Diagnostic accuracy of high-risk HPV genotyping in women with high-grade cervical lesions: evidence for improving the cervical cancer screening strategy in China.

PubMed

Xu, Huihui; Lin, Aifen; Shao, Xiujuan; Shi, Weiwu; Zhang, Yang; Yan, Weihua

2016-12-13

Currently, clinical data for primary HPV screening alone are lacking in China. Here, we evaluate cervical cancer screening with primary HPV genotyping, as well as possible future screening strategy. Overall, high-risk HPV (hrHPV) prevalence was 18.2% among hospital-based population in Taizhou area. For cervical intraepithelial neoplasia 2 or worse (CIN2+), the sensitivity of primary hrHPV genotyping strategy and current cervical cancer screening strategy were 93.5%, and 71.1%, respectively; whereas the specificity was 17.5%, and 62.4%, respectively. Current cervical screening strategy had slightly higher positive predictive values (28.4%) for CIN2+ than hrHPV genotyping strategy (21.9%), whereas primary hrHPV genotyping strategy demonstrated higher negative predictive values (94.7%) than current cervical screening strategy (91.1%). Compared to HPV35/39/45/51/56/59/66/68 genotypes, the odds ratios (OR) for CIN2+ in HPV16/18/31/33/52/58 infection women were 3.2 (95% confidence interval [CI] 2.3-4.1). Primary hrHPV genotyping strategy provides a better predictive value than HPV16/18 genotyping alone in guiding the clinical management of the current cervical cancer screening. HPV testing without adjunctive cytology may be sufficiently sensitive for primary cervical cancer screening.

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

PubMed

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

2017-02-01

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

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

PubMed

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

2015-02-01

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

Protocol for Compass: a randomised controlled trial of primary HPV testing versus cytology screening for cervical cancer in HPV-unvaccinated and vaccinated women aged 25-69 years living in Australia.

PubMed

Canfell, Karen; Saville, Marion; Caruana, Michael; Gebski, Val; Darlington-Brown, Jessica; Brotherton, Julia; Heley, Stella; Castle, Philip E

2018-01-26

Australia's National Cervical Screening Program (NCSP) currently recommends 2-year cytology in women aged 18-69 years. Following a review of the NCSP prompted by the implementation of human papillomavirus (HPV) vaccination, the programme will transition in 2017 to 5-year primary HPV screening with partial genotyping for HPV16/18 in women aged 25-74 years. Compass is a sentinel experience for the renewed NCSP and the first prospectively randomised trial of primary HPV screening compared with cytology to be conducted in a population with high uptake of HPV vaccination. This protocol describes the main Compass trial, which commenced after a pilot study of ~5000 women completed recruitment. Women aged 25-69 years will be randomised at a 1:2 allocation to (1) 2.5-year image-read, liquid-based cytology (LBC) screening with HPV triage of low-grade smears (active control Arm A) or (2) 5-year HPV screening with partial genotyping and referral of HPV16/18-positive women to colposcopy (intervention Arm B). Women in Arm B positive for other oncogenic HPV (not 16/18) will undergo secondary randomisation at a 1:1 allocation to either LBC or dual-stained (p16 INK4a and Ki-67) cytology testing (dual-stained cytology). The primary outcome is cumulative CIN3+ (CIN3, adenocarcinoma in situ and invasive cervical cancer) following a 5-year HPV exit testing round in both arms, in women randomised to the HPV arm versus women randomised to the LBC arm, based on an intention-to-treat analysis. The primary outcome will first be tested for non-inferiority and if declared, the primary outcome will be tested for superiority. A total of 36 300 women in birth cohorts not offered vaccination and 84 700 women in cohorts offered vaccination will be recruited, bringing the final sample size to 121 000. The trial is powered for the secondary outcome of cumulative CIN3+ in screen-negative women, adjusted for censoring after CIN2+ treatment and hysterectomy. Approved by the Bellberry Ethics Committee (2014-11-592). Findings will be reported in peer-reviewed journals and presented at scientific meetings. NCT02328872; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Danish method study on cervical screening in women offered HPV vaccination as girls (Trial23): a study protocol.

PubMed

Thamsborg, Lise Holst; Andersen, Berit; Larsen, Lise Grupe; Christensen, Jette; Johansen, Tonje; Hariri, Jalil; Christiansen, Sanne; Rygaard, Carsten; Lynge, Elsebeth

2018-05-26

The first birth cohorts of women offered human papillomavirus (HPV) vaccination as girls are now entering cervical screening. However, there is no international consensus on how to screen HPV vaccinated women. These women are better protected against cervical cancer and could therefore be offered less intensive screening. Primary HPV testing is more sensitive than cytology, allowing for a longer screening interval. The aim of Trial23 is to investigate if primary HPV testing with cytology triage of HPV positive samples is a reasonable screening scheme for women offered HPV vaccination as girls. Trial23 is a method study embedded in the existing cervical screening programme in four out of five Danish regions. Without affecting the screening programme, women born in 1994 are randomised to present screening with liquid-based cytology every third year (present programme arm) or present screening plus an HPV test (HPV arm). The study started 1 February 2017 and will run over three screening rounds corresponding to 7-8 years. The primary endpoint is cervical intraepithelial neoplasia grade 3 or above. The trial is undertaken as a non-inferiority study including intention-to-treat and per-protocol analyses. The potential effect of primary HPV screening with a 6-year interval will be calculated from the observed data. The study protocol has been submitted to the ethical committee and deemed a method study. All women are screened according to routine guidelines. The study will contribute new evidence on the future screening of HPV vaccinated birth cohorts of women. All results will be published in open-access journal. NCT03049553; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The clinical implementation of primary HPV screening.

PubMed

Mariani, Luciano; Igidbashian, Sarah; Sandri, Maria Teresa; Vici, Patrizia; Landoni, Fabio

2017-03-01

To evaluate, from a gynecology perspective, the transition from cytology-based HPV screening to primary HPV screening. Studies examining switching from cytology-based screening to primary HPV-DNA testing with triaging of patients with positive test results were retrieved and reviewed, with a particular focus on screening in an Italian setting. The increased complexity of patient-management decisions when implementing HPV-based screening was a critical issue discussed in the literature. The change in strategy represents a paradigm shift in moving from a medical perspective of identifying the disease in individual patients, to a public-healthcare perspective of excluding HPV from the healthy population and identifying a small sub-group of individuals at increased risk of HPV. With knowledge about HPV screening evolving rapidly, new programs and related algorithms need to be sufficiently flexible to be adjusted according to ongoing research and the validation of new assays. The establishment of a national working group (including epidemiologists, gynecologists, pathologists, and healthcare providers) will be necessary to properly implement and govern this important technical and cultural transition. © 2016 International Federation of Gynecology and Obstetrics.

Performance of a Cartridge-Based Assay for Detection of Clinically Significant Human Papillomavirus (HPV) Infection: Lessons from VALGENT (Validation of HPV Genotyping Tests)

PubMed Central

Geraets, Daan; Cuzick, Jack; Cadman, Louise; Moore, Catherine; Vanden Broeck, Davy; Padalko, Elisaveta; Quint, Wim; Arbyn, Marc

2016-01-01

The Validation of Human Papillomavirus (HPV) Genotyping Tests (VALGENT) studies offer an opportunity to clinically validate HPV assays for use in primary screening for cervical cancer and also provide a framework for the comparison of analytical and type-specific performance. Through VALGENT, we assessed the performance of the cartridge-based Xpert HPV assay (Xpert HPV), which detects 14 high-risk (HR) types and resolves HPV16 and HPV18/45. Samples from women attending the United Kingdom cervical screening program enriched with cytologically abnormal samples were collated. All had been previously tested by a clinically validated standard comparator test (SCT), the GP5+/6+ enzyme immunoassay (EIA). The clinical sensitivity and specificity of the Xpert HPV for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and CIN3+ relative to those of the SCT were assessed as were the inter- and intralaboratory reproducibilities according to international criteria for test validation. Type concordance for HPV16 and HPV18/45 between the Xpert HPV and the SCT was also analyzed. The Xpert HPV detected 94% of CIN2+ and 98% of CIN3+ lesions among all screened women and 90% of CIN2+ and 96% of CIN3+ lesions in women 30 years and older. The specificity for CIN1 or less (≤CIN1) was 83% (95% confidence interval [CI], 80 to 85%) in all women and 88% (95% CI, 86 to 91%) in women 30 years and older. Inter- and intralaboratory agreements for the Xpert HPV were 98% and 97%, respectively. The kappa agreements for HPV16 and HPV18/45 between the clinically validated reference test (GP5+/6+ LMNX) and the Xpert HPV were 0.92 and 0.91, respectively. The clinical performance and reproducibility of the Xpert HPV are comparable to those of well-established HPV assays and fulfill the criteria for use in primary cervical cancer screening. PMID:27385707

Protecting the underscreened women in developed countries: the value of HPV test.

PubMed

Ibáñez, Raquel; Autonell, Josefina; Sardà, Montserrat; Crespo, Nayade; Pique, Pilar; Pascual, Amparo; Martí, Clara; Fibla, Montserrat; Gutiérrez, Cristina; Lloveras, Belén; Moreno-Crespi, Judit; Torrent, Anna; Baixeras, Núria; Alejo, María; Bosch, Francesc Xavier; de Sanjosé, Silvia

2014-08-08

Poor attendance to cervical cancer (CC) screening is a major risk factor for CC. Efforts to capture underscreened women are considerable and once women agree to participate, the provision of longitudinal validity of the screening test is of paramount relevance. We evaluate the addition of high risk HPV test (HPV) to cervical cytology as a primary screening test among underscreened women in the longitudinal prediction of intraepithelial lesions grade 2 or worse (CIN2+). Women were included in the study if they were older than 39 years and with no evidence of cervical cytology in the previous five years within the Public Primary Health Care System in Catalonia (Spain). 1,832 underscreened women from eight public primary health areas were identified during 2007-2008 and followed-up for over three years to estimate longitudinal detection of CIN2+. Accuracy of each screening test and the combination of both to detect CIN2+ was estimated. The risk of developing CIN2+ lesions according to histology data by cytology and HPV test results at baseline was estimated using the Kaplan-Meier method. At baseline, 6.7% of participants were HPV positive, 2.2% had an abnormal cytology and 1.3% had both tests positive. At the end of follow-up, 18 out of 767 (2.3%) underscreened women had a CIN2+, two of which were invasive CC. The three-year longitudinal sensitivity and specificity estimates to detect CIN2+ were 90.5% and 93.0% for HPV test and 38.2% and 97.8% for cytology. The negative predictive value was >99.0% for each test. No additional gains in validity parameters of HPV test were observed when adding cytology as co-test. The referral to colposcopy was higher for HPV but generated 53% higher detection of CIN2+ compared to cytology. Underscreened women had high burden of cervical disease. Primary HPV screening followed by cytology triage could be the optimal strategy to identify CIN2+ leading to longer and safe screen intervals.

Perceptions and Experiences of Human Papillomavirus (HPV) Infection and Testing among Low-Income Mexican Women

PubMed Central

León-Maldonado, Leith; Wentzell, Emily; Brown, Brandon; Allen-Leigh, Betania; Torres-Ibarra, Leticia; Salmerón, Jorge; Billings, Deborah L.; Thrasher, James F.; Lazcano-Ponce, Eduardo

2016-01-01

Background HPV infection causes cervical cancer, a major contributor to morbidity and mortality among low-income Mexican women. Human papillomavirus (HPV) DNA testing is now a primary screening strategy in Mexico’s early cervical cancer detection program (ECDP). Research on Mexican women’s perceptions of HPV and testing is necessary for establishing culturally appropriate protocols and educational materials. Here, we explore perceptions about HPV and HPV-related risk factors among low-income Mexican ECDP participants. Methods We conducted semi-structured interviews with 24 ECDP participants from two primary care health clinics in Michoacán state, Mexico. Interviews addressed women’s understandings of and experiences with HPV and HPV testing. Analysis was inductive and guided by the Health Belief Model with a focus on gender. Results Women’s confusion about HPV and HPV screening caused emotional distress. They understood HPV to be a serious disease that would always cause severe symptoms, often characterizing it as analogous to HIV or inevitably carcinogenic. Women also attributed it to men’s sexual behaviors, specifically infidelity and poor hygiene. Women described both sexes’ desire for sex as natural but understood men’s negative practices of masculinity, like infidelity, as the causes of women’s HPV infection. Some women believed dirty public bathrooms or heredity could also cause HPV transmission. Conclusions These results are consistent with prior findings that geographically and economically diverse populations lack clear understandings of the nature, causes, or symptoms of HPV, even among those receiving HPV testing. Our findings also reveal that local cultural discourse relating to masculinity, along with failure to provide sufficient education to low-income and indigenous-language speaking patients, exacerbate women’s negative emotions surrounding HPV testing. While negative emotions did not deter women from seeking testing, they could be ameliorated with better health education and communication. PMID:27149525

HPV testing for primary cervical screening: Laboratory issues and evolving requirements for robust quality assurance.

PubMed

Carozzi, Francesca Maria; Del Mistro, Annarosa; Cuschieri, Kate; Frayle, Helena; Sani, Cristina; Burroni, Elena

2016-03-01

This review aims to highlight the importance of Quality Assurance for Laboratories performing HPV test for Cervical Cancer Screening. An HPV test, to be used as primary screening test, must be validated according to international criteria, based on comparison of its clinical accuracy to HC2 or GP5+/6+ PCR-EIA tests. The number of validated platforms is increasing and appropriate Quality Assurance Programs (QAPs) which can interrogate longitudinal robustness and quality are paramount. This document describes the following topics: (1) the characteristics of an HPV laboratory and the personnel training needs, to ensure an elevated quality of the entire process and the optimal use of the resources; (2) the Quality Assurance, as both internal (IQA) and external quality assessment (EQA) systems, to be implemented and performed, and the description of the existing EQAs, including limitations; (3) general considerations for an optimal EQA program for hrHPV primary screening Due to the importance of Quality Assurance for this field, international efforts are necessary to improve QA International Collaboration. Copyright © 2015 Elsevier B.V. All rights reserved.

HPV outcomes in an access to care laryngeal cancer cohort

PubMed Central

Stephen, Josena K.; Chen, Kang Mei; Shah, Veena; Havard, Shaleta; Lu, Mei; Schweitzer, Vanessa G.; Gardner, Glendon; Worsham, Maria J.

2013-01-01

Objective Human papillomavirus (HPV), particularly HPV16, is a causative agent for 25% of head and neck squamous cell cancer, including laryngeal squamous cell cancer (LSCC). HPV positive (HPV+ve) patients, particularly oropharyngeal SCC, have improved prognosis. For LSCC, this remains to be established. The goal was to determine stage and survival outcomes in LSCC in the context of HPV infection. Study Design Historical cohort study. Setting Primary care academic health system. Subjects and Methods In 79 primary LSCC, HPV was determined using real-time quantitative PCR. Chi-square or Fisher’s exact test was used to test association of HPV+ve with 21 risk factors including race, stage, gender, age, smoking, alcohol, treatment, and health insurance. Kaplan-Meier and log rank test were used to study the association of HPV and LSCC survival outcome. Results HPV16 was detected in 27% LSCC. There was a trend towards higher HPV prevalence in Caucasian American (CA, 33%) vs African American (AA, 16%) (p=0.058). HPV was significantly associated with gender (p=0.016) and insurance type (p=0.001). HPV+ve LSCC had a slightly longer survival than HPV-negative (HPV−ve) patients, but the differences were not significant. There was no association with HPV and other risk factors including stage (early vs late). Conclusion We found high prevalence of HPV in males and lower prevalence of HPV infection in AA compared to CA. A slightly better survival for HPV+ve LSCC versus HPV−ve was noted but was not significant. Larger multi ethnic LSCC cohorts are needed to more clearly delineate HPV related survival across ethnicities. PMID:22267491

Introduction of molecular HPV testing as the primary technology in cervical cancer screening: Acting on evidence to change the current paradigm.

PubMed

Tota, Joseph E; Bentley, James; Blake, Jennifer; Coutlée, François; Duggan, Máire A; Ferenczy, Alex; Franco, Eduardo L; Fung-Kee-Fung, Michael; Gotlieb, Walter; Mayrand, Marie-Hélène; McLachlin, Meg; Murphy, Joan; Ogilvie, Gina; Ratnam, Sam

2017-05-01

Since being introduced in the 1940s, cervical cytology - despite its limitations - has had unequivocal success in reducing cervical cancer burden in many countries. However, we now know that infection with human papillomavirus (HPV) is a necessary cause of cervical cancer and there is overwhelming evidence from large-scale clinical trials, feasibility studies and real-world experience that supports the introduction of molecular testing for HPV as the primary technology in cervical cancer screening (i.e., "HPV primary screening"). While questions remain about the most appropriate age groups for screening, screening interval and triage approach, these should not be considered barriers to implementation. Many countries are in various stages of adopting HPV primary screening, whereas others have not taken any major steps towards introduction of this approach. As a group of clinical experts and researchers in cervical cancer prevention from across Canada, we have jointly authored this comprehensive examination of the evidence to implement HPV primary screening. Our intention is to create a common understanding among policy makers, agencies, clinicians, researchers and other stakeholders about the evidence concerning HPV primary screening to catalyze the adoption of this improved approach to cervical cancer prevention. With the first cohort of vaccinated girls now turning 21, the age when routine screening typically begins, there is increased urgency to introduce HPV primary screening, whose performance may be less adversely affected compared with cervical cytology as a consequence of reduced lesion prevalence post-vaccination. Published by Elsevier Inc.

The clinical effectiveness and cost-effectiveness of primary human papillomavirus cervical screening in England: extended follow-up of the ARTISTIC randomised trial cohort through three screening rounds.

