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

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.

Surgical Treatment of Persistent Vaginal Granulation Tissue Using CO2 Laser Vaporization Under Colposcopic and Laparoscopic Guidance

PubMed Central

Mapp, Tiffany; Mama, Saifuddin; Echols, Karolynn T.

2012-01-01

Introduction: There have been many reports in the literature on vaginal mesh erosion as a complication of pelvic floor reconstructive surgery. Several reports describe successful surgical excision of the exposed mesh as a resolution. However, in rare cases of mesh erosion, poor surgical outcomes and multiple resection failures have been reported. We describe an innovative surgical approach to persistent vaginal mesh erosion using CO2 laser vaporization under colposcopic and laparoscopic guidance. Case Description: A 58-y-old postmenopausal woman first presented with a 3-y history of vaginal discharge and spotting after undergoing a Mentor ObTape transobturator sling (Mentor Corp, Santa Barbara, CA), for the treatment of stress urinary incontinence. Despite surgical removal of the mesh and multiple attempts at cauterization of persistent granulation tissue, her symptoms persisted. Discussion: Using a CO2 laser under colposcopic and laparoscopic guidance, we were able to safely expose and remove the remaining portion of retained mesh. To our knowledge, this is the first report describing CO2 laser vaporization as a surgical approach for the successful treatment of recurrent mesh erosion. PMID:23318081

Quantification of confocal fluorescence microscopy for the detection of cervical intraepithelial neoplasia.

PubMed

Sheikhzadeh, Fahime; Ward, Rabab K; Carraro, Anita; Chen, Zhao Yang; van Niekerk, Dirk; Miller, Dianne; Ehlen, Tom; MacAulay, Calum E; Follen, Michele; Lane, Pierre M; Guillaud, Martial

2015-10-24

Cervical cancer remains a major health problem, especially in developing countries. Colposcopic examination is used to detect high-grade lesions in patients with a history of abnormal pap smears. New technologies are needed to improve the sensitivity and specificity of this technique. We propose to test the potential of fluorescence confocal microscopy to identify high-grade lesions. We examined the quantification of ex vivo confocal fluorescence microscopy to differentiate among normal cervical tissue, low-grade Cervical Intraepithelial Neoplasia (CIN), and high-grade CIN. We sought to (1) quantify nuclear morphology and tissue architecture features by analyzing images of cervical biopsies; and (2) determine the accuracy of high-grade CIN detection via confocal microscopy relative to the accuracy of detection by colposcopic impression. Forty-six biopsies obtained from colposcopically normal and abnormal cervical sites were evaluated. Confocal images were acquired at different depths from the epithelial surface and histological images were analyzed using in-house software. The features calculated from the confocal images compared well with those features obtained from the histological images and histopathological reviews of the specimens (obtained by a gynecologic pathologist). The correlations between two of these features (the nuclear-cytoplasmic ratio and the average of three nearest Delaunay-neighbors distance) and the grade of dysplasia were higher than that of colposcopic impression. The sensitivity of detecting high-grade dysplasia by analysing images collected at the surface of the epithelium, and at 15 and 30 μm below the epithelial surface were respectively 100, 100, and 92 %. Quantitative analysis of confocal fluorescence images showed its capacity for discriminating high-grade CIN lesions vs. low-grade CIN lesions and normal tissues, at different depth of imaging. This approach could be used to help clinicians identify high-grade CIN in clinical settings.

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.

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.

Optical design of low cost imaging systems for mobile medical applications

NASA Astrophysics Data System (ADS)

Kass, Alexander; Slyper, Ronit; Levitz, David

2015-03-01

Colposcopes, the gold standard devices for imaging the cervix at high magnfication, are expensive and sparse in low resource settings. Using a lens attachment, any smartphone camera can be turned into an imaging device for tissues such as the cervix. We create a smartphone-based colposcope using a simple lens design for high magnification. This particular design is useful because it allows parameters such as F-number, depth of field, and magnification to be controlled easily. We were therefore able to determine a set of design steps which are general to mobile medical imaging devices and allow them to maintain requisite image quality while still being rugged and affordable.

Untitled

Cancer.gov

A collaborative study on colposcopic biopsy with aims to study cervical disease on the lesion level, optimize criteria for biopsy placement, and analyze the incremental benefit of taking multiple biopsies

Laser vaporization in treatment of superficial endometriosis of the uterine cervix

NASA Astrophysics Data System (ADS)

Wozniak, Jakub; Wilczak, Maciej; Opala, Tomasz; Pisarska-Krawczyk, Magdalena; Cwojdzinski, Marek; Pisarski, Tadeusz

1996-03-01

The study shows the treatment of superficial endometriosis of the uterine cervix in 79 patients. After first vaporization 74 patients were cured successfully. In two cases the laser procedure should be repeated and in 3 women the operation should be performed for the third time. All patients are still under control in our department and there is no recurrence observed. Carbon- dioxide laser vaporization under colposcopic control is an efficient method of treatment of superficial endometriosis of the uterine cervix that requires no anaesthesia. The healing process after laser procedures is fast and without complications. The number of recurrences is low. Use of carbon-dioxide laser under colposcopic control because of precise destruction of lesions, fast healing and a low number of recurrences seems to be the method of choice.

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.

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.

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

Clinical study of quantitative diagnosis of early cervical cancer based on the classification of acetowhitening kinetics

NASA Astrophysics Data System (ADS)

Wu, Tao; Cheung, Tak-Hong; Yim, So-Fan; Qu, Jianan Y.

2010-03-01

A quantitative colposcopic imaging system for the diagnosis of early cervical cancer is evaluated in a clinical study. This imaging technology based on 3-D active stereo vision and motion tracking extracts diagnostic information from the kinetics of acetowhitening process measured from the cervix of human subjects in vivo. Acetowhitening kinetics measured from 137 cervical sites of 57 subjects are analyzed and classified using multivariate statistical algorithms. Cross-validation methods are used to evaluate the performance of the diagnostic algorithms. The results show that an algorithm for screening precancer produced 95% sensitivity (SE) and 96% specificity (SP) for discriminating normal and human papillomavirus (HPV)-infected tissues from cervical intraepithelial neoplasia (CIN) lesions. For a diagnostic algorithm, 91% SE and 90% SP are achieved for discriminating normal tissue, HPV infected tissue, and low-grade CIN lesions from high-grade CIN lesions. The results demonstrate that the quantitative colposcopic imaging system could provide objective screening and diagnostic information for early detection of cervical cancer.

How many histological levels should be examined from tissue blocks originating in cone biopsy and large loop excision of the transformation zone specimens of cervix?

PubMed Central

Heatley, M

2001-01-01

Aims—To establish the value of examining additional histological levels in cone biopsy and large loop excision of the transformation zone (LLETZ) specimens of cervix. Methods—Three deeper levels were examined from 200 consecutive cone biopsy and LLETZ specimens reported by a single pathologist. Results—Examination of the first deeper level resulted in cervical intraepithelial neoplasia (CIN) being identified for the first time in five cases and in CIN1 being upgraded in five more. Invasive cancer was discovered in two cases that had shown high grade CIN initially. Conclusion—Examination of a single further level appears to be sufficient in those patients in whom a specimen is compromised because epithelium including the squamocolumnar junction is missing, or if there is a discrepancy between the histological findings and the preceding colposcopic or cytological history. If invasive disease is suspected on the basis of the cytological, colposcopic, or histological features, one or preferably two further levels should be examined. Key Words: cervix uteri • quality control • diagnosis PMID:11477125

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.

ASCCP Colposcopy Standards: Risk-Based Colposcopy Practice.

PubMed

Wentzensen, Nicolas; Schiffman, Mark; Silver, Michelle I; Khan, Michelle J; Perkins, Rebecca B; Smith, Katie M; Gage, Julia C; Gold, Michael A; Conageski, Christine; Einstein, Mark H; Mayeaux, Edward J; Waxman, Alan G; Huh, Warner K; Massad, L Stewart

2017-10-01

The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of and approach to colposcopy for cervical cancer prevention in the United States. The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. This article describes the rationale, evidence, and recommendations related to risk-based colposcopy practice. Women referred to colposcopy have a wide range of underlying precancer risk, which can be estimated by referral screening tests including cytology and human papillomavirus testing, in conjunction with the colposcopic impression. Multiple targeted biopsies, at least 2 and up to 4, are recommended to improve detection of prevalent precancers. At the lowest end of the risk spectrum, untargeted biopsies are not recommended, and women with a completely normal colposcopic impression can be observed. At the highest end of the risk spectrum, immediate treatment is an alternative to biopsy confirmation. Assessing the risk of cervical precancer at the colposcopy visit allows for modification of colposcopy procedures consistent with a woman's risk. Implementation of these recommendations is expected to lead to improved detection of cervical precancers at colposcopy, while providing more reassurance of negative colposcopy results.

Prognostic relevance of human papillomavirus L1 capsid protein detection within mild and moderate dysplastic lesions of the cervix uteri in combination with p16 biomarker.

PubMed

Hilfrich, Ralf; Hariri, Jalil

2008-04-01

To proof the prognostic relevance of HPV L1 capsid protein detection on colposcopically-guided punch biopsies in combination with p16. Sections of colposcopically-guided punch biopsies from 191 consecutive cases with at least 5 years of follow-up were stained with HPV L1 capsid protein antibodies (Cytoactiv screening antibody) and a monoclonal anti-p16 antibody. Fifty sections were derived from a benign group, 91 from low-grade (cervical intraepithelial neoplasia [CIN 1]) lesions and 50 from high-grade (CIN 2 and 3) lesions. Overall only 16.1% of the 87 L1-negative, p16-positive CIN lesions showed remission of the lesion compared to 72.4% of the double positive cases. None of the L1/p16 double negative CIN lesions progressed. HPV L1 capsid protein detection with Cytoactiv screening antibody seems to be a promising new tool to predict the behavior of HPV-associated (p16-positive) early dysplastic lesions.

Normal versus Abnormal Genital Findings in Children: How Well Do Examiners Agree?

ERIC Educational Resources Information Center

Adams, Joyce A.; Wells, Robert

1993-01-01

Preselected colposcopic photographs of the anogenital area of 16 patients were shown to 170 medical examiners, who rated their level of suggestion or indication of penetrating injury. Agreement between the participants and experts was higher on the abnormal cases than on the normal cases, and higher on genital findings than on anal findings.…

Standardized Digital Colposcopy with Dynamic Spectral Imaging for Conservative Patient Management.

PubMed

Kaufmann, Angelika; Founta, Christina; Papagiannakis, Emmanouil; Naik, Raj; Fisher, Ann

2017-01-01

Colposcopy is subjective and management of young patients with high-grade disease is challenging, as treatments may impair subsequent pregnancies and adversely affect obstetric outcomes. Conservative management of selected patients is becoming more popular amongst clinicians; however it requires accurate assessment and documentation. Novel adjunctive technologies for colposcopy could improve patient care and help individualize management decisions by introducing standardization, increasing sensitivity, and improving documentation. A nulliparous 27-year-old woman planning pregnancy underwent colposcopy following high-grade cytology. The colposcopic impression was of low-grade changes, whilst the Dynamic Spectral Imaging (DSI) map of the cervix suggested potential high-grade. A DSI-directed biopsy confirmed CIN2. At follow-up, both colposcopy and DSI were suggestive of low-grade disease only, and image comparison confirmed the absence of previously present acetowhite epithelium areas. Histology of the transformation zone following excisional treatment, as per patient's choice, showed no high-grade changes. Digital colposcopy with DSI mapping helps standardize colposcopic examinations, increase diagnostic accuracy, and monitor cervical changes over time, improving patient care. When used for longitudinal tracking of disease and when it confirms a negative colposcopy, it can help towards avoiding overtreatment and hence decrease morbidity related to cervical excision.

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.

Cervical collagen imaging for determining preterm labor risks using a colposcope with full Mueller matrix capability

NASA Astrophysics Data System (ADS)

Stoff, Susan; Chue-Sang, Joseph; Holness, Nola A.; Gandjbakhche, Amir; Chernomordik, Viktor; Ramella-Roman, Jessica

2016-02-01

Preterm birth is a worldwide health issue, as the number one cause of infant mortality and neurological disorders. Although affecting nearly 10% of all births, an accurate, reliable diagnostic method for preterm birth has, yet, to be developed. The primary constituent of the cervix, collagen, provides the structural support and mechanical strength to maintain cervical closure, through specific organization, during fetal gestation. As pregnancy progresses, the disorganization of the cervical collagen occurs to allow eventual cervical pliability so the baby can be birthed through the cervical opening. This disorganization of collagen affects the mechanical properties of the cervix and, if the changes occur prematurely, may be a significant factor leading to preterm birth. The organization of collagen can be analyzed through the use of Mueller Matrix Polarimetric imaging of the characteristic birefringence of collagen. In this research, we have built a full Mueller Matrix Polarimetry attachment to a standard colposcope to enable imaging of human cervixes during standard prenatal exams at various stages of fetal gestation. Analysis of the polarimetric images provides information of quantity and organization of cervical collagen at specific gestational stages of pregnancy. This quantitative information may provide an indication of risk of preterm birth.

Triage of the abnormal Papanicolaou smear in pregnancy.

PubMed

Apgar, B S; Zoschnick, L B

1998-06-01

Triage of the abnormal Papanicolaou smear in pregnancy requires colposcopic evaluation and directed biopsy. If histologic cervical intraepithelial neoplasia is confirmed, the patient can be managed with observations and can be re-evaluated in the postpartum period. If evidence of microinvasion is present, conization must be performed. For patients with invasive disease, a delay in therapy until fetal maturity is achieved does not compromise survival.

Application of laser technology in treatment of diseases of the external genitals

NASA Astrophysics Data System (ADS)

Wilczak, Maciej; Wozniak, Jakub; Sajdak, Stefan; Opala, Tomasz; Rabiega, Dorota

2000-11-01

Lasersurgery is the very profitable method of treatment of diseases of external sexual organs, with regard to high efficiency and little relapses. Lasersurgery is recommended especially for pregnant women considering possibility of physiological childbirth. We prefer laser CO2 in connexion with colposcope in treatment of diseases of external sexual organs. The application of this method is limited by the high cost of equipment.

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.

Real-Time Monitoring and Evaluation of a Visual-Based Cervical Cancer Screening Program Using a Decision Support Job Aid.

PubMed

Peterson, Curtis W; Rose, Donny; Mink, Jonah; Levitz, David

2016-05-16

In many developing nations, cervical cancer screening is done by visual inspection with acetic acid (VIA). Monitoring and evaluation (M&E) of such screening programs is challenging. An enhanced visual assessment (EVA) system was developed to augment VIA procedures in low-resource settings. The EVA System consists of a mobile colposcope built around a smartphone, and an online image portal for storing and annotating images. A smartphone app is used to control the mobile colposcope, and upload pictures to the image portal. In this paper, a new app feature that documents clinical decisions using an integrated job aid was deployed in a cervical cancer screening camp in Kenya. Six organizations conducting VIA used the EVA System to screen 824 patients over the course of a week, and providers recorded their diagnoses and treatments in the application. Real-time aggregated statistics were broadcast on a public website. Screening organizations were able to assess the number of patients screened, alongside treatment rates, and the patients who tested positive and required treatment in real time, which allowed them to make adjustments as needed. The real-time M&E enabled by "smart" diagnostic medical devices holds promise for broader use in screening programs in low-resource settings.

Image processing and machine learning techniques to automate diagnosis of Lugol's iodine cervigrams for a low-cost point-of-care digital colposcope

NASA Astrophysics Data System (ADS)

Asiedu, Mercy Nyamewaa; Simhal, Anish; Lam, Christopher T.; Mueller, Jenna; Chaudhary, Usamah; Schmitt, John W.; Sapiro, Guillermo; Ramanujam, Nimmi

2018-02-01

The world health organization recommends visual inspection with acetic acid (VIA) and/or Lugol's Iodine (VILI) for cervical cancer screening in low-resource settings. Human interpretation of diagnostic indicators for visual inspection is qualitative, subjective, and has high inter-observer discordance, which could lead both to adverse outcomes for the patient and unnecessary follow-ups. In this work, we a simple method for automatic feature extraction and classification for Lugol's Iodine cervigrams acquired with a low-cost, miniature, digital colposcope. Algorithms to preprocess expert physician-labelled cervigrams and to extract simple but powerful color-based features are introduced. The features are used to train a support vector machine model to classify cervigrams based on expert physician labels. The selected framework achieved a sensitivity, specificity, and accuracy of 89.2%, 66.7% and 80.6% with majority diagnosis of the expert physicians in discriminating cervical intraepithelial neoplasia (CIN +) relative to normal tissues. The proposed classifier also achieved an area under the curve of 84 when trained with majority diagnosis of the expert physicians. The results suggest that utilizing simple color-based features may enable unbiased automation of VILI cervigrams, opening the door to a full system of low-cost data acquisition complemented with automatic interpretation.

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.

Factors influencing histologic confirmation of high-grade squamous intraepithelial lesion cytology.

PubMed

Castle, Philip E; Cox, J Thomas; Schiffman, Mark; Wheeler, Cosette M; Solomon, Diane

2008-09-01

To examine the predictors of histologic confirmation of high-grade squamous intraepithelial lesion (HSIL) cytology occurring in follow-up of young women originally referred into a trial because of less severe cytology. We used enrollment HSIL cytology (N=411) as read by clinical center pathologists for women participating in the ASCUS-LSIL Triage Study (ALTS). The primary outcome was histologic cervical intraepithelial neoplasia (CIN) grade 3 and early cancer (n=195; 191 CIN 3 and four cancers) as diagnosed by the Pathology Quality Control Group during the 2-year duration of ALTS. The 2-year absolute risk of CIN 3 or worse after an HSIL cytology was 47.4% (95% confidence interval 42.5-52.4%). The 2-year absolute risk of CIN 3 or worse was lowest (14.3%) for women who were human papillomavirus (HPV)-16-negative, had colposcopic impression of less than low-grade, and whose HSIL cytology as called by the clinical center was not also called HSIL or equivocal HSIL cytology by the Pathology Quality Control Group. The 2-year absolute risk of CIN 3 or worse was highest (82.4%) for women who were HPV16-positive, had colposcopic impression of low-grade or worse, and whose HSIL cytology also was called HSIL or equivocal HSIL cytology by the Pathology Quality Control Group. Histologic confirmation of precancer among young women with HSIL cytology was more likely when other risk factors (eg, HPV16) for cervical precancer were present.

Age-related changes in the diagnostic assessment of women with severe cervical lesions.

PubMed

Giannella, L; Fodero, C; Boselli, F; Mfuta, K; Rubino, T; Prandi, S

2015-01-01

To evaluate the effect of age on the diagnostic assessment of women with severe cervical intraepithelial neoplasia (CIN). This retrospective observational study included 338 consecutive women with a diagnosis of CIN3 on cone specimen. Patients were divided into three groups according to age: < 35 years (Group A), 35-49 years (Group B), and ≥ 50 years (Group C). Clinical and colposcopic variables were compared, and human papillomavirus (HPV) genotype distribution was measured. The most common HPV genotype was HPV-16 (63.65%), followed by HPV-33 (7%), HPV-18 (6.2%), and HPV-31 (5.4%). The rate of the following high-grade lesion predictors was lower in Group C than in Groups A and B: HPV-16 infections (55.9% vs. 75% vs. 70.9%, respectively, p = 0.022); high-grade colposcopic impression (29.4% vs. 51.8% vs. 51.7%, respectively, p < 0.0001); and high-grade cytological changes (30.9% vs. 56.2% vs. 45.4%, respectively, p = 0.025). An endocervical lesion location was more frequent in Group C than in Groups A and B (55.6% vs. 6.8% vs. 11.8%, respectively, p < 0.0001). Women aged 50 years and older with CIN3 showed a significant reduction of high-grade lesion predictors along with physiological confounding cervical changes (transformation zone type 3 and endocervical lesion location). The diagnostic work-up of cervical lesions in older women should provide their potential consideration as a special population.

The Colposcopic Atlas of Schistosomiasis in the Lower Female Genital Tract Based on Studies in Malawi, Zimbabwe, Madagascar and South Africa

PubMed Central

Norseth, Hanne M.; Ndhlovu, Patricia D.; Kleppa, Elisabeth; Randrianasolo, Bodo S.; Jourdan, Peter M.; Roald, Borghild; Holmen, Sigve D.; Gundersen, Svein G.; Bagratee, Jayanthilall; Onsrud, Mathias; Kjetland, Eyrun F.

2014-01-01

Background Schistosoma (S.) haematobium is a neglected tropical disease which may affect any part of the genital tract in women. Female genital schistosomiasis (FGS) may cause abnormal vaginal discharge, contact bleeding, genital tumours, ectopic pregnancies and increased susceptibility to HIV. Symptoms may mimic those typical of sexually transmitted infections (STIs) and women with genital schistosomiasis may be incorrectly diagnosed. An expert consensus meeting suggested that the following findings by visual inspection should serve as proxy indicators for the diagnosis of schistosomiasis of the lower genital tract in women from S. haematobium endemic areas: sandy patches appearing as (1) single or clustered grains or (2) sandy patches appearing as homogenous, yellow areas, or (3) rubbery papules. In this atlas we aim to provide an overview of the genital mucosal manifestations of schistosomiasis in women. Methodology/Principal findings Photocolposcopic images were captured from women, between 1994 and 2012 in four different study sites endemic for S. haematobium in Malawi, Zimbabwe, South Africa and Madagascar. Images and specimens were sampled from sexually active women between 15 and 49 years of age. Colposcopic images of other diseases are included for differential diagnostic purposes. Significance This is the first atlas to present the clinical manifestations of schistosomiasis in the lower female genital tract. It will be freely available for online use, downloadable as a presentation and for print. It could be used for training purposes, further research, and in clinical practice. PMID:25412334

The colposcopic atlas of schistosomiasis in the lower female genital tract based on studies in Malawi, Zimbabwe, Madagascar and South Africa.

PubMed

Norseth, Hanne M; Ndhlovu, Patricia D; Kleppa, Elisabeth; Randrianasolo, Bodo S; Jourdan, Peter M; Roald, Borghild; Holmen, Sigve D; Gundersen, Svein G; Bagratee, Jayanthilall; Onsrud, Mathias; Kjetland, Eyrun F

2014-01-01

Schistosoma (S.) haematobium is a neglected tropical disease which may affect any part of the genital tract in women. Female genital schistosomiasis (FGS) may cause abnormal vaginal discharge, contact bleeding, genital tumours, ectopic pregnancies and increased susceptibility to HIV. Symptoms may mimic those typical of sexually transmitted infections (STIs) and women with genital schistosomiasis may be incorrectly diagnosed. An expert consensus meeting suggested that the following findings by visual inspection should serve as proxy indicators for the diagnosis of schistosomiasis of the lower genital tract in women from S. haematobium endemic areas: sandy patches appearing as (1) single or clustered grains or (2) sandy patches appearing as homogenous, yellow areas, or (3) rubbery papules. In this atlas we aim to provide an overview of the genital mucosal manifestations of schistosomiasis in women. Photocolposcopic images were captured from women, between 1994 and 2012 in four different study sites endemic for S. haematobium in Malawi, Zimbabwe, South Africa and Madagascar. Images and specimens were sampled from sexually active women between 15 and 49 years of age. Colposcopic images of other diseases are included for differential diagnostic purposes. This is the first atlas to present the clinical manifestations of schistosomiasis in the lower female genital tract. It will be freely available for online use, downloadable as a presentation and for print. It could be used for training purposes, further research, and in clinical practice.

