the dissemination of knowledge, and more extensive application, these tests were finally included within the international guidelines. The implementation of programs with adequate coverage and quality allowed a significant reduction in the incidence and mortality of CC. However this did not occur widely, and CC is still a public health problem in developing countries. From the epidemiological and molecular viewpoint, knowledge on HPVs laid the foundations for the development of new prevention strategies based on vaccination and molecular detection of the causal agent, currently accepted as strategies for primary and secondary prevention. It is expected that the implementation of these strategies will have a greater impact on the control on CC and other malignancies associated with HPV infection.

Low-cost technology for screening uterine cervical cancer.

PubMed Central

Parashari, A.; Singh, V.; Sehgal, A.; Satyanarayana, L.; Sodhani, P.; Gupta, M. M.

2000-01-01

We report on an illuminated, low-cost (Rs 1500 (US$ 36)) magnifying device (Magnivisualizer) for detecting precancerous lesions of the uterine cervix. A total of 403 women attending a maternal and child health care clinic who had abnormal vaginal discharge and related symptoms were referred for detailed pelvic examination and visual inspection by means of the device after the application of 5% (v/v) acetic acid. Pap smears were obtained at the same time. The results were compared with those obtained using colposcopy and/or histology. The Magnivisualizer improved the detection rate of early cancerous lesions from 60%, for unaided visual inspection, to 95%. It also permitted detection of 58% of cases of low-grade dysplasia and 83% of cases of high-grade dysplasia; none of these cases were detectable by unaided visual inspection. For low-grade dysplasia the sensitivity of detection by means of the Magnivisualizer was 57.5%, in contrast with 75.3% for cytological examination. However, the two methodologies had similar sensitivities for higher grades of lesions. The specificity of screening with the Magnivisualizer was 94.3%, while that of cytology was 99%. The cost per screening was approximately US$ 0.55 for the Magnivisualizer and US$ 1.10 for cytology. PMID:10994279

Initial clinical testing of a multi-spectral imaging system built on a smartphone platform

NASA Astrophysics Data System (ADS)

Mink, Jonah W.; Wexler, Shraga; Bolton, Frank J.; Hummel, Charles; Kahn, Bruce S.; Levitz, David

2016-03-01

Multi-spectral imaging systems are often expensive and bulky. An innovative multi-spectral imaging system was fitted onto a mobile colposcope, an imaging system built around a smartphone in order to image the uterine cervix from outside the body. The multi-spectral mobile colposcope (MSMC) acquires images at different wavelengths. This paper presents the clinical testing of MSMC imaging (technical validation of the MSMC system is described elsewhere 1 ). Patients who were referred to colposcopy following abnormal screening test (Pap or HPV DNA test) according to the standard of care were enrolled. Multi-spectral image sets of the cervix were acquired, consisting of images from the various wavelengths. Image acquisition took 1-2 sec. Areas suspected for dysplasia under white light imaging were biopsied, according to the standard of care. Biopsied sites were recorded on a clockface map of the cervix. Following the procedure, MSMC data was processed from the sites of biopsied sites. To date, the initial histopathological results are still outstanding. Qualitatively, structures in the cervical images were sharper at lower wavelengths than higher wavelengths. Patients tolerated imaging well. The result suggests MSMC holds promise for cervical imaging.

Using of electrical impedance tomography for diagnostics of the cervix uteri diseases

NASA Astrophysics Data System (ADS)

Trokhanova, O. V.; Chijova, Y. A.; Okhapkin, M. B.; Korjenevsky, A. V.; Tuykin, T. S.

2010-04-01

The report presents results of investigation of the neck of the womb (cervix) of 64 women aged from 19 to 70, that formed 4 clinical groups (1st group: 15 women without any pathology of the cervix, 2nd group: 27 women with the erosion, 3rd group: 11 women with dysplasia, 4th group: 11 women with cancer of the cervix). The aim of this research is to assess the capabilities of electrical impedance tomography in the diagnostics of the cervix diseases. The methods of the research were: visual examination with the speculum, colposcopy, and biopsy of the cervix. Also the new method of visualization of the cervix was used - electrical impedance tomography with the help of gynecological impedance tomograph (GIT). The following results were obtained. The electrical conductivity of the cervix in norm and in different pathology has different indices, which allow differential diagnostics of benign and malignant diseases. Summary: the method of electrical impedance tomography allows not only visually estimate portio vaginalis, but receive indices of electrical conductivity of the cervix on the depth up to 0.8 cm and thereby reveal pathological changes in epithelium without invasive and operative intervention.

Development and bench testing of a multi-spectral imaging technology built on a smartphone platform

NASA Astrophysics Data System (ADS)

Bolton, Frank J.; Weiser, Reuven; Kass, Alex J.; Rose, Donny; Safir, Amit; Levitz, David

2016-03-01

Cervical cancer screening presents a great challenge for clinicians across the developing world. In many countries, cervical cancer screening is done by visualization with the naked eye. Simple brightfield white light imaging with photo documentation has been shown to make a significant impact on cervical cancer care. Adoption of smartphone based cervical imaging devices is increasing across Africa. However, advanced imaging technologies such as multispectral imaging systems, are seldom deployed in low resource settings, where they are needed most. To address this challenge, the optical system of a smartphone-based mobile colposcopy imaging system was refined, integrating components required for low cost, portable multi-spectral imaging of the cervix. This paper describes the refinement of the mobile colposcope to enable it to acquire images of the cervix at multiple illumination wavelengths, including modeling and laboratory testing. Wavelengths were selected to enable quantifying the main absorbers in tissue (oxyand deoxy-hemoglobin, and water), as well as scattering parameters that describe the size distribution of scatterers. The necessary hardware and software modifications are reviewed. Initial testing suggests the multi-spectral mobile device holds promise for use in low-resource settings.

In vivo photoacoustic imaging of uterine cervical lesion and its image processing based on light propagation in biological medium

NASA Astrophysics Data System (ADS)

Okawa, Shinpei; Sei, Kiguna; Hirasawa, Takeshi; Irisawa, Kaku; Hirota, Kazuhiro; Wada, Takatsugu; Kushibiki, Toshihiro; Furuya, Kenichi; Ishihara, Miya

2017-03-01

For diagnosis of cervical cancer, screening by colposcope and successive biopsy are usually carried out. Colposcope, which is a mesoscope, is used to examine surface of the cervix and to find precancerous lesion grossly. However, the accuracy of colposcopy depends on the skills of the examiner and is inconsistent as a result. Additionally, colposcope lacks depth information. It is known that microvessel density and blood flow in cervical lesion increases associated with angiogenesis. Therefore, photoacoustic imaging (PAI) to detect angiogenesis in cervical lesion has been studied. PAI can diagnose cervical lesion sensitively and provide depth information. The authors have been investigating the efficacy of PAI in the diagnoses of the cervical lesion and cancer by use of the PAI and ultrasonography system with transvaginal probe developed by Fujifilm Corporation. For quantitative diagnosis by use of PAI, it is required to take the light propagation in biological medium into account. The image reconstruction of the absorption coefficient from the PA image of cervix by use of the simulation of light propagation based on finite element method has been tried in this study. Numerical simulation, phantom experiment and in vivo imaging were carried out.

Regeneration of cervix after excisional treatment for cervical intraepithelial neoplasia: a study of collagen distribution.

PubMed

Phadnis, S V; Atilade, A; Bowring, J; Kyrgiou, M; Young, M P A; Evans, H; Paraskevaidis, E; Walker, P

2011-12-01

To study the distribution of collagen in the regenerated cervical tissue after excisional treatment for cervical intraepithelial neoplasia (CIN). Cohort study. A large tertiary teaching hospital in London. Women who underwent repeat excisional treatment for treatment failure or persistent CIN. Eligible women who underwent a repeat excisional treatment for treatment failure, including hysterectomy, between January 2002 and December 2007 in our colposcopy unit were identified by the Infoflex(®) database and SNOMED encoded histopathology database. Collagen expression was assessed using picro-Sirius red stain and the intensity of staining was compared in paired specimens from the first and second treatments. Differences in collagen expression were examined in the paired excisional treatment specimens. A total of 17 women were included. Increased collagen expression in the regenerated cervical tissue of the second cone compared with the first cone was noted in six women, decreased expression was noted in five women, and the pattern of collagen distribution was equivocal in six women. There is no overall change in collagen distribution during regeneration following excisional treatment for CIN. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

Incidence of High Grade Squamous Intraepithelial Lesions in Patients with Atypical Squamous Cells of Undetermined Significance Papanicolaou Smears at Naresuan University Hospital.

PubMed

Heng, Suttichai; Sirichaisutdhikorn, Daranee

2016-01-01

To determine the incidence of high-grade cervical intraepithelial neoplasia (CIN2-3) among patients with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou (Pap) smears. One-hundred and eighty-seven patients with ASC-US Pap smears who underwent colposcopy with histological study were enrolled between September 2007 and August 2015. Patient factors (including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners) were obtained. Logistic regression analysis was used to evaluate clinical factors associated with CIN2-3. CIN was diagnosed in 92 of 187 women (49.2%). Sixty-one of these (32.6%) had CIN1 and 31 (16.6%) had CIN2-3. There was no woman who had invasive cancer. There was no correlation of high-grade CIN with factors in this study including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners. Data from this study showed no invasive cervical cancer was found in patients with ASC-US. There was no patient factor associated with high grade intraepithelial neoplasia in patients with ASC-US Pap smears.

Squamous cell carcinoma of the uterine cervix associated with osteoclast-like giant cells: A case report and review of the literature.

PubMed

Yu, Guohua; Lin, Chunhua; Wang, Wei; Han, Yekun; Qu, Guimei; Zhang, Tingguo

2014-10-01

Squamous cell carcinoma is a common malignant tumor of the uterine cervix. The present study reports the case of squamous cell carcinoma of the uterine cervix with osteoclast-like giant cells (OGCs) in an 84-year-old female who had suffered from irregular vaginal bleeding for one month. Colposcopy was performed and a cauliflower-like mass was identified in the front lip of the uterine cervix. Biopsy was then performed, and the tumor was found to be composed of epithelial cell nests, ranging in size. The neoplastic cells exhibited unclear boundaries and eosinophilic cytoplasm. Additionally, the nuclei were atypical and mitosis was observed. Among the epithelial nests, there were numerous OGCs with abundant eosinophilic cytoplasm, as well as multinucleation with bland nuclei. By immunohistochemical staining, the epithelial cells were positive for cytokeratin, while negative for CD68 and vimentin. By contrast, the immunophenotype of the OGCs was the exact opposite. Based on the histological characters, a diagnosis of squamous cell carcinoma of the uterine cervix associated with OGCs was made. Considering the age of the patient, radiotherapy was administered. The patient succumbed to brain metastasis of the tumor after eight months of follow-up.

[Health technology assessment report. Use of liquid-based cytology for cervical cancer precursors screening].

PubMed

Ronco, Guglielmo; Confortini, Massimo; Maccallini, Vincenzo; Naldoni, Carlo; Segnan, Nereo; Sideri, Mario; Zappa, Marco; Zorzi, Manuel; Calvia, Maria; Giorgi Rossi, Paolo

2012-01-01

OBJECTIVE OF THE PROJECT: Purpose of this Report is to evaluate the impact of the introduction of liquid-based cytology (LBC) in cervical cancer screening in terms of efficacy, undesired effects, costs and implications for organisation. EFFICACY AND UNDESIRED EFFECTS: LBC WITH MANUAL INTERPRETATION: The estimates of cross-sectional accuracy for high-grade intraepithelial neoplasia (CIN2 or more severe and CIN3 or more severe) obtained by a systematic review and meta-analysis published in 2008 were used. This review considered only studies in which all women underwent colposcopy or randomised controlled trials (RCTs) with complete verification of test positives. A systematic search of RCTs published thereafter was performed. Three RCTs were identified. One of these studies was conducted in 6 Italian regions and was of large size (45,174 women randomised); a second one was conducted in another Italian region (Abruzzo) and was of smaller size (8,654 women randomised); a third RCT was conducted in the Netherlands and was of large size (89,784 women randomised). No longitudinal study was available. There is currently no clear evidence that LBC increases the sensitivity of cytology and even less that its introduction increases the efficacy of cervical screening in preventing invasive cancers. The Italian randomised study NTCC showed a decrease in specificity, which was not observed in the other two RCTs available. In addition, the 2008 meta-analysis observed a reduction - even if minimal - in specificity just at the ASC-US cytological cut-off, but also a remarkable heterogeneity between studies. These results suggest that the effect of LBC on specificity is variable and plausibly related to the local style of cytology interpretation. There is evidence that LBC reduces the proportion of unsatisfactory slides, although the size of this effect varies remarkably. LBC WITH COMPUTER-ASSISTED INTERPRETATION: An Australian study, based on double testing, showed a statistically significant increase of the sensitivity for CIN2 or more of LBC with computer-assisted interpretation vs. conventional cytology with manual interpretation. However, an English RCT estimated that LBC with computer-assisted interpretation has a lower sensitivity than LBC with manual interpretation. COST AND ECONOMIC EVALUATION: In the current Italian situation the use of liquid-based cytology for primary screening is estimated to increase the costs of cytological screening. Liquid-based cytology needs shorter time for interpretation than conventional cytology. However, in the Italian situation, savings obtained from this time reduction and from the decreased number of repeats due to unsatisfactory slides are not currently sufficient to compensate the cost increase due to the prices currently applied by producers and to a possible greater number of colposcopies caused by LBC. In any case, at current prices, cost is estimated to increase even when assuming a referral rate to colposcopy with LBC similar or slightly lower than that with conventional cytology. For the costs of computer-assisted interpretation of liquid-based cytology, readers are referred to the relative HTA report (Epidemiol Prev 2012;36(5) Suppl 3:e1-43). ORGANISATIONAL AND ETHICAL ASPECTS: Ethical, legal and communication problems are judged to remain unchanged when compared to screening with conventional cytology. After having used the test for some time, interpreters prefer liquid-based to conventional cytology. Reduced time for interpretation makes the adoption of LBC a possible approach to deal with shortenings of cytology interpreters which is happening in Italy. However, alternative solutions, such as computer-assisted interpretation of cytology and the use of HPV as primary screening test, should be considered. Liquid-based cytology allows performing molecular tests, in particular the HPV test. This property allows triaging women with borderline or mild cytology by "reflex" molecular or immunocytochemical tests with no need to recall them. LBC sampling can be used also if HPV is applied as the primary screening test, allowing "reflex" triaging of HPV positive women by cytology with no need to recall them nor to take two samples, one for HPV testing and one for conventional cytology. This represents a remarkable advantage in terms of organization. However, costs are high because only 5-7% of women screened with this approach need interpretation of cytology. In addition, HPV testing with the Hybrid Capture assay on material preserved in LBC transport media needs a preliminary conversion phase, which limits the use of LBC for triaging HPV positive women. It is advisable that in the near future industry develops sampling/transport systems that allow performing both the HPV test and cytology or other validated triage tests without additional manipulations and at sustainable costs.

[Prevalence of high-risk HPV and its distribution in cervical precancerous lesions among 35-64 years old women who received cervical cancer screening in Beijing].

PubMed

Shen, J; Gao, L L; Zhang, Y; Han, L L; Wang, J D

2018-05-06

Objective: To study the prevalence of high-risk HPV (HR HPV) in women who accepted cervical cancer screening in Beijing and its distribution in cervical precancerous lesions. Methods: From January 2014 to March 2015, all women aged 35-64 years old and received free screening in institutions of cervical cancer in Beijing were recruited. Stratified cluster random sampling method was used in selecting 31 091 women for gynecological examination and genotyping of HR-HPV. Those positive for HR-HPV (except for HPV 16/18) were examined for cervical cell. For those atypical squamous cells of uncertain significance (ASCUS) and above, who were positive for HPV 16/18 and with uncertain results for cervical cell, were transferred for colposcopy examination. For those with suspicious or abnormal results for colposcopy, were transferred for histopathology. The prevalence of HR-HPV, cervical cancer and precancerous lesions among the participants were analyzed. Results: Totally 31 091 women aged from 35-year-old to 64-year-old, with 44.3% (13 780 women) in the 35-49 age group and 55.7% (17 311 women) in the 50-64 age group. 66.1% (20 536 women) were rural women. The infection rate of HR-HPV was 7.4%(2 305 cases) among the women. High-risk infection rates of HPV except HPV 16/18 were 5.7% (1 758 cases), and multi-infection rate was 1.5% (477 cases). The highest infection rate was 7.9% (1 044 cases) among the 45-49 year-old and 50-54 year-old age groups (χ(2)=14.07, P= 0.015). The rate in rural women was significantly higher than that of the urban women (6.2%, 507 cases; 7.9%, 1 798 cases) (χ(2)=25.75, P< 0.001). The proportion of HPV16, HPV18, HPV52, HPV51, HPV58 was 17.0% (391 cases), 6.9% (161 cases), 8.6% (20 cases), 5.2% (12 cases) and 7.7% (18 cases), respectively. The detection rate of cervical cancer and precancerous lesions in the population was 395.6/100 000 (123 cases). In high-grade squamous intraepithelial lesions (HSIL), HPV16 and 18 infections accounted for 60.5% (72 cases) of all. HPV16 infection rate and detection rate of HSIL were the highest in 50-54 year-old group which were 1.5% (107 cases) and 25.2% (30 cases) (χ(2)=11.54, P= 0.042). Conclusion: Top five types of HR-HPV infection in women who accepted cervical cancer screening in Beijing were HPV16, 18, 52, 51 and 58. The infection rate of HPV16 and 18 increased significantly in HSIL women. HPV16 infection rate and detection rate of HSIL were the highest in 50-54 year-old age group.

Effectiveness of Photodynamic Therapy in Elimination of HPV-16 and HPV-18 Associated with CIN I in Mexican Women.

PubMed

Maldonado Alvarado, Elizabeth; Osorio Peralta, Martha Olivia; Moreno Vázquez, Alejandra; Martínez Guzmán, Lydia Alejandra; Melo Petrone, Maria Eugenia; Enriquez Mar, Zulma Iveth; Jovel Galdamez, Dora Estela; Carrión Solana, Bárbara; Balderas Martínez, Guadalupe; Parra, Eduarda; Castellanos Oliveros, Rossana Inés; Bello Leiva, Rosa Linda; Espinosa Montesinos, Araceli; Barrera Mendoza, Citlalli; Medina García, Selma Eugenia; Ramón Gallegos, Eva

2017-10-01

This study aimed to determine the effectiveness of photodynamic therapy (PDT), using δ-aminolevulinic acid (5-ALA), in the elimination of premalignant cervical lesions in Mexican patients with human papillomavirus (HPV) infection and/or cervical intraepithelial neoplasia (CIN). Thirty women diagnosed with CIN I and/or positive for HPV participated in the study. Topical 6% 5-ALA in gel form was applied to the uterine cervix; after 4 h, the lesion area was irradiated with a light dose of 200 J cm -2 at 635 nm. This procedure was performed three times at 48-h intervals. Clinical follow-up was performed at 3, 6, and 12 months after the initial PDT administration, by colposcopy, cervical cytology, histopathological analysis, polymerase chain reaction, and hybrid capture. Of HPV-infected patients without evidence of CIN I, 80% cleared the infection, while HPV associated with CIN I was eliminated in 83% of patients (P < 0.05). At 12 months, CIN I had regressed in 57% of patients, although this response was not statistically significant. PDT using 6% 5-ALA is concluded to be effective in eliminating HPV infection associated or not with CIN I. © 2017 The American Society of Photobiology.

Clinical use of a portable dual microscope system for smartphone (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kurachi, Cristina; Brognara, Gabriel; Gómez-García, Pablo A.; Carbinatto, Fernanda; Silva, Eduardo V.; Lombardi, Wellington; Inada, Natália M.; Bagnato, Vanderlei S.

2016-03-01

Cervical cancer is still one of the most relevant women cancer types, since the 5-year survival rate is of only around 68%. Prevention and early diagnosis are the best strategies to improve cervical cancer prognosis. Conventional diagnosis procedure in Gynecology is mainly based on the macroscopic clinical evaluation, Pap smear cytology, and biopsy, if needed. A portable microscope with dual configuration and its use for diagnosis in Gynecology is investigated. The microscope has interchangeable parts that allow its use for cytopathology smear samples or in situ endoscopic tissue interrogation, both using acriflavine as a nuclei marker. Patients of the Women Ambulatory of the School of Medicine (UNIARA, Araraquara, Brazil) were interrogated during the colposcopy examination. The cervix was initially cleaned using an acetic acid solution, and a 0.05% (wt/vol) acriflavine in saline solution was topically applied at the tissue surface using a cotton swab. Microendoscopy images were taken from clinically normal cervix mucosa and from detected lesions. An image processing is performed to evaluate the cell nuclei morphology and the cytoplasm/nuclei ratio. The Pap smear results and the histology analyses are taken as gold standard for the diagnosis. Preliminary results in 5 patients demonstrated the potential use of our microscope at the clinical setting.

Does hearing the patient perspective improve consultation skills in examinations? An exploratory randomized controlled trial in medical undergraduate education.

PubMed

Snow, Rosamund; Crocker, Joanna; Talbot, Katherine; Moore, Jane; Salisbury, Helen

2016-12-01

Medical education increasingly includes patient perspectives, but few studies look at the impact on students' proficiency in standard examinations. We explored students' exam performance after viewing video of patients' experiences. Eighty-eight medical students were randomized to one of two e-learning modules. The experimental group saw video clips of patients describing their colposcopy, while the control group viewed a clinician describing the procedure. Students then completed a Multiple Choice Questionnaire (MCQ) and were assessed by a blinded clinical examiner in an Objective Structured Clinical Examination (OSCE) with a blinded simulated patient (SP). The SP scored students using the Doctors' Interpersonal Skills Questionnaire (DISQ). Students rated the module's effect on their skills and confidence. Regression analyses were used to compare the effect of the two modules on these outcomes, adjusting for gender and graduate entry. The experimental group performed better in the OSCE than the control group (odds ratio 2.7 [95%CI 1.2-6.1]; p = 0.016). They also reported significantly more confidence in key areas, including comfort with patients' emotions (odds ratio 6.4 [95%CI 2.7-14.9]; p < 0.0005). There were no other significant differences. Teaching that included recorded elements of real patient experience significantly improved students' examination performance and confidence.

Development and testing of a homogenous multi-wavelength LED light source

NASA Astrophysics Data System (ADS)

Bolton, Frank J.; Bernat, Amir; Jacques, Steven L.; Levitz, David

2017-03-01

Multispectral imaging of human tissue is a powerful method that allows for quantify scattering and absorption parameters of the tissue and differentiate tissue types or identify pathology. This method requires imaging at multiple wavelengths and then fitting the measured data to a model based on light transport theory. Earlier, a mobile phone based multi-spectral imaging system was developed to image the uterine cervix from the colposcopy geometry, outside the patient's body at a distance of 200-300 mm. Such imaging of a distance object has inherent challenges, as bright and homogenous illumination is required. Several solutions addressing this problem were developed, with varied degrees of success. In this paper, several multi-spectral illumination setups were developed and tested for brightness and uniformity. All setups were specifically designed with low cost in mind, utilizing a printed circuit board with surface-mounted LEDs. The three setups include: LEDs illuminating the target directly, LEDs illuminating focused by a 3D printed miniature lens array, and LEDs coupled to a mixing lens and focusing optical system. In order to compare the illumination uniformity and intensity performance two experiments were performed. Test results are presented, and various tradeoffs between the three system configurations are discussed. Test results are presented, and various tradeoffs between the three system configurations are discussed.

In vivo Diagnosis of Cervical Intraepithelial Neoplasia Using 337-nm- Excited Laser-Induced Fluorescence

NASA Astrophysics Data System (ADS)

Ramanujam, N.; Mitchell, M. F.; Mahadevan, A.; Warren, S.; Thomsen, S.; Silva, E.; Richards-Kortum, R.

1994-10-01

Laser-induced fluorescence at 337-nm excitation was used in vivo to differentiate neoplastic [cervical intraepithelial neoplasia (CIN)], nonneoplastic abnormal (inflammation and human papilloma viral infection), and normal cervical tissues. A colposcope (low-magnification microscope used to view the cervix with reflected light) was used to identify 66 normal and 49 abnormal (5 inflammation, 21 human papilloma virus infection, and 23 CIN) sites on the cervix in 28 patients. These sites were then interrogated spectroscopically. A two-stage algorithm was developed to diagnose CIN. The first stage differentiated histologically abnormal tissues from colposcopically normal tissues with a sensitivity, specificity, and positive predictive value of 92%, 90%, and 88%, respectively. The second stage differentiated preneoplastic and neoplastic tissues from nonneoplastic abnormal tissues with a sensitivity, specificity, and positive predictive value of 87%, 73%, and 74%, respectively. Spectroscopic differences were consistent with a decrease in the absolute contribution of collagen fluorescence, an increase in the absolute contribution of oxyhemoglobin attenuation, and an increase in the relative contribution of reduced nicotinamide dinucleotide phosphate [NAD(P)H] fluorescence as tissue progresses from normal to abnormal in the same patient. These results suggest that in vivo fluorescence spectroscopy of the cervix can be used to diagnose CIN at colposcopy.

Visible light optical spectroscopy is sensitive to neovascularization in the dysplastic cervix

NASA Astrophysics Data System (ADS)

Chang, Vivide Tuan-Chyan; Bean, Sarah M.; Cartwright, Peter S.; Ramanujam, Nirmala

2010-09-01

Neovascularization in cervical intraepithelial neoplasia (CIN) is studied because it is the precursor to the third most common female cancer worldwide. Diffuse reflectance from 450-600 nm was collected from 46 patients (76 sites) undergoing colposcopy at Duke University Medical Center. Total hemoglobin, derived using an inverse Monte Carlo model, significantly increased in CIN 2+ (N=12) versus CIN 1 (N=16) and normal tissues (N=48) combined with P<0.004. Immunohistochemistry using monoclonal anti-CD34 was used to quantify microvessel density to validate the increased hemoglobin content. Biopsies from 51 sites were stained, and up to three hot spots per slide were selected for microvessel quantification by two observers. Similar to the optical study results, microvessel density was significantly increased in CIN 2+ (N=16) versus CIN 1 (N=21) and normal tissue (N=14) combined with P<0.007. Total vessel density, however, was not significantly associated with dysplastic grade. Hence, our quantitative optical spectroscopy system is primarily sensitive to dysplastic neovascularization immediately beneath the basement membrane, with minimal confounding from vascularity inherent in the normal stromal environment. This tool could have potential for in vivo applications in screening for cervical cancer, prognostics, and monitoring of antiangiogenic effects in chemoprevention therapies.

[ASCUS in screening].

PubMed

Caprara, L; Monari, F; De Bianchi, P S; Amadori, A; Bondi, A

2001-12-01

The significance and use of the cytological diagnosis "atypical squamous cells of undetermined significance" (ASCUS) remain a major problem in cervical cancer screening. The prevalence of ASCUS by patient age has seldom been investigated. The present paper reports the prevalence of ASCUS in a large series of screening Pap smears from the Italian region of Emilia-Romagna. The study was based on the data collected by the Department of Health of the Emilia-Romagna Region for the first 3-year round (1997-1999) of a population-based screening programme (target age, 25-64 years). The age-specific frequency of ASCUS has been calculated as a prevalence rate per 1000 screened patients. A total of 597,386 women participated in the programme. Women diagnosed with ASCUS (n = 8205 or 13.7 per 1000) accounted for 49% of the recalls for colposcopy (n = 16,871, or 28.2 per 1000). The prevalence of diagnoses of low-grade squamous intraepithelial lesions (LG-SIL) decreased progressively with age while that of high-grade SIL was slightly higher between 30 and 39 years. The prevalence of ASCUS peaked at age 45-49 years (17.3 per 1000 subjects). The observed peak reflects the prevalence of (1) cytological changes closely associated with perimenopausal age and at least compatible with the ASCUS diagnosis, and (2) cytological abnormalities induced by hormone replacement therapy.

Estrogen treatment of acetic acid burns to the vagina, cervix, and perineum: a case report and review of the literature.

PubMed

Ching, Jessica A; Kuykendall, Lauren V; Troy, Jared S; Smith, David J

2014-01-01

In colposcopic evaluation of the cervix, acetic acid of 3 to 5% is commonly used for identification of preneoplastic and neoplastic cells. Acetic acid is a known caustic substance and has the potential to cause irritation and chemical burns when there is sufficient concentration or duration of contact. The authors present a unique case of a woman who inadvertently received undiluted acetic acid during a routine colposcopy, resulting in significant chemical burns of the vagina, cervix, and perineum. Her burns were treated with topical estrogen cream of 1 g twice daily applied directly to the wounds. The burn wounds were fully healed within 8 weeks without complication or additional treatment. At 6 months after the injury, the patient was allowed to engage in sexual activity, and vaginal dilation and pelvic floor therapy were initiated. At 12 months postinjury, her only symptomatic scarring at the left vaginal wall continues to improve. Thus, topical estrogen treatment of 1 g applied twice daily should be continued until burn scar maturation is complete and treatment improvement plateaus in cases of burns to the vagina, cervix, and perineum. This case is further clinical evidence of estrogen's positive effect on wound healing and its potential role in burn treatment.

Management of precancerous cervical lesions in iran: a cost minimizing study.

PubMed

Nahvijou, Azin; Sari, Ali Akbari; Zendehdel, Kazem; Marnani, Ahmad Barati

2014-01-01

Cervical cancer is a common, preventable and manageable disease in women worldwide. This study was conducted to determine the cost of follow-up for suspicious precancerous cervical lesions within a screening program using Pap smear or HPV DNA test through the decision tree. Patient follow-up processes were determined using standard guidelines and consultation with specialists to design a decision tree model. Costs of treatment in both public and private sectors were identified according to the national tariffs in 2010 and determined based on decision tree and provided services (visits to specialists, colposcopy, and conization) with two modalities: Pap smear and HPV DNA test. The number of patients and the mean cost of treatment in each sector were calculated. The prevalence of lesions and HPV were obtained from literature to estimate the cost of treatment for each woman in the population. Follow-up costs were determined using seven processes for Pap smear and 11 processes for HPV DNA test. The total cost of using Pap smear and HPV DNA process for each woman in the population was 36.1$ and 174 $ respectively. The follow-up process for patients with suspicious cervical lesions needs to be included in the existing screening program. HPV DNA test is currently more expensive than Pap smear, it is suggested that we manage precancerous cervical lesions with this latter test.

An special epithelial staining agents: folic acid receptor-mediated diagnosis (FRD) effectively and conveniently screen patients with cervical cancer.

PubMed

Lu, Meng-Han; Hu, Ling-Yun; Du, Xin-Xin; Yang, Min; Zhang, Wei-Yi; Huang, Ke; Li, Li-An; Jiang, Shu-Fang; Li, Ya-Li

2015-01-01

High-quality screening with cytology has markedly reduced mortality from cervical cancer. However, it needs experienced pathologists to review and make the final decisions. We have developed folic acid receptor-mediated diagnosis (FRD) kits to effectively and conveniently screen patients with cervical cancer. We conduct present study aim to assess clinical significances of FRD in screening cervical cancer. A total of 169 patients were enrolled at Chinese People's liberation Army (PLA) general hospital. We compared diagnostic significances of FRD with thinprep cytology test (TCT). Meanwhile, colposcopy was also performed to confirm any lesion suspicious for cervical cancer. The sensitivity and specificity of FRD were 71.93% and 66.07% in diagnosis cervical cancer, respectively. Meanwhile, the positive predictive values (PPV), negative predictive values (NPV), Youden index were 51.90%, 82.22%, 0.38, respectively. On the other hand, the sensitivity and specificity of TCT in diagnosis cervical cancer were 73.68% and 61.61% respectively. PPV, NPV and Youden index for TCT were 49.41%, 82.14% and 0.35 respectively. Overall, FRD have high values of sensitivity, specificity and Youden index. However, this difference failed to statistical significance. FRD have comparable diagnostic significance with TCT. Therefore, FRD might serve as one effective method to screen cervical cancer. Especially for those patients living in remote regions of China, where cytology was unavailable.

An special epithelial staining agents: folic acid receptor-mediated diagnosis (FRD) effectively and conveniently screen patients with cervical cancer

PubMed Central

Lu, Meng-Han; Hu, Ling-Yun; Du, Xin-Xin; Yang, Min; Zhang, Wei-Yi; Huang, Ke; Li, Li-An; Jiang, Shu-Fang; Li, Ya-Li

2015-01-01

High-quality screening with cytology has markedly reduced mortality from cervical cancer. However, it needs experienced pathologists to review and make the final decisions. We have developed folic acid receptor-mediated diagnosis (FRD) kits to effectively and conveniently screen patients with cervical cancer. We conduct present study aim to assess clinical significances of FRD in screening cervical cancer. A total of 169 patients were enrolled at Chinese People’s liberation Army (PLA) general hospital. We compared diagnostic significances of FRD with thinprep cytology test (TCT). Meanwhile, colposcopy was also performed to confirm any lesion suspicious for cervical cancer. The sensitivity and specificity of FRD were 71.93% and 66.07% in diagnosis cervical cancer, respectively. Meanwhile, the positive predictive values (PPV), negative predictive values (NPV), Youden index were 51.90%, 82.22%, 0.38, respectively. On the other hand, the sensitivity and specificity of TCT in diagnosis cervical cancer were 73.68% and 61.61% respectively. PPV, NPV and Youden index for TCT were 49.41%, 82.14% and 0.35 respectively. Overall, FRD have high values of sensitivity, specificity and Youden index. However, this difference failed to statistical significance. FRD have comparable diagnostic significance with TCT. Therefore, FRD might serve as one effective method to screen cervical cancer. Especially for those patients living in remote regions of China, where cytology was unavailable. PMID:26221336

Transformation zone location and intraepithelial neoplasia of the cervix uteri.

PubMed Central

Autier, P.; Coibion, M.; Huet, F.; Grivegnee, A. R.

1996-01-01

We examined the relationship between the frequency of premalignant lesions of the cervix and location of the transformation zone on the cervix among 8758 women as assessed using cervicography. An endo- and exocervical smear test was performed at the same time. Women with smear test classified CIN I or more were recalled and any abnormal area was biopsied under colposcopy. The transformation zone was located on the exocervix in 94% of women younger than 25 years old; as age increased, the proportion of women with a transformation zone located on the exocervix steadily decreased to reach less than 2% after 64 years old. As compared with women having a transformation zone in the endocervical canal, the age-adjusted likelihood of discovering a histologically proven dysplastic lesion was 1.8 times more frequent among women with a transformation zone located on the exocervix (95% confidence interval 1.1-2.9). This higher frequency seemed not attributable to a lower sensitivity of the smear test when the transformation zone was hidden. The results also showed that deliveries tended significantly to maintain the transformation zone on the exocervix. Parity is a known risk factor for cervix cancer, but the mechanism by which it favours malignant lesions remain unknown. Our results suggest that with increasing numbers of livebirths, the transformation zone is directly exposed for longer periods to external agents involved in dysplastic lesions. PMID:8695371

Revised terminology for cervical histopathology and its implications for management of high-grade squamous intraepithelial lesions of the cervix.

PubMed

Waxman, Alan G; Chelmow, David; Darragh, Teresa M; Lawson, Herschel; Moscicki, Anna-Barbara

2012-12-01

In March 2012, the College of American Pathologists and American Society for Colposcopy and Cervical Pathology, in collaboration with 35 stakeholder organizations, convened a consensus conference called the Lower Anogenital Squamous Terminology (LAST) Project. The recommendations of this project include using a uniform, two-tiered terminology to describe the histology of human papillomavirus-associated squamous disease across all anogenital tract tissues: vulva, vagina, cervix, penis, perianus, and anus. The recommended terminology is "low-grade" or "high-grade squamous intraepithelial lesion (SIL)." This terminology is familiar to clinicians, because it parallels the terminology of the Bethesda System cytologic reports. Biopsy results using SIL terminology may be further qualified using "intraepithelial neoplasia" (IN) terminology in parentheses. Laboratory p16 tissue immunostaining is recommended to better classify histopathology lesions that morphologically would earlier have been diagnosed as IN 2. p16 is also recommended for differentiating between high-grade squamous intraepithelial lesions and benign mimics. The LAST Project recommendations potentially affect the application of current guidelines for managing cervical squamous intraepithelial lesions. The authors offer interim guidance for managing cervical lesions diagnosed using this new terminology with special attention paid to managing young women with cervical high-grade squamous intraepithelial lesions on biopsy. Clinicians should be aware of the LAST Project recommendations, which include important changes from prior terminology.

Automated image analysis of uterine cervical images

NASA Astrophysics Data System (ADS)

Li, Wenjing; Gu, Jia; Ferris, Daron; Poirson, Allen

2007-03-01

Cervical Cancer is the second most common cancer among women worldwide and the leading cause of cancer mortality of women in developing countries. If detected early and treated adequately, cervical cancer can be virtually prevented. Cervical precursor lesions and invasive cancer exhibit certain morphologic features that can be identified during a visual inspection exam. Digital imaging technologies allow us to assist the physician with a Computer-Aided Diagnosis (CAD) system. In colposcopy, epithelium that turns white after application of acetic acid is called acetowhite epithelium. Acetowhite epithelium is one of the major diagnostic features observed in detecting cancer and pre-cancerous regions. Automatic extraction of acetowhite regions from cervical images has been a challenging task due to specular reflection, various illumination conditions, and most importantly, large intra-patient variation. This paper presents a multi-step acetowhite region detection system to analyze the acetowhite lesions in cervical images automatically. First, the system calibrates the color of the cervical images to be independent of screening devices. Second, the anatomy of the uterine cervix is analyzed in terms of cervix region, external os region, columnar region, and squamous region. Third, the squamous region is further analyzed and subregions based on three levels of acetowhite are identified. The extracted acetowhite regions are accompanied by color scores to indicate the different levels of acetowhite. The system has been evaluated by 40 human subjects' data and demonstrates high correlation with experts' annotations.

Effectiveness Modelling and Economic Evaluation of Primary HPV Screening for Cervical Cancer Prevention in New Zealand

PubMed Central

Lew, Jie-Bin; Simms, Kate; Smith, Megan; Lewis, Hazel; Neal, Harold; Canfell, Karen

2016-01-01

Background New Zealand (NZ) is considering transitioning from 3-yearly cervical cytology screening in women 20–69 years (current practice) to primary HPV screening. We evaluated HPV-based screening in both HPV-unvaccinated women and cohorts offered HPV vaccination in New Zealand (vaccination coverage ~50%). Methods A complex model of HPV transmission, vaccination, cervical screening, and invasive cervical cancer was extensively validated against national population-based datasets. Sixteen potential strategies for HPV screening were considered. Results Most primary HPV strategies were more effective than current practice, for both unvaccinated women and cohorts offered vaccination. The optimal strategy for both groups was 5-yearly HPV screening in women aged 25–69 years with partial genotyping for HPV 16/18 and referral to colposcopy, and cytological triage of other oncogenic types. This is predicted to reduce cervical cancer incidence and mortality by a further 12–16% and to save 4–13% annually in program costs (excluding overheads). The findings are sensitive to assumptions about future adherence to initiating screening at 25 years. Conclusion Primary HPV screening with partial genotyping would be more effective and less costly than the current cytology-based screening program, in both unvaccinated women and cohorts offered vaccination. These findings have been considered in a review of cervical screening in NZ. PMID:27187495

Cervical cancer screening with naked-eye visual inspection in Colombia.

PubMed

Murillo, Raul; Luna, Joaquin; Gamboa, Oscar; Osorio, Elkin; Bonilla, Jairo; Cendales, Ricardo

2010-06-01

To assess the accuracy of visual inspection provided by nurses through combining acetic acid (VIA) and Lugol's iodine (VILI) in a low-resource region of Colombia. A cross-sectional study with 4957 women was conducted to evaluate visual inspection techniques as the basis for see-and-treat approaches in cervical cancer control. All women underwent conventional cytology, VIA performed by nurses, and a combination of VIA and VILI. All women underwent colposcopy and biopsies were obtained for any positive test. A total of 762 women underwent biopsy, 4945 women were included in the analysis of conventional cytology, and 4957 were included in the analysis of VIA and VIA-VILI. Positivity rates were 1.3% and 4.3% for HSIL and LSIL cytology, 7.4% for VIA, and 10.1% for VIA-VILI. Sensitivity for cytology was 52.9% and 36.8% for LSIL and HSIL thresholds, 53.6% for VIA, and 68.1% for VIA-VILI. The corresponding specificity was 95.0%, 99.2%, 93.2%, and 90.8% respectively. The parallel combination of VIA-VILI and cytology LSIL-threshold revealed the best performance as a screening strategy. The use of VIA-VILI simulating colposcopic procedures and provided by nurses represents a good alternative for implementing see-and-treat programs in Latin America. Program constraints should be taken into account. Copyright 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

The role of human papillomavirus in screening for cervical cancer.

PubMed

McFadden, S E; Schumann, L

2001-03-01

To review the options for effectively screening for cervical cancer, including human papilloma virus (HPV) identification, cytologic screening, colposcopy, or a combination approach. Current pathophysiology, diagnostic criteria, treatment approaches, and patient preparation and education related to cervical cancer screening and prevention are also included. Comprehensive review of current literature, including research and review articles. Because the Papanicolau (Pap) smear is a screening tool, not a diagnostic tool, further studies must be done to identify the actual nature of discovered abnormalities. Of particular concern is the classification of atypical squamous cells of undetermined significance (ASCUS), which may simply indicate inflammation, or may be the first indicator of serious pathology. Following ASCUS Pap smears with HPV screening will allow for a clarification of the best approach to treatment. A screening algorithm supported by a review of the literature is proposed. Cervical cancer is a preventable disease caused by certain forms of HPV. Current screening protocols are based on the use of the Pap smear; and in areas where this test is routine and available, morbidity and mortality rates have dropped dramatically. Many women throughout the world and in underserved regions of the U. S. do not have adequate access to routine screening with Pap smear technology. As long as women continue to die needlessly of cervical cancer, more comprehensive and accessible screening methods must be explored. (Cutting the unnecessary worldwide and in the U. S.).

Visual inspection of cervix with acetic acid: a good alternative to pap smear for cervical cancer screening in resource-limited setting.

PubMed

Khan, Momna; Sultana, Syeda Seema; Jabeen, Nigar; Arain, Uzma; Khans, Salma

2015-02-01

To determine the diagnostic accuracy of visual inspection of cervix using 3% acetic acid as a screening test for early detection of cervical cancer taking histopathology as the gold standard. The cross-sectional study was conducted at Civil Hospital Karachi from July 1 to December 31, 2012 and comprised all sexually active women aged 19-60 years. During speculum examination 3% acetic acid was applied over the cervix with the help of cotton swab. The observations were noted as positive or negative on visual inspection of the cervix after acetic acid application according to acetowhite changes. Colposcopy-guided cervical biopsy was done in patients with positive or abnormal looking cervix. Colposcopic-directed biopsy was taken as the gold standard to assess visual inspection readings. SPSS 17 was used for statistical analysis. There were 500 subjects with a mean age of 35.74 ± 9.64 years. Sensitivity, specifically, positive predicted value, negative predicted value of visual inspection of the cervix after acetic acid application was 93.5%, 95.8%, 76.3%, 99%, and the diagnostic accuracy was 95.6%. Visual inspection of the cervix after acetic acid application is an effective method of detecting pre-invasive phase of cervical cancer and a good alternative to cytological screening for cervical cancer in resource-poor setting like Pakistan and can reduce maternal morbidity and mortality.

Pharmacokinetics of 2 dapivirine vaginal microbicide gels and their safety vs. Hydroxyethyl cellulose-based universal placebo gel.

PubMed

Nel, Annalene M; Smythe, Shanique C; Habibi, Sepideh; Kaptur, Paulina E; Romano, Joseph W

2010-10-01

Dapivirine, a nonnucleoside reverse transcriptase inhibitor, is in development as a microbicide for the protection of women against HIV infection. A randomized, double-blind, phase 1 trial was conducted in 36 healthy HIV-negative women to compare the pharmacokinetics of 2 dapivirine vaginal gel formulations (0.05% each) and their safety with the hydroxyethyl cellulose-based universal placebo gel. Gel was self-administered once daily for a total of 11 days. Blood and vaginal fluid samples were collected sequentially over 24 days for pharmacokinetic analysis. Safety was evaluated by pelvic examination, colposcopy, adverse events, and clinical laboratory assessments. Adverse event profiles were similar for the 3 gels. Most events were mild and not related to study gel. Headache and vaginal hemorrhage (any vaginal bleeding) were most common. Plasma concentrations of dapivirine did not exceed 1.1 ng/mL. Steady-state conditions were reached within approximately 10 days. Dapivirine concentrations in vaginal fluids were slightly higher for Gel 4789, but Cmax values on days 1 and 14 were not significantly different. Terminal half-life was 72-73 hours in plasma and 15-17 hours in vaginal fluids. Both formulations of dapivirine gel were safe and well tolerated. Dapivirine was delivered to the lower genital tract at concentrations at least 5 logs greater than in vitro inhibitory concentrations.