PubMed

C Kitchener, Henry; Canfell, Karen; Gilham, Clare; Sargent, Alexandra; Roberts, Chris; Desai, Mina; Peto, Julian

2014-04-01

The ARTISTIC (A Randomised Trial In Screening To Improve Cytology) trial originally reported after two rounds of primary cervical screening with human papillomavirus (HPV). Extended follow-up of the randomised trial cohort through a third round could provide valuable insight into the duration of protection of a negative HPV test, which could allow extended screening intervals. If HPV primary screening is to be considered in the national programme, then determining its cost-effectiveness is key, and a detailed economic analysis using ARTISTIC data is needed. (1) To determine the round 3 and cumulative rates of cervical intraepithelial neoplasia (CIN) grade 2 or worse (2+) and CIN grade 3 or worse (CIN3+) between the revealed and concealed arms of ARTISTIC after three screening rounds over 6 years. (2) To compare the cumulative incidence of CIN2+ over three screening rounds following negative screening cytology with that following negative baseline HPV. (3) To determine whether or not HPV screening could safely extend the screening interval from 3 to 6 years. (4) To study the potential clinical utility of an increased cut-off of 2 relative light unit/mean control (RLU/Co) for Hybrid Capture 2 (HC2) and HPV genotyping in primary cervical screening. (5) To determine the potential impact of HPV vaccination with Cervarix™ in terms of preventing abnormal cytology and CIN2+. (6) To determine the cost-effectiveness of HPV primary screening compared with current practice using cervical cytology in England. The ARTISTIC study cohort was recalled for a third round of screening 3 years after round 2 and 6 years following their enrolment to the study. Both arms of the original trial used a single protocol during round 3. ARTISTIC study cohort undergoing cervical screening in primary care in Greater Manchester, UK. Between July 2007 and September 2009, 8873 women participated in round 3; 6337 had been screened in round 2 and 2536 had not been screened since round 1. All women underwent liquid-based cytology and HPV testing and genotyping. Colposcopy was offered to women with moderate dyskaryosis or worse and with HPV-positive mild dyskaryosis/borderline changes. Women with negative cytology or HPV-negative mild dyskaryosis/borderline changes were returned to routine recall. Principal outcomes were cumulative rates of CIN2+ over three screening rounds by cytology and HPV status at entry; HPV type specific rates of CIN2+; effect of age on outcomes correlated with cytology and HPV status; comparison of HC2 cut-off RLU/Co of both 1 and 2; and cost-effectiveness of HPV primary screening. The median duration of follow-up was 72.7 months in round 3. Over the three screening rounds, there was no significant difference in CIN2+ [odds ratio (OR): 1.06, 95% confidence interval (CI) 0.89 to 1.26, p = 0.5)] or CIN3+ (OR: 0.90, 95% CI 0.72 to 1.14, p = 0.4) rates between the trial arms (revealed vs. concealed). Overall, 16% of women were HC2 positive at entry, decreasing from 40% in women aged 20-24 years to around 7% in women aged over 50 years. Abnormal cytology rates at entry were 13% for borderline+ and 2% for moderate+ cytology. Following positive cytology at entry, the cumulative rate of CIN2+ was 20.5%, and was 20.1% following a HPV-positive result at baseline. The cumulative CIN2+ rate for women who were HPV negative at baseline was only 0.87% (95% CI 0.70% to 1.06%) after three rounds of screening, significantly lower than that for women with negative cytology, which was 1.41% (95% CI 1.19% to 1.65%). Women who were HPV negative at baseline had similar protection from CIN2+ after 6 years as women who were cytology negative at baseline after 3 years. Women who were HPV positive/cytology negative at baseline had a cumulative CIN2+ rate at 6 years of 7.7%, significantly higher than that for women who were cytology positive/HPV negative (3.2%). Women who were HPV type 16 positive at baseline had a cumulative CIN2+ rate over three rounds of 43.6% compared with 20.1% for any HPV-positive test. Using a HC2 cut-off of RLU/Co ≥ 2 would maintain acceptable sensitivity and result in 16% fewer HPV-positive results. Typing data suggested that around 55-60% of high-grade cytology and CIN2+, but less than 25% of low-grade cytology, would be prevented by HPV vaccine given current rates of coverage in the UK national programme. For the cost-effectiveness analysis, most of the primary HPV strategies examined where HPV was used as the sole primary test were cost saving in both unvaccinated and vaccinated cohorts under baseline cost assumptions, with a 7-18% reduction in annual screening-associated costs in unvaccinated cohorts and a 9-22% reduction for vaccinated cohorts. Utilising partial genotyping at the primary screening stage to identify women with HPV 16/18 and referring them to colposcopy was the most effective strategy (barring co-testing, which is significantly more costly than any other strategies considered), resulting in 83 additional life-years per 100,000 women for unvaccinated women when compared with current practice, and similar life-years saved compared with current practice for vaccinated women. In unvaccinated cohorts, however, this genotyping strategy is predicted to result in a 20% increase in the number of colposcopies performed in England, although in vaccinated cohorts the number of colposcopy referrals was predicted to be lower than in current practice. For all strategies in which HPV is used as the sole primary screening test, decreasing the follow-up interval for intermediate-risk women from 24 to 12 months increased the overall effectiveness of primary HPV screening. In exploratory analysis, strategies for which cytology screening was retained until either age 30 or 35 years, and for which HPV testing was used at older ages, were predicted to be of higher costs and intermediate effectiveness than those associated with full implementation of primary HPV screening from age 25 years. However, this finding should be interpreted with caution as it depends on assumptions made about screening behaviour and compliance with recommendations at the 'switch over' point. HPV testing as an initial screen was significantly more protective over three rounds (6 years) than the current practice of cytology and the use of primary HPV screening could allow a safe lengthening of the screening interval. A substantial decrease in high-grade cytology and CIN2+ can be expected as a consequence of the HPV vaccination programme. A HC2 cut-off of 2RLU/Co instead of the manufacturer's recommended cut-off of 1 would be clinically beneficial in terms of an optimal balance between sensitivity and specificity. Modelled analysis predicts that primary HPV screening would be both more effective and cost saving compared with current practice with cervical cytology for a number of potential strategies in both unvaccinated and vaccinated cohorts. Compliance with surveillance and optimal management of HPV-positive/cytology-negative women after primary HPV screening is of key importance. Limitations of the economic investigation included the need to make assumptions around compliance with screening attendance and follow-up for longer screening intervals in the future, assumptions regarding maintenance of current uptake vaccination in the future, and assumptions regarding the stability of cost of HPV and cytology tests in the future. Detailed sensitivity analysis across a range of possible assumptions was conducted to address these issues. This study and the economic evaluation lend support to convert from cytology to HPV-based screening. Future work should include researching (i) the attitudes of women who test HPV positive/cytology negative, (ii) the value of complementary biomarkers and (iii) activities relevant to primary HPV screening in unvaccinated and vaccinated populations from the point of view of QALY assessment. Current Controlled Trials ISRCTN25417821.

Human papillomavirus outcomes in an access-to-care laryngeal cancer cohort.

PubMed

Stephen, Josena K; Chen, Kang Mei; Shah, Veena; Havard, Shaleta; Lu, Mei; Schweitzer, Vanessa P; Gardner, Glendon; Worsham, Maria J

2012-05-01

Human papillomavirus (HPV), particularly HPV16, is a causative agent for 25% of head and neck squamous cell cancer, including laryngeal squamous cell cancer (LSCC). HPV-positive (HPV+ve) patients, particularly those with oropharyngeal SCC, have improved prognosis. For LSCC patients, this remains to be established. The goal was to determine stage and survival outcomes in LSCC in the context of HPV infection. Historical cohort study. Primary care academic health system. In 79 patients with primary LSCC, HPV was determined using real-time quantitative polymerase chain reaction. χ(2) or Fisher exact test was used to test the association of HPV+ve with 21 risk factors including race, stage, gender, age, smoking, alcohol, treatment, and health insurance. Kaplan-Meier and log-rank tests were used to study the association of HPV and LSCC survival outcome. HPV16 was detected in 27% of LSCC patients. Caucasian American (CA) patients had higher HPV prevalence (33%) than did African American (AA) LSCC patients (16%; P = .058). HPV was significantly associated with gender (P = .016) and insurance type (P = .001). There were no differences in survival between HPV+ve and HPV-negative (HPV-ve) patients. There was no association with HPV and other risk factors including stage (early vs late). We found a high prevalence of HPV in men and a lower prevalence of HPV infection in AA compared with CA. Despite the strikingly better survival of patients with HPV+ve oropharyngeal tumors, even when adjusted for smoking, this correlation does not seem to hold true in the larynx. Larger multiethnic LSCC cohorts are needed to more clearly delineate HPV-related survival across ethnicities.

CITRUS, cervical cancer screening trial by randomization of HPV testing intervention for upcoming screening: Design, methods and baseline data of 18,471 women.

PubMed

Morisada, Tohru; Teramoto, Katsuhiro; Takano, Hirokuni; Sakamoto, Ikuko; Nishio, Hiroshi; Iwata, Takashi; Hashi, Akihiko; Katoh, Ryohei; Okamoto, Aikou; Sasaki, Hiroshi; Nakatani, Eiji; Teramukai, Satoshi; Aoki, Daisuke

2017-10-01

To assess the efficacy of screening with concurrent liquid-based cytology and human papillomavirus (HPV) testing for primary cervical cancer screening, we initiated a randomized trial entitled CervIcal cancer screening Trial by Randomization of HPV testing intervention for Upcoming Screening (CITRUS). Between June 2013 and March 2015, women aged 30-64 years of age who participated in a regular cervical cancer screening program (every 2 years) were invited to enrollment of our study. After giving their informed consent, 18,402 women were randomly assigned to liquid-based cytology as the control group (n=9145) or to HPV DNA testing with liquid-based cytology as the intervention group (n=9257). We subsequently compared the incidence rate of cervical intraepithelial neoplasia (CIN), the rate of false positive tests and the rate of overdiagnosis, as well as assessing the risks and benefits of receiving screening for women in both groups. The primary outcome of our study was the incidence of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) during the study period of around 6 years. In the control group, 97.9% of women were NILM, and 2.06% ASC-US or worse (ASC-US+). In the intervention group, 87.13% of women were NILM/HPV negative, 0.72% ASC-US/HPV negative, 10.34% NILM/HPV positive, 0.69% ASC-US/HPV positive, 0.90% worse than ASC-US/either HPV. Positive HPV testing was not linearly related to age in our study. Insights from CITRUS will provide future prospects for cervical cancer screening focused on the use of HPV testing in Japan. NCT01895517, UMIN000010843, TRIUC1312. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Role of Human Papillomavirus Genotyping in Cervical Cancer Screening: A Large-Scale Evaluation of the cobas HPV Test.

PubMed

Schiffman, Mark; Boyle, Sean; Raine-Bennett, Tina; Katki, Hormuzd A; Gage, Julia C; Wentzensen, Nicolas; Kornegay, Janet R; Apple, Raymond; Aldrich, Carrie; Erlich, Henry A; Tam, Thanh; Befano, Brian; Burk, Robert D; Castle, Philip E

2015-09-01

The cobas HPV Test ("cobas"; Roche Molecular Systems) detects HPV16 and HPV18 individually, and a pool of 12 other high-risk (HR) HPV types. The test is approved for (i) atypical squamous cells of undetermined significance (ASC-US) triage to determine need for colposcopy, (ii) combined screening with cytology ("cotesting"), and (iii) primary HPV screening. To assess the possible value of HPV16/18 typing, >17,000 specimens from a longitudinal cohort study of initially HPV-positive women (HC2, Qiagen) were retested with cobas. To study accuracy, cobas genotyping results were compared with those of an established method, the Linear Array HPV Genotyping Test (LA, Roche Molecular Systems). Clinical value of the typing strategy was evaluated by linking the cobas results (supplemented by other available typing results) to 3-year cumulative risks of CIN3+. Grouped hierarchically (HPV16, else HPV18, else other HR types, else negative), the κ statistic for agreement between cobas and LA was 0.86 [95% confidence interval (CI), 0.86-0.87]. In all three scenarios, HPV16-positive women were at much higher 3-year risk of CIN3+ than HPV16-negative women: women ages 21 and older with ASC-US (14.5%; 95% CI, 13.5%-15.5% vs. 3.5%; 95% CI, 3.3-3.6); women ages 30 years and older that were HPV-positive cytology-negative (10.3%; 95% CI, 9.6-11.1 vs. 2.3%; 95% CI, 2.2-2.4); and all women 25 years and older that were HPV-positive (18.5%; 95% CI, 17.8-19.2 vs. 4.3%; 95% CI, 4.2-4.4). The cobas and LA results show excellent agreement. The data support HPV16 typing. HPV16 typing is useful in the management of HPV-positive/cytology-negative women in cotesting, of all HPV-positive women in primary HPV testing, and perhaps in the management of HPV-positive women with ASC-US. Cancer Epidemiol Biomarkers Prev; 24(9); 1304-10. ©2015 American Association for Cancer Research.

The Abbott RealTime High Risk HPV test is a clinically validated human papillomavirus assay for triage in the referral population and use in primary cervical cancer screening in women 30 years and older: a review of validation studies.

PubMed

Poljak, Mario; Oštrbenk, Anja

2013-01-01

Human papillomavirus (HPV) testing has become an essential part of current clinical practice in the management of cervical cancer and precancerous lesions. We reviewed the most important validation studies of a next-generation real-time polymerase chain reaction-based assay, the RealTime High Risk HPV test (RealTime)(Abbott Molecular, Des Plaines, IL, USA), for triage in referral population settings and for use in primary cervical cancer screening in women 30 years and older published in peer-reviewed journals from 2009 to 2013. RealTime is designed to detect 14 high-risk HPV genotypes with concurrent distinction of HPV-16 and HPV-18 from 12 other HPV genotypes. The test was launched on the European market in January 2009 and is currently used in many laboratories worldwide for routine detection of HPV. We concisely reviewed validation studies of a next-generation real-time polymerase chain reaction (PCR)-based assay: the Abbott RealTime High Risk HPV test. Eight validation studies of RealTime in referral settings showed its consistently high absolute clinical sensitivity for both CIN2+ (range 88.3-100%) and CIN3+ (range 93.0-100%), as well as comparative clinical sensitivity relative to the currently most widely used HPV test: the Qiagen/Digene Hybrid Capture 2 HPV DNA Test (HC2). Due to the significantly different composition of the referral populations, RealTime absolute clinical specificity for CIN2+ and CIN3+ varied greatly across studies, but was comparable relative to HC2. Four validation studies of RealTime performance in cervical cancer screening settings showed its consistently high absolute clinical sensitivity for both CIN2+ and CIN3+, as well as comparative clinical sensitivity and specificity relative to HC2 and GP5+/6+ PCR. RealTime has been extensively evaluated in the last 4 years. RealTime can be considered clinically validated for triage in referral population settings and for use in primary cervical cancer screening in women 30 years and older.

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

PubMed

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

2017-05-01

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

Molekulare Diagnostik der HPV Infektion

PubMed Central

Wentzensen, PD Dr. med. Nicolas

2014-01-01

Carcinogenic human papillomaviruses (HPV) cause the majority of cervical cancers and other anogentical cancers. Large randomized trials have shown that HPV testing can be efficiently used for primary cervical cancer screening. Other applications include the triage of abnormal cytology results and the follow-up of women after treatment. Many assays have been developed to measure DNA, RNA, and proteins of HPV. The various tests can have very different applications. It is important to validate HPV assays before they are implemented in screening or clinical care. PMID:21845360

Primary cervical cancer screening with HPV testing compared with liquid-based cytology: results of round 1 of a randomised controlled trial -- the HPV FOCAL Study.

PubMed

Ogilvie, G S; Krajden, M; van Niekerk, D J; Martin, R E; Ehlen, T G; Ceballos, K; Smith, L W; Kan, L; Cook, D A; Peacock, S; Stuart, G C E; Franco, E L; Coldman, A J

2012-12-04

Round 1 data of human papillomavirus (HPV) FOCAL, a three-arm, randomised trial, which aims to establish the efficacy of HPV DNA testing as a primary screen for cervical cancer, are presented. The three arms are: Control arm - liquid based cytology with atypical squamous cells of unknown significance (ASC-US) triage with hrHPV testing; Intervention Arm - hrHPV at entry with liquid-based cytology (LBC) triage of hrHPV positives, with exit screen at 4 years; Safety check arm - hrHPV at entry with LBC triage of hrHPV positives with exit screen at 2 years. A total of 6154 women were randomised to the control arm and 12 494 to the HPV arms (intervention and safety check). In the HPV arm, the baseline cervical intraepithelial neoplasia (CIN)2+ and CIN3+ rate was 9.2/1000 (95%CI; 7.4, 10.9) and 4.8/1000 (95%CI; 3.6, 6.1), which increased to 16.1/1000 (95%CI 13.2, 18.9) for CIN2+ and to 8.0/1000 (95%CI; 5.9, 10.0) for CIN3+ after subsequent screening of HPV-DNA-positive/cytology-negative women. Detection rate in the control arm remained unchanged after subsequent screening of ASC-US-positive/hrHPV DNA-negative women at 11.0/1000 for CIN2+ and 5.0/1000 for CIN3+. After subsequent screening of women who were either hrHPV positive/cytology negative or ASC-US positive/HPV negative, women randomised to the HPV arms had increased CIN2+ detection compared with women randomised to the cytology arm.

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

PubMed Central

Zhao, Chengquan

2015-01-01

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

[Genotyping of oncogenic human papilloma viruses in women with HG SIL diagnosis].

PubMed

Kedzia, Witold; Pruski, Dominik; Józefiak, Agata; Rokita, Wojciech; Spaczyński, Marek

2010-10-01

Development of primary prevention of cervical cancer in other words a vaccination against selected, oncogenic HPV types, entails an increasing importance of epidemiological studies and prevalence of various types of human papilloma virus. The incidence of HPV varies depending on the geographic location of the population. The effectiveness of primary prevention against HPV 16, 18, in the context of reducing the incidence of cervical cancer will depend, among others, on the prevalence of these types in the population and virus-like antigens, which are partially cross-resistant. Identification of the most frequent, oncogenic HPV types in women with HG SIL diagnosis from Central and Western Poland to assess the merits of the development of primary prevention. For the purpose of molecular tests identifying the presence of 13 DNA oncogenic virus types, swabs were taken with the cyto-brush from 76 women diagnosed with CIN 2 or CIN 3 (HG SIL). Patients eligible for the study were diagnosed at the Laboratory of Pathophysiology of Uterine Cervix, Gynecology and Obstetrics Clinical Hospital of Karol Marcinkowski University of Medical Sciences. Patients came from Central and Western parts of Poland. Cell material in which the method of Amplicor HPV (Roche Diagnostics) identified the presence of DNA of oncogenic HPV types was in each case subsequently subjected to genotyping using the molecular test - Linear Array HPV Genotyping (Roche Diagnostics). Five most common oncogenic HPV types in order of detection included: 16, 33, 18, 31, 56. Together these five types of virus comprised 75.86% (88/116) of all detected HPV types. 1. In women from Central and Western Poland, diagnosed with HG SIL, the most common HPV genotypes were HPV 16, HPV33, HPV 18, HPV31, HPV56. 2. Two HPV types 16 and 18, against which vaccinations are directed, belong to the group of three genotypes of HPV most commonly identified in the evolution of CIN 2, CIN 3 diagnosed in women from Central and Western Poland.

Test performance and acceptability of self- versus provider-collected swabs for high-risk HPV DNA testing in female-to-male trans masculine patients.

PubMed

Reisner, Sari L; Deutsch, Madeline B; Peitzmeier, Sarah M; White Hughto, Jaclyn M; Cavanaugh, Timothy P; Pardee, Dana J; McLean, Sarah A; Panther, Lori A; Gelman, Marcy; Mimiaga, Matthew J; Potter, Jennifer E

2018-01-01

High-risk human papillomavirus (hrHPV) causes virtually all cervical cancers. Trans masculine (TM) people (those assigned female at birth who identify with a gender other than female) have low uptake of conventional cervical cancer screening. Self-collected hrHPV DNA testing has high levels of acceptability among cisgender (non-transgender) females and may support increased cervical cancer screening uptake in TM individuals. To assess the test performance and acceptability of self-collected vaginal specimens in comparison to provider-collected cervical swabs for hrHPV DNA detection in TM individuals ages 21-64 years. Between March 2015-September 2016, 150 TM participants with a cervix (mean age = 27.5 years; SD = 5.7) completed a one-time study visit comprised of a self-report survey, self-collected vaginal HPV DNA swab, clinician-administered cervical HPV swab, and brief interview on acceptability of clinical procedures. Participants were randomized to complete either self- or provider-collection first to minimize ordering effects. Self- and provider-collected samples were tested for 13 hrHPV DNA types using a DNA Hybridization Assay. The primary outcome variable was the concordance (kappa statistic) and performance (sensitivity, specificity) of self-collected vaginal HPV DNA specimens versus provider-collected cervical HPV swabs as the gold standard. Of the 131 participants completing both the self- and provider-collected HPV tests, 21 cases of hrHPV were detected by the provider cervical swab (gold standard; 16.0% hrHPV prevalence); 15 of these cases were accurately detected by the self-collected vaginal swab (71.4% concordance) (Kappa = 0.75, 95% Confidence Interval [CI]: 0.59, 0.92; p<0.001). Compared to the provider-collected cervical hrHPV DNA sample (gold standard), the self-collected vaginal hrHPV DNA test demonstrated a sensitivity of 71.4% (95% CI: 0.52, 0.91; p = 0.0495) and specificity of 98.2% (95% CI: 0.96, 1.00; p<0.0001). Over 90% of participants endorsed a preference for the self-collected vaginal swab over provider-collected cervical swab. Self-collected vaginal swabs are highly acceptable to TM as a means to test for hrHPV DNA. Test performance of this self-collection method for hrHPV detection in TM is consistent with previous studies in cisgender females. Self-collected vaginal swab testing for hrHPV DNA represents a reasonable and patient-centered strategy for primary cervical cancer screening in TM patients unwilling to undergo provider collection of specimens via speculum exam.

Age-specific performance of careHPV versus Papanicolaou and visual inspection of cervix with acetic acid testing in a primary cervical cancer screening.