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

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

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

[Computerized evaluation of reparative processes of the cervix uteri].

PubMed

Pasquinucci, C; Contini, V

1990-01-01

This study was aimed to evaluate the effect of polydeoxyribonucleotide (PDRN), as reported in relevant literature, on cervical epithelia dynamics. Particularly, the interactions taking place between columnar epithelium and the squamous one have been examined. For the purposes of the study, the following computerized techniques, already widely known, have been used: The colposcope is joined to a videocamera connected with a computer (AT compatible). The computer is equipped with a graphic card capable to record and to digit the image, i.e. to make it recognizable by the computer itself. Thereafter, many operations can be performed on the colposcopic images: reductions, enlargements, retouches, record, recall, analysis, etc. Moreover, irregular epithelial areas can be easily determined to a good approximation and, using pre-established enlargement ratios, their evolution can be evaluated. By means of this technique 12 out-patients with uterine cervix ectopias, with or without normal transformation zone (NTZ), have been examined. The monthly therapy was 12 pessaries, each containing 5 mg polydeoxyribonucleotide (POLIDES 5--Farmigea), from the 7th to the 18th day of the cycle, repeated for 3 months. Since the first month of treatment a reduction of the ectopic columnar epithelium has been noted in most patients (9 on 12), with a squamous epithelium increase (peripheral reparative process). This process has kept on increasing during the following months in the 9 patients responding to the treatment, whose ectopic areas were covered by squamous epithelium (average 55% of the area; range 33%-78%). No response to the treatment has been shown in 3 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

CO2 laser in treatment of condylomata acuminata of male reproductive organs

NASA Astrophysics Data System (ADS)

Wozniak, Jakub; Opala, Tomasz; Pisarska-Krawczyk, Magdalena; Wilczak, Maciej; Pisarski, Tadeusz

1996-03-01

The results of laser therapy in the treatment of condylomata acuminata of male reproductive organs are reported. Between November 1991 and February 1995 in the Department of Reproduction, Institute of Gynecology and Obstetrics, Karol Marcinkowski University School of Medical Sciences, Poznan in 28 patients with condylomatous changes of reproductive organs carbon-dioxide laser therapy under colposcopic control was done. In 24 of them the healing was achieved. In four patients second laser therapy was done. All patients are still under control in the Department of Reproduction and there was no recurrence diagnosed.

Detection of Human Papillomavirus Type 16 DNA and Papillomavirus Genus‐specific Antigens in Vulva and Cervix from Patients with Bowenoid Papulosis

PubMed Central

Sugase, Motoyasu; Moriyama, Shin‐ichi; Hata, Satoru; Matsukura, Toshihiko

1989-01-01

The warty disordered lesions of the vulva in three female patients were diagnosed as Bowenoid papulosis on the basis of clinical and histopathological findings. In all three vulvar lesions, human Papillomavirus type 16 (HPV 16) DNA was identified hy Southern blot hybridization and Papillomavirus genus‐specific (PGS) antigen was detected in one case immunohistochemically. Furthermore, colposcopic examination revealed the presence of abnormal uterine cervical lesions in two cases. They were found to be intraepithelial neoplasia which harbored HPV 16 DNA and were positive for PGS antigen. PMID:2540130

Risk factors for early cytologic abnormalities after loop electrosurgical excision procedure.

PubMed

Dietrich, Charles S; Yancey, Michael K; Miyazawa, Kunio; Williams, David L; Farley, John

2002-02-01

To evaluate risk factors for early cytologic abnormalities and recurrent cervical dysplasia after loop electrosurgical excision procedure (LEEP). A retrospective analysis was performed of all pathology records for LEEPs performed at our institution from January 1996 through July 1998. Follow-up cytology from 2 through 12 months after LEEP was reviewed. Patients with abnormal cytology were referred for further colposcopic evaluation. Statistical analysis using chi2 test for trend, proportional hazards model test, Fisher exact tests, and life table analysis were performed to identify risk factors for early cytologic abnormalities after LEEP and to determine relative risk of recurrent dysplasia. A total of 298 women underwent LEEP during the study period, and 29% of these had cytologic abnormalities after LEEP. Grade of dysplasia, ectocervical marginal status, endocervical marginal status, and glandular involvement with dysplasia were not found to be independent risk factors for early cytologic abnormalities. However, when risk factors were analyzed cumulatively, the abnormal cytology rate increased from 24% with no risk factors to 67% with three risk factors present (P =.037). Of patients with abnormal cytology after LEEP, 40% developed subsequent dysplasia, and the mean time to diagnosis was approximately 6 months. The relative risk of subsequent dysplasia ranged from a 20% increase to twice the risk if post-LEEP cytology was low-grade squamous intraepithelial lesion or high-grade squamous intraepithelial lesion, respectively. Based on these results, consideration should be given for early colposcopic examination of patients who have evidence of marginal involvement or endocervical glandular involvement with dysplasia. These patients are at increased risk for abnormal cytology and recurrent dysplasia. This initial visit should occur at 6 months, as the mean time to recurrence of dysplasia was 6.5 months.

Smoking as a risk factor for preinvasive and invasive cervical lesions in female sex workers in Venezuela.

PubMed

Núñez, J T; Delgado, M; Pino, G; Girón, H; Bolet, B

2002-10-01

To determine whether the number of cigarettes smoked per day and years of smoking were risk factors for preinvasive and invasive cervical lesions in Venezuelan female sex workers. The clinical history of 438 female sex workers (FSWs) was taken and each received a gynecological examination, a Pap smear, and a colposcopic examination. A colposcopically-guided cervical biopsy was taken when the epithelium appeared abnormal. The FSWs' mean age was 32.16+/-8 years. Age at first sexual intercourse was 15.9+/-2 years, parity was 4.1+/-2.3, live births were 3+/-3, and age at first delivery was 16.6+/-4.7 years. Cervical biopsies were performed in 84 FSWs. Sixty-four of them (76.2%) had preinvasive or invasive lesions and 47 (73.4%) were current smokers (Relative Risk) (RR), 1.26; 95% confidence interval (CI), 1.02-1.55; P<0.03]. FSWs who smoked more than 20 cigarettes per day had an increased RR to get a premalignant or malignant cervical lesion (RR, 1.27; 95% CI, 1.02-1.52; P<0.03). There was no statistically significant difference between FSWs who smoked 20 cigarettes or more per day and FSWs who smoked less than 20 cigarettes per day (RR, 1.36; 95% CI, 0.81-2.29; P<0.25). FSWs who had been smoking for 5 years or more were at risk to develop preinvasive or invasive cervical lesions (RR, 1.37; 95% CI, 1.01-1.86; P<0.04). The risk for FSWs to develop preinvasive or invasive cervical lesions increased with the number of cigarettes they smoked per day and their years of smoking.

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.

Management of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions of the uterine cervix with human papilloma virus infection among young women aged less than 25 years.

PubMed

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

2016-12-01

Current ASCCP guidelines recommend repeat cytology 12 months after HPV-positive results in women aged 21-24 years with either atypical squamous cells of undetermined significance (ASCUS) or a low-grade squamous intraepithelial lesion (LSIL). The purpose of this study was to validate an algorithm in such women with ASCUS or LSIL. A multicenter cross-sectional study was carried out at three academic hospitals involving 40,847 Korean women who underwent cervical cancer screening with cytology and HPV testing with or without subsequent colposcopic biopsies between January 2007 and December 2013. Among a total of 3,193 women with available histopathology data, 762 women with ASCUS and 758 with LSIL were HPV-positive. Among HPV-positive women with ASCUS, 38.5% of women aged 21-24 years had ≥CIN2, compared to 20.8% of women aged 30-65 years and 21.1% of the total women. Among HPV-positive women with LSIL, 25.8% aged 21-24 years had ≥CIN2, compared to 21.2% of women aged 30-65 years and 21.9% of the total women. In HPV-positive women with ASCUS/LSIL aged less than 25 years, the prevalence of ≥CIN2 lesions was 34.5%, which was significantly higher than that (21.0%) in women aged ≥25 years. The risk of ≥CIN2 lesions in HPV-positive Korean women aged 21-24 years with ASCUS or LSIL was not lower than that in older women. Colposcopic examination should be considered for management of HPV-positive young women with ASCUS or LSIL. Diagn. Cytopathol. 2016;44:959-963. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Intraepithelial and invasive neoplasia of the vulva in association with human papillomavirus infection.

PubMed

Planner, R S; Hobbs, J B

1988-06-01

Colposcopic examination of 335 women with cytologically detected human papillomavirus (HPV) revealed involvement of the cervix in 316 patients (94%), vagina in 276 (82%) and vulva in 148 (44%). A symptom complex of pruritus and superficial dyspareunia was found in 98 of the 148 patients with vulvar infection (66%). Histologic examination revealed HPV-associated vulvar intraepithelial neoplasia (VIN) in 11 of 148 biopsies (7.4%). Follow-up of the patients with HPV infection with or without VIN showed a spontaneous regression rate of 56% but also demonstrated progression to VIN 3 in two patients and to invasive carcinoma of the vulva in one.

Laser surgery in the treatment of vaginal cysts

NASA Astrophysics Data System (ADS)

Wozniak, Jakub; Dydowicz, Piotr; Opala, Tomasz; Pisarska-Krawczyk, Magdalena; Wilczak, Maciej; Pisarski, Tadeusz

1997-10-01

The authors described the results of treatment of vaginal cysts with CO2 laser under colposcopic control in 12 women. In five of them the recurrent Bartholin's, in another five the Gartner's and in tow the endometrial cysts were diagnosed. All laser surgeries were done in the Department of Reproduction, Institute of Gynecology, Karol Marcinkowski School of Medical Sciences, Poznan, Poland between September 1995 and September 1996. In the authors' opinion the use of CO2 laser is the efficient method of treatment of vaginal cysts. The most of laser procedures are doing as the one-day surgery. There are no serious postoperative complications after laser surgery.

Costs and Cost Effectiveness of Three Approaches for Cervical Cancer Screening among HIV-Positive Women in Johannesburg, South Africa

PubMed Central

Lince-Deroche, Naomi; Phiri, Jane; Michelow, Pam; Smith, Jennifer S.; Firnhaber, Cindy

2015-01-01

Background South Africa has high rates of HIV and HPV and high incidence and mortality from cervical cancer. However, cervical cancer is largely preventable when early screening and treatment are available. We estimate the costs and cost-effectiveness of conventional cytology (Pap), visual inspection with acetic acid (VIA) and HPV DNA testing for detecting cases of CIN2+ among HIV-infected women currently taking antiretroviral treatment at a public HIV clinic in Johannesburg, South Africa. Methods Method effectiveness was derived from a validation study completed at the clinic. Costs were estimated from the provider perspective using micro-costing between June 2013-April 2014. Capital costs were annualized using a discount rate of 3%. Two different service volume scenarios were considered. Threshold analysis was used to explore the potential for reducing the cost of HPV DNA testing. Results VIA was least costly in both scenarios. In the higher volume scenario, the average cost per procedure was US$ 3.67 for VIA, US$ 8.17 for Pap and US$ 54.34 for HPV DNA. Colposcopic biopsies cost on average US$ 67.71 per procedure. VIA was least sensitive but most cost-effective at US$ 17.05 per true CIN2+ case detected. The cost per case detected for Pap testing was US$ 130.63 using a conventional definition for positive results and US$ 187.52 using a more conservative definition. HPV DNA testing was US$ 320.09 per case detected. Colposcopic biopsy costs largely drove the total and per case costs. A 71% reduction in HPV DNA screening costs would make it competitive with the conservative Pap definition. Conclusions Women need access to services which meet their needs and address the burden of cervical dysplasia and cancer in this region. Although most cost-effective, VIA may require more frequent screening due to low sensitivity, an important consideration for an HIV-positive population with increased risk for disease progression. PMID:26569487

Costs and Cost Effectiveness of Three Approaches for Cervical Cancer Screening among HIV-Positive Women in Johannesburg, South Africa.

PubMed

Lince-Deroche, Naomi; Phiri, Jane; Michelow, Pam; Smith, Jennifer S; Firnhaber, Cindy

2015-01-01

South Africa has high rates of HIV and HPV and high incidence and mortality from cervical cancer. However, cervical cancer is largely preventable when early screening and treatment are available. We estimate the costs and cost-effectiveness of conventional cytology (Pap), visual inspection with acetic acid (VIA) and HPV DNA testing for detecting cases of CIN2+ among HIV-infected women currently taking antiretroviral treatment at a public HIV clinic in Johannesburg, South Africa. Method effectiveness was derived from a validation study completed at the clinic. Costs were estimated from the provider perspective using micro-costing between June 2013-April 2014. Capital costs were annualized using a discount rate of 3%. Two different service volume scenarios were considered. Threshold analysis was used to explore the potential for reducing the cost of HPV DNA testing. VIA was least costly in both scenarios. In the higher volume scenario, the average cost per procedure was US$ 3.67 for VIA, US$ 8.17 for Pap and US$ 54.34 for HPV DNA. Colposcopic biopsies cost on average US$ 67.71 per procedure. VIA was least sensitive but most cost-effective at US$ 17.05 per true CIN2+ case detected. The cost per case detected for Pap testing was US$ 130.63 using a conventional definition for positive results and US$ 187.52 using a more conservative definition. HPV DNA testing was US$ 320.09 per case detected. Colposcopic biopsy costs largely drove the total and per case costs. A 71% reduction in HPV DNA screening costs would make it competitive with the conservative Pap definition. Women need access to services which meet their needs and address the burden of cervical dysplasia and cancer in this region. Although most cost-effective, VIA may require more frequent screening due to low sensitivity, an important consideration for an HIV-positive population with increased risk for disease progression.

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

The video fluorescent device for diagnostics of cancer of human reproductive system

NASA Astrophysics Data System (ADS)

Brysin, Nickolay N.; Linkov, Kirill G.; Stratonnikov, Alexander A.; Savelieva, Tatiana A.; Loschenov, Victor B.

2008-06-01

Photodynamic therapy (PDT) is one of the advanced methods of treatment of skin cancer and surfaces of internal organs. The basic advantages of PDT are high efficiency and low cost of treatment. PDT technique is needed for providing fluorescent diagnostics. Laser-based systems are widely applied to the fluorescence excitations for diagnostic because of a narrow spectrum of fluorescence excitation and high density of radiation. Application of laser systems for carrying out fluorescent diagnostics gives the image of a tumor distorted by speckles that does not give an opportunity to obtain full information about the form of a tumor quickly. Besides, these laser excitation systems have complicated structure and high cost. As a base for the development and creation of a video fluorescent device one of commercially produced colposcopes was chosen. It allows to decrease cost of the device, and also has enabled to make modernization for already used colposcopes. A LED-based light source was offered to be used for fluorescence excitation in this work. The maximum in a spectrum of radiation of LEDs corresponds to the general spectral maximum of protoporphyrin IX (PPIX) absorption. Irradiance in the center of a light spot is 31 mW/cm2. The receiving optical system of the fluorescent channel is adjusted at 635 nm where a general spectral maximum of fluorescence PPIX is located. Also the device contains a RGB video channel, a white light source and a USB spectrometer LESA-01-BIOSPEC, for measurement of spectra of fluorescence and diffusion reflections in treatment area. The software is developed for maintenance of the device. Some studies on laboratory animals were made. As a result, areas with the increased concentration of a PPIX were correctly detected. At present, the device is used for diagnostics of cancer of female reproductive system in Research Centre for Obstetrics, Gynecology and Perinatology of the Russian Academy of Medical Sciences (Moscow, Russia).

Factors associated with psychological distress following colposcopy among women with low-grade abnormal cervical cytology: a prospective study within the Trial Of Management of Borderline and Other Low-grade Abnormal smears (TOMBOLA).

PubMed

Sharp, Linda; Cotton, Seonaidh; Carsin, Anne-Elie; Gray, Nicola; Thornton, Alison; Cruickshank, Margaret; Little, Julian

2013-02-01

Little is known about psychological after-effects of colposcopy and associated investigations and treatment in women with low-grade abnormal cervical cytology. We investigated psychological distress following colposcopy and related procedures. Nine hundred and eighty-nine women aged 20-59 years with routine cytology showing low-grade abnormalities were recruited to the Trial of Management of Borderline and other Low-grade Abnormal smears and attended colposcopy. If the cervical transformation zone (TZ) was colposcopically abnormal, women had immediate loop excision or diagnostic punch biopsies, with treatment if these showed cervical intraepithelial neoplasia grade 2/3 (CIN2/3). Women completed socio-demographic and psychosocial questionnaires at recruitment and before colposcopy. Six weeks after their last procedure, women completed the Impact of Event Scale (IES). Logistic regression was used to determine factors associated with significant psychological distress (IES ≥ 9). Analyses were stratified by colposcopic impression. The response rate was 74%. Six weeks after the last procedure, 86 (21%) of 391 women with a normal TZ had significant distress compared with 144 (42%) of 337 with an abnormal TZ. In both groups, significant distress was associated with anxiety pre-colposcopy and pain or discharge afterwards. Additional variables predicting distress in women with a normal TZ were worries about having sex and dissatisfaction with support from others. In women with an abnormal TZ, additional predictors of distress were younger age, CIN2/3, bleeding following colposcopy and worries about having cancer. Substantial proportions of women experience psychological distress after colposcopy and related procedures, even when the colposcopy is normal. This is an important cost of cervical screening. Interventions to alleviate these adverse psychological effects are required. Copyright © 2011 John Wiley & Sons, Ltd.

CO2 laser surgery for vulvar intraepithelial neoplasia. Excisional, destructive and combined techniques.

PubMed

Penna, Carlo; Fallani, M Grazia; Fambrini, Massimiliano; Zipoli, Elisa; Marchionni, Mauro

2002-11-01

To evaluate CO2 laser excision, vaporization and combined techniques for treatment of vulvar intraepithelial neoplasia (VIN). Thirty-nine cases of VIN 3, 15 cases of VIN 2 and 9 of VIN 1, for a total of 63 patients with histologically proven VIN, underwent laser excision or vaporization under colposcopic guidance, using local anesthesia, in an outpatient setting or after day-surgery admission. Clinical aspects, cervical intraepithelial neoplasia (CIN) and vaginal intraepithelial neoplasia (VaIN) association, types of CO2 laser treatment, follow-up, recurrences and second treatments were evaluated. Twenty-seven (41.3%) patients underwent laser vaporization, and 37 (58.7%) with VIN 3, underwent laser excision or the combined technique. Colposcopic and biopsy examinations of patients with VIN revealed three cases of CIN 3 and nine cases of VaIN 3; two patients had concomitant VIN 3, CIN 3 and VaIN 3. Local anesthesia, using 2% carbocaine, and outpatient or day-surgery treatments were possible in all cases. A small incidence of intraoperative complications (4.8%) and absence of postoperative complications were observed. A single session was curative in 76.9% of patients treated with laser vaporization and in 78.4% of those treated with laser excision. Eleven cases of recurrent VIN and two cases of invasive vulvar carcinoma were observed during follow-up. A second laser procedure was carred out in all cases of relapsed VIN, with an overall cure rate of 96.8% after two treatments. Radical vulvectomy associated with inguinal-femoral lymphadenectomy was performed in the two cases of invasive carcinoma. CO2 laser surgery permits treatment of VIN in an outpatient or day-surgery setting under local anesthesia with excellent cosmetic and functional results. The treatment can also be adjusted to the patient's specific needs, with the possibility of calibrating the depth of the vaporized and removed tissues. Excisional treatment is the preferred method because it permits histologic evaluation of the excised tissue and detection of possible occult early invasion.

10-year experience of CO2-laser application in ambulance gynecology

NASA Astrophysics Data System (ADS)

Stachanov, Michael L.; Masychev, Victor I.; Velsher, Leonid Z.; Kirkin, Vladimir V.; Zhashkov, Roman V.; Kocharian, Emilia A.

2000-10-01

CO2-laser surgical systems have come to stay in everyday practice of modern physicians and are successfully used in colposcopic and laparoscopic surgery. Results, obtained in ambulance gynecology are especially impressing. CO2- laser provides high medical- and cost-effective treatment. Presented work describes many-years experience of CO2- laser application. 439 patients with various vulvaric and cervix diseases were operated within this period. Laser beam parameters were selected according to requirements ((tau) =4 J/cm2) treatment without carbonization. Analyses of the results showed that the laser successfully destructs uterine cervix erosion, endocervicosis, dysplasia, leukoplakia, eritoplakia of uterine cervix, various benignant pathologies and focus degenerative process in ambulate conditions.

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.

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.

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.

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.

[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.

LASER BIOLOGY AND MEDICINE: Combined application of optical methods to increase the information content of optical coherent tomography in diagnostics of neoplastic processes

NASA Astrophysics Data System (ADS)

Kuranov, R. V.; Sapozhnikova, V. V.; Shakhova, N. M.; Gelikonov, V. M.; Zagainova, E. V.; Petrova, S. A.

2002-11-01

A combined application of optical methods [optical coherent tomography (OCT), cross-polarisation optical coherent tomography, and fluorescence spectroscopy] is proposed for obtaining information on morphological and biochemical changes occurring in tissues in norm and pathology. It is shown that neoplastic and scar changes in esophagus can be distinguished using a combination of polarisation and standard OCT due to the difference between the depolarising properties of the tissues caused by the structural properties of collagenic fibres in stroma. It is shown that OCT combined with fluorescence spectroscopy with the use of 5-aminolevulinic acid is promising for determining the boundaries of carcinoma of the uterine cervix and vulva. It is found that the tumour boundary detected by optical methods coincides with the morphological boundary and extends beyond colposcopically determined boundary by about 2 mm.

Discordance between cytology and biopsy histology of the cervix: what to consider and what to do.

PubMed

Anschau, Fernando; Guimarães Gonçalves, Manoel Afonso

2011-01-01

Since cytology is the examination utilized for the screening of cervical cancer, it is important to determine its correlation with histologic examination, the gold standard in the diagnosis of cervical disease. A retrospective evaluation was made of 431 patients who presented with colposcopic indication for cervical biopsy between 2003 and 2007. In 90.8% (289/318) of the patients, cytology showing cervical intraepithelial neoplasia (CIN) was confirmed as CIN in the histology of the cervix, while 62.8% (71/113) of patients with normal cytology had a confirmation of a normal histology (κ = 0.558). Cytology demonstrated a sensitivity and specificity of 87.3 and 71.0%, respectively. The agreement between cervical cytology and histology, considering the presence of CIN, was moderate. Correlations between accuracy and errors of cytology are discussed with therapeutic emphasis. Copyright © 2011 S. Karger AG, Basel.