A case of usual (basaloid)-type vulvar intraepithelial neoplasia that failed to respond to imiquimod cream: clinical implications.

PubMed

Shiozaki, Takaya; Tabata, Tsutomu; Toriyabe, Kuniaki; Motohashi, Takashi; Kondo, Eiji; Tanida, Kouji; Okugawa, Toshiharu; Sagawa, Norimasa

2011-10-01

The authors report a case of usual-type (basaloid-type) vulvar intraepithelial neoplasia (VIN) 3 that failed to respond to imiquimod cream. A 51-year-old Japanese woman visited her local gynecologist complaining of vulvar itching. Atypical cells were noted in cytology smears, but nine vulvar biopsy specimens showed benign proliferation of epithelial tissue. The patient was placed under careful observation for 8 months, when the vulvar smears once again showed atypical cells and biopsy specimens revealed VIN3. The patient was then referred to our hospital where she was given a diagnosis of VIN 3, basaloid type of usual type. The biopsy specimens were positive for p16 and the lesions were confirmed to be human papilloma virus (HPV)-related. We recommended simple vulvectomy but the patient requested conservative treatment with imiquimod cream. With her written informed consent, we prescribed imiquimod cream to be self-administered 3 times a week. Colposcopy and pap smear test were performed every 2 weeks. Four weeks after the start of treatment, a fingertip-sized papule was detected at the patient's vaginal introitus. By 6 weeks, the lesion had enlarged, and biopsy specimens revealed invasive squamous cell carcinoma. At 7 weeks, we performed simple vulvectomy. The surgical specimen showed stage pT1b keratinizing-type squamous cell carcinoma. HPV-16 DNA was detected in the specimen.

Optical coherence tomography in diagnosing cervical cancer

NASA Astrophysics Data System (ADS)

Kuznetzova, Irina A.; Shakhova, Natalia M.; Kachalina, Tatiana S.; Gladkova, Natalia D.; Myakov, Alexey V.; Iksanov, Rashid R.; Feldchtein, Felix I.

2000-05-01

Cervical cancer remains one of the most significant problem in oncogynecology. It tends towards treatment approaches that provide termination of pathological processes along with preservation of the patient's life quality. There is a need in earlier and more accurate diagnosis of pathological states, objective assessment of physiological processes, and adequate monitoring of the course of treatment. In our previous publications we have reported unique capabilities of the Optical Coherence Tomography (OCT) to image in vivo the mucosa structure of the cervix and to monitor various physiological and pathological alterations. In this report, we present results of OCT application to diagnose different stages of cervical cancer and to control its treatment at early stages. We have performed OCT-colposcopy in 11 female patients with cervical cancer to derive OCT criteria of this disease, to provide exact demarcation of a pathological area, and to determine a real size of a tumor. We have found that, in general, borders of a tumor, defined visually and detected with OCT by violation of the basement membrane in exocervix, do not coincide. The mismatch depends on a stage of cancer and can be as much as several millimeters. This information is especially important for evaluation of linear dimension of tumors with 3 - 5 mm invasion and also for differential diagnosis between the T1 and T2 stages with cancer extension onto vagina.

Prognostic value of human papillomavirus 16/18 genotyping in low-grade cervical lesions preceded by mildly abnormal cytology.

PubMed

Ye, Jing; Cheng, Bei; Cheng, Yi-Fan; Yao, Ye-Li; Xie, Xing; Lu, Wei-Guo; Cheng, Xiao-Dong

Histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) preceded by normal or mildly abnormal cytology is recommended for conservative follow-up, with no separated management. In this study, we assessed the triage value of human papillomavirus (HPV) 16/18 genotyping in 273 patients with LSIL/CIN1. HPV16/18 genotyping was performed at baseline and follow-up was at 6-monthly intervals for up to 2 years. At each follow-up, women positive for cytology or high-risk HPV (hrHPV) were referred for colposcopy. Enrollment cytology, HPV16/18 genotyping, and questionnaire-obtained factors were linked to the 2-year cumulative progression rate. Univariate and multivariate analyses were performed taking into account time-to-event with Cox proportional hazard regression. The results showed that 190 cases (69.6%) regressed, 37 (13.6%) persisted, and 46 (16.8%) progressed. HPV16/18 positivity (hazard ratio (HR), 2.708; 95% confidence interval (CI), 1.432-5.121; P=0.002) is significantly associated with higher 2-year cumulative progression rate. Sub-analysis by enrollment cytology and age restricted the positive association among patients preceded by mildly abnormal cytology and aged 30 years or older. Immediate treatment is a rational recommendation for the high-risk subgroup, when good compliance is not assured.

Clinical significance of atypical squamous cells cannot exclude high grade squamous intraepithelial lesion with histologic correlation-: a 9-year experience.

PubMed

Selvaggi, Suzanne M

2013-11-01

Atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H) is a recognized category in the 2001 Bethesda Nomenclature System for cervical cytology. Although current ASCCP guidelines recommend colposcopic follow-up, more recent studies are suggesting prior triage for HPV-DNA analysis. We report on our experience at the University of Wisconsin Hospital and Clinics. From January 1, 2003 through December 31, 2011 (9-y), the cytopathology laboratory processed 109,424 Pap Tests, of which 281 (0.26%) were diagnosed as ASC-H. Tissue follow-up was available in 181 (64%) of these cases, of which 45 (25%) were negative/cervicitis, 41 (23%) were CIN 1, 36 (20%) were CIN 2 and 59 (32%) were CIN 3. Stratification by age groups showed a higher percentage of high grade (CIN 2+) lesions (65%) in the premenopausal age group as compared with high grade lesion (35%) in the postmenopausal age group, whereas negative/CIN1 biopsies were more common in postmenopausal (65%) as compared to premenopausal (44%) women. Our data support the use of colposcopy in the management of women with ASC-H on Pap Tests. However, in the older age group, prior HPV-DNA testing may be of benefit to better identify those women at risk for high grade lesions. Copyright © 2013 Wiley Periodicals, Inc.

Evaluation of clinical methods for diagnosing bacterial vaginosis.

PubMed

Gutman, Robert E; Peipert, Jeffrey F; Weitzen, Sherry; Blume, Jeffrey

2005-03-01

To determine whether the current clinical criteria for diagnosing bacterial vaginosis can be simplified by using 2 clinical criteria rather than the standard 3 of 4 criteria (Amsel's criteria). This was a prospective observational study of 269 women undergoing a vaginal examination in the Women's Primary Care Center, Division of Research, or Colposcopy Clinic at Women & Infants Hospital. All 4 clinical criteria for diagnosing bacterial vaginosis were collected, and Gram stain was used as the gold standard. Sensitivity and specificity were calculated for each individual criterion, combinations of criteria, and a colorimetric pH and amine card. Receiver operating characteristic curve was generated to estimate the preferred pH and percentage of clue cells for diagnosing bacterial vaginosis. The prevalence of bacterial vaginosis in our study population was 38.7%. Vaginal pH was the most sensitive of all the criteria, at 89%, and a positive amine odor was the individual criteria with the highest specificity, at 93%. Similar specificity was seen with combinations of 2 criteria and Amsel's criteria. Receiver operating characteristic curve analysis yielded a preferred pH and percentage of clue cells of 5.0 and 20%, respectively. However, a pH of 4.5 or greater improves sensitivity with minimal loss of specificity. The clinical criteria for diagnosing bacterial vaginosis can be simplified to 2 clinical criteria without loss of sensitivity and specificity.

Revised Terminology for Cervical Histopathology and Its Implications for Management of High-Grade Squamous Intraepithelial Lesions of the Cervix

PubMed Central

Waxman, Alan G.; Chelmow, David; Darragh, Teresa M.; Lawson, Herschel; Moscicki, Anna-Barbara

2014-01-01

In March 2012, the College of American Pathologists and American Society for Colposcopy and Cervical Pathology, in collaboration with 35 stakeholder organizations, convened a consensus conference called the Lower Anogenital Squamous Terminology (LAST) Project. The recommendations of this project include using a uniform, two-tiered terminology to describe the histology of human papillomavirus-associated squamous disease across all anogenital tract tissues: vulva, vagina, cervix, penis, perianus, and anus. The recommended terminology is “low-grade” or “high-grade squamous intraepithelial lesion (SIL).” This terminology is familiar to clinicians, because it parallels the terminology of the Bethesda System cytologic reports. Biopsy results using SIL terminology may be further qualified using “intraepithelial neoplasia” (IN) terminology in parentheses. Laboratory p16 tissue immunostaining is recommended to better classify histopathology lesions that morphologically would earlier have been diagnosed as IN 2. p16 is also recommended for differentiating between high-grade squamous intraepithelial lesions and benign mimics. The LAST Project recommendations potentially affect the application of current guidelines for managing cervical squamous intraepithelial lesions. The authors offer interim guidance for managing cervical lesions diagnosed using this new terminology with special attention paid to managing young women with cervical high-grade squamous intraepithelial lesions on biopsy. Clinicians should be aware of the LAST Project recommendations, which include important changes from prior terminology. PMID:23168774

Accuracy of visual inspection performed by community health workers in cervical cancer screening.

PubMed

Driscoll, Susan D; Tappen, Ruth M; Newman, David; Voege-Harvey, Kathi

2018-05-22

Cervical cancer remains the leading cause of cancer and mortality in low-resource areas with healthcare personnel shortages. Visual inspection is a low-resource alternative method of cervical cancer screening in areas with limited access to healthcare. To assess accuracy of visual inspection performed by community health workers (CHWs) and licensed providers, and the effect of provider training on visual inspection accuracy. Five databases and four websites were queried for studies published in English up to December 31, 2015. Derivations of "cervical cancer screening" and "visual inspection" were search terms. Visual inspection screening studies with provider definitions, colposcopy reference standards, and accuracy data were included. A priori variables were extracted by two independent reviewers. Bivariate linear mixed-effects models were used to compare visual inspection accuracy. Provider type was a significant predictor of visual inspection sensitivity (P=0.048); sensitivity was 15 percentage points higher among CHWs than physicians (P=0.014). Components of provider training were significant predictors of sensitivity and specificity. Community-based visual inspection programs using adequately trained CHWs could reduce barriers and expand access to screening, thereby decreasing cervical cancer incidence and mortality for women at highest risk and those living in remote areas with limited access to healthcare personnel. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Normal Anal Examination After Penetration: A Case Report.

PubMed

Slingsby, Brett; Goldberg, Amy

2018-03-01

Physical findings are rare after anal penetration. Furthermore, children delay in disclosing or are reticent to discuss penetration. A 12-year-old boy presented to medical care multiple times over a several-week period complaining of abdominal pain, bloody diarrhea, and poor appetite. On colonoscopy, he was found to have a cylindrical foreign body (measuring 7 cm tall and 7 cm in diameter) in his rectum, which had been present for at least 2 weeks. He initially denied knowing how the object got into his rectum and later stated that he inserted it himself out of curiosity. One week after the object was removed, follow-up examination using video colposcopy revealed a completely normal anal examination; the patient had a normal anal examination despite known anal penetration and removal of the object. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Children can have a normal anal examination despite anal penetration, and do not always disclose anal penetration. The aforementioned concepts can be applied to situations related to child sexual abuse in the emergency department, where physical examinations are frequently normal and children delay in disclosing the abuse. When there is concern for sexual abuse, even in the absence of a disclosure or examination findings, patients should be referred for a child abuse pediatrics evaluation if available. Copyright © 2017 Elsevier Inc. All rights reserved.

Fluorescence spectroscopy for diagnostic differentiation in uteri's cervix biopsies with cervical/vaginal atypical cytology.

PubMed

Rodero, Ademir Barianni; Silveira, Landulfo; Rodero, David Augusto; Racanicchi, Roberto; Pacheco, Marcos Tadeu T

2008-09-01

This work aims the diagnostic differentiation of chronic inflammation (CC), low-grade Intraepithelial squamous lesions (LGSIL) and high-grade intraepithelial squamous lesions (HGSIL) in biopsies of cervix of uterus from patients with atypias (ASC-US and ASC-H) and lesions (LGSIL and HGSIL), traced in the cervical/vaginal cytology by using Laser-Induced Fluorescence Spectroscopy (LIFS), with 488 nm excitation wavelength. Ninety seven biopsies from 32 patients with atypical cervical/vaginal cytology were collected. The biopsies were guided by colposcopy and taken at the squamous-columnar junction. Fluorescence emission spectra of each biopsy were collected by means of an optical fiber cable coupled to an argon laser at 488 nm as excitation source and addressed to a spectrograph and CCD camera/controller. Spectra were separated into three groups, CC, LGSIL and HGSIL, based on the cytopathology. It was detected similar mean spectra profiles for CC and LGSIL, and differences for HGSIL. An algorithm was developed for tissue classification based on the intensity of the multiplication of each spectrum by the mean spectrum of each group, searching for a discriminator that would address this spectral difference. The sensitivity and specificity of HGSIL identification, compared to CC and LGSIL was 89% and 100%, respectively. The LIFS using excitation wavelength of 488 nm could be used to differentiate HGSIL lesions from LGSIL and CC inflammation, and could help a precocious and less invasive diagnosis of cervix lesions.

Surgical Lasers In Gynecology

NASA Astrophysics Data System (ADS)

Schellhas, Helmut F.; Barnes, Alfonso E.

1982-12-01

Multipurpose surgical CO2 lasers marketed in the USA have been developed to be applicable to a variety of surgical procedures in many surgical fields. They are all suited for endoscopic surgical procedures and can be fitted to all standard surgical microscopes. They all can adjust the focal length of the laser beam to the different standard focal lengths of the surgical microscope which for instance in laryngoscopy is 400 mm and in colposcopy 300 mm. One laser instrument can even change the spot size in a given focal distance which is very advantageous for some microsurgical procedures (Merrimack Laboratories 820). All multipurpose surgical CO2 laser systems provide a multi-articulated surgical arm for free-hand surgery. The surgical arms are cumbersome to use but they are adapted to the surgeons needs with ingenuity. The practicality of the multi-articulated surgical arms depends mostly on the distance of the handpiece from the surgical console which now is also overbridged by the laser tube in most surgical laser system. The spot size of the beam is variable in most handpieces by interchangeable lenses which modify the focal distance of the beam and the power density. Another common feature in all systems is a coaxial He-Ne pilot light which provides a red spot which unfortunately becomes invisible in a bleeding surgical field. Most surgical laser systems have a spacial mode of TEM 00 which is essential for incisional surgery. The continuous mode of beam delivery is used for incisional surgery and also for most endoscopic procedures.

Quality improvement project in cervical cancer screening: practical measures for monitoring laboratory performance.

PubMed

Tarkkanen, Jussi; Geagea, Antoine; Nieminen, Pekka; Anttila, Ahti

2003-01-01

We conducted a quality improvement project in a cervical cancer screening programme in Helsinki in order to see if detection of precancerous lesions could be influenced by external (participation rate) and internal (laboratory praxis) quality measures. In order to increase the participation rate, a second personal invitation to Pap-test was mailed to nonparticipants of the first call. In order to improve the quality of screening, the cytotechnicians monitored their performance longitudinally by recording the number of slides reviewed per day, the pick-up rate of abnormal smears, the report of the consulting cytopathologist, and the number of histologically verified lesions detected from the cases that they had screened. Regular sessions were held to compare the histological findings with the cytological findings of all cases referred for colposcopy. No pressure was applied on the cytotechnicians to ensure that they felt comfortable with their daily workload. A total of 110 000 smears were screened for cervical cancer at the Helsinki City Hospital during 1996-99. Initially, the overall participation rate increased from 62% to 71%. The number of histologically confirmed precancerous lesions (CIN 1-3) more than doubled and their detection rate increased from 0.32% to 0.72%. Continuous education and feedback from daily work performance were important, yet rather inexpensive means in increasing laboratory performance. Additional measures are needed to further increase the participation rate. Impact of the quality measures on cancer incidence needs to be assessed later on.

Application of a Telecolposcopy Program in Rural Settings.

PubMed

Hitt, Wilbur C; Low, Gordon M; Lynch, Christian E; Gauss, C Heath; Magann, Everett F; Lowery, Curtis L; Eswaran, Hari

2016-10-01

Individuals in rural areas are often restricted by the amount of physicians' availability, thus limiting access to healthcare in those settings. While Pap smear screening has increased across the United States, the rural South still reports high rates of cervical cancer and mortality. One solution to improve patient outcomes related to cervical cancer in rural settings is telecolposcopy. Women with abnormal Pap results or an abnormal visual examination needing an evaluation by colposcopy were referred to a hospital-based telecolposcopy program. Descriptive data are provided that include patients' access to care based on travel time and transportation costs. Over a 15-month time period, 940 unique patients were seen using telecolposcopy. Telecolposcopy was done at eight spoke sites across Arkansas representing patients from 72 of the 75 counties. Data for risk factors that include smoking, first sexual experience, and number of sexual partners in past 12 months and in a lifetime are discussed. Pap results and impression are provided. In addition, avoided transportation costs and travel time have been calculated and included. Cervical cancer is important public health concern especially for women residing in rural areas. We were able to demonstrate that our telecolposcopy program has provided sustainability statewide since its inception and that patients are willing to participate. In addition to providing increased access to care, the program also reduced travel time and costs associated with a face-to-face visit. Telecolposcopy should be further explored and utilized in rural settings as a way to reduce patient costs and improve cervical cancer outcomes.

The impact of a community intervention to improve cervical cancer screening uptake in the Amazon region of Brazil.

PubMed

von Zuben, Marcus Vinicius; Derchain, Sophie Françoise; Sarian, Luis Otávio; Westin, Maria Cristina; Thuler, Luiz Claudio Santos; Zeferino, Luiz Carlos

2007-01-04

In the northern region of Brazil, cervical cancer is the most important cause of cancer-related deaths among women. There is considerable likelihood, however, that official incidence and mortality figures are greatly underestimated. The aim of this study was to estimate the repercussions from improvement in cervical cancer screening programs on the incidence of pre-invasive and invasive cervical lesions in a municipality in this region. This was a quasi-experimental study that assessed process dimensions relevant to the program objectives. The study comprised a sample of 2,226 women seen at primary healthcare units in Cruzeiro do Sul, a small city in the Brazilian Amazon region, from April 2003 to July 2004. Women were recruited through local radio advertisements and by oral communication from the investigators. The women answered a structured questionnaire and underwent pelvic examination, which included Papanicolaou (Pap) smears and naked-eye inspection of the cervix after applying diluted acetic acid. Women with positive Pap smears or abnormal gynecological examination were referred for colposcopy and possible biopsy, diathermic large loop excision of the transformation zone or conization. The results obtained were compared with historical official data retrieved from the Brazilian Ministry of Health's database. Intervention resulted in a 40% increase in positive Pap smears and detection of cancer was nine times higher than had been observed in routine screening. Detection of pre-invasive and invasive cervical lesions in the intervention group was remarkably higher than among women seen during routine screening.

JAM3 methylation status as a biomarker for diagnosis of preneoplastic and neoplastic lesions of the cervix

PubMed Central

Yin, Aijun; Zhang, Qing; Kong, Xiangnan; Jia, Lin; Yang, Ziyan; Meng, Lihua; Li, Li; Wang, Xiao; Qiao, Yunbo; Lu, Nan; Yang, Qifeng; Shen, Keng; Kong, Beihua

2015-01-01

DNA methylation is clinically relevant to important tumorigenic mechanisms. This study evaluated the methylation status of candidate genes in cervical neoplasia and determined their diagnostic performance in clinical practice. Cervical cancer and normal cervix tissue was used to select the top 5 discriminating loci among 27 loci in 4 genes (CCNA1, CADM1, DAPK1, JAM3), and one locus of JAM3 (region M4) was identified and confirmed with 267 and 224 cervical scrapings from 2 independent colposcopy referral studies. For patients with atypical squamous cells of unknown significance and those with low-grade squamous intraepithelial lesion, with JAM3-M4 compared to a triage marker of hrHPV testing, the specificity for cervical intraepithelial neoplasia 3 CIN3 and cancer cases (CIN3+) / no neoplasia and CIN1 (CIN1−) was significantly increased, from 21.88 to 81.82 and 15.38 to 85.18, respectively. The corresponding positive predictive value (PPV) was increased from 26.47 to 57.14 and 18.52 to 63.64, respectively. For hrHPV-positive patients, compared to a triage marker of cytology testing, JAM3-M4 showed increased specificity and PPV, from 30.67 to 87.65 and 38.82 to 82.14, respectively. We assessed whether JAM3-M4 could distinguish productive from transforming CIN2; the coincidence rate of JAM3-M4 and P16 was as high as 60.5%. PMID:26517242

High Risk Human Papillomavirus Persistence Among HIV-infected Young Women in South Africa

PubMed Central

Adler, David; Wallace, Melissa; Bennie, Thola; Abar, Beau; Sadeghi, Rokhsanna; Meiring, Tracy; Williamson, Anna-Lise; Bekker, Linda-Gail

2015-01-01

Objectives Persistence of infection with high-risk Human papillomaviruses (HR-HPV) increases the risk of incident and progressive precancerous lesions of the cervix. Rates of HR-HPV persistence have been shown to be increased among HIV-infected adult women, however there is a paucity of literature addressing HPV persistence in the young HIV-infected population. We compared rates of HR-HPV persistence between HIV-infected and HIV-uninfected young women. Methods We obtained self-collected vaginal swabs at six-month intervals from 50 HIV-uninfected and 33 HIV-infected young women recruited through a community youth center (age 17-21 years) and compared rates of HR-HPV persistence. HR-HPV testing was conducted using the Roche’s Linear Array® HPV Test. Results Eighty-three prevalent (upon baseline testing) and incident (upon subsequent testing) individual HR-HPV infections were identified among 43 members of the cohort (23 HIV-uninfected and 20 HIV-infected). At twelve months, 19% of baseline HR-HPV infections continued to be present with a statistically significant difference between HIV-uninfected and HIV-infected participants (4% versus 31%; p=0.01). Conclusions HIV-infected young women in our cohort had a seven-fold increased rate of persistence of HR-HPV overall at 12 months indicating an increased risk for incident and progressive precancerous lesions. Identification of persistent infection with HR-HPV may complement cytological findings in determining the need for colposcopy. PMID:25697074

Prevalence of Primary HPV in Djibouti: Feasibility of Screening for Early Diagnosis of Squamous Intraepithelial Lesions.

PubMed

Petrelli, Alessio; Di Napoli, Anteo; Giorgi Rossi, Paolo; Rossi, Alessandra; Luccini, Daniele; Di Marco, Ilaria; Traoré, Amadou Laico; Gillio Tos, Anna; Trevisan, Morena; Mirisola, Concetta; Costanzo, Gianfranco

2016-10-01

In many African Sub-Saharan countries, human papilloma virus (HPV) prevalence data are not available. The current study estimated the prevalence of HPV virus in the female population of Djibouti. Approximately 1000 asymptomatic women 16 to 64 years old were enrolled from 3 of the main health structures of Djibouti in 2014 and 2015; 998 cervical samples were tested for HPV-DNA of high risk types, 499 during the first year, and 499 during the second. Positive samples were typed with an HPV genotyping kit. The women were an average age of 38.8 years (SD, 10.2); 54 women tested positive for HPV (prevalence rate, 5.4% [95% confidence interval, 4.0-6.8]). The highest prevalence was observed among the women younger than 35 years. HPV66 was the most prevalent (15.4% of the infections), followed by HPV31 and HPV52 (10.8% both) and HPV16 (9.2%). All 54 women who tested HPV-positive underwent a Pap test, which was positive in 8 cases (14.8%): 2 high-grade squamous intraepithelial lesion (HSIL) and 6 low-grade (LSIL). The HPV prevalence shows a curve by age similar to that of other African countries. The proportion of HPV16 is among the lowest ever seen in similar studies. The findings suggest to Djibouti the choice of a strategy of screening that includes forms of cytological triage, thus limiting recourse to colposcopy.

Human papilloma virus infection and cervical dysplasia.

PubMed

Melinte-Popescu, Alina; Costăchescu, Gh

2012-01-01

Pap testing is considered to be the best screening tool for cervical cancer but there is currently great interest in the possible application of human papilloma virus (HPV) testing to supplement Pap screening for cervical cancer. To determine the prevalence of high-risk HPV types in the studied population and to explore the association between high-risk HPV types and cervical dysplasia. Cross-sectional study conducted at the Iasi Cuza Voda Obstetrics-Gynecology Hospital and Suceava County Hospital. 332 women who underwent colposcopy for cervical lesions between 2006 and 2011 were included in this study. The overall prevalence of HPV was 57.23%. HPV prevalence differs significantly in the three age groups up to 50 years. It was highest in patients below the age of 40 and progressively lower with advancing age. The overall prevalence of cervical dysplasia was 56.62%. The prevalence of cervical dysplasia was highest in the age groups up to 40 years. The most important determinant of HPV infection is age. Persistence of HPV appears to be associated with progression to squamous intraepithelial lesion. Dysplasia is often missed in a cervical sample either because of human error in screening and interpretation, or because of suboptimal quality of Pap smear. Incorporation of HPV testing into the present Pap screening program has the potential of making screening for cervical cancer more effective, and a necessary prelude to assessing this is by determining the prevalence of the high-risk types.

Effects on pain and anxiety of patients viewing their cystoscopy in addition to a detailed explanation: a controlled study.

PubMed

Kesari, D; Kovisman, V; Cytron, S; Benjamin, J

2003-11-01

To compare the effect of allowing patients to watch their cystoscopy on closed-circuit television and with an explanation during the procedure, with an explanation alone, as involving patients in the process of minimally invasive procedures like colonoscopy or colposcopy has been reported to alleviate pain and anxiety, but these effects may differ in patients who desire participation and those who do not. Of 51 patients undergoing cystoscopy for the first time, 27 watched the procedure and received explanations, and 24 received explanations alone. They completed an anxiety questionnaire and visual analogue scales (VAS) of anxiety before and after the procedure. Before the procedure they also completed an assessment of desire to be involved in medical decisions and procedures (Kranz Health Opinion Survey, KHOS), and afterwards recorded the pain they had experienced on a scale of 1-10. Anxiety (assessed by VAS) declined after the procedure (P < 0.001) but the anxiety questionnaire showed no change. There was a positive correlation between the KHOS and VAS after the procedure; the more the patient was an 'information seeker' the higher the anxiety. Neither pain nor anxiety were affected by watching the monitor, whether or not KHOS scores were entered as a cofactor. Age and sex had no effect on the results. There were no complications. There was no effect of watching the cystoscopy on anxiety and pain. Possibly the explanation received by both groups left no room for further improvement in the intervention group.

Epithelial cancers and photon migration: Monte Carlo simulations and diffuse reflectance measurements

NASA Astrophysics Data System (ADS)

Tubiana, Jerome; Kass, Alex J.; Newman, Maya Y.; Levitz, David

2015-07-01

Detecting pre-cancer in epithelial tissues such as the cervix is a challenging task in low-resources settings. In an effort to achieve low cost cervical cancer screening and diagnostic method for use in low resource settings, mobile colposcopes that use a smartphone as their engine have been developed. Designing image analysis software suited for this task requires proper modeling of light propagation from the abnormalities inside tissues to the camera of the smartphones. Different simulation methods have been developed in the past, by solving light diffusion equations, or running Monte Carlo simulations. Several algorithms exist for the latter, including MCML and the recently developed MCX. For imaging purpose, the observable parameter of interest is the reflectance profile of a tissue under some specific pattern of illumination and optical setup. Extensions of the MCX algorithm to simulate this observable under these conditions were developed. These extensions were validated against MCML and diffusion theory for the simple case of contact measurements, and reflectance profiles under colposcopy imaging geometry were also simulated. To validate this model, the diffuse reflectance profiles of tissue phantoms were measured with a spectrometer under several illumination and optical settings for various homogeneous tissues phantoms. The measured reflectance profiles showed a non-trivial deviation across the spectrum. Measurements of an added absorber experiment on a series of phantoms showed that absorption of dye scales linearly when fit to both MCX and diffusion models. More work is needed to integrate a pupil into the experiment.

Near-infrared Raman spectroscopy for assessing biochemical changes of cervical tissue associated with precarcinogenic transformation.

PubMed

Duraipandian, Shiyamala; Mo, Jianhua; Zheng, Wei; Huang, Zhiwei

2014-11-07

Raman spectroscopy measures the inelastically scattered light from tissue that is capable of identifying native tissue biochemical constituents and their changes associated with disease transformation. This study aims to characterize the Raman spectroscopic properties of cervical tissue associated with the multi-stage progression of cervical precarcinogenic sequence. A rapid-acquisition fiber-optic near-infrared (NIR) Raman diagnostic system was employed for tissue Raman spectral measurements at 785 nm excitation. A total of 68 Raman spectra (23 benign, 29 low-grade squamous intraepithelial lesions (LSIL) and 16 high grade squamous intraepithelial lesions (HSIL)) were measured from 25 cervical tissue biopsy specimens, as confirmed by colposcopy-histopathology. The semi-quantitative biochemical modeling based on the major biochemicals (i.e., DNA, proteins (histone, collagen), lipid (triolein) and carbohydrates (glycogen)) in cervical tissue uncovers the stepwise accumulation of biomolecular changes associated with progressive cervical precarcinogenesis. Multi-class partial least squares-discriminant analysis (PLS-DA) together with leave-one tissue site-out, cross-validation yielded the diagnostic sensitivities of 95.7%, 82.8% and 81.3%; specificities of 100.0%, 92.3% and 88.5%,for discrimination among benign, LSIL and HSIL cervical tissues, respectively. This work suggests that the Raman spectral biomarkers have identified the potential to be used for monitoring the multi-stage cervical precarcinogenesis, forming the foundation of applying NIR Raman spectroscopy for the early diagnosis of cervical precancer in vivo at the molecular level.

Retrospective study of the influence of HPV persistence on outcomes among women with high-risk HPV infections and negative cytology.

PubMed

Bogani, Giorgio; Taverna, Francesca; Lombardo, Claudia; Borghi, Chiara; Martinelli, Fabio; Signorelli, Mauro; Leone Roberti Maggiore, Umberto; Chiappa, Valentina; Scaffa, Cono; Ditto, Antonino; Lorusso, Domenica; Raspagliesi, Francesco

2017-07-01

To evaluate the outcomes of women diagnosed with high-risk HPV without cytology evidence of cervical dysplasia. The present retrospective observational study enrolled consecutive women aged at least 18 years diagnosed with high-risk HPV types with negative cytology results at the National Cancer Institute, Milan, Italy, between January 1, 2005, and December 31, 2015. The development of cervical intraepithelial neoplasia (CIN) was assessed. There were 212 patients with high-risk HPV infections with negative cytology included in the analysis. After a mean ± SD follow-up period of 48 ± 33 months, 65 (30.7%) and 26 (12.3%) patients had developed cytologic or histologic cervical dysplasia (low-grade squamous intraepithelial lesion [LSIL]/CIN1+) and high-grade cervical dysplasia (CIN2+), respectively. No patients had invasive cancer. No correlations were observed between type-specific HPV infections and LSIL/CIN1+ and CIN2+. HPV persistence correlated with both LSIL/CIN1+ (P<0.001) and CIN2+ (P<0.001) in univariate analyses; a 6-month increase in HPV persistence was associated with increased risk of developing LSIL/CIN1+ (P=0.010) and CIN2+ (P=0.012) in multivariate analyses. Regardless of cytology findings, patients diagnosed with high-risk HPV types should receive strict colposcopy follow-up, particularly with persistent HPV infections. Further prospective studies are needed to defined optimal surveillance strategies for these patients. © 2017 International Federation of Gynecology and Obstetrics.

Towards improving cervical cancer screening in Nigeria: a review of the basics of cervical neoplasm and cytology.

PubMed

Dim, C C

2012-01-01

Cervical cancer screening is the key to reducing the incidence and mortality of cervical cancer in developing countries. In the absence of a national screening program, healthcare givers in Nigeria are encouraged to routinely inform and screen eligible women. This review aims at equipping health workers for this task by re-educating them on the basics of the disease and its screening by cytology. Relevant texts and online databases including Pubmed, African Journal Online, and Google Scholar, were searched for relevant literature on the subject area. Persistent infection by a high-risk human papilloma virus, especially types 16 and 18, is necessary for the development of cervical cancer. The exfoliation of cells from the metaplastic squamous cells of transformation zone of the cervix is the basis of cervical cytology. Organized Pap screening reduces the incidence and mortality of cervical cancer, but screening protocols vary. Nevertheless, annual screening is not recommended except for high-risk women such as HIV-positive women. Abnormal Pap smear results are currently reported using either the Bethesda System or the British Society for Clinical Cytology classification, and colposcopy with or without biopsy are necessary when indicated. In conclusion, the use of cervical cytology to detect pre-cancerous lesions followed by an appropriate treatment when necessary is the key to reducing invasive cervical cancer. The task of provider-initiated counseling and testing for cervical cancer by health practitioners requires update on the current etio-pathology of cervical cancer, and its screening as reviewed.

Scattering and absorption measurements of cervical tissues measures using low cost multi-spectral imaging

NASA Astrophysics Data System (ADS)

Bernat, Amir S.; Bar-Am, Kfir; Cataldo, Leigh; Bolton, Frank J.; Kahn, Bruce S.; Levitz, David

2018-02-01

Cervical cancer is a leading cause of death for women in low resource settings. In order to better detect cervical dysplasia, a low cost multi-spectral colposcope was developed utilizing low costs LEDs and an area scan camera. The device is capable of both traditional colposcopic imaging and multi-spectral image capture. Following initial bench testing, the device was deployed to a gynecology clinic where it was used to image patients in a colposcopy setting. Both traditional colposcopic images and spectral data from patients were uploaded to a cloud server for remote analysis. Multi-spectral imaging ( 30 second capture) took place before any clinical procedure; the standard of care was followed thereafter. If acetic acid was used in the standard of care, a post-acetowhitening colposcopic image was also captured. In analyzing the data, normal and abnormal regions were identified in the colposcopic images by an expert clinician. Spectral data were fit to a theoretical model based on diffusion theory, yielding information on scattering and absorption parameters. Data were grouped according to clinician labeling of the tissue, as well as any additional clinical test results available (Pap, HPV, biopsy). Altogether, N=20 patients were imaged in this study, with 9 of them abnormal. In comparing normal and abnormal regions of interest from patients, substantial differences were measured in blood content, while differences in oxygen saturation parameters were more subtle. These results suggest that optical measurements made using low cost spectral imaging systems can distinguish between normal and pathological tissues.

Cervical cancer screening among women who attend sexually transmitted diseases (STD) clinics: background paper for 2010 STD Treatment Guidelines.

PubMed

Datta, S Deblina; Saraiya, Mona

2011-12-01

In April 2008, experts reviewed updates on sexually transmitted disease (STD) prevention and treatment in preparation for the revision of the Centers for Disease Control and Prevention (CDC) STD Treatment Guidelines. This included a review of cervical cancer screening in the STD clinical setting. Key questions were identified with assistance from an expert panel. Reviews of the literature were conducted using the PubMed computerized database and shared with the panel. Updated information was incorporated in the 2010 CDC STD Treatment Guidelines. We recommend that STD clinics offering cervical screening services screen and treat women according to guidelines by the American College of Obstetrics and Gynecology, the American Cancer Society, the US Preventive Services Task Force, and the American Society for Colposcopists and Cervical Pathologists. New to the 2010 guidelines are higher age for initiating cervical screening (age ≥ 21 years) and less frequent intervals of screening (at least every 3 years). New recommendations include new technologies, such as liquid-based cytology and high-risk human papillomavirus (HPV) DNA tests. Liquid-based technologies are not recommended over conventional testing. HPV DNA tests are recommended as adjunct tests and with new indications for use in cervical screening and management. Stronger recommendations were issued for STD clinics offering cervical screening services to have protocols in place for follow-up of test results and referral (eg, colposcopy). Important additions to the 2010 STD Treatment Guidelines include information on updated algorithms for screening and management of women and recommendations for use of liquid-based cytology and high-risk HPV testing.

Clinical and Economic Value of p16INK4a for the Differential Diagnosis of Morphologic Cervical Intraepithelial Neoplasia 2.

PubMed

Fishkel, Vanina S; Monge, Fernando C; von Petery, Felicitas M; Tapper, Karen E; Peña, Teresa M; Torres, Florencia; Poletta, Fernando A; Elgart, Jorge F; Avagnina, Alejandra; Denninghoff, Valeria

2018-05-04

The detection of high-grade intraepithelial lesions requires highly sensitive and specific methods that allow more accurate diagnoses. This contributes to a proper management of preneoplastic lesions, thus avoiding overtreatment. The purpose of this study was to analyze the value of immunostaining for p16 in the morphologic assessment of cervical intraepithelial neoplasia 2 lesions, to help differentiate between low-grade (p16-negative) and high-grade (p16-positive) squamous intraepithelial lesions. The direct medical cost of the treatment of cervical intraepithelial neoplasia 2 morphologic lesions was estimated. A retrospective observational cross-sectional study was carried out. This study analyzed 46 patients treated with excisional procedures because of cervical intraepithelial neoplasia 2 lesions, using loop electrosurgical excision procedures. Immunostaining for the biomarker was performed. For the estimation of overtreatment, percentages (%) and their 95% confidence interval were calculated. Of the 41 patients analyzed, 32 (78%) showed overexpression of p16 and 9 (22%) were negative (95% confidence interval, 11%-38%). Mean follow-up was 2.9 years, using cervical cytology testing (Pap) and colposcopy. High-risk human papillomavirus DNA tests were performed in 83% of patients. These retrospective results reveal the need for larger biopsy samples, which would allow a more accurate prediction of lesion risk. Considering the cost of p16 staining, and assuming the proper management of the low-grade lesion, an average of US$919 could be saved for each patient with a p16-negative result, which represents a global direct cost reduction of 10%.

Cellphone based mobile colposcope for the evaluation of women with abnormal cervical cancer screening

NASA Astrophysics Data System (ADS)

Kahn, Bruce S.; Kass, Alex J.; Waalen, Jill; Levitz, David

2015-03-01

Objective: Compare an inexpensive cell-phone based Mobile Colposcope, with a standard colposcope in the evaluation of women with abnormal Pap smear screening. Methodology: The study was a prospective, parallel noninferiority trial. Thirty women underwent colposcopy for the evaluation of an abnormal Pap smear. After application of acetic acid, images of the cervix were obtained with both a standard colposcope and the Mobile Colposcope. An additional set of images using both devices were obtained using the red-free (green filter) mode. Eight experienced gynecologists then evaluated 100 paired images (plain and green filter) from two different sites in random order using a web based assessment program. After reviewing each set of paired images, the expert would make an assessment of: 1) normal (no biopsy/ random biopsy), or 2) abnormal. For abnormal images, the expert then electronically marked the site(s) on the image where a biopsy was recommended. In image analysis, the cervical image was divided into 12 radial sectors and the marked sites for biopsy on the matched pairs were compared. Matched pairs that were considered normal, or those where biopsy site recommendations were within +/- 30° were considered equivalent; unmatched biopsy sites were considered non-equivalent. Results were compared using Wilcoxon Matched Pairs Signed Ranks Test. Expert assessment of Mobile Colposcope images compared with assessment by standard colposcope is currently onging. Conclusions: if the Mobile Colposcope demonstrates non-inferiority to imaging obtained with a standard colposcope and due to its low cost, it has the potential help improve cervical cancer screening in low resource settings.

Differential proteins among normal cervix cells and cervical cancer cells with HPV-16 infection, through mass spectrometry-based Proteomics (2D-DIGE) in women from Southern México.

PubMed

Serafín-Higuera, Idanya; Garibay-Cerdenares, Olga Lilia; Illades-Aguiar, Berenice; Flores-Alfaro, Eugenia; Jiménez-López, Marco Antonio; Sierra-Martínez, Pavel; Alarcón-Romero, Luz Del Carmen

2016-01-01

Cervical cancer (CC) is the fourth most common cancer in women worldwide with an estimated 528,000 new cases in 2012. The same year México had an incidence of 13,960 and a mortality of 4769 cases. There are several diagnosis methods of CC; among the most frequents are the conventional Pap cytology (Pap), colposcopy, and visual inspection with acetic acid (VIA), histopathological examination, tests of imaging and detection of high-risk papilloma virus (HR-HPV) with molecular tests (PCR, hybridization, sequencing). Proteomics is a tool for the detection of new biomarkers that can be associated with clinical stage, histological type, prognosis, and/or response to treatment. In this study we performed a comparative analysis of CC cells with normal cervical cells. The proteomic analysis was carried out with the fluorescent two-dimensional electrophoresis (2D-DIGE) technique to subsequently identify differential protein profiles using Decyder Software, and the selected proteins were identified by Mass Spectrometry (MALDI-TOF). The proteins that showed an increased expression in cervical cancer in comparison with normal cervix cells were: Mimecan, Actin from aortic smooth muscle and Lumican. While Keratin, type II cytoskeletal 5, Peroxiredoxin-1 and 14-3-3 protein sigma showed a decrease in their protein expression level in cervical cancer in comparison with normal cervix cells. Thus, this study was successful in identifying biomarker signatures for cervical cancer, and might provide new insights into the mechanism of CC progression.

[Human papillomavirus testing in cervical cancer screening at a public health service of Santiago, Chile].

PubMed

Terrazas, Solana; Ibáñez, Carolina; Lagos, Marcela; Poggi, Helena; Brañes, Jorge; Barriga, María Isabel; Cartagena, Jaime; Núñez, Felipe; González, Francisca; Cook, Paz; Van De Wyngard, Vanessa; Ferreccio, Catterina

2015-01-01

Molecular techniques for human papillomavirus (HPV) detection have a good performance as screening tests and could be included in cervical cancer early detection programs. We conducted a population-based trial comparing HPV detection and Papanicolaou as primary screening tests, in a public health service in Santiago, Chile. To describe the experience of implementing this new molecular test and present the main results of the study. Women aged 25 to 64 enrolled in three public health centers were invited to participate. In all women, samples were collected for Papanicolaou and HPV DNA testing, and naked-eye visual inspection of the cervix with acetic acid was performed. Women with any positive screening test were referred to the local area hospital for diagnostic confirmation with colposcopy and biopsy of suspicious lesions. Screening results were obtained for 8265 women, of whom 931 (11.3%) were positive to any test. The prevalence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was 1.1%; nine women had invasive cervical cancer. Sensitivities for the detection of CIN2+ were 22.1% (95% confidence interval (CI) 16.4-29.2) for Papanicolaou and 92.7% (95% CI 84.4-96.8) for HPV testing; specificities were 98.9% (95% CI 98.7-99.0) and 92.0% (95% CI 91.4-92.6) respectively. This experience showed that the implementation of a molecular test for cervical cancer screening is not a major challenge in Chile: it was well accepted by both the health team and the participants, and it may improve the effectiveness of the screening program.

[Implementation of cytology images classification--the Bethesda 2001 System--in a group of screened women from Podlaskie region--effect evaluation].

PubMed

Zbroch, Tomasz; Knapp, Paweł Grzegorz; Knapp, Piotr Andrzej

2007-09-01

Increasing knowledge concerning carcinogenesis within cervical epithelium has forced us to make continues modifications of cytology classification of the cervical smears. Eventually, new descriptions of the submicroscopic cytomorphological abnormalities have enabled the implementation of Bethesda System which was meant to take place of the former Papanicolaou classification although temporarily both are sometimes used simultaneously. The aim of this study was to compare results of these two classification systems in the aspect of diagnostic accuracy verified by further tests of the diagnostic algorithm for the cervical lesion evaluation. The study was conducted in the group of women selected from general population, the criteria being the place of living and cervical cancer age risk group, in the consecutive periods of mass screening in Podlaski region. The performed diagnostic tests have been based on the commonly used algorithm, as well as identical laboratory and methodological conditions. Performed assessment revealed comparable diagnostic accuracy of both analyzing classifications, verified by histological examination, although with marked higher specificity for dysplastic lesions with decreased number of HSIL results and increased diagnosis of LSILs. Higher number of performed colposcopies and biopsies were an additional consequence of TBS classification. Results based on Bethesda System made it possible to find the sources and reasons of abnormalities with much greater precision, which enabled causing agent treatment. Two evaluated cytology classification systems, although not much different, depicted higher potential of TBS and better, more effective communication between cytology laboratory and gynecologist, making reasonable implementation of The Bethesda System in the daily cytology screening work.

Specific features of cytological and colposcopical pattern in pregnant women with benign cervix uteri pathology in anamnesis.