PubMed

Labani, Satyanarayana; Asthana, Smita

2016-01-01

Human papillomavirus (HPV) is recommended as a primary screening tool for cervical screening. Assessment of age-specific performance of newer HPV careHPV DNA testing is important as risk of cervical intraepithelial neoplasia (CIN) varies at different ages. We aim to evaluate careHPV in comparison to Papanicolaou (Pap) test and visual inspection of the cervix with acetic acid (VIA) cervical screening tests for the detection of high-grade CIN. The cross sectional study was conducted in a rural population of North India. Ever-married women 30-59 years of age were invited for screening by careHPV (self-collected vaginal and physician-collected cervical samples), Pap test and VIA. Associations for trend in age for detecting histological-confirmed CINII+ and CINIII+ for each screening test were evaluated. Age-specific association with each screening test was evaluated. Of a total of 7761 women invited, 5032 were screened and analysis was performed on 4658 with all screen test results. No significant (p>0.05) association of age for any screening test in the detection of CINII+ or CINIII+ was observed. For the older age group, cervical HPV (CHPV) showed high sensitivity and specificity for CINII+ detection. Specificity of CHPV or vaginal HPV (VHPV) was equal or higher than Pap in all age groups. Cervical screening options of CHPV or VHPV, or Pap, performed equally in the younger age group while CHPV might be an option for all ages in the detection of high-grade CIN. 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/

Utility of the Roche Cobas 4800 for detection of high-risk human papillomavirus in formalin-fixed paraffin-embedded oropharyngeal squamous cell carcinoma.

PubMed

Pettus, Jason R; Wilson, Terri L; Steinmetz, Heather B; Lefferts, Joel A; Tafe, Laura J

2017-02-01

Clinical laboratories are expected to reliably identify human papilloma virus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) for prognostic and potential therapeutic applications. In addition to surrogate p16 immunohistochemistry (IHC) testing, DNA-based HPV-specific testing strategies are widely utilized. Recognizing the efficiency of the Roche Cobas 4800 platform for testing gynecological cytology specimens for high-risk HPV, we elected to evaluate the potential utility of this platform for testing formalin-fixed paraffin-embedded (FFPE) OPSCC tissue. Using the Roche Linear Array assay for comparison, we tested twenty-eight samples (16 primary OPSCC, 2 lymph node metastases from primary OPSCC, 1 oral tongue carcinoma, 3 benign squamous papillomas, and 3 non-oropharyngeal carcinoma tissues). Excluding two invalid results, the Roche Cobas 4800 testing resulted in excellent inter-assay concordance (25/26, 96.2%) and 100% concordance for HPV-16/HPV-18 positive samples. This data suggests that the Roche Cobas 4800 platform may be a cost-effective method for testing OPSCC FFPE tissues in a clinical molecular pathology laboratory setting. Copyright © 2016 Elsevier Inc. All rights reserved.

Primary hrHPV DNA testing in cervical cancer screening: how to manage screen-positive women? A POBASCAM trial substudy.

PubMed

Dijkstra, Maaike G; van Niekerk, Dirk; Rijkaart, Dorien C; van Kemenade, Folkert J; Heideman, Daniëlle A M; Snijders, Peter J F; Meijer, Chris J L M; Berkhof, Johannes

2014-01-01

High-risk human papillomavirus (hrHPV) testing has higher sensitivity but lower specificity than cytology for cervical (pre)-cancerous lesions. Therefore, triage of hrHPV-positive women is needed in cervical cancer screening. A cohort of 1,100 hrHPV-positive women, from a population-based screening trial (POBASCAM: n = 44,938; 29-61 years), was used to evaluate 10 triage strategies, involving testing at baseline and six months with combinations of cytology, HPV16/18 genotyping, and/or repeat hrHPV testing. Clinical endpoint was cervical intraepithelial neoplasia grade 3 or worse (CIN3(+)) detected within four years; results were adjusted for women not attending repeat testing. A triage strategy was considered acceptable, when the probability of no CIN3(+) after negative triage (negative predictive value, NPV) was at least 98%, and the CIN3(+) risk after positive triage (positive predictive value, PPV) was at least 20%. Triage at baseline with cytology only yielded an NPV of 94.3% [95% confidence interval (CI), 92.0-96.0] and a PPV of 39.7% (95% CI, 34.0-45.6). An increase in NPV, against a modest decrease in PPV, was obtained by triaging women with negative baseline cytology by repeat cytology (NPV 98.5% and PPV 34.0%) or by baseline HPV16/18 genotyping (NPV 98.8% and PPV 28.5%). The inclusion of both HPV16/18 genotyping at baseline and repeat cytology testing provided a high NPV (99.6%) and a moderately high PPV (25.6%). Triaging hrHPV-positive women by cytology at baseline and after 6 to 12 months, possibly in combination with baseline HPV16/18 genotyping, seems acceptable for cervical cancer screening. Implementable triage strategies are provided for primary hrHPV screening in an organized setting.

Projected future impact of HPV vaccination and primary HPV screening on cervical cancer rates from 2017-2035: Example from Australia.

PubMed

Hall, Michaela T; Simms, Kate T; Lew, Jie-Bin; Smith, Megan A; Saville, Marion; Canfell, Karen

2018-01-01

Many countries are transitioning from cytology-based to longer-interval HPV screening. Trials comparing HPV-based screening to cytology report an increase in CIN2/3 detection at the first screen, and longer-term reductions in CIN3+; however, population level year-to-year transitional impacts are poorly understood. We undertook a comprehensive evaluation of switching to longer-interval primary HPV screening in the context of HPV vaccination. We used Australia as an example setting, since Australia will make this transition in December 2017. Using a model of HPV vaccination, transmission, natural history and cervical screening, Policy1-Cervix, we simulated the planned transition from recommending cytology every two years for sexually-active women aged 18-20 to 69, to recommending HPV screening every five years for women aged 25-74 years. We estimated rates of CIN2/3, cervical cancer incidence, and mortality for each year from 2005 to 2035, considering ranges for HPV test accuracy and screening compliance in the context of HPV vaccination (current coverage ~82% in females; ~76% in males). Transient increases are predicted to occur in rates of CIN2/3 detection and invasive cervical cancer in the first two to three years following the screening transition (of 16-24% and 11-14% in respectively, compared to 2017 rates). However, by 2035, CIN2/3 and invasive cervical cancer rates are predicted to fall by 40-44% and 42-51%, respectively, compared to 2017 rates. Cervical cancer mortality rates are predicted to remain unchanged until ~2020, then decline by 34-45% by 2035. Over the period 2018-2035, switching to primary HPV screening in Australia is expected to avert 2,006 cases of invasive cervical cancer and save 587 lives. Transient increases in detected CIN2/3 and invasive cancer, which may be detectable at the population level, are predicted following a change to primary HPV screening. This is due to improved test sensitivity bringing forward diagnoses, resulting in longer term reductions in both cervical cancer incidence and mortality. Fluctuations in health outcomes due to the transition to a longer screening interval are predicted to occur for 10-15 years, but cervical cancer rates will be significantly reduced thereafter due to the impact of HPV vaccination and HPV screening. In order to maintain confidence in primary HPV screening through the transitional phase, it is important to widely communicate that an initial increase in CIN2/3 and perhaps even invasive cervical cancer is expected after a national transition to primary HPV screening, that this phenomenon is due to increased prevalent disease detection, and that this effect represents a marker of screening success.

Incidence of human papillomavirus contamination of transvaginal probes in Japan and possible contamination prevention strategy.

PubMed

Kuwata, Tomoyuki; Takahashi, Hironori; Koibuchi, Harumi; Ichizuka, Kiyotake; Natori, Michiya; Matsubara, Shigeki

2016-10-01

To clarify the present status of human papillomavirus (HPV) contamination of transvaginal probes in Japan and propose a preventive method. This study was performed at three institutes: a tertiary center, secondary hospital, and primary facility. To identify contamination rates, probes were disinfected and covered with probe covers and condoms; the cover was changed for each patient. The probes were tested for HPV, and those with HPV detected were analyzed to identify the type of HPV. Next, nurses put on new gloves before covering the probe for each patient, and the probes were similarly tested for HPV. A total of 120 probes were tested, and HPV was detected from a total of five probes, a contamination rate of 4.2 % (5/120). HPV was detected in all three institutes. Importantly, high-risk HPV, i.e., HPV-52, 56, and 59, was detected. After the "glove change strategy" was implemented, HPV was not detected on any of 150 probes tested at any of the three institutions. In Japan, the HPV contamination rate of vaginal probes in routine practice was 4.2 %. There was no HPV contamination of probes after changing the gloves for cover exchange for each patient. This strategy may prevent HPV probe contamination.

Detection and genotyping of HPV in urine samples from Chilean women attending primary health care centers.

PubMed

Vergara, Nicolás; Balanda, Monserrat; Hidalgo, Wilma; Martín, Héctor San; Aceituno, Alexis; Roldán, Francisco; Villalón, Tania; Hott, Melissa; Espinoza, Gloria; Quiero, Andrea; Valenzuela, María T; Ramírez, Eugenio

2018-04-01

Cervical cancer is the second most common malignant neoplasm in women worldwide representing approximately 10% of all types of cancers. Triage of women through cervical cytology has been an important strategy for the surveillance and control of new cases of cervical cancer. However, in many regions around the world cervical cytology has a low coverage compared to developed countries. The molecular detection of HPV is the most effective method to increase the screening sensitivity of women at risk of developing cervical cancer. There are very few studies about the efficacy of urine testing for detection of HPV in women followed up in primary health care centers. Consequently, the efficacy of using urine HPV screening in these populations has not been addressed yet. Here, we compared the detection of HPV in simultaneous urine and cervical samples of women followed up in primary health care centers. Urine and cervical samples were analyzed in 543 women attending at primary health care centers. HPV was detected by real time PCR, and HPV typing performed by PCR-RLB. A general HPV concordance of 86.2% (κ = 0.72) was determined between urine and cervical samples. The concordance for HPV-16 and 18 was almost perfect (κ = 0.82) and strong (κ = 0.77), respectively. The sensitivity and specificity for all HPV genotypes in urine using cervical samples as reference were 82.1 and 93.7%, respectively. The results showed that urine is a good alternative as clinical sample for HPV screening in women attending primary health care centers. Therefore, urine should be used as an alternative sample for increasing triage coverage either in refractory women participating in Pap surveillance programs or when cervical samples are not available.

Test performance and acceptability of self- versus provider-collected swabs for high-risk HPV DNA testing in female-to-male trans masculine patients

PubMed Central

Deutsch, Madeline B.; Peitzmeier, Sarah M.; White Hughto, Jaclyn M.; Cavanaugh, Timothy P.; Pardee, Dana J.; McLean, Sarah A.; Panther, Lori A.; Gelman, Marcy; Mimiaga, Matthew J.; Potter, Jennifer E.

2018-01-01

Background High-risk human papillomavirus (hrHPV) causes virtually all cervical cancers. Trans masculine (TM) people (those assigned female at birth who identify with a gender other than female) have low uptake of conventional cervical cancer screening. Self-collected hrHPV DNA testing has high levels of acceptability among cisgender (non-transgender) females and may support increased cervical cancer screening uptake in TM individuals. Objective To assess the test performance and acceptability of self-collected vaginal specimens in comparison to provider-collected cervical swabs for hrHPV DNA detection in TM individuals ages 21–64 years. Methods Between March 2015-September 2016, 150 TM participants with a cervix (mean age = 27.5 years; SD = 5.7) completed a one-time study visit comprised of a self-report survey, self-collected vaginal HPV DNA swab, clinician-administered cervical HPV swab, and brief interview on acceptability of clinical procedures. Participants were randomized to complete either self- or provider-collection first to minimize ordering effects. Self- and provider-collected samples were tested for 13 hrHPV DNA types using a DNA Hybridization Assay. The primary outcome variable was the concordance (kappa statistic) and performance (sensitivity, specificity) of self-collected vaginal HPV DNA specimens versus provider-collected cervical HPV swabs as the gold standard. Results Of the 131 participants completing both the self- and provider-collected HPV tests, 21 cases of hrHPV were detected by the provider cervical swab (gold standard; 16.0% hrHPV prevalence); 15 of these cases were accurately detected by the self-collected vaginal swab (71.4% concordance) (Kappa = 0.75, 95% Confidence Interval [CI]: 0.59, 0.92; p<0.001). Compared to the provider-collected cervical hrHPV DNA sample (gold standard), the self-collected vaginal hrHPV DNA test demonstrated a sensitivity of 71.4% (95% CI: 0.52, 0.91; p = 0.0495) and specificity of 98.2% (95% CI: 0.96, 1.00; p<0.0001). Over 90% of participants endorsed a preference for the self-collected vaginal swab over provider-collected cervical swab. Conclusion Self-collected vaginal swabs are highly acceptable to TM as a means to test for hrHPV DNA. Test performance of this self-collection method for hrHPV detection in TM is consistent with previous studies in cisgender females. Self-collected vaginal swab testing for hrHPV DNA represents a reasonable and patient-centered strategy for primary cervical cancer screening in TM patients unwilling to undergo provider collection of specimens via speculum exam. PMID:29538411

Prevalence of high-risk human papillomavirus among women in two English-speaking Caribbean countries.

PubMed

Andall-Brereton, Glennis; Brown, Eulynis; Slater, Sherian; Holder, Yvette; Luciani, Silvana; Lewis, Merle; Irons, Beryl

2017-06-08

To characterize high-risk human papillomavirus (HPV) infections in a sample of women in two small English-speaking Caribbean countries: Saint Kitts and Nevis and Saint Vincent and the Grenadines. Sexually active women ≥ 30 years old attending primary care health facilities participated in the study. Each participant had a gynecological examination, and two cervical specimens were collected: (1) a specimen for a Papanicolaou (Pap) test and (2) a sample of exfoliated cervical cells for HPV DNA testing, using the HPV High Risk Screen Real-TM (Sacace). High-risk HPV genotypes were assessed in 404 women in Saint Kitts and Nevis and 368 women in Saint Vincent and the Grenadines. High-risk HPV was detected in 102 of 404 (25.2%) in Saint Kitts and Nevis and in 109 of 368 (29.6%) in Saint Vincent and the Grenadines. High-risk HPV genotypes 52, 35, 51, 45, and 31 were the most common high-risk types in Saint Kitts and Nevis. In Saint Vincent and the Grenadines, the most common high-risk HPV genotypes were 45, 35, 31, 18, and 51. Current age was found to be significantly associated with high-risk HPV infection in both countries. In addition, in Saint Vincent and the Grenadines, high parity (> 3 pregnancies) and having had an abnormal Pap smear were found to be independent risk factors for high-risk HPV. These results contribute to the evidence on HPV prevalence for small island states of the Caribbean and support the accelerated introduction of the 9-valent HPV vaccine in the two countries and elsewhere in the English-speaking Caribbean. Use of the study's results to guide the development of policy regarding implementation of HPV testing as the primary screening modality for older women is recommended.

Value of high-risk HPV-DNA testing in the triage of ASCUS.

PubMed

Silverloo, Iréne; Andrae, Bengt; Wilander, Erik

2009-01-01

OBJECTIVE. Atypical squamous cells of undetermined significance (ASCUS) cells, occurring in organized cytological screening, may be either high-risk human papillomavirus (HPV) positive or negative. To refine the assessment of women with ASCUS, a high-risk HPV-DNA test is recommended as triage in Sweden. A total of 197 consecutive women (mean age 39 years, range 21-60) with a diagnosis of ASCUS from the primary screening were selected for triage. Their cervical smears were collected and evaluated by using conventional cytological examination in combination with a high-risk HPV-DNA test (hybrid capture 2). The women were categorized into four groups: Group A, Cytology + /HPV + ; Group B, Cytology-/HPV + ; Group C, Cytology + /HPV-; and Group D, Cytology-/ HPV-. Women within Groups A-C were admitted for colposcopy and cervical biopsy. The women in Group D were considered as a low-risk group for tumor development, and were re-examined after three years in the next round of the organized screening. In women in Group A (n=58) the prevalence of histological verified CIN2-3 was 41%, in Group B (n=41) 20%, and in Group C (n=9) 0%. In Group D (n=89), repeated primary screening three years later revealed CIN2-3 in two biopsies from 74 women studied (<3%). The prevalence of a high-risk HPV infection decreased with age in women with ASCUS. It was 74% in women <30 years and 19% in women > or =50 years. Adding a high-risk HPV test in secondary screening increased the identification of women with CIN2-3 lesions by 33% in comparison with repeat cytology (p=0.01). The clinical significance of the ASCUS diagnosis varied with age of the women.

Discrepant HPV/cytology cotesting results: Are there differences between cytology-negative versus HPV-negative cervical intraepithelial neoplasia?

PubMed

Tracht, Jessica M; Davis, Antoinette D; Fasciano, Danielle N; Eltoum, Isam-Eldin A

2017-10-01

The objective of this study was to compare cervical high-grade squamous intraepithelial lesions subcategorized as cervical intraepithelial neoplasia-3 (CIN-3)-positive after a negative cytology result but positive for high-risk human papillomavirus (HR-HPV) testing to those with a negative HR-HPV test but positive cytology (atypical squamous cells of undetermined significance [ASCUS]-positive/HPV-negative) and to assess reasons for discrepancies. The authors retrospectively analyzed women who underwent screening with cytology and HPV testing from 2010 through 2013. After a review of surgical specimens and cytology, discrepancies were classified as sampling or interpretation error. Clinical and pathologic findings were compared. In total, 15,173 women (age range, 25-95 years; 7.1% were aged < 30 years) underwent both HPV and cytologic testing, and 1184 (8.4%) underwent biopsy. Cytology was positive in 19.4% of specimens, and HPV was positive in 14.5%. Eighty-four CIN-3-positive specimens were detected, including 55 that tested ASCUS-positive/HPV-positive, 11 that tested negative for intraepithelial lesion or malignancy (NILM)/HPV-positive, 10 that tested ASCUS-positive/HPV-negative, 3 that tested NILM/HPV-negative, and 5 tests that were unsatisfactory. There was no significant difference between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3 in terms of size, time to occurrence, the presence of a cytopathic effect, screening history, race, or age. Six of 11 NILM/HPV-positive cases were reclassified as ASCUS, indicating an interpreting error of 55% and a sampling error of 45%. No ASCUS-positive/HPV-negative cases were reclassified. Seven cases of CIN-3 with positive cytology were HPV-negative. There are no significant clinical or pathologic differences between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3-positive specimens. Cytologic sampling or interpretation remains the main reason for discrepancies. However, HPV-negative CIN-3 with positive cytology exists and may be missed by primary HPV screening. Cancer Cytopathol 2017;125:795-805. © 2017 American Cancer Society. © 2017 American Cancer Society.