Combined application of optical methods to increase the information content of optical coherent tomography in diagnostics of neoplastic processes

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

Kuranov, R V; Sapozhnikova, V V; Shakhova, N M

2002-11-30

A combined application of optical methods [optical coherent tomography (OCT), cross-polarisation optical coherent tomography, and fluorescence spectroscopy] is proposed for obtaining information on morphological and biochemical changes occurring in tissues in norm and pathology. It is shown that neoplastic and scar changes in esophagus can be distinguished using a combination of polarisation and standard OCT due to the difference between the depolarising properties of the tissues caused by the structural properties of collagenic fibres in stroma. It is shown that OCT combined with fluorescence spectroscopy with the use of 5-aminolevulinic acid is promising for determining the boundaries of carcinoma ofmore » the uterine cervix and vulva. It is found that the tumour boundary detected by optical methods coincides with the morphological boundary and extends beyond colposcopically determined boundary by about 2 mm. (laser biology and medicine)« less

Participant recruitment and motivation for participation in optical technology for cervical cancer screening research trials.

PubMed

Shuhatovich, Olga M; Sharman, Mathilde P; Mirabal, Yvette N; Earle, Nan R; Follen, Michele; Basen-Engquist, Karen

2005-12-01

In order to improve recruitment for cervical cancer screening trials, it is necessary to analyze the effectiveness of recruitment strategies used in current trials. A trial to test optical spectroscopy for the diagnosis of cervical neoplasia recruited 1000 women from the community; the trial evaluated the emerging technology against Pap smears and colposcopically directed biopsies for cervical dysplasia. We have examined women's reasons for participating as well as the effectiveness and efficiency for each recruitment strategy. Reasons for participation were identified and compared between trials. The recruitment method that resulted in the most contacts was newspaper reportorial coverage and advertising, followed by family and friends, then television news coverage. The most cost-effective method for finding eligible women who attend the research appointment is word of mouth from a family member or friend. Recommendations are given for maximizing the efficiency of recruitment for cervical cancer screening trials.

[Changes in the vitamin A status in dysplastic epithelium of the cervix].

PubMed

Volz, J; van Rissenbeck, A; Blanke, M; Melchert, F; Schneider, A; Biesalski, H K

1995-01-01

In 34 patients with HVP-infection of the cervix and in 40 patients with CIN III standardised biopsies were taken from the involved area and normal cervical epithelium for determination of the local concentration of retinylester. In all cases diagnosis was confirmed colposcopically, cytologically and by histology. HPV infection was confirmed by in situ hybridisation. Determination of retinylester was performed by HPLC. No significant difference of local retinyl-plamitate concentration was detectable in HPV infected versus normal tissue. Retinyl-palmitate concentration was extremely lower in CIN III compared with normal cervical epithelium and HPV-infected tissue. The determination of plasma level of retinol showed no significant difference between the two groups. So it can be presumed that the reduction of retinyl-palmitat in CIN III is a local process and a local supplementation of Vitamin A might contribute to the prevention of cervical neoplasia.

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.

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

The acetic acid test in evaluation of subclinical genital papillomavirus infection: a comparative study on penoscopy, histopathology, virology and scanning electron microscopy findings.

PubMed Central

Wikström, A; Hedblad, M A; Johansson, B; Kalantari, M; Syrjänen, S; Lindberg, M; von Krogh, G

1992-01-01

OBJECTIVES--To evaluate colposcopic criteria in acetowhite lesions of the penis ("penoscopy") for the diagnosis of subclinical genitoanal papillomavirus infection (GPVI) compared with histopathological criteria of HPV involvement and to various hybridisation assays for HPV DNA detection, and to depict typical lesions by scanning electron microscopy. DESIGN--The study included 101 randomly selected male partners of females with known GPVI, or with penile symptoms such as itching, burning and dyspareunia who did not exhibit overt genital warts but appeared to be afflicted with acetowhite penile lesions after topical application of 5% acqueous acetic acid. Lesions were judged by penoscopy as either typical, conspicuous or nontypical for underlying HPV infection. Biopsy specimens from 91 men were examined by light microscopy and by either Southern blot (SB), polymerase chain reaction (PCR) and/or in situ hybridisation (ISH) assays for the presence of HPV DNA of the HPV types 6, 11, 16, 18, 31, 33 and 42 (Group A). From another ten men lesions clinically typical for GPVI were also examined topographically by scanning electronic microscopy (Group B). SETTING--The STD out-patient clinic of the Department of Dermatovenereology of Karolinska Hospital, Stockholm, Sweden. RESULTS--Group A Seventy eight (86%) of the biopsied lesions met the penoscopy criteria of being either typical of or conspicuous for GVPI. The agreement between penoscopy and histopathology was fairly good, as HPV diagnosis was made by both methods in 56 (62%) of the cases. The reliability of applying strict colposcopic hallmarks was further substantiated by the finding that 55 (60%) of the biopsy specimens taken from penoscopically typical/conspicuous lesions contained HPV DNA. However, there are diagnostic pitfalls for the acetic acid test. Coexistence of an eczematoid reaction with changes indicative of HPV influence was detected in six (7%) of the cases, while an inflammatory response only occurred in 17 (19%) of the specimens. Additional histopathological diagnoses (normal epithelium, lichen sclerosus et atrophicus, balanitis circinata parakeratotica, verruca plana) were established in another eight (9%) of the cases. Among the HPV DNA positive cases, all of the HPV types tested for were detected with the exception of HPV 18. A severe penile intraepithelial neoplasia (PIN III) was revealed in five (5%) of biopsies; HPV 16 was present in two and HPV 42 in one of these biopsy specimens. GROUP B--Scanning electron microscopy depiction harmonised with the penoscopy findings showing that subclinical GPVI characteristically exhibits a well demarcated, slightly elevated border and that the central area of lesions often displays a "groove" in which the epithelium appears to be thin with protrusions from beneath that probably represent capillaries. CONCLUSION--Use of the acetic acid test for evaluation of GPVI should be combined with a colposcopic evaluation based on strict topographic hallmarks, followed by a directed biopsy for light microscopic evaluation. We found that the positive predictive value of colposcopy was as high when correlated with histopathological findings (72%) as when virological methods were used, whether HPV DNA hybridisation testing was performed with the well established SB and ISH assays (45%), or by applying the newly introduced and highly sensitive PCR assay as well (71%). False positivity from the acetic acid test occurs and is mainly due to inflammatory conditions but also to the presence of other conditions. Epithelial fissures are evidently associated with some subclinical GPVI lesions and may potentially represent loci minores for infectious stimuli and perhaps facilitate the transmission of some blood-borne STDs. We prose that the term "papillomavirus balanoposthitis" should be used for penile HPV infection associated with inflammatory responses. Our study indicates that PIN III frequently occurs in a subclinical form and may be associated with not only previously identified "high-risk" HPV types such as type 16, but also with the HPV type 42 that has not previously been considered as oncogenic. Images PMID:1316310

Vaginal health in contraceptive vaginal ring users - A review.

PubMed

Lete, Iñaki; Cuesta, María C; Marín, Juan M; Guerra, Sandra

2013-08-01

To provide an overview of the available data from clinical studies of vaginal conditions in women who use a vaginal ring as a contraceptive. A systematic review of the literature. Millions of women have already used the ethylene vinyl acetate vaginal ring that releases ethinylestradiol and etonogestrel for contraception. Because of its small size, more than four out of five women using the ring report that they do not feel it, even during sexual intercourse. No colposcopic or cytological changes have been observed in users, although approximately 10% have increased vaginal discharge. While in vitro studies have shown adhesion of Candida yeasts to the vaginal ring surface, clinical studies have not demonstrated a greater incidence of Candida infections compared to users of equivalent oral contraceptives. Some clinical studies suggest a lower incidence of bacterial vaginosis. No interaction exists between concomitant use of the vaginal ring and other drugs or products for vaginal use. The use of a contraceptive vaginal ring does not alter the vaginal ecosystem and therefore does not substantially affect vaginal health.

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.

[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.

Phase II Trial of β-All-trans-Retinoic Acid for Cervical Intraepithelial Neoplasia Delivered via a Collagen Sponge and Cervical Cap

PubMed Central

Graham, Vivian; Surwit, Earl S.; Weiner, Sheldon; Meyskens, Frank L.

1986-01-01

Retinoids are effective suppressors of the phenotypic development of cancer in many animal systems, whether the process is initiated by chemical, physical or viral carcinogens. Cases of cervical intraepithelial neoplasia are excellent for studying the effectiveness of retinoids as chemopreventive agents because the process can be closely followed by serial colposcopic and pathologic (cytology or biopsy) means and changes in the condition safely monitored. We have previously conducted a phase I study of trans-retinoic acid (Tretinoin) given topically by a collagen sponge and cervical cap. A dose of 0.372% was selected for phase II trial. We have treated 20 patients with topical retinoic acid, and a complete response with total regression of disease was obtained in 50%. Systemic and cervical side effects were mild and vaginal side effects moderate but tolerable. These results provide a clinical basis for a randomized, double-blind phase III study to definitely answer the question of whether retinoic acid is an effective chemopreventive agent for cervical cancer. ImagesFigure. 1. PMID:3765597

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.

[Squamous intraepithlelial lesions in women's lupus].

PubMed

Mercado, Ulises

2009-09-01

previous studies have suggested an association between systemic lupus erythematosus (SLE), abnormal cervical smears and squamous intraepithelial lesions (SIL), but the underlying cause of this association is not well defined. To review Pap smear and biopsy results in SLE women compared with healthy controls and to identify traditional risk factors associated with abnormal smears. Retrospective cohort study. Sixty-two SLE patients and 1719 controls were included. Women with abnormal Pap smear results were referred to colposcopic biopsy histology. Information on traditional risk factors was obtained. Among SLE patients, activity score (Mex-SLEDAI) and immunosuppressive drugs exposure also were determined. Fourteen (22%) out of 62 patients had abnormal Pap smear results, compared with 120 (7%) out of 1719 controls. Thirteen (92%) out of 14 patients showed SIL by histological examination, compared with 27 (22%) out of 120 controls. Two SLE women had condylomata. There were no significant differences in the use of immunosuppressive agents among SLE patients with and without SIL. Abnormal Pap smears, SIL by biopsy and changes in the sexual behavioral were more common among SLE patients than in controls. The immunosuppressive drug exposure was not associated with abnormal Pap smears.

Computerized image analysis for acetic acid induced intraepithelial lesions

NASA Astrophysics Data System (ADS)

Li, Wenjing; Ferris, Daron G.; Lieberman, Rich W.

2008-03-01

Cervical Intraepithelial Neoplasia (CIN) exhibits certain morphologic features that can be identified during a visual inspection exam. Immature and dysphasic cervical squamous epithelium turns white after application of acetic acid during the exam. The whitening process occurs visually over several minutes and subjectively discriminates between dysphasic and normal tissue. Digital imaging technologies allow us to assist the physician analyzing the acetic acid induced lesions (acetowhite region) in a fully automatic way. This paper reports a study designed to measure multiple parameters of the acetowhitening process from two images captured with a digital colposcope. One image is captured before the acetic acid application, and the other is captured after the acetic acid application. The spatial change of the acetowhitening is extracted using color and texture information in the post acetic acid image; the temporal change is extracted from the intensity and color changes between the post acetic acid and pre acetic acid images with an automatic alignment. The imaging and data analysis system has been evaluated with a total of 99 human subjects and demonstrate its potential to screening underserved women where access to skilled colposcopists is limited.

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.

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.

Detection of cervical intraepithelial neoplasia by using optical coherence tomography in combination with microscopy

NASA Astrophysics Data System (ADS)

Gallwas, Julia; Jalilova, Aydan; Ladurner, Roland; Kolben, Theresa Maria; Kolben, Thomas; Ditsch, Nina; Homann, Christian; Lankenau, Eva; Dannecker, Christian

2017-01-01

Optical coherence tomography (OCT) is a noninvasive high-resolution imaging technique that permits the detection of cancerous and precancerous lesions of the uterine cervix. The purpose of this study was to evaluate a new system that integrates an OCT device into a microscope. OCT images were taken from loop electrosurgical excision procedure (LEEP) specimens under microscopic guidance. The images were blinded with respect to their origin within the microscopic image and analyzed independently by two investigators using initially defined criteria and later compared to the corresponding histology. Sensitivity and specificity were calculated with respect to the correct identification of high-grade squamous intraepithelial lesions (HSIL). The interinvestigator agreement was assessed by using Cohen's kappa statistics. About 160 OCT images were obtained from 20 LEEP specimens. Sixty randomly chosen images were used to define reproducible criteria for evaluation. The assessment of the remaining 100 images showed a sensitivity of 88% (second investigator 84%) and a specificity of 69% (65%) in detecting HSIL. Surgical microscopy-guided OCT appears to be a promising technique for immediate assessment of microanatomical changes. In the gynecological setting, the combination of OCT with a colposcope may improve the detection of high-grade squamous intraepithelial lesions.

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.

Optoelectronic method for detection of cervical intraepithelial neoplasia and cervical cancer

NASA Astrophysics Data System (ADS)

Pruski, D.; Przybylski, M.; Kędzia, W.; Kędzia, H.; Jagielska-Pruska, J.; Spaczyński, M.

2011-12-01

The optoelectronic method is one of the most promising concepts of biophysical program of the diagnostics of CIN and cervical cancer. Objectives of the work are evaluation of sensitivity and specificity of the optoelectronic method in the detection of CIN and cervical cancer. The paper shows correlation between the pNOR number and sensitivity/specificity of the optoelectronic method. The study included 293 patients with abnormal cervical cytology result and the following examinations: examination with the use of the optoelectronic method — Truscreen, colposcopic examination, and histopathologic biopsy. Specificity of the optoelectronic method for LGSIL was estimated at 65.70%, for HGSIL and squamous cell carcinoma of cervix amounted to 90.38%. Specificity of the optoelectronic method used to confirm lack of cervical pathology was estimated at 78.89%. The field under the ROC curve for the optoelectronic method was estimated at 0.88 (95% CI, 0.84-0.92) which shows high diagnostic value of the test in the detection of HGSIL and squamous cell carcinoma. The optoelectronic method is characterised by high usefulness in the detection of CIN, present in the squamous epithelium and squamous cell carcinoma of cervix.

Vaginosis-associated bacteria and its association with HPV infection.

PubMed

Romero-Morelos, Pablo; Bandala, Cindy; Jiménez-Tenorio, Julián; Valdespino-Zavala, Mariana; Rodríguez-Esquivel, Miriam; Gama-Ríos, Reyna Anaid; Bandera, Artfy; Mendoza-Rodríguez, Mónica; Taniguchi, Keiko; Marrero-Rodríguez, Daniel; López-Romero, Ricardo; Ramón-Gallegos, Eva; Salcedo, Mauricio

2018-03-12

Cervical cancer is an important health problem in our country. It is known that there are several risk factors for this neoplasm, and it has been suggested that cervical microbiome alterations could play a role in the development and progress of cancer. Bacterial vaginosis associated bacteria such as Atopobium vaginae and Gardnerella vaginalis has been suggested as potential risk factor for cervical lesions and cervical cancer. DNA from 177 cervical scraping samples was studied: 104 belonged to women without cytological or colposcopic alterations and 73 samples from precursor lesions with previous human papillomavirus (HPV) infection history. All samples were screened for Atopobium vaginae, Gardnerella vaginalis and HPV by PCR. High HPV prevalence was found in precursor samples, and 30% of samples without lesions were positive for HPV. Virtually all samples contained sequences of both bacteria, and interestingly, there was not HPV association observed; these results could suggest that these microorganisms could be part of the cervical microbiome in Mexican population. The results obtained indicate that the bacteria analysed could be part of normal biome in Mexican women, suggesting a potential reconsideration of the pathogen role of these microorganisms. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Application of PDT for Uterine Cervical Cancer.

PubMed

Muroya, T; Kawasaki, K; Suehiro, Y; Kunugi, T; Umayahara, K; Akiya, T; Iwabuchi, H; Sakunaga, H; Sakamoto, M; Sugishita, T; Tenjin, Y

1999-01-01

We have been performing PDT using Excimer Dye Laser (EDL) or YAG-OPO laser, a type of low power laser, both of which have a considerably higher degree of tissue penetration even when compared to PDT using Argon Dye Laser (ADL).PDT is a relatively simple procedure without any bleeding and does not require anesthesia since it causes no pain. PDT is performed 48 h after intravenous injection of 1.5-2.0 mg/kg of PHE (Photofrin((R))). Precise spot irradiation is possible using a colposcope with an optical laser path. We also use a cervical probe which enables photoirradiation of the entire cervical canal.We have performed PDT on 131 cases (95 CIS, 31 dysplasia, 1 vulval dysplasia (VIN), 3 squamous cell carcinoma, microinvasion, and 1 CIS + endocervical adenocarcinoma, microinvasion). Of these cases, 127 became CR (96.9%). The first CR case was 10 years ago and no recurrence has been observed yet.PDT is extremely effective to preserve fertility. Except for sensitive reactions to sunlight, there are no noticeable side effects or difficulties related to pregnancy or delivery. We expect that in the near future PDT will be performed using diode lasers and without hospitalization due to new photosensitizers which have shorter retention times.

WE-FG-201-01: Patient Centric Technologies for Diagnosis of Breast and Cervical Cancer

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

Ramanujam, N.

Many low- and middle-income countries lack the resources and services to manage cancer, from screening and diagnosis to radiation therapy planning, treatment and quality assurance. The challenges in upgrading or introducing the needed services are enormous, and include severe shortages in equipment and trained staff. In this symposium, we will describe examples of technology and scientific research that have the potential to impact all these areas. These include: (1) the development of high-quality/low-cost colposcopes for cervical cancer screening, (2) the application of automated radiotherapy treatment planning to reduce staffing shortages, (3) the development of a novel radiotherapy treatment unit, andmore » (4) utilizing a cloud-based infrastructure to facilitate collaboration and QA. Learning Objectives: Understand some of the issues in cancer care in low- resource environments, including shortages in staff and equipment, and inadequate physical infrastructure for advanced radiotherapy. Understand the challenges in developing and deploying diagnostic and treatment devices and services for low-resource environments. Understand some of the emerging technological solutions for cancer management in LMICs. NCI; L. Court, NIH, Varian, Elekta; I. Feain, Ilana Feain is founder and CTO of Nano-X Pty Ltd.« less

WE-FG-201-00: High Impact Technologies for Low Resource Environments

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

NONE

Many low- and middle-income countries lack the resources and services to manage cancer, from screening and diagnosis to radiation therapy planning, treatment and quality assurance. The challenges in upgrading or introducing the needed services are enormous, and include severe shortages in equipment and trained staff. In this symposium, we will describe examples of technology and scientific research that have the potential to impact all these areas. These include: (1) the development of high-quality/low-cost colposcopes for cervical cancer screening, (2) the application of automated radiotherapy treatment planning to reduce staffing shortages, (3) the development of a novel radiotherapy treatment unit, andmore » (4) utilizing a cloud-based infrastructure to facilitate collaboration and QA. Learning Objectives: Understand some of the issues in cancer care in low- resource environments, including shortages in staff and equipment, and inadequate physical infrastructure for advanced radiotherapy. Understand the challenges in developing and deploying diagnostic and treatment devices and services for low-resource environments. Understand some of the emerging technological solutions for cancer management in LMICs. NCI; L. Court, NIH, Varian, Elekta; I. Feain, Ilana Feain is founder and CTO of Nano-X Pty Ltd.« less

WE-FG-201-03: Lean Innovation Transforming Global Access to Best Practice Radiotherapy Treatment

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

Feain, I.

Many low- and middle-income countries lack the resources and services to manage cancer, from screening and diagnosis to radiation therapy planning, treatment and quality assurance. The challenges in upgrading or introducing the needed services are enormous, and include severe shortages in equipment and trained staff. In this symposium, we will describe examples of technology and scientific research that have the potential to impact all these areas. These include: (1) the development of high-quality/low-cost colposcopes for cervical cancer screening, (2) the application of automated radiotherapy treatment planning to reduce staffing shortages, (3) the development of a novel radiotherapy treatment unit, andmore » (4) utilizing a cloud-based infrastructure to facilitate collaboration and QA. Learning Objectives: Understand some of the issues in cancer care in low- resource environments, including shortages in staff and equipment, and inadequate physical infrastructure for advanced radiotherapy. Understand the challenges in developing and deploying diagnostic and treatment devices and services for low-resource environments. Understand some of the emerging technological solutions for cancer management in LMICs. NCI; L. Court, NIH, Varian, Elekta; I. Feain, Ilana Feain is founder and CTO of Nano-X Pty Ltd.« less

WE-FG-201-02: Automated Treatment Planning for Low-Resource Settings

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

Court, L.

Many low- and middle-income countries lack the resources and services to manage cancer, from screening and diagnosis to radiation therapy planning, treatment and quality assurance. The challenges in upgrading or introducing the needed services are enormous, and include severe shortages in equipment and trained staff. In this symposium, we will describe examples of technology and scientific research that have the potential to impact all these areas. These include: (1) the development of high-quality/low-cost colposcopes for cervical cancer screening, (2) the application of automated radiotherapy treatment planning to reduce staffing shortages, (3) the development of a novel radiotherapy treatment unit, andmore » (4) utilizing a cloud-based infrastructure to facilitate collaboration and QA. Learning Objectives: Understand some of the issues in cancer care in low- resource environments, including shortages in staff and equipment, and inadequate physical infrastructure for advanced radiotherapy. Understand the challenges in developing and deploying diagnostic and treatment devices and services for low-resource environments. Understand some of the emerging technological solutions for cancer management in LMICs. NCI; L. Court, NIH, Varian, Elekta; I. Feain, Ilana Feain is founder and CTO of Nano-X Pty Ltd.« less

WE-FG-201-04: Cloud-Based Collaboration for Radiotherapy Clinical Trials, Research and Training

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

Palta, J.

Many low- and middle-income countries lack the resources and services to manage cancer, from screening and diagnosis to radiation therapy planning, treatment and quality assurance. The challenges in upgrading or introducing the needed services are enormous, and include severe shortages in equipment and trained staff. In this symposium, we will describe examples of technology and scientific research that have the potential to impact all these areas. These include: (1) the development of high-quality/low-cost colposcopes for cervical cancer screening, (2) the application of automated radiotherapy treatment planning to reduce staffing shortages, (3) the development of a novel radiotherapy treatment unit, andmore » (4) utilizing a cloud-based infrastructure to facilitate collaboration and QA. Learning Objectives: Understand some of the issues in cancer care in low- resource environments, including shortages in staff and equipment, and inadequate physical infrastructure for advanced radiotherapy. Understand the challenges in developing and deploying diagnostic and treatment devices and services for low-resource environments. Understand some of the emerging technological solutions for cancer management in LMICs. NCI; L. Court, NIH, Varian, Elekta; I. Feain, Ilana Feain is founder and CTO of Nano-X Pty Ltd.« less

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.