PubMed

Bysaha, Nataliya Yu

2016-01-01

a tendency of increasing incidence of the cervix uteri precancer and cancer in women of reproductive age is noticed recently being related to the growth of number of the sexually-transmitted infections. The cervix uteri pathology incidence in women of fertile age is 20-25%. to study the specific features of the cytological and colposcopical pattern in pregnant patients with benign cervix uteri pathology in the anamnesis and the character of its change post partum. we have examined 195 women during their pregnancy and 3-5 months post partum. All pregnant women, alongside with generally accepted clinical and laboratory examinations, were subjected to the simple and extended colposcopy, cytology of the targeted smears and, according to indications, the histological studies of bioptate. according to the results of the colcoscopical studies and the signs of the cervix uteri pathology found, the patients were divided into several groups. A control group included 49 pregnant women. The clinical and instrumental examination of 146 women with cervix uteri pathology has been carried out both during pregnancy and post partum. the structure of the clinical forms of benign and premalignant changes in the cervix uteri epithelium in pregnant patients has been found. Specific features of the cytological and colposcopical pattern in pregnant patients with benign cervix uteri pathology in anamnesis have been studied. The relationship between the parity of pregnancy, delivery, route of delivery and regress of both benign and premalignant changes in the cervix uteri epithelium 3-5 months post partum has been determined.

Human papillomavirus type-16 variants in Quechua aboriginals from Argentina.

PubMed

Picconi, María Alejandra; Alonio, Lidia Virginia; Sichero, Laura; Mbayed, Viviana; Villa, Luisa Lina; Gronda, Jorge; Campos, Rodolfo; Teyssié, Angélica

2003-04-01

Cervical carcinoma is the leading cause of cancer death in Quechua indians from Jujuy (northwestern Argentina). To determine the prevalence of HPV-16 variants, 106 HPV-16 positive cervical samples were studied, including 33 low-grade squamous intraepithelial lesions (LSIL), 28 high-grade squamous intraepithelial lesions (HSIL), 9 invasive cervical cancer (ICC), and 36 samples from women with normal colposcopy and cytology. HPV genome variability was examined in the L1 and E6 genes by PCR-hybridization. In a subset of 20 samples, a LCR fragment was also analyzed by PCR-sequencing. Most variants belonged to the European branch with subtle differences that depended on the viral gene fragment studied. Only about 10% of the specimens had non-European variants, including eight Asian-American, two Asian, and one North-American-1. E6 gene analysis revealed that 43% of the samples were identical to HPV-16 prototype, while 57% corresponded to variants. Interestingly, the majority (87%) of normal smears had HPV-16 prototype, whereas variants were detected mainly in SIL and ICC. LCR sequencing yielded 80% of variants, including 69% of European, 19% Asian-American, and 12% Asian. We identified a new variant, the Argentine Quechua-51 (AQ-51), similar to B-14 plus two additional changes: G7842-->A and A7837-->C; phylogenetic inference allocated it in the Asian-American branch. The high proportion of European variants may reflect Spanish colonial influence on these native Inca descendants. The predominance of HPV-16 variants in pathologic samples when compared to normal controls could have implications for the natural history of cervical lesions. Copyright 2003 Wiley-Liss, Inc.

Predicting Factors for High-Grade Cervical Dysplasia in Women With Low-Grade Cervical Cytology and Nonvisible Squamocolumnar Junction.

PubMed

Bogani, Giorgio; Taverna, Francesca; Lombardo, Claudia; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Leone Roberti Maggiore, U; Mosca, Lavinia; Sabatucci, Ilaria; Scaffa, Cono; Lorusso, Domenica; Raspagliesi, Francesco

2018-01-01

To assess the risk of developing high-grade cervical dysplasia among women with low-grade cervical cytology and nonvisible squamocolumnar junction (SCJ) at colposcopic examination. Data of consecutive women with low-grade intraepithelial lesion(≤LSIL) undergoing colposcopic examination, which was unsatisfactory (due to the lack of the visualization of the entire SCJ), were retrospectively reviewed. The risk of developing high-grade cervical intraepithelial neoplasia (CIN2+) was assessed using Kaplan-Meier and Cox models. Data of 86 women were retrieved. Mean (standard deviation [SD]) age was 36.3 (13.4) years. A total of 71 (82.5%) patients had high-risk human papillomavirus (HR-HPV) at the time of diagnosis. Among the 63 patients undergoing repetition of HPV testing, 15 (24%) and 48 (76%) women had positive and negative tests for HR-HPV at 12 months, respectively. We observed that 5 (33%) of 15 patients with HPV persistence developed CIN2+, while only 1 (2%) patient of 48 patients without HPV persistence developed CIN2+ (odds ratio [OR]: 23.5; 95% confidence interval [CI]: 2.46-223.7; P < .001). The length of HR-HPV persistence correlated with an increased risk of developing CIN2+ ( P < .001; P for trend). High-risk HPV persistence is the only factor predicting for CIN2+ (hazard ratio: 3.19; 95% CI: 1.55-6.57; P = .002). High-risk HPV persistence predicts the risk of developing CIN2+ in patients with unsatisfactory colposcopic examination. Further studies are warranted in order to implement the use of HPV testing in patients with unsatisfactory colposcopy.

Skinning vulvectomy for the treatment of vulvar intraepithelial neoplasia 2-3: a study of 21 cases.

PubMed

Ayhan, A; Tuncer, Z S; Doğan, L; Yüce, K; Küçükali, T

1998-01-01

Twenty-one cases of patients with vulvar intraepithelial neoplasia (VIN) 2-3 were reviewed. The mean age at diagnosis was 45.4 years. All of the patients presented with vulvar pruritus. Five of the patients had hypertension, two had coronary heart disease and two had diabetes mellitus as complicating medical illnesses. None of the patients had history or evidence of vaginal intraepithelial neoplasia (VAIN) or cervical intraepithelial neoplasia (CIN), and only one patient had invasive cervical cancer at diagnosis. Provided the histology confirmed VIN, the patients were subjected to a skinning vulvectomy procedure. Of the patients, 15 (71.4%) had VIN 2, and the remaining 6 (28.6%) had VIN 3 at preoperative evaluation. Histologic analysis of skinning vulvectomy specimens revealed no evidence of neoplasia in three patients (14.2%). Multifocality was observed in only three patients (14.2%). The areas involved were the perineum in four patients, labia in 15 and clitoris in two patients. Associated vulvar pathologies were condyloma acuminata in one, squamous vulvar hyperplasia in three and lichen sclerosus with squamous hyperplasia in one patient. The complications of the procedure included febrile morbidity in three patients and minor wound break-down in one patient. None of the patients in this series experienced recurrence. Skinning vulvectomy seems to have a high success rate in treatment of VIN 2-3 with minimal postoperative complications and satisfactory cosmetic results. However, observation of only three patients with multifocal lesions as well as no patient with invasive cancer adds credence to an ablative procedure after appropriate evaluation under colposcopy.

Human papillomavirus infections in vulvar precancerous lesions and cancer.

PubMed

Costa, S; Syrjänen, S; Vendra, C; Chang, F; Guida, G; Hippeläinen, M; Terzano, P; Tervahauta, A; Yliskoski, M; Syrjänen, K

1995-04-01

To elucidate some of the recently arisen issues related to the bimodal disease pattern of vulvar intraepithelial lesions (VIN) and vulvar cancer, a series of 27 consecutive women with vulvar symptoms was analyzed for human papillomavirus (HPV) involvement by colposcopy, light microscopy and in situ hybridization (ISH) for HPV types 6, 11, 16, 18, 31, 33 and 42. Altogether, HPV DNA was discovered in 13/27 (48.1%) of the lesions by ISH; the rest were HPV DNA negative for the seven HPV types tested. HPV DNA was present in both of two exophytic lesions (HPV 6 in condyloma and HPV 16 in verrucous cancer). Of the flat lesions, 7/13 (53.8%) were HPV DNA positive. HPV 6 was confined to low grade lesions (HPV/non-VIN and VIN 1), whereas HPV 11 was found in a case of VIN 3 as well. Of the invasive carcinomas, three of four were HPV DNA positive (2 HPV 16 and 1 HPV 31). Dystrophic changes were detected in three of four invasive carcinomas and in all three HPV 16-positive lesions. Dystrophic changes were absent in 9 of 14 (64.3%) of HPV DNA-negative lesions. Fifty percent (7/14) of vulvar warty lesions (without concomitant VIN) were found in women younger than 60. Three of four invasive carcinomas occurred in women older than 60. This small series provided additional evidence of HPV involvement in the pathogenesis of VIN lesions, and the findings support the hypothesis of a multifactorial etiology in vulvar carcinogenesis in which HPV, dystrophic changes and chronic inflammatory disease play a synergistic role.

Evolution of terminology for human-papillomavirus-infection-related vulvar squamous intraepithelial lesions.

PubMed

Wilkinson, Edward J; Cox, J Thomas; Selim, Maria Angelica; O'Connor, Dennis M

2015-01-01

The aim of this study was to review the nearly 100-year evolution of terminology applicable to oncogenic human papillomavirus (HPV)-related vulvar intraepithelial squamous lesions and present current consensus terminology. An extensive literature search of the English language was performed, which included articles that reviewed French and German publications, from 1922 to 2012. The database search was assisted by representatives of the American Society for Colposcopy and the College of American Pathologists as part of a comprehensive study and consensus effort to achieve unified terminology among gynecologists, dermatologists, pathologists, and other related experts to develop for reporting female and male lower genital and anal HPV related squamous lesions. This was done by the committee referred to as the "LAST" Committee. Some of the results and conclusions have been previously presented and published. This presentation is specifically related to vulvar squamous intraepithelial lesion (SIL)/vulvar intraepithelial neoplasia terminology. This work will review past terminology related to HPV-related vulvar SIL, beginning in 1922. The most current terminology will be presented as proposed by the LAST Committee and considered by the World Health Organization this year in accord with the US-Canadian Academy of Pathology. A consensus of terminology for HPV-related vulvar SIL has been sought for some time, and currently, some consensus has been achieved. The term "squamous intraepithelial lesion" is favored over "intraepithelial neoplasia." A 2-tier classification, of "high grade (HSIL)" or "low grade (LSIL)," is favored over a 3- or 4-tier classification. The application of this terminology will be discussed.

Clinical diagnosis of oral erosive lichen planus by direct oral microscopy

PubMed Central

Drogoszewska, Barbara; Polcyn, Adam; Michcik, Adam

2014-01-01

Introduction Direct oral microscopy is a novel, non-invasive diagnostic technique that aids clinical examination of the oral cavity. The basic principles of this method derive from colposcopy and dermoscopy. The principle is to reveal precancerous lesions of oral mucosae in their subclinical phase in order to begin their treatment as early as possible and prevent malignant transformation. Oral lichen planus (OLP) is an autoimmune, inflammatory, chronic disease affecting oral mucous membranes. Buccal mucosae are most often affected. Aim To describe the in vivo picture of erosive OLP in direct oral microscopy in terms of the pattern and density of subepithelial blood vessels, surface texture, color, transparency and borders of the lesions. The study also demonstrates the utility of the method in the selection of the most appropriate biopsy site. Material and methods A total of 30 patients with erosive OLP were examined. Clinical examination of the oral cavity with the naked eye was performed, followed by direct oral microscopy. The most appropriate biopsy sites based on both examinations were chosen for every individual and biopsies were taken for histopathological evaluation. Results Biopsies obtained based on direct oral microscopy revealed dysplasia in 16 patients (53.3%). Biopsies obtained based on clinical examination with the naked eye revealed dysplasia in 3 cases (10%). Conclusions Direct oral microscopy makes it possible to obtain a repeated picture of erosive OLP and constitutes an alternative to the clinical examination with the naked eye in election of the most appropriate biopsy site. Thus, introduction of the most accurate and early therapy is possible. PMID:25254007

Prevalence of anal cytological abnormalities in women with positive cervical cytology.

PubMed

Calore, Edenilson E; Giaccio, Claudia Maria Serafim; Nadal, Sidney R

2011-05-01

The objective of this study was to estimate the prevalence of cytological abnormalities of the anal mucosa in women with positive cervical cytology, but without macroscopic anal lesion. Ultimately we postulated if the anal mucosa may be a reservoir of HPV, which would allow the reinfection of cervix. Forty-nine patients with abnormal cervical cytology were selected for this work. In a period not exceeding one week of collecting cervix cytology, two swab specimens of the anal canal were also collected. Women diagnosed with cervical HSIL by Pap smear were referred for colposcopy with biopsy of the lesions, to confirm the cytologic diagnosis and ablation of the lesion. We demonstrated a high prevalence of anal squamous intraepithelial lesions in patients with cervical squamous intraepithelial lesions (29 of the total of 49 patients = 59.2%). Of the 20 cases of cervical LSIL, 11 (55%) had abnormal anal cytology. Of the 26 cases with cervical HSIL, 16 (61.5%) had abnormal anal cytology. So, there was a discrete higher prevalence of abnormal anal cytology in cases of high-grade cervical squamous lesions (cervical HSIL). These results help to support the hypothesis that the anal mucosa is a reservoir of HPV, which can be a source of re-infection for the cervix. However, there was no significant association between the practice of anal sex and the prevalence of anal cytological abnormalities. These facts are epidemiologically important for future programs for population eradication of cervical lesions related to HPV. Diagn. Cytopathol. 2011;39:323-327. © 2010 Wiley-Liss, Inc. Copyright © 2010 Wiley-Liss, Inc.

Acceptability of OCT and Abstinence Requirements among Women Participating in Microbicide Safety Trials

PubMed Central

Breitkopf, Carmen Radecki; Loza, Melissa; Vincent, Kathleen; Moench, Thomas; Stanberry, Lawrence R.; Rosenthal, Susan L.

2011-01-01

Background Developing effective and safe microbicides requires study procedures (e.g. technology used, abstinence requirements, and product use) that are acceptable to participants. Methods Thirty women completed 4 study visits including pelvic examination, colposcopy, optical coherence tomography (OCT), and semi-structured, qualitative interviews. Additional requirements included abstinence (for approximately 16 days) and twice daily vaginal product use (for 5.5 days). Interviews were audio-recorded, transcribed, and analyzed using framework analysis. Themes addressing OCT experiences, acceptability of abstinence, and vaginal product use were examined. Results OCT was viewed favorably as an imaging technology. Some women reported feeling the fiber-optic probe “poking” them and over one-third spontaneously reported feeling pressure or pinching upon rotation of the speculum in connection with the OCT evaluation. Compliance with vaginal gel use was high, but for many women assigned to use a product containing nonoxynol-9 (versus placebo), the post-product use exam was more uncomfortable, relative to the initial exam or one week following product discontinuation. Nearly all women experienced product leakage; acceptability of leakage varied. Two women were not abstinent and several more found abstinence challenging. Some women involved their partner in decision making regarding trial enrollment. Strategies to remain abstinent included participating when the partner was away, avoiding early intimacy, and engaging in alternative sexual activities. Conclusions Qualitative interviews in early-phase studies provide insights and capture information that would be missed by behavioral inference alone. Understanding participant’s experiences is important in order to provide anticipatory guidance and plan future microbicide studies that facilitate adherence with trial requirements. PMID:22183842

The clinical effectiveness and cost-effectiveness of primary human papillomavirus cervical screening in England: extended follow-up of the ARTISTIC randomised trial cohort through three screening rounds.

PubMed

C Kitchener, Henry; Canfell, Karen; Gilham, Clare; Sargent, Alexandra; Roberts, Chris; Desai, Mina; Peto, Julian

2014-04-01

The ARTISTIC (A Randomised Trial In Screening To Improve Cytology) trial originally reported after two rounds of primary cervical screening with human papillomavirus (HPV). Extended follow-up of the randomised trial cohort through a third round could provide valuable insight into the duration of protection of a negative HPV test, which could allow extended screening intervals. If HPV primary screening is to be considered in the national programme, then determining its cost-effectiveness is key, and a detailed economic analysis using ARTISTIC data is needed. (1) To determine the round 3 and cumulative rates of cervical intraepithelial neoplasia (CIN) grade 2 or worse (2+) and CIN grade 3 or worse (CIN3+) between the revealed and concealed arms of ARTISTIC after three screening rounds over 6 years. (2) To compare the cumulative incidence of CIN2+ over three screening rounds following negative screening cytology with that following negative baseline HPV. (3) To determine whether or not HPV screening could safely extend the screening interval from 3 to 6 years. (4) To study the potential clinical utility of an increased cut-off of 2 relative light unit/mean control (RLU/Co) for Hybrid Capture 2 (HC2) and HPV genotyping in primary cervical screening. (5) To determine the potential impact of HPV vaccination with Cervarix™ in terms of preventing abnormal cytology and CIN2+. (6) To determine the cost-effectiveness of HPV primary screening compared with current practice using cervical cytology in England. The ARTISTIC study cohort was recalled for a third round of screening 3 years after round 2 and 6 years following their enrolment to the study. Both arms of the original trial used a single protocol during round 3. ARTISTIC study cohort undergoing cervical screening in primary care in Greater Manchester, UK. Between July 2007 and September 2009, 8873 women participated in round 3; 6337 had been screened in round 2 and 2536 had not been screened since round 1. All women underwent liquid-based cytology and HPV testing and genotyping. Colposcopy was offered to women with moderate dyskaryosis or worse and with HPV-positive mild dyskaryosis/borderline changes. Women with negative cytology or HPV-negative mild dyskaryosis/borderline changes were returned to routine recall. Principal outcomes were cumulative rates of CIN2+ over three screening rounds by cytology and HPV status at entry; HPV type specific rates of CIN2+; effect of age on outcomes correlated with cytology and HPV status; comparison of HC2 cut-off RLU/Co of both 1 and 2; and cost-effectiveness of HPV primary screening. The median duration of follow-up was 72.7 months in round 3. Over the three screening rounds, there was no significant difference in CIN2+ [odds ratio (OR): 1.06, 95% confidence interval (CI) 0.89 to 1.26, p = 0.5)] or CIN3+ (OR: 0.90, 95% CI 0.72 to 1.14, p = 0.4) rates between the trial arms (revealed vs. concealed). Overall, 16% of women were HC2 positive at entry, decreasing from 40% in women aged 20-24 years to around 7% in women aged over 50 years. Abnormal cytology rates at entry were 13% for borderline+ and 2% for moderate+ cytology. Following positive cytology at entry, the cumulative rate of CIN2+ was 20.5%, and was 20.1% following a HPV-positive result at baseline. The cumulative CIN2+ rate for women who were HPV negative at baseline was only 0.87% (95% CI 0.70% to 1.06%) after three rounds of screening, significantly lower than that for women with negative cytology, which was 1.41% (95% CI 1.19% to 1.65%). Women who were HPV negative at baseline had similar protection from CIN2+ after 6 years as women who were cytology negative at baseline after 3 years. Women who were HPV positive/cytology negative at baseline had a cumulative CIN2+ rate at 6 years of 7.7%, significantly higher than that for women who were cytology positive/HPV negative (3.2%). Women who were HPV type 16 positive at baseline had a cumulative CIN2+ rate over three rounds of 43.6% compared with 20.1% for any HPV-positive test. Using a HC2 cut-off of RLU/Co ≥ 2 would maintain acceptable sensitivity and result in 16% fewer HPV-positive results. Typing data suggested that around 55-60% of high-grade cytology and CIN2+, but less than 25% of low-grade cytology, would be prevented by HPV vaccine given current rates of coverage in the UK national programme. For the cost-effectiveness analysis, most of the primary HPV strategies examined where HPV was used as the sole primary test were cost saving in both unvaccinated and vaccinated cohorts under baseline cost assumptions, with a 7-18% reduction in annual screening-associated costs in unvaccinated cohorts and a 9-22% reduction for vaccinated cohorts. Utilising partial genotyping at the primary screening stage to identify women with HPV 16/18 and referring them to colposcopy was the most effective strategy (barring co-testing, which is significantly more costly than any other strategies considered), resulting in 83 additional life-years per 100,000 women for unvaccinated women when compared with current practice, and similar life-years saved compared with current practice for vaccinated women. In unvaccinated cohorts, however, this genotyping strategy is predicted to result in a 20% increase in the number of colposcopies performed in England, although in vaccinated cohorts the number of colposcopy referrals was predicted to be lower than in current practice. For all strategies in which HPV is used as the sole primary screening test, decreasing the follow-up interval for intermediate-risk women from 24 to 12 months increased the overall effectiveness of primary HPV screening. In exploratory analysis, strategies for which cytology screening was retained until either age 30 or 35 years, and for which HPV testing was used at older ages, were predicted to be of higher costs and intermediate effectiveness than those associated with full implementation of primary HPV screening from age 25 years. However, this finding should be interpreted with caution as it depends on assumptions made about screening behaviour and compliance with recommendations at the 'switch over' point. HPV testing as an initial screen was significantly more protective over three rounds (6 years) than the current practice of cytology and the use of primary HPV screening could allow a safe lengthening of the screening interval. A substantial decrease in high-grade cytology and CIN2+ can be expected as a consequence of the HPV vaccination programme. A HC2 cut-off of 2RLU/Co instead of the manufacturer's recommended cut-off of 1 would be clinically beneficial in terms of an optimal balance between sensitivity and specificity. Modelled analysis predicts that primary HPV screening would be both more effective and cost saving compared with current practice with cervical cytology for a number of potential strategies in both unvaccinated and vaccinated cohorts. Compliance with surveillance and optimal management of HPV-positive/cytology-negative women after primary HPV screening is of key importance. Limitations of the economic investigation included the need to make assumptions around compliance with screening attendance and follow-up for longer screening intervals in the future, assumptions regarding maintenance of current uptake vaccination in the future, and assumptions regarding the stability of cost of HPV and cytology tests in the future. Detailed sensitivity analysis across a range of possible assumptions was conducted to address these issues. This study and the economic evaluation lend support to convert from cytology to HPV-based screening. Future work should include researching (i) the attitudes of women who test HPV positive/cytology negative, (ii) the value of complementary biomarkers and (iii) activities relevant to primary HPV screening in unvaccinated and vaccinated populations from the point of view of QALY assessment. Current Controlled Trials ISRCTN25417821.

Clinical evaluation of human papillomavirus detection by careHPV™ test on physician-samples and self-samples using the indicating FTA Elute® card.

PubMed

Wang, Shao-Ming; Hu, Shang-Ying; Chen, Feng; Chen, Wen; Zhao, Fang-Hui; Zhang, Yu-Qing; Ma, Xin-Ming; Qiao, You-Lin

2014-01-01

To make the clinical evaluation of a solid-state human papillomavirus (HPV) sampling medium in combination with an economical HPV testing method (careHPV™) for cervical cancer screening. 396 women aged 25-65 years were enrolled for cervical cancer screening, and four samples were collected. Two samples were collected by woman themselves, among which one was stored in DCM preservative solution (called "liquid sample") and the other was applied on the Whatman Indicating FTA Elute® card (FTA card). Another two samples were collected by physician and stored in DCM preservative solution and FTA card, respectively. All the samples were detected by careHPV™ test. All the women were administered a colposcopy examination, and biopsies were taken for pathological confirmation if necessary. FTA card demonstrated a comparable sensitivity of detecting high grade Cervical Intraepithelial Neoplasia (CIN) with the liquid sample carrier for self and physician-sampling, but showed a higher specificity than that of liquid sample carrier for self-sampling (FTA vs Liquid: 79.0% vs 71.6%, p=0.02). Generally, the FTA card had a comparable accuracy with that of Liquid-based medium by different sampling operators, with an area under the curve of 0.807 for physician and FTA, 0.781 for physician and Liquid, 0.728 for self and FTA, and 0.733 for self and Liquid (p>0.05). FTA card is a promising sample carrier for cervical cancer screening. With appropriate education programmes and further optimization of the experimental workflow, FTA card based self-collection in combination with centralized careHPV™ testing can help expand the coverage of cervical cancer screening in low-resource areas.

[Comparison of the diagnostic utility from visual inspection with acetic acid and cervical cytology].

PubMed

Velázquez-Hernández, Nadia; Sánchez-Anguiano, Luis Francisco; Lares-Bayona, Edgar Felipe; Cisneros-Pérez, Vicente; Milla-Villeda, Reinaldo Humberto; Arreola-Herrera, Francisco de Asís; Navarrete-Flores, José Antonio; Aguilar-Durán, Maricela; Núñez-Márquez, Teresita; Rueda-Cisneros, Dora Alicia

2010-05-01

In Mexico, cervical cancer is the second leading cause of death in women after breast cancer. The human papillomavirus is associated with intraepithelial lesions, detected up to 99.7% of cervical carcinomas. Despite being easy to detect is a condition that many women suffer. To determine the diagnostic utility of the visual inspection with acetic acid of the uterine cervix compared with the cervical cytology. Study of diagnostic tests. The study was realized in the Centro de Atención Materno Infantil y Planificación Familiar of the Instituto de Investigación Científica, Durango, Mexico, research of the Juárez University of the State of Durango, from August 23, 2005 to November 13, 2006. 1,521 participants were examined who went consecutively to opportune detection of cervical cancer. One doctor practiced the test of acetic acid and cervical cytology to them, and one digital photograph, which was evaluated by three inter-observers triple blind. Those that was positive to anyone of these tests, were remitted to colposcopy and/or biopsy; also to 10% of selected negative population randomly was realized this procedure. Sensitivity, specificity, positive and negative predictive values and exactitude were determined. For the agreement inter-observer index of Kappa was used. Sensitivity, specificity, values predictive positive, negative and exactitude for the visual inspection with acetic acid were 20, 97, 5 and 99%, respectively. For the cervical cytology were of 80, 99, 57 and 99%, respectively. The force of agreement between the interobservant was poor. In this study cervical cytology was more useful than visual inspection with acetic acid to detect dysplasias or cervical cancer opportunely, due to detect all the positive true cases confirmed by biopsy.

Use of the HPV MLPA assay in cervical cytology for the prediction of high grade lesions.

PubMed

Litjens, Rogier J N T M; Theelen, Wendy; van de Pas, Yvonne; Ossel, Jessica; Reijans, Martin; Simons, Guus; Speel, Ernst-Jan M; Slangen, Brigitte F M; Ramaekers, Frans C S; Kruitwagen, Roy F P M; Hopman, Anton H N

2013-08-01

Current screening methods for uterine cervical cancer such as Papanicolaou smears and/or high risk human Papillomavirus (HR-HPV) detection have a high negative predictive value but a low positive predictive value for the presence of high grade cervical lesions. Therefore, new parameters are needed to reduce the rate of unnecessary referrals for colposcopy. The predictive value of the HPV multiplex ligation-dependent probe amplification (MLPA) assay, which can assess simultaneously HPV16/18 viral load and viral integration, was evaluated. The assay was applied to 170 cervical cytological samples, and the results were correlated with the matching histological follow-up. The GP5+/6+ assay and qPCR were used as a control for HR-HPV typing. The MLPA assay classified a higher percentage of cases as high-risk (high-viral load and/or viral integration) with higher grades of dysplasia. There was a high correlation between the HPV MLPA assay and qPCR for viral load and HPV genotyping, and between the MLPA assay and the GP5+/6+ assay for HPV genotyping. The sensitivity and specificity of the HPV MLPA assay for the detection of high-grade lesions were 44% and 93%, respectively. This study demonstrates that the HPV MLPA assay can reliably detect HPV 16/18, viral load, and viral integration in cytological samples. Also, high-risk classification correlated well with the presence of high-grade dysplasia. However, for the implementation of the MLPA assay into clinical practice, additional HR-HPV types need to be included to increase the sensitivity of the assay, and thereby increase its negative predictive value. Copyright © 2013 Wiley Periodicals, Inc.

HPV prevalence and HPV-related dysplasia in elderly women

PubMed Central

Hermansson, Ruth S.; Olovsson, Matts; Hoxell, Emelie

2018-01-01

Introduction In Sweden, where screening ends at the age of 60, about 30% of the cervical cancer cases occur in women older than 60. The aim of the present study was to investigate the prevalence of HPV and cervical dysplasia in women of 60 years and above. Patients and methods From September 2013 until June 2015, 1051 women aged 60–89 years (mean 68 years) were sampled for an HPV test when attending an outpatient gynecology clinic. Women with positive results had a second HPV test and liquid based cytology (LBC), after 3.5 months on average. Those with a positive second HPV test were examined by colposcopy, and biopsy and a sample for LBC was obtained. Results The prevalence of HPV was 4.1%, (95%CI 3.0–5.5, n = 43) at the first test, and at the second test 2.6% remained positive (95%CI 1.7–3.8, n = 27). The majority of women positive in both HPV tests, had dysplasia in histology, 81.5% (22/27) (4 CIN 2–0.4%, 18 CIN 1–1.7%). HPV-related dysplasia was found in 2.1%, (95%CI 1.3–3.2, n = 22) of the 1051 women. Four of the 22 women with positive HPV tests also had abnormal cytology, one ASCUS and three CIN 1. No cancer or glandular dysplasia was detected. Conclusion A significant proportion of elderly women were found to have a persistent cervical HPV infection. Among them there was a high prevalence of CIN diagnosed by histology. The HPV test showed high sensitivity and specificity in detecting CIN in elderly women, while cytology showed extremely low sensitivity. PMID:29320507

Assessment of HPV-mRNA test to predict recurrent disease in patients previously treated for CIN 2/3.

PubMed

Frega, Antonio; Sesti, Francesco; Lombardi, Danila; Votano, Sergio; Sopracordevole, Francesco; Catalano, Angelica; Milazzo, Giusi Natalia; Lombardo, Riccardo; Assorgi, Chiara; Olivola, Sara; Chiusuri, Valentina; Ricciardi, Enzo; French, Deborah; Moscarini, Massimo

2014-05-01

The use of HPV-mRNA test in the follow-up after LEEP is still matter of debate, with regard to its capacity of prediction relapse. The aim of the present study is to evaluate the reliability of HPV-mRNA test to predict the residual and recurrent disease, and its accuracy in the follow-up of patients treated for CIN 2/3. Multicenter prospective cohort study. Patients who underwent LEEP after a biopsy diagnosing CIN 2/3 were followed at 3, 6, 12, 24 and 36 months. Each check up included cytology, colposcopy, HPV-DNA test (LiPA) and HPV-mRNA test (PreTect HPV Proofer Kit NorChip). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), of HPV-DNA test and HPV-mRNA test to predict relapse, recurrent and residual disease. Using multiple logistic regression, the statistical significant variables as assessed in univariate analysis were entered and investigated as predictors of relapse disease. The mRNA-test in predicting a residual disease had a sensitivity of 52% and a NPV of 91%, whereas DNA-test had 100% and 100%, respectively. On the contrary in the prediction of recurrent disease mRNA-test had a sensitivity and a NPV of 73.5% and 97%, whereas DNA-test had 44% and 93%. On the multivariate analysis, age, cytology, HPV DNA and mRNA test achieved the role of independent predictors of relapse. HPV-mRNA test has a higher sensitivity and a higher NPV in predicting recurrent disease, for this reason it should be used in the follow-up of patients treated with LEEP for CIN 2/3 in order to individualize the timing of check up. Copyright © 2014 Elsevier B.V. All rights reserved.

Outcomes after management of young women with cervical intraepithelial neoplasia 2 with a 6-month observation protocol.

PubMed

Bleecker, Elizabeth; Koehler, Elizabeth; Smith, Jennifer; Budwit, Debra; Rahangdale, Lisa

2014-01-01

Recommendations regarding treatment of cervical intraepithelial neoplasia (CIN) 2 in women have evolved over the years: young women with CIN 2 may be offered observation with Pap smears and colposcopy every 6 months instead of immediate excision or ablation of disease. The purpose of this study was to observe patient follow-up during the initiation of this management protocol for young women with CIN 2. This was a retrospective review of clinical outcomes of women younger than 30 years with CIN 2 on index biopsy and planned follow-up at UNC between July 2009 and August 2010. A chart review for clinical variables, follow-up visits, and progression of disease was conducted. Primary analysis determined the rate of follow-up and pathology at 6 months. Secondary analysis investigated risk factors for incomplete follow-up. Seventy women met inclusion criteria; 46 were managed with observation. Twenty-eight (60.8%; 28/46) women completed a follow-up visit. Demographic and clinical variables did not reach statistical significance in predicting the likelihood of completion of a follow-up visit, although there was a trend toward greater follow-up in employed patients (odds ratio = 5.25, 95% confidence interval = 0.84-34.78). Approximately half (52.4%; 11/21) of women with a completed cervical biopsy demonstrated regression of disease during the study period. On the basis of these data, follow-up in this population was unpredictable based on basic demographic or clinical factors that we often use to judge likelihood of compliance with medical recommendations. The percentage of patients with regression at follow-up was as expected from the natural history of CIN 2.

Limited Impact of Music Therapy on Patient Anxiety with the Large Loop Excision of Transformation Zone Procedure - a Randomized Controlled Trial.

PubMed

Kongsawatvorakul, Chompunoot; Charakorn, Chuenkamon; Paiwattananupant, Krissada; Lekskul, Navamol; Rattanasiri, Sasivimol; Lertkhachonsuk, Arb-Aroon

2016-01-01

Many studies have pointed to strategies to cope with patient anxiety in colposcopy. Evidence shows that patients experienced considerable distress with the large loop excision of transformation zone (LLETZ) procedure and suitable interventions should be introduced to reduce anxiety. This study aimed to investigate the effects of music therapy in patients undergoing LLETZ. A randomized controlled trial was conducted with patients undergoing LLETZ performed under local anesthesia in an out patient setting at Ramathibodi Hospital, Bangkok, Thailand, from February 2015 to January 2016. After informed consent and demographic data were obtained, we assessed the anxiety level using State Anxiety Inventory pre and post procedures. Music group patients listened to classical songs through headphones, while the control group received the standard care. Pain score was evaluated with a visual analog scale (VAS). Statistical analysis was conducted using Pearson Chi-square, Fisher's Exact test and T-Test and p-values less than 0.05 were considered statistically significant. A total of 73 patients were enrolled and randomized, resulting in 36 women in the music group and 37 women in the non-music control group. The preoperative mean anxiety score was higher in the music group (46.8 VS 45.8 points). The postoperative mean anxiety scores in the music and the non-music groups were 38.7 and 41.3 points, respectively. VAS was lower in music group (2.55 VS 3.33). The percent change of anxiety was greater in the music group, although there was no significant difference between two groups. Music therapy did not significantly reduce anxiety in patients undergoing the LLETZ procedure. However, different interventions should be developed to ease the patients' apprehension during this procedure.

Yield of Cytology Surveillance After High-Grade Vulvar Intraepithelial Neoplasia or Cancer.

PubMed

Kuroki, Lindsay M; Frolova, Antonina I; Wu, Ningying; Liu, Jingxia; Powell, Matthew; Thaker, Premal H; Massad, L Stewart

2017-07-01

The aim of the study was to estimate the risk of high-grade cervical and vaginal intraepithelial neoplasia (CIN/VAIN 2+) and cancer among women treated surgically for high-grade vulvar intraepithelial neoplasia (HGVIN) and vulvar cancer. We performed a retrospective cohort study of women who underwent surgery for HGVIN/vulvar cancer between 2006 and 2010. Univariate and multivariate analyses using stepwise selection were used to identify correlates of abnormal cytology after treatment for VIN and vulvar cancer. Among 191 women under surveillance for a median of 3.7 years who underwent treatment for HGVIN/vulvar cancer, primary vulvar lesions included VIN 2 (10, 5%), VIN 3 (102, 53%), and carcinoma (79, 41%). During follow-up, 71 (37%) had abnormal cytology, including 47 (25%) low grade, 23 (12%) high grade, and 1 (0.5%) carcinoma. Subsequent risk for VAIN 2+ was 11% (6/57) after previous hysterectomy and 8% for CIN 2+ (10/124) with intact cervix. Overall risk for CIN 3+ was 5%. Correlates of high-grade cytology after treatment for HGVIN/vulvar cancer included nonwhite race (odds ratio [OR] = 3.3, 95% CI = 1.50-7.36), immunodeficiency (OR = 4.2, 95% CI = 1.76-9.94), and previous abnormal cytology (OR = 2.7, 95% CI = 1.29-5.78). Stepwise multivariate analysis revealed immunosuppression as the only significant correlate of high-grade cytology after vulvar treatment (adjusted OR = 3.7, 95% CI = 1.26-10.83). Women with HGVIN/cancer should have cervical/vaginal cytology before vulvar surgery. Those with a negative cervical or vaginal cytology result should undergo cytology testing at 1- to 3-year intervals, based on the threshold for CIN 3+ set forth by the American Society for Colposcopy and Cervical Pathology.

Withdrawing low risk women from cervical screening programmes: mathematical modelling study.

PubMed

Sherlaw-Johnson, C; Gallivan, S; Jenkins, D

1999-02-06

To evaluate the impact of policies for removing women before the recommended age of 64 from screening programmes for cervical cancer in the United Kingdom. A mathematical model of the clinical course of precancerous lesions which accounts for the influence of infection with the human papillomavirus, the effects of screening on the progression of disease, and the accuracy of the testing procedures. Two policies are compared: one in which women are withdrawn from the programme if their current smear is negative and they have a recent history of regular, negative results and one in which women are withdrawn if their current smear test is negative and a simultaneous test is negative for exposure to high risk types of human papillomavirus. United Kingdom cervical screening programme. The incidence of invasive cervical cancer and the use of resources. Early withdrawal of selected women from the programme is predicted to give rise to resource savings of up to 25% for smear tests and 18% for colposcopies when withdrawal occurs from age 50, the youngest age considered in the study. An increase in the incidence of invasive cervical cancer, by up to 2 cases/100 000 women each year is predicted. Testing for human papillomavirus infection to determine which women should be withdrawn from the programme makes little difference to outcome. This model systematically analyses the consequences of screening options using available data and the clinical course of precancerous lesions. If further audit studies confirm the model's forecasts, a policy of early withdrawal might be considered. This would be likely to release substantial resources which could be channelled into other aspects of health care or may be more effectively used within the cervical screening programme to counteract the possible increase in cancer incidence that early withdrawal might bring.

High-risk human papilloma virus management in pregnancy with cervical intraepithelial neoplasia during pregnancy and postpartum in China.

PubMed

He, Yue; Wu, Yu-Mei; Zhao, Qun; Wang, Tong; Song, Fang; Zhu, Li

2014-02-01

To investigate the relationship between cervical intraepithelial neoplasia (CIN) and high-risk human papilloma virus (HR-HPV) during pregnancy and postpartum in China. In this prospective case-control study, 168 pregnant women with CIN and cervicitis were diagnosed by colposcopic cervical biopsy. All the cases underwent hybrid capture assay version II (HCII) to detect HR-HPV DNA load amounts and the tests were completed in 3-6 months after childbirth. During pregnancy: as the CIN grade increased, the HR-HPV infection rates increased (P = 0.002), but HR-HPV DNA load amounts (in logarithms) did not change obviously (P = 0.719). 3-6 months postpartum: as the CIN grade increased, the natural negative rate of HR-HPV decreased (P = 0.000), while the amount of HR-HPV DNA (in logarithms) increased (P = 0.036); especially the amount of HR-HPV DNA in pregnant women with CINIII was significantly higher than that of other grades. During pregnancy and 3-6 months postpartum : the amount of HR-HPV DNA (in logarithms) during pregnancy was higher than that of 3-6 months postpartum with the same grade of CIN. The findings emphasize the importance of undergoing the HCII test 3-6 months postpartum. It should be noted that HR-HPV may turn negative in pregnancy with CINIII 3-6 months after childbirth. Further treatments of pregnancy with CIN should be considered according to the CIN grade diagnosed by cervical biopsy via colposcopy 3-6 months after birth, but not according to the persistence of HR-HPV during pregnancy. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

Quantivirus® HPV E6/E7 RNA 3.0 assay (bDNA) is as sensitive, but less specific than Hybrid Capture 2 test.

PubMed

Shen, Yong; Gong, Jiaomei; He, Yanxia; Cheng, Guomei; Okunieff, Paul; Li, Xiaofu

2013-02-01

Human papillomavirus (HPV) infection is the primary cause of cervical cancer. The Quantivirus(®) HPV E6/E7 RNA 3.0 assay (DiaCarta, CA, USA) detects E6/E7 mRNA of 13 high risk subtypes and 6 low risk subtypes. Cervical specimens collected in PreservCyt were processed for HPV detection. Cervical biopsies were taken only from those women with abnormal colposcopy. 200 out of 272 (73.5%) cases were mRNA positive. The percentage of HPV E6/E7 mRNA positive samples increases with the severity of the cytological diagnosis, but not in histological diagnosis. In 146 patients with both tests, the E6/E7 mRNA assay had significant higher positivity rate than the Hybrid Capture 2 assay (75.3% versus 62.3%). The HPV mRNA assay and the HC2 assay had the same sensitivity of high grade cervical intraepithelial neoplasia (CIN 2+), 82.4% (14/17) (95% confidence interval [CI], 64.3, 100). However, the specificity of CIN 2+ for the HPV mRNA assay was significantly lower than HC2 assay. Receiver operating characteristic curve analysis was used to compare the diagnostic performance of the E6/E7 mRNA and HC2. E6/E7 mRNA achieved 58.8% sensitivity with 74.1% specificity, HC2, achieved 47.1% sensitivity with 70.7% specificity. The overall performance of HPV E6/E7 mRNA assay for detecting CIN 2+ was lower than HC2. This study does not support the use of this assay in screening for cervical cancer prevention alone. Copyright © 2012 Elsevier B.V. All rights reserved.

Preclinical, Clinical, and Over-the-Counter Postmarketing Experience with a New Vaginal Cup: Menstrual Collection

PubMed Central

North, Barbara B.

2011-01-01

Abstract Background Menstrual cups have been available for decades, but their use is limited by bulky design and the need for multiple sizes. The Softcup® (Instead, Inc., San Diego, CA) is a simple single-size disposable over-the-counter (OTC) menstrual cup that compresses to tampon shape to facilitate insertion and can be worn during coitus. This report describes preclinical evaluation, clinical testing, and postmarketing monitoring of the Softcup. Methods Preclinical testing complied with U.S. Food and Drug Administration (FDA) guidelines and used standard United States Pharmacopoeia methodologies for assessment of potential toxicity. Clinical testing enrolled 406 women in seven U.S. centers. A detailed written questionnaire assessed safety, acceptability, and effectiveness for menstrual collection. Study safety parameters included pelvic examinations, Pap smears, colposcopy, urinalysis, vaginal pH, wet mounts, gram stain, and vaginal microflora cultures. Postmarketing surveillance of over 100 million Softcups has been conducted by the manufacturer and by the FDA Medwatch system. Results No toxicity or mutagenicity was observed in preclinical evaluations. In clinical testing, after three cycles of cup use, 37% of subjects rated the cup as better than, 29% as worse than, and 34% as equal to pads or tampons. The cup was preferred for comfort, dryness, and less odor. Cups received lower ratings for disposal and convenience. Eighty-one percent of enrolled women were able to insert and remove their first cup using only written instructions. Use difficulties resulting in study discontinuations included cramping (1%), leakage (1%), and improper fit (3%). No safety parameters were adversely affected. No significant health risks were reported during postmarketing surveillance. Conclusions These results demonstrate that a single-size vaginal device has no significant health risks and is acceptable to many women without the need for fitting or other medical services. PMID:21194348

Preclinical, clinical, and over-the-counter postmarketing experience with a new vaginal cup: menstrual collection.

PubMed

North, Barbara B; Oldham, Michael J

2011-02-01

Menstrual cups have been available for decades, but their use is limited by bulky design and the need for multiple sizes. The Softcup® (Instead, Inc., San Diego, CA) is a simple single-size disposable over-the-counter (OTC) menstrual cup that compresses to tampon shape to facilitate insertion and can be worn during coitus. This report describes preclinical evaluation, clinical testing, and postmarketing monitoring of the Softcup. Preclinical testing complied with U.S. Food and Drug Administration (FDA) guidelines and used standard United States Pharmacopoeia methodologies for assessment of potential toxicity. Clinical testing enrolled 406 women in seven U.S. centers. A detailed written questionnaire assessed safety, acceptability, and effectiveness for menstrual collection. Study safety parameters included pelvic examinations, Pap smears, colposcopy, urinalysis, vaginal pH, wet mounts, gram stain, and vaginal microflora cultures. Postmarketing surveillance of over 100 million Softcups has been conducted by the manufacturer and by the FDA Medwatch system. No toxicity or mutagenicity was observed in preclinical evaluations. In clinical testing, after three cycles of cup use, 37% of subjects rated the cup as better than, 29% as worse than, and 34% as equal to pads or tampons. The cup was preferred for comfort, dryness, and less odor. Cups received lower ratings for disposal and convenience. Eighty-one percent of enrolled women were able to insert and remove their first cup using only written instructions. Use difficulties resulting in study discontinuations included cramping (1%), leakage (1%), and improper fit (3%). No safety parameters were adversely affected. No significant health risks were reported during postmarketing surveillance. These results demonstrate that a single-size vaginal device has no significant health risks and is acceptable to many women without the need for fitting or other medical services.

Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia

PubMed Central

Baumann, Marc; Mueller, Michael; Fink, Daniel; Heinzl, Siegfried; Imesch, Patrick; Dedes, Konstantin

2013-01-01

Objective The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. Methods Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. Conclusion Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary. PMID:23875073

Female genital schistosomiasis due to Schistosoma haematobium. Clinical and parasitological findings in women in rural Malawi.

PubMed

Kjetland, E F; Poggensee, G; Helling-Giese, G; Richter, J; Sjaastad, A; Chitsulo, L; Kumwenda, N; Gundersen, S G; Krantz, I; Feldmeier, H

1996-12-30

A total of 51 women with urinary schistosomiasis haematobium were examined in order to identify diagnostic indicators for female genital schistosomiasis (FGS). Patients were selected at random from the outpatient department of the Mangochi District Hospital, Malawi. The medical histories were recorded according to a pre-designed questionnaire and the women were subjected to a thorough gynaecological examination including colposcopy and photographic documentation of lesions. Microscopy of genital biopsies revealed that 33 of the 51 women had S. haematobium ova in cervix, vagina and/or vulva in addition to the presence of ova in urine. The most sensitive diagnostic procedure was beside microscopic examination of a wet cervix biopsy crushed between two glass slides, which revealed 25 of the 33 genital infections. There was a significant correlation between the size of genital lesions and the number of ova counted per mm2 of crushed tissue. Women with FGS had significantly more tumours in the vulva than women with schistosomiasis limited to the urinary tract. Most of the observed genital pathology could easily be identified by the naked eye, but colposcopic examination yielded valuable additional information like the demonstration of neovascularisation around cervical sandy patches. Few of the symptoms previously regarded as indicators for FGS could be linked to the presence of schistosome ova in genital tissue. Husbands of infertile women with FGS had children with other women significantly more often than husbands of women who only had urinary schistosomiasis. This, together with the finding that the majority of the divorced women had FGS, indicates that the manifestation of this disease may have implications for the marital and sexual life of the affected women.

Toward early safety alert endpoints: exploring biomarkers suggestive of microbicide failure.

PubMed

Mauck, Christine K; Lai, Jaim Jou; Weiner, Debra H; Chandra, Neelima; Fichorova, Raina N; Dezzutti, Charlene S; Hillier, Sharon L; Archer, David F; Creinin, Mitchell D; Schwartz, Jill L; Callahan, Marianne M; Doncel, Gustavo F

2013-11-01

Several microbicides, including nonoxynol-9 (N-9) and cellulose sulfate (CS), looked promising during early trials but failed in efficacy trials. We aimed to identify Phase I mucosal safety endpoints that might explain that failure. In a blinded, randomized, parallel trial, 60 healthy premenopausal sexually abstinent women applied Universal HEC placebo, 6% CS or 4% N-9 gel twice daily for 13½ days. Endpoints included immune biomarkers in cervicovaginal lavage (CVL) and endocervical cytobrushes, inflammatory infiltrates in vaginal biopsies, epithelial integrity by naked eye, colposcopy, and histology, CVL anti-HIV activity, vaginal microflora, pH, and adverse events. Twenty women enrolled per group. Soluble/cellular markers were similar with CS and placebo, except secretory leukocyte protease inhibitor (SLPI) levels decreased in CVL, and CD3(+) and CD45(+) cells increased in biopsies after CS use. Increases in interleukin (IL)-8, IL-1, IL-1RA, and myeloperoxidase (MPO) and decreases in SLPI were significant with N-9. CVL anti-HIV activity was significantly higher during CS use compared to N-9 or placebo. CS users tended to have a higher prevalence of intermediate Nugent score, Escherichia coli, and Enterococcus and fewer gram-negative rods. Most Nugent scores diagnostic for bacterial vaginosis were in N-9 users. All cases of histological inflammation or deep epithelial disruption occurred in N-9 users. While the surfactant N-9 showed obvious biochemical and histological signs of inflammation, more subtle changes, including depression of SLPI, tissue influx of CD45(+) and CD3(+) cells, and subclinical microflora shifts were associated with CS use and may help to explain the clinical failure of nonsurfactant microbicides.

Performance of P16/Ki67 dual staining in triaging hr-HPV-positive population during cervical Cancer screening in the younger women.

PubMed

Qian, Qiu-Ping; Zhang, Xiaoan; Ding, Bo; Jiang, Shi-Wen; Li, Ze-Min; Ren, Mu-Lan; Shen, Yang

2018-08-01

Cervical cancer is the most common malignancy from the female reproductive tract, and usually develops from low-grade or high-grade squamous intraepithelial lesions (LSIL or HSIL). Detecting the precancerous lesion during the LSIL-HSIL-invasive cancer sequelae can effectively interrupt the oncogenesis and decrease the incidence of invasive carcinoma. The aim of this study is to evaluate the performance of P16/Ki67 dual staining in triaging hr-HPV-positive population. Conventional gynecological examination, cervical cytology and hr-HPV testing were given to all patients. Specimens were collected for cytology examination and HPV genotyping. According to cytology results, patients were divided into cervical cancer group, HSIL group, LSIL group and benign lesion group. Sensitivity and specificity of the dual staining method in each histopathologic group was obtained and compared. Among the108 patients participated in the study, 65 were diagnosed as normal, 15 as LSIL, 20 as HSIL and 8 as CC, by histopathologic examination. Dual staining of p16/Ki67 on cytology specimen provided a positive predictive value of 86% and the negative predictive value of 96%. The sensitivity approached 96.43% when combining ThinPrep cytological test (TCT) with the dual staining, with a specificity of 60% in detecting HSIL. Joint detection of TCT and p16/Ki67 dual staining displayed the highest specificity among all the attempted combinations of detection methods. This study demonstrated that p16/Ki-67 dual staining represents an effective method for cervical cancer screening. Application of this method could lead to a reduction of unnecessary colposcopy referrals and misdiagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Regression of Human Papillomavirus Intraepithelial Lesions Is Induced by MVA E2 Therapeutic Vaccine

PubMed Central

López-Contreras, Mario; Rosales, Carlos; Magallanes-Molina, Jose-Roberto; Gonzalez-Vergara, Roberto; Arroyo-Cazarez, Jose Martin; Ricardez-Arenas, Antonio; del Follo-Valencia, Armando; Padilla-Arriaga, Santiago; Guerrero, Miriam Veronica; Pirez, Miguel Angel; Arellano-Fiore, Claudia; Villarreal, Freddy

2014-01-01

Abstract Human papilloma viruses can induce warts, condylomas, and other intraepithelial cervical lesions that can progress to cancer. Cervical cancer is a serious problem in developing countries because early detection is difficult, and thus proper early treatment is many times missing. In this phase III clinical trial, we evaluated the potential use of MVA E2 recombinant vaccinia virus to treat intraepithelial lesions associated with papillomavirus infection. A total of 1176 female and 180 male patients with intraepithelial lesions were studied. They were injected with 107 MVA E2 virus particles directly into their uterus, urethra, vulva, or anus. Patients were monitored by colposcopy and cytology. Immune response was determined by measuring the antibody titer against MVA E2 virus and by analyzing the cytotoxic activity against cancer cells bearing papillomavirus DNA. Papillomavirus was determined by the Hybrid Capture method or by polymerase chain reaction analysis. By histology, 1051 (89.3%) female patients showed complete elimination of lesions after treatment with MVA E2. In 28 (2.4%) female patients, the lesion was reduced to CIN 1. Another 97 (8.3%) female patients presented isolated koilocytes after treatment. In men, all lesions were completely eliminated. All MVA E2–treated patients developed antibodies against the MVA E2 vaccine and generated a specific cytotoxic response against papilloma-transformed cells. Papillomavirus DNA was not detected after treatment in 83% of total patients treated. MVA E2 did not generate any apparent side effects. These data suggest that therapeutic vaccination with MVA E2 vaccine is an excellent candidate to stimulate the immune system and generate regression in intraepithelial lesions when applied locally. PMID:25275724

Risks of cervical intraepithelial neoplasia grade 3 or invasive cancers in ASCUS women with different management: a population-based cohort study.

PubMed

Tai, Yi Jou; Chen, Yun Yuan; Hsu, Huang Cheng; Chiang, Chun Ju; You, San Lin; Chen, Chi An; Cheng, Wen Fang

2018-07-01

To investigate the progression risk of atypical squamous cells of undetermined significance (ASCUS) with different clinical managements. Women with their first diagnosis of ASCUS cytology were retrieved from the national cervical cancer screening database and linked to the national health insurance research database to identify the management of these women. The incidences of developing cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+) were calculated, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. This study was approved by the Research Ethics Committee of the National Taiwan University Hospital and is registered at ClinicalTrials.gov (Identifier: NCT02063152). There were total 69,741 women included. Various management strategies including colposcopy, cervical biopsies and/or endocervical curettage, and cryotherapy, failed to reduce the risk of subsequent CIN3+ compared with repeat cervical smears. Loop electrosurgical excision procedure/conization significantly decreased risk of subsequent CIN3+ lesions (HR=0.22; 95% confidence interval [CI]=0.07-0.68; p=0.010). Women in their 40s-50s had an approximately 30% risk reduction compared to other age groups. Women with a previous screening history >5 years from the present ASCUS diagnosis were at increased risk for CIN3+ (HR=1.24; 95% CI=1.03-1.49; p=0.020). In women of first-time ASCUS cytology, a program of repeat cytology can be an acceptable clinical option in low-resource settings. Caution should be taken especially in women with remote cervical screening history more than 5 years. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Ultrahigh-resolution optical coherence microscopy accurately classifies precancerous and cancerous human cervix free of labeling

PubMed Central

Zeng, Xianxu; Zhang, Xiaoan; Li, Canyu; Wang, Xiaofang; Jerwick, Jason; Xu, Tao; Ning, Yuan; Wang, Yihong; Zhang, Linlin; Zhang, Zhan; Ma, Yutao; Zhou, Chao

2018-01-01

Cervical cancer remains the fourth most common cause of cancer worldwide and the third leading cause of cancer deaths for women in developing countries. Traditional screening tools, such as human papillomavirus and Pap tests, cannot provide results in real-time and cannot localize suspicious regions. Colposcopy-directed biopsies are invasive in nature and only a few sites of the cervix may be chosen for investigation. A non-invasive, label-free and real-time imaging method with a resolution approaching that of histopathology is desirable for early detection of the disease. Methods: Ultrahigh-resolution optical coherence microscopy (OCM) is an emerging imaging technique used to obtain 3-dimensional (3-D) “optical biopsies” of biological samples with cellular resolution. In this study, 497 3-D OCM datasets from 159 specimens were collected from 92 patients. Results: Distinctive patterns for normal cervix, squamocolumnar junction, ectropion, low-grade and high-grade squamous intraepithelial lesions (LSIL and HSIL) and invasive cervical lesions were clearly observed from OCM images, which matched well with corresponding histological slides. OCM images demonstrated a sensitivity of 80% (95% confidence interval, CI, 72%-86%) and a specificity of 89% (95% CI, 84%-93%) for detecting high-risk lesions (HSIL and invasive lesions) when blindly tested by three investigators. A substantial inter-observer agreement was observed (κ=0.627), which showed high diagnostic consistency among three investigators. Conclusion: These results laid the foundation for future non-invasive optical evaluation of cervical tissue in vivo, which could lead to a less invasive and more effective screening and “see-and-treat” strategy for the management of cervical cancer. PMID:29896305

Beneficial effects of a Coriolus versicolor-based vaginal gel on cervical epithelization, vaginal microbiota and vaginal health: a pilot study in asymptomatic women.

PubMed

Palacios, Santiago; Losa, Fernando; Dexeus, Damián; Cortés, Javier

2017-03-16

To assess the effect of a 12-day treatment using a vaginal gel based on niosomes containing hyaluronic acid, ß-glucan, alpha-glucan oligosaccharide, Coriolus versicolor, Asian centella, Azadirachta indica and Aloe vera on vaginal microbiota, cervical epithelization and vaginal health. Open-label, prospective pilot study conducted in asymptomatic women in daily practice. Cervical epithelization was evaluated by colposcopy using an ectopy epithelization score (from 5: no ectopy to 1: severe ectopy and bleeding), vaginal microbiota using the VaginaStatus-Diagnostic test (Instiüt für Mikroökologie, Herborn, Germany) and further rated by the investigator using a 5-point Liker scale (from 5: normal to 1: very severe deterioration in which all evaluated species were altered), and vaginal health using the Vaginal Health Index. In 21 women, a positive effect to improve epithelization of the cervical mucosa, with a mean score of 4.42 at the final visit as compared to 3.09 at baseline (P < 0.0001) (43% improvement). In 10 women, there was a trend of improving of vaginal microbiota status, with a mean score of 4.0 at the final visit vs. 3.3 at baseline (P = NS) (21.2% improvement). In 11 women, the Vaginal Health Index increased from 19.0 at baseline to 22.3 at the final visit (P = 0.007). The concentration of Lactobacillus spp. increased 54.5% of women and pH decreased from 4.32 to 4.09. These encouraging preliminary results provide the basis for designing a randomized controlled study, and for potential use in human papilloma virus infection. ISRCTN77955077 . Registration date: February 15, 2017. Retrospectively registered.

Long-Term Clinical Outcome after Treatment for High-Grade Cervical Lesions: A Retrospective Monoinstitutional Cohort Study

PubMed Central

Del Mistro, Annarosa; Matteucci, Mario; Insacco, Egle Alba; Onnis, GianLibero; Da Re, Filippo; Baboci, Lorena; Minucci, Daria

2015-01-01

Background. The aim of this retrospective observational study of women treated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was to assess the long-term risk of residual/recurrent high-grade CIN. Materials and Methods. We evaluated 760 women treated by loop electrosurgical excision procedure (684) or conization (76) between 2000 and 2009, and followed up to June 30, 2014 (median follow-up 6.7 years, range 4–14). Visits every 6 months for the first year after treatment and yearly for up to the following 10 years included cytology, colposcopy when indicated, and HPV testing (search and typing). Results. CIN2+ or vaginal intraepithelial neoplasia grade 2 or worse (VAIN2+) was detected in 67 cases (8.8%), 39 at first follow-up and 28 after one/more negative visits. The risk of CIN2+ was higher in case of positive margins (odds ratio (OR) 8.04, 95% CI 4.31–15.0), type 3 transformation zone (OR for CIN3 27.7, 95% CI 2.07–36.9), CIN3+ excision (OR 6.02, 95% CI 1.73–20.9), and positive high-risk HPV test at first follow-up (OR for HPV16: 20.6, 95% CI 6.8–62.6; OR for other hrHPV types: 18.3, 95% CI 5.9–57.0). Conclusion. Residual/recurrent high-grade CIN occurred in <9% cases, and the risk was associated with transformation zone type, lesion grade, margins status, and hrHPV test result at 6–12 months of follow-up. PMID:26180819

[Cervical screening: toward a new paradigm?].

PubMed

Lavoué, V; Bergeron, C; Riethmuller, D; Daraï, E; Mergui, J-L; Baldauf, J-J; Gondry, J; Douvier, S; Lopès, P; de Reilhac, P; Quéreux, C; Letombe, B; Marchetta, J; Boulanger, J-C; Levêque, J

2010-04-01

Analysis of the trials which compare the virologic testing (HPV testing) and the cytology in the cervical screening. The MedLine database was consulted using the Keywords: "cervical screening", "pap smear", "liquid based cytology", "HPV testing", "adults", "adolescents", "cervical intraepithelial neoplasia (CIN)", "uterine cervix cancer". Articles were selected according their concern about the debate of the uterine cervix cancer screening in France. The HPV testing seems interesting allowing a decreasing delay in the diagnosis of CIN (more diagnosis of CIN2+ in the first round and less during the second one). But, when the two rounds are added, the number of CIN2+ are identical in the two arms (cytology and HPV testing) in all the trials (except the Italian NTCC trial). A negative HPV testing protects the women much longer than cytology can do: a delay of five years between two rounds seems ideal. The HPV testing alone increases the detection rate of cervical lesions, which could regress spontaneously and may induce an overtreatment, especially in the youngest population: a triage is necessary and the cytology appears to be the best way to select the candidates for colposcopy in case of positive HPV testing and cytology. The HPV infection presents some particularities in adolescent females: for this reason, the HPV testing should not be used in this special population. In vaccinated women, a consensus for the screening is necessary. The health care providers in France have to understand the characteristics of the HPV testing: its advantages compared to the cytologic screening are only evident in case of an organization of the screening in France and even in Europe. (c) 2010 Elsevier Masson SAS. All rights reserved.

[Crosssectional survey of human papilloma virus subtype distribution and cervical intraepithelial neoplasia in Shenzhen].

PubMed

Liang, Ling-yun; Du, Hui; Wang, Chun; Zhang, Wei; Chen, Yun; Qu, Xin-feng; Yang, Bin; Wu, Bo; Wu, Ruo-song; Belinson, Jerome L; Wu, Rui-fang

2013-02-18

To investigate the prevalence of human papilloma virus (HPV) infection and cervical intraepithelial neoplasia (CIN) and pathogenecity of the HPV subtyping and virus loads in Shenzhen district. In the study, 10 000 sexually active women from Shenzhen city and rural areas around were screened for cervical cancer, and all the cases were examined with cytology tests and several kinds of high risk HPV (HR-HPV) tests. Those with cytology ≥atypical squamous cells of undetermined sign (ASC-US) or positive HPV results underwent colposcopy with biopsy for a pathological diagnosis. The average age of this study population was 38.9 years. The total prevalence of HPV infection was 16.6%, with age-specific prevalence increasing with age. The morbidity rate of the low grade cervical intraepithelial neoplasia CIN1 was 17.0%, but that with those aged ≥55 years showed a sharp drop. The morbidity rate of the high grade cervical intraepithelial neoplasia CIN2/3 was 2.6%, and was higher in the 45 to 59 years age group than in the 25 to 44 years age group. HR-HPV infection was an obvious relevant factor of CIN1 and CIN2/3, and the OR values increased as the virus loads increased, but they had different relevant HPV subtypes. We found that HPV-16, -58, -31, -33, -18 were the first five ones for CIN2/3 while HPV-39, -58, -59, -52, -66 for CIN1. There is a high level of HPV infection and CIN in Shenzhen district. The prevalence of HPV infection has a trend to increase with age, and the people aged 45 years and more are key objects for CIN2/3 screening, with the virus load and subtyping of HR-HPV infection as indicative factors.

Feasibility of clinical detection of cervical dysplasia using angle-resolved low coherence interferometry measurements of depth-resolved nuclear morphology.

PubMed

Ho, Derek; Drake, Tyler K; Smith-McCune, Karen K; Darragh, Teresa M; Hwang, Loris Y; Wax, Adam

2017-03-15

This study sought to establish the feasibility of using in situ depth-resolved nuclear morphology measurements for detection of cervical dysplasia. Forty enrolled patients received routine cervical colposcopy with angle-resolved low coherence interferometry (a/LCI) measurements of nuclear morphology. a/LCI scans from 63 tissue sites were compared to histopathological analysis of co-registered biopsy specimens which were classified as benign, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). Results were dichotomized as dysplastic (LSIL/HSIL) versus non-dysplastic and HSIL versus LSIL/benign to determine both accuracy and potential clinical utility of a/LCI nuclear morphology measurements. Analysis of a/LCI data was conducted using both traditional Mie theory based processing and a new hybrid algorithm that provides improved processing speed to ascertain the feasibility of real-time measurements. Analysis of depth-resolved nuclear morphology data revealed a/LCI was able to detect a significant increase in the nuclear diameter at the depth bin containing the basal layer of the epithelium for dysplastic versus non-dysplastic and HSIL versus LSIL/Benign biopsy sites (both p < 0.001). Both processing techniques resulted in high sensitivity and specificity (>0.80) in identifying dysplastic biopsies and HSIL. The hybrid algorithm demonstrated a threefold decrease in processing time at a slight cost in classification accuracy. The results demonstrate the feasibility of using a/LCI as an adjunctive clinical tool for detecting cervical dysplasia and guiding the identification of optimal biopsy sites. The faster speed from the hybrid algorithm offers a promising approach for real-time clinical analysis. © 2016 UICC.

Feasibility of clinical detection of cervical dysplasia using angle-resolved low coherence interferometry measurements of depth-resolved nuclear morphology

PubMed Central

Ho, Derek; Drake, Tyler K.; Smith-McCune, Karen K.; Darragh, Teresa M.; Hwang, Loris Y.; Wax, Adam

2017-01-01

This study sought to establish the feasibility of using in situ depth-resolved nuclear morphology measurements for detection of cervical dysplasia. Forty (40) enrolled patients received routine cervical colposcopy with angle-resolved low coherence interferometry (a/LCI) measurements of nuclear morphology. a/LCI scans from 63 tissue sites were compared to histopathological analysis of co-registered biopsy specimens which were classified as benign, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). Results were dichotomized as dysplastic (LSIL/HSIL) versus non-dysplastic and HSIL versus LSIL/benign to determine both accuracy and potential clinical utility of a/LCI nuclear morphology measurements. Analysis of a/LCI data was conducted using both traditional Mie theory based processing and a new hybrid algorithm that provides improved processing speed to ascertain the feasibility of real-time measurements. Analysis of depth-resolved nuclear morphology data revealed a/LCI was able to detect a significant increase in the nuclear diameter at the depth bin containing the basal layer of the epithelium for dysplastic versus non-dysplastic and HSIL versus LSIL/Benign biopsy sites (both p < 0.001). Both processing techniques resulted in high sensitivity and specificity (> 0.80) in identifying dysplastic biopsies and HSIL. The hybrid algorithm demonstrated a threefold decrease in processing time at a slight cost in classification accuracy. The results demonstrate the feasibility of using a/LCI as an adjunctive clinical tool for detecting cervical dysplasia and guiding the identification of optimal biopsy sites. The faster speed from the hybrid algorithm offers a promising approach for real-time clinical analysis. PMID:27883177

Self-sampling with HPV mRNA analyses from vagina and urine compared with cervical samples.

PubMed

Asciutto, Katrin Christine; Ernstson, Avalon; Forslund, Ola; Borgfeldt, Christer

2018-04-01

In order to increase coverage in the organized cervical screening program, self-sampling with HPV analyses has been suggested. The aim was to compare human papillomavirus (HPV) mRNA detection in vaginal and urine self-collected samples with clinician-taken cervical samples and the corresponding clinician-taken histological specimens. Self-collected vaginal, urine and clinician-taken cervical samples were analyzed from 209 women with the Aptima mRNA assay (Hologic Inc, MA, USA). Cervical cytology, colposcopy, biopsy and/or the loop electrosurgical excision procedure (LEEP) were performed in every examination. The sensitivity of the HPV mRNA test in detecting high-grade squamous intraepithelial lesions (HSIL)/adenocarcinoma in situ (AIS)/cancer cases was as follows: for the vaginal self-samples 85.5% (95% CI; 75.0-92.8), the urinary samples 44.8% (95% CI; 32.6-57.4), and for routine cytology 81.7% (95% CI; 70.7-89.9). For the clinician-taken cervical HPV samples the sensitivity of the HPV mRNA test in detecting HSIL/AIS/cancer was 100.0% (95% CI; 94.9-100.0). The specificity of the HPV mRNA was similar for the clinician-taken cervical HPV samples and the self-samples: 49.0% vs. 48.1%. The urinary HPV samples had a specificity of 61.9% and cytology had a specificity of 93.3%. The sensitivity of the Aptima HPV mRNA test in detecting HSIL/AIS/cancer from vaginal self-samples was similar to that of routine cytology. The Aptima HPV mRNA vaginal self-sampling analysis may serve as a complement in screening programs. Copyright © 2018 Elsevier B.V. All rights reserved.

Efficacy of human papillomavirus-based screen-and-treat for cervical cancer prevention among HIV-infected women.

PubMed

Kuhn, Louise; Wang, Chunhui; Tsai, Wei-Yann; Wright, Thomas C; Denny, Lynette

2010-10-23

Cervical cancer prevention should be provided as part of primary healthcare services for HIV-infected women but conventional screening programs are difficult to implement in low-resource settings. Here, we evaluate the efficacy among HIV-infected women of a simpler, screen-and-treat strategy in which all women with a positive screening test are treated with cryotherapy. We conducted a randomized clinical trial of two screen-and-treat strategies among 6555 women in Cape Town, South Africa, among whom 956 were HIV-positive. Women were randomized to screen-and-treat utilizing either human papillomavirus DNA testing or visual inspection with acetic acid as the screening method or to a control group. Women were followed for up to 36 months after randomization with colposcopy and biopsy to determine the study endpoint of cervical intraepithelial neoplasia grade 2 or higher. In the control group, HIV-positive women had higher rates of cervical intraepithelial neoplasia grade 2 or higher detected by 36 months (14.9%) than HIV-negative women (4.6%) (P = 0.0006). Screen-and-treat utilizing human papillomavirus DNA testing significantly reduced cervical intraepithelial neoplasia grade 2 or higher through 36 months in both HIV-positive (relative risk = 0.20, 95% confidence interval 0.06-0.69) and HIV-negative women (relative risk = 0.31, 95% confidence interval 0.20-0.50). Reductions in the visual inspection with acetic acid-and-treat group were less marked. Complications of cryotherapy were mostly minor and did not differ in frequency between HIV-positive and HIV-negative women. Screen-and-treat using human papillomavirus testing is a simple and effective method to reduce high-grade cervical cancer precursors in HIV-infected women.

The Peru Cervical Cancer Prevention Study (PERCAPS): the technology to make screening accessible.

PubMed

Levinson, Kimberly L; Abuelo, Carolina; Salmeron, Jorge; Chyung, Eunice; Zou, Jing; Belinson, Suzanne E; Wang, Guixiang; Ortiz, Carlos Santos; Vallejos, Carlos Santiago; Belinson, Jerome L

2013-05-01

This study utilized a combination of HPV self-sampling, iFTA elute specimen cards, and long distance transport for centralized processing of specimens to determine the feasibility of large-scale screening in remote and transient populations. This study was performed in two locations in Peru (Manchay and Iquitos). The "Just For Me" cervico-vaginal brush and iFTA elute cards were used for the collection and transport of specimens. Samples were shipped via FedEx to China and tested for 14 types of high-risk HPV using PCR based MALDI-TOF. HPV positive women were treated with cryotherapy after VIA triage, and followed-up with colposcopy, biopsy, ECC, and repeat HPV testing at 6 months. Six hundred and forty three women registered, and 632 returned a sample over a 10 day period. Within 2 weeks, specimens were shipped, samples tested, and results received by study staff. Sixty-eight women (10.8%) tested positive, and these results were delivered over 4 days. Fifty-nine HPV positive women (87%) returned for evaluation and treatment, and 2 had large lesions not suitable for cryotherapy. At 6 months, 42 women (74%) returned for follow-up, and 3 had CIN 2 (all positive samples from the endocervical canal). Ninety eight percent of participants reported that they would participate in this type of program again. Utilizing HPV self-sampling, solid media specimen cards for long distance transport, and centralized high throughput processing, we achieved rapid delivery of results, high satisfaction levels, and low loss to follow-up for cervical cancer screening in remote and transient populations. Copyright © 2013 Elsevier Inc. All rights reserved.

Lymphoma of the Cervix: Case Report and Review of the Literature.

PubMed

Hilal, Ziad; Hartmann, Franziska; Dogan, Askin; Cetin, Cem; Krentel, Harald; Schiermeier, Sven; Schultheis, Beate; Tempfer, Clemens B

2016-09-01

Lymphoma of the uterine cervix (LUCX) is rare and may occur as a primary or secondary manifestation of this disease. Clinical and cytological presentations of LUCX vary and establishing diagnosis is often difficult. Surgery followed by radiation or chemotherapy is the mainstay of treatment. We present the case of a 73-year-old woman with recurrent pathological PAP smears of the cervix and a history of chronic lymphatic leukemia 15 years ago. Colposcopy of the cervix showed no acetowhite lesion and a conization was performed. Histology revealed endocervical lymphoid cells, specified as low-malignant B-Non-Hodgkin lymphoma of the cervix based on the expression of CD5, CD20, and CD23, whilst CD10 and cyclin D1 were negative. The diagnosis was confirmed by flow cytometry of peripheral blood. Staging revealed enlarged iliacal, para-aortic, mediastinal, cervical, subclavicular, and inguinal lymph nodes and hepatosplenomegaly. Bone marrow analysis confirmed lymphoid infiltration consistent with B-cell lymphoma. The patient was scheduled for a combined immuno-chemotherapy with obinutuzumab and chlorambucil. In a MEDLINE literature search, 246 cases of LUCX were identified. One hundred and eighty-five cases were primary and 61 cases were secondary manifestations of LUCX. With a mean follow-up time of 38 months, overall survival was 81%. Data in the literature including clinical and histological characteristics of LUCX as well as the clinical management and prognosis are discussed herein. LUCX is rare and has distinct clinical and histological features. LUCX is usually treated with local surgical excision followed by radiotherapy or chemotherapy. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Non-invasive analysis of hormonal variations and effect of postmenopausal Vagifem treatment on women using in vivo high wavenumber confocal Raman spectroscopy.

PubMed

Duraipandian, Shiyamala; Zheng, Wei; Ng, Joseph; Low, Jeffrey J H; Ilancheran, A; Huang, Zhiwei

2013-07-21

This study aims to evaluate the feasibility of applying high wavenumber (HW) confocal Raman spectroscopy for non-invasive assessment of menopause-related hormonal changes in the cervix as well as for determining the effect of Vagifem(®) treatment on postmenopausal women with atrophic cervix. A rapid HW confocal Raman spectroscopy system coupled with a ball lens fiber-optic Raman probe was utilized for in vivo cervical tissue Raman measurements at 785 nm excitation. A total of 164 in vivo HW Raman spectra (premenopausal (n = 104), postmenopausal-prevagifem (n = 34), postmenopausal-postvagifem (n = 26)) were measured from the normal cervix of 26 patients undergoing colposcopy. We established the biochemical basis of premenopausal, postmenopausal-prevagifem and postmenopausal-postvagifem cervix using semiquantitative biomolecular modeling derived from Raman-active biochemicals (i.e., lipids, proteins and water) that play a critical role in HW Raman spectral changes associated with the menopausal process. The diagnostic algorithms developed based on partial least squares-discriminant analysis (PLS-DA) together with leave-one patient-out, cross-validation yielded the diagnostic sensitivities of 88.5%, 91.2% and 88.5%, and specificities of 91.7%, 90.8% and 99.3%, respectively, for non-invasive in vivo discrimination among premenopausal, postmenopausal-prevagifem and postmenopausal-postvagifem cervix. This work demonstrates for the first time that HW confocal Raman spectroscopy in conjunction with biomolecular modeling can be a powerful diagnostic tool for identifying hormone/menopause-related variations in the native squamous epithelium of normal cervix, as well as for assessing the effect of Vagifem treatment on postmenopausal atrophic cervix in vivo during clinical colposcopic inspections.

What women want. Women's preferences for the management of low-grade abnormal cervical screening tests: a systematic review.

PubMed

Frederiksen, M E; Lynge, E; Rebolj, M

2012-01-01

If human papillomavirus (HPV) testing will replace cytology in primary cervical screening, the frequency of low-grade abnormal screening tests will double. Several available alternatives for the follow-up of low-grade abnormal screening tests have similar outcomes. In this situation, women's preferences have been proposed as a guide for management decisions. To determine women's preferences for the follow-up of low-grade cervical screening abnormalities. Using Medical Subject Headings (MeSH) terms, PubMed was searched for articles published up to December 2010. The reference lists of the retrieved studies were consulted. Studies asking women to state a preference between active follow-up and observation for the management of low-grade abnormalities on screening cytology or HPV tests. Information on study design, participants and outcomes was retrieved using a prespecified form. Studies were sorted by design. Thirteen studies were included in the review. In all five studies that surveyed women with abnormal tests before any management had started, two-thirds preferred active follow-up, predominantly as immediate colposcopy, to observation, predominantly as repeated Pap smears. In all but two studies testing other situations, women more often expressed a preference for active follow-up than for observation; however, women appeared to be somewhat more willing to accept observation if reassured of the low risk of cervical cancer. Even for low-grade abnormal cervical tests, women tend to prefer active management strategies. It may be a challenge to meet their expectations of optimal follow-up when HPV testing is used in primary screening. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

US Navy Women's Experience of an Abnormal Cervical Cancer Screening.

PubMed

Braun, Lisa A; Kennedy, Holly Powell; Sadler, Lois S; Dixon, Jane; Womack, Julie; Wilson, Candy

2016-01-01

Recent policy revisions allow greater inclusion of military women in operational and/or deployable positions (ie, shipboard, overseas, and war zone duty assignments), but these positions can create unique health care challenges. Military members are often transient due to deployments and change of duty stations, impacting timely follow-up care for treatable health conditions. There has been minimal research on challenges or strategies in preventive health screening and follow-up for US military women. The purpose of this qualitative research study was to describe US Navy women's experiences with abnormal cervical cancer screenings requiring colposcopic follow-up care. Ship- and shored-based women receiving care at a military colposcopy clinic completed interviews about their experience. Two forms of narrative analysis, Labov's sociolinguistic structural analysis and Braun and Clarke's thematic analysis, were employed to gain a more robust understanding of the women's experiences. The sample was comprised of 26 women (16 ship-based, 10 shore-based). Five themes were identified: 1) It's like this bombshell (initial abnormal results notification); 2) I didn't understand (self-discovery process); 3) Freaked (emotional toll); 4) It's kind of like this back and forth (scheduling and navigating care); and 5) It really opened my eyes (lessons learned). The women's stories highlighted some issues unique to military health care, such as operational demands and follow-up care; other issues are likely common for most women learning about an abnormal cervical cancer screening result. Areas important for practice and future research include improving notification practices, providing information, understanding women's fear, and continuity of care. Research exploring educational initiatives and self-management practices are critical within military populations. © 2016 by the American College of Nurse-Midwives.

A comparison of two visual inspection methods for cervical cancer screening among HIV-infected women in Kenya

PubMed Central

Sneden, Jennifer; Leslie, Hannah H; Abdulrahim, Naila; Maloba, May; Bukusi, Elizabeth; Cohen, Craig R

2014-01-01

Abstract Objective To determine the optimal strategy for cervical cancer screening in women with human immunodeficiency virus (HIV) infection by comparing two strategies: visual inspection of the cervix with acetic acid (VIA) and VIA followed immediately by visual inspection with Lugol’s iodine (VIA/VILI) in women with a positive VIA result. Methods Data from a cervical cancer screening programme embedded in two HIV clinic sites in western Kenya were evaluated. Women at a central site underwent VIA, while women at a peripheral site underwent VIA/VILI. All women positive for cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) on VIA and/or VILI had a confirmatory colposcopy, with a biopsy if necessary. Overall test positivity, positive predictive value (PPV) and the CIN 2+ detection rate were calculated for the two screening methods, with biopsy being the gold standard. Findings Between October 2007 and October 2010, 2338 women were screened with VIA and 1124 with VIA/VILI. In the VIA group, 26.4% of the women tested positive for CIN 2+; in the VIA/VILI group, 21.7% tested positive (P < 0.01). Histologically confirmed CIN 2+ was detected in 8.9% and 7.8% (P = 0.27) of women in the VIA and VIA/VILI groups, respectively. The PPV of VIA for biopsy-confirmed CIN 2+ in a single round of screening was 35.2%, compared with 38.2% for VIA/VILI (P = 0.41). Conclusion The absence of any differences between VIA and VIA/VILI in detection rates or PPV for CIN 2+ suggests that VIA, an easy testing procedure, can be used alone as a cervical cancer screening strategy in low-income settings. PMID:24700979

Prevalence of anal infection due to high-risk human papillomavirus and analysis of E2 gene integrity among women with cervical abnormalities.

PubMed

Gonzalez-Losa, María Del Refugio; Puerto-Solís, Marylin; Ayora-Talavera, Guadalupe; Gómez-Carvallo, Jesús; Euán-López, Alejandra; Cisneros-Cutz, José I; Rosado-López, Ariel; Echeverría Salazar, Jesúa; Conde-Ferráez, Laura

2018-04-01

High-risk human papillomaviruses (HR-HPV) infection has been associated with 90% of anal cancer cases. Women with abnormal cytology are a high-risk group to develop anal neoplasia. The aim of this study is to describe the prevalence and epidemiology of HR-HPV 16, 18, 45, and 58 anal infections in women with cervical abnormalities, as well as to assess E2 gene integrity. A cross-sectional study was performed on 311 cervical and 311 anal samples from patients with abnormal cytology in two colposcopy clinics in Yucatan, Mexico. A specific PCR for oncogenes was performed in order to identify HVP 16, 18, 45 and 58. Real time PCR was used to amplify the whole HPV 16, 18, and 58 E2 gene to verify its integrity in anal samples. High risk HPV 16, 18, 58, and/or 45 were found in 41.47% (129/311) of cervical samples, and in 30.8% (96/331) of anal samples, with 18% (57/311) of the patients being positive in both samples. The same genotypes in both anatomical sites were observed in 11.25% (35/311). The E2 gene was disrupted in 82% of all tested samples. The frequency of genome disruption viral integration in anal samples by genotype was: HPV 58 (97.2%); HPV 16 (72.4%), and HPV 18 (0%). Women with cervical disease have HR-HPV anal infections, and most of them have the E2 gene disrupted, which represents a risk to develop anal cancer. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

[Hysterectomy and intraepithelial neoplasia of the lower female genital tract].

PubMed

Spuhler, S; De Grandi, P

1992-01-01

Delimiting the place of hysterectomy in cases of lower genital tract intraepithelial neoplasias in women. The laser and colposcopy centre (CCL) of a maternity unit in Lausanne in the Vaudois University Hospital Centre (CHUV). THE TYPE OF STUDY: Retrospective on 1,303 patients between 1986 and 1990. THE SUBJECTS AND TREATMENT: 853 cases of cervical intraepithelial neoplasia (CIN) and 79 cases of vaginal intraepithelial neoplasia (VAIN) were treated with CO2 laser. The situations in which hysterectomy could be considered in the course of treatment are discussed. They are: 1) Dysplasia persisting after treatment, 2) when pathological tissue is found on examining slides from conisation specimens, 3) micro-invasive carcinoma, 4) post-operative obstructive stenosis. The multiple location of dysplasia lesions of the lower genital tract was calculated for all the patients examined. It shows that hysterectomy itself will be insufficient to remove all dysplasias since frequently (9.2%) of lesions are found in the vagina in cases that have dysplasia of the cervix. Residual lesions after hysterectomy are shown up by VAIN which are responsible for the persistence of changes in the control smears (in which there were 9 cases of VAIN3 after hysterectomy in this series). Treatment therefore is hazardous and only poorly successful because the site of these lesions is often hidden in the scar through the top of the vagina. Furthermore their discovery in uncertain since there is a tendency at present to avoid out cytological screening of these patients once they have undergone hysterectomy. The high incidence of multifocal lesions and the possibility that is very real of residual dysplasia after hysterectomy has made the authors limit the place of hysterectomy in these cases, preferring to use conservative treatments and emphasizing the need to continue cytological controls for after treatment.

High-grade vulval intraepithelial neoplasia (VIN 3): a retrospective analysis of patient characteristics, management, outcome and relationship to squamous cell carcinoma of the vulva 1989-1999.

PubMed

Sykes, Peter; Smith, Natasha; McCormick, Peter; Frizelle, Frank A

2002-02-01

To determine patient and disease characteristics, treatment patterns and long-term outcomes, in order to help direct management of patients with VIN 3, to examine the risk of development of cancer following a diagnosis of VIN 3 and the risk of recurrent disease requiring multiple treatment episodes, and to review patients with vulval cancer, in order to establish the relative prevalence of VIN 3 related vulval cancers. Retrospective chart review of 65 consecutive patients diagnosed with VIN 3 between 1989 and 1999. All patients diagnosed with VIN 3 at Christchurch Womens' Hospital (1 January 1989 to 31 December 1999) and Dunedin Public Hospital (1 January 1990 to 31 December 1999). Age at diagnosis, symptoms, medical history disease characteristics, treatment, outcome and follow-up. The median age at diagnosis was 38 years. Smokers were younger than non-smokers. Two-thirds had associated dysplasia of the lower genital tract, 43% had high-grade lesions. Seventy-nine per cent were symptomatic for a median of 9.5 months. All had macroscopically visible disease. Colposcopy and histology diagnoses correlated in 72% of cases. Treatment by local excision was undertaken in 84% of cases of which 65% had involved margins. Fifty-one per cent required further treatment, risk factors were positive margins and multifocal disease. Three developed micro-invasive cancer. Treatment by local excision is both diagnostic and therapeutic. Excision may reveal micro-invasive cancer, patients are usually symptomatic and VIN 3 has some potential to become invasive. Treated patients may develop microinvasive disease but frank invasion was not seen. The true rate of malignant progression in untreated patients remains unclear and radical surgery is rarely indicated. All patients require long-term follow up.

Clinical significance of the qualification of atypical squamous cells of undetermined significance: An analysis on the basis of histologic diagnoses.

PubMed

Vlahos, N P; Dragisic, K G; Wallach, E E; Burroughs, F H; Fluck, S; Rosenthal, D L

2000-04-01

This study was undertaken to evaluate the significance of further qualification of atypical squamous cells of undetermined significance in routine Papanicolaou smears. A retrospective medical records review was conducted on 316 women whose Papanicolaou smears yielded diagnoses of either atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion or atypical squamous cells of undetermined significance suggestive of a reactive process. The overall incidence of a squamous intraepithelial lesion (cervical intraepithelial neoplasia grades I, II, and III) was higher in the group with atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion than in the group with results suggestive of a reactive process (41.1% vs 22.3%; P =.0344). Women with atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion were 9.7 times more likely to have high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia III) develop than were women with atypical squamous cells of undetermined significance suggestive of a reactive process (95% confidence interval, 1.26-74.64). The incidence of high-grade squamous intraepithelial lesion was higher among women 35 years old (17.8% vs 6.3%; P =.0378). Women with a diagnosis of atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion are more likely to have intraepithelial lesions develop than are those with atypical squamous cells of undetermined significance suggestive of a reactive process. Aggressive evaluation of cases of atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion with colposcopy and cervical biopsies may be appropriate. Age should be considered as an independent factor in the plan of management.

Value of high-risk HPV-DNA testing in the triage of ASCUS.

PubMed

Silverloo, Iréne; Andrae, Bengt; Wilander, Erik

2009-01-01

OBJECTIVE. Atypical squamous cells of undetermined significance (ASCUS) cells, occurring in organized cytological screening, may be either high-risk human papillomavirus (HPV) positive or negative. To refine the assessment of women with ASCUS, a high-risk HPV-DNA test is recommended as triage in Sweden. A total of 197 consecutive women (mean age 39 years, range 21-60) with a diagnosis of ASCUS from the primary screening were selected for triage. Their cervical smears were collected and evaluated by using conventional cytological examination in combination with a high-risk HPV-DNA test (hybrid capture 2). The women were categorized into four groups: Group A, Cytology + /HPV + ; Group B, Cytology-/HPV + ; Group C, Cytology + /HPV-; and Group D, Cytology-/ HPV-. Women within Groups A-C were admitted for colposcopy and cervical biopsy. The women in Group D were considered as a low-risk group for tumor development, and were re-examined after three years in the next round of the organized screening. In women in Group A (n=58) the prevalence of histological verified CIN2-3 was 41%, in Group B (n=41) 20%, and in Group C (n=9) 0%. In Group D (n=89), repeated primary screening three years later revealed CIN2-3 in two biopsies from 74 women studied (<3%). The prevalence of a high-risk HPV infection decreased with age in women with ASCUS. It was 74% in women <30 years and 19% in women > or =50 years. Adding a high-risk HPV test in secondary screening increased the identification of women with CIN2-3 lesions by 33% in comparison with repeat cytology (p=0.01). The clinical significance of the ASCUS diagnosis varied with age of the women.

Association between concurrent genital bleeding and cervical cancer: a cross-sectional study.