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

PubMed

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

2012-01-01

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

Projected future impact of HPV vaccination and primary HPV screening on cervical cancer rates from 2017–2035: Example from Australia

PubMed Central

Smith, Megan A.; Saville, Marion; Canfell, Karen

2018-01-01

Background Many countries are transitioning from cytology-based to longer-interval HPV screening. Trials comparing HPV-based screening to cytology report an increase in CIN2/3 detection at the first screen, and longer-term reductions in CIN3+; however, population level year-to-year transitional impacts are poorly understood. We undertook a comprehensive evaluation of switching to longer-interval primary HPV screening in the context of HPV vaccination. We used Australia as an example setting, since Australia will make this transition in December 2017. Methods Using a model of HPV vaccination, transmission, natural history and cervical screening, Policy1-Cervix, we simulated the planned transition from recommending cytology every two years for sexually-active women aged 18–20 to 69, to recommending HPV screening every five years for women aged 25–74 years. We estimated rates of CIN2/3, cervical cancer incidence, and mortality for each year from 2005 to 2035, considering ranges for HPV test accuracy and screening compliance in the context of HPV vaccination (current coverage ~82% in females; ~76% in males). Findings Transient increases are predicted to occur in rates of CIN2/3 detection and invasive cervical cancer in the first two to three years following the screening transition (of 16–24% and 11–14% in respectively, compared to 2017 rates). However, by 2035, CIN2/3 and invasive cervical cancer rates are predicted to fall by 40–44% and 42–51%, respectively, compared to 2017 rates. Cervical cancer mortality rates are predicted to remain unchanged until ~2020, then decline by 34–45% by 2035. Over the period 2018–2035, switching to primary HPV screening in Australia is expected to avert 2,006 cases of invasive cervical cancer and save 587 lives. Conclusions Transient increases in detected CIN2/3 and invasive cancer, which may be detectable at the population level, are predicted following a change to primary HPV screening. This is due to improved test sensitivity bringing forward diagnoses, resulting in longer term reductions in both cervical cancer incidence and mortality. Fluctuations in health outcomes due to the transition to a longer screening interval are predicted to occur for 10–15 years, but cervical cancer rates will be significantly reduced thereafter due to the impact of HPV vaccination and HPV screening. In order to maintain confidence in primary HPV screening through the transitional phase, it is important to widely communicate that an initial increase in CIN2/3 and perhaps even invasive cervical cancer is expected after a national transition to primary HPV screening, that this phenomenon is due to increased prevalent disease detection, and that this effect represents a marker of screening success. PMID:29444073

Human Papillomavirus Assays and Cytology in Primary Cervical Screening of Women Aged 30 Years and Above

PubMed Central

Rebolj, Matejka; Bonde, Jesper; Preisler, Sarah; Ejegod, Ditte; Rygaard, Carsten; Lynge, Elsebeth

2016-01-01

In women aged ≥30 years, Human Papillomavirus testing will replace cytology for primary cervical screening. We compared Hybrid Capture 2 (HC2), cobas, CLART, and APTIMA HPV assays with cytology on 2869 SurePath samples from women undergoing routine screening at 30–65 years in Copenhagen, Denmark. Women with cytological abnormalities were managed according to routine recommendations, with 92% completeness. Those with cytology-normal/HPV-positive samples (on any of the four assays) were invited for repeated cytology and HPV testing in 1.5 year, and 58% had additional testing. HPV testing detected more ≥CIN3 than cytology (HC2: 35, cobas, CLART: 37, APTIMA: 34, cytology: 31), although statistically the differences were not significant. Cobas and CLART detected significantly more ≥CIN2 than cytology (cobas, CLART: 49, cytology: 39). The proportion of women with false-positive test results (positive test results without ≥CIN3) varied between 3.3% with cytology and 14.9% with cobas. All HPV assays led to significantly more false-positive tests, whereas compared to HC2 cobas and CLART were associated with a significantly higher and APTIMA with a significantly lower proportion. Detection of CIN1 was particularly increased for the three DNA assays. With APTIMA combined with cytological triage, about 20% more women were referred for colposcopy than with cytology screening. With the three DNA assays, the increase was ≥50%. The number of women with repeated testing was twice as high with APTIMA and almost five times as high with cobas compared to cytology. To our knowledge, Horizon was the only study set in routine practice that compared more than two HPV assays in the same women while also ascertaining the histological status of women with normal cytology/HPV-positive test results. HPV-based screening of Danish women aged 30–65 detected more high-grade CIN but decreased the screening specificity, and increased the demand for additional testing. PMID:26789267

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

PubMed

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

2018-05-01

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

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2015-01-01

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

Cost-Effectiveness of Cervical Cancer Screening With Human Papillomavirus DNA Testing and HPV-16,18 Vaccination

PubMed Central

Goldhaber-Fiebert, Jeremy D.; Stout, Natasha K.; Salomon, Joshua A.; Kuntz, Karen M.; Goldie, Sue J.

2011-01-01

Background The availability of human papillomavirus (HPV) DNA testing and vaccination against HPV types 16 and 18 (HPV-16,18) motivates questions about the cost-effectiveness of cervical cancer prevention in the United States for unvaccinated older women and for girls eligible for vaccination. Methods An empirically calibrated model was used to assess the quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (2004 US dollars per QALY) of screening, vaccination of preadolescent girls, and vaccination combined with screening. Screening varied by initiation age (18, 21, or 25 years), interval (every 1, 2, 3, or 5 years), and test (HPV DNA testing of cervical specimens or cytologic evaluation of cervical cells with a Pap test). Testing strategies included: 1) cytology followed by HPV DNA testing for equivocal cytologic results (cytology with HPV test triage); 2) HPV DNA testing followed by cytology for positive HPV DNA results (HPV test with cytology triage); and 3) combined HPV DNA testing and cytology. Strategies were permitted to switch once at age 25, 30, or 35 years. Results For unvaccinated women, triennial cytology with HPV test triage, beginning by age 21 years and switching to HPV testing with cytology triage at age 30 years, cost $78 000 per QALY compared with the next best strategy. For girls vaccinated before age 12 years, this same strategy, beginning at age 25 years and switching at age 35 years, cost $41 000 per QALY with screening every 5 years and $188 000 per QALY screening triennially, each compared with the next best strategy. These strategies were more effective and cost-effective than screening women of all ages with cytology alone or cytology with HPV triage annually or biennially. Conclusions For both vaccinated and unvaccinated women, age-based screening by use of HPV DNA testing as a triage test for equivocal results in younger women and as a primary screening test in older women is expected to be more cost-effective than current screening recommendations. PMID:18314477

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

PubMed

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

2016-08-23

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

Present and future of cervical cancer prevention in Spain: a cost-effectiveness analysis.

PubMed

Georgalis, Leonidas; de Sanjosé, Silvia; Esnaola, Mikel; Bosch, F Xavier; Diaz, Mireia

2016-09-01

Human papillomavirus (HPV) vaccination within a nonorganized setting creates a poor cost-effectiveness scenario. However, framed within an organized screening including primary HPV DNA testing with lengthening intervals may provide the best health value for invested money. To compare the effectiveness and cost-effectiveness of different cervical cancer (CC) prevention strategies, including current status and new proposed screening practices, to inform health decision-makers in Spain, a Markov model was developed to simulate the natural history of HPV and CC. Outcomes included cases averted, life expectancy, reduction in the lifetime risk of CC, life years saved, quality-adjusted life years (QALYs), net health benefits, lifetime costs, and incremental cost-effectiveness ratios. The willingness-to-pay threshold is defined at 20 000&OV0556;/QALY. Both costs and health outcomes were discounted at an annual rate of 3%. A strategy of 5-year organized HPV testing has similar effectiveness, but higher efficiency than 3-year cytology. Screening alone and vaccination combined with cytology are dominated by vaccination followed by 5-year HPV testing with cytology triage (12 214&OV0556;/QALY). The optimal age for both ending screening and switching age from cytology to HPV testing in older women is 5 years later for unvaccinated than for vaccinated women. Net health benefits decrease faster with diminishing vaccination coverage than screening coverage. Primary HPV DNA testing is more effective and cost-effective than current cytological screening. Vaccination uptake improvements and a gradual change toward an organized screening practice are critical components for achieving higher effectiveness and efficiency in the prevention of CC in Spain.

Prevalence of Primary HPV in Djibouti: Feasibility of Screening for Early Diagnosis of Squamous Intraepithelial Lesions.

PubMed

Petrelli, Alessio; Di Napoli, Anteo; Giorgi Rossi, Paolo; Rossi, Alessandra; Luccini, Daniele; Di Marco, Ilaria; Traoré, Amadou Laico; Gillio Tos, Anna; Trevisan, Morena; Mirisola, Concetta; Costanzo, Gianfranco

2016-10-01

In many African Sub-Saharan countries, human papilloma virus (HPV) prevalence data are not available. The current study estimated the prevalence of HPV virus in the female population of Djibouti. Approximately 1000 asymptomatic women 16 to 64 years old were enrolled from 3 of the main health structures of Djibouti in 2014 and 2015; 998 cervical samples were tested for HPV-DNA of high risk types, 499 during the first year, and 499 during the second. Positive samples were typed with an HPV genotyping kit. The women were an average age of 38.8 years (SD, 10.2); 54 women tested positive for HPV (prevalence rate, 5.4% [95% confidence interval, 4.0-6.8]). The highest prevalence was observed among the women younger than 35 years. HPV66 was the most prevalent (15.4% of the infections), followed by HPV31 and HPV52 (10.8% both) and HPV16 (9.2%). All 54 women who tested HPV-positive underwent a Pap test, which was positive in 8 cases (14.8%): 2 high-grade squamous intraepithelial lesion (HSIL) and 6 low-grade (LSIL). The HPV prevalence shows a curve by age similar to that of other African countries. The proportion of HPV16 is among the lowest ever seen in similar studies. The findings suggest to Djibouti the choice of a strategy of screening that includes forms of cytological triage, thus limiting recourse to colposcopy.

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

PubMed

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

2014-08-01

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

Molecular tests potentially improving HPV screening and genotyping for cervical cancer prevention

PubMed Central

Gradíssimo, Ana

2018-01-01

INTRODUCTION Human papillomavirus (HPV)-related cancers can be averted by type-specific vaccination (primary prevention) and/or through detection and ablation of precancerous cervical lesions (secondary prevention). This review presents current challenges to cervical cancer screening programs, focusing on recent molecular advances in HPV testing and potential improvements on risk stratification. AREAS COVERED High-risk (HR)-HPV DNA detection has been progressively incorporated into cervix cancer prevention programs based on its increased sensitivity. Advances in next-generation sequencing (NGS) are being rapidly applied to HPV typing. However, current HPV DNA tests lack specificity for identification of cervical precancer (CIN3). HPV typing methods were reviewed based on published literature, with a focus on these applications for screening and risk stratification in the emerging complex clinical scenario post-vaccine introduction. In addition, the potential for NGS technologies to increase specificity is discussed in regards to reflex testing of specimens for emerging biomarkers for cervix precancer/cancer. EXPERT COMMENTARY Integrative multi-disciplinary molecular tests accurately triaging exfoliated cervical specimens will improve cervical cancer prevention programs while simplifying healthcare procedures in HPV-infected women. Hence, the concept of a “liquid-biopsy” (i.e., “molecular” Pap test) highly specific for early identification of cervical precancerous lesions is of critical importance in the years to come. PMID:28277144

Effects of Direct-to-Consumer Advertising and Clinical Guidelines on Appropriate Use of Human Papillomavirus DNA Tests

PubMed Central

2011-01-01

Background Both clinical guidelines and direct-to-consumer (DTC) advertising influence use of new health care technologies, but little is known about their relative effects. The introduction of a cervical cancer screening test in 2000 offered a unique opportunity to assess the two strategies. Objective To evaluate the effects of clinical guidelines and a targeted DTC advertising campaign on overall and appropriate use of human papillomavirus (HPV) DNA tests. Research Design Quasi-experimental study using difference-in-differences analysis. Data were MarketScan private insurance claims for 500,000 women ages 21 to 64 enrolled at least 12 consecutive months from January 2001 through December 2005. Results Both clinical guidelines and DTC advertising were associated with increases in overall HPV DNA test use. DTC advertising was associated with a statistically significant increase in HPV DNA test use in two groups of DTC cities (+5.57 percent, p<0.0001; +2.54 percent, p<0.0001). DTC advertising was associated with comparable increases in the probability of appropriate and inappropriate use of the HPV DNA test in primary screening. Clinical guideline releases from the American College of Obstetricians and Gynecologists, and by a co-sponsored panel, were associated with greater increases in HPV DNA tests for appropriate primary screening than for inappropriate primary screening (β=0.3347, p<0.05 and β=0.4175, p<0.01). Conclusions DTC advertising was associated with increased overall use of a cervical cancer screening test, while clinical guidelines were differentially associated with increased appropriate use. These findings suggest distinct influences of consumer marketing and professional guidelines on the use of health care products and services. PMID:21150798

Effects of direct-to-consumer advertising and clinical guidelines on appropriate use of human papillomavirus DNA tests.

PubMed

Price, Rebecca Anhang; Frank, Richard G; Cleary, Paul D; Goldie, Sue J

2011-02-01

Both clinical guidelines and direct-to-consumer (DTC) advertising influence the use of new health care technologies, but little is known about their relative effects. The introduction of a cervical cancer screening test in 2000 offered a unique opportunity to assess the 2 strategies. To evaluate the effects of clinical guidelines and a targeted DTC advertising campaign on overall and appropriate use of human papillomavirus (HPV) DNA tests. Quasi-experimental study using difference-in-differences analysis. Data were MarketScan private insurance claims for 500,000 women aged 21 to 64 enrolled at least 12 consecutive months from January 2001 through December 2005. Both clinical guidelines and DTC advertising were associated with increases in overall HPV DNA test use. DTC advertising was associated with a statistically significant increase in HPV DNA test use in 2 groups of DTC cities (+5.57%, P < 0.0001; +2.54%, P < 0.0001). DTC advertising was associated with comparable increases in the probability of appropriate and inappropriate use of the HPV DNA test in primary screening. Clinical guideline releases from the American College of Obstetricians and Gynecologists, and by a cosponsored panel, were associated with greater increases in HPV DNA tests for appropriate primary screening than for inappropriate primary screening (β = 0.3347, P < 0.05 and β = 0.4175, P < 0.01). DTC advertising was associated with increased overall use of a cervical cancer screening test, whereas clinical guidelines were differentially associated with increased appropriate use. These findings suggest distinct influences of consumer marketing and professional guidelines on the use of health care products and services.

Human Papillomavirus Laboratory Testing: the Changing Paradigm

PubMed Central

2016-01-01

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

Relationship status impacts primary reasons for interest in the HPV vaccine among young adult women.

PubMed

Thompson, Erika L; Vamos, Cheryl A; Sappenfield, William M; Straub, Diane M; Daley, Ellen M

2016-06-08

The HPV vaccine prevents HPV-related cancers and genital warts, which cause significant morbidity and mortality in the US. The vaccine is targeted toward 11-12 year old males and females, but is recommended for "catch-up" vaccination until age 26 for females. Young adult females (18-26 years) represent a unique group that may face distinct barriers to HPV vaccination, one of which is relationship status. The purpose of this study was to assess how relationship status impacts interest in HPV vaccination and primary reasons for non-vaccination among 18-26 year old young adult women. The National Health Interview Survey 2010 was examined among unvaccinated females, 18-26 years (N=1457). A survey-weighted logistic regression analysis with conversion to prevalence ratios assessed how interest in the HPV vaccine (yes/no) was influenced by relationship status (married, living with a partner, other, single) among young adult women. A Rao-Scott chi-square test examined differences between primary reasons for non-vaccination and relationship status among HPV vaccine uninterested women. Among unvaccinated women, 31.4% were interested in the HPV vaccine. Women who were living with a partner (PR=1.45, 95%CI 1.06-1.90) and single (PR=1.42, 95%CI 1.11-1.76) were significantly more likely than married women to be interested in the HPV vaccine, while controlling for socio-demographic and other known risk factors. Additionally, primary reasons for non-vaccination differed based on relationship status among uninterested women (p<0.01). Women who were married were more likely to cite not needing the vaccine compared to never married women (p<0.05). Relationship status in young adulthood impacts HPV vaccine interest and decision-making among a national sample of women. Primary reasons for non-interest in the vaccine may be shaped by attitudes and knowledge about the HPV vaccine that differ by relationship status. Future research is needed to elucidate ways to overcome relationship status as a barrier to HPV vaccination. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2017-01-01

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

Human papillomavirus detection with genotyping by the cobas and Aptima assays: Significant differences in HPV 16 detection?

PubMed

Chorny, Joseph A; Frye, Teresa C; Fisher, Beth L; Remmers, Carol L

2018-03-23

The primary high-risk human papillomavirus (hrHPV) assays in the United States are the cobas (Roche) and the Aptima (Hologic). The cobas assay detects hrHPV by DNA analysis while the Aptima detects messenger RNA (mRNA) oncogenic transcripts. As the Aptima assay identifies oncogenic expression, it should have a lower rate of hrHPV and genotype detection. The Kaiser Permanente Regional Reference Laboratory in Denver, Colorado changed its hrHPV assay from the cobas to the Aptima assay. The rates of hrHPV detection and genotyping were compared over successive six-month periods. The overall hrHPV detection rates by the two platforms were similar (9.5% versus 9.1%) and not statistically different. For genotyping, the HPV 16 rate by the cobas was 1.6% and by the Aptima it was 1.1%. These differences were statistically different with the Aptima detecting nearly one-third less HPV 16 infections. With the HPV 18 and HPV 18/45, there was a slightly higher detection rate of HPV 18/45 by the Aptima platform (0.5% versus 0.9%) and this was statistically significant. While HPV 16 represents a low percentage of hrHPV infections, it was detected significantly less by the Aptima assay compared to the cobas assay. This has been previously reported, although not highlighted. Given the test methodologies, one would expect the Aptima to detect less HPV 16. This difference appears to be mainly due to a significantly increased number of non-oncogenic HPV 16 infections detected by the cobas test as there were no differences in HPV 16 detection rates in the high-grade squamous intraepithelial lesions indicating that the two tests have similar sensitivities for oncogenic HPV 16. © 2018 Wiley Periodicals, Inc.

Cross-reactivity profiles of hybrid capture II, cobas, and APTIMA human papillomavirus assays: split-sample study.

PubMed

Preisler, Sarah; Rebolj, Matejka; Ejegod, Ditte Møller; Lynge, Elsebeth; Rygaard, Carsten; Bonde, Jesper

2016-07-20

High-risk Human Papillomavirus (HPV) testing is replacing cytology in cervical cancer screening as it is more sensitive for preinvasive cervical lesions. However, the bottleneck of HPV testing is the many false positive test results (positive tests without cervical lesions). Here, we evaluated to what extent these can be explained by cross-reactivity, i.e. positive test results without evidence of high-risk HPV genotypes. The patterns of cross-reactivity have been thoroughly studied for hybrid capture II (HC2) but not yet for newer HPV assays although the manufacturers claimed no or limited frequency of cross-reactivity. In this independent study we evaluated the frequency of cross-reactivity for HC2, cobas, and APTIMA assays. Consecutive routine cervical screening samples from 5022 Danish women, including 2859 from women attending primary screening, were tested with the three evaluated DNA and mRNA HPV assays. Genotyping was undertaken using CLART HPV2 assay, individually detecting 35 genotypes. The presence or absence of cervical lesions was determined with histological examinations; women with abnormal cytology were managed as per routine recommendations; those with normal cytology and positive high-risk HPV test results were invited for repeated testing in 18 months. Cross-reactivity to low-risk genotypes was detected in 109 (2.2 %) out of 5022 samples on HC2, 62 (1.2 %) on cobas, and 35 (0.7 %) on APTIMA with only 10 of the samples cross-reacting on all 3 assays. None of the 35 genotypes was detected in 49 (1.0 %), 162 (3.2 %), and 56 (1.1 %) samples, respectively. In primary screening at age 30 to 65 years (n = 2859), samples of 72 (25 %) out of 289 with high-risk infections on HC2 and < CIN2 histology were due to cross-reactivity. On cobas, this was 106 (26 %) out of 415, and on APTIMA 48 (21 %) out of 224. Despite manufacturer claims, all three assays showed cross-reactivity. In primary cervical screening at age ≥30 years, cross-reactivity accounted for about one quarter of false positive test results regardless of the assay. Cross-reactivity should be addressed in EU tenders, as this primarily technical shortcoming imposes additional costs on the screening programmes.

A randomized controlled trial of Human Papillomavirus (HPV) testing for cervical cancer screening: trial design and preliminary results (HPV FOCAL Trial)

PubMed Central

2010-01-01

Background In the HPV FOCAL trial, we will establish the efficacy of hr-HPV DNA testing as a stand-alone screening test followed by liquid based cytology (LBC) triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with ≥ CIN3 as the outcome. Methods/Design HPV-FOCAL is a randomized, controlled, three-armed study over a four year period conducted in British Columbia. It will recruit 33,000 women aged 25-65 through the province's population based cervical cancer screening program. Control arm: LBC at entry and two years, and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases; Two Year Safety Check arm: hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives; Four Year Intervention Arm: hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases Discussion To date, 6150 participants have a completed sample and epidemiologic questionnaire. Of the 2019 women enrolled in the control arm, 1908 (94.5%) were cytology negative. Women aged 25-29 had the highest rates of HSIL (1.4%). In the safety arm 92.2% of women were hr-HPV negative, with the highest rate of hr-HPV positivity found in 25-29 year old women (23.5%). Similar results were obtained in the intervention arm HPV FOCAL is the first randomized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population-based cervical cancer screening program. Trial Registration International Standard Randomised Controlled Trial Number Register, ISRCTN79347302 PMID:20334685

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2008-04-02

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

The clinical utility of HPV DNA testing in cervical cancer screening strategies.