[Human papillomavirus infection and cervical intraepithelial neoplasia morbidity of women from different occupations in Shenzhen city, China].

PubMed

Tang, Hui-ru; Zhou, Yan-qiu; Wu, Lan-na; Liu, Zhi-hong; Zhang, Li-jie; Wu, Rui-fang

2007-10-01

To investigate the human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) morbidity of women from different occupations in Shenzhen city. 2045 women of five kinds of occupation in Shenzhen city, including 130 teachers, 385 workers, 316 service women, 199 poverish women, 420 doctors or nurses and 595 general residents were included. We screened these women by methods of detecting high risk HPV of hc2 combing with LCT. Women with screening positive results were diagnosed CIN by colposcopic biopsy. (1) High risk factors on HPV infection rate in different occupations were different with the highest in service occupation (19.3%) while the lowest appeared in medical workers (11.9%). (2) In those 2045 women, we found 199 cervical lesions including pathological HPV infection, CIN1, 2, 3 and cervical cancers, with morbidity rates as 4.11%, 3.28%, 1.67%, 0.54% and 0.15% respectively. Along with the progress of the cervical lesions, the morbidity decreased. (3) The morbidity rates of CIN in different occupations were different, with the highest of HSIL in service occupation and the lowest in teachers. Women of different occupations in Shenzhen city had different high risk HPV infection rates and CIN morbidity. The HPV infection rate and HSIL morbidity were highest among women having service related jobs.

Calibration schemes of a field-compatible optical spectroscopic system to quantify neovascular changes in the dysplastic cervix

NASA Astrophysics Data System (ADS)

Chang, Vivide Tuan-Chyan; Merisier, Delson; Yu, Bing; Walmer, David K.; Ramanujam, Nirmala

2011-03-01

A significant challenge in detecting cervical pre-cancer in low-resource settings is the lack of effective screening facilities and trained personnel to detect the disease before it is advanced. Light based technologies, particularly quantitative optical spectroscopy, have the potential to provide an effective, low cost, and portable solution for cervical pre-cancer screening in these communities. We have developed and characterized a portable USB-powered optical spectroscopic system to quantify total hemoglobin content, hemoglobin saturation, and reduced scattering coefficient of cervical tissue in vivo. The system consists of a high-power LED as light source, a bifurcated fiber optic assembly, and two USB spectrometers for sample and calibration spectra acquisitions. The system was subsequently tested in Leogane, Haiti, where diffuse reflectance spectra from 33 colposcopically normal sites in 21 patients were acquired. Two different calibration methods, i.e., a post-study diffuse reflectance standard measurement and a real time self-calibration channel were studied. Our results suggest that a self-calibration channel enabled more accurate extraction of scattering contrast through simultaneous real-time correction of intensity drifts in the system. A self-calibration system also minimizes operator bias and required training. Hence, future contact spectroscopy or imaging systems should incorporate a selfcalibration channel to reliably extract scattering contrast.

Dose-ranging phase 1 study of TMC120, a promising vaginal microbicide, in HIV-negative and HIV-positive female volunteers.

PubMed

Jespers, Vicky A; Van Roey, Jens M; Beets, Greet I; Buvé, Anne M

2007-02-01

To evaluate the short-term safety, tolerability, and systemic exposure of a vaginal microbicide gel containing the nonnucleoside reverse transcriptase inhibitor TMC120. Randomized, controlled, double-blind, phase 1 trial of a gel containing 3 different concentrations of TMC120 versus placebo. Of the 48 HIV-negative and 16 HIV-positive women enrolled, 52 women received active product. Participants applied the gel twice daily for 7 days and were assessed on 6 occasions. Colposcopic evaluation was performed before and after first gel application and on day 8. Laboratory safety assessments were carried out on all visits except day 7. Plasma levels of TMC120 were measured on days 1 and 7. All TMC120 concentrations were well tolerated, and there were no apparent differences in safety parameters. Four women (6%) had treatment-emergent mild cervical findings (petechiae in 3 women and erythema in 1 woman) of <5 mm. Plasma levels of TMC120 were quantifiable on day 1 in 7 (13%) participants and on day 7 in 39 (75%) participants using TMC120 gel. The TMC120 vaginal gel was well-tolerated in this short study by HIV-negative and HIV-positive women. The implications of the absorption of TMC120 should be studied further in expanded safety and effectiveness trials.

Application of PDT for Uterine Cervical Cancer

PubMed Central

Kawasaki, K.; Suehiro, Y.; Kunugi, T.; Umayahara, K.; Akiya, T.; Iwabuchi, H.; Sakunaga, H.; Sakamoto, M.; Sugishita, T.; Tenjin, Y.

1999-01-01

We have been performing PDT using Excimer Dye Laser (EDL) or YAG-OPO laser, a type of low power laser, both of which have a considerably higher degree of tissue penetration even when compared to PDT using Argon Dye Laser (ADL). PDT is a relatively simple procedure without any bleeding and does not require anesthesia since it causes no pain. PDT is performed 48 h after intravenous injection of 1.5–2.0 mg/kg of PHE (Photofrin®). Precise spot irradiation is possible using a colposcope with an optical laser path. We also use a cervical probe which enables photoirradiation of the entire cervical canal. We have performed PDT on 131 cases (95 CIS, 31 dysplasia, 1 vulval dysplasia (VIN), 3 squamous cell carcinoma, microinvasion, and 1 CIS + endocervical adenocarcinoma, microinvasion). Of these cases, 127 became CR (96.9%). The first CR case was 10 years ago and no recurrence has been observed yet. PDT is extremely effective to preserve fertility. Except for sensitive reactions to sunlight, there are no noticeable side effects or difficulties related to pregnancy or delivery. We expect that in the near future PDT will be performed using diode lasers and without hospitalization due to new photosensitizers which have shorter retention times. PMID:18493501

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.

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.

Complementary use of optical coherence tomography and 5-aminolevulinic acid induced fluorescent spectroscopy for diagnosis of neoplastic processes in cervix and vulva

NASA Astrophysics Data System (ADS)

Sapozhnikova, Veronika V.; Shakhova, Natalia M.; Kamensky, Vladislav A.; Kuranov, Roman V.; Loshenov, Victor B.; Petrova, Svetlana A.

2003-07-01

A new approach to improving the diagnostic value of optical methods is suggested, which is based on a complementary investigation of different optical parameters of biotissues. The aim of this paper is comparative study of the feasibility of two optical methods - fluorescence spectroscopy and optical coherence tomography - for visualization of borders of neoplastic processes in the uterine cervix and vulva. Fluorescence spectroscopy is based on the detection of biochemical and optical coherence tomography on backscattering properties in norm and pathological changes of tissues. By means of these optical methods changes in biochemical and morphological properties of tissues were investigated. A parallel analysis of these two optical methods and histology from the center of tumors and their optical borders was made. Thirteen female patients with neoplastic changes in uterine cervix and vulva were enrolled in this study. The borders of the tumor determined by optical methods (fluorescence spectroscopy and optical coherence tomography) are coinciding with the biopsy proved ones. In addition, OCT and fluorescence borders of tumor in the uterine cervix and vulva exceeds colposcopically detectable borders, the averaging difference 2 mm. In future optical methods would considerably enhance diagnostic accuracy of conventional methods used in oncogynecology.

Variation of fluorescence spectroscopy during the menstrual cycle

NASA Astrophysics Data System (ADS)

Macaulay, Calum; Richards-Kortum, Rebecca; Utzinger, Urs; Fedyk, Amanda; Neely Atkinson, E.; Cox, Dennis; Follen, Michele

2002-06-01

Cervical autofluorescence has been demonstrated to have potential for real-time diagnosis. Inter-patient and intra-patient variations in fluorescence intensity have been measured. Inter-patient measurements may vary by a factor of ten, while intra-patient measurements may vary by a factor of two. Age and menopausal status have been demonstrated to account for some of the variations, while race and smoking have not. In order to explore in detail the role of the menstrual cycle in intra-patient variation, a study was designed to measure fluorescence excitation emission matrices (EEMs) in patients daily throughout one cycle. Ten patients with a history of normal menstrual cycles and normal Papanicolaou smears underwent daily measurements of fluorescence EEMs from three colposcopically normal sites throughout one menstrual cycle. Changes in signals from porphyrin, NADH, and FAD fluorescence and blood absorption were noted when the data was viewed in a graphical format. Visually interpreted features of the EEMs in this graphical format did not appear to correlate with the day of the menstrual cycle with the exception that blood absorption features were more prominent during the menstrual phase (during which bleeding occurs), suggesting that measurements during the menstrual phase should be avoided. Variations in cycle date likely do not account for inter- or intra-patient variations.

Cervical neoplasia and human papilloma virus infection in prostitutes.

PubMed

Gitsch, G; Kainz, C; Reinthaller, A; Kopp, W; Tatra, G; Breitenecker, G

1991-12-01

To evaluate the prevalence and incidence of PAP smears indicating cervical dysplasia as well as human papillomavirus (HPV) infection in prostitutes. Prevalence and incidence study of cervical dysplasia and HPV infection in prostitutes. For detection and typing of HPV-DNA In Situ Hybridisation (ISH) was performed in tissue samples with CIN gained by colposcopically directed punch biopsies. Second Department of Obstetrics and Gynecology, University of Vienna Medical School and STD Clinic of the Public Health Office, Vienna. Registered prostitutes attending the STD Clinic of the Public Health Office and a control group. 978 prostitutes and 5493 women with unknown cytological anamnesis were compared. Frequency of positive PAP smears was significantly higher in prostitutes (6.13% versus 1.43%). To determine the pick-up rate of cervical dysplasia during one year after negative cytology we compared 722 prostitutes and 3162 controls. Prostitutes showed a significant higher dysplasia pick-up rate (3.05% to 1.07%) compared with controls. HPV detection rate in prostitutes was similar to that in the control group. The distribution of HPV types revealed a higher frequency of "high risk" HPV 16/18 and 31/33 in prostitutes. The results demonstrate a higher incidence and prevalence of cervical dysplasia in prostitutes and therefore suggest regular cervical PAP smear screening in registered prostitutes twice a year.

Heat shock fusion protein-based immunotherapy for treatment of cervical intraepithelial neoplasia III

PubMed Central

Einstein, Mark H.; Kadish, Anna S.; Burk, Robert D.; Kim, Mimi Y.; Wadler, Scott; Streicher, Howard; Goldberg, Gary L.; Runowicz, Carolyn D.

2007-01-01

Objectives SGN-00101 (HspE7, Nventa, San Diego, CA) is a novel therapeutic vaccine consisting of a fusion protein containing an M. bovis BCG heat shock protein (Hsp65) covalently linked to the entire sequence of HPV 16 E7. This trial was designed to evaluate the efficacy and toxicities of HspE7 in women with CIN III. Methods HIV (−) women with biopsy-proven CIN III were eligible. Two cohorts were accrued; one cohort to establish efficacy and a second cohort with a longer follow-up period to improve the precision of the trial to estimate response rates. Each patient underwent 3 monthly subcutaneous vaccinations with 500 µg of HspE7 followed by monthly colposcopic follow-up for 1 month in cohort 1 and an extended observation period (2 months) in cohort 2. All patients then underwent a LEEP or cone biopsy of the cervix. A complete pathologic response (pCR) was defined as no evidence of CIN or CIN I (only HPV changes). A partial response (PR) was defined as colposcopic lesion regression of >50% in size. Cervicovaginal lavage samples were obtained at each visit for HPV typing using MY09/ MY11 HPV PCR. Results Seventy-two patients were registered and screened, of whom 64 were eligible. Fifty-eight patients completed the trial and were evaluable (31 in cohort 1, 27 in cohort 2). There were no significant epidemiologic or HPV type differences between the 2 cohorts so responses were combined for analysis. Of the 58 evaluable patients, 13 (22.5%) had a pCR; 32 (55%) had a PR and 11 (19%) had stable disease. Two (3.5%) patients in cohort 2 had microinvasive disease and were defined as progressive disease. Thirty-three of 58 (57%) of the patients were infected with HPV 16 prior to vaccination or in subsequent visits. There was no significant difference in regression in women infected with HPV 16 compared to those without HPV 16 infection (88% vs. 70%; p=0.12). Women who had a previous LEEP or ablation for CIN were 2.7 times more likely to have a complete response compared to patients without previous treatment, although the difference was not statistically significant (95% CI for rate ratio: 0.95–6.19, p=0.10). At a cellular level, there was a significant association between local inflammation and response; lower grade of lesional inflammation correlated with a response to HspE7 (p=0.04 using Wilcoxon rank sum test). Conclusions HspE7 appeared to demonstrate activity in women with CIN III and met a priori assumptions for efficacy; however, it is unclear whether this response was due to natural regression rather than treatment effect. HspE7, which targets the HPV 16 E7 oncoprotein, had efficacy in patients infected with HPV types other than 16, suggesting cross-reactivity. A larger randomized, controlled trial is needed to better define efficacy and to identify subsets of women most likely to benefit from immunotherapy. PMID:17586030

[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.

Human Papillomavirus Testing in the Prevention of Cervical Cancer

PubMed Central

Wentzensen, Nicolas; Wacholder, Sholom; Kinney, Walter; Gage, Julia C.; Castle, Philip E.

2011-01-01

Strong evidence now supports the adoption of cervical cancer prevention strategies that explicitly focus on persistent infection with the causal agent, human papillomavirus (HPV). To inform an evidence-based transition to a new public health approach for cervical cancer screening, we summarize the natural history and cervical carcinogenicity of HPV and discuss the promise and uncertainties of currently available screening methods. New HPV infections acquired at any age are virtually always benign, but persistent infections with one of approximately 12 carcinogenic HPV types explain virtually all cases of cervical cancer. In the absence of an overtly persistent HPV infection, the risk of cervical cancer is extremely low. Thus, HPV test results predict the risk of cervical cancer and its precursors (cervical intraepithelial neoplasia grade 3) better and longer than cytological or colposcopic abnormalities, which are signs of HPV infection. The logical and inevitable move to HPV-based cervical cancer prevention strategies will require longer screening intervals that will disrupt current gynecologic and cytology laboratory practices built on frequent screening. A major challenge will be implementing programs that do not overtreat HPV-positive women who do not have obvious long-term persistence of HPV or treatable lesions at the time of initial evaluation. The greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment. PMID:21282563

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.

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

High-resolution anoscopy: Unchartered territory for gastroenterologists?

PubMed

Albuquerque, Andreia

2015-09-25

High-resolution anoscopy (HRA) is a procedure where patients with an increased risk of anal cancer, like men who have sex with men, human immunodeficiency virus infected individuals, transplant patients and women with a history of lower genital tract neoplasia, with abnormal anal cytology results, are submitted to anal and perianal visualization under magnification. This will allow for a better detection of anal high-grade lesions that can be treated, in an effort to prevent anal cancer. Anal cancer screening follows the same principles that cervical cancer screening. During this procedure, an anoscope is inserted and a colposcope is used to examine systematically the squamocolumnar junction, the transformation zone and the perianal skin. Initially the observation is done with no staining and then with the application of acetic acid and Lugol's iodine solution, allowing for better lesion identification and characterization. Any suspicious lesion seen should be carefully evaluated and biopsied. Without HRA only a small percentage of suspicious lesions are identified. High-grade lesions that are detected can be ablated under HRA. This is a challenging exam to perform, with a long learning curve and the number of clinicians performing it is limited, although the growing number of patients that need to been screened. Specific equipment is required, with these patients ideally been followed by a multidisciplinary team, in a reference centre. HRA remains unfamiliar for many gastroenterologists.

Possible non-sexual modes of transmission of human papilloma virus.

PubMed

Sabeena, Sasidharanpillai; Bhat, Parvati; Kamath, Veena; Arunkumar, Govindakarnavar

2017-03-01

There is strong evidence to suggest vertical and horizontal modes of transmission of human papilloma virus (HPV), an established etiologic agent of cervical cancer. Infants, children, and adults can acquire both high-risk and low-risk infections by birth or by close contact even though HPV is mainly transmitted sexually. A thorough review of the literature was performed to assess the possible non-sexual modes of transmission of HPV. An electronic search of databases for review articles, cross-sectional studies, cohort studies, and case reports on non-sexual modes of transmission among sexually unexposed women and children was carried out using search terms such as "human papilloma virus, HPV, transmission, horizontal transmission, vertical transmission, and fomites". Articles published between 1983 and 2015 were retrieved. Epidemiological and clinical data support various non-sexual modes of transmission especially at the time of birth and by close contact. Even though the role of fomites in the transmission of HPV is not well established, HPV-DNA positivity has been reported in transvaginal ultrasound probes and colposcopes after routine disinfection. Awareness needs to be spread among the public about alternate modes of transmission. For a proper understanding of the exact natural history of HPV infection acquired via the non-sexual route, long-term prospective studies need to be undertaken. © 2017 Japan Society of Obstetrics and Gynecology.

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.

In vivo diagnosis of cervical precancer using Raman spectroscopy and genetic algorithm techniques.

PubMed

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

2011-10-21

This study aimed to evaluate the clinical utility of applying near-infrared (NIR) Raman spectroscopy and genetic algorithm-partial least squares-discriminant analysis (GA-PLS-DA) to identify biomolecular changes of cervical tissues associated with dysplastic transformation during colposcopic examination. A total of 105 in vivo Raman spectra were measured from 57 cervical sites (35 normal and 22 precancer sites) of 29 patients recruited, in which 65 spectra were from normal sites, while 40 spectra were from cervical precancerous lesions (i.e., 7 low-grade CIN and 33 high-grade CIN). The GA feature selection technique incorporated with PLS was utilized to study the significant biochemical Raman bands for differentiation between normal and precancer cervical tissues. The GA-PLS-DA algorithm with double cross-validation (dCV) identified seven diagnostically significant Raman bands in the ranges of 925-935, 979-999, 1080-1090, 1240-1260, 1320-1340, 1400-1420, and 1625-1645 cm(-1) related to proteins, nucleic acids and lipids in tissue, and yielded a diagnostic accuracy of 82.9% (sensitivity of 72.5% (29/40) and specificity of 89.2% (58/65)) for precancer detection. The results of this exploratory study suggest that Raman spectroscopy in conjunction with GA-PLS-DA and dCV methods has the potential to provide clinically significant discrimination between normal and precancer cervical tissues at the molecular level.

Time from cervical conization to pregnancy and preterm birth.

PubMed

Himes, Katherine P; Simhan, Hyagriv N

2007-02-01

To estimate whether the time interval between cervical conization and subsequent pregnancy is associated with risk of preterm birth. Our study is a case control study nested in a retrospective cohort. Women who underwent colposcopic biopsy or conization with loop electrosurgical excision procedure, large loop excision of the transformation zone, or cold knife cone and subsequently delivered at our hospital were identified with electronic databases. Variables considered as possible confounders included maternal race, age, marital status, payor status, years of education, self-reported tobacco use, history of preterm delivery, and dimensions of cone specimen. Conization was not associated with preterm birth or any subtypes of preterm birth. Among women who underwent conization, those with a subsequent preterm birth had a shorter conization-to-pregnancy interval (337 days) than women with a subsequent term birth (581 days) (P=.004). The association between short conization-to-pregnancy interval and preterm birth remained significant when controlling for confounders including race and cone dimensions. The effect of short conization-to-pregnancy interval on subsequent preterm birth was more persistent among African Americans when compared with white women. Women with a short conization-to-pregnancy interval are at increased risk for preterm birth. Women of reproductive age who must have a conization procedure can be counseled that conceiving within 2 to 3 months of the procedure may be associated with an increased risk of preterm birth. II.

Safety and pharmacokinetics of dapivirine delivery from matrix and reservoir intravaginal rings to HIV-negative women.

PubMed

Nel, Annalene; Smythe, Shanique; Young, Katherine; Malcolm, Karl; McCoy, Clare; Rosenberg, Zeda; Romano, Joseph

2009-08-01

Vaginal microbicides for the prevention of HIV transmission may be an important option for protecting women from infection. Incorporation of dapivirine, a lead candidate nonnucleoside reverse transcriptase inhibitor, into intravaginal rings (IVRs) for sustained mucosal delivery may increase microbicide product adherence and efficacy compared with conventional vaginal formulations. Twenty-four healthy HIV-negative women 18-35 years of age were randomly assigned (1:1:1) to dapivirine matrix IVR, dapivirine reservoir IVR, or placebo IVR. Dapivirine concentrations were measured in plasma and vaginal fluid samples collected at sequential time points over the 33-day study period (28 days of IVR use, 5 days of follow-up). Safety was assessed by pelvic/colposcopic examinations, clinical laboratory tests, and adverse events. Both IVR types were safe and well tolerated with similar adverse events observed in the placebo and dapivirine groups. Dapivirine from both IVR types was successfully distributed throughout the lower genital tract at concentrations over 4 logs greater than the EC50 against wild-type HIV-1 (LAI) in MT4 cells. Maximum concentration (Cmax) and area under the concentration-time curve (AUC) values were significantly higher with the matrix than reservoir IVR. Mean plasma concentrations of dapivirine were <2 ng/mL. These findings suggest that IVR delivery of microbicides is a viable option meriting further study.

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.

The effect of "breathable" panty liners on the female lower genital tract.

PubMed

Giraldo, Paulo C; Amaral, Rose L G; Juliato, Cássia; Eleutério, José; Brolazo, Eliane; Gonçalves, Ana K S

2011-10-01

To evaluate whether the use of "breathable" panty liners (BPLs) alters the normal vaginal flora, increases the incidence of bacterial vaginosis and/or vaginal candidiasis, or causes vulvar irritation. A randomized controlled trial assessed the vaginal ecosystem of women without complaints of vaginal discharge. The study group (n=53) wore BPLs for 10-12 hours each day for 75 consecutive days, whereas the control group (n=54) wore only their usual underwear. At each of 6 visits during 3 menstrual cycles, participants underwent gynecologic examination with colposcopic evaluation and pH measurement, in addition to assessment of vaginal microbial flora, intensity of inflammatory processes, and presence of vaginal candidiasis/bacterial vaginosis in Gram-stained smears. After 75 consecutive days of BPL use, 40/44 (90.9%) and 42/44 (95.5%) women reported no complaints of vaginal discharge or vulvar itching/burning, respectively. There was no significant difference between the study group and the control group with regard to positive vaginal fungus cultures (5/44 [11.4%] vs 8/50 [16.0%]; P=0.7848) or bacterial vaginosis (3/44 [6.8%] vs 2/50 [4.0%]; P=0.7974) at the end of the study period. After 75 days of BPL use, there was no significant increase in vulvovaginal candidiasis, bacterial vaginosis, vulvovaginal irritation, or vulvovaginal inflammation. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Micronuclei as biomarkers for evaluating the risk of malignant transformation in the uterine cervix.