PubMed

Xavier-Júnior, José C C; Vale, Diama B; Zeferino, Luiz C; Dufloth, Rozany M

2015-09-01

Genital bleeding may be a common symptom among women with cervical cancer. Cross-sectional study evaluating whether the prevalence of cervical smear results is different in women with and without clinical information about concurrent genital bleeding. The sample consisted of 2 324 836 smears; of these, 0.4% had clinical information on genital bleeding. When stratified by age group, women with genital bleeding had a higher chance of a cytological result of a high-grade squamous intraepithelial lesion [30-49 years odds ratio (OR) 2.38; 95% confidence interval (CI) 1.60-3.53 and ≥50 years OR 6.30; 95%CI 3.72-10.67), of squamous cell carcinoma (SCC) (30-49 years OR 24.70; 95%CI 11.96-51.03 and ≥50 years OR 48.91; 95%CI 31.28-76.47) and of atypical glandular cells (30-49 years OR 5.72; 95%CI 3.30-9.93 and ≥50 years OR 11.56; 95%CI 5.96-22.45); there was also a higher chance of adenocarcinoma for women ≥50 years (OR 53.13; 95%CI 28.08-100.51). The sensitivity of genital bleeding for women aged 18-29 years was 0.4% for high-grade squamous intraepithelial lesion (HSIL); for women 30-49 years old the rate was 0.9% for HSIL, 8.6% for SCC and 2.1% for atypical glandular cells of undetermined significance (AGUS), while for women aged from 50 years or more the rates were 2.0% for HSIL, 13.7% for SCC, 3.6% for AGUS and 14.7% for adenocarcinoma. Women ≥30 years old with genital bleeding should be referred for colposcopy to rule out the possibility of cervical cancer. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Glycerol Monolaurate Does Not Alter Rhesus Macaque (Macaca mulatta) Vaginal Lactobacilli and Is Safe for Chronic Use▿

PubMed Central

Schlievert, Patrick M.; Strandberg, Kristi L.; Brosnahan, Amanda J.; Peterson, Marnie L.; Pambuccian, Stefan E.; Nephew, Karla R.; Brunner, Kevin G.; Schultz-Darken, Nancy J.; Haase, Ashley T.

2008-01-01

Glycerol monolaurate (GML) is a fatty acid monoester that inhibits growth and exotoxin production of vaginal pathogens and cytokine production by vaginal epithelial cells. Because of these activities, and because of the importance of cytokine-mediated immune activation in human immunodeficiency virus type 1 (HIV-1) transmission to women, our laboratories are performing studies on the potential efficacy of GML as a topical microbicide to interfere with HIV-1 transmission in the simian immunodeficiency virus-rhesus macaque model. While GML is generally recognized as safe by the FDA for topical use, its safety for chronic use and effects on normal vaginal microflora in this animal model have not been evaluated. GML was therefore tested both in vitro for its effects on vaginal flora lactobacilli and in vivo as a 5% gel administered vaginally to monkeys. In vitro studies demonstrated that lactobacilli are not killed by GML; GML blocks the loss of their viability in stationary phase and does not interfere with lactic acid production. GML (5% gel) does not quantitatively alter monkey aerobic vaginal microflora compared to vehicle control gel. Lactobacilli and coagulase-negative staphylococci are the dominant vaginal aerobic microflora, with beta-hemolytic streptococci, Staphylococcus aureus, and yeasts sporadically present; gram-negative rods are not part of their vaginal flora. Colposcopy and biopsy studies indicate that GML does not alter normal mucosal integrity and does not induce inflammation; instead, GML reduces epithelial cell production of interleukin 8. The studies suggest that GML is safe for chronic use in monkeys when applied vaginally; it does not alter either mucosal microflora or integrity. PMID:18838587

HPV genotype profile in a Norwegian cohort with ASC-US and LSIL cytology with three year cumulative risk of high grade cervical neoplasia.

PubMed

Lie, A K; Tropé, A; Skare, G B; Bjørge, T; Jonassen, C M; Brusegard, K; Lönnberg, S

2018-01-01

To explore the HPVgenotype profile in Norwegian women with ASC-US/LSIL cytology and the subsequent risk of high-grade cervical neoplasia (CIN 3+). In this observational study delayed triage of ASC-US/LSIL of 6058 women were included from 2005 to 2010. High-risk HPV detection with Hybrid Capture 2 (HC2) was used and the HC2+ cases were genotyped with in-house nmPCR. Women were followed-up for histologically confirmed CIN3+ within three years of index HPV test by linkage to the screening databases at the Cancer Registry of Norway. HC2 was positive in 45% (2756/6058) of the women. Within 3years CIN3+ was diagnosed in 26% of women<34year and in 15%≥34year. HC2 was positive at index in 94% of CIN3+ cases and negative in 64 cases including three women with cervical carcinomas. Women<34years with single infections of HPV 16, 35, 58 or 33 or multiple infections including HPV 16, 52, 33 or 31 were associated with highest proportions of CIN 3+. Older women with single infection with HPV 16, 33, 31 or 35 or multiple infections including HPV 16, 33, 31 or 18/39 were more likely to develop CIN 3+. HPV 16 and HPV 33 at baseline both as single or multiple infections, were associated with the highest risk for CIN3+. Among older women, all 13 high-risk genotypes as single infection were associated with >20% risk of CIN3+. Further studies are necessary to risk stratify the individual genotypes to reduce the number of colposcopies in Norway. Copyright © 2017 Elsevier Inc. All rights reserved.

An evaluation of clinical performance of FTA cards for HPV 16/18 detection using cobas 4800 HPV Test compared to dry swab and liquid medium.

PubMed

Dong, Li; Lin, Chunqing; Li, Li; Wang, Margaret; Cui, Jianfeng; Feng, Ruimei; Liu, Bin; Wu, Zeni; Lian, Jia; Liao, Guangdong; Chen, Wen; Qiao, Youlin

2017-09-01

Effective dry storage and transport media as an alternative to conventional liquid-based medium would facilitate the accessibility of women in the low-resource settings to human papillomavirus (HPV)- based cervical cancer screening. To evaluate analytical and clinical performance of indicating FTA™ Elute Cartridge (FTA card) for the detection of HPV16/18 and cervical precancerous lesions and cancer compared to dry swab and liquid medium. Ninety patients with abnormal cytology and/or HPV infection were included for analysis. Three specimens of cervical exfoliated cells from each woman were randomly collected by FTA card, dry swab or liquid-based medium prior to colposcopy examination. The subsequent HPV DNA tests were performed on cobas 4800 HPV platform. High-risk HPV (hrHPV) positivity rate was 63.3%, 62.2% and 65.6% for samples collected by FTA card, dry swab and liquid medium, respectively. The overall agreements and kappa values for the detection of hrHPV, HPV 16 and HPV 18 between FTA card and liquid-based medium were 88.9% (κ=0.76), 97.8% (κ=0.94) and 100% (κ=1.0),respectively; between FTA card and dry swab were 92.1% (κ=0.83), 94.5% (κ=0.87) and 100% (κ=1.0), respectively. The performances of hrHPV tested by FTA card, dry swab, and liquid-based medium for detecting CIN2+ were comparable in terms of the sensitivity and specificity. The specificity of detection of CIN2+ by HPV16/18 increased by approximately 40% compared to hrHPV for any medium albeit at cost of a moderate loss of sensitivity. Dry medium might offer an alternative to conventional liquid-based medium in the HPV-based cervical cancer screening program especially in low-resource settings but still needs further evaluation. Copyright © 2017. Published by Elsevier B.V.

Clinical evaluation of high-risk HPV detection on self-samples using the indicating FTA-elute solid-carrier cartridge.

PubMed

Geraets, D T; van Baars, R; Alonso, I; Ordi, J; Torné, A; Melchers, W J G; Meijer, C J L M; Quint, W G V

2013-06-01

High-risk human papillomavirus (hrHPV) testing in cervical screening is usually performed on physician-taken cervical smears in liquid-based medium. However, solid-state specimen carriers allow easy, non-hazardous storage and transportation and might be suitable for self-collection by non-responders in screening and in low-resource settings. We evaluated the adequacy of self-collected cervicovaginal (c/v) samples using a Viba-brush stored on an Indicating FTA-elute cartridge (FTA-based self-sampling) for hrHPV testing in women referred to a gynecology clinic due to an abnormal smear. 182 women accepted to self-collect a c/v sample. After self-sampling, a physician obtained a conventional liquid-based cervical smear. Finally, women were examined by colposcopy and a biopsy was taken when clinically indicated. Self-samples required only simple DNA elution, and DNA was extracted from physician-obtained samples. Both samples were tested for 14 hrHPVs by GP5+/6+-EIA-LQ Test and SPF(10)-DEIA-LiPA(25). Both assays detected significantly more hrHPV in physician-collected specimens than in self-collected samples (75.3% and 67.6% by SPF(10); 63.3% and 53.3% by GP5+/6+, respectively). The combination of physician-collected specimen and GP5+/6+ testing demonstrated the optimal balance in sensitivity (98.0%) and specificity (48.1%) for CIN2+ detection in this referral population. A test system of FTA-based self-collection and SPF(10) hrHPV detection approached this sensitivity (95.9%) and specificity (42.9%). These results show that the clinical performance of hrHPV detection is determined by both the sample collection system and the test method. FTA-based self-collection with SPF(10) testing might be valuable when a liquid-based medium cannot be used, but requires further investigation in screening populations. Copyright © 2013 Elsevier B.V. All rights reserved.

Safety of a silicone elastomer vaginal ring as potential microbicide delivery method in African women: A Phase 1 randomized trial.

PubMed

Nel, Annaléne; Martins, Janine; Bekker, Linda-Gail; Ramjee, Gita; Masenga, Gileard; Rees, Helen; van Niekerk, Neliëtte

2018-01-01

Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with vaginal rings. This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo vaginal ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania. 170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo vaginal ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo vaginal ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuring no signs or symptoms of genital irritation at crossover. No safety concerns were identified for any safety variables assessed during the trial. No serious adverse events were reported considered related to the placebo vaginal ring. Vaginal candidiasis was the most common adverse event occurring in 11% of participants during each trial period. Vaginal discharge (2%), vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the vaginal ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive during the trial. The silicone elastomer vaginal ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides.

Project for the National Program of Early Diagnosis of Endometrial Cancer Part I.

PubMed

Bohîlțea, R E; Ancăr, V; Cirstoiu, M M; Rădoi, V; Bohîlțea, L C; Furtunescu, F

2015-01-01

Endometrial cancer recorded a peak incidence in ages 60-64 years in Romania, reaching in 2013 the average value of 8.06/ 100,000 women, and 15.97/ 100,000 women within the highest risk age range, having in recent years an increasing trend, being higher in urban than in rural population. Annually, approximately 800 new cases are registered in our country. The estimated lifetime risk of a woman to develop endometrial cancer is of about 1,03%. Based on an abnormal uterine bleeding, 35% of the endometrial cancers are diagnosed in an advanced stage of the disease, with significantly diminished lifetime expectancy. Drafting a national program for the early diagnosis of endometrial cancer. We proposed a standardization of the diagnostic steps and focused on 4 key elements for the early diagnosis of endometrial cancer: investigation of abnormal uterine bleeding occurring in pre/ post-menopausal women, investigating features/ anomalies of cervical cytology examination, diagnosis, treatment and proper monitoring of precursor endometrial lesions or cancer associated endometrial lesions and screening high risk populations (Lynch syndrome, Cowden syndrome). Improving medical practice based on diagnostic algorithms addresses the four risk groups, by improving information system reporting and record keeping. Improving addressability cases by increasing the health education of the population will increase the rate of diagnosis of endometrial cancer in the early stages of the disease. ACOG = American Society of Obstetricians and Gynecologists, ASCCP = American Society for Colposcopy and Cervical Pathology, PATT = Partial Activated Thromboplastin Time, BRCA = Breast Cancer Gene, CT = Computerized Tomography, IFGO = International Federation of Gynecology and Obstetrics, HLG = Hemoleucogram, HNPCC = Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome), IHC = Immunohistochemistry, BMI = Body Mass Index, INR = International Normalized Ratio, MSI = Microsatellites instability, MSI-H/ MSI-L = high (positive test)/ low (negative test) microsatellites instability, WHO = World Health Organization, PCR = Polymerase chain reaction, MRI = Magnetic Resonance Imaging, SGO = Society of Gynecologic Oncologists, SHG = Sonohysterography, SRU = Society of Radiologists in Ultrasound, TQ = Time Quick, BT = Bleeding Time, TVUS = Transvaginal ultrasound, USPIO = Ultrasmall superparamagnetic iron oxide.

Human Papillomavirus Assays and Cytology in Primary Cervical Screening of Women Aged 30 Years and Above

PubMed Central

Rebolj, Matejka; Bonde, Jesper; Preisler, Sarah; Ejegod, Ditte; Rygaard, Carsten; Lynge, Elsebeth

2016-01-01

In women aged ≥30 years, Human Papillomavirus testing will replace cytology for primary cervical screening. We compared Hybrid Capture 2 (HC2), cobas, CLART, and APTIMA HPV assays with cytology on 2869 SurePath samples from women undergoing routine screening at 30–65 years in Copenhagen, Denmark. Women with cytological abnormalities were managed according to routine recommendations, with 92% completeness. Those with cytology-normal/HPV-positive samples (on any of the four assays) were invited for repeated cytology and HPV testing in 1.5 year, and 58% had additional testing. HPV testing detected more ≥CIN3 than cytology (HC2: 35, cobas, CLART: 37, APTIMA: 34, cytology: 31), although statistically the differences were not significant. Cobas and CLART detected significantly more ≥CIN2 than cytology (cobas, CLART: 49, cytology: 39). The proportion of women with false-positive test results (positive test results without ≥CIN3) varied between 3.3% with cytology and 14.9% with cobas. All HPV assays led to significantly more false-positive tests, whereas compared to HC2 cobas and CLART were associated with a significantly higher and APTIMA with a significantly lower proportion. Detection of CIN1 was particularly increased for the three DNA assays. With APTIMA combined with cytological triage, about 20% more women were referred for colposcopy than with cytology screening. With the three DNA assays, the increase was ≥50%. The number of women with repeated testing was twice as high with APTIMA and almost five times as high with cobas compared to cytology. To our knowledge, Horizon was the only study set in routine practice that compared more than two HPV assays in the same women while also ascertaining the histological status of women with normal cytology/HPV-positive test results. HPV-based screening of Danish women aged 30–65 detected more high-grade CIN but decreased the screening specificity, and increased the demand for additional testing. PMID:26789267

Comparative performance of novel self-sampling methods in detecting high-risk human papillomavirus in 30,130 women not attending cervical screening.

PubMed

Bosgraaf, Remko P; Verhoef, Viola M J; Massuger, Leon F A G; Siebers, Albert G; Bulten, Johan; de Kuyper-de Ridder, Gabriëlle M; Meijer, Chris J M; Snijders, Peter J F; Heideman, Daniëlle A M; IntHout, Joanna; van Kemenade, Folkert J; Melchers, Willem J G; Bekkers, Ruud L M

2015-02-01

We determined whether the participation rate for a brush-based cervicovaginal self-sampling device is noninferior to the participation rate for a lavage-based one for testing for hrHPV (high-risk human papillomavirus). Additionally, positivity rates for hrHPV, the detection rates for cervical intraepithelial neoplasia grades 2 and 3 or worse (CIN2+/3+), and user comfort were compared. A total of 35,477 non-responders of the regular cervical screening program aged 33-63 years were invited to participate. Eligible women (n = 30,130) were randomly assigned to receive either a brush-based or a lavage-based device, and a questionnaire for reporting user convenience. Self-sampling responders testing hrHPV-positive were invited for a physician-taken sample for cytology; triage-positive women were referred for colposcopy. A total of 5,218 women participated in the brush-based sampling group (34.6%) and 4809 women in the lavage-based group (31.9%), i.e. an absolute difference of 2.7% (95%CI 1.8-4.2). The hrHPV-positivity rates in the two groups were identical (8.3%, relative risk (RR) 0.99, 95%CI 0.87-1.13). The detection of CIN2+ and CIN3+ in the brush group (2.0% for CIN2+; 1.3% for CIN3+) was similar to that in the lavage group (1.9% for CIN2+; 1.0% for CIN3+) with a cumulative RR of 1.01, 95%CI 0.83-1.24 for CIN2+ and 1.25, 95%CI 0.92-1.70 for CIN3+. The two self-sampling devices performed similarly in user comfort. In conclusion, offering a brush-based device to non-responders is noninferior to offering a lavage-based device in terms of participation. The two self-sampling methods are equally effective in detecting hrHPV, CIN2+/CIN3+ and are both well accepted. © 2014 UICC.

Accuracy of reading liquid based cytology slides using the ThinPrep Imager compared with conventional cytology: prospective study

PubMed Central

d'Assuncao, Jefferson; Irwig, Les; Macaskill, Petra; Chan, Siew F; Richards, Adele; Farnsworth, Annabelle

2007-01-01

Objective To compare the accuracy of liquid based cytology using the computerised ThinPrep Imager with that of manually read conventional cytology. Design Prospective study. Setting Pathology laboratory in Sydney, Australia. Participants 55 164 split sample pairs (liquid based sample collected after conventional sample from one collection) from consecutive samples of women choosing both types of cytology and whose specimens were examined between August 2004 and June 2005. Main outcome measures Primary outcome was accuracy of slides for detecting squamous lesions. Secondary outcomes were rate of unsatisfactory slides, distribution of squamous cytological classifications, and accuracy of detecting glandular lesions. Results Fewer unsatisfactory slides were found for imager read cytology than for conventional cytology (1.8% v 3.1%; P<0.001). More slides were classified as abnormal by imager read cytology (7.4% v 6.0% overall and 2.8% v 2.2% for cervical intraepithelial neoplasia of grade 1 or higher). Among 550 patients in whom imager read cytology was cervical intraepithelial neoplasia grade 1 or higher and conventional cytology was less severe than grade 1, 133 of 380 biopsy samples taken were high grade histology. Among 294 patients in whom imager read cytology was less severe than cervical intraepithelial neoplasia grade 1 and conventional cytology was grade 1 or higher, 62 of 210 biopsy samples taken were high grade histology. Imager read cytology therefore detected 71 more cases of high grade histology than did conventional cytology, resulting from 170 more biopsies. Similar results were found when one pathologist reread the slides, masked to cytology results. Conclusion The ThinPrep Imager detects 1.29 more cases of histological high grade squamous disease per 1000 women screened than conventional cytology, with cervical intraepithelial neoplasia grade 1 as the threshold for referral to colposcopy. More imager read slides than conventional slides were satisfactory for examination and more contained low grade cytological abnormalities. PMID:17604301

Role of p16 testing in cervical cancer screening among HIV-infected women.

PubMed

McGrath, Christine J; Garcia, Rochelle; Trinh, Trong T; Richardson, Barbra A; John-Stewart, Grace C; Nyongesa-Malava, Evans; Mugo, Nelly R; Glynn, Emily H; Sakr, Samah R; De Vuyst, Hugo; Chung, Michael H

2017-01-01

p16 immunohistochemistry is used to evaluate for HPV-associated cervical intraepithelial neoplasia. The diagnostic performance of p16 in HIV infection is unclear. Between June-December 2009, HIV-infected women underwent Papanicolaou (Pap) smear, human papillomavirus (HPV) testing, visual inspection with acetic acid (VIA), and colposcopy-directed biopsy as the disease gold standard at a HIV clinic in Kenya. Pap smears were evaluated for p16 expression. Sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC) of p16 to detect CIN2/3 on histology and the impact of immunosuppression and ART was assessed. Of 331 cervical samples with p16 expression, p16 sensitivity and specificity to detect CIN2/3 was 54.1% and 72.4% respectively, which was lower than Pap and HPV in sensitivity, but higher in specificity than Pap, HPV, and VIA. Combining tests and p16 reduced sensitivity and increased specificity of Pap from 90.5% to 48.7% and 51.4% to 81.7%; of VIA from 59.5% to 37.8% and 67.6% to 89.9%; and of HPV from 82.4% to 50.0% and 55.3% to 84.8%. Combination p16 increased the PPV of Pap from 34.9% to 43.4%; of HPV from 34.7% to 48.7%; and VIA from 34.9% to 51.9%. Adjunctive p16 did not change AUC (P>0.05). P16 performance was not altered by immunosuppression or ART use. Combining p16 with HPV and VIA reduced the variation in HPV and VIA performance associated with CD4 and ART. As an adjunctive test in HIV-infected women, p16 immunohistochemistry increased specificity and PPV of HPV and VIA for CIN2/3, and was not altered in performance by immunosuppression, ART, or age.

The Clinical and Economic Benefits of Co-Testing Versus Primary HPV Testing for Cervical Cancer Screening: A Modeling Analysis.

PubMed

Felix, Juan C; Lacey, Michael J; Miller, Jeffrey D; Lenhart, Gregory M; Spitzer, Mark; Kulkarni, Rucha

2016-06-01

Consensus United States cervical cancer screening guidelines recommend use of combination Pap plus human papillomavirus (HPV) testing for women aged 30 to 65 years. An HPV test was approved by the Food and Drug Administration in 2014 for primary cervical cancer screening in women age 25 years and older. Here, we present the results of clinical-economic comparisons of Pap plus HPV mRNA testing including genotyping for HPV 16/18 (co-testing) versus DNA-based primary HPV testing with HPV 16/18 genotyping and reflex cytology (HPV primary) for cervical cancer screening. A health state transition (Markov) model with 1-year cycling was developed using epidemiologic, clinical, and economic data from healthcare databases and published literature. A hypothetical cohort of one million women receiving triennial cervical cancer screening was simulated from ages 30 to 70 years. Screening strategies compared HPV primary to co-testing. Outcomes included total and incremental differences in costs, invasive cervical cancer (ICC) cases, ICC deaths, number of colposcopies, and quality-adjusted life years for cost-effectiveness calculations. Comprehensive sensitivity analyses were performed. In a simulation cohort of one million 30-year-old women modeled up to age 70 years, the model predicted that screening with HPV primary testing instead of co-testing could lead to as many as 2,141 more ICC cases and 2,041 more ICC deaths. In the simulation, co-testing demonstrated a greater number of lifetime quality-adjusted life years (22,334) and yielded $39.0 million in savings compared with HPV primary, thereby conferring greater effectiveness at lower cost. Model results demonstrate that co-testing has the potential to provide improved clinical and economic outcomes when compared with HPV primary. While actual cost and outcome data are evaluated, these findings are relevant to U.S. healthcare payers and women's health policy advocates seeking cost-effective cervical cancer screening technologies.

Photodynamic therapy for premalignant lesions of the vulva and vagina: A long-term follow-up study.

PubMed

Choi, Min Chul; Kim, Mi Sun; Lee, Gee Hoon; Jung, Sang Geun; Park, Hyun; Joo, Won Duk; Lee, Chan; Lee, Je Ho; Hwang, Yoon Young; Kim, Seung Jo

2015-07-14

We aimed to evaluate responses to photodynamic therapy (PDT) and its long-term efficacy in preserving normal anatomy and function in women with premalignant lesions of the lower genital tract. Fifteen patients received PDT for vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VAIN), or vulvar Paget's disease between January 2003 and December 2013. Patients underwent colposcopy and/or vulvoscopy for assessment of lesions. Surface photoillumination with a 630-nm red laser light was applied to the lesions 48 hours after intravenous injection of 2 mg/kg photosensitizer (PSZ; Photogem®). The light dose to the lesions was 150 J/cm 2 . The median age of the 15 patients (VIN II: 3, VIN III: 4, VAIN II: 2, VAIN III: 3, Paget's disease: 3) was 42.3 years. The complete response (CR) rate was 80% (12/15) at the 3-month follow-up and 71.4% (10/14) at the 1-year follow-up. There were two cases of persistent disease at the 3-month follow-up. One patient with persistent disease underwent partial vulvectomy three times for repetitive recurrence, and the other received secondary PDT with topical 5-aminolevulinic acid (5-ALA) and subsequently showed no evidence of disease (NED). Another patient achieved 90% remission through a combination of additional alternative treatments after showing partial response (PR). In two cases of CR, recurrence was observed at the 1-year follow-up. Regarding adverse events, photosensitivity reactions such as facial edema and urticaria occurred in 13.3% (2/15) and perineal pain occurred in one patient. PDT may be an effective alternative treatment for premalignant lesions of the female lower genital tract to preserve normal anatomy and sexual function without therapeutic impairment. Lasers Surg. Med. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Scientific research in obstetrics and gynecology: changes in the trends over three decades.

PubMed

Kassem, Gamal A

2015-01-01

The aim of this work was to assess scientific research of master's and doctoral theses and essays in the Department of Obstetrics and Gynecology, Zagazig University, Egypt. All master's and doctoral theses and essays since the foundation of Department of Obstetrics and Gynecology, Zagazig University, Egypt, in 1975 till end of 2012 were reviewed. A total of 703 theses and essays were reviewed. The important topics in the specialty of obstetrics and gynecology were covered and updated. Infertility, in vitro fertilization-embryo transfer (IVF-ET) and related techniques, and polycystic ovarian disease were the most common gynecologic topics (27.2%), followed by gynecologic oncology (18.5%). Preeclampsia was the most common obstetrics topic (18.8%), followed by issues of high-risk pregnancy, fetal growth restriction, and fetal well-being (11.6%). The number of researches that allow the candidates to learn skills was 183 and it was increased from 4.4% of all research in the period 1979-1988 to 33.2% in period 1989-2000 then slightly decreased to 31.2% in period 2001-2012. Ultrasonography was on the top and was present in 99 out of 183 (54.1%) followed by laparoscopy (30, 16.4%), hysteroscopy (25, 13.7%), IVF-ET and related techniques (16, 8.7%) and colposcopy (13, 7.1%) researches. Multi-disciplinary research was decreased by 61.7% in the period 2001-2012. Researches in academic fields were abandoned and in some clinically important areas like preeclampsia were decreased. Scientific research of master's and doctoral theses and essays was comprehensive, updated, and had some autonomy independent of plans. Research which enable the candidate to learn skills were increased on the expense of academic, clinical and multidisciplinary research. It could be recommended that plans for scientific research should be flexible and should leave a space for local departmental views. Proper training of residents during their rotation in these subspecialties may help to revive the lost interest in clinically important areas.

Clinical significance of atypical squamous cells of undetermined significance in detecting preinvasive cervical lesions in post- menopausal Turkish women.

PubMed

Tokmak, Aytekin; Guzel, Ali Irfan; Ozgu, Emre; Oz, Murat; Akbay, Serap; Erkaya, Salim; Gungor, Tayfun

2014-01-01

To evaluate the clinical significance of atypical squamous cells of undetermined significance (ASCUS) in PAP test in post-menopausal women and compare with reproductive age women. A total of 367 patients who referred to our gynecologic oncology clinic were included to the study between September 2012 and August 2013. Data for 164 post-menopausal (group 1) and 203 pre-menopausal (group 2) women with ASCUS cytology were evaluated retrospectively. Immediate colposcopy and endocervical curettage was performed for both groups and conization for all women with a result suggestive of CIN2-3. Histopathological results and demographic features of patients were compared between the two groups. Mean age of the patients was 54.6±6.5 years in group 1 and 38±6.6 years in group 2. Some 14 (8.5%) of post- menopausal women and 36 (17.7%) of pre-menopausal women were current smokers (p=011). Totals of 38 (23.2%) post-menopausal and 64 (31.5%) pre-menopausal women were assessed for HPV-DNA. High risk HPV was detected in 7 (4.3%) and 21 (10.3%), respectively (p=0.029). Final histopathological results recorded were normal cervix, low grade cervical intra-epithelial neoplasia (CIN 1), and high grade cervical intra-epithelial neoplasia (CIN2-3). In group 1 results were 84.8%, 12.2% and 1.8%, respectively, and in group 2 were 71.9%, 23.2% and 4.9%. There were no cases of micro invasive or invasive cervical carcinoma in either group. Two cases were detected as endometrial carcinoma in the menopausal group (1.2%). In current study we found that preinvasive lesions were statistically significantly higher in pre-menopausal women than post- menopausal women with ASCUS. Cervicitis was more common in menopausal women. Therefore, we think that in case of ASCUS in a post-menopausal woman there is no need for radical management.

Repeat Cytology and Human Papillomavirus Screening Strategies in Detecting Preinvasive Cervical Lesions

PubMed Central

Li, Kemin; Yin, Rutie

2015-01-01

Abstract The aim of the present study was to determine the value of human papillomavirus (HPV) testing in screening patients with preinvasive cervical lesions. Seven hundred thirty-four women diagnosed with atypical squamous cells of undetermined significance (ASCUS+) cervical cytology during routine screening had additional cytologic testing and HPV DNA testing within 6 months of their diagnosis, after which all women who tested positive were referred for colposcopy and biopsy. The test findings were then used to determine the screening value of HPV for diagnosing preinvasive cervical lesions. Cytology and HPV testing were compared by conventional cytology. The odds ratio (OR) of sensitivity using ASCUS+ or low-grade squamous intraepithelial neoplasia (LSIL+) as a cutoff for detecting cervical intraepithelial neoplasia (CIN) II+ was, respectively, 0.78 (0.72, 0.85) and 0.82 (0.70, 0.95) (P < 0.01). The cytology for triage and conventional cytology had different sensitivities using ASCUS+ or LSIL+ as the cutoff (P < 0.01). The cytology or HPV testing and conventional cytology had a difference in sensitivity using ASCUS+, LSIL+, or high-grade squamous intraepithelial neoplasia (HSIL+) as the cutoff (P < 0.01). Cytology and HPV testing were also compared with conventional cytology. The OR of specificity using ASCUS+ or LSIL+ as the cutoff for the detection of CIN II+ was 1.97 (1.68, 2.31) and 1.10 (1.02, 1.18), respectively (P < 0.01). The cytology for triage and conventional cytology had a difference in specificity when ASCUS+ or LSIL+ was used as the cutoff (P < 0.01). Finally, the cytology or HPV testing and conventional cytology had a difference in specificity when ASCUS+, LSIL+, or HSIL+ was used as the cutoff (P < 0.01). Cytology and HPV testing and cytology for triage improved the specificity of detecting CIN II+, but this did not improve the sensitivity. Additionally, cytology or HPV testing improved the sensitivity of detecting CIN II+ but not the specificity. PMID:25654377

Effect of age and cone dimensions on cervical regeneration: an Italian multicentric prospective observational study

PubMed Central

Ciavattini, Andrea; Delli Carpini, Giovanni; Moriconi, Lorenzo; Clemente, Nicolò; Montik, Nina; De Vincenzo, Rosa; Del Fabro, Anna; Buttignol, Monica; Ricci, Caterina; Moro, Francesca; Sopracordevole, Francesco

2018-01-01

Objectives To evaluate cervical regeneration at 6 months following excisional treatment for high-grade cervical intraepithelial neoplasia (CIN), and to investigate the effect of cone dimensions, age of patients and technique of excision on the efficacy of the regeneration process. Design Prospective observational multicentric study. Setting Three tertiary care and research centres. Participants Among the 197 eligible women of childbearing age, older than 25 years of age, undergoing for the first time a loop electrosurgical excision procedure or carbon dioxide laser cervical excision for a high-grade CIN at the colposcopy-directed cervical punch biopsy, and with a final diagnosis of high-grade CIN, 165 completed the 6-month follow-up and were included in the analysis. Primary outcome measures The cervical length and volume regeneration (%) after 6 months from procedure were determined by three-dimensional ultrasound, and the correlation of regeneration with cone dimensions, age and excision technique was evaluated. Results The mean±SD cervical length regeneration at 6 months was 89.5%±6.3% and the mean±SD cervical volume regeneration was 86.3%±13.2%. At the multivariate analysis, a significant and independent inverse correlation between excised cone length and cervical regeneration emerged (r=−0.39, P<0.001). A significantly negative trend in length regeneration at 6 months from procedure with an increasing class of cone length was found (P<0.001). No significant association was found in relation with patient age at the time of procedure or with the technique of excision. Conclusions Cervical length regeneration at 6 months from excisional treatments is negatively affected by an increasing cone length but not from the age of the patient or the technique of excision. While still achieving equal clinical efficacy, it is crucial to contain cone dimensions, in order to favour a greater length regeneration, reducing the cervical harm and the potential future obstetric complications. PMID:29555794

Specificity of L1 Peptides versus Virus-Like Particles for Detection of Human Papillomavirus-Positive Cervical Lesions in Females Attending Engativa Hospital, Bogota, Colombia▿

PubMed Central

Urquiza, Mauricio; Sánchez, Ricardo; Amaya, Jairo; León, Sandra; Acosta, Jenny; Patarroyo, Manuel A.; Camargo, Milena; Patarroyo, Manuel E.

2008-01-01

A serological test for the detection of human papillomavirus (HPV) infection in females at risk of developing cervical cancer could be based on conserved L1 peptides with low levels of antigenicity specifically recognized by antibodies from patients with cervical lesions infected with high-risk HPV (HR-HPV) types. The aim was to assess the ability of L1 peptides 18283, 18294, and 18301 compared with the ability of virus-like particles (VLPs) to identify these infections in females. A total of 391 HPV-infected female volunteers were interviewed, and peripheral blood and cervical cells were obtained for detection of anti-HPV antibodies and HPV DNA; all of the patients had a Pap smear test; 287 patients were referred for colposcopy or biopsy, according to gynecological criteria. The level of agreement, as determined by the use of the Lin coefficient (rho value), showed that 75 to 83% of females with HR-HPV DNA-positive cervical lesions had antibodies that recognized VLPs and peptide 18283, 18294, or 18301, while 15 to 23% of the HPV DNA-negative females with a normal cytology had antibodies that recognized these three peptides and 45% had antibodies that recognized VLPs. The rate of agreement between peptides and VLPs for antibody detection was higher for patients with HPV DNA-positive cervical lesions. Peptides 18283, 18294, and 18301 showed similar sensitivities for the detection of HR-HPV DNA-positive cervical lesions and were more specific than VLPs. Peptide 18301 might be detecting protective antibodies in HPV DNA-negative females with atypical squamous cells of undetermined significance. These peptides could be useful for the design of a serology test for the detection of HR-HPV infection in females with cervical lesions and at risk of cervical cancer. PMID:18799706

First-in-Human Trial of MIV-150 and Zinc Acetate Coformulated in a Carrageenan Gel: Safety, Pharmacokinetics, Acceptability, Adherence, and Pharmacodynamics

PubMed Central

Hoesley, Craig J.; Plagianos, Marlena; Hoskin, Elena; Zhang, Shimin; Teleshova, Natalia; Alami, Mohcine; Novak, Lea; Kleinbeck, Kyle R.; Katzen, Lauren L.; Zydowsky, Thomas M.; Fernández-Romero, José A.; Creasy, George W.

2016-01-01

Objective: To evaluate the safety and pharmacokinetics of MIV-150 and zinc acetate in a carrageenan gel (PC-1005). Acceptability, adherence, and pharmacodynamics were also explored. Design: A 3-day open-label safety run-in (n = 5) preceded a placebo-controlled, double-blind trial in healthy, HIV-negative, abstinent women randomized (4:1) to vaginally apply 4 mL of PC-1005 or placebo once daily for 14 days. Methods: Assessments included physical examinations, safety labs, colposcopy, biopsies, cervicovaginal lavages (CVLs), and behavioral questionnaires. MIV-150 (plasma, CVL, tissue), zinc (plasma, CVL), and carrageenan (CVL) concentrations were determined with LC-MS/MS, ICP-MS, and ELISA, respectively. CVL antiviral activity was measured using cell-based assays. Safety, acceptability, and adherence were analyzed descriptively. Pharmacokinetic parameters were calculated using noncompartmental techniques and actual sampling times. CVL antiviral EC50 values were calculated using a dose–response inhibition analysis. Results: Participants (n = 20) ranged from 19–44 years old; 52% were black or African American. Among those completing the trial (13/17, PC-1005; 3/3, placebo), 11/17 reported liking the gel overall; 7 recommended reducing the volume. Adverse events, which were primarily mild and/or unrelated, were comparable between groups. Low systemic MIV-150 levels were observed, without accumulation. Plasma zinc levels were unchanged from baseline. Seven of seven CVLs collected 4-hour postdose demonstrated antiviral (HIV, human papillomavirus) activity. High baseline CVL anti–herpes-simplex virus type-2 (HSV-2) activity precluded assessment of postdose activity. Conclusions: PC-1005 used vaginally for 14 days was well tolerated. Low systemic levels of MIV-150 were observed. Plasma zinc levels were unchanged. Postdose CVLs had anti-HIV and anti–human papillomavirus activity. These data warrant further development of PC-1005 for HIV and sexually transmitted infection prevention. PMID:27437826

Evidence supporting see-and-treat management of cervical intraepithelial neoplasia: a systematic review and meta-analysis.

PubMed

Ebisch, R M F; Rovers, M M; Bosgraaf, R P; van der Pluijm-Schouten, H W; Melchers, W J G; van den Akker, P A J; Massuger, L F A G; Bekkers, R L M

2016-01-01

Studies of see-and-treat management of cervical intraepithelial neoplasia (CIN) vary in their inclusion criteria, resulting in a broad range of overtreatment rates. To determine overtreatment rates in see-and-treat management of women referred for colposcopy because of suspected CIN, in order to define circumstances supporting see-and-treat management. MEDLINE, EMBASE, and the Cochrane Library were searched from inception up to 12 May 2014. Studies of see-and-treat management in women with a reported cervical smear result, colposcopic impression, and histology result were included. Methodological quality was assessed with the Newcastle-Ottawa scale. We used the inverse variance method for pooling incidences, and a random-effects model was used to account for heterogeneity between studies. Overtreatment was defined as treatment in patients with no CIN or CIN1. Thirteen studies (n = 4611) were included. The overall overtreatment rate in women with a high-grade cervical smear and a high-grade colposcopic impression was 11.6% (95% CI 7.8-15.3%). The overtreatment rate in women with a high-grade cervical smear and low-grade colposcopic impression was 29.3% (95% CI 16.7-41.9%), and in the case of a low-grade smear and high-grade colposcopic impression it was 46.4% (95% CI 15.7-77.1%). In women with a low-grade smear and low-grade colposcopic impression, the overtreatment rate was 72.9% (95% CI 68.1-77.7%). The pooled overtreatment rate in women with a high-grade smear and high-grade colposcopic impression is at least comparable with the two-step procedure, which supports the use of see-and-treat management in this subgroup of women. See-and-treat management is justified in the case of a high-grade smear and a high-grade colposcopic impression. © 2015 Royal College of Obstetricians and Gynaecologists.

Human papillomavirus infection and risk factors in a cohort of Tuscan women aged 18-24: results at recruitment

PubMed Central

2010-01-01

Background There is conclusive evidence that human papillomavirus (HPV) infections of the cervix are a necessary cause of cervical cancer. In Italy there are consistent data of HPV prevalence in women aged 25 - 64 years, but there is limited data for younger women. The objective of this on-going 3-year prospective cohort study is to investigate the prevalence, acquisition, clearance and persistence of HPV infections in young Tuscan women and the risk factors correlated with such events. Methods One thousand and sixty-six women aged between 18 and 24 years were enrolled and received an initial HPV test. They were asked to return to the clinic over the study period for further tests every 12 months, if their HPV HR result was negative, or every 6 months, if positive. Additionally, women with an HPV positive result were given a cytological examination and if the cytological diagnosis was ASC-US or more severe, only women with HPV HR, were referred for colposcopy. Results We present here data for the enrolment phase of the study. At baseline, within the study sample, just under 30% of women were infected by HPV and 19.3% of women were infected with oncogenic types. A relationship was highlighted between HPV infection, number of sexual partners (in particularly in the last 3 years) and the lifetime number of partner's partners. Condom use showed a slight protective effect in univariate analysis but these data were not statistically significant in multivariate analysis. The association between HPV infection and demographic and behavioural variables were tested by crude odds ratio (OR). Multivariate logistic regression was applied to compute the adjusted odds ratios. Conclusions The prevalence of oncogenic HPV types was high in young Tuscan women. The 3-year follow-up of this cohort may provide a better understanding of the processes of acquisition, clearance and persistence of infection and the correlated risk factors. PMID:20529280

Improved sensitivity of vaginal self-collection and high-risk human papillomavirus testing.

PubMed

Belinson, Jerome L; Du, Hui; Yang, Bin; Wu, Ruifang; Belinson, Suzanne E; Qu, Xinfeng; Pretorius, Robert G; Yi, Xin; Castle, Philip E

2012-04-15

Self-collected vaginal specimens tested for high-risk human papillomavirus (HR-HPV) have been shown to be less sensitive for the detection of cervical intraepithelial neoplasia or cancer (≥CIN 3) than physician-collected endocervical specimens. To increase the sensitivity of self-collected specimens, we studied a self-sampling device designed to obtain a larger specimen from the upper vagina (POI/NIH self-sampler) and a more sensitive polymerase chain reaction (PCR)-based HR-HPV assay. Women (10,000) were screened with cervical cytology and HR-HPV testing of vaginal self-collected and endocervical physician-collected specimens. Women were randomly assigned to use either a novel self-collection device (POI/NIH self-sampler) or conical-shaped brush (Qiagen). The self-collected and clinician-collected specimens were assayed by Cervista (Hologic) and the research only PCR-based matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). Women with any abnormal screening test underwent colposcopy and biopsy. Women (8,556), mean age of 38.9, had complete data; 1.6% had ≥ CIN 3. For either HR-HPV assay, the sensitivity was similar for the two self-collection devices. Tested with Cervista, the sensitivity for ≥CIN 3 of self-collected specimens was 70.9% and for endocervical specimens was 95.0% (p = 0.0001). Tested with MALDI-TOF, the sensitivity for ≥CIN 3 of self-collected specimens was 94.3% and for endocervical specimens was also 94.3% (p = 1.0). A self-collected sample using a PCR-based assay with the capability of very high throughput has similar sensitivity as a direct endocervical specimen obtained by a physician. Large population-based screening "events" in low-resource settings could be achieved by promoting self-collection and centralized high-throughput, low-cost testing by PCR-based MALDI-TOF. Copyright © 2011 UICC.

Cost of Preventing, Managing, and Treating Human Papillomavirus (HPV)-Related Diseases in Sweden before the Introduction of Quadrivalent HPV Vaccination

PubMed Central

Östensson, Ellinor; Fröberg, Maria; Leval, Amy; Hellström, Ann-Cathrin; Bäcklund, Magnus; Zethraeus, Niklas; Andersson, Sonia

2015-01-01

Objective Costs associated with HPV-related diseases such as cervical dysplasia, cervical cancer, and genital warts have not been evaluated in Sweden. These costs must be estimated in order to determine the potential savings if these diseases were eradicated and to assess the combined cost-effectiveness of HPV vaccination and cervical cancer screening. The present study aimed to estimate prevention, management, and treatment costs associated with cervical dysplasia, cervical cancer, and genital warts from a societal perspective in Sweden in 2009, 1 year before the quadrivalent HPV vaccination program was implemented. Methods and Materials Data from the Swedish cervical cancer screening program was used to calculate the costs associated with prevention (cytological cervical cancer screening), management (colposcopy and biopsy following inadequate/abnormal cytological results), and treatment of CIN. Swedish official statistics were used to estimate treatment costs associated with cervical cancer. Published epidemiological data were used to estimate the number of incident, recurrent, and persistent cases of genital warts; a clinical expert panel assessed management and treatment procedures. Estimated visits, procedures, and use of medications were used to calculate the annual cost associated with genital warts. Results From a societal perspective, total estimated costs associated with cervical cancer and genital warts in 2009 were €106.6 million, of which €81.4 million (76%) were direct medical costs. Costs associated with prevention, management, and treatment of CIN were €74 million; screening and management costs for women with normal and inadequate cytology alone accounted for 76% of this sum. The treatment costs associated with incident and prevalent cervical cancer and palliative care were €23 million. Estimated costs for incident, recurrent and persistent cases of genital warts were €9.8 million. Conclusion Prevention, management, and treatment costs associated with cervical dysplasia, cervical cancer, and genital warts are substantial. Defining these costs is important for future cost-effectiveness analyses of the quadrivalent HPV vaccination program in Sweden. PMID:26398189

Camp based awareness and screening programme of cervical cancer in rural area of Bangladesh.