PubMed

Bhatla, Neerja; Moda, Nidhi

2009-09-01

Cervical cancer continues to be the commonest cause of death among women in developing countries, largely due to the failure to the inability to sustain effective cytology-based screening programs. While this burden may come down following implementation of the human papillomavirus (HPV) vaccine, screening will still be required. HPV DNA testing is a promising new technology for cervical cancer prevention and is the most reproducible of all cervical cancer screening tests. Presently, the two assays most widely used for the detection of genital types are the polymerase chain reaction (PCR) and Hybrid Capture 2 assays (hc2). Rapid, affordable tests are expected to be available soon. HPV DNA testing can be used in a variety of clinical scenarios that include primary screening in women older than 30 yr; as an adjunctive test to cytology; in the triage of women with an equivocal cytologic report, e.g., ASC-US; or for follow-up post-treatment for cervical intraepithelial neoplasia (CIN). HPV DNA testing can also be performed on self-collected samples, which allows screening in remote areas and also in women who refuse gynecologic examination.

Human Papillomavirus Testing in Head and Neck Carcinomas: Guideline From the College of American Pathologists.

PubMed

Lewis, James S; Beadle, Beth; Bishop, Justin A; Chernock, Rebecca D; Colasacco, Carol; Lacchetti, Christina; Moncur, Joel Todd; Rocco, James W; Schwartz, Mary R; Seethala, Raja R; Thomas, Nicole E; Westra, William H; Faquin, William C

2018-05-01

Context Human papillomavirus (HPV) is a major cause of oropharyngeal squamous cell carcinomas, and HPV (and/or surrogate marker p16) status has emerged as a prognostic marker that significantly impacts clinical management. There is no current consensus on when to test oropharyngeal squamous cell carcinomas for HPV/p16 or on which tests to choose. Objective To develop evidence-based recommendations for the testing, application, interpretation, and reporting of HPV and surrogate marker tests in head and neck carcinomas. Design The College of American Pathologists convened a panel of experts in head and neck and molecular pathology, as well as surgical, medical, and radiation oncology, to develop recommendations. A systematic review of the literature was conducted to address 6 key questions. Final recommendations were derived from strength of evidence, open comment period feedback, and expert panel consensus. Results The major recommendations include (1) testing newly diagnosed oropharyngeal squamous cell carcinoma patients for high-risk HPV, either from the primary tumor or from cervical nodal metastases, using p16 immunohistochemistry with a 70% nuclear and cytoplasmic staining cutoff, and (2) not routinely testing nonsquamous oropharyngeal carcinomas or nonoropharyngeal carcinomas for HPV. Pathologists are to report tumors as HPV positive or p16 positive. Guidelines are provided for testing cytologic samples and handling of locoregional and distant recurrence specimens. Conclusions Based on the systematic review and on expert panel consensus, high-risk HPV testing is recommended for all new oropharyngeal squamous cell carcinoma patients, but not routinely recommended for other head and neck carcinomas.

High-risk human papillomavirus (hrHPV) E6/E7 mRNA testing by PreTect HPV-Proofer for detection of cervical high-grade intraepithelial neoplasia and cancer among hrHPV DNA-positive women with normal cytology.

PubMed

Rijkaart, D C; Heideman, D A M; Coupe, V M H; Brink, A A T P; Verheijen, R H M; Skomedal, H; Karlsen, F; Morland, E; Snijders, P J F; Meijer, C J L M

2012-07-01

Our aim was to investigate whether high-risk HPV (hrHPV) mRNA detection by PreTect HPV-Proofer can be used to stratify hrHPV DNA-positive women of different cytology classes for risk of high-grade cervical intraepithelial neoplasia or worse (cervical precancer or cancer, i.e., cervical intraepithelial neoplasia grade 2 or higher [≥ CIN2]). A total of 375 women participating in population-based screening, with a GP5+/6+-PCR hrHPV DNA-positive cervical scrape with normal cytology (n = 202), borderline or mild dyskaryosis (BMD) (n = 88), or moderate dyskaryosis or worse (>BMD) (n = 85), were enrolled. Cervical scrapes were additionally subjected to HPV16/18/31/33/45 E6/E7 mRNA analysis by PreTect HPV-Proofer (mRNA test). Referral and follow-up policies were based on cytology, hrHPV DNA, and mRNA testing. The primary study endpoint was the number of ≥CIN2 detected within 3 years of follow-up. The mRNA positivity increased with the severity of cytological abnormality, ranging from 32% (64/202) in hrHPV DNA-positive women with normal cytology to 47% (41/88) in BMD and 68% (58/85) in >BMD groups (P < 0.01). Women with ≥ CIN2 were more likely to test positive by mRNA test (63%) than women without evidence of ≥ CIN2 (32%; P < 0.01). A positive mRNA test result conferred an increased ≥ CIN2 risk in hrHPV DNA-positive women with normal cytology, i.e., 0.55 (95% confidence interval [95% CI], 0.34 to 0.76) in mRNA-positive versus 0.20 (95% CI, 0.07 to 0.33) in mRNA-negative women. In hrHPV DNA-positive women with BMD or >BMD, the result of the mRNA test did not influence the ≥ CIN2 risk. In conclusion, mRNA testing by PreTect HPV-Proofer might be of value to select hrHPV DNA-positive women with normal cytology in need of immediate referral for colposcopy.

High-Risk Human Papillomavirus (hrHPV) E6/E7 mRNA Testing by PreTect HPV-Proofer for Detection of Cervical High-Grade Intraepithelial Neoplasia and Cancer among hrHPV DNA-Positive Women with Normal Cytology

PubMed Central

Rijkaart, D. C.; Heideman, D. A. M.; Coupe, V. M. H.; Brink, A. A. T. P.; Verheijen, R. H. M.; Skomedal, H.; Karlsen, F.; Morland, E.; Snijders, P. J. F.

2012-01-01

Our aim was to investigate whether high-risk HPV (hrHPV) mRNA detection by PreTect HPV-Proofer can be used to stratify hrHPV DNA-positive women of different cytology classes for risk of high-grade cervical intraepithelial neoplasia or worse (cervical precancer or cancer, i.e., cervical intraepithelial neoplasia grade 2 or higher [≥CIN2]). A total of 375 women participating in population-based screening, with a GP5+/6+-PCR hrHPV DNA-positive cervical scrape with normal cytology (n = 202), borderline or mild dyskaryosis (BMD) (n = 88), or moderate dyskaryosis or worse (>BMD) (n = 85), were enrolled. Cervical scrapes were additionally subjected to HPV16/18/31/33/45 E6/E7 mRNA analysis by PreTect HPV-Proofer (mRNA test). Referral and follow-up policies were based on cytology, hrHPV DNA, and mRNA testing. The primary study endpoint was the number of ≥CIN2 detected within 3 years of follow-up. The mRNA positivity increased with the severity of cytological abnormality, ranging from 32% (64/202) in hrHPV DNA-positive women with normal cytology to 47% (41/88) in BMD and 68% (58/85) in >BMD groups (P < 0.01). Women with ≥CIN2 were more likely to test positive by mRNA test (63%) than women without evidence of ≥CIN2 (32%; P < 0.01). A positive mRNA test result conferred an increased ≥CIN2 risk in hrHPV DNA-positive women with normal cytology, i.e., 0.55 (95% confidence interval [95% CI], 0.34 to 0.76) in mRNA-positive versus 0.20 (95% CI, 0.07 to 0.33) in mRNA-negative women. In hrHPV DNA-positive women with BMD or >BMD, the result of the mRNA test did not influence the ≥CIN2 risk. In conclusion, mRNA testing by PreTect HPV-Proofer might be of value to select hrHPV DNA-positive women with normal cytology in need of immediate referral for colposcopy. PMID:22553244

Evolution of cervical cancer screening and prevention in United States and Canada: Implications for public health practitioners and clinicians☆,☆☆

PubMed Central

Saraiya, M.; Steben, M.; Watson, M.; Markowitz, L.

2015-01-01

Objective Declines in cervical cancer incidence and mortality in Canada and in the United States have been widely attributed to the introduction of the Papanicolaou (Pap) test. This article reviews changes in screening and introduction of HPV vaccination. Method Sentinel events in cervical cancer screening and primary prevention through HPV vaccination in the US and Canada are described. Results Despite commonalities, cervical cancer screening and prevention differ between the two countries. Canada has a combination of opportunistic and organized programs at the provincial and territorial level, while the US has opportunistic screening and vaccination systems. In the US, the HPV test along with the Pap test (co-testing) is part of national recommendations for routine cervical cancer screening for women age 30 and older. Co-testing is not being considered anywhere in Canada, but primary HPV testing is currently recommended (but not implemented) in one province in Canada. Conclusion Many prevention strategies are available for cervical cancer. Continued public health efforts should focus on increasing vaccine coverage in the target age groups and cervical cancer screening for women at appropriate intervals. Ongoing evaluation will be needed to ensure appropriate use of health resources, as vaccinated women become eligible for screening. PMID:23402963

Looking ahead: a case for HPV testing of self-sampled vaginal specimens as a cervical cancer screening strategy

PubMed Central

Gravitt, Patti E.; Belinson, Jerome L.; Salmeron, Jorge; Shah, Keerti V.

2012-01-01

Even in the era of highly effective HPV prophylactic vaccines, substantial reduction in worldwide cervical cancer mortality will only be realized if effective early detection and treatment of the millions of women already infection and the millions who may not receive vaccination in the next decade can be broadly implemented through sustainable cervical cancer screening programs. Effective programs must meet three targets: 1) at least 70% of the targeted population should be screened at least once in a lifetime, 2) screening assays and diagnostic tests must be reproducible and sufficiently sensitive and specific for the detection of high-grade precursor lesions (i.e., CIN2+), and 3) effective treatment must be provided. We review the evidence that HPV DNA screening from swabs collected by the women in their home or village is sufficiently sound for consideration as a primary screening strategy in the developing world, with sensitivity and specificity for detection of CIN2+ as good or better than Pap smear cytology and VIA. A key feature of a self-collected HPV testing strategy (SC-HPV) is the move of the primary screening activities from the clinic to the community. Efforts to increase the affordability and availability of HPV DNA tests, community education and awareness, development of strong partnerships between community advocacy groups, health care centers and regional or local laboratories, and resource appropriate strategies to identify and treat screen-positive women should now be prioritized to ensure successful public health translation of the technologic advancements in cervical cancer prevention. PMID:21384341

Human Papillomavirus-associated oropharyngeal cancer: an observational study of diagnosis, prevalence and prognosis in a UK population

PubMed Central

2013-01-01

Background The incidence of Human Papillomavirus (HPV) associated oropharyngeal cancer (OPC) is increasing. HPV-associated OPC appear to have better prognosis than HPV-negative OPC. The aim of this study was to robustly determine the prevalence of HPV-positive OPC in an unselected UK population and correlate HPV positivity with clinical outcome. Methods HPV testing by GP5+/6+ PCR, In Situ Hybridisation (ISH) and p16 immunohistochemistry (IHC) was performed on 138 OPCs diagnosed in South Wales (UK) between 2001–06. Kaplan-Meier analysis was used to correlate HPV status with clinical outcome. Results Using a composite definition of HPV positivity (HPV DNA and p16 overexpression), HPV was detected in 46/83 (55%) samples where DNA quality was assured. Five year overall survival was 75.4% (95% CI: 65.2 to 85.5) in HPV-positives vs 25.3% (95% CI: 14.2 to 36.4) in HPV negatives, corresponding to a 78% reduction in death rate (HR 0.22, p < 0.001). HPV-positives had less locoregional recurrence but second HPV-positive Head and Neck primaries occurred. Poor quality DNA in fixed pathological specimens reduced both HPV prevalence estimates and the prognostic utility of DNA-based HPV testing methods. As a single marker, p16 was least affected by sample quality and correlated well with prognosis, although was not sufficient on its own for accurate HPV prevalence reporting. Conclusions This study highlights the significant burden of OPC associated with HPV infection. HPV positive cases are clinically distinct from other OPC, and are associated with significantly better clinical outcomes. A composite definition of HPV positivity should be used for accurate prevalence reporting and up-front DNA quality assessment is recommended for any DNA-based HPV detection strategy. PMID:23634887

Prevalence of and risk factors for anal human papillomavirus infection in men who have sex with women: a cross-national study.

PubMed

Nyitray, Alan G; Smith, Dan'elle; Villa, Luisa; Lazcano-Ponce, Eduardo; Abrahamsen, Martha; Papenfuss, Mary; Giuliano, Anna R

2010-05-15

Although the primary cause of anal cancer is human papillomavirus (HPV) infection in the anal canal, little attention has been paid to the epidemiology of anal HPV infection in men who have sex with women (MSW). Exfoliated cells from the anal canal of 902 MSW in Brazil (São Paulo), Mexico (Cuernavaca), and the United States (Tampa) were tested for HPV DNA. The prevalence of HPV infection in the anal canal (12.0%) was similar among MSW in each city (P=.77), whereas 7.0% had infection with oncogenic types. Men in Tampa had a 4-fold higher prevalence of infection with HPV type 16 (HPV-16) than that among men in São Paulo or Cuernavaca (P<.001). Duration of relationship with a primary sex partner and ever having oral or anal sex with a man was associated with infection with any HPV type and with any oncogenic type, whereas lifetime number of female sex partners was associated with infection with any HPV type. Anal canal HPV infection is commonly found among MSW, and the prevalence of infection with HPV-16 may differ substantially by geography. Men who have a larger lifetime number of female sex partners, who are in a sexual relationship of <1 year in duration, and who have a history of oral or anal sex with men were most likely to have an anal HPV infection.

Oncogenic Viral Prevalence in Invasive Vulvar Cancer Specimens from HIV Positive and Negative Women in Botswana

PubMed Central

Tesfalul, Martha; Simbiri, Kenneth; Wheat, Chikoti M.; Motsepe, Didintle; Goldbach, Hayley; Armstrong, Kathleen; Hudson, Kathryn; Kayembe, Mukendi K.; Robertson, Erle; Kovarik, Carrie

2014-01-01

Objective The primary aim of this study is to describe the prevalence of select oncogenic viruses within vulvar squamous cell carcinoma (VSCC) and their association with Human Immunodeficiency Virus (HIV) status in women in Botswana, where the national HIV prevalence is the third highest in the world. Methods/materials A cross-sectional study of biopsy-confirmed VSCC specimens and corresponding clinical data was conducted in Gaborone, Botswana. Polymerase Chain Reaction (PCR) and Immunohistochemistry (IHC) viral testing were done for Epstein-Barr Virus (EBV), Human Papilloma Virus (HPV) strains, and Kaposi's Sarcoma Herpesvirus (KSHV), and PCR viral testing alone was done for John Cunningham Virus (JCV). Results HPV prevalence by PCR was 100% (39/39 35/35) among tested samples. HPV16 was the most prevalent HPV strain (82.9% by PCR, 94.7% by either PCR or IHC). KSHV prevalence by PCR had a significant association with HIV status (p = 0.013), but not by IHC (p = 0.650). Conclusions The high burden of HPV, specifically HPV16, in VSCC in Botswana suggests a distinct HPV profile that differs from other studied populations, which provides increased motivation for HPV vaccination efforts. Oncogenic viruses KSHV and EBV were also more prevalent in our study population though their potential role in VSCC pathology is unclear. PMID:24651632

Warts and All: HPV in Primary Immunodeficiencies

PubMed Central

Leiding, Jennifer W.; Holland, Steven M.

2012-01-01

Infection with human papilloma virus (HPV) is almost universal and eventually asymptomatic, but pathologic infection with HPV is severe, recurrent, and recalcitrant to therapy. It is also an underappreciated manifestation of primary immunodeficiency. Mutations in EVER1, EVER2, GATA2, CXCR4, and DOCK8 are typically associated with extensive HPV infections, whereas several other primary immune defects have severe HPV much less frequently. We review immunodeficiencies with severe HPV infections and the mechanisms underlying them. PMID:23036745

A review of the use of human papilloma virus (HPV) in cervical screening.

PubMed

Crossley, B; Crossley, J

2017-07-01

Using key words online databases were searched to identify relevant publications to review the use of Human papilloma virus (HPV) in cervical screening. The mode of cervical screening in the UK has been decided but implementation plans have yet to be announced. The protracted uncertainty surrounding the initial announcement to move to HPV primary screening together with the lack of a national steer has resulted in a flight of staff which threatens the provision of the current and future service. The transition will be a challenging time but analysis of data from more than 176,000 women has shown clear evidence of a reduction in the incidence of cancer where HPV testing is used. There will however, be a population of women who are cytologically negative but high-risk HPV positive and the management of these women will be key to maximising the benefits of HPV primary screening. As cervical cytology becomes increasingly rare its effectiveness and role in cervical screening will come under scrutiny and we must ensure the specificity of reporting is maintained in order for it to survive.

Comparison of detection methods for HPV status as a prognostic marker for loco-regional control after radiochemotherapy in patients with HNSCC.

PubMed

Linge, Annett; Schötz, Ulrike; Löck, Steffen; Lohaus, Fabian; von Neubeck, Cläre; Gudziol, Volker; Nowak, Alexander; Tinhofer, Inge; Budach, Volker; Sak, Ali; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Bunea, Hatice; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Ganswindt, Ute; Lauber, Kirsten; Pigorsch, Steffi; Combs, Stephanie E; Mönnich, David; Zips, Daniel; Baretton, Gustavo B; Buchholz, Frank; Krause, Mechthild; Belka, Claus; Baumann, Michael

2018-04-01

To compare six HPV detection methods in pre-treatment FFPE tumour samples from patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who received postoperative (N = 175) or primary (N = 90) radiochemotherapy. HPV analyses included detection of (i) HPV16 E6/E7 RNA, (ii) HPV16 DNA (PCR-based arrays, A-PCR), (iii) HPV DNA (GP5+/GP6+ qPCR, (GP-PCR)), (iv) p16 (immunohistochemistry, p16 IHC), (v) combining p16 IHC and the A-PCR result and (vi) combining p16 IHC and the GP-PCR result. Differences between HPV positive and negative subgroups were evaluated for the primary endpoint loco-regional control (LRC) using Cox regression. Correlation between the HPV detection methods was high (chi-squared test, p < 0.001). While p16 IHC analysis resulted in several false positive classifications, A-PCR, GP-PCR and the combination of p16 IHC and A-PCR or GP-PCR led to results comparable to RNA analysis. In both cohorts, Cox regression analyses revealed significantly prolonged LRC for patients with HPV positive tumours irrespective of the detection method. The most stringent classification was obtained by detection of HPV16 RNA, or combining p16 IHC with A-PCR or GP-PCR. This approach revealed the lowest rate of recurrence in patients with tumours classified as HPV positive and therefore appears most suited for patient stratification in HPV-based clinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Impact of HPV testing, HPV vaccine development, and changing screening frequency on national Pap test volume: projections from the National Health Interview Survey (NHIS).

PubMed

Eltoum, Isam A; Roberson, Janie

2007-02-25

The frequently cited number of 50 million annual Papanicolaou cervical screening (Pap) tests performed in the US was based on the National Health Interview Survey (NHIS) of the 1980s. Since then, monumental changes have occurred. More change will soon follow when primary human papilloma virus (HPV) testing and/or HPV vaccine delivery are fully accepted and implemented. The objectives of this study were 1) to estimate the total annual Pap tests performed in the US based on recent NHIS surveys, and 2) to estimate the potential change in the total annual Pap volume produced by changing demographics, reduced screening frequency, HPV testing, and the HPV vaccine. In the NHIS 2000 and NHIS 2005, women were asked to report the frequency of their Pap tests for the 6 years prior to the interview and to report whether they had abnormal findings. The authors analyzed the survey respondents answers to these questions by using SAS Survey Procedures (SAS Institute, NC). The results were stratified by age, and the total national volume was then extrapolated from a similarly stratified 2000 US census. The projected increase of total Pap tests for the next 25 years was determined by using the projected census data. Potential reductions of Pap tests performed secondarily to HPV testing of women >30 years old and of HPV vaccination were also determined. Based on NHIS 2000 and NHIS 2005, 66 million (95% CI, 65-68) and 65 million (95% CI, 64-67) Pap tests were performed in the US, respectively. Had HPV testing been performed in women older than 30 years who had both negative HPV and negative 3-year Pap tests, then 30% (95% CI, 29-32%) of Pap tests would not have been performed. If both HPV testing and vaccination are performed, the total number of Pap tests performed annually is predicted to be reduced by 43% (95% CI, 35-38%). Therefore, despite an expected increase in the population of women eligible for Pap tests, the total number will likely decrease substantially in the future. This, in turn, will decrease the demand for a traditionally trained cytotechnology workforce. (c) 2007 American Cancer Society.