PubMed

Aires, G M A; Meireles, J R C; Oliveira, P C; Oliveira, J L; Araújo, E L; Pires, B C; Cruz, E S A; Jesus, N F; Pereira, C A B; Cerqueira, E M M

2011-01-01

We evaluated micronucleus and apoptosis occurrence among women with normal smears and women with different kinds of cervical abnormalities, i.e., inflammatory processes and low- and high-grade squamous intraepithelial lesions (N = 12, N = 10 and N = 27, respectively). The sample included 59 women who were seen at a public medical service for cervical cancer prevention in Feira de Santana, Bahia, Brazil. The diagnosis was established by means of cytological, colposcopic, and histopathological examination. Cytogenetic analysis was performed on 2000 cells from each woman and included assessment of micronuclei and nuclear degenerative abnormalities indicative of apoptosis (karyorrhexis, pyknosis and condensed chromatin). Micronucleus frequency was significantly higher in the women with high-grade squamous intraepithelial lesions than in the women without cervical abnormalities or inflammatory processes (P< 0.001) or in the women with low-grade squamous intraepithelial lesions (P < 0.005). The frequency of apoptosis was similar in women without cervical abnormalities and women showing high-grade squamous intraepithelial lesions (P > 0.50), and significantly lower in women without cervical abnormalities and in women showing high-grade squamous intraepithelial lesions than in women showing inflammatory processes or low-grade squamous intraepithelial lesions (P < 0.0001). These results indicate that, in addition to Papanicolaou cervical cytological analysis, it would be useful to use micronucleus analysis to screen women who are at risk of developing cervical cancer. The assessment of nuclear degenerative abnormalities indicative of apoptosis increased the sensitivity of this test.

[The Development of First Operating Microscopes from Zeiss Jena and Oberkochen to Series Production].

PubMed

Gudziol, H; Gottschall, R; Luther, E

2017-01-01

Introduction: The history of the first operating microscopes from Zeiss is often confusing, not painstaking and partly contradictory because of the parallel development of Zeiss Jena (East Germany) and Zeiss Oberkochen (West Germany). Methods: To investigate the early beginnings of the construction of the operating microscopes documents of the Carl Zeiss Archive and the Optical Museum in Jena, the memoirs of Prof. Dr. Rosemarie Albrecht and some relevant publications were used. Results: The development of the first Jena operating microscope was initiated in 1949 by the ENT-physician Prof. Dr. Rosemarie Albrecht in the Soviet occupation zone. The first prototype was tested in the University ENT Clinic, Jena since summer of 1950. On the Leipzig Trade Fair in autumn 1952 the VEB Optik Carl Zeiss Jena presented the first operating microscope nationally and internationally. Series production began in 1953. The first operating microscope of Zeiss Oberkochen was primarily developed by technical designers (H. Littmann) as a colposcope. But in the Carl Zeiss Archive no documents could be found related to the cooperation with gynecologists. 1953 the operating microscope (OPMI 1) came into public and its series production started. From this date on, it was adopted by the otologist Prof. Dr. Horst Ludwig Wullstein to the needs of Otorhinolaryngology. Conclusion: The first Zeiss operating microscope came from Jena. The operating microscope from Zeiss Oberkochen had some advantages for the surgeons and won the competition in the future. © Georg Thieme Verlag KG Stuttgart · New York.

Assessing exploitation experiences of girls and boys seen at a Child Advocacy Center

PubMed Central

Edinburgh, Laurel; Pape-Blabolil, Julie; Harpin, Scott B.; Saewyc, Elizabeth

2015-01-01

The primary aim of this study was to describe the abuse experiences of sexually exploited runaway adolescents seen at a Child Advocacy Center (N = 62). We also sought to identify risk behaviors, attributes of resiliency, laboratory results for sexually transmitted infection (STI) screens, and genital injuries from colposcopic exams. We used retrospective mixed-methods with in-depth forensic interviews, together with self-report survey responses, physical exams and chart data. Forensic interviews were analyzed using interpretive description analytical methods along domains of experience and meaning of sexual exploitation events. Univariate descriptive statistics characterized trauma responses and health risks. The first sexual exploitation events for many victims occurred as part of seemingly random encounters with procurers. Older adolescent or adult women recruited some youth working for a pimp. However, half the youth did not report a trafficker involved in setting up their exchange of sex for money, substances, or other types of consideration. 78% scored positive on the UCLA PTSD tool; 57% reported DSM IV criteria for problem substance use; 71% reported cutting behaviors, 75% suicidal ideation, and 50% had attempted suicide. Contrary to common depictions, youth may be solicited relatively quickly as runaways, yet exploitation is not always linked to having a pimp. Avoidant coping does not appear effective, as most patients exhibited significant symptoms of trauma. Awareness of variations in youth’s sexual exploitation experiences may help researchers and clinicians understand potential differences in sequelae, design effective treatment plans, and develop community prevention programs. PMID:25982287

ThinPrep Pap-smear and cervical intraepithelial neoplasia in reproductive-aged Thai women.

PubMed

Rugpao, S; Koonlertkit, S; Ruengkrist, T; Lamlertkittikul, S; Pinjaroen, S; Limtrakul, A; Werawatakul, Y; Sinchai, W

2009-06-01

To estimate the incidence of abnormal cervical cytology by ThinPrep Pap-tests and cervical intraepithelial neoplasia (CIN) in young adult reproductive-aged Thai women. A total of 1254 women distributed in all regions of Thailand were monitored from 2002 through 2004. Women were screened for abnormal cervical cytology using the ThinPrep method every 6 months. Interpretation of cervical cytology was based on the Bethesda system, version 2001. Women who had the ThinPrep Pap results as atypical squamous cells of undetermined significance or worse underwent colposcopic examination. The ThinPrep and all cervical tissue samples obtained from diagnostic or therapeutic procedures were analyzed and reviewed by Covance Central Laboratory Service, Inc., Indianapolis, USA. The cumulative incidence of abnormal ThinPrep Pap-tests was as follows: 15.3 per 100 woman years (WY) (95% confidence interval [CI] 12.3, 18.9) at 6 months; 12.3 per 100 WY (95% CI 10.3, 14.6) at 12 months; and 11.6 per 100 WY (95% CI 10.0, 13.5) at 18 months. Of 1448.6 woman years of follow up, the incidence of CIN1 was 4.1 per 100 WY (95% CI 3.2, 5.3); CIN2 0.8 per 100 WY (95% CI 0.4, 1.4); and CIN3 0.6 per 100 WY (95% CI 0.3, 1.2). The incidence of abnormal ThinPrep Pap-test and CIN in young adult Thai women had been reported. No comparable data is available.

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.

A case control study of nutritional factors and cervical dysplasia.

PubMed

Liu, T; Soong, S J; Wilson, N P; Craig, C B; Cole, P; Macaluso, M; Butterworth, C E

1993-01-01

The association of nutritional factors with cervical dysplasia was examined through a case-control study. Analysis was conducted in 257 cases and 133 controls confirmed both by cytological examination and colposcopic findings. A 24-h dietary recall questionnaire was used to assess nutritional intake. Various risk factors (including age at first intercourse, number of sexual partners, parity, cigarette smoking, oral contraceptive use, human papillomavirus type 16 infection, and age and race) were adjusted for their potential confounding effects. While analyses were also performed to adjust for total calories, results were not changed significantly. Among the nutrients examined, vitamin A intake showed a significantly increased risk at the lowest quartile compared to the highest quartile, with an odds ratio of 2.2 (95% confidence interval, 1.2-4.2). A significant trend of increasing risk was also observed with lower intake of vitamin A (P = 0.05). Riboflavin showed increased risk at the two lower quartiles of intake with a trend test P value of 0.04. Increased risk was also found for lower intakes of vitamin C compared to the highest intake level. For folate, increased risk was found in the second highest quartile compared with the highest quartile with an odds ratio of 2.0 (95% confidence interval, 1.0-3.8). The calcium:phosphorus ratio showed an increased risk at the lowest level (odds ratio, 2.0; 95% confidence interval, 1.0-4.3). Insufficient intake of vitamin A, riboflavin, ascorbate, and folate is associated with an increased risk of cervical dysplasia.

Assessing exploitation experiences of girls and boys seen at a Child Advocacy Center.

PubMed

Edinburgh, Laurel; Pape-Blabolil, Julie; Harpin, Scott B; Saewyc, Elizabeth

2015-08-01

The primary aim of this study was to describe the abuse experiences of sexually exploited runaway adolescents seen at a Child Advocacy Center (N=62). We also sought to identify risk behaviors, attributes of resiliency, laboratory results for sexually transmitted infection (STI) screens, and genital injuries from colposcopic exams. We used retrospective mixed-methods with in-depth forensic interviews, together with self-report survey responses, physical exams and chart data. Forensic interviews were analyzed using interpretive description analytical methods along domains of experience and meaning of sexual exploitation events. Univariate descriptive statistics characterized trauma responses and health risks. The first sexual exploitation events for many victims occurred as part of seemingly random encounters with procurers. Older adolescent or adult women recruited some youth working for a pimp. However, half the youth did not report a trafficker involved in setting up their exchange of sex for money, substances, or other types of consideration. 78% scored positive on the UCLA PTSD tool; 57% reported DSM IV criteria for problem substance use; 71% reported cutting behaviors, 75% suicidal ideation, and 50% had attempted suicide. Contrary to common depictions, youth may be solicited relatively quickly as runaways, yet exploitation is not always linked to having a pimp. Avoidant coping does not appear effective, as most patients exhibited significant symptoms of trauma. Awareness of variations in youth's sexual exploitation experiences may help researchers and clinicians understand potential differences in sequelae, design effective treatment plans, and develop community prevention programs. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Measurement and evaluation of digital cervicography programs in two cervical cancer screening camps in East Africa

NASA Astrophysics Data System (ADS)

Peterson, Curtis W.; Mink, Jonah; Levitz, David

2017-03-01

Cervical cancer disproportionately affects women living in low- and middle-income countries. To address this global crisis, many governments and NGOs have implemented community-based screening and treatment programs at outreach camps. Here, high volumes of patients are able to access care: screening and diagnosis followed by immediate treatment of precancerous lesions onsite. However, monitoring and evaluation (M&E) of these efforts presents challenges, since each event typically relies on a different health workforce, and refers patients to different facilities for follow up and advanced care. To address these challenges, a digital imaging intervention was deployed at several screening camps in East Africa. Trained nurses screened women using a connected low-cost mobile colposcope built around a smartphone. A decision support job aid was integrated into the app controlling the device, guiding nurses and recording their diagnosis and treatment decisions. Aggregating the data from the job aid allowed M&E of the screening camp in real-time. In this paper, the M&E data from 2 different screening camps in East Africa are compared. Additionally, screening camps are compared to stationary clinics. Differences in the patient screening times, treatment rates, and individual nurse statistics were all documented through the job aid allowing for much improved epidemiological information following outreach events thus enabling targeted program improvements and provider training. Reporting data from screening camps were also shared online via public web pages, facilitating broader dissemination of health needs in specific East African communities, and sparking conversations with regional stakeholders about local disease burden.

Clinical significance of hTERC gene amplification detection by FISH in the screening of cervical lesions.

PubMed

Zhang, Yuan; Wang, Xiaobei; Ma, Ling; Wang, Zehua; Hu, Lihua

2009-06-01

This study evaluated the clinical significance of hTERC gene amplification detection by fluorescence in situ hybridization (FISH) in the screening of cervical lesions. Cervical specimens of 50 high risk patients were detected by thin liquid-based cytology. The patients whose cytological results were classified as ASCUS or above were subjected to the subsequent colposcopic biopsies. Slides prepared from these 50 cervical specimens were analyzed for hTERC gene amplification using interphase FISH with the two-color hTERC probe. The results of the cytological analysis and those of subsequent biopsies, when available, were compared with the FISH-detected hTERC abnormalities. It was found that the positive rates of hTERC gene amplification in NILM, ASCUS, LSIL, HSIL, and SCC groups were 0.00, 28.57%, 57.14%, 100%, and 100%, respectively. The positive rates of hTERC gene amplification in HSIL and SCC groups were significantly higher than those in NILM, ASCUS and LSIL groups (all P<0.05). The mean percentages of cells with hTERC gene amplification in NILM, ASCUS, LSIL, HSIL, and SCC groups were 0.00, 10.50%, 36.00%, 79.00%, and 96.50%, respectively. Patients with HSIL or SCC cytological diagnoses had significantly higher mean percentages of cells with hTERC gene amplification than did patients with NILM, ASCUS or LSIL cytological diagnoses (all P<0.05). It was concluded that two-color interphase FISH could detect hTERC gene amplification to accurately distinguish HSIL and ISIL of cervical cells. It may be an adjunct to cytology screening, especially high-risk patients.

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.

Value-based medicine analysis on loop electrosurgical excision procedure and CO2 laser vaporization for the treatment of cervical intraepithelial neoplasia 2.

PubMed

Sun, Lu-lu; Cao, Dong-yan; Yang, Jia-xin; Bian, Mei-lu; Wei, Li-hui; Shen, Keng

2012-08-01

The best treatment option for cervical intraepithelial neoplasia 2 (CIN2) is controversial and there is a lack of studies in value-based medicine. This multicenter comparative study was undertaken to evaluate the effectiveness, cost-effectives and quality of life (QOL) of loop electrosurgical excision procedure (LEEP) and CO(2) laser vaporization for the treatment of CIN2. A database of LEEP and laser vaporizations performed at three research centers was created. Patients with colposcopic-histopathologically confirmed CIN2 were randomly submitted to LEEP and laser vaporization. Cytology, human papilloma virus (HPV) DNA test and histology were performed, and a questionnaire on QOL was filled out during follow-up. Effectiveness, cost-effectives and QOL were analyzed. Three hundred and thirty-eight women with CIN2 were included in the study. Frequencies of remission, and persistent and recurrent CIN were 89.2%, 7.2%, and 3.6% for LEEP, and 86.7%, 12.6%, 0.70% for laser, respectively. There was no significant difference in remission and persistence of CIN. There was a significant difference in the number of operations, recovery time and costs. Women treated with two methods showed relatively identical QOL. Both LEEP and CO(2) laser vaporization are effective and reliable treatments for CIN2, whereas cervical tissue can be obtained for histology by LEEP. Preoperative evaluation and postoperative follow-up are important. Gynecologists should pay attention to QOL of patients with CIN. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Comparison of human papillomavirus DNA tests, liquid-based cytology and conventional cytology for the early detection of cervix uteri cancer.

PubMed

Girianelli, Vania R; Thuler, Luiz Claudio S; Szklo, Moyses; Donato, Alexandre; Zardo, Lucilia M G; Lozana, José A; Almeida Neto, Olimpio F; Carvalho, Aurenice C L; Matos, Jorge H; Figueiredo, Valeska

2006-12-01

To compare the performance of human papillomavirus DNA tests (samples collected by a healthcare professional and self-collected) and liquid-based cytology with conventional cytology in the detection of cervix uteri cancer and its precursor lesions. A cross-sectional study was carried out in 1777 women living in poor communities in Rio de Janeiro State, Brazil. Eligibility criteria included ages 25-59 years and not having had a Papanicolau test within at least 3 years prior to the study. Cytology (conventional or liquid-based) and human papillomavirus DNA (collected by a healthcare professional or self-collected) tests were performed using samples collected in a single visit. Women with abnormalities in at least one test and a systematic sample of 70 women with negative test results were referred to a colposcopic examination. Test readings were double-masked, and the outcome of interest was high-grade squamous intraepithelial lesion or worse. The pathology report was used as the gold standard. The prevalence of high-grade squamous intraepithelial lesion or worse was 2.0%. Human papillomavirus DNA test collected by a health professional alone or combined with conventional cytology had the highest sensitivity (91.4 and 97.1%, respectively). The highest specificity was found for conventional cytology (91.6%) and for a human papillomavirus DNA test collected by a healthcare professional (90.2%). On the basis of only test performance, the use of human papillomavirus DNA tests, alone or combined with cytology, would seem to be recommended. Its population-wide implementation, however, is conditional on a cost-effectiveness analysis.

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.

Analyses of atypical glandular cells re-defined by the 2006 Bethesda System: histologic outcomes and clinical implication of follow-up management.

PubMed

Ulker, V; Numanoglu, C; Akyol, A; Kuru, O; Akbayir, O; Erim, A; Ongut, C

2013-01-01

To evaluate the histopathology and the long-term follow-up outcome of women who had atypical glandular cells on Pap smears. All women with atypical glandular cells (AGC) who underwent colposcopic and histopathologic evaluation between January 2005 and October 2010 were reviewed. Patient data were examined up to October 2012, allowing for at least two years of follow-up for all patients. Forty-four women with AGC Pap test underwent histologic follow-up during the study period. Overall, upon reclassification of smears, 35 (79.5%) cases were diagnosed with AGC "not otherwise specified" (NOS) and nine (20.5%) with AGC "favour neoplasia". Seven out of nine patients (77.7%) with AGC "favour neoplasia" had significant pathology. On the other hand, only 11 out of 35 cases (31.4%) with AGC "NOS" had significant pathology. Significant correlation was found between AGC "favour neoplasia" smears and a significant pathology (p: 0.01). Of the 44 patients, 18 (40.9%) had significant pathology. Eight patients (18.2%) had low grade cervical intraepithelial neoplasia (CIN 1), four (9%) had high-grade cervical intraepithelial neoplasia (CIN 2/3), one (2.2%) had microinvasive squamous cell carcinoma of uterine cervix, one (2.2%) had cervical adenocarcinoma in situ, one (2.2%) had cervical adenocarcinoma, one (2.2%) had endometrial adenocarcinoma, and two (4.5%) had endometrial hyperplasia. Reporting AGC in the population is clinically significant due to the high prevalence of underlying preinvasive and invasive diseases (40.9%). The subtypes of the AGC category are significant predictor of such lesions.

Phase 2a study assessing colonization efficiency, safety, and acceptability of Lactobacillus crispatus CTV-05 in women with bacterial vaginosis.

PubMed

Hemmerling, Anke; Harrison, William; Schroeder, Adrienne; Park, Jeanna; Korn, Abner; Shiboski, Stephen; Foster-Rosales, Anne; Cohen, Craig R

2010-12-01

Bacterial vaginosis (BV) is a common vaginal infection caused by a lack of endogenous lactobacilli and overgrowth of pathogens that frequently recurs following antibiotic treatment. A phase 2a study assessed colonization efficiency, safety, tolerability, and acceptability of Lactobacillus crispatus CTV-05 (LACTIN-V) administered by a vaginal applicator. Twenty-four women with BV were randomized in a 3:1 ratio of active product to placebo. Participants used LACTIN-V at 2 × 10 colony-forming units (cfu)/dose or placebo for 5 initial consecutive days, followed by a weekly application over 2 weeks. They returned for follow-up on Days 10 and 28. Sixty-one percent of the 18 women randomized to the LACTIN-V group were colonized with L. crispatus CTV-05 at Day 10 or Day 28. Among LACTIN-V users with complete adherence to the study regimen, 78% were colonized at Day 10 or Day 28. Of the 120 adverse events (AEs) that occurred, 108 (90%) and 12 (10%) were of mild and moderate severity, respectively. AEs were evenly distributed between the LACTIN-V and placebo group. Of the total AEs, 93 (78%) were genitourinary in origin. The most common genitourinary AEs included vaginal discharge (46%), abdominal pain (46%), dysuria (21%), pollakiuria (21%), vaginal odor (21%), and genital pruritus (17%). No grade 3 or 4 AEs or serious AEs occurred and no deep epithelial disruption was seen during colposcopic evaluation. The product was well tolerated and accepted. LACTIN-V colonized well, and was safe and acceptable in women treated for BV.

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.

Feasibility and accuracy evaluation of three human papillomavirus assays for FTA card-based sampling: a pilot study in cervical cancer screening.

PubMed

Wang, Shao-Ming; Hu, Shang-Ying; Chen, Wen; Chen, Feng; Zhao, Fang-Hui; He, Wei; Ma, Xin-Ming; Zhang, Yu-Qing; Wang, Jian; Sivasubramaniam, Priya; Qiao, You-Lin

2015-11-04

Liquid-state specimen carriers are inadequate for sample transportation in large-scale screening projects in low-resource settings, which necessitates the exploration of novel non-hazardous solid-state alternatives. Studies investigating the feasibility and accuracy of a solid-state human papillomavirus (HPV) sampling medium in combination with different down-stream HPV DNA assays for cervical cancer screening are needed. We collected two cervical specimens from 396 women, aged 25-65 years, who were enrolled in a cervical cancer screening trial. One sample was stored using DCM preservative solution and the other was applied to a Whatman Indicating FTA Elute® card (FTA card). All specimens were processed using three HPV testing methods, including Hybrid capture 2 (HC2), careHPV™, and Cobas®4800 tests. All the women underwent a rigorous colposcopic evaluation that included using a microbiopsy protocol. Compared to the liquid-based carrier, the FTA card demonstrated comparable sensitivity for detecting high grade Cervical Intraepithelial Neoplasia (CIN) using HC2 (91.7 %), careHPV™ (83.3 %), and Cobas®4800 (91.7 %) tests. Moreover, the FTA card showed a higher specificity compared to a liquid-based carrier for HC2 (79.5 % vs. 71.6 %, P = 0.015), comparable specificity for careHPV™ (78.1 % vs. 73.0 %, P > 0.05), but lower specificity for the Cobas®4800 test (62.4 % vs. 69.9 %, P = 0.032). Generally, the FTA card-based sampling medium's accuracy was comparable with that of liquid-based medium for the three HPV testing assays. FTA cards are a promising sample carrier for cervical cancer screening. With further optimization, it can be utilized for HPV testing in areas of varying economic development.

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.

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.

A Phase I Trial of a Human Papillomavirus (HPV) DNA Vaccine for HPV16+ Cervical Intraepithelial Neoplasia 2/3

PubMed Central

Trimble, Cornelia L.; Peng, Shiwen; Kos, Ferdynand; Gravitt, Patti; Viscidi, Raphael; Sugar, Elizabeth; Pardoll, Drew; Wu, TC

2010-01-01

Purpose: To evaluate the safety and immunogenicity of a therapeutic HPV16 DNA vaccine administered to women with HPV16+CIN2/3. Experimental Design: This phase I trial incorporated the standard ‘3+3” dose escalation design with an additional 6 patients allocated to the maximally tolerated dose (MTD). Healthy adult women with colposcopically-directed biopsy-proven HPV16+ CIN2/3 received three intramuscular (IM) vaccinations (0.5 mg, 1 mg, or 3mg) of a plasmid expressing a Sig-E7(detox)-HSP70 fusion protein on days 0, 28 and 56, and underwent standard therapeutic resection of the cervical squamocolumnar junction at day 105 (week 15). Safety and immunogenicity of the vaccine and histologic outcome based on resection at week 15 were assessed. Results: Fifteen patients were evaluable (3 each at 0.5 mg and 1mg, 9 at 3mg). The vaccine was well tolerated: most adverse events were mild transient injection-site discomfort; no dose-limiting toxicities were observed. Although HPVE7-specific T-cell responses to E7 detected by enzyme-linked immunospot assays (IFNγ) were of low frequency and magnitude, detectable increases in response subsequent to vaccination were identified in subjects in the second and third cohorts. Complete histologic regression occurred in 3/9 (33%, CI: 7%-70%)) individuals in the highest dose cohort, Although the difference is not significant, it is slightly higher than would be expected in an unvaccinated cohort (25%). Conclusions: This HPV16 DNA vaccine was safe and well tolerated. While it appears possible to elicit HPV-specific T cell responses in patients with established dysplastic lesions, other factors are likely to play a role in lesion regression. PMID:19118066

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.