PubMed

Shahida, S M; Saha, K; Banu, K A; Islam, M A

2013-10-01

This population based cross sectional study was carried out in Muktagacha Upazilla Health Complex, Mymensingh, Bangladesh during the period of 26th to 28th June, 2012. The objective was to create awareness, to find out the precancerous lesion of cervix and to evaluate the effectiveness of this approach for prevention of cervical carcinoma. Women who were married and between 30-60 years and also women of below 30 years (who were married below the age of 18) were included in this study. All pregnant women were excluded from this study. After counseling, pelvic examination and VIA (visual inspection of cervix with application of 5% acetic acid) test was done. If the squamo-columner junction of cervix turned to white then it was called VIA positive (+ve) cases. Then they were referred to colposcopy clinic of Mymensingh Medical College with a red card for evaluation and management. During the 3 days campaign, 395 cases were examined. Among them, majority (49%) of the women were below the age of 30. It was observed that still 48.2% were married below the age of 18 and 31% had first pregnancy at an age or below 18 years. But number of grand multiparity is lowering now a days. Only 25% had para ≥4. Others have para 1-3. During pelvic examination, the common cervico-uterine pathologies like chronic cervicities (16.5%), cervical erosion (14.4%), uterine prolapse (2.3%), cervical polyp (1%), myomatous polyp (0.3%) and advanced cervical carcinoma (0.5%) were also diagnosed clinically. Among the participants, 11.9% was detected as VIA+ve cases. A significant association of VIA+ve cases with low socio-economic conditions, hindu religion, early age at marriage and high parity were observed in this study (p<0.05). The findings of this study highlight the utility and need of camp based cervical cancer screening service at regular interval in the community.

p16INK4a immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis

PubMed Central

Tsoumpou, I; Arbyn, M; Kyrgiou, M; Wentzensen, N; Koliopoulos, G; Martin-Hirsch, P; Paraskevaidis, E

2009-01-01

Background P16INK4a is a biomarker for transforming HPV infections that could act as an adjunct to current cytological and histological assessment of cervical smears and biopsies, allowing the identification of those women with ambiguous results that require referral to colposcopy and potentially treatment. Material and Methods We conducted a systematic review of all studies that evaluated the use of p16INK4a in cytological or histological specimens from the uterine cervix. We also estimated the mean proportion of samples that were positive for p16INK4a in cytology and histology, stratified by the grade of the lesion. Results Sixty-one studies were included. The proportion of cervical smears overexpressing p16INK4a increased with the severity of cytological abnormality. Among normal smears, only 12% (95% CI: 7–17%) were positive for the biomarker compared to 45% of ASCUS and LSIL (95% CI: 35–54% and 37– 57% respectively) and 89% of HSIL smears (95% CI: 84–95%). Similarly, in histology only 2% of normal biopsies (95% CI: 0.4– 30%) and 38% of CIN1 (95% CI: 23– 53%) showed diffuse staining for p16INK4a compared to 68% of CIN2 (95% CI: 44– 92%) and 82% of CIN3 (95% CI: 72– 92%). Conclusion Although there is good evidence that p16INK4a immunostaining correlates with the severity of cytological/histological abnormalities, the reproducibility is limited due to insufficiently standardized interpretation of the immunostaining. Therefore, a consensus needs to be reached regarding the evaluation of p16INK4a staining and the biomarker needs to be evaluated in various clinical settings addressing specific clinical questions. PMID:19261387

Difference Between Cryotherapy and Follow Up Low Grade Squamous Lesion of Cervix Uteri.

PubMed

Jahic, Mahira; Jahic, Elmir; Mulavdic, Mirsada; Hadzimehmedovic, Azra

2017-08-01

Cervical cancer can be successfully prevented by effective treatment. Analyse of success of cryotherapy in LSIL and ASCUS. In retrospective study between January 2016 to March 2017, 3244 PAP test were analysed. 257 patients who had been diagnosed with LSIL and ASCUS from PAP smear were divided in two groups: women who had HPV positive, colposcopic positive and cytologic finding of LSIL or ASCUS treathed with cryotherapy and women with LSIL, ASCUS and negative colposcopy. χ 2 test was used for statistical analysis of data. Analysis of 3244 PAP smears showed negative for intraepithelial lesion or malignancy (NILM) in 90,10% (N-2923), and abnormal in 9,8% (N-321) of women. ASCUS was found in 4,8% (N-156) and ASC-H in 0,2% (N-6), LSIL in 3,1% (N-101), HSIL in 0,64% (N-21). The average age of patients with ASCUS lesion was 41 ± 12 years. After cryotherapy, HSIL had progression in 1,5% (N-1), persistence in 6,3% (N-4) and regression in 91,7% (N-58). Progression occured in 10,5% (N-4) of HSIL, persistence in 52,6% (N-20) and regression in 36,7% (N-14) in 38 women with LSIL lesion after repeated PAP test. Progression occured in 8% (N-10) of LSIL and 4% HSIL (N-5), persistence in 58% (N-72) and regression in 29,8% (N-37) in 124 women with ASCUS lesion after treatment and repeated PAP test. Difference in progression lesions in HSIL between women with cryotherapy (1,5%) and follow-up (10,5%) after LSIL is not significant, but progression to CIN II occured after cryotherapy. CIN III or cervical cancer was not found. Cryotherapy prevents progression of LSIL in HSIL and in cervical cancer. Because of that cryotherapy is successful method in prevention of cervical cancer.

Simultaneous fingerprint and high-wavenumber confocal Raman spectroscopy enhances early detection of cervical precancer in vivo.

PubMed

Duraipandian, Shiyamala; Zheng, Wei; Ng, Joseph; Low, Jeffrey J H; Ilancheran, A; Huang, Zhiwei

2012-07-17

Raman spectroscopy is a vibrational spectroscopic technique capable of nondestructively probing endogenous biomolecules and their changes associated with dysplastic transformation in the tissue. The main objectives of this study are (i) to develop a simultaneous fingerprint (FP) and high-wavenumber (HW) confocal Raman spectroscopy and (ii) to investigate its diagnostic utility for improving in vivo diagnosis of cervical precancer (dysplasia). We have successfully developed an integrated FP/HW confocal Raman diagnostic system with a ball-lens Raman probe for simultaneous acquistion of FP/HW Raman signals of the cervix in vivo within 1 s. A total of 476 in vivo FP/HW Raman spectra (356 normal and 120 precancer) are acquired from 44 patients at clinical colposcopy. The distinctive Raman spectral differences between normal and dysplastic cervical tissue are observed at ~854, 937, 1001, 1095, 1253, 1313, 1445, 1654, 2946, and 3400 cm(-1) mainly related to proteins, lipids, glycogen, nucleic acids and water content in tissue. Multivariate diagnostic algorithms developed based on partial least-squares-discriminant analysis (PLS-DA) together with the leave-one-patient-out, cross-validation yield the diagnostic sensitivities of 84.2%, 76.7%, and 85.0%, respectively; specificities of 78.9%, 73.3%, and 81.7%, respectively; and overall diagnostic accuracies of 80.3%, 74.2%, and 82.6%, respectively, using FP, HW, and integrated FP/HW Raman spectroscopic techniques for in vivo diagnosis of cervical precancer. Receiver operating characteristic (ROC) analysis further confirms the best performance of the integrated FP/HW confocal Raman technique, compared to FP or HW Raman spectroscopy alone. This work demonstrates, for the first time, that the simultaneous FP/HW confocal Raman spectroscopy has the potential to be a clinically powerful tool for improving early diagnosis and detection of cervical precancer in vivo during clinical colposcopic examination.

Evaluation of human papillomavirus detection by Abbott m2000 system on samples collected by FTA Elute™ Card in a Chinese HIV-1 positive population.

PubMed

Qin, Yu; Zhang, Hongyun; Marlowe, Natalia; Fei, Mandong; Yu, Judy; Lei, Xiaoqin; Yu, Lulu; Zhang, Jia; Cao, Di; Ma, Li; Chen, Wen

2016-12-01

HIV+/AIDS women have an increased risk of developing into CIN and cervical cancer compared to the general population. Limited medical resource and the lack of AIDS relevant knowledge impair the coverage and efficiency of cervical cancer screening. To compare the clinical performance of self-collected dry storage medium (FTA Elute card) and physician-collected PreservCyt medium in detection of high risk human papillomavirus (HR HPV) among HIV-1 positive population. Three hundred HIV-1 positive women (aged 25-65) were recruited from Yunnan infectious hospital. Two cervicovaginal samples were collected from each participant: one was collected by the women themselves and applied on a FTA Elute card; the other one was collected by a physician and stored in PreservCyt solution. All the samples were tested for 14 HR HPV using Abbott RealTime High Risk HPV assay. Biopsies were taken for histological diagnosis if any abnormal impression was noticed under colposcopy. 291 (97.0%) of participants were eligible for this study. 101 (34.70%) participants were found HR HPV positive in both FTA card and PreservCyt samples, and 19 (6.53%) women were diagnosed as CIN2+. The HR HPV positive rate on samples collected by FTA Elute card and PreservCyt solution was 42.61% and 39.86%, respectively. The overall agreement was 87% (kappa=0.731) between FTA card and PreservCyt. The clinical sensitivity and specificity of FTA card and PreservCyt were 100%, 61.39% and 100%, 64.33%, respectively. In this study, FTA Elute card demonstrated a good performance on self-collected sample for HR HPV detection in HIV-1 positive population. For the women from low-resource area with HIV-1 infection, FTA Elute card could be an attractive sample collection method for cervical cancer screening. Copyright © 2016 Elsevier B.V. All rights reserved.

Technologic advances for evaluation of cervical cytology: is newer better?

PubMed

Hartmann, K E; Nanda, K; Hall, S; Myers, E

2001-12-01

Among those women who have cervical cancer and have been screened, 14% to 33% of the cases represent failure to detect abnormalities that existed at the time of screening. New technologies intended to improve detection of cytologic abnormalities include liquid-based, thin-layer cytology (ThinPrep, AutoCyte), computerized rescreening (PAPNET), and algorithm-based computer rescreening (AutoPap). This report combines evidence reviews conducted for the U.S. Preventive Services Task Force and the Agency for Healthcare Research and Quality, in which we systematically identified articles on cervical neoplasia, cervical dysplasia, and screening published between January 1966 and March 2001. We note the challenges for improving screening methods, providing an overview of methods for collecting and evaluating cytologic samples, and examining the evidence about the diagnostic performance of new technologies for detecting cervical lesions. Using standard criteria for evaluation of the diagnostic tests, we determined that knowledge about the sensitivity, specificity, and predictive values of new technologies is meager. Only one study of liquid-based cytology used a reference standard of colposcopy, with histology as indicated, to assess participants with normal screening results. Lack of an adequate reference standard is the overwhelming reason that test characteristics cannot be properly assessed or compared. Most publications compare results of screening using the new technology with expert panel review of the cytologic specimen. In that case, the tests are not independent measures and do nothing to relate the screening test findings to the true status of the cervix, making determination of false-negatives, and thus sensitivity, specificity, and negative predictive value, impossible. We did not identify any literature about health outcomes or cost effectiveness of using these tools in a system of screening. For the purposes of guiding decision making about choice of screening tools, the current evidence is inadequate to gauge whether new technologies are "better" than conventional cytology..

Cervical Cancer Screening in Cameroon: Interobserver Agreement on the Interpretation of Digital Cervicography Results.

PubMed

Manga, Simon; Parham, Groesbeck; Benjamin, Nkoum; Nulah, Kathleen; Sheldon, Lisa Kennedy; Welty, Edith; Ogembo, Javier Gordon; Bradford, Leslie; Sando, Zacharie; Shields, Ray; Welty, Thomas

2015-10-01

The World Health Organization recommends visual inspection with acetic acid (VIA) for cervical cancer screening in resource-limited settings. In Cameroon, we use digital cervicography (DC) to capture images of the cervix after VIA. This study evaluated interobserver agreement of DC results, compared DC with histopathologic results, and examined interobserver agreement among screening methods. Three observers, blinded to each other's interpretations, evaluated 540 DC photographs as follows: (1) negative/positive for acetowhite lesions or cancer and (2) assigned a presumptive diagnosis of histopathologic lesion grade in the 91 cases that had a histopathologic diagnosis. Observer A was the actual screening nurse; B, a reproductive health nurse; C, a gynecologic oncologist; and D, the histopathologic diagnosis. We compared inter-rater agreement of DC impressions among observers A, B, and C, and with D, with Cohen kappas. For interpretations of DC, (negative/positive) strengths of agreement of paired observers were the following: A/B, moderate [K, 0.54; 95% confidence interval (CI), 0.47-0.61], A/C, fair (K, 0.37; 95% CI, 0.29-0.44), and B/C, moderate (K, 0.45; 95% CI, 0.37-0.53). For presumptive pathologic grading, strengths of agreement for weighted Ks were as follows: A/B, moderate (K, 0.42; 95% CI, 0.28-0.56); A/C, fair (K, 0.33; 95% CI, 0.20-0.46); B/C, fair (K, 0.54; 95% CI, 0.40-0.67); A/D, moderate (K, 0.59; 95% CI, 0.45-0.74); B/D, moderate (K, 0.58; 95% CI, 0.46-0.70); and C/D, moderate (K, 0.50; 95% CI, 0.37-0.63). Interobserver agreement of DC interpretations was mostly moderate among the 3 observers, between them and histopathology, and comparable to that of other visual-based screening methods, i.e., VIA, cytology, or colposcopy.

Safety, Acceptability and Adherence of Dapivirine Vaginal Ring in a Microbicide Clinical Trial Conducted in Multiple Countries in Sub-Saharan Africa.

PubMed

Nel, Annalene; Bekker, Linda-Gail; Bukusi, Elizabeth; Hellstrӧm, Elizabeth; Kotze, Philip; Louw, Cheryl; Martinson, Francis; Masenga, Gileard; Montgomery, Elizabeth; Ndaba, Nelisiwe; van der Straten, Ariane; van Niekerk, Neliëtte; Woodsong, Cynthia

2016-01-01

This was the first microbicide trial conducted in Africa to evaluate an antiretroviral-containing vaginal ring as an HIV prevention technology for women. The trial assessed and compared the safety, acceptability and adherence to product use of a 4-weekly administered vaginal ring containing the antiretroviral microbicide, dapivirine, with a matching placebo ring among women from four countries in sub-Saharan Africa. 280 Healthy, sexually active, HIV-negative women, aged 18 to 40 years were enrolled with 140 women randomised to a dapivirine vaginal ring (25 mg) and 140 women to a matching placebo ring, inserted 4-weekly and used over a 12-week period. Safety was evaluated by pelvic examination, colposcopy, clinical laboratory assessments, and adverse events. Blood samples for determination of plasma concentrations of dapivirine were collected at Weeks 0, 4 and 12. Residual dapivirine levels in returned rings from dapivirine ring users were determined post-trial. Participant acceptability and adherence to ring use were assessed by self-reports. No safety concerns or clinically relevant differences were observed between the dapivirine and placebo ring groups. Plasma dapivirine concentrations immediately prior to ring removal were similar after removal of the first and third ring, suggesting consistent ring use over the 12-week period. No clear relationship was observed between the residual amount of dapivirine in used rings and corresponding plasma concentrations. Self-reported adherence to daily use of the vaginal rings over the 12-week trial period was very high. At the end of the trial, 96% of participants reported that the ring was usually comfortable to wear, and 97% reported that they would be willing to use it in the future if proven effective. The dapivirine vaginal ring has a favourable safety and acceptability profile. If proven safe and effective in large-scale trials, it will be an important component of combination HIV prevention approaches for women. ClinicalTrials.gov NCT01071174.

Safety of a silicone elastomer vaginal ring as potential microbicide delivery method in African women: A Phase 1 randomized trial

PubMed Central

Nel, Annaléne; Bekker, Linda-Gail; Ramjee, Gita; Masenga, Gileard; Rees, Helen; van Niekerk, Neliëtte

2018-01-01

Background Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with vaginal rings. Objectives This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo vaginal ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania. Methods 170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo vaginal ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo vaginal ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuring no signs or symptoms of genital irritation at crossover. Results No safety concerns were identified for any safety variables assessed during the trial. No serious adverse events were reported considered related to the placebo vaginal ring. Vaginal candidiasis was the most common adverse event occurring in 11% of participants during each trial period. Vaginal discharge (2%), vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the vaginal ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive during the trial. Conclusions The silicone elastomer vaginal ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides. PMID:29813074

Difference Between Cryotherapy and Follow Up Low Grade Squamous Lesion of Cervix Uteri

PubMed Central

Jahic, Mahira; Jahic, Elmir; Mulavdic, Mirsada; Hadzimehmedovic, Azra

2017-01-01

Introduction: Cervical cancer can be successfully prevented by effective treatment. Aim: Analyse of success of cryotherapy in LSIL and ASCUS. Materials et methods: In retrospective study between January 2016 to March 2017, 3244 PAP test were analysed. 257 patients who had been diagnosed with LSIL and ASCUS from PAP smear were divided in two groups: women who had HPV positive, colposcopic positive and cytologic finding of LSIL or ASCUS treathed with cryotherapy and women with LSIL, ASCUS and negative colposcopy. χ2 test was used for statistical analysis of data. Results: Analysis of 3244 PAP smears showed negative for intraepithelial lesion or malignancy (NILM) in 90,10% (N-2923), and abnormal in 9,8% (N-321) of women. ASCUS was found in 4,8% (N-156) and ASC-H in 0,2% (N-6), LSIL in 3,1% (N-101), HSIL in 0,64% (N-21). The average age of patients with ASCUS lesion was 41 ± 12 years. After cryotherapy, HSIL had progression in 1,5% (N-1), persistence in 6,3% (N-4) and regression in 91,7% (N-58). Progression occured in 10,5% (N-4) of HSIL, persistence in 52,6% (N-20) and regression in 36,7% (N-14) in 38 women with LSIL lesion after repeated PAP test. Progression occured in 8% (N-10) of LSIL and 4% HSIL (N-5), persistence in 58% (N-72) and regression in 29,8% (N-37) in 124 women with ASCUS lesion after treatment and repeated PAP test. Difference in progression lesions in HSIL between women with cryotherapy (1,5%) and follow-up (10,5%) after LSIL is not significant, but progression to CIN II occured after cryotherapy. CIN III or cervical cancer was not found. Conclusion: Cryotherapy prevents progression of LSIL in HSIL and in cervical cancer. Because of that cryotherapy is successful method in prevention of cervical cancer. PMID:28974850

Evaluation of p16/Ki-67 dual staining in detection of cervical precancer and cancers: a multicenter study in China

PubMed Central

Yu, Lu-Lu; Chen, Wen; Lei, Xiao-Qin; Qin, Yu; Wu, Ze-Ni; Pan, Qin-Jing; Zhang, Xun; Chang, Bai-Feng; Zhang, Shao-Kai; Guo, Hui-Qin; Qiao, You-Lin

2016-01-01

Purpose To analyze the clinical performance of p16/Ki-67 dual-stained cytology identifying high-grade cervical intraepithelial neoplasia (CIN2+) in Chinese women. Methods 1079 women attending ongoing cervical cancer screening and 211 “enriched” women aged ≥30yrs with biopsy-confirmed CIN2+ from five Chinese hospitals were enrolled during year 2014-2015. Cervical specimens were collected for high-risk human papillomavirus (HR-HPV) DNA analysis, Liquid-based cytology (LBC) and p16/Ki-67 dual staining. Colposcopy and biopsy were performed on women with any abnormal result. Results p16/Ki-67 positivity increased with histologic severity. It was 18.4%(183/996) in normal histology, 54.0%(34/63) in CIN1, 81.0%(34/42) in CIN2, 93.3%(111/119) in CIN3, 71.4% (5/7) in adenocarcinoma and 95.2%(60/63) in squamous cell carcinoma. Compared with the HR-HPV negatives, p16/Ki-67 expression was significantly higher in the HPV16/18 positive (OR: 35.45(95%CI: 23.35-53.84)) and other 12 HR-HPV types positive group (OR: 8.01(95%CI: 5.81-11.05). The sensitivity and specificity of p16/Ki-67 to detect CIN2+ in the entire population were 90.9% and 79.5%, respectively. In women with ASC-US and LSIL, sensitivity and specificity for detection of CIN2+ were 87.5% and 66.4%, respectively, with a referral rate of 43.8%. In women who tested positive for HR-HPV, sensitivity and specificity of dual-staining for detection of CIN2+ were 92.7% and 52.7%, respectively, and the referral rate was 68.7%. Conclusions p16/Ki-67 dual-stained cytology provided a high sensitivity and moderate specificity to detect underlying cervical precancer and cancers in various settings, and might be considered as an efficient screening tool in China. PMID:27029033

Stability Study of Cervical Specimens Collected by Swab and Stored Dry Followed by Human Papillomavirus DNA Detection Using the cobas 4800 Test.

PubMed

Lin, Chun-Qing; Zeng, Xi; Cui, Jian-Feng; Liao, Guang-Dong; Wu, Ze-Ni; Gao, Qian-Qian; Zhang, Xun; Yu, Xiu-Zhang; Chen, Wen; Xi, Ming-Rong; Qiao, You-Lin

2017-02-01

Safer, more convenient methods for cervical sample collection and storage are necessary to facilitate human papillomavirus (HPV) DNA testing in low-resource settings. Our study aimed to evaluate the stability of cervical specimens collected with dry swabs and stored dry, compared to liquid-based cytology (LBC) samples, as detected by HPV DNA testing. Women with abnormal cytological findings or HPV-positive results at colposcopy were recruited from the West China Second University Hospital, Sichuan University, between October 2013 and March 2014. From each woman, physicians collected cervical specimens with a swab placed into a Sarstedt tube and a CytoBrush placed into LBC medium. Samples were randomly assigned to be stored at uncontrolled ambient temperature for 2, 7, 14, or 28 days and then were tested for 14 high-risk HPV (HR-HPV) types using the cobas HPV test. The rates of agreement between dry swab and LBC samples for any HR-HPV type, HPV16, HPV18, and the 12 pooled HR-HPV types were 93.8%, 97.8%, 99.4%, and 93.2%, respectively, with kappa values of 0.87 (95% confidence interval [CI], 0.83 to 0.91), 0.94 (95% CI, 0.91 to 0.97), 0.94 (95% CI, 0.87 to 1.00), and 0.86 (95% CI, 0.82 to 0.90). The performance of swab samples for detection of cervical precancerous lesions by means of cobas HPV testing was equal to that of LBC samples, even with stratification by storage time. Dry storage of swab-collected cervical samples can last for 1 month without loss of test performance by cobas HPV testing, compared to LBC samples, which may offer a simple inexpensive approach for cervical cancer screening in low-resource settings. Copyright © 2017 American Society for Microbiology.

Prior human papillomavirus-16/18 AS04-adjuvanted vaccination prevents recurrent high grade cervical intraepithelial neoplasia after definitive surgical therapy: Post-hoc analysis from a randomized controlled trial.

PubMed

Garland, Suzanne M; Paavonen, Jorma; Jaisamrarn, Unnop; Naud, Paulo; Salmerón, Jorge; Chow, Song-Nan; Apter, Dan; Castellsagué, Xavier; Teixeira, Júlio C; Skinner, S Rachel; Hedrick, James; Limson, Genara; Schwarz, Tino F; Poppe, Willy A J; Bosch, F Xavier; de Carvalho, Newton S; Germar, Maria Julieta V; Peters, Klaus; Del Rosario-Raymundo, M Rowena; Catteau, Grégory; Descamps, Dominique; Struyf, Frank; Lehtinen, Matti; Dubin, Gary

2016-12-15

We evaluated the efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in preventing HPV-related disease after surgery for cervical lesions in a post-hoc analysis of the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT00122681). Healthy women aged 15-25 years were randomized (1:1) to receive vaccine or control at months 0, 1 and 6 and followed for 4 years. Women were enrolled regardless of their baseline HPV DNA status, HPV-16/18 serostatus, or cytology, but excluded if they had previous or planned colposcopy. The primary and secondary endpoints of PATRICIA have been reported previously; the present post-hoc analysis evaluated efficacy in a subset of women who underwent an excisional procedure for cervical lesions after vaccination. The main outcome was the incidence of subsequent HPV-related cervical intraepithelial neoplasia grade 2 or greater (CIN2+) 60 days or more post-surgery. Other outcomes included the incidence of HPV-related CIN1+, and vulvar or vaginal intraepithelial neoplasia (VIN/VaIN) 60 days or more post-surgery. Of the total vaccinated cohort of 18,644 women (vaccine = 9,319; control = 9,325), 454 (vaccine = 190, control = 264) underwent an excisional procedure during the trial. Efficacy 60 days or more post-surgery for a first lesion, irrespective of HPV DNA results, was 88.2% (95% CI: 14.8, 99.7) against CIN2+ and 42.6% (-21.1, 74.1) against CIN1+. No VIN was reported and one woman in each group had VaIN2+ 60 days or more post-surgery. Women who undergo surgical therapy for cervical lesions after vaccination with the HPV-16/18 vaccine may continue to benefit from vaccination, with a reduced risk of developing subsequent CIN2+. © 2016 UICC.

Evaluation of a new APTIMA specimen collection and transportation kit for high-risk human papillomavirus E6/E7 messenger RNA in cervical and vaginal samples.

PubMed

Chernesky, Max; Jang, Dan; Gilchrist, Jodi; Elit, Laurie; Lytwyn, Alice; Smieja, Marek; Dockter, Janel; Getman, Damon; Reid, Jennifer; Hill, Craig

2014-06-01

An APTIMA specimen collection and transportation (SCT) kit was developed by Hologic/Gen-Probe. To compare cervical SCT samples to PreservCyt and SurePath samples and self-collected vaginal samples to physician-collected vaginal and cervical SCT samples. To determine ease and comfort of self-collection with the kit. Each woman (n = 580) self-collected a vaginal SCT, then filled out a questionnaire (n = 563) to determine ease and comfort of self-collection. Colposcopy physicians collected a vaginal SCT and cervical PreservCyt, SCT, and SurePath samples. Samples were tested by APTIMA HPV (AHPV) assay. Agreement between testing of cervical SCT and PreservCyt was 91.1% (κ = 0.82), and that of SurePath samples was 86.7% (κ = 0.72). Agreement of self-collected vaginal SCT to physician-collected SCT was 84.7% (κ = 0.68), and that of self-collected vaginal to cervical SCT was 82.0% (κ = 0.63). For 30 patients with CIN2+, AHPV testing of cervical SCT was 100% sensitive and 59.8% specific compared with PreservCyt (96.6% and 66.2%) and SurePath (93.3% and 70.9%). Vaginal SCT sensitivity was 86.7% for self-collection and 80.0% for physician collection. Most patients found that vaginal self-collection was easy, 5.3% reported some difficulty, and 87.6% expressed no discomfort. Cervical samples collected with the new SCT kit compared well to traditional liquid-based samples tested by AHPV. Although there was good agreement between self-collected and physician-collected samples with the SCT, in a limited number of 30 women, vaginal sampling identified fewer with CIN2+ precancerous cervical lesions than cervical SCT sampling. Comfort, ease of use, and detection of high-risk HPV demonstrated that the kit could be used for cervical and vaginal sampling.

Inefficiencies and high-value improvements in U.S. cervical cancer screening practice: A cost-effectiveness analysis

PubMed Central

Kim, Jane J.; Campos, Nicole G.; Sy, Stephen; Burger, Emily A.; Cuzick, Jack; Castle, Philip E.; Hunt, William C.; Waxman, Alan; Wheeler, Cosette M.

2016-01-01

Background Studies suggest that cervical cancer screening practice in the United States is inefficient. The cost and health implications of non-compliance in the screening process compared to recommended guidelines are uncertain. Objective To estimate the benefits, costs, and cost-effectiveness of current cervical cancer screening practice and assess the value of screening improvements. Design Model-based cost-effectiveness analysis. Data Sources New Mexico HPV Pap Registry; medical literature. Target Population Cohort of women eligible for routine screening. Time Horizon Lifetime. Perspective Societal. Interventions Current cervical cancer screening practice; improved compliance to guidelines-based screening interval, triage testing, diagnostic referrals, and precancer treatment referrals. Outcome Measures Reductions in lifetime cervical cancer risk, quality-adjusted life-years (QALYs), lifetime costs, incremental cost-effectiveness ratios (ICERs), incremental net monetary benefits (INMBs Results of Base-Case Analysis Current screening practice was associated with lower health benefit and was not cost-effective relative to guidelines-based strategies. Improvements in the screening process were associated with higher QALYs and small changes in costs. Perfect c4mpliance to a 3-yearly screening interval and to colposcopy/biopsy referrals were associated with the highest INMBs ($759 and $741, respectively, at a willingness-to-pay threshold of $100,000 per QALY gained); together, the INMB increased to $1,645. Results of Sensitivity Analysis Current screening practice was inefficient in 100% of simulations. The rank ordering of screening improvements according to INMBs was stable over a range of screening inputs and willingness-to-pay thresholds. Limitations The impact of HPV vaccination was not considered. Conclusions The added health benefit of improving compliance to guidelines, especially the 3-yearly interval for cytology screening and diagnostic follow-up, may justify additional investments in interventions to improve U.S. cervical cancer screening practice. Funding Source U.S. National Cancer Institute. PMID:26414147

Accuracy and Cost-Effectiveness of Cervical Cancer Screening by High-Risk HPV DNA Testing of Self-Collected Vaginal Samples

PubMed Central

Balasubramanian, Akhila; Kulasingam, Shalini L.; Baer, Atar; Hughes, James P.; Myers, Evan R.; Mao, Constance; Kiviat, Nancy B.; Koutsky, Laura A.

2010-01-01

Objective Estimate the accuracy and cost-effectiveness of cervical cancer screening strategies based on high-risk HPV DNA testing of self-collected vaginal samples. Materials and Methods A subset of 1,665 women (18-50 years of age) participating in a cervical cancer screening study were screened by liquid-based cytology and by high-risk HPV DNA testing of both self-collected vaginal swab samples and clinician-collected cervical samples. Women with positive/abnormal screening test results and a subset of women with negative screening test results were triaged to colposcopy. Based on individual and combined test results, five screening strategies were defined. Estimates of sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or worse were calculated and a Markov model was used to estimate the incremental cost-effectiveness ratios (ICERs) for each strategy. Results Compared to cytology-based screening, high-risk HPV DNA testing of self-collected vaginal samples was more sensitive (68%, 95%CI=58%-78% versus 85%, 95%CI=76%-94%) but less specific (89%, 95%CI=86%-91% versus 73%, 95%CI=67%-79%). A strategy of high-risk HPV DNA testing of self-collected vaginal samples followed by cytology triage of HPV positive women, was comparably sensitive (75%, 95%CI=64%-86%) and specific (88%, 95%CI=85%-92%) to cytology-based screening. In-home self-collection for high-risk HPV DNA detection followed by in-clinic cytology triage had a slightly lower lifetime cost and a slightly higher quality-adjusted life expectancy than did cytology-based screening (ICER of triennial screening compared to no screening was $9,871/QALY and $12,878/QALY, respectively). Conclusions Triennial screening by high-risk HPV DNA testing of in-home, self-collected vaginal samples followed by in-clinic cytology triage was cost-effective. PMID:20592553

A randomized controlled trial in non-responders from Newcastle upon Tyne invited to return a self-sample for Human Papillomavirus testing versus repeat invitation for cervical screening.

PubMed

Cadman, Louise; Wilkes, Scott; Mansour, Diana; Austin, Janet; Ashdown-Barr, Lesley; Edwards, Rob; Kleeman, Michelle; Szarewski, Anne

2015-03-01

Non-attenders for cervical screening are at increased risk of cervical cancer. Studies offering self-sampling for high-risk Human Papillomavirus (HrHPV) testing have shown greater uptake than sending another invitation for cytology. To explore whether uptake would increase in a less diverse, more stable population than the previous English study, which demonstrated a lower response rate than other studies. The primary objective was whether non-attenders were more likely to respond to a postal invitation, including kit, to collect a self-sample compared with a further invitation for cytology screening. The secondary objective was whether women with an abnormal result would attend for follow-up. 6000 non-attenders for screening in this pragmatic, randomized (1:1) controlled trial in Newcastle-upon-Tyne were sent an HPV self-sample kit (intervention) or a further invitation for cytology screening (comparator). 411(13%) responded to the intervention, returning a self-sample (247(8%)) or attending for cytology (164(5%)), compared with 183(6%) attending for cytology, relative risk 2.25 (95% CI 1.90-2.65) (comparator arm). Of those testing hrHPV positive (32(13%)), 19(59%) subsequently attended cytology screening. Of those in the intervention group who attended for cytology screening without returning an hrHPV self-sample (n = 164), 5% (n = 8) were referred for colposcopy - all attended. In the comparator group eight of the nine referred for colposcopy attended. Persistent non-responders to invitations for cervical screening are significantly more likely to respond to a postal invitation to return a self-collected sample for HPV testing than a further invitation for cytology screening. However, just over half followed up on this positive HPV result. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

VIA/VILI is more suitable for cervical cancer prevention in Chinese poverty-stricken region: a health economic evaluation.

PubMed

Xie, Yu; Tan, Xiaodong; Shao, Haiyan; Liu, Qing; Tou, Jiyu; Zhang, Yuling; Luo, Qiong; Xiang, Qunying

2017-01-25

Screening is the main preventive method for cervical cancer in developing countries, but each type of screening has advantages and disadvantages. To investigate the most suitable method for low-income areas in China, we conducted a health economic analysis comparing three methods: visual inspection with acetic acid and Lugol's iodine (VIA/VILI), ThinPrep cytology test (TCT), and human papillomavirus (HPV) test. We recruited 3086 women aged 35-65 years using cluster random sampling. Each participant was randomly assigned to one of three cervical cancer screening groups: VIA/VILI, TCT, or HPV test. In order to calculate the number of disability-adjusted life years (DALYs) averted by each screening method, we used Markov models to estimate the natural development of cervical cancer over a 15-year period to estimate the age of onset and duration of each disease stage. The cost-effectiveness ratios (CERs), net present values (NPVs), benefit-cost ratios (BCRs), and cost-utility ratios (CURs) were used as outcomes in the health economic analysis. The positive detection rate in the VIA/VILI group was 1.39%, which was 4.6 and 2.0 times higher than the rates in the TCT and HPV test groups, respectively. The positive predictive value of VIA/VILI (10.53%) was highest while the rate of referral for colposcopy was lowest for those in the HPV + TCT group (0.60%). VIA/VILI performed the best in terms of health economic evaluation results, as the cost of per positive case detected was 8467.9 RMB, which was 24503.0 RMB lower than that for TCT and 5755.9 RMB lower than that for the HPV test. In addition, the NPV and BCR values were 258011.5 RMB and 3.18 (the highest), and the CUR was 2341.8 RMB (the lowest). The TCT performed the worst, since its NPV was <0 and the BCR was <1, indicative of being poorly cost-beneficial. With the best economic evaluation results and requiring minimum medical resources, VIA/VILI is recommended for cervical cancer screening in poverty-stricken areas in China with high incidence of cervical cancer and lack of medical resources.

Sexual Activity, Psychosexual Distress, and Fear of Progression in Women With Human Papillomavirus-Related Premalignant Genital Lesions.

PubMed

Nagele, Eva; Reich, Olaf; Greimel, Elfriede; Dorfer, Martha; Haas, Josef; Trutnovsky, Gerda

2016-02-01

Genital human papillomavirus (HPV) infections are very common in women 18 to 30 years old and substantially affect women's sexual health. To examine sexual activity, psychosexual distress, and fear of progression in women diagnosed with HPV-related precancerous genital lesions. In this observational study, women diagnosed with premalignant lesions of the cervix, vagina, or vulva were recruited from a university hospital-based colposcopy clinic. Quantitative data from three validated patient-administered questionnaires (Sexual Activity Questionnaire, German version of the Cervical Dysplasia Distress Questionnaire, and Fear of Progression Questionnaire) were compared within the study population, according to the location of the genital lesion, and with relevant reference populations. Qualitative data from two written open-ended questions about women's thoughts regarding diagnosis and information were analyzed. Two-hundred nine women completed the questionnaires. Seventy-eight percent of women (n = 162) were referred for evaluation of suspect lesions of the cervix, 8% (n = 17) of the vagina, and 14% (n = 30) of the vulva. There were no significant differences in questionnaire results among the three patient groups, except for sexual consequences (Cervical Dysplasia Distress Questionnaire) and recent sexual activity (Sexual Activity Questionnaire). Women with vulvar lesions were most likely to worry about sexual consequences (ie, being unable to have children, being sexually less attractive, or infecting a sexual partner; P = .04). The Sexual Activity Questionnaire subscales sexual pleasure (P = .15) and sexual habits (P = 1.00) were similar to those in a healthy control population, whereas sexual discomfort (P = .51) was comparable to that in a reference population of women who survived cervical cancer. The subscale partner-specific concerns (Fear of Progression Questionnaire) was similar to that in a reference population of patients with cancer (P = .28). HPV-related precancerous genital lesions, especially of the vulva, are likely to cause concerns about sexual health. Effective information and communication are important to lessen negative sexual consequences and anxiety. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Autoclave sterilization of instruments used on women with cervical neoplasia is an effective method of eradicating residual human papillomavirus DNA: a polymerase chain reaction-based evaluation.

PubMed

Estes, Jacob M; Kirby, Tyler O; Huh, Warner K

2007-01-01

To determine whether autoclave sterilization eradicates human papillomavirus (HPV) DNA on specula and instruments used to treat women with cervical neoplasia. Specula and instruments used in two referral colposcopy clinics were evaluated to determine the PGMY9/11 primer system's ability to amplify residual HPV DNA. Each speculum and instrument was sampled with a Dacron swab and stored in PreservCyt solution (Cytyc Corporation, Marlborough, MA) at 4 degrees C. DNA amplification was performed under standard conditions with appropriate controls followed by HPV typing using the reverse line blot test (Roche Molecular Systems, Alameda, CA). Once validated, the same polymerase chain reaction method was used on autoclave-sterilized specula and biopsy instruments and heated glass bead- and Cidex bath (Johnson & Johnson, New Brunswick, NJ)-sterilized instruments. All results, with appropriate positive and negative controls, were confirmed in triplicate. A total of 140 instruments (70 used and 70 autoclaved) were sampled for residual HPV DNA. Five samples in the contaminated specula arm were excluded from analysis secondary to insufficient sampling. Of the remaining samples, 52.3% (34/65) of contaminated instruments-both specula and biopsy instruments-had detectable HPV DNA. Fifty-five percent of contaminated biopsy instruments (11/20) were positive and 51.1% of contaminated specula (23/45) were positive. All 70 autoclaved samples (50 specula and 20 biopsy instruments) were negative for residual HPV DNA or beta-globin. One instrument in the glass bead and Cidex group that was presumed sterile was positive for HPV 16 DNA. The PGMY9/11 primer system is an effective method to detect residual HPV DNA. Autoclave sterilization appears to eradicate HPV DNA to levels undetectable with this sensitive assay, whereas heated glass beads followed by Cidex bath appears to be inadequate methods. These results suggest that autoclave sterilization is effective when using nondisposable instruments and should be the method of choice in studies using polymerase chain reaction-based amplification of HPV DNA.

Establishment of the Certification System “Gynaecological Dysplasia” in Germany

PubMed Central

Beckmann, M. W.; Quaas, J.; Bischofberger, A.; Kämmerle, A.; Lux, M. P.; Wesselmann, S.

2014-01-01

Gynaecological cancer centres have been established nationwide in Germany since 2008 according to the certification system of the German Cancer Society (Deutsche Krebsgesellschaft e. V. [DKG]) and the German Society for Gynaecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe e. V. [DGGG]). However, patient access to the certified gynaecological cancer centres is currently only possible through direct referrals. A longitudinal structure with the corresponding long-term documentation of both the high-grade precursors as well as the cancers does not exist as yet. According to the aims of the National Cancer Plan, a corresponding structure for the cancer entity “cervix carcinoma” should be established. The foundations for such a structure are appropriate diagnostic units that are responsible, after nationwide screening, for clarification according to guideline-conform principles. On the basis of the vote of the certification commission for gynaecological cancer centres under the chairmanship of the DKG, the Working Group for Gynaecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie e. V. [AGO]), the Committee on Cervical Pathology and Colposcopy (Arbeitsgemeinschaft Zervixpathologie & Kolposkopie [AG-CPC]) and the DGGG the certification system for gynaecological dysplasia has been established. As a general principle, a distinction is made between the certification of a consulting practice for gynaecological dysplasia and a gynaecological dysplasia facility in order to integrate both outpatient and inpatient health-care facilities into the certification system. In analogy to the further catalogue of requirements from the DKG, quantitative and qualitative minimum numbers are demanded. Furthermore, the requirements of the certification process include a summary of patient information, the applied guidelines, continuing and further training, interdisciplinary cooperation in tumour boards, contents or, respectively, procedure descriptions for consulting practices and the trial participations. Central components of the questionnaire are quality indicators that can be used as specific and measurable elements to evaluate the quality of treatment. After successful pilot certification, finalisation of the updated version of the questionnaire and a completed specialist auditor training course for the certification of gynaecological dysplasia, it will be possible to establish a nationwide treatment system for dysplasia within certified structures. PMID:25278628

Cytology and human papillomavirus testing 6 to 12 months after ASCUS or LSIL cytology in organized screening to predict high-grade cervical neoplasia between screening rounds.

PubMed

Tropé, Ameli; Sjøborg, Katrine D; Nygård, Mari; Røysland, Kjetil; Campbell, Suzanne; Alfsen, G Cecilie; Jonassen, Christine M

2012-06-01

We carried out a prospective study comparing the performance of human papillomavirus (HPV) E6/E7 mRNA (PreTect HPV-Proofer; NorChip, Klokkarstua, Norway) and DNA (Amplicor HPV test; Roche Diagnostics, Basel, Switzerland) triage testing of women 6 to 12 months after atypical-squamous-cells-of-undetermined-significance (ASCUS) or low-grade-squamous-intraepithelial-lesion (LSIL) cytology in organized screening to predict high-grade cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) between screening rounds. Between January 2005 and April 2008, 692 study women with screening-detected ASCUS/LSIL cytology 6 to 12 months earlier returned for HPV mRNA and DNA testing and repeat cytology. The median follow-up time was 3 years, using existing health care facilities. Follow-up test results were available for 625 women. Of the 145 CIN2+ cases detected during the study period, 95 (65.5%) were HPV mRNA positive 6 to 12 months after screening-detected ASCUS/LSIL, 44 (30.4%) were HPV mRNA negative, and 6 (4.1%) were invalid. The corresponding HPV DNA results were 139 (95.9%), 5 (3.4%), and 1 (0.7%), respectively. The cumulative incidences of CIN2+ 3 years after a negative HPV mRNA and DNA test were 10.3% (95% confidence interval [CI], 7.2 to 13.3%) and 1.8% (95% CI, 0.0 to 3.6%), respectively. The cumulative incidences of CIN2+ 3 years after positive HPV mRNA and DNA tests were 52.8% (95% CI, 40.1 to 60.1%) and 41.3% (95% CI, 35.5 to 46.6%), respectively. In conclusion, both positive HPV mRNA and DNA test results have a high enough long-term prediction of CIN2+ risk to consider referral to colposcopy as good practice when performed in delayed triage of women with ASCUS/LSIL cytology. In addition, the low CIN2+ risk among women with a negative Amplicor HPV test in our study confirms its safe use in a clinical setting.

Cost-effectiveness of HPV-based cervical cancer screening in the public health system in Nicaragua.

PubMed

Campos, Nicole G; Mvundura, Mercy; Jeronimo, Jose; Holme, Francesca; Vodicka, Elisabeth; Kim, Jane J

2017-06-15

To evaluate the cost-effectiveness of human papillomavirus (HPV) DNA testing (versus Papanicolaou (Pap)-based screening) for cervical cancer screening in Nicaragua. A previously developed Monte Carlo simulation model of the natural history of HPV infection and cervical cancer was calibrated to epidemiological data from Nicaragua. Cost data inputs were derived using a micro-costing approach in Carazo, Chontales and Chinandega departments; test performance data were from a demonstration project in Masaya department. Nicaragua's public health sector facilities. Women aged 30-59 years. Screening strategies included (1) Pap testing every 3 years, with referral to colposcopy for women with an atypical squamous cells of undetermined significance or worse result ('Pap'); (2) HPV testing every 5 years, with referral to cryotherapy for HPV-positive eligible women (HPV cryotherapy or 'HPV-Cryo'); (3) HPV testing every 5 years, with referral to triage with visual inspection with acetic acid (VIA) for HPV-positive women ('HPV-VIA'); and (4) HPV testing every 5 years, with referral to Pap testing for HPV-positive women ('HPV-Pap'). Reduction in lifetime risk of cancer and incremental cost-effectiveness ratios (ICER; 2015 US$ per year of life saved (YLS)). HPV-based screening strategies were more effective than Pap testing. HPV-Cryo was the least costly and most effective strategy, reducing lifetime cancer risk by 29.5% and outperforming HPV-VIA, HPV-Pap and Pap only, which reduced cancer risk by 19.4%, 12.2% and 10.8%, respectively. With an ICER of US$320/YLS, HPV-Cryo every 5 years would be very cost-effective using a threshold based on Nicaragua's per capita gross domestic product of US$2090. Findings were robust across sensitivity analyses on test performance, coverage, compliance and cost parameters. HPV testing is very cost-effective compared with Pap testing in Nicaragua, due to higher test sensitivity and the relatively lower number of visits required. Increasing compliance with recommended follow-up will further improve the health benefits and value for public health dollars. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Clinical significance of HPV L1 capsid protein detection in cervical exfoliated cells in high-risk HPV positive women].