Understanding Transgender Men's Experiences with and Preferences for Cervical Cancer Screening: A Rapid Assessment Survey.

PubMed

Seay, Julia; Ranck, Atticus; Weiss, Roy; Salgado, Christopher; Fein, Lydia; Kobetz, Erin

2017-08-01

Transgender men are less likely than cisgender women to receive cervical cancer screening. The purpose of the current study was to understand experiences with and preferences for cervical cancer screening among transgender men. Ninety-one transgender men ages 21-63 completed the survey. The survey evaluated experiences with and preferences for screening, including opinions regarding human papillomavirus (HPV) self-sampling as a primary cervical cancer screening. Half (50.5%) of participants did not have Pap smear screening within the past 3 years. The majority (57.1%) of participants preferred HPV self-sampling over provider-collected Pap smear screening. Participants who reported discrimination were more likely to prefer HPV self-sampling (odds ratio = 3.29, 95% confidence interval 1.38-7.84, P = 0.007). Primary HPV testing via HPV self-sampling may improve cervical cancer screening uptake among transgender men. Future work should pilot this innovative cervical cancer screening method within this population.

Cervical Cancer Risk for 330,000 Women Undergoing Concurrent HPV Testing and Cervical Cytology in Routine Clinical Practice at a Large Managed Care Organization

PubMed Central

Katki, Hormuzd A.; Kinney, Walter K.; Fetterman, Barbara; Lorey, Thomas; Poitras, Nancy E.; Cheung, Li; Demuth, Franklin; Schiffman, Mark; Wacholder, Sholom; Castle, Philip E.

2011-01-01

Background Concurrent HPV testing and cervical cytology (co-testing) is an approved and promising alternative to cytology alone in women aged 30 and older. However, broad acceptance of co-testing is being hindered by a lack of evidence about its performance in routine clinical practice. We evaluated the safety of three-year screening intervals for women testing HPV-negative with normal cytology (Pap-negative) and assessed the ability of co-testing to identify women at high risk of CIN3+ or cervical cancer over five years. Methods We analyzed five-year cumulative incidence of cervical cancer and cervical intraepithelial neoplasia grade 3 or worse (CIN3+) for 331,818 women aged 30 and older who enrolled in co-testing at Kaiser Permanente Northern California starting 2003-2005 (and had adequate enrollment co-test results) and were followed through December 31, 2009. Findings Five-year cumulative incidence of cancer for all 315,061 HPV-negative women was extremely low (3.8 per 100,000 women per year), only slightly higher than for the 306,969 women who were both HPV-negative and Pap-negative (3.2 per 100,000 women per year), and half the cancer risk of all 319,177 women who were Pap-negative (7.5 per 100,000 women per year). Almost all (99.5%; 313,465) HPV-negative women had either normal cytology or minor abnormalities. Abnormal cytology greatly increased cumulative incidence of CIN3+ over five years for the 16,757 HPV-positive women (12% vs. 5.9%, p<0.0001). In contrast, although statistically significant, abnormal cytology did not increase 5-year CIN3+ risk for HPV-negative women to a substantial level (0.86% vs. 0.16%). 73% of HPV-positive women had no cytologic abnormality (12,208 women). HPV-positive women with no cytologic abnormality experienced 34% of the CIN3+, 29% of the cancers, and 63% of the adenocarcinomas. Interpretation For women aged 30 and older in routine clinical practice, a single negative HPV test sufficed to provide strong reassurance against cervical cancer over five years, demonstrating the safety of 3-year screening intervals for HPV-negative/Pap-negative women and suggesting that five-year intervals may also be safe. Concurrent HPV testing resulted in earlier identification of the women at high risk of cervical cancer, especially adenocarcinoma. HPV testing without adjunctive cytology may be sufficiently sensitive for primary cervical cancer screening. PMID:21684207

Developing a new diagnostic algorithm for human papilloma virus associated oropharyngeal carcinoma: an investigation of HPV DNA assays.

PubMed

Cohen, Natasha; Gupta, Michael; Doerwald-Munoz, Lilian; Jang, Dan; Young, James Edward Massey; Archibald, Stuart; Jackson, Bernard; Lee, Jenny; Chernesky, Max

2017-02-13

Human papilloma virus (HPV) has been implicated in the development of a large proportion of oropharyngeal squamous cell carcinoma (OPSCC). Current techniques used to diagnose HPV etiology require histopathologic analysis. We aim to investigate the diagnostic accuracy of a new application non-histopathologic diagnostic tests to help assist diagnosis of HPV-related oropharyngeal tumors. Patients with OPSCC with nodal metastasis were consecutively recruited from a multidisciplinary cancer clinic. Appropriate samples were collected and analyzed. The various tests examined included COBAS® 4800, Cervista® HR and Genotyping. These tests were compared to p16 staining, which was used as the diagnostic standard. StataIC 14.2 was used to perform analysis, including sensitivity, specificity and receiver operator characteristic [ROC] curves. The COBAS® FNA (area under ROC 0.863) and saliva (area under ROC 0.847) samples performed well in diagnosing HPV positive and negative tumors. Samples tested with Cervista® did not corroborate p16 status reliably. We were able to increase the diagnostic yield of the COBAS® FNA samples by applying the results of the saliva test to negative FNA samples which correctly identified 11 additional p16 positive tumors (area under ROC 0.915). Surrogate testing for HPV using alternate methods is feasible and closely predicts the results of standard diagnostic methods. In the future, these could minimize invasive procedures for diagnosing HPV-related oropharyngeal cancer, but also help to diagnose and treat patients with unknown primaries.

Feasibility of community-based careHPV for cervical cancer prevention in rural Thailand.

PubMed

Trope, Lee A; Chumworathayi, Bandit; Blumenthal, Paul D

2013-07-01

This study aimed to assess the safety, acceptability and feasibility of primary human papillomavirus (HPV) testing for cervical cancer prevention at the community level in a low-resource setting. After training a technician to run specimens on the careHPV unit, the study team traveled to a different village each day in rural Roi-et Province, Thailand. Women were tested for HPV using self-swab, followed by careHPV testing. Those with positive result were assessed immediately by visual inspection with acetic acid. Women positive for HPV and visual inspection with acetic acid were offered cryotherapy. Safety was determined by monitoring adverse events. Exit surveys assessed acceptability and feasibility. Feasibility was also assessed by measuring testing and triage throughputs. Technician training required 2.5 days to achieve competency. A total of 431 women were screened in 14 days, with an average of 31 women screened daily. No adverse events were reported. Women deemed the program overwhelmingly acceptable: 90.5% reported that they would take the self-swab again, 71.3% preferred the self-swab to a clinician swab. The program was also feasible: 99.8% of eligible women agreed to testing, 94.8% returned for same-day follow-up, and women only spent 30 to 50 minutes of their total time with the program from screening to results. Cervical cancer prevention programs based on self-swab HPV testing could be safe, acceptable, feasible, and effective at the community level in low-resource settings.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-09-01

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

Knowledge, opinions and attitudes of Italian mothers towards HPV vaccination and Pap test.

PubMed

La Torre, Giuseppe; De Vito, Elisabetta; Ficarra, Maria Giovanna; Firenze, Alberto; Gregorio, Pasquale; Miccoli, Silvia; Giraldi, Guglielmo; Unim, Brigid; De Belvis, Giulio; Boccia, Antonio; Saulle, Rosella; Semyonov, Leda; Ferrara, Maria; Langiano, Elisa; Capizzi, Silvio; Nardella, Rosaria; Marsala, Maria Grazia Laura; Bonanno, Valentina; Ferrara, Clara; Guidi, Enrica; Bergamini, Mauro; Lupi, Silvia

2015-01-01

This study evaluated the knowledge and attitudes of Italian mothers - whose daughters had been vaccinated in 2012 - towards primary (anti-HPV vaccination) and secondary (Pap test screening) cervical cancer prevention, as well as sources of information and mother-daughter communication on health issues. The survey - part of a multicenter study carried out in 4 Italian cities (Ferrara, Rome, Cassino and Palermo) - was conducted through self-administered questionnaires. The first univariate analysis evaluated differences between mothers of under-18s and over-18s relative to knowledge and attitudes on HPV vaccination and Pap test. The second univariate analysis evaluated differences between the 2 groups of mothers and possible geographical variations regarding the sources of information on HPV and Pap test. The sample proved knowledgeable about the correlation between HPV and cervical cancer (>85%) but less aware of other HPV-related diseases. HPV vaccination should be administered before first sexual intercourse according to mothers of over-18s, and to 14- to 17-year-olds according to mothers of under-18s. Up to 88% of mothers of under-18s and 80% of mothers of over-18s declared that the vaccine should be given free of charge. More mothers of under-18s consulted a general practitioner (GP) or gynecologist before deciding to vaccinate their daughters. Mothers of under-18s received information on HPV vaccination mainly from GPs and gynecologists, while mothers of over-18s were informed through TV and books/journals. Over 80% of the sample declared satisfaction with the information received from their gynecologist during the Pap test. The findings provide useful information for the development of effective public health interventions that may help improve acceptance of HPV vaccination among mothers.

Nuclear translocation of β-catenin and decreased expression of epithelial cadherin in human papillomavirus-positive tonsillar cancer: an early event in human papillomavirus-related tumour progression?

PubMed

Stenner, Markus; Yosef, Basima; Huebbers, Christian U; Preuss, Simon F; Dienes, Hans-Peter; Speel, Ernst-Jan M; Odenthal, Margarete; Klussmann, Jens P

2011-06-01

High-risk human papillomaviruses (HPVs) constitute an important risk factor for tonsillar cancer. This study describes changes in cell adhesion molecules during metastasis of HPV-related and HPV-unrelated tonsillar carcinomas. We examined 48 primary tonsillar carcinoma samples (25 HPV-16 DNA-positive, 23 HPV-16 DNA-negative) and their respective lymph node metastases for their HPV status and for the expression of p16, epithelial cadherin (E-cadherin), β-catenin, and vimentin. A positive HPV-specific polymerase chain reaction finding correlated significantly with p16 overexpression in both primary tumours and their metastases (P<0.0001 for both). In HPV-unrelated carcinomas, the expression of E-cadherin was significantly lower in metastases than in primary tumours (P<0.001). In contrast, the expression of nuclear β-catenin was significantly higher in metastases than in primary tumours (P=0.016). In HPV-related carcinomas, nuclear localization of β-catenin expression was already apparent in primary tumours (P=0.030). The expression of vimentin significantly correlated with the grading of the primary tumour (P=0.021). Our data indicate that the down-regulation of E-cadherin and the up-regulation of nuclear β-catenin expression might be crucial steps during tumour progression of tonsillar carcinomas, being already present in primary tumours in HPV-driven carcinomas, but becoming apparent in HPV-unrelated tumours later in the process of metastasis. © 2011 Blackwell Publishing Limited.

Comparing self- and provider-collected swabbing for HPV DNA testing in female-to-male transgender adult patients: a mixed-methods biobehavioral study protocol.

PubMed

Reisner, Sari L; Deutsch, Madeline B; Peitzmeier, Sarah M; White Hughto, Jaclyn M; Cavanaugh, Timothy; Pardee, Dana J; McLean, Sarah; Marrow, Elliot J; Mimiaga, Matthew J; Panther, Lori; Gelman, Marcy; Green, Jamison; Potter, Jennifer

2017-06-23

Cervical cancer, nearly all cases of which are caused by one of several high-risk strains of the human papillomavirus (hr-HPV), leads to significant morbidity and mortality in individuals with a cervix. Trans masculine (TM) individuals were born with female reproductive organs and identify as male, man, transgender man, or another diverse gender identity different from their female assigned sex at birth. Routine preventive sexual health screening of TM patients is recommended, including screening for cervical cancer and other sexually transmitted infections (STIs); however, as many as one in three TM patients are not up-to-date per recommended U.S. Among cisgender (non-transgender) women, self-swab hr.-HPV DNA testing as a primary cervical cancer screening method and self-swab specimen collection for other STIs have high levels of acceptability. No study has yet been conducted to compare the performance and acceptability of self- and provider-collected swabs for hr.-HPV DNA testing and other STIs in TM patients. This article describes the study protocol for a mixed-methods biobehavioral investigation enrolling 150 sexually active TM to (1) assess the clinical performance and acceptability of a vaginal self-swab for hr.-HPV DNA testing compared to provider cervical swab and cervical cytology, and (2) gather acceptability data on self-collected specimens for other STIs. Study participation entails a one-time clinical visit at Fenway Health in Boston, MA comprised of informed consent, quantitative assessment, venipuncture for syphilis testing and HIV (Rapid OraQuick) testing, randomization, collection of biological specimens/biomarkers, participant and provider satisfaction survey, and qualitative exit interview. Participants are compensated $100. The primary study outcomes are concordance (kappa statistic) and performance (sensitivity and specificity) of self-collected vaginal HPV DNA specimens vs provider-collected cervical HPV swabs as a gold standard. This study addresses critical gaps in current clinical knowledge of sexual health in TM patients, including comparing alternative strategies for screening and diagnosis of cervical cancer, hr.-HPV, and other STIs. Findings have implications for improving the delivery of sexual health screening to this often overlooked and underserved patient population. Less-invasive patient-centered strategies may also generalize to other at-risk cisgender female populations that face barriers to timely and needed STI and cervical cancer screening. ClinicalTrials.gov ID: NCT02401867.

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

PubMed

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

2014-06-01

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

Performance of alternative strategies for primary cervical cancer screening in sub-Saharan Africa: systematic review and meta-analysis of diagnostic test accuracy studies

PubMed Central

Combescure, Christophe; Fokom-Defo, Victoire; Tebeu, Pierre Marie; Vassilakos, Pierre; Kengne, André Pascal; Petignat, Patrick

2015-01-01

Objective To assess and compare the accuracy of visual inspection with acetic acid (VIA), visual inspection with Lugol’s iodine (VILI), and human papillomavirus (HPV) testing as alternative standalone methods for primary cervical cancer screening in sub-Saharan Africa. Design Systematic review and meta-analysis of diagnostic test accuracy studies. Data sources Systematic searches of multiple databases including Medline, Embase, and Scopus for studies published between January 1994 and June 2014. Review methods Inclusion criteria for studies were: alternative methods to cytology used as a standalone test for primary screening; study population not at particular risk of cervical cancer (excluding studies focusing on HIV positive women or women with gynaecological symptoms); women screened by nurses; reference test (colposcopy and directed biopsies) performed at least in women with positive screening results. Two reviewers independently screened studies for eligibility and extracted data for inclusion, and evaluated study quality using the quality assessment of diagnostic accuracy studies 2 (QUADAS-2) checklist. Primary outcomes were absolute accuracy measures (sensitivity and specificity) of screening tests to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Results 15 studies of moderate quality were included (n=61 381 for VIA, n=46 435 for VILI, n=11 322 for HPV testing). Prevalence of CIN2+ did not vary by screening test and ranged from 2.3% (95% confidence interval 1.5% to 3.3%) in VILI studies to 4.9% (2.7% to 7.8%) in HPV testing studies. Positivity rates of VILI, VIA, and HPV testing were 16.5% (9.8% to 24.7%), 16.8% (11.0% to 23.6%), and 25.8% (17.4% to 35.3%), respectively. Pooled sensitivity was higher for VILI (95.1%; 90.1% to 97.7%) than VIA (82.4%; 76.3% to 87.3%) in studies where the reference test was performed in all women (P<0.001). Pooled specificity of VILI and VIA were similar (87.2% (78.1% to 92.8%) v 87.4% (77.1% to 93.4%); P=0.85). Pooled sensitivity and specificity were similar for HPV testing versus VIA (both P≥0.23) and versus VILI (both P≥0.16). Accuracy of VIA and VILI increased with sample size and time period. Conclusions For primary screening of cervical cancer in sub-Saharan Africa, VILI is a simple and affordable alternative to cytology that demonstrates higher sensitivity than VIA. Implementation studies are needed to assess the effect of these screening strategies on the incidence and outcomes of cervical cancer in the region. PMID:26142020

Human Papillomavirus Infection and its Vaccines: Knowledge and Attitudes of Primary Health Clinic Nurses in Kelantan, Malaysia.

PubMed

Jeyachelvi, K; Juwita, S; Norwati, D

2016-01-01

Cervical cancer though preventable is still the leading cause of cancer death among women secondary to breast cancer. Persistent infection with HPV has been causally linked to the disease. A school based HPV vaccination program was introduced in late 2010 in Malaysia and nurse support is essential for its success. To determine nurses knowledge and attitudes about HPV infection and its vaccines, and factors associated with their knowledge. This cross-sectional study was conducted among nurses working at primary health clinics in Kelantan from mid-June till the end of July 2014. Its involved 330 nurses selected through multistage random sampling. A validated self-administered questionnaire consisting of 11 items for the knowledge domain and eight items for the attitude domain was used. The response rate of the study was 93.7%. The mean knowledge and mean attitude (SD) scores were 5.37 (1.76) and 29.8 (3.51) respectively. Only 24% knew that HPV is the most common sexually transmitted infection and 67% correctly answered that Gardasil vaccine can protect against four types of HPV. Nearly 60% of participants wrongly answered that HPV vaccines cannot be offered to sexually active women. Likewise, 70.9% participants were not aware that HPV vaccine may be appropriate for females aged 9 through 26 years. Though 90% of participants believed that the vaccine is safe, nearly half of them were unsure about efficacy. From multiple linear regression analysis, among the factors tested only participant's level of education showed a statistically significant association with the HPV knowledge score (<0.001). This study indicates nurses have favorable attitudes towards HPV vaccination; however they have significant knowledge deficit and major misunderstanding in critical knowledge items. Among the factors tested, nursing qualification is the only factor that is significantly associated with the nurses knowledge score.

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

PubMed Central

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

2010-01-01

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

Assessment of a New Lower-Cost Real-Time PCR Assay for Detection of High-Risk Human Papillomavirus: Useful for Cervical Screening in Limited-Resource Settings?

PubMed Central

Schiffman, Mark; Wentzensen, Nicolas H.; Gage, Julia C.; Castle, Philip E.; Raine-Bennett, Tina R.; Fetterman, Barbara; Lorey, Thomas; Poitras, Nancy E.; Befano, Brian; Xie, Yi; Miachon, Lais S.; Dean, Michael

2017-01-01

ABSTRACT Inexpensive and easy-to-perform human papillomavirus (HPV) tests are needed for primary cervical cancer screening in lower-resource regions. In a convenience sample of 516 residual exfoliative cervical specimens from the Kaiser Permanente Northern California and U.S. National Cancer Institute Persistence and Progression Study, we assessed the agreement and clinical performance of a simple, inexpensive real-time PCR assay for the detection of 13 carcinogenic HPV types (the H13 assay; Hybribio, Hong Kong) that is marketed in limited-resource settings compared to previous testing by the Hybrid Capture 2 assay (HC2; Qiagen, Germantown, MD) and the Onclarity assay (BD Diagnostics, Sparks, MD). The test set was chosen to include many HPV-positive specimens. The reference standard was a combination of HC2 and Onclarity results for HPV detection and histologic diagnosis of controls (less than cervical intraepithelial neoplasia grade 2 [

Assessment of a New Lower-Cost Real-Time PCR Assay for Detection of High-Risk Human Papillomavirus: Useful for Cervical Screening in Limited-Resource Settings?