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.

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.

The impact of bivalent HPV vaccine on cervical intraepithelial neoplasia by deprivation in Scotland: reducing the gap.

PubMed

Cameron, Ross L; Kavanagh, Kimberley; Cameron Watt, D; Robertson, Chris; Cuschieri, Kate; Ahmed, Syed; Pollock, Kevin G

2017-10-01

Cervical cancer disproportionately affects women from lower socioeconomic backgrounds. A human papillomavirus (HPV) vaccination programme was introduced in Scotland in 2008 with uptake being lower and inequitable in a catch-up cohort run for the first three years of the programme compared with the routine programme. The socioeconomic differences in vaccine uptake have the potential to further increase the inequality gap in regards to cervical disease. Vaccination status was linked to demographic, cytological and colposcopic data, which are routinely collected by the Scottish HPV surveillance system. Incidence rates and relative risk of cervical intraepithelial neoplasia (CIN) 1, 2 and 3 in unvaccinated and vaccinated women were stratified by birth year and deprivation status using Poisson regression. Women who received three doses of HPV vaccine have significantly decreased risk of CIN 1, 2 and 3. Vaccine effectiveness was greater in those women from the most deprived backgrounds against CIN 2 and 3 lesions. Compared with the most deprived, unvaccinated women, the relative risk of CIN 3 in fully vaccinated women in the same deprivation group was 0.29 (95% CI 0.2 to 0.43) compared with 0.62 (95% CI 0.4 to 0.97) in vaccinated women in the least-deprived group. The HPV vaccine is associated with significant reductions in both low-grade and high-grade CIN for all deprivation categories. However, the effect on high-grade disease was most profound in the most-deprived women. These data are welcoming and allay the concern that inequalities in cervical cancer may persist or increase following the introduction of the vaccine in Scotland. © 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.

HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA.

PubMed

Vidal, Adriana C; Smith, Jennifer S; Valea, Fidel; Bentley, Rex; Gradison, Maggie; Yarnall, Kimberly S H; Ford, Anne; Overcash, Francine; Grant, Kathy; Murphy, Susan K; Hoyo, Cathrine

2014-08-01

For poorly understood reasons, invasive cervical cancer (ICC) incidence and mortality rates are higher in women of African descent. Oncogenic human papillomavirus (HPV) genotypes distribution may vary between European American (EA) and African-American (AA) women and may contribute to differences in ICC incidence. The current study aimed at disentangling differences in HPV distribution among AA and EA women. Five-hundred and seventy-two women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV infections were detected using HPV linear array, and chi-squared tests and linear regression models were used to compare HPV genotypes across racial/ethnic groups by CIN status. Of the 572 participants, 494 (86 %) had detectable HPV; 245 (43 %) had no CIN lesion, 239 (42 %) had CIN1, and 88 (15 %) had CIN2/3. Seventy-three percent of all women were infected with multiple HPV genotypes. After adjusting for race, age, parity, income, oral contraception use, and current smoking, AAs were two times less likely to harbor HPV 16/18 (OR 0.48, 95 % CI 0.21-0.94, p = 0.03) when all women were considered. This association remained unchanged when only women with CIN2/3 lesions were examined (OR 0.22, 95 % CI 0.05-0.95, p = 0.04). The most frequent high-risk HPV genotypes detected among EAs were 16, 18, 56, 39, and 66, while HPV genotypes 33, 35, 45, 58, and 68 were the most frequent ones detected in AAs. Our data suggest that while HPV 16/18 are the most common genotypes among EA women with CIN, AAs may harbor different genotypes.

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.

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.

Evaluation of the performance of Human Papillomavirus testing in paired urine and clinician-collected cervical samples among women aged over 30 years in Bhutan.

PubMed

Tshomo, Ugyen; Franceschi, Silvia; Tshokey, Tshokey; Tobgay, Tashi; Baussano, Iacopo; Tenet, Vanessa; Snijders, Peter J F; Gheit, Tarik; Tommasino, Massimo; Vorsters, Alex; Clifford, Gary M

2017-04-08

Urine sampling may offer a less invasive solution than cervical sampling to test for human papillomavirus (HPV) for HPV vaccine impact monitoring. Paired samples of urine and exfoliated cervical cells were obtained for 89 women with history of high-risk (HR) HPV-positive normal cytology in Bhutan. Urine sampling protocol included self-collection of first-void urine immediately into a conservation medium and procedures to optimize DNA yield. Colposcopical abnormalities were biopsied. Two HPV assays were used: a multiplex type-specific PCR (E7-MPG) and a less analytically sensitive GP5+/6+ PCR followed by reverse line blot. HPV positivity for 21 types common to both assays was similar in urine and cells by E7-MPG (62.9% and 57.3%, respectively, p = 0.32) but lower in urine by GP5+/6+ (30.3% and 40.4%, p = 0.05). HPV6/11/16/18 positivity did not significantly differ between urine and cells by either assay. Sensitivity of urine (using cells as gold standard) to detect 21 HPV types was 80% and 58% for E7-MPG and GP5+/6+, respectively, with specificity 61% and 89%. HPV type distribution in urine and cells was similar, regardless of assay. The 5 detected CIN3+ were HR-HPV positive in cells by both assays, compared to 4 and 3 by E7-MPG and GP5+/6+, respectively, in urine samples. For the monitoring of vaccine impact, we demonstrate validity of a urine sampling protocol to obtain HPV prevalence data that are broadly comparable to that from cervical cells. However, detection of HPV in urine varies according to assay sensitivity, presumably because low level infections are frequent.

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).

Cryotherapy Reduces Progression of Cervical Intraepithelial Neoplasia Grade 1 in South African HIV-Infected Women: A Randomized, Controlled Trial.

PubMed

Firnhaber, Cynthia; Swarts, Avril; Goeieman, Bridgette; Rakhombe, Ntombi; Mulongo, Masangu; Williamson, Anna-Lise; Michelow, Pam; Ramotshela, Sibongile; Faesen, Mark; Levin, Simon; Wilkin, Timothy

2017-12-15

HIV-infected women are at an increased risk of cervical cancer, especially in resource-limited countries. Cervical cancer prevention strategies focus treating cervical high-grade squamous intraepithelial lesions (HSIL). The management of low-grade squamous intraepithelial lesions (LSIL) in HIV-infected women is unknown. HIV treatment clinic in Johannesburg, South Africa. We randomized HIV-infected women with histologic cervical LSIL to cervical cryotherapy vs. no treatment (standard of care). Cervical high-risk human papillomavirus testing (hrHPV) was performed at baseline. All women underwent cervical cytology and colposcopic biopsies 12 months after enrollment. The primary end point was HSIL on histology at month 12. Chi-square was used to compare arms. Overall, 220 HIV-infected women were randomized to cryotherapy (n = 112) or no treatment (n = 108). Median age was 38 years, 94% were receiving antiretroviral therapy; median CD4 was 499 cells per cubic millimeter, and 59% were hrHPV positive. Cryotherapy reduced progression to HSIL: 2/99 (2%) in the cryotherapy arm and 15/103 (15%) in the no treatment arm developed HSIL, 86% reduction (95% confidence interval: 41% to 97%; P = 0.002). Among 17 HSIL end points, 16 were hrHPV+ at baseline. When restricting the analysis to hrHPV+ women, HSIL occurred in 2/61 (3%) in the cryotherapy arm vs. 14/54 (26%) in the no treatment arm, 87% reduction (95% confidence interval: 47% to 97%; P = 0.0004). Participants in the cryotherapy arm experienced greater regression to normal histology and improved cytologic outcomes. Treatment of cervical LSIL with cryotherapy decreased progression to HSIL among HIV-infected women especially if hrHPV positive. These results support treatment of LSIL in human papillomavirus test-and-treat approaches for cervical cancer prevention in resource-constrained settings.

Early invasive (FIGO stage IA) carcinoma of the cervix: a clinico-pathologic study of 476 cases.

PubMed

Elliott, P.; Coppleson, M.; Russell, P.; Liouros, P.; Carter, J.; MacLeod, C.; Jones, M.

2000-01-01

The clinical and histologic features of 476 tumors fitting the 1995 FIGO definition of stage IA cervical cancer, treated at a Sydney tertiary referral hospital between 1953 and 1992, are reviewed. Five-year follow-up was complete with a median of 10 years. The diagnosis was increasingly made by histologic examination of colposcopically directed cone biopsy. The majority (88%) of tumors were squamous. The proportion of both younger women (3 mm. Treatment was surgical in 99% and was increasingly more conservative as the study progressed with no apparent increase in treatment failure. From 1973 treatment by cone biopsy rose from 6.5 to 35%, by radical hysterectomy fell from 51 to 21% and by lymphadenectomy from 53 to 26%. Only one of 115 patients treated by cone biopsy died. Positive lymph nodes were detected in 1.7% of 180 patients undergoing lymphadenectomy. There were 16 recurrences (3.4%); six vaginal with no cancer deaths, nine pelvic and one distant, with nine deaths and three new cancers (two deaths). Univariate analysis suggests that older age, glandular tumors and those invading 3 mm were associated with more treatment failures and multivariate analysis showed that both conservative hysterectomy and the omission of lymphadenectomy are associated with higher recurrence rates with >3 mm invasion. The study failed to resolve the dilemma of predicting those tumors with a poor prognosis.

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.

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.

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.

[Use of the CO2 laser in the treatment of pathologic changes in the vulva, vagina and uterine cervix].

PubMed

Stanimirović, B; Zivanović, Z; Popović-Lazić, J

1990-01-01

In the period from April 1987 to April 1990, 230 patients with pathological changes of the vulva, vagina and cervix uteri were treated with the CO2-laser. The diagnosis and pretreatment stages of the diseases were confirmed by the cytodiagnostic, colposcopic and histopathological results of the biophysics. In most cases, DNA-hybridization of human papilloma viruses confirmed their virus etiology. Twenty patients had peak condyloma of the vulva and vagina, 34 had benign cervical diseases, 65 were at the premalignant and 111 in the first stages of malignant cervical disease. Vaporizations, conical or cylindrical excisions were performed depending on the nature of disease and its localisation. The average age of operated patients was 30.6 years and the average parity 0.69. Operations were performed using analgesia and in rare cases total anesthesia. After the excision treatment, the tissue was checked histo-pathologically according to the principle of series. The complications were very rare. After operation, postoperative control was performed after 3.9 and 15 months, and later once a year. The results have shown that one treatment was sufficient in 80% of patients for curing vulvar and vaginal disease and 20% patients needed repeat because of the condyloma that relapsed. After the first treatment, benign and premalignant cervical diseases were cured in 100% of cases. In 95.4% operated patients at the first stages of cervical malignant diseases, the excisional treatment was final and in 4.6% needed an additional radical therapy because of a higher stage of lesion found by the conular histo-pathological analysis. There were no relapses relating to the cervix.

Safety, tolerability, and systemic absorption of dapivirine vaginal microbicide gel in healthy, HIV-negative women.

PubMed

Nel, Annalene M; Coplan, Paul; van de Wijgert, Janneke H; Kapiga, Saidi H; von Mollendorf, Claire; Geubbels, Eveline; Vyankandondera, Joseph; Rees, Helen V; Masenga, Gileard; Kiwelu, Ireen; Moyes, Jocelyn; Smythe, Shanique C

2009-07-31

To assess the local and systemic safety of dapivirine vaginal gel vs. placebo gel as well as the systemic absorption of dapivirine in healthy, HIV-negative women. Two prospective, randomized, double-blind, placebo-controlled phase I/II studies were conducted at five research centers, four in Africa and one in Belgium. A total of 119 women used dapivirine gel (concentrations of 0.001, 0.002, 0.005, or 0.02%), and 28 used placebo gel twice daily for 42 days. The primary endpoints were colposcopic findings, adverse events, Division of AIDS grade 3 or grade 4 laboratory values, and plasma levels of dapivirine. Safety data were similar for the dapivirine and placebo gels. None of the adverse events with incidence more than 5% occurred with greater frequency in the dapivirine than placebo groups. Similar percentages of placebo and dapivirine gel users had adverse events that were considered by the investigator to be related to study gel. A total of five serious adverse events occurred in the two studies, and none was assessed as related to study gel. Mean plasma concentrations of dapivirine were approximately dose proportional, and, within each dose group, mean concentrations were similar on days 7, 28, and 42. The maximum observed mean concentration was 474 pg/ml in the 0.02% gel group on day 28. Two weeks after the final application of study gel, mean concentrations decreased to 5 pg/ml or less. Twice daily administration of dapivirine vaginal gel for 42 days was safe and well tolerated with low systemic absorption in healthy, HIV-negative women suggesting that continued development is warranted.

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.

High-risk oncogenic HPV genotype infection associates with increased immune activation and T cell exhaustion in ART-suppressed HIV-1-infected women

PubMed Central

Papasavvas, Emmanouil; Surrey, Lea F.; Glencross, Deborah K.; Azzoni, Livio; Joseph, Jocelin; Omar, Tanvier; Feldman, Michael D.; Williamson, Anna-Lise; Siminya, Maureen; Swarts, Avril; Yin, Xiangfan; Liu, Qin; Firnhaber, Cynthia; Montaner, Luis J.

2016-01-01

ABSTRACT Persistence of human papillomavirus (HPV) and cervical disease in the context of HIV co-infection can be influenced by introduction of antiretroviral therapy (ART) and sustained immune activation despite ART. We conducted a cross-sectional study in order to evaluate immune activation/exhaustion in ART-suppressed HIV+ women with or without high-risk (HR) HPV-related cervical intraepithelial neoplasia (CIN). 55 South African women were recruited in three groups: HR (-) (n = 16) and HR (+) (n = 15) HPV with negative cervical histopathology, and HR (+) HPV with CIN grade 1/2/3 (n = 24). Sampling included endocervical brushing (HPV DNA genotyping), Pap smear (cytology), colposcopic punch biopsy (histopathology, histochemical evaluation of immune cells), and peripheral blood (clinical assessment, flow cytometry-based immune subset characterization). Statistics were done using R2.5.1. Irrespective of the presence of CIN, HR (+) HPV women had higher circulating levels of T cells expressing markers of activation/exhaustion (CD38, PD1, CTLA-4, BTLA, CD160), Tregs, and myeloid subsets expressing corresponding ligands (PDL1, PDL2, CD86, CD40, HVEM) than HR (-) HPV women. A decrease in circulating NK cells was associated with CIN grade. CD4+ T cell count associated negatively with T cell exhaustion and expression of negative regulators on myeloid cells. Women with CIN when compared to HR (-) HPV women, had higher cervical cell density in stroma and epithelium for CD4+, CD68+, and CD11c+ cells, and only in stroma for CD8+ cells. We conclude that in ART-suppressed HIV-infected women with HPV co-infection the levels of T and myeloid cell activation/exhaustion are associated with the presence of HR HPV genotypes. PMID:27467943

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.

Rationale and Safety Assessment of a Novel Intravaginal Drug-Delivery System with Sustained DL-Lactic Acid Release, Intended for Long-Term Protection of the Vaginal Microbiome.

PubMed

Verstraelen, Hans; Vervaet, Chris; Remon, Jean-Paul

2016-01-01

Bacterial vaginosis is a prevalent state of dysbiosis of the vaginal microbiota with wide-ranging impact on human reproductive health. Based on recent insights in community ecology of the vaginal microbiome, we hypothesize that sustained vaginal DL-lactic acid enrichment will enhance the recruitment of lactobacilli, while counteracting bacterial vaginosis-associated bacteria. We therefore aimed to develop an intravaginal device that would be easy to insert and remove, while providing sustained DL-lactic acid release into the vaginal lumen. The final prototype selected is a vaginal ring matrix system consisting of a mixture of ethylene vinyl acetate and methacrylic acid-methyl methacrylate copolymer loaded with 150 mg DL-lactic acid with an L/D-lactic acid ratio of 1:1. Preclinical safety assessment was performed by use of the Slug Mucosal Irritation test, a non-vertebrate assay to evaluate vaginal mucosal irritation, which revealed no irritation. Clinical safety was evaluated in a phase I trial with six healthy nulliparous premenopausal volunteering women, with the investigational drug left in place for 7 days. Colposcopic monitoring according to the WHO/CONRAD guidelines for the evaluation of vaginal products, revealed no visible cervicovaginal mucosal changes. No adverse events related to the investigational product occurred. Total release from the intravaginal ring over 7 days was estimated through high performance liquid chromatography at 37.1 (standard deviation 0.9) mg DL-lactic acid. Semisolid lactic acid formulations have been studied to a limited extent in the past and typically consist of a large volume of excipients and very high doses of lactic acid, which is of major concern to mucosal safety. We have documented the feasability of enriching the vaginal environment with pure DL-lactic acid with a prototype intravaginal ring. Though the efficacy of this platform remains to be established possibly requiring further development, this approach may offer a novel avenue to modulate and protect the vaginal microbiota.

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

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.

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.

The Cellient automated cell block system is useful in the differential diagnosis of atypical glandular cells in Papanicolaou tests.

PubMed

Xing, Wei; Hou, April Y; Fischer, Andrew; Owens, Christopher L; Jiang, Zhong

2014-01-01

Atypical glandular cells (AGC) is a very important diagnosis in gynecological cytology. In the current study, the authors investigated the usefulness of Cellient cell blocks (CB) for characterizing AGC on Papanicolaou (Pap) tests. A total of 148 patients with an AGC diagnosis based on Pap tests by cytotechnologists and referred to cytopathologists were studied. Among these patients, there were 68 patients with CB preparations and 80 patients with Pap tests only (TP-AGC group). Follow-up results by Pap tests or biopsies were obtained in 117 of 148 patients. The median follow-up was 13 months (range, 1 month-36 months). Of the 68 patients with CBs, 31 (46%) were reclassified as negative for dysplasia or low-grade intraepithelial lesion; 30 patients (44%) retained a diagnosis of AGC (CB-AGC group); and 7 patients (10%) were given specific diagnoses of high-grade intraepithelial lesion (3 patients), endocervical adenocarcinoma in situ (1 patient), and invasive adenocarcinoma (3 patients). On follow-up, the CB-AGC group was found to have a significantly lower rate of negative/low-grade squamous intraepithelial lesion diagnoses compared with the TP-AGC group (55% vs 85%; P= .006). The CB-AGC group had a significantly higher rate of endocervical or endometrial adenocarcinoma compared with the TP-AGC group (36% vs 8%; P= .003) at the time of follow-up. The rates of high-grade squamous intraepithelial lesion were not found to be statistically different between these 2 groups (9% vs 7%; P= .66). The Cellient CB is a useful technique to further categorize a diagnosis of AGC on Pap tests. Using the Cellient CB system, the pathologist has the ability to improve the diagnostic accuracy of AGC so that unnecessary colposcopic evaluation or biopsies can be avoided. © 2013 American Cancer Society.

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.

A prospective study of risk-based colposcopy demonstrates improved detection of cervical precancers.

PubMed

Wentzensen, Nicolas; Walker, Joan; Smith, Katie; Gold, Michael A; Zuna, Rosemary; Massad, L Stewart; Liu, Angela; Silver, Michelle I; Dunn, S Terence; Schiffman, Mark

2018-06-01

Sensitivity for detection of precancers at colposcopy and reassurance provided by a negative colposcopy are in need of systematic study and improvement. We sought to evaluate whether selecting the appropriate women for multiple targeted cervical biopsies based on screening cytology, human papillomavirus testing, and colposcopic impression could improve accuracy and efficiency of cervical precancer detection. In all, 690 women aged 18-67 years referred to colposcopy subsequent to abnormal cervical cancer screening results were included in the study (ClinicalTrials.gov: NCT00339989). Up to 4 cervical biopsies were taken during colposcopy to evaluate the incremental benefit of multiple biopsies. Cervical cytology, human papillomavirus genotyping, and colposcopy impression were used to establish up to 24 different risk strata. Outcomes for the primary analysis were cervical precancers, which included p16 + cervical intraepithelial neoplasia 2 and all cervical intraepithelial neoplasia 3 that were detected by colposcopy-guided biopsy during the colposcopy visit. Later outcomes in women without cervical intraepithelial neoplasia 2 + at baseline were abstracted from electronic medical records. The risk of detecting precancer ranged from 2-82% across 24 strata based on colposcopy impression, cytology, and human papillomavirus genotyping. The risk of precancer in the lowest stratum increased only marginally with multiple biopsies. Women in the highest-risk strata had risks of precancer consistent with immediate treatment. In other risk strata, multiple biopsies substantially improved detection of cervical precancer. Among 361 women with cervical intraepithelial neoplasia <2 at baseline, 195 (54%) had follow-up cytology or histology data with a median follow-up time of 508 days. Lack of detection of precancer at initial colposcopy that included multiple biopsies predicted low risk of precancer during follow-up. Risk assessment at the colposcopy visit makes identification of cervical precancers more effective and efficient. Not finding precancer after a multiple-biopsy protocol provides high reassurance and allows releasing women back to regular screening. Published by Elsevier Inc.

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

A prospective study of women with ASCUS or LSIL pap smears at baseline and HPV E6/E7 mRNA positive: a 3-year follow-up.

PubMed

Bruno, M T; Ferrara, M; Fava, V; Barrasso, G; Panella, M M

2018-04-01

Human papillomavirus (HPV) testing is used in the triage of women with a borderline smear result. The efficiency of testing women with a low-grade squamous intraepithelial lesion (LSIL) and atypical squamous cells of undetermined significance (ASCUS) is less clear. For this reason we used a new HPV test that detects E6/E7 messenger RNA (mRNA), which might have a higher specificity. The objective of this prospective study was to assess whether HPV E6/E7 mRNA positivity in women with ASCUS and LSIL at baseline, is able to predict those women who have a high risk of developing a histological cervical intraepithelial neoplasia (CIN2) or worse lesion. We took into consideration the women's age and HPV DNA genotype and followed them up for 3 years. Cervical samples from women with high-risk HPV (HR-HPV) DNA-positive ASCUS (n = 90) or LSIL (n = 222) were tested for the presence of HR-HPV E6/E7 mRNA and the women were monitored for the development of histopathologically verified CIN2+. Thirteen patients with ASCUS and 17 with LSIL did not complete follow-up. All patients with LSIL and ASCUS, enrolled in this study, had confirmed lesions at the colposcopic examination. Follow-up was available for 312 women, 193 were positive in the HR-HPV DNA test and 93 had a HPV E6/E7 mRNA positive test. Finally, 22 women positive in the HPV DNA test for high-risk genotypes and with positive E6/E7 mRNA had a histologically confirmed CIN2+. Only two cases with negative HPV E6/E7 mRNA had CIN2+. The study shows that women positive in the HPV E6/E7 mRNA test have a greater risk of malignant progression of cervical lesions and therefore deserve greater attention and earlier check-ups.