PubMed

Wang, Jiajian; Tian, Qifang; Zhang, Su; Lyu, Liping; Dong, Jie; Lyu, Weiguo

2015-04-01

To explore the clinical significance of human papillomavirus L1 capsid protein detection in cervical exfoliated cells in high-risk HPV positive women. From November 2012 to June 2013, 386 high-risk HPV positive (detected by hybrid capture II) cases were enrolled as eligible women from Huzhou Maternity & Child Care Hospital and Women's Hospital, School of Medicine, Zhejiang University. All eligible women underwent liquid-based cytology (ThinPrep) followed by colposcopy. Biopsies were taken if indicated. Cervical exfoliated cells were collected for HPV L1 capsid protein detection by immunocytochemistry. Expression of HPV L1 capsid protein in groups with different histological diagnosis were compared, and the role of HPV L1 capsid protein detection in cervical exfoliated cells in cervical lesions screening was accessed. Total 386 enrolled eligible women were finally diagnosed histologically as follwed: 162 normal cervix, 94 low-grade squamous intraepithelial lesion (LSIL), 128 high-grade squamous intraepithelial lesion (HSIL) and 2 squamous cervical cancer (SCC). The positive expression rate of HPV L1 in HSIL+ (HSIL or worse) group was significantly lower than that in LSIL- (LSIL or better) group (19.2% vs 66.4%, P=0.000). While identifying HSIL+ in HPV positive cases and compared with cytology, HPV L1 detection resulted in significant higher sensitivity (80.77% vs 50.77%, P=0.000) and negative predictive value (NPV; 87.18% vs 76.47%, P=0.004), significant lower specificity (66.41% vs 81.25%, P=0.000), and comparable positive predictive value (PPV; 54.97% vs 57.89%, P=0.619). To identify HSIL+ in HPV-positive/cytology-negative women, the sensitivity, specificity, PPV, and NPV of HPV L1 detection were 87.50%, 61.54%, 41.18%, and 94.12% respectively, while 80.00%, 86.36%, 80.00% and 86.36% respectively in HPV-positive/atypical squamous cell of undetermined significance (ASCUS) women. HPV L1 capsid detection in cervical exfoliated cells have a role in cervical lesions screening in high-risk HPV positive women, and may be a promising triage for high-risk HPV-positive/cytology-negative or ASCUS women.

The Role of Human Papillomavirus Genotyping in Cervical Cancer Screening: A Large-Scale Evaluation of the cobas HPV Test.

PubMed

Schiffman, Mark; Boyle, Sean; Raine-Bennett, Tina; Katki, Hormuzd A; Gage, Julia C; Wentzensen, Nicolas; Kornegay, Janet R; Apple, Raymond; Aldrich, Carrie; Erlich, Henry A; Tam, Thanh; Befano, Brian; Burk, Robert D; Castle, Philip E

2015-09-01

The cobas HPV Test ("cobas"; Roche Molecular Systems) detects HPV16 and HPV18 individually, and a pool of 12 other high-risk (HR) HPV types. The test is approved for (i) atypical squamous cells of undetermined significance (ASC-US) triage to determine need for colposcopy, (ii) combined screening with cytology ("cotesting"), and (iii) primary HPV screening. To assess the possible value of HPV16/18 typing, >17,000 specimens from a longitudinal cohort study of initially HPV-positive women (HC2, Qiagen) were retested with cobas. To study accuracy, cobas genotyping results were compared with those of an established method, the Linear Array HPV Genotyping Test (LA, Roche Molecular Systems). Clinical value of the typing strategy was evaluated by linking the cobas results (supplemented by other available typing results) to 3-year cumulative risks of CIN3+. Grouped hierarchically (HPV16, else HPV18, else other HR types, else negative), the κ statistic for agreement between cobas and LA was 0.86 [95% confidence interval (CI), 0.86-0.87]. In all three scenarios, HPV16-positive women were at much higher 3-year risk of CIN3+ than HPV16-negative women: women ages 21 and older with ASC-US (14.5%; 95% CI, 13.5%-15.5% vs. 3.5%; 95% CI, 3.3-3.6); women ages 30 years and older that were HPV-positive cytology-negative (10.3%; 95% CI, 9.6-11.1 vs. 2.3%; 95% CI, 2.2-2.4); and all women 25 years and older that were HPV-positive (18.5%; 95% CI, 17.8-19.2 vs. 4.3%; 95% CI, 4.2-4.4). The cobas and LA results show excellent agreement. The data support HPV16 typing. HPV16 typing is useful in the management of HPV-positive/cytology-negative women in cotesting, of all HPV-positive women in primary HPV testing, and perhaps in the management of HPV-positive women with ASC-US. Cancer Epidemiol Biomarkers Prev; 24(9); 1304-10. ©2015 American Association for Cancer Research.

Protecting the underscreened women in developed countries: the value of HPV test.

PubMed

Ibáñez, Raquel; Autonell, Josefina; Sardà, Montserrat; Crespo, Nayade; Pique, Pilar; Pascual, Amparo; Martí, Clara; Fibla, Montserrat; Gutiérrez, Cristina; Lloveras, Belén; Moreno-Crespi, Judit; Torrent, Anna; Baixeras, Núria; Alejo, María; Bosch, Francesc Xavier; de Sanjosé, Silvia

2014-08-08

Poor attendance to cervical cancer (CC) screening is a major risk factor for CC. Efforts to capture underscreened women are considerable and once women agree to participate, the provision of longitudinal validity of the screening test is of paramount relevance. We evaluate the addition of high risk HPV test (HPV) to cervical cytology as a primary screening test among underscreened women in the longitudinal prediction of intraepithelial lesions grade 2 or worse (CIN2+). Women were included in the study if they were older than 39 years and with no evidence of cervical cytology in the previous five years within the Public Primary Health Care System in Catalonia (Spain). 1,832 underscreened women from eight public primary health areas were identified during 2007-2008 and followed-up for over three years to estimate longitudinal detection of CIN2+. Accuracy of each screening test and the combination of both to detect CIN2+ was estimated. The risk of developing CIN2+ lesions according to histology data by cytology and HPV test results at baseline was estimated using the Kaplan-Meier method. At baseline, 6.7% of participants were HPV positive, 2.2% had an abnormal cytology and 1.3% had both tests positive. At the end of follow-up, 18 out of 767 (2.3%) underscreened women had a CIN2+, two of which were invasive CC. The three-year longitudinal sensitivity and specificity estimates to detect CIN2+ were 90.5% and 93.0% for HPV test and 38.2% and 97.8% for cytology. The negative predictive value was >99.0% for each test. No additional gains in validity parameters of HPV test were observed when adding cytology as co-test. The referral to colposcopy was higher for HPV but generated 53% higher detection of CIN2+ compared to cytology. Underscreened women had high burden of cervical disease. Primary HPV screening followed by cytology triage could be the optimal strategy to identify CIN2+ leading to longer and safe screen intervals.

Scientific research in obstetrics and gynecology: changes in the trends over three decades

PubMed Central

Kassem, Gamal A

2015-01-01

Aim The aim of this work was to assess scientific research of master’s and doctoral theses and essays in the Department of Obstetrics and Gynecology, Zagazig University, Egypt. Materials and methods All master’s and doctoral theses and essays since the foundation of Department of Obstetrics and Gynecology, Zagazig University, Egypt, in 1975 till end of 2012 were reviewed. Results A total of 703 theses and essays were reviewed. The important topics in the specialty of obstetrics and gynecology were covered and updated. Infertility, in vitro fertilization–embryo transfer (IVF-ET) and related techniques, and polycystic ovarian disease were the most common gynecologic topics (27.2%), followed by gynecologic oncology (18.5%). Preeclampsia was the most common obstetrics topic (18.8%), followed by issues of high-risk pregnancy, fetal growth restriction, and fetal well-being (11.6%). The number of researches that allow the candidates to learn skills was 183 and it was increased from 4.4% of all research in the period 1979–1988 to 33.2% in period 1989–2000 then slightly decreased to 31.2% in period 2001–2012. Ultrasonography was on the top and was present in 99 out of 183 (54.1%) followed by laparoscopy (30, 16.4%), hysteroscopy (25, 13.7%), IVF-ET and related techniques (16, 8.7%) and colposcopy (13, 7.1%) researches. Multi-disciplinary research was decreased by 61.7% in the period 2001–2012. Researches in academic fields were abandoned and in some clinically important areas like preeclampsia were decreased. Conclusion Scientific research of master’s and doctoral theses and essays was comprehensive, updated, and had some autonomy independent of plans. Research which enable the candidate to learn skills were increased on the expense of academic, clinical and multidisciplinary research. It could be recommended that plans for scientific research should be flexible and should leave a space for local departmental views. Proper training of residents during their rotation in these subspecialties may help to revive the lost interest in clinically important areas. PMID:25565900

Comparison of DNA testing strategies in monitoring human papillomavirus infection prevalence through simulation.

PubMed

Lin, Carol Y; Li, Ling

2016-11-07

HPV DNA diagnostic tests for epidemiology monitoring (research purpose) or cervical cancer screening (clinical purpose) have often been considered separately. Women with positive Linear Array (LA) polymerase chain reaction (PCR) research test results typically are neither informed nor referred for colposcopy. Recently, a sequential testing by using Hybrid Capture 2 (HC2) HPV clinical test as a triage before genotype by LA has been adopted for monitoring HPV infections. Also, HC2 has been reported as a more feasible screening approach for cervical cancer in low-resource countries. Thus, knowing the performance of testing strategies incorporating HPV clinical test (i.e., HC2-only or using HC2 as a triage before genotype by LA) compared with LA-only testing in measuring HPV prevalence will be informative for public health practice. We conducted a Monte Carlo simulation study. Data were generated using mathematical algorithms. We designated the reported HPV infection prevalence in the U.S. and Latin America as the "true" underlying type-specific HPV prevalence. Analytical sensitivity of HC2 for detecting 14 high-risk (oncogenic) types was considered to be less than LA. Estimated-to-true prevalence ratios and percentage reductions were calculated. When the "true" HPV prevalence was designated as the reported prevalence in the U.S., with LA genotyping sensitivity and specificity of (0.95, 0.95), estimated-to-true prevalence ratios of 14 high-risk types were 2.132, 1.056, 0.958 for LA-only, HC2-only, and sequential testing, respectively. Estimated-to-true prevalence ratios of two vaccine-associated high-risk types were 2.359 and 1.063 for LA-only and sequential testing, respectively. When designated type-specific prevalence of HPV16 and 18 were reduced by 50 %, using either LA-only or sequential testing, prevalence estimates were reduced by 18 %. Estimated-to-true HPV infection prevalence ratios using LA-only testing strategy are generally higher than using HC2-only or using HC2 as a triage before genotype by LA. HPV clinical testing can be incorporated to monitor HPV prevalence or vaccine effectiveness. Caution is needed when comparing apparent prevalence from different testing strategies.

Cost-effectiveness of HPV-based cervical cancer screening in the public health system in Nicaragua

PubMed Central

Mvundura, Mercy; Jeronimo, Jose; Holme, Francesca; Vodicka, Elisabeth; Kim, Jane J

2017-01-01

Objectives To evaluate the cost-effectiveness of human papillomavirus (HPV) DNA testing (versus Papanicolaou (Pap)-based screening) for cervical cancer screening in Nicaragua. Design A previously developed Monte Carlo simulation model of the natural history of HPV infection and cervical cancer was calibrated to epidemiological data from Nicaragua. Cost data inputs were derived using a micro-costing approach in Carazo, Chontales and Chinandega departments; test performance data were from a demonstration project in Masaya department. Setting Nicaragua’s public health sector facilities. Participants Women aged 30–59 years. Interventions Screening strategies included (1) Pap testing every 3 years, with referral to colposcopy for women with an atypical squamous cells of undetermined significance or worse result (‘Pap’); (2) HPV testing every 5 years, with referral to cryotherapy for HPV-positive eligible women (HPV cryotherapy or ‘HPV-Cryo’); (3) HPV testing every 5 years, with referral to triage with visual inspection with acetic acid (VIA) for HPV-positive women (‘HPV-VIA’); and (4) HPV testing every 5 years, with referral to Pap testing for HPV-positive women (‘HPV-Pap’). Outcome measures Reduction in lifetime risk of cancer and incremental cost-effectiveness ratios (ICER; 2015 US$ per year of life saved (YLS)). Results HPV-based screening strategies were more effective than Pap testing. HPV-Cryo was the least costly and most effective strategy, reducing lifetime cancer risk by 29.5% and outperforming HPV-VIA, HPV-Pap and Pap only, which reduced cancer risk by 19.4%, 12.2% and 10.8%, respectively. With an ICER of US$320/YLS, HPV-Cryo every 5 years would be very cost-effective using a threshold based on Nicaragua’s per capita gross domestic product of US$2090. Findings were robust across sensitivity analyses on test performance, coverage, compliance and cost parameters. Conclusions HPV testing is very cost-effective compared with Pap testing in Nicaragua, due to higher test sensitivity and the relatively lower number of visits required. Increasing compliance with recommended follow-up will further improve the health benefits and value for public health dollars. PMID:28619772

Screening for the Prevention of Cervical Cancer: The Good, the Bad, and the Ugly

Cancer.gov

Dr. Philip Castle is a Professor in the Department of Epidemiology and Population Health at Albert Einstein College of Medicine, Bronx, N.Y., USA and the CEO and Co-Founder of the Global Coalition Against Cervical Cancer (Arlington, VA, USA). He is also a Visiting Professor at the Cancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, P.R. China and was Honorary Professor at the University of New South Wales, Sydney, Australia. Previously, Dr. Castle was the Chief Scientific Officer of the American Society for Clinical Pathology (ASCP) (2011-2). He was a Senior, Tenured Investigator (2010-11) and Tenure-Track Investigator (2003-10) in the Division of Cancer Epidemiology and Genetics (DCEG) at the U.S. National Cancer Institute (NCI). He received his Ph.D. in Biophysics in 1995 and M.P.H. in Epidemiology in 2000 from the Johns Hopkins University. Dr. Castle regularly participates in the development of national and international guidelines for cervical cancer prevention. Dr. Castle serves as a consultant for several countries, including Nicaragua, Norway, and Australia, on the development of national cervical cancer prevention programs and is participating in/consulting on pilot/demonstration projects in El Salvador and Botswana. He was recently a member of the Centers for Disease Control and Prevention’s (CDC) National Breast and Cervical Cancer Early Detection and Prevention (NBCCEDP) Advisory Committee. Dr. Castle is a member of the Board of Directors of the American Society for Colposcopy and Cervical Pathology (ASCCP). He serves as steering committee member of the American Society for Clinical Oncology’s Cervical Cancer Resource Stratified Secondary Prevention Guideline Panel. For his work in cervical cancer prevention, Dr. Castle has received (1) An EUROGIN Distinguished Service Award (2006); (2) a NIH Merit Award for introduction of HPV testing into low-resource settings in the U.S. (2007); (3) a Distinguished Scientific Achievement Award from the ASCCP (2010), its highest honor; (4) The Arthur S. Flemming Award for Exceptional Achievement in Federal Government Service for Applied Science, Engineering and Mathematics (2010); and (5) NCI Cancer Prevention Fellowship Program Distinguished Alumni (2017-8).

Clinical response to glycyrrhizinic acid in genital infection due to human papillomavirus and low-grade squamous intraepithelial lesion

PubMed Central

Valencia, Marcelino Hernández; Pacheco, Adia Carrillo; Quijano, Tomás Hernández; Girón, Antonio Vargas; López, Carlos Vargas

2011-01-01

Human papilloma virus (HPV) can infect any of the mucosal areas of the body and cause cervical cancer. Until recently, no specific treatments were available for this condition; therefore, any damaged tissue had to be removed or destroyed, which may have presented obstetrical repercussions for some women. Recently, new drugs have been developed that have shown to be effective for the cure of HPV infection. Glycyrrhizinic acid (GA) has shown fewer side effects and its systemic use makes it possible to reach difficult-to-treat lesions. The purpose of this study was to evaluate the clinical outcome of GA to eliminate the epithelial lesion and HPV. We carried out a longitudinal, descriptive study that included women of reproductive age who were diagnosed with HPV associated with low-grade squamous intraepithelial lesion (LSIL). Subjects began treatment based on GA using two routes of administration - systemic (oral) and topical (spray) - with assessments every month to determine the clinical changes of the lesions through colposcopy and Papanicolaou (Pap) smear. Simple statistics were used along with two-tailed Student's t-test; P<0.05 was considered statistically significant before and after treatment. There were 70 eligible patients, of whom 62 fulfilled the inclusion criteria. Age of subjects was 27.8±9.5 years. At the time of the study, 100% of the patients had HPV infection, 40% were associated with LSIL, and only 16% used a barrier contraceptive (condom) method. Resolution was achieved in all patients from 4 weeks of treatment initiation and improvement was achieved in the majority of patients at 12 weeks (74%) (P<0.001). However, there was persistence of LSIL in 27.7% of patients and only one patient progressed to cervical intraepithelial neoplasia (CIN) II. The use of GA proved to be effective in resolving clinical HPV lesions. For cervical lesions with epithelial changes (LSIL), treatment may be required for a longer period as with other drugs used for this infection, as well as monitoring for at least 1 year according to the natural evolution of the disease. PMID:24765393

Safety, Acceptability and Adherence of Dapivirine Vaginal Ring in a Microbicide Clinical Trial Conducted in Multiple Countries in Sub-Saharan Africa

PubMed Central

Nel, Annalene; Bekker, Linda-Gail; Bukusi, Elizabeth; Hellstrӧm, Elizabeth; Kotze, Philip; Louw, Cheryl; Martinson, Francis; Masenga, Gileard; Montgomery, Elizabeth; Ndaba, Nelisiwe; van der Straten, Ariane; van Niekerk, Neliëtte; Woodsong, Cynthia

2016-01-01

Background This was the first microbicide trial conducted in Africa to evaluate an antiretroviral-containing vaginal ring as an HIV prevention technology for women. Objectives The trial assessed and compared the safety, acceptability and adherence to product use of a 4-weekly administered vaginal ring containing the antiretroviral microbicide, dapivirine, with a matching placebo ring among women from four countries in sub-Saharan Africa. Methods 280 Healthy, sexually active, HIV-negative women, aged 18 to 40 years were enrolled with 140 women randomised to a dapivirine vaginal ring (25 mg) and 140 women to a matching placebo ring, inserted 4-weekly and used over a 12-week period. Safety was evaluated by pelvic examination, colposcopy, clinical laboratory assessments, and adverse events. Blood samples for determination of plasma concentrations of dapivirine were collected at Weeks 0, 4 and 12. Residual dapivirine levels in returned rings from dapivirine ring users were determined post-trial. Participant acceptability and adherence to ring use were assessed by self-reports. Results No safety concerns or clinically relevant differences were observed between the dapivirine and placebo ring groups. Plasma dapivirine concentrations immediately prior to ring removal were similar after removal of the first and third ring, suggesting consistent ring use over the 12-week period. No clear relationship was observed between the residual amount of dapivirine in used rings and corresponding plasma concentrations. Self-reported adherence to daily use of the vaginal rings over the 12-week trial period was very high. At the end of the trial, 96% of participants reported that the ring was usually comfortable to wear, and 97% reported that they would be willing to use it in the future if proven effective. Conclusions The dapivirine vaginal ring has a favourable safety and acceptability profile. If proven safe and effective in large-scale trials, it will be an important component of combination HIV prevention approaches for women. Trial Registration ClinicalTrials.gov NCT01071174 PMID:26963505

Physics of light and lasers.

PubMed

Absten, G T

1991-09-01

Because most laser procedures use the heating effect of the light and given the number of parameters that may be varied--such as power density, power, pulsing, and heating of fiber tips and probes--significant overlap in applications of the various lasers can result. This is readily apparent in the conflicting claims of laser manufacturers seen in promotional materials. Despite this, each type has its strengths. The CO2 laser is a specialty instrument, particularly for microscopic applications in neurosurgery, otolaryngology, and gynecology. Its hemostasis and vaporizing abilities allow its use in dermatology and in general surgery for tumor resection and hemostasis. In gynecology it seems best for colposcopy (cervical and vaginal) and, through a micromanipulator, for laparotomy. The beam is focused and delivered by handpieces and micromanipulators on microscopes. Through the laparoscope, it requires the use of a special laser coupler on a special laser laparoscope to allow for line-of-sight delivery of the beam through the operating channel. Waveguide delivery systems have been introduced for CO2 laser laparoscopy using standard laparoscopes. These function as hollow, slender tubes through which the beam is transmitted by means of hundreds of glancing internal reflections in the tube, which emits the beam at its tip. This eliminates many of the alignment problems of coupler cube-type systems and allows the beam to be delivered close to the target. The Nd:YAG laser is the primary endoscopic instrument in pulmonology, gastroenterology, and urology. The use of contact tips, though not a panacea, increases its applications, particularly in general surgery. Its primary use in gynecology is for endometrial ablation with bare fibers for deep coagulation. Its use for laparoscopy with contact probes or sculpted fibers is quickly growing. Green light lasers (argon and KTP) are color-selective photocoagulators and may be used to cut tissue. They are fiberoptically delivered like the Nd:YAG laser. Their best use in gynecology appears to be a versatile instruments for operative laparoscopy and the simple treatment of endometriosis. A standard quartz fiber with these lasers is usually more versatile than a contact tip with an Nd:YAG laser when used for cutting.

Evaluating cytology for the detection of invasive cervical cancer.

PubMed

Landy, R; Castanon, A; Hamilton, W; Lim, A W W; Dudding, N; Hollingworth, A; Sasieni, P D

2016-06-01

To assess the sensitivity, the number needed to screen (NNS) and the positive predictive value (PPV) of cervical cytology for the diagnosis of cancer by age in a screening population. A retrospective cohort of women with invasive cervical cancer nested within a census of cervical cytology. All (c. 8 million) women aged 20-64 years with cervical cytology (excluding tests after an earlier abnormality). From April 2007 to March 2010, 3372 women had cervical cancer diagnosed within 12 months of such cytology in England. The sensitivity of cervical cytology to cancer, NNS to detect one cancer and predictive values of cytology were calculated for various 'referral' thresholds. These were calculated for ages 20-24, 25-34, 35-49 and 50-64 years. The sensitivity of at least moderate dyskaryosis [equivalent to a high-grade squamous intraepithelial lesion (HSIL) or worse] for cancer of 89.4% [95% confidence interval (CI) 88.3-90.4%] in women offered screening was independent of age. At all ages, women with borderline-early recall or mild dyskaryosis on cytology (equivalent to ASC-US and LSIL, respectively, in the Bethesda system) had a similar risk of cervical cancer to the risk in all women tested. The PPV of severe dyskaryosis/?invasive and ?glandular neoplasia cytology (equivalent to squamous cell carcinoma and adenocarcinoma/adenocarcinoma in situ, respectively, in the Bethesda System) were 34% and 12%, respectively; the PPV of severe dyskaryosis (HSIL: severe dysplasia) was 4%. The NNS was lowest when the incidence of cervical cancer was highest, at ages 25-39 years, but the proportion of those with abnormal cytology who have cancer was also lowest in younger women. The PPV of at least severe dyskaryosis (HSIL: severe dysplasia) for cancer was 4-10% of women aged 25-64 years, justifying a 2-week referral to colposcopy and demonstrating the importance of failsafe monitoring for such patients. The sensitivity of cytology for cervical cancer was excellent across all age groups. © 2015 The Authors Cytopathology Published by John Wiley & Sons Ltd.

Improving the performance of reflex Human Papilloma Virus (HPV) testing in triaging women with atypical squamous cells of undetermined significance (ASCUS): A restrospective study in a tertiary hospital in United Arab Emirates (UAE).

PubMed

Fakhreldin, Marwa; Elmasry, Karim

2016-02-03

Cervical cancer is the second commonest cancer in women worldwide. Infection with oncogenic types of human Papillomavirus (HPV) is the most important risk factor for developing cervical cancer. Reflex High risk HPV (HR-HPV) testing is of significant value in the assessment of Papanicolaou (Pap) smear results where ASCUS are identified. To improve the performance of reflex HR-HPV testing in triage of ASCUS and analyze the factors impacting it. In this study, we generated a database of 9641 women who had cervical smears collected during the study period from the cytopathology record in a large tertiary hospital in UAE. These included 297 smears with ASCUS diagnosis. All cases were retrospectively followed up with a mean duration of 2.44 years. We analyzed data according to the outcome based on several follow-up Pap smear analysis as the reference assessment. We detected HR-HPV infection in 17.9% of cases. 9.1% <25, 28.8% 25-34 and 62.1% ≥35 years old. HR-HPV prevalence was higher among premenopausal women (20.7%) compared to postmenopausal women (9.5%) (P-value=0.044). The rate of progression to high grade lesions was also higher (28.7%) in the premenopausal group compared to (12.8%) in the postmenopausal group. Reflex HPV testing had an overall sensitivity of 41.1%, specificity of 88.2%, positive predictive value (PPV) of 62.1%, and negative predictive value (NPV) of 75.9% in detection of cervical lesions. These figures were higher on combining premenopausal status and complaint of abnormal bleeding or discharge/itching (66.7%, 93.3%, 66.8% and 93.3% respectively). The sensitivity, specificity and NPV of reflex HPV testing in the triage of ASCUS cases can be more accurate in premenopausal women upon adding age group and presenting complaint as a triage item. This improves the performance of reflex HPV testing and the subsequent selection of high risk patients for colposcopy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical significance of HPV DNA cotesting in Korean women with ASCUS or ASC-H.

PubMed

Lee, Sanghoon; Kim, Jae Won; Hong, Jin Hwa; Song, Jae Yun; Lee, Jae Kwan; Kim, In Sun; Lee, Nak Woo

2014-12-01

The purpose of this study was to evaluate the clinical significance of Human papillomavirus (HPV) DNA cotesting in Korean women with abnormal Papanicolaou (Pap) smear results based on colposcopic pathology. A total of 1012 women underwent liquid-based Pap smears and hybrid capture II HPV DNA tests followed by colposcopy at the Korea University Hospital from January 2007 to May 2012. Of these women, 832 women were included in this retrospective study. The mean patient age was 45.4 ± 13.7 years (range:15-80). The distribution of Pap smear results was normal (4.7%), atypical squamous cells of uncertain significance (ASCUS) (42.1%), low-grade squamous intraepithelial lesion (26.8%), ASC-H (7.0%), and high-grade squamous intraepithelial lesion (HSIL) (19.5%). In women with ASCUS, none of the 87 HPV-negative had ≥cervical intraepithelial neoplasia (CIN2) (P < 0.001). In women with ASC-H, only one out of 17 HPV-negative vs. 14 out of 41 HPV-positive had ≥CIN2 (P = 0.025). In patients with HSIL, 54.5% of HPV-negative had ≥CIN2, as compared to 80.8% of HPV-positive with ≥CIN2 (P = 0.039). Patients were further analyzed by age groups: <30 and ≥30 years. In HPV-negative women, there was a significant difference in the ratio of ≥CIN2 (30.8% <30 vs. 4.5% ≥30, P = 0.005). When the HPV DNA test was negative in women ≥30, the risk of ≥CIN2 was significantly lower (P < 0.001). HPV DNA cotesting in women with ASCUS and ASC-H furnish healthcare providers with informative data. There is a lower proportion of ≥CIN2 in HPV-negative women and a higher proportion of ≥CIN2 in HPV-positive. When HPV data were further evaluated by age group, the risk of ≥CIN2 was lower in HPV-negative women, especially in women ≥30. © 2014 Wiley Periodicals, Inc.

Cytology and Human Papillomavirus Testing 6 to 12 Months after ASCUS or LSIL Cytology in Organized Screening To Predict High-Grade Cervical Neoplasia between Screening Rounds

PubMed Central

Sjøborg, Katrine D.; Nygård, Mari; Røysland, Kjetil; Campbell, Suzanne; Alfsen, G. Cecilie; Jonassen, Christine M.

2012-01-01

We carried out a prospective study comparing the performance of human papillomavirus (HPV) E6/E7 mRNA (PreTect HPV-Proofer; NorChip, Klokkarstua, Norway) and DNA (Amplicor HPV test; Roche Diagnostics, Basel, Switzerland) triage testing of women 6 to 12 months after atypical-squamous-cells-of-undetermined-significance (ASCUS) or low-grade-squamous-intraepithelial-lesion (LSIL) cytology in organized screening to predict high-grade cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) between screening rounds. Between January 2005 and April 2008, 692 study women with screening-detected ASCUS/LSIL cytology 6 to 12 months earlier returned for HPV mRNA and DNA testing and repeat cytology. The median follow-up time was 3 years, using existing health care facilities. Follow-up test results were available for 625 women. Of the 145 CIN2+ cases detected during the study period, 95 (65.5%) were HPV mRNA positive 6 to 12 months after screening-detected ASCUS/LSIL, 44 (30.4%) were HPV mRNA negative, and 6 (4.1%) were invalid. The corresponding HPV DNA results were 139 (95.9%), 5 (3.4%), and 1 (0.7%), respectively. The cumulative incidences of CIN2+ 3 years after a negative HPV mRNA and DNA test were 10.3% (95% confidence interval [CI], 7.2 to 13.3%) and 1.8% (95% CI, 0.0 to 3.6%), respectively. The cumulative incidences of CIN2+ 3 years after positive HPV mRNA and DNA tests were 52.8% (95% CI, 40.1 to 60.1%) and 41.3% (95% CI, 35.5 to 46.6%), respectively. In conclusion, both positive HPV mRNA and DNA test results have a high enough long-term prediction of CIN2+ risk to consider referral to colposcopy as good practice when performed in delayed triage of women with ASCUS/LSIL cytology. In addition, the low CIN2+ risk among women with a negative Amplicor HPV test in our study confirms its safe use in a clinical setting. PMID:22518869

Comparing triage algorithms using HPV DNA genotyping, HPV E7 mRNA detection and cytology in high-risk HPV DNA-positive women.

PubMed

Luttmer, Roosmarijn; Berkhof, Johannes; Dijkstra, Maaike G; van Kemenade, Folkert J; Snijders, Peter J F; Heideman, Daniëlle A M; Meijer, Chris J L M

2015-06-01

High-risk human papillomavirus (hrHPV) DNA positive women require triage testing to identify those with high-grade cervical intraepithelial neoplasia or cancer (≥CIN2). Comparing three triage algorithms (1) E7 mRNA testing following HPV16/18/31/33/45/52/58 genotyping (E7 mRNA test), (2) HPV16/18 DNA genotyping and (3) cytology, for ≥CIN2 detection in hrHPV DNA-positive women. hrHPV DNA-positive women aged 18-63 years visiting gynecology outpatient clinics were included in a prospective observational cohort study. From these women a cervical scrape and colposcopy-directed biopsies were obtained. Cervical scrapes were evaluated by cytology, HPV DNA genotyping by bead-based multiplex genotyping of GP5+6+-PCR-products, and presence of HPV16/18/31/33/45/52/58 E7 mRNA using nucleic acid sequence-based amplification (NASBA) in DNA positive women for respective HPV types. Sensitivities and specificities for ≥CIN2 were compared between E7 mRNA test and HPV16/18 DNA genotyping in the total group (n=348), and E7 mRNA test and cytology in a subgroup of women referred for non-cervix-related gynecological complaints (n=133). Sensitivity for ≥CIN2 of the E7 mRNA test was slightly higher than that of HPV16/18 DNA genotyping (66.9% versus 60.9%; ratio 1.10, 95% CI: 1.0002-1.21), at similar specificity (54.8% versus 52.3%; ratio 1.05, 95% CI: 0.93-1.18). Neither sensitivity nor specificity of the E7 mRNA test differed significantly from that of cytology (sensitivity: 68.8% versus 75.0%; ratio 0.92, 95% CI: 0.72-1.17; specificity: 59.4% versus 65.3%; ratio 0.91, 95% CI: 0.75-1.10). For detection of ≥CIN2 in hrHPV DNA-positive women, an algorithm including E7 mRNA testing following HPV16/18/31/33/45/52/58 DNA genotyping performs similar to HPV16/18 DNA genotyping or cytology. Copyright © 2015 Elsevier B.V. All rights reserved.

High-risk human papillomavirus (hrHPV) E6/E7 mRNA testing by PreTect HPV-Proofer for detection of cervical high-grade intraepithelial neoplasia and cancer among hrHPV DNA-positive women with normal cytology.

PubMed

Rijkaart, D C; Heideman, D A M; Coupe, V M H; Brink, A A T P; Verheijen, R H M; Skomedal, H; Karlsen, F; Morland, E; Snijders, P J F; Meijer, C J L M

2012-07-01

Our aim was to investigate whether high-risk HPV (hrHPV) mRNA detection by PreTect HPV-Proofer can be used to stratify hrHPV DNA-positive women of different cytology classes for risk of high-grade cervical intraepithelial neoplasia or worse (cervical precancer or cancer, i.e., cervical intraepithelial neoplasia grade 2 or higher [≥ CIN2]). A total of 375 women participating in population-based screening, with a GP5+/6+-PCR hrHPV DNA-positive cervical scrape with normal cytology (n = 202), borderline or mild dyskaryosis (BMD) (n = 88), or moderate dyskaryosis or worse (>BMD) (n = 85), were enrolled. Cervical scrapes were additionally subjected to HPV16/18/31/33/45 E6/E7 mRNA analysis by PreTect HPV-Proofer (mRNA test). Referral and follow-up policies were based on cytology, hrHPV DNA, and mRNA testing. The primary study endpoint was the number of ≥CIN2 detected within 3 years of follow-up. The mRNA positivity increased with the severity of cytological abnormality, ranging from 32% (64/202) in hrHPV DNA-positive women with normal cytology to 47% (41/88) in BMD and 68% (58/85) in >BMD groups (P < 0.01). Women with ≥ CIN2 were more likely to test positive by mRNA test (63%) than women without evidence of ≥ CIN2 (32%; P < 0.01). A positive mRNA test result conferred an increased ≥ CIN2 risk in hrHPV DNA-positive women with normal cytology, i.e., 0.55 (95% confidence interval [95% CI], 0.34 to 0.76) in mRNA-positive versus 0.20 (95% CI, 0.07 to 0.33) in mRNA-negative women. In hrHPV DNA-positive women with BMD or >BMD, the result of the mRNA test did not influence the ≥ CIN2 risk. In conclusion, mRNA testing by PreTect HPV-Proofer might be of value to select hrHPV DNA-positive women with normal cytology in need of immediate referral for colposcopy.

High-Risk Human Papillomavirus (hrHPV) E6/E7 mRNA Testing by PreTect HPV-Proofer for Detection of Cervical High-Grade Intraepithelial Neoplasia and Cancer among hrHPV DNA-Positive Women with Normal Cytology

PubMed Central

Rijkaart, D. C.; Heideman, D. A. M.; Coupe, V. M. H.; Brink, A. A. T. P.; Verheijen, R. H. M.; Skomedal, H.; Karlsen, F.; Morland, E.; Snijders, P. J. F.

2012-01-01

Our aim was to investigate whether high-risk HPV (hrHPV) mRNA detection by PreTect HPV-Proofer can be used to stratify hrHPV DNA-positive women of different cytology classes for risk of high-grade cervical intraepithelial neoplasia or worse (cervical precancer or cancer, i.e., cervical intraepithelial neoplasia grade 2 or higher [≥CIN2]). A total of 375 women participating in population-based screening, with a GP5+/6+-PCR hrHPV DNA-positive cervical scrape with normal cytology (n = 202), borderline or mild dyskaryosis (BMD) (n = 88), or moderate dyskaryosis or worse (>BMD) (n = 85), were enrolled. Cervical scrapes were additionally subjected to HPV16/18/31/33/45 E6/E7 mRNA analysis by PreTect HPV-Proofer (mRNA test). Referral and follow-up policies were based on cytology, hrHPV DNA, and mRNA testing. The primary study endpoint was the number of ≥CIN2 detected within 3 years of follow-up. The mRNA positivity increased with the severity of cytological abnormality, ranging from 32% (64/202) in hrHPV DNA-positive women with normal cytology to 47% (41/88) in BMD and 68% (58/85) in >BMD groups (P < 0.01). Women with ≥CIN2 were more likely to test positive by mRNA test (63%) than women without evidence of ≥CIN2 (32%; P < 0.01). A positive mRNA test result conferred an increased ≥CIN2 risk in hrHPV DNA-positive women with normal cytology, i.e., 0.55 (95% confidence interval [95% CI], 0.34 to 0.76) in mRNA-positive versus 0.20 (95% CI, 0.07 to 0.33) in mRNA-negative women. In hrHPV DNA-positive women with BMD or >BMD, the result of the mRNA test did not influence the ≥CIN2 risk. In conclusion, mRNA testing by PreTect HPV-Proofer might be of value to select hrHPV DNA-positive women with normal cytology in need of immediate referral for colposcopy. PMID:22553244

Type- and age-specific distribution of human papillomavirus in women attending cervical cancer screening in Finland

PubMed Central

Leinonen, M K; Anttila, A; Malila, N; Dillner, J; Forslund, O; Nieminen, P

2013-01-01

Background: Large-scale data on type-specific HPV prevalences and disease burden are needed to monitor the impact of HPV vaccination and to plan for HPV-based cervical screening. Methods: 33 043 women (aged 25–65) were screened for HPV by a Hybrid Capture 2 (HC2) in a population-based programme. HPV-positive women (n=2574) were triaged by cytology and HPV genotyped using PCR-Luminex. Type-specific prevalence of HPV infection and its correlation to findings in cytology triage and histology as well as Population Attributable Fractions for a referral to colposcopy and findings in histology were calculated. Results: Among HC2-positive women, 61.5% had normal, 23.1% had ASC-US and 15.5% had LSIL or more severe (LSIL+) results in cytology. Out of HC2-positive samples, 57% contained the 13 Group 1/2A HPV types, which were targeted by the HC2, 15% contained Group 2B types, 8.5% Group 3 types and 30% were found to be negative in HPV genotyping. The proportion of samples positive for HPV by the HC2, but negative in HPV genotyping increased with age and decreased with increasing cytological abnormality. The most frequent types were HPV 16 (0.9% of screened women and 12.1% of the HC2-positive women), HPV 31 (0.7% and 8.9%, respectively) and HPV 52 (0.5% and 6.3%, respectively). The prevalence of Group 1/2A HPV types increased with increasing CIN grade and attributed 78.3% (95% CI 53.4–89.9) of the CIN 3+ lesions, while HPV 16 attributed 55.8% (40.0–67.5) of them. Conclusion: The type-specific prevalence of HPV were slightly lower than the average in international meta-analyses. Genotyping for HPV 16 better identified women with CIN 3+ than cytology triage at the threshold of LSIL+. The high proportion of women that were HC2-positive but HPV-negative in genotyping suggests that HPV genotyping may be useful also for validation of results in HPV screening. The large-scale HPV genotyping data were found to be directly useful for planning further preventive efforts for cervical cancer. PMID:24136148

Physician attitudes toward dissemination of optical spectroscopy devices for cervical cancer control: an industrial-academic collaborative study.

PubMed

Shinn, Eileen; Qazi, Usman; Gera, Shalini; Brodovsky, Joan; Simpson, Jessica; Follen, Michele; Basen-Engquist, Karen; Macaulay, Calum

2012-02-01

Optical spectroscopy has been studied for biologic plausibility, technical efficacy, clinical effectiveness, patient satisfaction, and cost-effectiveness. We sought to identify health care provider attitudes or practices that might act as barriers or to the dissemination of this new technology. Through an academic-industrial partnership, we conducted a series of focus groups to examine physician barriers to optical diagnosis. The study was conducted in 2 stages. First, a pilot group of 10 physicians (8 obstetrician gynecologists and 2 family practitioners) was randomly selected from 8 regions of the United States and each physician was interviewed individually. Physicians were presented with the results of a large trial (N = 980) testing the accuracy of a spectroscopy-based device in the detection of cervical neoplasia. They were also shown a prototype of the device and were given a period of time to ask questions and receive answers regarding the device. They were also asked to provide feedback on a questionnaire that was then revised and presented to 3 larger focus groups (n = 13, 15, and 17 for a total N = 45). The larger focus groups were conducted during national scientific meetings with 20 obstetrician gynecologists and 25 primary care physicians (family practitioners and internists). When asked about the dissemination potential of the new cervical screening technology, all study groups tended to rely on established clinical guidelines from their respective professional societies with regard to the screening and diagnosis of cervical cancer. In addition, study participants consistently agreed that real-time spectroscopy would be viewed positively by their patients. Participants were positive about the new technology's potential as an adjunct to colposcopy and agreed that the improved accuracy would result in reduced health care costs (due to decreased biopsies and decreased visits). Although all participants saw the potential of real-time diagnosis, there were many perceived barriers. These barriers included changes in scheduling and work-flow, liability, documentation, ease of use, length of training, device cost, and reimbursement by third-party payers. Barriers exist to the dissemination of optical technologies into physician practice. These will need to be addressed before cervical screening and diagnosis programs can take advantage of spectroscopy-based instruments for cancer control. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

The Accuracy of p16/Ki-67 and HPV Test in the Detection of CIN2/3 in Women Diagnosed with ASC-US or LSIL

PubMed Central

Possati-Resende, Júlio C.; Fregnani, José H. T. G.; Kerr, Ligia M.; Mauad, Edmundo C.; Longatto-Filho, Adhemar; Scapulatempo-Neto, Cristovam

2015-01-01

The objective of this study was to compare the accuracies of double staining for p16/Ki-67 and the molecular test for high-risk HPV (hr-HPV) to identify high-grade cervical intraepithelial neoplasia (CIN2/CIN3) in women with cervical cytology of atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL). Data were collected from 201 women who underwent cervical cytology screening in the Barretos Cancer Hospital and their results were categorized as ASC-US (n=96) or LSIL (n=105). All patients underwent colposcopy with or without cervical biopsy for diagnosis of CIN2/CIN3. The hr-HPV test (Cobas 4800 test) and immunocytochemistry were performed to detect biomarkers p16/Ki-67 (CINtec PLUS test). Two samples (1 ASC-US/1 LSIL) were excluded from the analysis due to inconclusive results of the histologic examination. There were 8 cases of CIN2/CIN3 among 95 women with ASC-US (8.4%), and 23 cases of CIN2/CIN3 among 104 women with LSIL (22.1%). In the group of women with ASC-US, the sensitivity and specificity in diagnosing CIN2/CIN3 were 87.5% and 79.5% for the HPV test and 62.5% and 93.1% for p16/Ki-67. Among women with LSIL, the sensitivity and specificity in the diagnosis of CIN2/CIN3 were 87% and 34.7% for the HPV test and 69.6% and 75.3% for immunocytochemistry. Superior performance was observed for p16/Ki-67 double staining, especially among women under 30 for whom the test had an area under the ROC curve of 0.762 (p<0.001). Both p16/Ki-67 double staining and the hr-HPV DNA test had similar performance in predicting high-grade cervical intraepithelial neoplasia among women with ASC-US. The best performance was observed in women aged >30 years. In younger women (≤30 years) with LSIL, p16/Ki-67 had greater accuracy in identifying precursor lesions. Among women >30 years diagnosed with LSIL, the two methods showed similar performance. PMID:26230097

Secondary Prevention of Cervical Cancer: ASCO Resource-Stratified Clinical Practice Guideline.

PubMed

Jeronimo, Jose; Castle, Philip E; Temin, Sarah; Denny, Lynette; Gupta, Vandana; Kim, Jane J; Luciani, Silvana; Murokora, Daniel; Ngoma, Twalib; Qiao, Youlin; Quinn, Michael; Sankaranarayanan, Rengaswamy; Sasieni, Peter; Schmeler, Kathleen M; Shastri, Surendra S

2017-10-01

To provide resource-stratified, evidence-based recommendations on the secondary prevention of cervical cancer globally. ASCO convened a multidisciplinary, multinational panel of oncology, primary care, epidemiology, health economic, cancer control, public health, and patient advocacy experts to produce recommendations reflecting four resource-tiered settings. A review of existing guidelines, a formal consensus-based process, and a modified ADAPTE process to adapt existing guidelines were conducted. Other experts participated in formal consensus. Seven existing guidelines were identified and reviewed, and adapted recommendations form the evidence base. Four systematic reviews plus cost-effectiveness analyses provided indirect evidence to inform consensus, which resulted in ≥ 75% agreement. Human papillomavirus (HPV) DNA testing is recommended in all resource settings; visual inspection with acetic acid may be used in basic settings. Recommended age ranges and frequencies by setting are as follows: maximal: ages 25 to 65, every 5 years; enhanced: ages 30 to 65, if two consecutive negative tests at 5-year intervals, then every 10 years; limited: ages 30 to 49, every 10 years; and basic: ages 30 to 49, one to three times per lifetime. For basic settings, visual assessment is recommended as triage; in other settings, genotyping and/or cytology are recommended. For basic settings, treatment is recommended if abnormal triage results are present; in other settings, colposcopy is recommended for abnormal triage results. For basic settings, treatment options are cryotherapy or loop electrosurgical excision procedure; for other settings, loop electrosurgical excision procedure (or ablation) is recommended. Twelve-month post-treatment follow-up is recommended in all settings. Women who are HIV positive should be screened with HPV testing after diagnosis and screened twice as many times per lifetime as the general population. Screening is recommended at 6 weeks postpartum in basic settings; in other settings, screening is recommended at 6 months. In basic settings without mass screening, infrastructure for HPV testing, diagnosis, and treatment should be developed.Additional information can be found at www.asco.org/rs-cervical-cancer-secondary-prev-guideline and www.asco.org/guidelineswiki.It is the view of of ASCO that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement, but not replace, local guidelines.