PubMed

Fokom Domgue, Joel; Schiffman, Mark; Wentzensen, Nicolas H; Gage, Julia C; Castle, Philip E; Raine-Bennett, Tina R; Fetterman, Barbara; Lorey, Thomas; Poitras, Nancy E; Befano, Brian; Xie, Yi; Miachon, Lais S; Dean, Michael

2017-08-01

Inexpensive and easy-to-perform human papillomavirus (HPV) tests are needed for primary cervical cancer screening in lower-resource regions. In a convenience sample of 516 residual exfoliative cervical specimens from the Kaiser Permanente Northern California and U.S. National Cancer Institute Persistence and Progression Study, we assessed the agreement and clinical performance of a simple, inexpensive real-time PCR assay for the detection of 13 carcinogenic HPV types (the H13 assay; Hybribio, Hong Kong) that is marketed in limited-resource settings compared to previous testing by the Hybrid Capture 2 assay (HC2; Qiagen, Germantown, MD) and the Onclarity assay (BD Diagnostics, Sparks, MD). The test set was chosen to include many HPV-positive specimens. The reference standard was a combination of HC2 and Onclarity results for HPV detection and histologic diagnosis of controls (less than cervical intraepithelial neoplasia grade 2 [

Decision making in cancer primary prevention and chemoprevention.

PubMed

Gorin, Sherri Sheinfeld; Wang, Catharine; Raich, Peter; Bowen, Deborah J; Hay, Jennifer

2006-12-01

We know very little about how individuals decide to undertake, maintain, or discontinue cancer primary prevention or chemoprevention. The aims of this article are to (a) examine whether and, if so, how traditional health behavior change models are relevant for decision making in this area; (b) review the application of decision aids to forming specific, personal choices between options; and (c) identify the challenges of evaluating these decision processes to suggest areas for future research. Theoretical models and frameworks derived from the health behavior change and decision-making fields were applied to cancer primary prevention choices. Decision aids for the human papillomavirus (HPV) vaccine, Hormone Replacement Therapy (HRT), and tamoxifen were systematically examined. Traditional concepts such as decisional balance and cues to action are relevant to understanding cancer primary prevention choices; Motivational Interviewing, Self-Determination Theory, and the Preventive Health Model may also explain the facilitators of decision making. There are no well-tested HPV vaccine decision aids, although there have been some studies on aids for HPV testing. There are several effective decision aids for HRT and tamoxifen; evidence-based decision aid components have also been identified. Additional theory-based empirical research on decision making in cancer primary prevention and chemoprevention, particularly at the interface of psychology and behavioral economics, is suggested.

Prevalence of high-risk human papilloma virus genotypes and associated risk of cervical precancerous lesions in a large U.S. screening population: data from the ATHENA trial.

PubMed

Monsonego, Joseph; Cox, J Thomas; Behrens, Catherine; Sandri, Maria; Franco, Eduardo L; Yap, Poh-Sin; Huh, Warner

2015-04-01

We assessed the age-related prevalence of high risk human papillomavirus (HR-HPV) genotypes and the genotype-associated risk for high-grade cervical intraepithelial neoplasia (CIN) in a large U.S. screening population. A total of 40,901 women aged ≥25 years were screened with liquid-based cytology and HPV testing in the ATHENA (Addressing the Need for Advanced HPV Diagnostics) trial. Genotyping was performed using the LINEAR ARRAY HPV Genotyping Test. HPV16 was the most prevalent genotype in all age groups, ranging from 3.5% to 0.8% in women aged 25-29 and ≥50 years, respectively. The next most prevalent genotypes were HPV52, HPV31 and HPV18. In the overall population, HPV16 conferred the greatest absolute risk of ≥CIN3 both in women aged 25-29 and ≥30 years (14.2% and 15.1%, respectively) followed by HPV31 (8.0% and 7.9%), HPV52 (6.7% and 4.4%) and HPV18 (2.7% and 9.0%). Similar trends were seen in women with negative cytology. The percent positivity increased markedly with disease progression for HPV16 and HPV18 which were responsible for 45.6% and 8.4% of ≥CIN3, respectively. Of note, HPV 18 was responsible for 50% of adenocarcinoma in situ (AIS) and 50% of invasive cancer cases. HPV16 played a major role in the development of ≥CIN3 irrespective of age, supporting the identification of HPV16 in primary screening for all women. Identification of HPV18 is also warranted, given its significant contribution to AIS and cancer. Identification of non-16/18 genotypes as a pool should provide sufficient information for screening. Copyright © 2015. Published by Elsevier Inc.

Prediction of cervical cancer incidence in England, UK, up to 2040, under four scenarios: a modelling study.

PubMed

Castanon, Alejandra; Landy, Rebecca; Pesola, Francesca; Windridge, Peter; Sasieni, Peter

2018-01-01

In the next 25 years, the epidemiology of cervical cancer in England, UK, will change: human papillomavirus (HPV) screening will be the primary test for cervical cancer. Additionally, the proportion of women screened regularly is decreasing and women who received the HPV vaccine are due to attend screening for the first time. Therefore, we aimed to estimate how vaccination against HPV, changes to the screening test, and falling screening coverage will affect cervical cancer incidence in England up to 2040. We did a data modelling study that combined results from population modelling of incidence trends, observable data from the individual level with use of a generalised linear model, and microsimulation of unobservable disease states. We estimated age-specific absolute risks of cervical cancer in the absence of screening (derived from individual level data). We used an age period cohort model to estimate birth cohort effects. We multiplied the absolute risks by the age cohort effects to provide absolute risks of cervical cancer for unscreened women in different birth cohorts. We obtained relative risks (RRs) of cervical cancer by screening history (never screened, regularly screened, or lapsed attender) using data from a population-based case-control study for unvaccinated women, and using a microsimulation model for vaccinated women. RRs of primary HPV screening were relative to cytology. We used the proportion of women in each 5-year age group (25-29 years to 75-79 years) and 5-year period (2016-20 to 2036-40) who have a combination of screening and vaccination history, and weighted to estimate the population incidence. The primary outcome was the number of cases and rates per 100 000 women under four scenarios: no changes to current screening coverage or vaccine uptake and HPV primary testing from 2019 (status quo), changing the year in which HPV primary testing is introduced, introduction of the nine-valent vaccine, and changes to cervical screening coverage. The status quo scenario estimated that the peak age of cancer diagnosis will shift from the ages of 25-29 years in 2011-15 to 55-59 years in 2036-40. Unvaccinated women born between 1975 and 1990 were predicted to have a relatively high risk of cervical cancer throughout their lives. Introduction of primary HPV screening from 2019 could reduce age-standardised rates of cervical cancer at ages 25-64 years by 19%, from 15·1 in 2016 to 12·2 per 100 000 women as soon as 2028. Vaccination against HPV types 16 and 18 (HPV 16/18) could see cervical cancer rates in women aged 25-29 years decrease by 55% (from 20·9 in 2011-15 to 9·5 per 100 000 women by 2036-40), and introduction of nine-valent vaccination from 2019 compared with continuing vaccination against HPV 16/18 will reduce rates by a further 36% (from 9·5 to 6·1 per 100 000 women) by 2036-40. Women born before 1991 will not benefit directly from vaccination; therefore, despite vaccination and primary HPV screening with current screening coverage, European age-standardised rates of cervical cancer at ages 25-79 years will decrease by only 10% (from 12·8 in 2011-15 to 11·5 per 100 000 women in 2036-40). If screening coverage fell to 50%, European age-standardised rates could increase by 27% (from 12·8 to 16·3 per 100 000 by 2036-40). Going forward, focus should be placed on scenarios that offer less intensive screening for vaccinated women and more on increasing coverage and incorporation of new technologies to enhance current cervical screening among unvaccinated women. Jo's Cervical Cancer Trust and Cancer Research UK. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

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

PubMed

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

2015-01-01

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

Daily self-sampling for high-risk human papillomavirus (HR-HPV) testing.

PubMed

Sanner, Karin; Wikström, Ingrid; Gustavsson, Inger; Wilander, Erik; Lindberg, Julia Hedlund; Gyllensten, Ulf; Olovsson, Matts

2015-12-01

Self-sampling for HPV as part of primary screening is a well-tolerated method for women not attending organized Pap smear screening and could increase coverage of cervical cancer screening. To investigate if the prevalence of HR-HPV varies from day to day in infected women and if one single sample is reliable for detecting an ongoing infection. This is a prospective cohort study on 12 premenopausal and 13 postmenopausal women performing daily self-sampling for HR-HPV testing. They were all HR-HPV-positive 1-3 months ago. Postmenopausal women were sampled for 28 days and premenopausal women sampled during bleeding-free days in one menstrual cycle. A possible difference in viral load between the estrogen-dominated proliferative phase and the progesterone-dominated secretory phase was analyzed. Consistent results throughout the sampling period were observed for 19 women, with either a daily presence of HPV (14 women) or no HPV at all during the sampling period (5 women). Of 607 samples from 25 women, 596 were consistently positive or negative for HPV during the sampling period and 11 were inconsistent (2%). There was no difference in HPV copy number between the estrogen dominated proliferative or progesterone dominated secretory menstrual cycle phases. The major finding was a high degree of consistency concerning HR-HPV positivity and negativity of HR-HPV in vaginal fluid during a sustained period of daily self-sampling. It does not appear to matter whether the sample is collected in the proliferative or secretory phase. Copyright © 2015 Elsevier B.V. All rights reserved.

Effectiveness Modelling and Economic Evaluation of Primary HPV Screening for Cervical Cancer Prevention in New Zealand

PubMed Central

Lew, Jie-Bin; Simms, Kate; Smith, Megan; Lewis, Hazel; Neal, Harold; Canfell, Karen

2016-01-01

Background New Zealand (NZ) is considering transitioning from 3-yearly cervical cytology screening in women 20–69 years (current practice) to primary HPV screening. We evaluated HPV-based screening in both HPV-unvaccinated women and cohorts offered HPV vaccination in New Zealand (vaccination coverage ~50%). Methods A complex model of HPV transmission, vaccination, cervical screening, and invasive cervical cancer was extensively validated against national population-based datasets. Sixteen potential strategies for HPV screening were considered. Results Most primary HPV strategies were more effective than current practice, for both unvaccinated women and cohorts offered vaccination. The optimal strategy for both groups was 5-yearly HPV screening in women aged 25–69 years with partial genotyping for HPV 16/18 and referral to colposcopy, and cytological triage of other oncogenic types. This is predicted to reduce cervical cancer incidence and mortality by a further 12–16% and to save 4–13% annually in program costs (excluding overheads). The findings are sensitive to assumptions about future adherence to initiating screening at 25 years. Conclusion Primary HPV screening with partial genotyping would be more effective and less costly than the current cytology-based screening program, in both unvaccinated women and cohorts offered vaccination. These findings have been considered in a review of cervical screening in NZ. PMID:27187495

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

PubMed Central

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

2013-01-01

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

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

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

Human Papillomavirus (HPV) Infection in Squamous Cell Carcinomas Arising From the Oropharynx: Detection of HPV DNA and p16 Immunohistochemistry as Diagnostic and Prognostic Indicators—A Pilot Study

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

Bussu, Francesco, E-mail: francesco.bussu.md@gmail.com; Sali, Michela; Gallus, Roberto

Purpose: Human papillomavirus (HPV) 16 infection is associated with oropharyngeal carcinogenesis and is likely the cause of the reported increase in disease incidence. We evaluated the prevalence of HPV infection and the reliability of different diagnostic tools using primary tumor samples from a cohort of 50 patients. Methods and Materials: Formalin-fixed paraffin-embedded (FFPE) tumor samples were collected from all 50 consecutive primary oropharyngeal SCC patients who were enrolled in the study; fresh tumor samples were available in 22 cases. NucliSENS EasyQ HPVv1 was used for RNA, and Digene Hybrid Capture-2(HC2) was used for DNA detection. p16 Expression was evaluated bymore » immunohistochemistry in FPPE specimens. Results: Based on the DNA detection assay on FFPE samples, the frequency of high-risk HPV infection was 32%. The agreement rate between HPV RNA and HPV DNA detection in fresh samples was 100%. The agreement rate between p16 immunohistochemistry (IHC) and the detection of HPV DNA in the FFPE samples was fair but not excellent (κ = 0.618). HPV DNA detection was highly significant, as measured by disease-specific survival and determined using a Wilcoxon test (P=.001). p16 IHC also exhibited a prognostic value but with a lower statistical significance (P=.0475). The detection of HPV DNA, but not p16 IHC, was also significantly correlated with locoregional control (P=.0461). Conclusion: Diagnostic methods based on the detection of HPV nucleic acids appear to be more reliable and objective because they do not require reading by a trained histopathologist. Furthermore, the detection of HPV DNA exhibits an improved correlation with survival, and therefore appears definitely more reliable than p16 IHC for routine use in clinical practice.« less

Detection of human papillomaviruses by polymerase chain reaction and ligation reaction on universal microarray.

PubMed

Ritari, Jarmo; Hultman, Jenni; Fingerroos, Rita; Tarkkanen, Jussi; Pullat, Janne; Paulin, Lars; Kivi, Niina; Auvinen, Petri; Auvinen, Eeva

2012-01-01

Sensitive and specific detection of human papillomaviruses (HPV) in cervical samples is a useful tool for the early diagnosis of epithelial neoplasia and anogenital lesions. Recent studies support the feasibility of HPV DNA testing instead of cytology (Pap smear) as a primary test in population screening for cervical cancer. This is likely to be an option in the near future in many countries, and it would increase the efficiency of screening for cervical abnormalities. We present here a microarray test for the detection and typing of 15 most important high-risk HPV types and two low risk types. The method is based on type specific multiplex PCR amplification of the L1 viral genomic region followed by ligation detection reaction where two specific ssDNA probes, one containing a fluorescent label and the other a flanking ZipCode sequence, are joined by enzymatic ligation in the presence of the correct HPV PCR product. Human beta-globin is amplified in the same reaction to control for sample quality and adequacy. The genotyping capacity of our approach was evaluated against Linear Array test using cervical samples collected in transport medium. Altogether 14 out of 15 valid samples (93%) gave concordant results between our test and Linear Array. One sample was HPV56 positive in our test and high-risk positive in Hybrid Capture 2 but remained negative in Linear Array. The preliminary results suggest that our test has accurate multiple HPV genotyping capability with the additional advantages of generic detection format, and potential for high-throughput screening.

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

PubMed

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

2011-08-15

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

77 FR 9660 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-17

... target age range with a normal Pap test and a negative HPV DNA test. Primary goals of the study are to... Description The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) is the only organized... secondary screening tool for ASCUS (Atypical Squamous Cells of Undetermined Significance), and as a primary...

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

PubMed

Tjalma, Wiebren A A

2017-03-01

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

Long-term HPV type-specific risks for ASCUS and LSIL: a 14-year follow-up of a randomized primary HPV screening trial.

PubMed

Elfström, K Miriam; Smelov, Vitaly; Johansson, Anna L V; Eklund, Carina; Naucler, Pontus; Arnheim-Dahlström, Lisen; Dillner, Joakim

2015-01-15

Human papillomavirus (HPV) infections result in a significant burden of low-grade cervical lesions. Between 1997 and 2000, our randomized trial of primary HPV screening enrolled 12,527 women participating in population-based screening. Women between 32 and 38 years of age (median: 34, interquartile range: 33-37) were randomized to HPV and cytology double testing (intervention arm, n = 6,257 enrolled, n = 5,888 followed-up) or to cytology, with samples frozen for future HPV testing (control arm, n = 6,270 enrolled, n = 5,795 followed-up). We estimated the HPV type-specific, long-term absolute risks (AR), and population attributable proportions (PAR) for cytological diagnoses of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) and for histopathologically diagnosed cervical intraepithelial neoplasia grade 1 (CIN1). The women were followed using comprehensive, nationwide register-based follow-up. During a mean follow-up time of 11.07 years, 886 ASCUS and LSIL lesions were detected, 448 in the intervention arm and 438 in the control arm. Poisson regression estimated the incidence rate ratios (IRRs) of low-grade lesions by HPV type. The IRRs were strongly dependent on follow-up time. The IRRs for ASCUS/LSIL associated with high-risk HPV positivity were 18.6 (95% CI: 14.9-23.4) during the first screening round, 4.1 (95% CI: 2.8-6.2) during the second, 2.6 (95% CI: 1.7-4.1) during the third, and 1.1 (95% CI: 0.7-1.8) for >9 years of follow-up, with similar declines seen for the individual types. Type 16 contributed consistently to the greatest proportion of ASCUS, LSIL, and CIN1 risk in the population (first screening round PAR: ASCUS: 15.5% (95% CI: 9.7-21.9), LSIL: 14.7% (95% CI: 8.0-20.9), and CIN1: 13.4% (95% CI: 3.2-22.5)), followed by type 31 [8.4% (95% CI: 4.2-12.5) for ASCUS to 17.3% (95% CI: 6.8-26.6) for CIN1]. In summary, most ASCUS/LSIL lesions associated with HPV infection are caused by new HPV infections and most lesions are found during the first screening round. © 2014 UICC.

A comparison of the MeltPro® HPV Test with the Cobas® HPV Test for detecting and genotyping 14 high-risk human papillomavirus types.

PubMed

Tang, Zhiteng; Xu, Ye; Song, Najie; Zou, Dongqing; Liao, Yiqun; Li, Qingge; Pan, Chao

2018-03-01

The clinical performance of the newly developed MeltPro ® HPV Test, based on multicolor melting curve analysis, was evaluated and compared with the commercially available Cobas ® HPV Test for detection of HPV and genotyping of HPV-16 and HPV-18. A total of 1647 cervical samples were analyzed with both tests. The agreement values were 96.2% for HPV detection, 99.6% for HPV-16 identification, and 99.7% for HPV-18 identification. All genotyping results from MeltPro ® HPV Test showed that HPV-52, HPV-58, and HPV-16 were the most common types in this study. Intra-laboratory reproducibility studies showed 97.8% agreement while inter-laboratory reproducibility studies showed 96.9% agreement for the MeltPro ® HPV Test. The MeltPro ® HPV Test and Cobas ® HPV Test are highly correlative and are useful for monitoring HPV infection.

Correlation of human papilloma virus status with quantitative perfusion/diffusion/metabolic imaging parameters in the oral cavity and oropharyngeal squamous cell carcinoma: comparison of primary tumour sites and metastatic lymph nodes.

PubMed

Han, M; Lee, S J; Lee, D; Kim, S Y; Choi, J W

2018-05-17

To investigate the differences in perfusion/diffusion/metabolic imaging parameters according to human papilloma virus (HPV) status in the oral cavity and oropharyngeal squamous cell carcinoma (OC-OPSCC), separately in primary tumour sites and metastatic lymph nodes. This retrospective study comprised 41 patients with primary OC-OPSCCs and 29 patients with metastatic lymph nodes. The perfusion/diffusion/metabolic imaging parameters were measured at the primary tumour and the largest ipsilateral metastatic lymph node. The quantitative parameters were compared between the HPV-positive and -negative groups. The HPV-positivity was 39% (16 patients) for the primary tumours and 51.7% (15 patients) for the metastatic lymph nodes. Patients with HPV-positive tumours had a lower T stage (p=0.034). The metastatic lymph nodes for the HPV-positive patients were bulkier (p=0.016) and more frequently had cystic morphology (p=0.005). The perfusion parameters were not different, regardless of HPV status. The diffusion parameter (ADC min , p=0.011) of the metastatic lymph nodes in the HPV-positive groups was lower and metabolic parameter (metabolic tumour volume p=0.035 and total lesion glycolysis p=0.037) were higher than those in HPV-negative groups. The diffusion and metabolic parameters of metastatic lymph nodes from OC-OPSCC were different according to HPV status. The perfusion parameters did not clearly represent HPV status. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-09-01

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

Human Papillomavirus as a Diagnostic and Prognostic Tool in Cancer of Unknown Primary in the Head and Neck Region.

PubMed

Sivars, Lars; Tani, Edneia; Näsman, Anders; Ramqvist, Torbjörn; Munck-Wikland, Eva; Dalianis, Tina

2016-02-01

Human papillomavirus (HPV) is recognized as a risk factor for oropharyngeal squamous cell carcinomas (SCC), especially tonsillar and base of tongue cancer. Furthermore, HPV-positive tonsillar and base of tongue SCC have a significantly better prognosis than their HPV-negative counterparts and head and neck cancer (HNSCC) in general. HPV has recently also been implicated in cancer of unknown primary (CUP) in the head and neck region, where a primary tumour is not found despite extensive workup. Using fine-needle aspiration cytology to determine CUP HPV status in cervical lymph nodes could be of advantage, since it is minimally invasive and it is assumed that an HPV-positive lymph node metastasis likely has an HPV-positive otopharyngeal SCC origin. We review the current knowledge of HPV in HNSCC, with an emphasis on CUP of the head and neck region, its relation to oropharyngeal, tonsillar and base of tongue SCC and implications of HPV status for diagnosis, prognosis and treatment. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Human papilloma virus status and chromosomal imbalances in primary cervical carcinomas and tumour cell lines.