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.

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.

SNIPER: a novel assay for human papillomavirus testing among women in Guizhou, China.

PubMed

Belinson, Suzanne E; Wulan, Na; Li, Ruizhen; Zhang, Wei; Rong, Xuan; Zhu, Yasha; Wu, Ruifang; Belinson, Jerome L

2010-08-01

Clinically validate the SNIPER human papillomavirus (HPV) DNA assay for the detection of cervical intraepithelial neoplasia (CIN)2 or higher and CIN2 or higher in a prospective cross-sectional screening study in Guizhou Province, China. Between March and April, 2008, 1000 nonpregnant women aged 30 or older were recruited in Guizhou Province, China. Women positive by SNIPER or cytological examination were requested to return for follow-up. A biopsy of all colposcopically detected abnormalities was performed by quadrant. In normal quadrants, biopsies were obtained at the squamocolumnar junction (2-, 4-, 8-, and 10-o'clock positions depending on the quadrant). Samples were placed in 2 mL of saline solution and maintained between 2 degrees C and 30 degrees C for up to 1 week. One milliliter of this suspension was then prepared and tested. For polymerase chain reaction amplification, a pool of HPV primers was designed to amplify HPV DNA from 13 high-risk-HPV genotypes (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68). Test characteristics were calculated according to standard definitions. One thousand women were screened; 175 tested HPV positive, 36 women tested negative but had positive Papanicolaou test results. All but 21 (90%) returned for follow-up. Median age and proportions having CIN2 or higher and CIN3 or higher differed by HPV status. Twenty-five women had CIN2 or higher and 16 had CIN3 or higher. The SNIPER assay was 93.3% and 94% sensitive and 86% and 85% specific for the detection of CIN2 or higher and CIN3 or higher, respectively. The positive predictive value was 17.4 % and 9.9% for CIN2 or higher and CIN3 or higher, respectively. Negative predictive value approached 100% for CIN2 or higher and CIN3 or higher. The SNIPER assay is functionally competitive and in terms of cost holds an advantage over Hybrid Capture 2 in a Chinese healthcare market, and potentially others, around the world.

Rationale and Safety Assessment of a Novel Intravaginal Drug-Delivery System with Sustained DL-Lactic Acid Release, Intended for Long-Term Protection of the Vaginal Microbiome

PubMed Central

Verstraelen, Hans; Vervaet, Chris; Remon, Jean-Paul

2016-01-01

Bacterial vaginosis is a prevalent state of dysbiosis of the vaginal microbiota with wide-ranging impact on human reproductive health. Based on recent insights in community ecology of the vaginal microbiome, we hypothesize that sustained vaginal DL-lactic acid enrichment will enhance the recruitment of lactobacilli, while counteracting bacterial vaginosis-associated bacteria. We therefore aimed to develop an intravaginal device that would be easy to insert and remove, while providing sustained DL-lactic acid release into the vaginal lumen. The final prototype selected is a vaginal ring matrix system consisting of a mixture of ethylene vinyl acetate and methacrylic acid-methyl methacrylate copolymer loaded with 150 mg DL-lactic acid with an L/D-lactic acid ratio of 1:1. Preclinical safety assessment was performed by use of the Slug Mucosal Irritation test, a non-vertebrate assay to evaluate vaginal mucosal irritation, which revealed no irritation. Clinical safety was evaluated in a phase I trial with six healthy nulliparous premenopausal volunteering women, with the investigational drug left in place for 7 days. Colposcopic monitoring according to the WHO/CONRAD guidelines for the evaluation of vaginal products, revealed no visible cervicovaginal mucosal changes. No adverse events related to the investigational product occurred. Total release from the intravaginal ring over 7 days was estimated through high performance liquid chromatography at 37.1 (standard deviation 0.9) mg DL-lactic acid. Semisolid lactic acid formulations have been studied to a limited extent in the past and typically consist of a large volume of excipients and very high doses of lactic acid, which is of major concern to mucosal safety. We have documented the feasability of enriching the vaginal environment with pure DL-lactic acid with a prototype intravaginal ring. Though the efficacy of this platform remains to be established possibly requiring further development, this approach may offer a novel avenue to modulate and protect the vaginal microbiota. Trial Registration U.S. National Institutes of Health ClinicalTrials.gov NCT02314429 PMID:27093291

Treatment of bowenoid and basaloid vulvar intraepithelial neoplasia 2/3 with imiquimod 5% cream.

PubMed

Marchitelli, Claudia; Secco, Graciela; Perrotta, Myriam; Lugones, Leonor; Pesce, Romina; Testa, Roberto

2004-11-01

To evaluate the effectiveness and safety of imiquimod 5% for the treatment of bowenoid and basaloid vulvar intraepithelial neoplasia (VIN) and to evaluate recurrences following treatment. Eight patients <55 years old (range, 32-51; mean, 39.7), with bowenoid or basaloid VIN 2/3 diagnosed by biopsy were treated with imiquimod 5%. Women with other types of intraepithelial neoplasia of the lower genital tract, immunosuppressed women, pregnant women and women with other types of vulvar pathology were excluded. Two patients previously treated for VIN 3 (surgical resection, resection by loop electrosurgical excision procedure) had recurrences. Patients applied imiquimod cream 3 times a week until total clearance of the lesions or up to a maximum of 16 weeks. Responses were categorized as total when there was no colposcopic evidence of a lesion, partial when the lesion area diminished >50% and progressive when there was an increase in the lesion area. A biopsy was performed at the end of treatment. Follow-up was carried out monthly (10-30 months). Total clearance of lesions was observed in 6 patients after 10-16 weeks. Two patients had a partial response (1 with 75% and the other with 50% reduction of the lesions). Posttreatment histopathology showed the absence of precancerous lesions in 7 patients (87.5%). Biopsy was positive for VIN 3 (12.5%) only in the patient showing a clinical response of 50%. Of the 7 patients with biopsies negative for VIN, 2 (25%) were positive for viral infection; 1 gave a negative reading after 2 months after treatment, and the other 1 remained positive for human papillomavirus. The patient with persistent VIN received surgical treatment. The side effects were as follows: erythema in 8 patients (100%), erosions in 1 patient (12.5%) and edema in 1 patient (12.5%). No relapses occurred after treatment during 10-30 months of follow-up. In this initial series, imiquimod proved to be effective for the treatment of bowenoid and basaloid VIN 2/3 in a group of young women and was less aggressive treatment than surgical ones. The treatment was well tolerated, causing local reactions that enabled the therapy to be completed.

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.

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.

Performance of self-collected cervical samples in screening for future precancer using human papillomavirus DNA testing.

PubMed

Porras, Carolina; Hildesheim, Allan; González, Paula; Schiffman, Mark; Rodríguez, Ana Cecilia; Wacholder, Sholom; Jiménez, Silvia; Quint, Wim; Guillen, Diego; Kreimer, Aimée R; Herrero, Rolando

2015-01-01

Self-collected human papillomavirus (HPV) testing could reduce barriers to cervical cancer screening, with performance comparable to clinician-collected specimens. The ability of self-collected specimens to cross-sectionally and prospectively detect precursor lesions was investigated in an HPV vaccine randomized trial in Costa Rica. In the trial, 7466 women age 18 to 25 years received an HPV16/18 or control vaccine and were followed at least annually for four years. In this secondary analysis, we included all women who provided a self-collected cervicovaginal specimen six months after enrollment (5109 women = full analytical cohort). A subset (615 women = restricted cohort) also had clinician-collected specimens at the six-month postenrollment visit. High-grade squamous intraepithelial lesion or repeat low-grade squamous intraepithelial lesion prompted colposcopic referral throughout the study. HPV testing was performed with SPF10PCR/DEIA/LiPA25. Cross-sectional and prospective sensitivity, specificity, and predictive values were estimated. In the full cohort, one-time HPV testing on self-collected samples detected prevalent CIN2+ with a sensitivity of 88.7% (95% confidence interval [CI] =77.0% to 95.7%) and a specificity of 68.9% (95% CI = 67.6% to 70.1%). For predicting incident CIN2+ in the subsequent four years, sensitivity was 73.9% (95% CI = 65.8% to 81.0%) and specificity 69.4% (95% CI = 68.1% to 70.7%). In the restricted cohort, for incident CIN2+, self-collected HPV was much more sensitive than cytology (80.0% vs 10.0%); relative sensitivity was 0.1 (95% CI = 0.03% to 0.5%). Furthermore, three times more women with normal baseline cytology developed incident CIN2+ than those with negative self-collected HPV. Self-collected and clinician-collected HPV testing had comparable performance. Agreement between self- and clinician-collected samples was 89.7% (kappa = 0.78, McNemar χ2 = 0.62) for carcinogenic HPV types. Self-collected specimens can be used for HPV-based screening, providing sensitivity and specificity comparable with clinician-collected specimens and detecting disease earlier than cytology. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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.

Evaluation of 3D-CPA, HR-HPV, and TCT joint detection on cervical disease screening.

PubMed

Liang, Hui; Fu, Min; Zhou, Jian; Song, Lei

2016-08-01

The application value of three-dimensional color power angiography (3D-CPA), high-risk human papillomavirus (HR-HPV), ThinPrep cytology test (TCT) joint detection on cervical disease screening was investigated. In total, 1,900 patients that were examined in Gynecological and Cervix Clinic of Maternal and Child Care Service Center of Xuzhou from June 2012 to March 2015 were enrolled in the present study. After admission, the patients underwent TCT, HR-HPV and 3D-CPA examinations, and vascular morphology and typing, vascularization index (VI) were recorded. Colposcopic biopsy was performed in patients with a positive outcome of any of the three indices. Pathological diagnosis was taken as the golden standard to assess the sensitivity, specificity, diagnostic rate, and Youden index of the three methods being used independently or jointly. Of the 1,900 patients, 276 cases (14.53%) were HR-HPV-positive, 214 cases (11.26%) were VI-positive and 164 cases (8.63%) were TCT-positive. A total of 418 cases were confirmed with a positive outcome of any of the three indices and a cervical biopsy was obtained. Of the 418 cases, 162 cases (38.75%) were diagnosed with chronic cervicitis, 146 cases with low-level cervical intraepithelial neoplasia (CIN) (34.93%), 104 cases (24.88%) with high level CIN, 6 cases (1.44%) with cervical cancer. Histology more than low level CIN was defined as positive: i) screening results when the three methods were used independently: HPV was confirmed with the highest sensitivity (90.63%), VI with the highest specificity (83.95%), and HPV with the highest diagnostic accuracy (83.73%); ii) screening results under HPV+TCT and HPV+TCT+VI: HPV+TCT+VI was confirmed with the highest sensitivity and specificity: sensitivity (94.53%), specificity (81.48%), diagnosis coincidence rate (89.47%) and the highest Youden index of 0.760; and iii) vascular morphology and grading were significantly different in the early stage cervical carcinoma, high level CIM, and cervicitis groups. In conclusion, the joint detection of 3D-CPA, HR-HPV, and TCT improved the sensitivity and accuracy of cervical disease screening. 3D-CPA technology may therefore be used as an auxiliary screening method for cervical cancer.

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

Development of biomarker panel to predict, prevent and create treatments tailored to the persons with human papillomavirus-induced cervical precancerous lesions

PubMed Central

2014-01-01

Introduction Human papillomavirus (HPV) induce many cancer conditions and cause cervical cancer, second in frequency of malignant disease in women. The aim was to develop biomarker panel for HPV-induced cervical precancerous diseases in patients infected with herpes simplex virus (HSV). Material and methods The study involved 71 women with cervical precancerous diseases (mean age 26 ± 5 years) revealed by colposcopic, cytomorphological, and ultrasound signs which were assessed according to the following: first group, 44 patients infected with HPV; second group, 27 HPV-negative patients; and third group, 30 healthy patients (controls). In cervical specimen, we identified HPV DNA of different oncogenic risk types by polymerase chain reaction (PCR). Enzyme-linked immunosorbent assay (ELISA) kits (JSC SPC ‘DiaprofMed’) were used for detecting antibodies to HSV1 and/or HSV2 and for determining the avidity index. The production of pro-inflammatory cytokines, interferon-γ (IFN-γ), IFN-α, TNF-α, and interleukin-1β (IL-1β), and anti-inflammatory cytokines, IL-4, IL-10, and transforming growth factor-β1 (TGF-β1), were studied by ELISA. Results In HPV-induced cervix precancerous diseases, we identified low-avidity IgG antibodies to HSV serum of 20 patients; in the serum of 17 patients, we identified average-avidity antibodies, and high-avidity antibodies were found in 2 patients only. In 14 HPV-negative patients, we found low-avidity IgG antibodies to HSV; in 10 patients, medium avidity. Patients with low-avidity IgG antibodies to herpes virus showed high and medium oncogenic risk HPV types and a decrease of IFN-γ compared to patients with medium-avidity IgG antibodies. Production of IFN-γ was suppressed also in HPV-negative patients with cervical precancers, but we found low- and medium-avidity IgG antibodies to herpes virus. In patients with low-avidity antibodies, we observed increased level of IL-10. Level of IFN-α, IL-1β, IL-2, and IL-4 did not change in patients of all groups, but TGF-β1 increased. Conclusions In HPV-positive patients, those with low-avidity IgG antibodies to HSV had immunosuppression, confirmed by increased TGF-β1 and violation of IFN-γ production. Therefore, in pro- and anti-inflammatory cytokines and IgG antibodies to HSV, their avidity is an important diagnostic biomarker of HPV-induced precancerous cervical diseases. Low-avidity IgG antibodies may be an indication for treatment with immunomodulators and antiviral drugs. PMID:24386936

Prevalence of cervical neoplastic lesions and Human Papilloma Virus infection in Egypt: National Cervical Cancer Screening Project

PubMed Central

Abd El All, Howayda S; Refaat, Amany; Dandash, Khadiga

2007-01-01

Background Data from Egyptian studies provide widely varying estimates on the prevalence of pre-malignant and malignant cervical abnormalities and human papilloma virus (HPVs) infection. To define the prevalence and risk factors of pre-invasive and invasive cervical cancer (cacx), a community based full-scale cross sectional, household survey including 5453 women aged between 35 and 60 years was conducted. Methods The study period was between February 2000 and December 2002. Initially, conventional Papanicolaou (Pap) smears were evaluated using the Bethesda system (TBS), followed by colposcopic guided biopsy (CGB) for all epithelial abnormalities (EA). In a third step, HPV was tested on all EA by in-situ hybridization (ISH) using first the broad spectrum HPV probe recognizing HPVs 6, 11, 16, 18, 30, 31, 35, 45, 51 and 52 followed by subtyping with probes 6/11, 16/18 and 31/33. Lastly, unequivocal cases were immunostained for herpes simplex type-2 (HSV-2), cytomegalovirus (CMV), and human immunodeficiency virus (HIV). Results EA representing 7.8% (424/5453), were categorized into atypical squamous cell of undetermined significance (ASCUS) (34.4%), atypical glandular cell of undetermined significance (AGCUS) (15.3%), combined ASCUS and AGCUS (3.1%), low grade squamous intraepithelial lesions (SIL) (41.0%), high grade SIL (5.2%) and invasive lesions (1%). CGB of EA (n = 281) showed non neoplastic lesions (12.8%), atypical squamous metaplasia (ASM) (19.2%), cervical intraepithelial neoplasia I (CIN) (44.4%), CIN II (4.4%), CINIII (2.8%), endocervical lesions (5.2%), combined squamous and endocervical lesions (10.0%), invasive squamous cell carcinoma (SCC) (0.02%) and extranodal marginal zone B cell lymphoma (MZBCL) (0.02%). The overall predictive value of cytology was 87% while the predictive value for high grade lesions was 80%. On histological basis, HPVs were present in 94.3% of squamous lesions while it was difficult to be identified in endocervical ones. ISH revealed positivity for pan HPV in 65.9% of the studied biopsies (n = 217), with incorporation of the viral genome HPV 6/11, 16/18 and 31/33 in 11.1%, 33.3% and 17.1% respectively. Multiple HPVs infections were identified in 0.02%. Conclusion Pre-invasive high grade lesions and invasive cervical carcinoma represent 0.5% and 0.04% respectively in Egyptian women. HPV mostly 16/18 as a risk factor (p < 0.001), was frequently associated with mixed infections (p < 0.001) and bilharzial infestation (p < 0.001). PMID:17610742

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/

Evaluation of scaling-up of HPV self-collection offered by community health workers at home visits to increase screening among socially vulnerable under-screened women in Jujuy Province, Argentina.

PubMed

Arrossi, Silvina; Paolino, Melisa; Thouyaret, Laura; Laudi, Rosa; Campanera, Alicia

2017-02-13

Self-collection has been proposed as a strategy to increase cervical screening coverage among hard-to-reach women. However, evaluations of the implementation of this strategy on a large scale are scarce. This paper describes the process and measurement of the scaling-up of self-collection offered by community health workers during home visits as a strategy to reach under-screened women aged 30+ with public health coverage, defined as the target women. We used an adaptation of the Health System Framework to analyze key drivers of scaling-up. A content analysis approach was used to collect and analyze information from different sources. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) model was used to evaluate the impact of the strategy. HPV self-collection was scaled-up in the province of Jujuy in 2014 after a RCT (Self-collection Modality Trial, initials EMA in Spanish) was carried out locally in 2012 and demonstrated effectiveness of the strategy to increase screening uptake. Facilitators of scaling-up were the organizational capacity of the provincial health system, sustainable funding for HPV testing, and local consensus about the value of the technology. Reach: In 2014, 9% (2983/33,245) of target women were screened through self-collection in the Jujuy public health sector. Effectiveness: In 2014, 17% (n = 5657/33,245) of target women were screened with any HPV test (self-collected and clinician-collected tests) vs. 11.7% (4579/38,981) in 2013, the pre-scaling-up period (p < 0.0001). Training about the strategy was provided to 84.2% (n = 609/723) of total community health workers (CHWs). Of 414 HPV+ women, 77.5% (n = 320) had follow-up procedures. Of 113 women with positive triage, 66.4% (n = 75) had colposcopic diagnosis. Treatment was provided to 80.7% of CIN2+ women (n = 21/26). Adoption: Of trained CHWs, 69.3% (n = 422/609) had at least one woman with self-collection; 85.2% (n = 315/368) of CHWs who responded to an evaluation survey were satisfied with self-collection strategy. Maintenance: During 2015, 100.0% (723/723) CHWs were operational and 63.8% (461/723) had at least one woman with self-collection. The strategy was successfully scaled-up, with a high level of adoption among CHWs, which resulted in increased screening among socially vulnerable under-screened women.

Do health care providers have a lower prevalence of abnormal pap smears than the general public?

PubMed

Suwannarurk, Komsun; Bhamarapravatana, Konkarn; Kheolamai, Pakpoom; Thaweekul, Yuttadej; Mairaing, Karicha; Poomtavorn, Yenrudee; Pattaraarchachai, Junya

2010-12-01

Most Thai people believe that health care providers have a lower risk of any disease than their patients. This belief may lull Thai health care providers into accepting the false belief that they are at a lower risk of having the precancerous conditions that lead to cervical cancer. This study compares the prevalence of abnormal Pap smears from health care providers (HC) and non health care providers (NHC) by using the standard liquid-based Pap smear processing at Thammasat University Hospital's pathology department, Thailand. Both health care providers (HC) and non health care providers (NHC) were patients at the outpatient clinic, Thammasat University Hospital. They were screened for cervical cancer by using liquid-based Pap smear (LBP). Cytological diagnoses and specimen adequacy were classified using the Bethesda system 2001. All subjects who had abnormal cytology more than atypical squamous cells or atypical glandular cells were counseled to have performed a colposcopic directed biopsy for confirmation of pathology. A total of 250 liquid-base Pap smears were processed and evaluated at the Gynecology clinic, Thammasat University Hospital from April 2008 to May 2008. The groups of HC and NHC consisted of 122 and 128 women, respectively. In general, both the HC and NHC groups were similar in their age, religion, income and education level distributions. The range of ages was between 16 and 75 years, with the mean age equal to 40.2 +/- 10.5 years. Prevalence of abnormal Pap smears was 9.8% in HC and 9.4% in NHC (p-value = 0.90). HC showed atypical change (ASC, AGC), low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) at 0.8%, 1.6% and 7.4%, respectively. NHC had an incidence of atypical change, LSIL and HSIL at 0.8%, 0.8% and 7.8%. HC had an equal incidence of abnormal Pap smears prevalence to NHC. Further, the percentage of HC and NHC groups with histological confirmed cervical intraepithelial neoplasia (CIN) 1 were not significantly different (4.92% vs. 6.25%, p-value = 0.70), likewise CIN 2/3 (1.64% vs. 1.56%, p-value = 1.00). According to our study the rate of abnormal Pap smears observed in both health care providers and clients was essentially the same. The prevalence of abnormal Pap smears in health care providers was statistically equivalent to that in their clients.

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

Virologic versus cytologic triage of women with equivocal Pap smears: a meta-analysis of the accuracy to detect high-grade intraepithelial neoplasia.

PubMed

Arbyn, Marc; Buntinx, Frank; Van Ranst, Marc; Paraskevaidis, Evangelos; Martin-Hirsch, Pierre; Dillner, Joakim

2004-02-18

The appropriate management of women with minor cytologic lesions in their cervix is unclear. We performed a meta-analysis to assess the accuracy of human papillomavirus (HPV) DNA testing as an alternative to repeat cytology in women who had equivocal results on a previous Pap smear. Data were extracted from articles published between 1992 and 2002 that contained results of virologic and cytologic testing followed by colposcopically directed biopsy in women with an index smear showing atypical cells of undetermined significance (ASCUS). Fifteen studies were identified in which HPV triage and the histologic outcome (presence or absence of a cervical intraepithelial neoplasia of grade II or worse [CIN2+]) was documented. Nine, seven, and two studies also documented the accuracy of repeat cytology when the cutoff for abnormal cytology was set at a threshold of ASCUS or worse, low-grade squamous intraepithelial lesion (LSIL) or worse, or high-grade squamous intraepithelial lesion (HSIL) or worse, respectively. Random-effects models were used for pooling of accuracy parameters in case of interstudy heterogeneity. Differences in accuracy were assessed by pooling the ratio of the sensitivity (or specificity) of HPV testing to that of repeat cytology. The sensitivity and specificity were 84.4% (95% confidence interval [CI] = 77.6% to 91.1%) and 72.9% (95% CI = 62.5% to 83.3%), respectively, for HPV testing overall and 94.8% (95% CI = 92.7% to 96.9%) and 67.3% (95% CI = 58.2% to 76.4%), respectively, for HPV testing in the eight studies that used the Hybrid Capture II assay. Sensitivity and specificity of repeat cytology at a threshold for abnormal cytology of ASCUS or worse was 81.8% (95% CI = 73.5% to 84.3%) and 57.6% (95% CI = 49.5% to 65.7%), respectively. Repeat cytology that used higher cytologic thresholds yielded substantially lower sensitivity but higher specificity than triage with the Hybrid Capture II assay. The ratio of the sensitivity of the Hybrid Capture II assay to that of repeat cytology at a threshold of ASCUS or worse pooled from the four studies that used both triage tests was 1.16 (95% CI = 1.04 to 1.29). The specificity ratio was not statistically different from unity. The published literature indicates that the Hybrid Capture II assay has improved accuracy (higher sensitivity, similar specificity) than the repeat Pap smear using the threshold of ASCUS for an outcome of CIN2+ among women with equivocal cytologic results. The sensitivity of triage at higher cytologic cutoffs is poor.