Can human papillomavirus DNA testing of self-collected vaginal samples compare with physician-collected cervical samples and cytology for cervical cancer screening in developing countries?

PubMed Central

Bhatla, Neerja; Dar, Lalit; Patro, A. Rajkumar; Kumar, Pankaj; Kriplani, Alka; Gulati, Arti; Iyer, Venkateswaran K.; Mathur, Sandeep R.; Sreenivas, Vishnubhatla; Shah, Keerti V.; Gravitt, Patti E.

2013-01-01

Background To determine human papillomavirus (HPV) types by polymerase chain reaction (PCR)-reverse line blot assay and examine the concordance between HPV by Hybrid Capture 2 (HC2) and PCR on self-collected vaginal and physician-collected cervical samples and cytology. Methods This was a cross-sectional study of 546 sexually active women aged ≥30 years with persistent vaginal discharge, intermenstrual or postcoital bleeding or an unhealthy cervix. Participants self-collected vaginal samples (HPV-S) and physicians collected cervical samples for conventional Pap smear and HPV DNA (HPV-P) testing and performed colposcopy, with directed biopsy, if indicated. HPV testing and genotyping was done by HC2 and PCR reverse line blot assay. Concordance between HC2 and PCR results of self- and physician-collected samples was determined using a Kappa statistic (κ) and Chi-square test. Results Complete data were available for 512 sets with 98% of women providing a satisfactory self-sample. PCR detected oncogenic HPV in 12.3% of self- and 13.0% of physician-collected samples. Overall, there was 93.8% agreement between physician-collected and self-samples (κ = 76.31%, 95% confidence interval [CI]: 64.97–82.29%, p = 0.04)—complete concordance in 473 cases (57 positive, 416 negative), partial concordance in seven pairs and discordance in 32 pairs. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of self-sampling for detection of cervical intraepithelial neoplasia (CIN)2+ disease were 82.5%, 93.6%, 52.4% and 98.4%, respectively; for physician-sampling they were 87.5%, 93.2%, 52.2% and 98.9%, respectively; and for cytology they were 77.5%, 87.3%, 34.1% and 97.9%, respectively. Concordance between HC2 and PCR was 90.9% for self-samples (κ = 63.7%, 95% CI: 55.2–72.2%) and 95.3% for physician-collected samples (κ = 80.4%, 95% CI: 71.8–89.0%). Conclusions Self-HPV sampling compares favourably with physician-sampling and cytology. A rapid, affordable, HPV self-test kit can be used as the primary method of cervical cancer screening in low-resource situations. PMID:19931499

Screen-and-treat approaches for cervical cancer prevention in low-resource settings: a randomized controlled trial.

PubMed

Denny, Lynette; Kuhn, Louise; De Souza, Michelle; Pollack, Amy E; Dupree, William; Wright, Thomas C

2005-11-02

Non-cytology-based screen-and-treat approaches for cervical cancer prevention have been developed for low-resource settings, but few have directly addressed efficacy. To determine the safety and efficacy of 2 screen-and-treat approaches for cervical cancer prevention that were designed to be more resource-appropriate than conventional cytology-based screening programs. Randomized clinical trial of 6555 nonpregnant women, aged 35 to 65 years, recruited through community outreach and conducted between June 2000 and December 2002 at ambulatory women's health clinics in Khayelitsha, South Africa. All patients were screened using human papillomavirus (HPV) DNA testing and visual inspection with acetic acid (VIA). Women were subsequently randomized to 1 of 3 groups: cryotherapy if she had a positive HPV DNA test result; cryotherapy if she had a positive VIA test result; or to delayed evaluation. Biopsy-confirmed high-grade cervical cancer precursor lesions and cancer at 6 and 12 months in the HPV DNA and VIA groups compared with the delayed evaluation (control) group; complications after cryotherapy. The prevalence of high-grade cervical intraepithelial neoplasia and cancer (CIN 2+) was significantly lower in the 2 screen-and-treat groups at 6 months after randomization than in the delayed evaluation group. At 6 months, CIN 2+ was diagnosed in 0.80% (95% confidence interval [CI], 0.40%-1.20%) of the women in the HPV DNA group and 2.23% (95% CI, 1.57%-2.89%) in the VIA group compared with 3.55% (95% CI, 2.71%-4.39%) in the delayed evaluation group (P<.001 and P = .02 for the HPV DNA and VIA groups, respectively). A subset of women underwent a second colposcopy 12 months after enrollment. At 12 months the cumulative detection of CIN 2+ among women in the HPV DNA group was 1.42% (95% CI, 0.88%-1.97%), 2.91% (95% CI, 2.12%-3.69%) in the VIA group, and 5.41% (95% CI, 4.32%-6.50%) in the delayed evaluation group. Although minor complaints, such as discharge and bleeding, were common after cryotherapy, major complications were rare. Both screen-and-treat approaches are safe and result in a lower prevalence of high-grade cervical cancer precursor lesions compared with delayed evaluation at both 6 and 12 months. Trial Registration http://clinicaltrials.gov Identifier: NCT00233727.

Secondary Prevention of Cervical Cancer: ASCO Resource-Stratified Clinical Practice Guideline

PubMed Central

Jeronimo, Jose; Castle, Philip E.; Temin, Sarah; Denny, Lynette; Gupta, Vandana; Kim, Jane J.; Luciani, Silvana; Murokora, Daniel; Ngoma, Twalib; Qiao, Youlin; Quinn, Michael; Sankaranarayanan, Rengaswamy; Sasieni, Peter; Schmeler, Kathleen M.; Shastri, Surendra S.

2017-01-01

Purpose To provide resource-stratified, evidence-based recommendations on the secondary prevention of cervical cancer globally. Methods ASCO convened a multidisciplinary, multinational panel of oncology, primary care, epidemiology, health economic, cancer control, public health, and patient advocacy experts to produce recommendations reflecting four resource-tiered settings. A review of existing guidelines, a formal consensus-based process, and a modified ADAPTE process to adapt existing guidelines were conducted. Other experts participated in formal consensus. Results Seven existing guidelines were identified and reviewed, and adapted recommendations form the evidence base. Four systematic reviews plus cost-effectiveness analyses provided indirect evidence to inform consensus, which resulted in ≥ 75% agreement. Recommendations Human papillomavirus (HPV) DNA testing is recommended in all resource settings; visual inspection with acetic acid may be used in basic settings. Recommended age ranges and frequencies by setting are as follows: maximal: ages 25 to 65, every 5 years; enhanced: ages 30 to 65, if two consecutive negative tests at 5-year intervals, then every 10 years; limited: ages 30 to 49, every 10 years; and basic: ages 30 to 49, one to three times per lifetime. For basic settings, visual assessment is recommended as triage; in other settings, genotyping and/or cytology are recommended. For basic settings, treatment is recommended if abnormal triage results are present; in other settings, colposcopy is recommended for abnormal triage results. For basic settings, treatment options are cryotherapy or loop electrosurgical excision procedure; for other settings, loop electrosurgical excision procedure (or ablation) is recommended. Twelve-month post-treatment follow-up is recommended in all settings. Women who are HIV positive should be screened with HPV testing after diagnosis and screened twice as many times per lifetime as the general population. Screening is recommended at 6 weeks postpartum in basic settings; in other settings, screening is recommended at 6 months. In basic settings without mass screening, infrastructure for HPV testing, diagnosis, and treatment should be developed. Additional information can be found at www.asco.org/rs-cervical-cancer-secondary-prev-guideline and www.asco.org/guidelineswiki. It is the view of of ASCO that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement, but not replace, local guidelines. PMID:29094101

Les aspects des frottis cervico-vaginaux chez les femmes vivants avec le VIH suivies à Thiès/Sénégal et association avec le degré d'immunodépression

PubMed Central

Bammo, Mariama; Dioussé, Pauline; Thiam, Marietou; Diop, Madoky Maguatte; Berthe, Adama; Faye, Flugence Abdou; Diallo, Thierno Abdoul Aziz; Sarr, Fatou Seck; Dione, Haby; Toure, Papa Souleymane; Diop, Bernard Marcel; Ka, Mamadou Mortalla

2015-01-01

De nombreuses études ont démontré que les femmes infectées par le VIH ont un risque accru de survenue de néoplasies cervicales intra épithéliales. L'association entre les deux affections étant bidirectionnelle, l'objectif était de décrire les anomalies cervicales chez les femmes séropositives au virus de l'immunodéficience humaine (VIH), de rechercher des facteurs associés et de proposer des recommandations en termes de suivi de ces femmes. Il s'agissait d'une étude transversale, multicentrique recensant l'ensemble des frottis cervico-vaginaux (FCV) et des colposcopies des patientes infectées par le VIH entre 2012 et 2014 dans les services de dermatologie de Thiès et de Mbour. Les données étaient recueillies et analysées par le logiciel EPI Info 2012 version 3.5.4. Les tests statistiques ont été effectués avec un seuil de significativité p <0,05. Etaient inclus 125 patientes. L’âge moyen était de 38,98 ± 10.2 ans [20-77]. Il n'y avait aucun signe d'appels dans 82.4%. Le FCV était normal dans 32.8%, inflammatoire dans 44.8%. Les anomalies cytologiques concernaient 22,4% dont, ASC-H (suspicion de lésions de haut grade: 2.4%), LSIL (lésions de bas grade: 8.8%), HSIL (lésions de haut grade: 4%). Leur majorité (60.7%) avaient un taux de CD4 < 500 et étaient au stade 3 de l'OMS dans 64.3%; la biopsie montrait une dysplasie sévère chez 37.5% des patientes ayant pu réaliser cet examen. Deux patientes ont bénéficié d'un traitement curatif notamment l'exérèse chirurgicale. La survenue de dysplasies cervicales même précoces semble être associée à un stade avancé de l'infection VIH. Un dépistage et un traitement précoces sont absolument nécessaires. PMID:26834915

Efficacy and safety of vitamin C vaginal tablets in the treatment of non-specific vaginitis. A randomised, double blind, placebo-controlled study.

PubMed

Petersen, E Eiko; Magnani, Paola

2004-11-10

This was a randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of Vitamin C vaginal tablets (250 mg) given once a day in patients suffering from non-specific vaginitis. The total length of the study was 20 days, including a treatment phase of 6 days. The primary end-point was the presence in the two groups of non-specific vaginitis 1 and 2 weeks after the end of treatment, as assessed by at least 3 out of the 4 characteristic symptoms: discharge, fishy odour, vaginal pH >/= 4.7, and presence of clue cells. Secondary end-points were the individual symptoms and signs, above reported, and pruritus, fever, superinfections, microscopic findings on vaginal smear, and colposcopy. One hundred female patients aged 18 years or older and suffering from non-specific vaginitis were included in the study after giving their informed consent. Fifty were randomised to the active treatment and 50 to placebo. Seven patients, three in the Vitamin C group and four in the placebo group, were lost to follow-up and did not complete the treatment period. Two patients in the active group showed protocol deviations (age under 18 years and HIV-positive, respectively). The two groups resulted comparable for demographics, history and baseline clinical picture. A cluster analysis of the four main symptoms showed a statistically significant difference between the active group and the placebo group; significantly more patients were still affected by non-specific vaginitis after placebo (35.7%) compared to patients treated with Vitamin C tablets (14.0%). The meaningful secondary variable, referring to the microscopic examination of vaginal smear, supported the trend for efficacy in the Vitamin C treated group. The clue cells disappeared in 79% of patients treated with the drug and in 53% of patients on placebo. Similarly, bacteria disappeared in 77 and 54%, respectively, while lactobacilli reappeared in 79.1 and 53.3%, respectively. Vaginal pH values decreased significantly in both groups, but the frequency rate of subjects with pH >/= 4.7, as measured 1 week after the drug discontinuation, was significantly lesser in the Vitamin C group (16.3%) than in the placebo group (38.6%). Adverse events occurred in four patients, two on placebo (pruritus, cystitis) and two on Vitamin C (two candidiasis).

Human papillomavirus testing and liquid-based cytology: results at recruitment from the new technologies for cervical cancer randomized controlled trial.

PubMed

Ronco, Guglielmo; Segnan, Nereo; Giorgi-Rossi, Paolo; Zappa, Marco; Casadei, Gian Piero; Carozzi, Francesca; Dalla Palma, Paolo; Del Mistro, Annarosa; Folicaldi, Stefania; Gillio-Tos, Anna; Nardo, Gaetano; Naldoni, Carlo; Schincaglia, Patrizia; Zorzi, Manuel; Confortini, Massimo; Cuzick, Jack

2006-06-07

Although testing for human papillomavirus (HPV) has higher sensitivity and lower specificity than cytology alone for detecting cervical intraepithelial neoplasia (CIN), studies comparing conventional and liquid-based cytology have had conflicting results. In the first phase of a two-phase multicenter randomized controlled trial, women aged 35-60 years in the conventional arm (n = 16,658) were screened using conventional cytology, and women in the experimental arm (n = 16,706) had liquid-based cytology and were tested for high-risk HPV types using the Hybrid Capture 2 assay. Women in the conventional arm were referred to colposcopy with atypical cells of undetermined significance (ASCUS) or higher and those in the experimental arm were referred with ASCUS or higher cytology or with a positive (> or = 1 pg/mL) HPV test. Sensitivity and positive predictive value (PPV) for detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were calculated. The screening methods and referral criterion applied in the experimental arm had higher sensitivity than that in the conventional arm (relative sensitivity = 1.47; 95% confidence interval [CI] = 1.03 to 2.09) but a lower PPV (relative PPV = 0.40; 95% CI = 0.23 to 0.66). With HPV testing alone at > or = 1 pg/mL and at > or = 2 pg/mL, the gain in sensitivity compared with the conventional arm remained similar (relative sensitivity = 1.43, 95% CI = 1.00 to 2.04 and relative sensitivity = 1.41, 95% CI = 0.98 to 2.01, respectively) but PPV progressively improved (relative PPV = 0.58, 95% CI = 0.33 to 0.98 and relative PPV = 0.75, 95% CI = 0.45 and 1.27, respectively). Referral based on liquid-based cytology alone did not increase sensitivity compared with conventional cytology (relative sensitivity = 1.06; 95% CI = 0.72 to 1.55) but reduced PPV (relative PPV = 0.57; 95% CI = 0.39 to 0.82). HPV testing alone was more sensitive than conventional cytology among women 35-60 years old. Adding liquid-based cytology improved sensitivity only marginally but increased false-positives. HPV testing using Hybrid Capture 2 with a 2 pg/mL cutoff may be more appropriate than a 1 pg/mL cutoff for primary cervical cancer screening.

[Assessment of cervical intraepithelial neoplasia (CIN) lesions by DNA image cytometry].

PubMed

Sun, Xiao-rong; Che, Dong-yuan; Tu, Hong-zhang; Li, Dan; Wang, Jian

2006-11-01

To compare the value of conventional cytology and DNA image cytometry (DNA-ICM) assisted cytology in detection and prognostic assessment of cervical CIN lesions. 87 women were enrolled in this study. Cervical samples were collected employing cervix brushes which were then washed in Sedfix. After preparing single cell suspensions by mechanical procedure, cell monolayers were prepared by cyto-spinning the cells onto microscope slides. Two slides were prepared from each case: one slide was stained by Papanicolou staining for conventional cytology, another was stained by Feulgen-Thionin method for measurements of the amount of DNA in the cell nuclei using an automated DNA imaging cytometer. Biopsies from the cervical lesions were also taken for histopathology and Ki-67 immunohistochemistry. Of the total of 20 ASCUS cases called by conventional cytology, no CIN, nor greater lesions were found. Among the 20 cases, 7 cases did not show any cells with DNA amount greater than 5c, while CIN2 lesions were found in 11 of other 13 cases that had some aneuploid cells with DNA amount greater than 5c. Of 30 LSIL cases called by conventional cytology, CIN2 lesions were detected in 3 out of 7 cases that did not contain any aneuploid cells with DNA greater than 5c, but in 22 out of the other 23 cases that contained aneuploid cells with DNA amount greater than > 5c. Of the remaining 7 cases called HSIL by conventional cytology, all case contained aneuploid cells containing DNA greater than 5c. If cytology was used to refer all cases of LSIL and HSIL to colposcopy procedure to detect potential CIN2 or greater lesions, the sensitivity, specificity, positive predictive value and negative predictive value were 58.2%, 84.4%, 86.5% and 54.0%, respectively. If DNA-ICM were used and all cases having 3 or more cells with a DNA amount greater than 5c were assessed to be referred to pathology to detect potential CIN2 or greater lesions, the sensitivity, specificity, positive predictive value and negative predictive were 72.7% , 87.5%, 90.9% and 65.1%, respectively. We also compared Ki67 positive cells in these samples and found that DNA-ICM results were comparable to this biomarker method. The study demonstrated that DNA-ICM approach can be successfully used to detect significant (i.e. CIN2 or greater) lesions, and also provide a prognostic assessment of CIN lesions.

Protocol for Compass: a randomised controlled trial of primary HPV testing versus cytology screening for cervical cancer in HPV-unvaccinated and vaccinated women aged 25-69 years living in Australia.

PubMed

Canfell, Karen; Saville, Marion; Caruana, Michael; Gebski, Val; Darlington-Brown, Jessica; Brotherton, Julia; Heley, Stella; Castle, Philip E

2018-01-26

Australia's National Cervical Screening Program (NCSP) currently recommends 2-year cytology in women aged 18-69 years. Following a review of the NCSP prompted by the implementation of human papillomavirus (HPV) vaccination, the programme will transition in 2017 to 5-year primary HPV screening with partial genotyping for HPV16/18 in women aged 25-74 years. Compass is a sentinel experience for the renewed NCSP and the first prospectively randomised trial of primary HPV screening compared with cytology to be conducted in a population with high uptake of HPV vaccination. This protocol describes the main Compass trial, which commenced after a pilot study of ~5000 women completed recruitment. Women aged 25-69 years will be randomised at a 1:2 allocation to (1) 2.5-year image-read, liquid-based cytology (LBC) screening with HPV triage of low-grade smears (active control Arm A) or (2) 5-year HPV screening with partial genotyping and referral of HPV16/18-positive women to colposcopy (intervention Arm B). Women in Arm B positive for other oncogenic HPV (not 16/18) will undergo secondary randomisation at a 1:1 allocation to either LBC or dual-stained (p16 INK4a and Ki-67) cytology testing (dual-stained cytology). The primary outcome is cumulative CIN3+ (CIN3, adenocarcinoma in situ and invasive cervical cancer) following a 5-year HPV exit testing round in both arms, in women randomised to the HPV arm versus women randomised to the LBC arm, based on an intention-to-treat analysis. The primary outcome will first be tested for non-inferiority and if declared, the primary outcome will be tested for superiority. A total of 36 300 women in birth cohorts not offered vaccination and 84 700 women in cohorts offered vaccination will be recruited, bringing the final sample size to 121 000. The trial is powered for the secondary outcome of cumulative CIN3+ in screen-negative women, adjusted for censoring after CIN2+ treatment and hysterectomy. Approved by the Bellberry Ethics Committee (2014-11-592). Findings will be reported in peer-reviewed journals and presented at scientific meetings. NCT02328872; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Design and preliminary analysis of a vaginal inserter for speculum-free cervical cancer screening

PubMed Central

Agudogo, Júlia; Krieger, Marlee S.; Miros, Robert; Proeschold-Bell, Rae Jean; Schmitt, John W.; Ramanujam, Nimmi

2017-01-01

Objective Cervical cancer screening usually requires use of a speculum to provide a clear view of the cervix. The speculum is one potential barrier to screening due to fear of pain, discomfort and embarrassment. The aim of this paper is to present and demonstrate the feasibility of a tampon-sized inserter and the POCkeT Colposcope, a miniature pen sized-colposcope, for comfortable, speculum-free and potentially self-colposcopy. Study design We explored different designs using 3D computer-aided design (CAD) software and performed mechanical testing simulations on each. Designs were rapid prototyped and tested using a custom vaginal phantom across a range of vaginal pressures and uterine tilts to select an optimal design. Two final designs were tested with fifteen volunteers to assess cervix visualization, comfort and usability compared to the speculum and the optimal design, the curved-tip inserter, was selected for testing in volunteers. Results We present a vaginal inserter as an alternative to the standard speculum for use with the POCkeT Colposcope. The device has a slim tubular body with a funnel-like curved tip measuring approximately 2.5 cm in diameter. The inserter has a channel through which a 2 megapixel (MP) mini camera with LED illumination fits to enable image capture. Mechanical finite element testing simulations with an applied pressure of 15 cm H2O indicated a high factor of safety (90.9) for the inserter. Testing of the device with a custom vaginal phantom, across a range of supine vaginal pressures and uterine tilts (retroverted, anteverted and sideverted), demonstrated image capture with a visual area comparable to the speculum for a normal/axial positioned uteri and significantly better than the speculum for anteverted and sideverted uteri (p<0.00001). Volunteer studies with self-insertion and physician-assisted cervix image capture showed adequate cervix visualization for 83% of patients. In addition, questionnaire responses from volunteers indicated a 92.3% overall preference for the inserter over the speculum and all indicated that the inserter was more comfortable than the speculum. The inserter provides a platform for self-cervical cancer screening and also enables acetic acid/Lugol’s iodine application and insertion of swabs for Pap smear sample collection. Conclusion This study demonstrates the feasibility of an inserter and miniature-imaging device for comfortable cervical image capture of women with potential for synergistic HPV and Pap smear sample collection. PMID:28562669

A comparative study of the safety and efficacy of FemCap, a new vaginal barrier contraceptive, and the Ortho All-Flex diaphragm. The FemCap Investigators' Group.

PubMed

Mauck, C; Callahan, M; Weiner, D H; Dominik, R

1999-08-01

The FemCap is a new silicone rubber barrier contraceptive shaped like a sailor's hat, with a dome that covers the cervix, a rim that fits into the fornices, and a brim that conforms to the vaginal walls around the cervix. It was designed to result in fewer dislodgments and less pressure on the urethra than the cervical cap and diaphragm, respectively, and to require less clinician time for fitting. This was a phase II/III, multicenter, randomized, open-label, parallel group study of 841 women at risk for pregnancy. A subset of 42 women at one site underwent colposcopy. Women were randomized to use the FemCap or Ortho All-Flex contraceptive diaphragm, both with 2% nonoxynol-9 spermicide, for 28 weeks. The objectives were to compare the two devices with regard to their safety and acceptability and to determine whether the probability of pregnancy among FemCap users was no worse than that of the diaphragm (meaning not more than 6 percentage points higher). The 6-month Kaplan-Meier cumulative unadjusted typical use pregnancy probabilities were 13.5% among FemCap users and 7.9% among diaphragm users. The adjusted risk of pregnancy among FemCap users was 1.96 times that among diaphragm users, with an upper 95% confidence limit of 3.01. Clinical equivalence (noninferiority) of the FemCap compared with the diaphragm, as defined in this study, would mean that the true risk of pregnancy among FemCap users was no more than 1.73 times the pregnancy risk of diaphragm users. Because the observed upper 95% confidence limit (and even the point estimate) exceeded 1.73, the probability of pregnancy among FemCap users, compared with that among diaphragm users, did not meet the definition of clinical equivalence used in this study. The FemCap was believed to be safe and was associated with significantly fewer urinary tract infections. More women reported problems with the FemCap with regard to insertion, dislodgement, and especially removal, although their general assessments were positive. The two devices were comparable with regard to safety and acceptability, but a 6-point difference in the true 6-month pregnancy probabilities of the two devices could not be ruled out. Further studies are needed to determine whether design modifications can simplify insertion and removal.

High risk human papillomavirus prevalence and genotype distribution among women infected with HIV in Manaus, Amazonas.

PubMed

Teixeira, Monique Figueiredo; Sabidó, Meritxell; Leturiondo, André Luiz; de Oliveira Ferreira, Cynthia; Torres, Kátia Luz; Benzaken, Adele Schwartz

2018-02-17

Human immunodeficiency virus (HIV)-positive women have a high prevalence of human papillomavirus (HPV), and are infected with a broader range of HPV types than HIV-negative women. We aimed to determine the prevalence of cervical cytologic abnormalities, high-risk (HR)-HPV prevalence, type distribution according to the severity of cervical lesions and CD4 cell count and identify factors associated with HR-HPV infection among women living with HIV in Manaus, Amazonas. We enrolled 325 women living with HIV that attended an infectious diseases referral hospital. Each woman underwent a gynecological exam, cervical cytology, HR-HPV detection by Polymerase chain Reaction (PCR) using the BD Onclarity™ HPV Assay, colposcopy and biopsy, when necessary. We assessed the associations between potential risk factors and HR-HPV infection. Overall, 299 (92.0%) women had a PCR result. The prevalence of HR-HPV- infection was 31.1%. The most prevalent HR-HPV types were: 56/59/66 (32.2%), 35/39/68 (28.0%), 52 (21.5%), 16 (19.4%), and 45 (12.9%). Among the women with HR-HPV infection (n = 93), 43.0% had multiple infections. Women with HPV infection showed higher prevalence of cervical abnormalities than that HPV-negative (LSIL: 22.6% vs. 1.5%; HSIL: 10.8% vs. 0.0%). The prevalence of HR-HPV among women with cytological abnormalities was 87.5% for LSIL and 100.0% for HSIL. Women with CD4 < 200 cell/mm 3 showed the highest HR-HPV prevalence (59.3%) although this trend was not statistically significant (p-value = 0.62). The mean CD4 cell count decreased with increasing severity of cervical lesions (p-value = 0.001). The multivariable analysis showed that increasing age was associated with a decreased risk of HR-HPV infection with an adjusted prevalence odds ratio of 0.9 (95.0% CI: 0.9-1.0, p-value: 0.03) for each additional year. The only factor statistically significant associated with HR-HPV infection was CD4 cell count. HR-HPV and abnormal cytology prevalence are high among women in the Amazonas. The low CD4 cell count was an important determinant of HPV infection and abnormal cytological findings. HPV quadrivalent vaccination used in Brazil might not offer protection for an important fraction of HPV-related disease burden in women living with HIV. This is partly explained by the high presence of non targeted vaccine HR-HPVs, such as the HPV genotype groups 56/59/66, 35/39/68 and individually HPV-52 and HPV-45, some of which contribute to high-grade lesion.

Performance of alternative strategies for primary cervical cancer screening in sub-Saharan Africa: systematic review and meta-analysis of diagnostic test accuracy studies

PubMed Central

Combescure, Christophe; Fokom-Defo, Victoire; Tebeu, Pierre Marie; Vassilakos, Pierre; Kengne, André Pascal; Petignat, Patrick

2015-01-01

Objective To assess and compare the accuracy of visual inspection with acetic acid (VIA), visual inspection with Lugol’s iodine (VILI), and human papillomavirus (HPV) testing as alternative standalone methods for primary cervical cancer screening in sub-Saharan Africa. Design Systematic review and meta-analysis of diagnostic test accuracy studies. Data sources Systematic searches of multiple databases including Medline, Embase, and Scopus for studies published between January 1994 and June 2014. Review methods Inclusion criteria for studies were: alternative methods to cytology used as a standalone test for primary screening; study population not at particular risk of cervical cancer (excluding studies focusing on HIV positive women or women with gynaecological symptoms); women screened by nurses; reference test (colposcopy and directed biopsies) performed at least in women with positive screening results. Two reviewers independently screened studies for eligibility and extracted data for inclusion, and evaluated study quality using the quality assessment of diagnostic accuracy studies 2 (QUADAS-2) checklist. Primary outcomes were absolute accuracy measures (sensitivity and specificity) of screening tests to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Results 15 studies of moderate quality were included (n=61 381 for VIA, n=46 435 for VILI, n=11 322 for HPV testing). Prevalence of CIN2+ did not vary by screening test and ranged from 2.3% (95% confidence interval 1.5% to 3.3%) in VILI studies to 4.9% (2.7% to 7.8%) in HPV testing studies. Positivity rates of VILI, VIA, and HPV testing were 16.5% (9.8% to 24.7%), 16.8% (11.0% to 23.6%), and 25.8% (17.4% to 35.3%), respectively. Pooled sensitivity was higher for VILI (95.1%; 90.1% to 97.7%) than VIA (82.4%; 76.3% to 87.3%) in studies where the reference test was performed in all women (P<0.001). Pooled specificity of VILI and VIA were similar (87.2% (78.1% to 92.8%) v 87.4% (77.1% to 93.4%); P=0.85). Pooled sensitivity and specificity were similar for HPV testing versus VIA (both P≥0.23) and versus VILI (both P≥0.16). Accuracy of VIA and VILI increased with sample size and time period. Conclusions For primary screening of cervical cancer in sub-Saharan Africa, VILI is a simple and affordable alternative to cytology that demonstrates higher sensitivity than VIA. Implementation studies are needed to assess the effect of these screening strategies on the incidence and outcomes of cervical cancer in the region. PMID:26142020

A Novel Use of a Statewide Telecolposcopy Network for Recruitment of Participants in a Phase I Clinical Trial of a Human Papillomavirus Therapeutic Vaccine

PubMed Central

Stratton, Shawna L.; Spencer, Horace J.; Greenfield, William W.; Low, Gordon; Hitt, W. Chuck; Quick, Charles M.; Jeffus, Susanne K.; Blackmon, Victoria; Nakagawa, Mayumi

2015-01-01

Background Historically, recruitment and retention of young women in intervention-based clinical trials has been challenging. In August 2012, enrollment for a clinical trial testing of an investigational human papillomavirus (HPV) therapeutic vaccine called PepCan was opened at our institution. This study was an open-label, single arm, single institution, dose-escalation Phase I clinical trial. Women with recent Papanicolau smear results showing high-grade squamous intraepithelial lesions (HSILs) or cannot rule out HSIL were eligible to enroll. Patients with biopsy-confirmed HSIL were also eligible. Colposopy was performed at the screening visit, and participants became eligible for vaccination when the diagnosis of HSIL was confirmed with biopsy and other inclusion criteria were met. Purpose The aim of this study was to identify strategies and factors effective in recruitment and retention of study participants. Methods Potential vaccine candidates were recruited through direct advertisement as well as referrals, including through the Arkansas telecolposcopy network. The network is a federally funded program, administered by physicians and advanced practice nurses. The network telemedically links rural health sites and allows physician-guided colposcopy and biopsies to be conducted by advanced practice nurses. A variety of strategies were employed to assure good retention including face-to-face contact with the study coordinator at the time of consent and most of study visits, frequent contact using text messaging, phone calls, and e-mails, and creation of a private Facebook page to improve communication among research staff and study participants. A questionnaire, inquiring about motivation for joining the study, occupation, education, household income, number of children, and number of sexual partners, was administered at the screening visit with the intent of identifying factor(s) associated with recruitment and retention. Results Thirty-seven participants were enrolled between September 2012 and March 2014. The largest proportion of participants (46%) was enrolled from the telecolposcopy network. Others were enrolled through outside institutions (43%), in-house referrals (8%), or direct advertisement (3%). Most participants were motivated to join the study to take care of their health issues. Only 2 participants joined the Facebook private page. Of 24 participants who qualified for vaccination, only 1 terminated early due to an unanticipated move. Limitations As with most Phase I clinical trials, the number of participants is small. Conclusions The availability of a large number of potential participants from the telecolposcopy network increased recruitment to this clinical trial by 85% over other traditional means of recruitment. The telecolposcopy network is not only a means of providing a gynecological service to women who otherwise would forego care, but also a novel and valuable resource in recruiting participants for a clinical trial. PMID:25576067

The application of human papilloma virus genotyping for the identification of neoplasm lesions in the cervix of women with abnormal cytology smears.

PubMed

Ciszek, Barbara; Heimrath, Jerzy; Ciszek, Marian

2012-01-01

A connection between infections with a highly oncogenic type of human papilloma virus and the development of cervical intraepithelial neoplasia and preinvasive cervical cancer has been proven both experimentally and clinically. The period after which persistent virus infection will lead to the development of precancerous and invasive lesions is dependent on, among others, the HPV genotype. The oncogenic types of human papilloma virus destabilize the genome of an infected cell and thus initiate the carcinogenesis process. The aim of this work was to analyze the frequency of occurrence of different oncogenic HPV genotypes among women with abnormal cytological smears and the correlation of this data with the degree of cervical intraepithelial neoplasia exacerbation. The sample consisted of 75 women of child-bearing age (16-43 years old) with an abnormal cytological smear and positive test identifying an infection with an oncogenic type of human papilloma virus. In every case histopathological verification, aimed at excluding pathologies in the endocervix, was conducted using a colposcopy with guided biopsy and cervix abrasion. The authors found that the frequency of occurrence of different HPV genotypes of the groups of cytological diagnoses ASC-US, LSIL and HSIL do not differ statistically (p = 0.57). However, what is noteworthy is the more common occurrence of HPV 16 in type LSIL lesions (45.45%) and HPV 18 of a more advanced type HSIL (37.50%) pathology. Through the verification of the cytology results with histopathological diagnosis of the above groups the authors obtained statistically significant differences (p < 0.001) of individual pathological states. When regarding cytological HSIL diagnosis, CIN 1 was never diagnosed, while in other cytological groups cervical intraepithelial neoplasia of a low degree constituted over 40%. Analogically about 40% of HSIL diagnoses after histopathological verification turned out to be cancer of a pre-invasive state (CIS/AIS), the presence of which was not revealed by ASC-US and LSIL. What is more, CIN2/3 diagnosis was less frequent in the ASC-US cytological group than in the other two groups. While analyzing a share of other than HPV 16 and HPV 18 oncogenic types of human papilloma virus, the authors found that the most common were HPV 31, 45 and 33. In CIN 1 and CIN 2 their share was over 60%. In CIS/AIS type pathologies, no other types of human papilloma virus than HPV 16 and HPV 18 were shown. Positive results of DNA HR HPV testing of women with abnormal cytology results identified a risk group for the development of cervical cancer. No statistically significant differences of the frequency of HPV 16 and HPV 18 type occurrences were found in analyzed groups with cytological and histopathological diagnoses.

Withdrawing low risk women from cervical screening programmes: mathematical modelling study

PubMed Central

Sherlaw-Johnson, C; Gallivan, S; Jenkins, D

1999-01-01

Objective To evaluate the impact of policies for removing women before the recommended age of 64 from screening programmes for cervical cancer in the United Kingdom. Design A mathematical model of the clinical course of precancerous lesions which accounts for the influence of infection with the human papillomavirus, the effects of screening on the progression of disease, and the accuracy of the testing procedures. Two policies are compared: one in which women are withdrawn from the programme if their current smear is negative and they have a recent history of regular, negative results and one in which women are withdrawn if their current smear test is negative and a simultaneous test is negative for exposure to high risk types of human papillomavirus. Setting United Kingdom cervical screening programme. Main outcome measures The incidence of invasive cervical cancer and the use of resources. Results Early withdrawal of selected women from the programme is predicted to give rise to resource savings of up to 25% for smear tests and 18% for colposcopies when withdrawal occurs from age 50, the youngest age considered in the study. An increase in the incidence of invasive cervical cancer, by up to 2 cases/100 000 women each year is predicted. Testing for human papillomavirus infection to determine which women should be withdrawn from the programme makes little difference to outcome. Conclusions This model systematically analyses the consequences of screening options using available data and the clinical course of precancerous lesions. If further audit studies confirm the model’s forecasts, a policy of early withdrawal might be considered. This would be likely to release substantial resources which could be channelled into other aspects of health care or may be more effectively used within the cervical screening programme to counteract the possible increase in cancer incidence that early withdrawal might bring. Key messagesIn the United Kingdom there is concern that the cervical screening programme uses a large amount of resources to screen postmenopausal women who are at low risk of cervical cancerThere may be advantages to withdrawing these women from the screening programme before they reach the recommended age of 64A mathematical modelling approach can be used to evaluate the effectiveness of different policies for early withdrawal from screening with or without an additional test for human papillomavirus DNAEarly withdrawal could lead to a substantial reduction in the resources devoted to screening which could be channelled more effectively into other aspects of health careEarly withdrawal is likely to increase the overall incidence of cervical cancer unless other steps are taken to compensate PMID:9933195

Prediction of cervical intraepithelial neoplasia grade 2+ (CIN2+) using HPV DNA testing after a diagnosis of atypical squamous cell of undetermined significance (ASC-US) in Catalonia, Spain.

PubMed

Ibáñez, Raquel; Moreno-Crespi, Judit; Sardà, Montserrat; Autonell, Josefina; Fibla, Montserrat; Gutiérrez, Cristina; Lloveras, Belen; Alejo, María; Català, Isabel; Alameda, Francesc; Casas, Miquel; Bosch, F Xavier; de Sanjosé, Silvia

2012-01-26

A protocol for cervical cancer screening among sexually active women 25 to 65 years of age was introduced in 2006 in Catalonia, Spain to increase coverage and to recommend a 3-year-interval between screening cytology. In addition, Human Papillomavirus (HPV) was offered as a triage test for women with a diagnosis of atypical squamous cells of undetermined significance (ASC-US). HPV testing was recommended within 3 months of ASC-US diagnosis. According to protocol, HPV negative women were referred to regular screening including a cytological exam every 3 years while HPV positive women were referred to colposcopy and closer follow-up. We evaluated the implementation of the protocol and the prediction of HPV testing as a triage tool for cervical intraepithelial lesions grade two or worse (CIN2+) in women with a cytological diagnosis of ASC-US. During 2007-08 a total of 611 women from five reference laboratories in Catalonia with a novel diagnosis of ASC-US were referred for high risk HPV (hrHPV) triage using high risk Hybrid Capture version 2. Using routine record linkage data, women were followed for 3 years to evaluate hrHPV testing efficacy for predicting CIN2+ cases. Logistic regression analysis was used to estimate the odds ratio for CIN2 +. Among the 611 women diagnosed with ASC-US, 493 (80.7%) had at least one follow-up visit during the study period. hrHPV was detected in 48.3% of the women at study entry (mean age 35.2 years). hrHPV positivity decreased with increasing age from 72.6% among women younger than 25 years to 31.6% in women older than 54 years (p < 0.01). At the end of the 3 years follow-up period, 37 women with a diagnosis of CIN2+ (18 CIN2, 16 CIN3, 2 cancers, and 1 with high squamous intraepithelial lesions--HSIL) were identified and all but one had a hrHPV positive test at study entry. Sensitivity to detect CIN2+ of hrHPV was 97.2% (95%confidence interval (CI) = 85.5-99.9) and specificity was 68.3% (95%CI = 63.1-73.2). The odds ratio for CIN2+ was 45.3 (95% CI: 6.2-333.0), when among ASC-US hrHPV positive women were compared to ASC-US hrHPV negative women. Triage of ASC-US with hrHPV testing showed a high sensitivity for the detection of CIN2+ and a high negative predictive value after 3 years of follow-up. The results of this study are in line with the current guidelines for triage of women with ASC-US in the target age range of 25-65. Non adherence to guidelines will lead to unnecessary medical interventions. Further investigation is needed to improve specificity of ASC-US triage.

Effects of Long-Term Vitamin D Supplementation on Regression and Metabolic Status of Cervical Intraepithelial Neoplasia: a Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Vahedpoor, Zahra; Jamilian, Mehri; Bahmani, Fereshteh; Aghadavod, Esmat; Karamali, Maryam; Kashanian, Maryam; Asemi, Zatollah

2017-02-01

We are not aware of any study examining the effects of long term vitamin D administration on regression and metabolic status of patients with cervical intraepithelial neoplasia grade 1 (CIN1). This study was performed to evaluate the effects of long-term vitamin D administration on regression and metabolic status of patients with CIN1. This randomized, double-blind, placebo-controlled trial was performed among 58 women diagnosed with CIN1. CIN1 diagnosis was performed based on specific diagnostic procedures of biopsy, pathological diagnosis, and colposcopy. Patients were randomly allocated into two groups to take 50,000 IU vitamin D3 supplements (n = 29) or placebo (n = 29) every 2 weeks for 6 months. Fasting blood samples were taken at the beginning of the study and end-of-trial to measure related markers. After 6 months of vitamin D administration, greater percentage of women in the vitamin D group had regressed CIN1 (84.6 vs. 53.8%, P = 0.01) than those in the placebo group. Long-term vitamin D supplementation increased serum-25(OH) vitamin D levels in the intervention group compared to the placebo group (+12.3 ± 11.4 vs. -0.1 ± 3.7 ng/mL, P < 0.001). In addition, vitamin D intake led to significant decreases in serum insulin levels (-5.3 ± 7.3 vs. +2.4 ± 5.9 μIU/mL, P < 0.001), homeostasis model of assessment-insulin resistance (-1.2 ± 1.6 vs. +0.5 ± 1.2, P < 0.001), homeostatic model assessment-Beta cell function (P = 0.005) and a significant elevation in quantitative insulin sensitivity check index (+0.03 ± 0.04 vs. -0.007 ± 0.02, P < 0.001) compared with the placebo group. Additionally, significant increases in plasma nitric oxide (NO) (+15.5 ± 10.3 vs. +4.0 ± 13.4 μmol/L, P = 0.001), total antioxidant capacity (TAC) (P = 0.04), total glutathione (GSH) (+11.8 ± 153.5 vs. -294.2 ± 595.1 μmol/L, P = 0.01) and a significant reduction in plasma malondialdehyde (MDA) levels (-0.8 ± 1.0 vs. -0.03 ± 1.4 μmol/L, P = 0.03) were observed following the administration of vitamin D supplements compared with the placebo group. In conclusion, vitamin D3 administration for 6 months among women with CIN1 resulted in its regression and had beneficial effects on markers of insulin metabolism, plasma NO, TAC, GSH and MDA levels. Clinical trial registration number www.irct.ir : IRCT201412065623N30.

Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment

PubMed Central

Hildesheim, Allan; Gonzalez, Paula; Kreimer, Aimee R.; Wacholder, Sholom; Schussler, John; Rodriguez, Ana C.; Porras, Carolina; Schiffman, Mark; Sidawy, Mary; Schiller, John T.; Lowy, Douglas R.; Herrero, Rolando

2016-01-01

BACKGROUND Human papillomavirus (HPV) vaccines prevent HPV infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an HPV-associated lesion is not fully understood. OBJECTIVES To determine whether HPV-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions. STUDY DESIGN We included 1711 women (18–25 years) with carcinogenic human papillomavirus infection and 311 women of similar age who underwent treatment for cervical precancer and who participated in a community-based trial of the AS04-adjuvanted HPV-16/18 virus-like particle vaccine. Participants were randomized (human papillomavirus or hepatitis A vaccine) and offered 3 vaccinations over 6 months. Follow-up included annual visits (more frequently if clinically indicated), referral to colposcopy of high-grade and persistent low-grade lesions, treatment by loop electrosurgical excisional procedure when clinically indicated, and cytologic and virologic follow-up after treatment. Among women with human papillomavirus infection at the time of vaccination, we considered type-specific viral clearance, and development of cytologic (squamous intraepithelial lesions) and histologic (cervical intraepithelial neoplasia) lesions. Among treated women, we considered single-time and persistent human papillomavirus infection, squamous intraepithelial lesions, and cervical intraepithelial neoplasia 2+. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated. RESULTS Median follow-up was 56.7 months (women with human papillomavirus infection) and 27.3 months (treated women). There was no evidence of vaccine efficacy to increase clearance of human papillomavirus infections or decrease incidence of cytologic/histologic abnormalities associated with human papillomavirus types present at enrollment. Vaccine efficacy for human papillomavirus 16/18 clearance and against human papillomavirus 16/18 progression from infection to cervical intraepithelial neoplasia 2+ were −5.4% (95% confidence interval −19,10) and 0.3% (95% confidence interval −69,41), respectively. Among treated women, 34.1% had oncogenic infection and 1.6% had cervical intraepithelial neoplasia 2+ detected after treatment, respectively, and of these 69.8% and 20.0% were the result of new infections. We observed no significant effect of vaccination on rates of infection/lesions after treatment. Vaccine efficacy estimates for human papillomavirus 16/18 associated persistent infection and cervical intraepithelial neoplasia 2+ after treatment were 34.7% (95% confidence interval −131, 82) and −211% (95% confidence interval −2901, 68), respectively. We observed evidence for a partial and nonsignificant protective effect of vaccination against new infections absent before treatment. For incident human papillomavirus 16/18, human papillomavirus 31/33/45, and oncogenic human papillomavirus infections post-treatment, vaccine efficacy estimates were 57.9% (95% confidence interval −44, 88), 72.9% (95% confidence interval 29, 90), and 36.7% (95% confidence interval 1.5, 59), respectively. CONCLUSION We find no evidence for a vaccine effect on the fate of detectable human papillomavirus infections. We show that vaccination does not protect against infections/lesions after treatment. Evaluation of vaccine protection against new infections and resultant lesions warrants further consideration in future studies. PMID:26892991