Real-time colorimetric detection of DNA methylation of the PAX1 gene in cervical scrapings for cervical cancer screening with thiol-labeled PCR primers and gold nanoparticles

PubMed Central

Huang, Jin; Liou, Yu-Ligh; Kang, Ya-Nan; Tan, Zhi-Rong; Peng, Ming-Jing; Zhou, Hong-Hao

2016-01-01

Background DNA methylation can induce carcinogenesis by silencing key tumor suppressor genes. Analysis of aberrant methylation of tumor suppressor genes can be used as a prognostic and predictive biomarker for cancer. In this study, we propose a colorimetric method for the detection of DNA methylation of the paired box gene 1 (PAX1) gene in cervical scrapings obtained from 42 patients who underwent cervical colposcopic biopsy. Methods A thiolated methylation-specific polymerase chain reaction (MSP) primer was used to generate MSP products labeled with the thiol group at one end. After bisulfite conversion and MSP amplification, the unmodified gold nanoparticles (AuNPs) were placed in a reaction tube and NaCl was added to induce aggregation of bare AuNPs without generating polymerase chain reaction products. After salt addition, the color of AuNPs remained red in the methylated PAX1 gene samples because of binding to the MSP-amplified products. By contrast, the color of the AuNP colloid solution changed from red to blue in the non-methylated PAX1 gene samples because of aggregation of AuNPs in the absence of the MSP-amplified products. Furthermore, PAX1 methylation was quantitatively detected in cervical scrapings of patients with varied pathological degrees of cervical cancer. Conventional quantitative MSP (qMSP) was also performed for comparison. Results The two methods showed a significant correlation of the methylation frequency of the PAX1 gene in cervical scrapings with severity of cervical cancer (n=42, P<0.05). The results of the proposed method showed that the areas under the receiver operating characteristic curve (AUCs) of PAX1 were 0.833, 0.742, and 0.739 for the detection of cervical intraepithelial neoplasms grade 2 and worse lesions (CIN2+), cervical intraepithelial neoplasms grade 3 and worse lesions (CIN3+), and squamous cell carcinoma, respectively. The sensitivity and specificity for detecting CIN2+ lesions were 0.941 and 0.600, respectively, with a cutoff value of 31.27%. The proposed method also showed superior sensitivity over qMSP methods for the detection of CIN2+ and CIN3+ (0.941 vs 0.824 and 1.000 vs 0.800, respectively). Furthermore, the novel method exhibited higher AUC (0.833) for the detection of CIN2+ than qMSP (0.807). Conclusion The results of thiol-labeled AuNP method were clearly observed by the naked eyes without requiring any expensive equipment. Therefore, the thiol-labeled AuNP method could be a simple but efficient strategy for cervical cancer screening. PMID:27789946

[Verification of doubtful PAP smear results of women included in the screening program in the Podlaskie province].

PubMed

Błońska, Ewa; Knapp, Piotr Andrzej

2013-08-01

Verification of uncertain PAP-smear results in a group of women covered by the cervical screening program in the Podlaski province. The main aim of the study was to identify CIN (Cervical Intraepithelial Neoplasia) lesions present, with varying degrees of severity in women with cytological diagnosis of ASCUS (atypical squamous cells of undetermined significance), LSIL (low grade squamous intraepithelial lesion), and ASC-H (atypical squamous cells - cannot exclude high grade squamous intraepithelial lesion). The study evaluated 101 cervical smears taken from the vaginal part of the cervix in a group of screened women in the Podlaski province. Cytological evaluation was performed according the Bethesda System. We analyzed abnormal smears selected from a total of 7296 cytological examinations performed during 2012 at the University Center for Pathomorphological and Genetic - Molecular Diagnosis, Medical University in Białystok. The cytological results which were of interest to us included 19 cases with ASCUS, 59 with LSIL, and 23 with ASC-H, as well as with morphological features of the presence of Human Papilloma Virus (HPV). Staining was performed using CINtecPLUS test according to the manufacturer's instructions. CINtecPLUS is a immunocytochemical test based on specially designed monoclonal antibodies (E6H4TM) that let us identify protein p16ink4a within the cervical smear Additionally the diagnostic kit was provided with antibodies for diagnosing the presence of Ki-67 protein, a known marker of cell proliferation. The result was considered positive when staining of the nucleus and the cytoplasm appeared in red and brown, respectively. All abnormal results were eventually verified by histological examination of the tissue taken from cervical lesions by diagnostic-therapeutic procedure following colposcopic evaluation of cervical lesion topography In the group of cytological smears with ASCUS, the diagnosis was positive in 5 cases (26.3%), negative in 14 (73.7%). In the group with the diagnosis of LSIL, the cytology results were positive in 32 cases (54.2%), negative in 27 (45.8%). In the cytological diagnosis of ASC-H there were 20 positive (87%) and 3 negative (13%) results. Test CINtecPLUS could be a helpful tool in the final diagnosis of cervical abnormality in patients with the cytological diagnosis of ASCUS, LSIL and ASC-H. The combination of conventional cytological test and CINtecPLUS can help create a new procedure algorithm for cases with abnormal or ambiguous cytological screening results. It could be especially useful in a group of young women of childbearing age, when it is common to avoid a more radical treatment of cervical lesions.

Diagnosis of 25 genotypes of human papillomaviruses for their physical statuses in cervical precancerous/cancerous lesions: a comparison of E2/E6E7 ratio-based vs. multiple E1-L1/E6E7 ratio-based detection techniques.

PubMed

Zhang, Rong; He, Yi-feng; Chen, Mo; Chen, Chun-mei; Zhu, Qiu-jing; Lu, Huan; Wei, Zhen-hong; Li, Fang; Zhang, Xiao-xin; Xu, Cong-jian; Yu, Long

2014-10-02

Cervical lesions caused by integrated human papillomavirus (HPV) infection are highly dangerous because they can quickly develop into invasive cancers. However, clinicians are currently hampered by the lack of a quick, convenient and precise technique to detect integrated/mixed infections of various genotypes of HPVs in the cervix. This study aimed to develop a practical tool to determine the physical status of different HPVs and evaluate its clinical significance. The target population comprised 1162 women with an HPV infection history of > six months and an abnormal cervical cytological finding. The multiple E1-L1/E6E7 ratio analysis, a novel technique, was developed based on determining the ratios of E1/E6E7, E2/E6E7, E4E5/E6E7, L2/E6E7 and L1/E6E7 within the viral genome. Any imbalanced ratios indicate integration. Its diagnostic and predictive performances were compared with those of E2/E6E7 ratio analysis. The detection accuracy of both techniques was evaluated using the gold-standard technique "detection of integrated papillomavirus sequences" (DIPS). To realize a multigenotypic detection goal, a primer and probe library was established. The integration rate of a particular genotype of HPV was correlated with its tumorigenic potential and women with higher lesion grades often carried lower viral loads. The E1-L1/E6E7 ratio analysis achieved 92.7% sensitivity and 99.0% specificity in detecting HPV integration, while the E2/E6E7 ratio analysis showed a much lower sensitivity (75.6%) and a similar specificity (99.3%). Interference due to episomal copies was observed in both techniques, leading to false-negative results. However, some positive results of E1-L1/E6E7 ratio analysis were missed by DIPS due to its stochastic detection nature. The E1-L1/E6E7 ratio analysis is more efficient than E2/E6E7 ratio analysis and DIPS in predicting precancerous/cancerous lesions, in which both positive predictive values (36.7%-82.3%) and negative predictive values (75.9%-100%) were highest (based on the results of three rounds of biopsies). The multiple E1-L1/E6E7 ratio analysis is more sensitive and predictive than E2/E6E7 ratio analysis as a triage test for detecting HPV integration. It can effectively narrow the range of candidates for colposcopic examination and cervical biopsy, thereby lowering the expense of cervical cancer prevention.

Comparison of imiquimod, topical fluorouracil, and electrocautery for the treatment of anal intraepithelial neoplasia in HIV-positive men who have sex with men: an open-label, randomised controlled trial.

PubMed

Richel, Olivier; de Vries, Henry J C; van Noesel, Carel J M; Dijkgraaf, Marcel G W; Prins, Jan M

2013-04-01

Anal cancer is an increasing issue in HIV-positive men who have sex with men (MSM). Screening for its precursor, anal intraepithelial neoplasia (AIN), is subject of discussion. Current treatment options are suboptimum and have not been compared in a prospective trial. We compared efficacy and side-effects of imiquimod, topical fluorouracil, and electrocautery for the treatment of AIN. In this open-label randomised trial, we included HIV-positive MSM older than 18 years visiting the HIV outpatient clinic of the Academic Medical Center, Amsterdam, Netherlands. Patients with histologically confirmed AIN were randomly assigned to receive either 16 weeks of imiquimod (three times a week), 16 weeks of topical fluorouracil (twice a week), or monthly electrocautery for 4 months. Randomisation was done with random block sizes of three and six, stratified for AIN grade (AIN grades 1, 2, or 3) and AIN location (peri-anal or intra-anal). Participants were assessed by high-resolution anoscopy 4 weeks after treatment. Responding patients returned for follow-up 24 weeks, 48 weeks, and 72 weeks after treatment. The primary endpoint was histological resolution of AIN measured 4 weeks after treatment and AIN recurrence at week 24, week 48, and week 72 after treatment. The primary analysis was done in a modified intention-to-treat population, including all patients who had received their assigned treatment at least once. The trial is registered at the Netherlands Trial Register, number NTR1236. Between Aug 12, 2008, and Dec 1, 2010, we screened 388 HIV-positive MSM for AIN by high resolution anoscopy. Of the 246 (63%) patients who had AIN, 156 (63%) were randomly assigned to either receive imiquimod (54 patients), topical fluorouracil (48 patients), or electrocautery (46 patients) following withdrawing of consent by eight patients. Modified intention-to-treat analysis showed a complete response in 13 (24%, 95% CI 15-37) patients in the imiquimod group, eight (17%, 8-30) of patients in the fluorouracil group, and 18 (39%, 26-54) of patients in the electrocautery group (p=0·027). At week 24, 11 (22%) of 50 responders had recurrence; at week 48, 22 (46%) of 48 had recurred; and at week 72, 30 (67%) of 45 had recurred. Recurrence was observed at 72 weeks in 10 (71%) of 14 patients treated with imiquimod, seven (58%) of 12 patients treated with fluorouracil, and 13 (68%) of 19 patients treated with electrocautery. Grade 3-4 side-effects were noted in 23 (43%) of 53 patients in the imiquimod group, 13 (27%) of 48 patients in the fluorouracil group, and eight (18%) patients in the electrocautery group (p=0·019). The most common side-effects were pain, bleeding, and itching. Seven serious adverse events occurred, all not related to the study. Electrocautery is better than imiquimod and fluorouracil in the treatment of AIN, but recurrence rates are substantial. Anna Maurits de Cock foundation provided funding for the video colposcope. Copyright © 2013 Elsevier Ltd. All rights reserved.

[High-risk HPV genotyping PCR testing as a means of cervical cancer and precancerous lesions early screening].

PubMed

Ma, Li; Cong, Xiao; Bian, Meilu; Shi, Mai; Wang, Xiuhong; Liu, Jun; Liu, Haiyan

2015-04-01

To explored high-risk HPV genotyping PCR testing whether as a feasible means for the early screening of cervical cancer and precancerous lesions. From January 2013 to June 2014, 15,192 outpatients in China-Japan Friendship Hospital voluntary were tested by high-risk type HPV genotyping PCR. The average age of them were (33±8) years old. High-risk HPV types genotyping PCR tested by fluorescence PCR technology, in which 13 kinds of high-risk HPV subtypes were detected, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68. A total of 4,315 cases of them were tested by the liquid-based cytology (LCT), among them with positive of high-risk HPV genotyping tested by PCR (n=2,366) were biopsy under colposcope (648 cases) in those LCT results were positive or LCT negative but HPV16 positive or LCT negative but had the clear clinical symptoms or and non-HPV16 positive but with clear clinical symptoms. (1) Analysis high-risk HPV infection status of 15 192 women. (2) As the pathological diagnosis was the gold standard in the diagnosis of cervical lesions, analysis of the relationship among high-risk HPV infection, virus loads and cervical lesions. (3) To evaluated the value of high-risk HPV genotyping PCR tested method in screening of cervical cancer and precancerous lesions. ⑴ Of 15,192 cases tested by high-risk HPV genotyping PCR, 2,366 cases were HPV positive (HPV infection), the overall infection rate was 15.57% (2,366/15,192), in which a single subtype of HPV infection in 1,767 cases, infection rate was 11.63% (1,767/15,192), and multiple subtypes of HPV infection (two and more subtypes HPV infection) in 599 cases, infection rate was 3.94% (599/15,192). The HPV16, 52 and 58 infections were the most common HPV subtypes in 13 subtypes, the infection rate was 3.95% (600/15,192), 2.86% (435/15,192) and 2.67% (406/15,192), respectively. (2) The most relevant subtypes with cervical intraepithelial neoplasia (CIN) II and even higher lesion were HPV16, 52 and 58, accounted for 57.7% (154/267) of all above CIN II lesions. The most relevant subtype with the cervical glandular intraepithelial neoplasia (CGIN) II or above lesions was HPV18, 3 cases with CGIN II or above lesions were all single HPV18 infection. The pathologic examination positive percentage of patients which HPV virus loads≤10(3) copys/10(4) cells was 18.2% (25/137), while the pathologic examination positive proportion was 33.3% (247/742) which HPV virus loads≥10(4) copys/10(4) cells, there was statistically significant difference between them (χ2=27.06, P=0.000). (3) Sensitivity, specificity, positive predictive value and negative predictive value for detection of CIN II or above using HPV genotyping PCR were 96.11%, 85.76%, 30.94% and 99.70%, respectively. There were a guiding significance for high-risk HPV genotyping PCR tested in screening of cervical cancer and precancerous lesion. HPV16, 52 and 58 were related to the severe cervical squamous epithelial lesions, while HPV18 was related to cervical severe glandular cell pathological changes. HPV genotyping is feasible and economical as the first choice of opportunistic screening in tertiary hospitals.

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.

Exploiting Optical Contrasts for Cervical Precancer Diagnosis via Diffuse Reflectance Spectroscopy

NASA Astrophysics Data System (ADS)

Chang, Vivide Tuan-Chyan

Among women worldwide, cervical cancer is the third most common cancer with an incidence rate of 15.3 per 100,000 and a mortality rate of 7.8 per 100,000 women. This is largely attributed to the lack of infrastructure and resources in the developing countries to support the organized screening and diagnostic programs that are available to women in developed nations. Hence, there is a critical global need for a screening and diagnostic paradigm that is effective in low-resource settings. Various strategies are described to design an optical spectroscopic sensor capable of collecting reliable diffuse reflectance data to extract quantitative optical contrasts for cervical cancer screening and diagnosis. A scalable Monte Carlo based optical toolbox can be used to extract absorption and scattering contrasts from diffuse reflectance acquired in the cervix in vivo. [Total Hb] was shown to increase significantly in high-grade cervical intraepithelial neoplasia (CIN 2+), clinically the most important tissue grade to identify, compared to normal and low-grade intraepithelial neoplasia (CIN 1). Scattering was not significantly decreased in CIN 2+ versus normal and CIN 1, but was significantly decreased in CIN relative to normal cervical tissues. Immunohistochemistry via anti-CD34, which stains the endothelial cells that line blood vessels, was used to validate the observed absorption contrast. The concomitant increase in microvessel density and [total Hb] suggests that both are reactive to angiogenic forces from up-regulated expression of VEGF in CIN 2+. Masson's trichrome stain was used to assess collagen density changes associated with dysplastic transformation of the cervix, hypothesized as the dominant source of decreased scattering observed. Due to mismatch in optical and histological sampling, as well as the small sample size, collagen density and scattering did not change in a similar fashion with tissue grade. Dysplasia may also induce changes in cross-linking of collagen without altering the amount of collagen present. Further work would be required to elucidate the exact sources of scattering contrast observed. Common confounding variables that limit the accuracy and clinical acceptability of optical spectroscopic systems are calibration requirements and variable probe-tissue contact pressures. Our results suggest that using a real-time self-calibration channel, as opposed to conventional post-experiment diffuse reflectance standard calibration measurements, significantly improved data integrity for the extraction of scattering contrast. Extracted [total Hb] and scattering were also significantly associated with applied contact probe pressure in colposcopically normal sites. Hence, future contact probe spectroscopy or imaging systems should incorporate a self-calibration channel and ensure spectral acquisition at a consistent contact pressure to collect reliable data with enhanced absorption and scattering contrasts. Another method to enhance optical contrast is to selectively interrogate different depths in the dysplastic cervix. For instance, scattering has been shown to increase in the epithelium (increase in nuclear-to-cytoplasmic ratio) while decrease in the stroma (re-organization of the extra-cellular matrix and changes in of collagen fiber cross-links). A fiber-optic probe with 45° illumination and collection fibers with a separation distance of 330 μm was designed and constructed to selectively interrogate the cervical epithelium. Mean extraction errors from liquid phantoms with optical properties mimicking the cervical epithelium for μa and μs' were 11.3 % and 12.7 %, respectively. Diffuse reflectance spectra from 9 sites in four loop electrosurgical excision procedure (LEEP) patients were analyzed. Preliminary data demonstrate the utility of the oblique fiber geometry in extracting scattering contrast in the cervical epithelium. Further work is needed to study the systematic error in optical property extraction and to incorporate simultaneous extraction of epithelial and stromal contrasts using both flat and oblique illumination and collection fibers. Various strategies, namely self-calibration, consistent contact pressure, and the incorporation of depth-selective sensing, have been proposed to improve the data integrity of an optical spectroscopic system for maximal contrast. In addition to addressing field operation requirements (such as power and operator training requirement), these improvements should enable the collection of reliable spectral data to aid in the adoption of optical smart sensors in the screening and diagnosis of cervical precancer, especially in a global health setting.

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.

Cervical cancer screening: A never-ending developing program

PubMed Central

Comparetto, Ciro; Borruto, Franco

2015-01-01

With the term “oncological screening”, we define the overall performances made to detect early onset of tumors. These tests are conducted on a population that does not have any signs or symptoms related to a neoplasm. The whole population above a certain age, only one sex, only subjects with a high risk of developing cancer due to genetic, professional, discretionary reasons may be involved. Screening campaigns should be associated, when risk factors that can be avoided are known, with campaigns for the prevention of cancer by means of suitable behavior. The goal of cancer screening cannot however be limited to the diagnosis of a greater number of neoplasms. Screening will be useful only if it leads to a reduction in overall mortality or at least in mortality related to the tumor. Screening should then allow the diagnosis of the disease at a stage when there is a possibility of healing, possibility that is instead difficult when the disease is diagnosed at the appearance of signs or symptoms. This is the reason why not all campaigns of cancer screening have the same effectiveness. In Italy, every year there are about 150000 deaths due to cancer. Some of these tumors can be cured with a very high percentage of success if diagnosed in time. Cervical cancer can be diagnosed with non-invasive tests. The screening test used all over the world is Papanicolaou (Pap) test. This test may be carried out over the entire healthy population potentially exposed to the risk of contracting cancer. Public health has begun the screening campaigns in the hope of saving many of the approximately 270000 new cases of cancer reported each year. Screening is done following protocols that guarantee quality at the national level: these protocols are subject to change over time to reflect new realities or to correct any errors in the system. A simplified sketch of a possible route of cancer screening is as follows: (1) after selecting the target population, for example all women between 25 and 64 years (in the case of monitoring of cervical cancer), an invitation letter with the date and time of the appointment, planned according to the acceptance capacity of the hospital, is sent to all individuals; (2) an examination, which depending on the individual and the type of cancer to be monitored, for example, can be a Pap smear, is performed and the patient can go home; (3) once available the results of examinations, if negative, they shall be communicated to the person concerned that will be notified by mail and will be recalled for a second test at a few years of distance, in the case of non-negativity, instead, the patient is contacted by telephone and informed of the need to carry out further examinations: it is said that the patient is in the “phase two” of the screening pathway; (4) in phase two, reached by only a small portion of the interested parties (usually less than 3%-5%), more in-depth tests are carried out, which, depending on the individual and the type of cancer, can be: cytological and colposcopic examinations, the removal of a fragment of tissue (biopsy) and subsequent histological examination, additional tests such as ultrasound, radiography, or others such as computerized tomography, magnetic resonance imaging, positron emission tomography, etc., in case of negativity, the concerned person will be called for new control tests at a a few years of distance, in case of non-negativity, it will be proposed instead an oncologic therapeutic plan and/or surgery to treat the diagnosed tumor; and (5) once the treatment plan is completed, the individual enters the follow-up protocol, which is monitored over time to see if the tumor has been completely removed or if instead it is still developing. Cervical cancer is undoubtedly the most successful example of a cancer screening campaign. Paradoxically, its effectiveness is one of the strongest reasons to criticize the usefulness of vaccination against human papillomavirus (HPV) in countries where the screening service with Pap test is organized in an efficient manner. Cervical cancer screening protocols are directed to sexually active women aged 25-64 years: they provide the Pap test performed by examining under a microscope or by staining with a specific “thin prep” the material taken from the cervix with a small spatula and a brush. It is recommended to repeat the test every two or three years. It is important to emphasize that women vaccinated against HPV must continue the screening with Pap test. Although some screening programs (e.g., Pap smears) have had remarkable success in reducing mortality from a specific cancer, any kind of screening is free from inherent limitations. The screening methods are in fact applied to large parts of the apparently healthy population. In particular, the limits for certain cancers may be as obvious as to prohibit the introduction of an organized screening program. Potential limitations of organized screenings are basically of two types: organizational and medical. The limits of organizational type relate to the ability of a program to recruit the whole target population. Although well organized, a screening program will hardly be able to exceed a coverage of 70%-80% of the target population, and in fact the results of the current programs are often much smaller. The limits of medical type are represented by the possibility of reducing the overall mortality, or specific mortality, using a specific screening campaign. PMID:26244153