PubMed

Hidalgo, A; Schewe, C; Petersen, S; Salcedo, M; Gariglio, P; Schlüns, K; Dietel, M; Petersen, I

2000-03-01

Human papilloma virus (HPV) infection is the crucial step in the initiation of cervical carcinomas. In addition, HPV18 has been implicated in tumour progression and adverse clinical outcome. We determined the HPV types in 12 primary cervical carcinomas and 12 cell lines and compared the findings with the comparative genetic hybridisation (CGH) pattern of chromosomal alterations. The most frequent alteration was the deletion at 3p14 followed by the loss of 2q34-q36 along with 3q gain. High risk HPV types were detected in all samples except one primary tumour. In contrast to the normal distribution, HPV18 was present in 75% of cases including all cell lines. The cell lines carried a higher number of genetic alterations and a different CGH pattern for several chromosomes than the primary tumours, despite microdissection. Purely HPV18 positive cases indicated a high incidence of imbalances at specific loci with peaks of the histogram coinciding with known HPV integration sites. The study suggests that HPV infection is associated with a recurrent pattern of chromosomal changes in cervical carcinomas and that the development and progression of these alterations is triggered by integration into the host genome.

Atypical Clinical Behavior of p16-Confirmed HPV-Related Oropharyngeal Squamous Cell Carcinoma Treated With Radical Radiotherapy

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

Huang Shaohui; Perez-Ordonez, Bayardo; Liu Feifei

Purpose: To report atypical clinical behavior observed in human papillomavirus (HPV)-related oropharyngeal carcinoma (OPC) treated with radiotherapy. Methods and Materials: A retrospective cohort study was conducted for all newly diagnosed OPC cases treated with radiotherapy on July 1, 2003 to April 30, 2009. HPV positivity was determined by p16 immunostaining in tumors. The incidence of additional malignancies and the pattern of distant metastases (DMs) were compared between the HPV-positive (HPV+) and HPV-negative (HPV-) cohorts. Results: HPV status was evaluated in 318 of 613 consecutive OPC cases (52%), showing 236 HPV+ and 82 HPV- patients. Compared with HPV-, HPV+ cases weremore » less likely to have additional malignancies (prior: 11% vs. 20%, p = 0.038; synchronous: 1% vs. 9%, p = 0.001; metachronous: 6% vs. 16%, p = 0.003). Whereas the majority (10 of 12) of HPV- additional head-and-neck (HN) mucosal malignancies were in the oral cavity, there was none (0 of 7) in the HPV+ cohort (p < 0.001). HPV+ synchronous HN second primaries (SPs) were in the supraglottis, post-cricoid, and nasopharynx; metachronous HN SPs were in the glottis, supraglottis, and ethmoid plus glottis/post-cricoid region. All SPs that could be tested were HPV+. There was no difference in DM rate (10% vs. 15%, p = 0.272), but HPV+ DMs were more likely to involve multiple organs (46% vs. 0%, p = 0.005) and unusual sites. Conclusions: This study reports atypical clinical behavior seen in HPV+ OPC, including multicentric lesions in HN mucosa and DM to multiple organs and unusual sites. The frequency of these events is low, but they may have clinical implications. The routine assessment of HPV status for all OPC is warranted.« less

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

PubMed

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

2016-04-01

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

Communication technologies to improve HPV vaccination initiation and completion: A systematic review.

PubMed

Francis, Diane B; Cates, Joan R; Wagner, Kyla P Garrett; Zola, Tracey; Fitter, Jenny E; Coyne-Beasley, Tamera

2017-07-01

This systematic review examines the effectiveness of communication technology interventions on HPV vaccination initiation and completion. A comprehensive search strategy was used to identify existing randomized controlled trials testing the impact of computer-, mobile- or internet-based interventions on receipt of any dose of the HPV vaccine. Twelve relevant studies were identified with a total of 38,945 participants. The interventions were delivered using several different methods, including electronic health record (i.e. recall/reminder) prompts, text messaging, automated phone calls, interactive computer videos, and email. Vaccine initiation and completion was greater for technology-based studies relative to their control conditions. There is evidence that interventions utilizing communication technologies as their sole or primary mode for HPV vaccination intervention delivery may increase vaccination coverage. Communication technologies hold much promise for the future of HPV vaccination efforts, especially initiatives in practice-based settings. Copyright © 2017 Elsevier B.V. All rights reserved.

Acceptability of unsupervised HPV self-sampling using written instructions.

PubMed

Waller, J; McCaffery, K; Forrest, S; Szarewski, A; Cadman, L; Austin, J; Wardle, J

2006-01-01

The study measured the acceptability of self-sampling for human papillomavirus (HPV) testing in the context of cervical cancer screening. Women carried out self-sampling unsupervised, using a written instruction sheet. Participants were women attending either a family planning clinic or a primary care trust for routine cervical screening. Women (n = 902) carried out self-sampling for HPV testing and then a clinician did a routine cervical smear and HPV test. Immediately after having the two tests, participants completed a measure of acceptability for both tests, and answered questions about ease of using the instruction sheet and willingness to use self-sampling in the future. The majority of women found self-sampling more acceptable than the clinician-administered test, but there was a lack of confidence that the test had been done correctly. Significant demographic differences in attitudes were found, with married women having more favourable attitudes towards self-sampling than single women, and Asian women having more negative attitudes than women in other ethnic groups. Intention to use self-sampling in the future was very high across all demographic groups. Self-sampling for HPV testing was highly acceptable in this large and demographically diverse sample, and women were able to carry out the test alone, using simple written instructions. Consistent with previous studies, women were concerned about doing the test properly and this issue will need to be addressed if self-sampling is introduced. More work is needed to see whether the demographic differences we found are robust and to identify reasons for lower acceptability among single women and those from Asian background.

The impact of virus in N3 node dissection for head and neck cancer.

PubMed

Armas, Gian Luca; Su, Chih-Ying; Huang, Chao-Cheng; Fang, Fu-Min; Chen, Ching-Mei; Chien, Chih-Yen

2008-11-01

This study is to determine the impact of virus in surgical outcomes among patients of head and neck cancer with N3 lymph node metastasis. A retrospective analysis was conducted for 32 patients with operable N3 neck metastasis undergoing surgical treatment between January 1987 and October 2006. The nuclei of the tumor cells were investigated for the presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) DNAs and were taken into account as the variable for survival analysis. The primary sites were oropharynx in 11 patients, tongue in 3, buccal mucosa in 1, hypopharynx in 8 and unknown primary in 9. The five-year cumulative overall survival rate was 40.7% and 5-year cumulative regional control rate was 55.8%. The 5-year cumulative overall survival rate of patients with unknown primary site (72.9%) and HPV or EBV positive in the tumor (77.8%) were significantly higher than those patients with known primary site (31.3%) and HPV or EBV negative in the tumor (27.4%), respectively (P = 0.0335 and P = 0.0348, log rank test). In conclusion, surgery with adjuvant therapy offers reasonable outcomes for operable N3 node in head and neck cancer in our cohort. In addition, patients with HPV or EBV positive in the tumor have a better survival.

Comparative Assessment of a Self-sampling Device and Gynecologist Sampling for Cytology and HPV DNA Detection in a Rural and Low Resource Setting: Malaysian Experience.

PubMed

Latiff, Latiffah A; Ibrahim, Zaidah; Pei, Chong Pei; Rahman, Sabariah Abdul; Akhtari-Zavare, Mehrnoosh

2015-01-01

This study was conducted to assess the agreement and differences between cervical self-sampling with a Kato device (KSSD) and gynecologist sampling for Pap cytology and human papillomavirus DNA (HPV DNA) detection. Women underwent self-sampling followed by gynecologist sampling during screening at two primary health clinics. Pap cytology of cervical specimens was evaluated for specimen adequacy, presence of endocervical cells or transformation zone cells and cytological interpretation for cells abnormalities. Cervical specimens were also extracted and tested for HPV DNA detection. Positive HPV smears underwent gene sequencing and HPV genotyping by referring to the online NCBI gene bank. Results were compared between samplings by Kappa agreement and McNemar test. For Pap specimen adequacy, KSSD showed 100% agreement with gynecologist sampling but had only 32.3% agreement for presence of endocervical cells. Both sampling showed 100% agreement with only 1 case detected HSIL favouring CIN2 for cytology result. HPV DNA detection showed 86.2%agreement (K=0.64, 95% CI 0.524-0.756, p=0.001) between samplings. KSSD and gynaecologist sampling identified high risk HPV in 17.3% and 23.9% respectively (p= 0.014). The self-sampling using Kato device can serve as a tool in Pap cytology and HPV DNA detection in low resource settings in Malaysia. Self-sampling devices such as KSSD can be used as an alternative technique to gynaecologist sampling for cervical cancer screening among rural populations in Malaysia.

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

PubMed

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

2016-01-01

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

Practice towards human papillomavirus vaccines among Malaysian women: a survey of a general youth population.

PubMed

Al-Naggar, Redhwan Ahmed; Bobryshev, Yuri V

2011-01-01

This study was performed to determine the practice of HPV vaccine among Malaysian women in the general population. A cross-sectional study was conducted among 233 women during the Academic Year 2010/2011. Written consent was obtained from the participants and written information about the study was given enclosed with the questionnaire form, consisting of questions on socio-demographic characteristics, knowledge about HPV and practice of HPV vaccination. The protocol was approved by the ethics committee of Management and Science University (MSU). Data were analyzed using Statistical Package for Social Sciences (SPSS) version 13. The T-test and ANOVA test were used to explore the relation between socio-demographic characteristics and the practice of HPV vaccine. The majority of the participants were from the age group 17-30 years old, Malay, single and having tertiary education (67.8, 62.7, 62.2, 86.3%; respectively). As for knowledge, the majority of them heard about HPV (82.4%), knew that multiple sex partners increase the risk (71.7%). Regarding the practice of HPV vaccine among respondents, slightly more than half had been vaccinated (51.5%). Regarding the factors that influenced the practice of HPV vaccine among general population; age, marital status and family monthly income were significant (p=0.001, p=0.001, p=0.001; respectively). Age, marital status and income significantly influence the practice of HPV vaccine. Therefore promotion of HPV vaccine and inclusion in the national vaccination program is very important for primary prevention of cervical cancer among women.

HPV Vaccination of Boys in Primary Care Practices

PubMed Central

Allison, Mandy A.; Dunne, Eileen F.; Markowitz, Lauri E.; O’Leary, Sean T.; Crane, Lori A.; Hurley, Laura P.; Stokley, Shannon; Babbel, Christine I.; Brtnikova, Michaela; Beaty, Brenda L.; Kempe, Allison

2018-01-01

OBJECTIVE In October 2011, the Advisory Committee on Immunization Practices (ACIP) recommended the quadrivalent human papillomavirus vaccine (HPV4) for the routine immunization schedule for 11- to 12-year-old boys. Before October 2011, HPV4 was permissively recommended for boys. We conducted a study in 2010 to provide data that could guide efforts to implement routine HPV4 immunization in boys. Our objectives were to describe primary care physicians’: 1) knowledge and attitudes about human papillomavirus (HPV)-related disease and HPV4, 2) recommendation and administration practices regarding HPV vaccine in boys compared to girls, 3) perceived barriers to HPV4 administration in boys, and 4) personal and practice characteristics associated with recommending HPV4 to boys. METHODS We conducted a mail and Internet survey in a nationally representative sample of pediatricians and family medicine physicians from July 2010 to September 2010. RESULTS The response rate was 72% (609 of 842). Most physicians thought that the routine use of HPV4 in boys was justified. Although it was permissively recommended, 33% recommended HPV4 to 11- to 12-year-old boys and recommended it more strongly to older male adolescents. The most common barriers to HPV4 administration were related to vaccine financing. Physicians who reported recommending HPV4 for 11- to 12-year-old boys were more likely to be from urban locations, perceive that HPV4 is efficacious, perceive that HPV-related disease is severe, and routinely discuss sexual health with 11- to 12-year-olds. CONCLUSIONS Although most physicians support HPV4 for boys, physician education and evidence-based tools are needed to improve implementation of a vaccination program for males in primary care settings. PMID:24011749

Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel: a subset analysis of EORTC 24971 study.

PubMed

Psyrri, A; Fortpied, C; Koutsodontis, G; Avgeris, M; Kroupis, C; Goutas, N; Menis, J; Herman, L; Giurgea, L; Remenár, É; Degardin, M; Pateras, I S; Langendijk, J A; van Herpen, C M L; Awada, A; Germà-Lluch, J R; Kienzer, H R; Licitra, L; Vermorken, J B

2017-09-01

EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell carcinomas. We conducted a retrospective analysis of prospectively collected data aiming to evaluate whether only HPV(-) patients (pts) benefit from adding docetaxel to PF, in which case deintensifying induction treatment in HPV(+) pts could be considered. Pretherapy tumor biopsies (blocks or slides) were assessed for high-risk HPV by p16 immunohistochemistry, PCR and quantitative PCR. HPV-DNA+ and/or p16+ tumors were subjected to in situ hybridization (ISH) and HPV E6 oncogene expression qRT-PCR analysis. Primary and secondary objectives were to evaluate the value of HPV/p16 status as predictive factor of treatment benefit in terms of PFS and OS. The predictive effect was analyzed based on the model used in the primary analysis of the study with the addition of a treatment by marker interaction term and tested at two-sided 5% significance level. Of 358, 119 pts had available tumor samples and 58 of them had oropharyngeal cancer. Median follow-up was 8.7 years. Sixteen of 119 (14%) evaluable samples were p16+ and 20 of 79 (25%) evaluable tumors were HPV-DNA+. 13 of 40 pts (33%) assessed with HPV-DNA ISH and 12 of 28 pts (43%) assessed for HPV E6 mRNA were positive. The preplanned analysis showed no statistical evidence of predictive value of HPV/p16 status for PFS (P = 0.287) or OS (P = 0.118). The incidence of HPV positivity was low in the subset of EORTC 24971 pts analyzed. In this analysis only powered to detect a large treatment by marker interaction, there was no statistical evidence that treatment effect found overall was different in magnitude in HPV(+) or HPV(-) pts. These results do not justify selection of TPF versus PF according to HPV status. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

p16-positive lymph node metastases from cutaneous head and neck squamous cell carcinoma: No association with high-risk human papillomavirus or prognosis and implications for the workup of the unknown primary.

PubMed

McDowell, Lachlan J; Young, Richard J; Johnston, Meredith L; Tan, Tze-Jian; Kleid, Stephen; Liu, Chen S; Bressel, Mathias; Estall, Vanessa; Rischin, Danny; Solomon, Benjamin; Corry, June

2016-04-15

The incidence of p16 overexpression and the role of human papillomavirus (HPV) in cutaneous head and neck squamous cell carcinoma (cHNSCC) are unclear. One hundred forty-three patients with cHNSCC lymph node metastases involving the parotid gland were evaluated for p16 expression by immunohistochemistry. The detection of 18 high-risk HPV subtypes was performed with HPV RNA in situ hybridization for a subset of 59 patients. The results were correlated with clinicopathological features and outcomes. The median follow-up time was 5.3 years. No differences were observed in clinicopathological factors with respect to the p16 status. p16 was positive, weak, and negative in 45 (31%), 21 (15%), and 77 cases (54%), respectively. No high-risk HPV subtypes were identified, regardless of the p16 status. The p16 status was not prognostic for overall (hazard ratio, 1.08; 95% confidence interval [CI], 0.85-1.36; P = .528), cancer-specific (hazard ratio, 1.12; 95% CI, 0.77-1.64; P = .542), or progression-free survival (hazard ratio, 1.03; 95% CI, 0.83-1.29; P = .783). Distant metastasis-free survival, freedom from locoregional failure, and freedom from local failure were also not significantly associated with the p16 status. p16 positivity is common but not prognostic in cHNSCC lymph node metastases. High-risk HPV subtypes are not associated with p16 positivity and do not appear to play a role in this disease. HPV testing, in addition to the p16 status in the unknown primary setting, may provide additional information for determining a putative primary site. © 2016 American Cancer Society.

HPV16 synthetic long peptide (HPV16-SLP) vaccination therapy of patients with advanced or recurrent HPV16-induced gynecological carcinoma, a phase II trial.

PubMed

van Poelgeest, Mariette I E; Welters, Marij J P; van Esch, Edith M G; Stynenbosch, Linda F M; Kerpershoek, Gijs; van Persijn van Meerten, Els L; van den Hende, Muriel; Löwik, Margriet J G; Berends-van der Meer, Dorien M A; Fathers, Lorraine M; Valentijn, A Rob P M; Oostendorp, Jaap; Fleuren, Gert Jan; Melief, Cornelis J M; Kenter, Gemma G; van der Burg, Sjoerd H

2013-04-04

Human papilloma virus type 16 (HPV16)-induced gynecological cancers, in particular cervical cancers, are found in many women worldwide. The HPV16 encoded oncoproteins E6 and E7 are tumor-specific targets for the adaptive immune system permitting the development of an HPV16-synthetic long peptide (SLP) vaccine with an excellent treatment profile in animal models. Here, we determined the toxicity, safety, immunogenicity and efficacy of the HPV16 SLP vaccine in patients with advanced or recurrent HPV16-induced gynecological carcinoma. Patients with HPV16-positive advanced or recurrent gynecological carcinoma (n = 20) were subcutaneously vaccinated with an HPV16-SLP vaccine consisting of a mix of 13 HPV16 E6 and HPV16 E7 overlapping long peptides in Montanide ISA-51 adjuvant. The primary endpoints were safety, toxicity and tumor regression as determined by RECIST. In addition, the vaccine-induced T-cell response was assessed by proliferation and associated cytokine production as well as IFNγ-ELISPOT. No systemic toxicity beyond CTCAE grade II was observed. In a few patients transient flu-like symptoms were observed. In 9 out of 16 tested patients vaccine-induced HPV16-specific proliferative responses were detected which were associated with the production of IFNγ, TNFα, IL-5 and/or IL-10. ELISPOT analysis revealed a vaccine-induced immune response in 11 of the 13 tested patients. The capacity to respond to the vaccine was positively correlated to the patient's immune status as reflected by their response to common recall antigens at the start of the trial. Median survival was 12.6 ± 9.1 months. No regression of tumors was observed among the 12 evaluable patients. Nineteen patients died of progressive disease. The HPV16-SLP vaccine was well tolerated and induced a broad IFNγ-associated T-cell response in patients with advanced or recurrent HPV16-induced gynecological carcinoma but neither induced tumor regression nor prevented progressive disease. We, therefore, plan to use this vaccine in combination with chemotherapy and immunomodulation.

Identifying Human Papillomavirus Vaccination Practices Among Primary Care Providers of Minority, Low-Income and Immigrant Patient Populations

PubMed Central

Bruno, Denise M.; Wilson, Tracey E.; Gany, Francesca; Aragones, Abraham

2014-01-01

Objective Minority populations in the United States are disproportionally affected by Human Papillomavirus (HPV) infection and HPV-related cancer. We sought to understand physician practices, knowledge and beliefs that affect utilization of the HPV vaccine in primary care settings serving large minority populations in areas with increased rates of HPV-related cancer. Study Design Cross-sectional survey of randomly selected primary care providers, including pediatricians, family practice physicians and internists, serving large minority populations in Brooklyn, N.Y. and in areas with higher than average cervical cancer rates. Results Of 156 physicians randomly selected, 121 eligible providers responded to the survey; 64% were pediatricians, 19% were internists and 17% were family practitioners. Thirty-four percent of respondents reported that they routinely offered HPV vaccine to their eligible patients. Seventy percent of physicians reported that the lack of preventive care visits for patients in the eligible age group limited their ability to recommend the HPV vaccine and 70% of those who reported this barrier do not routinely recommend HPV vaccine. The lack of time to educate parents about the HPV vaccine and cost of the vaccine to their patients were two commonly reported barriers that affected whether providers offered the vaccine. Conclusions Our study found that the majority of providers serving the highest risk populations for HPV infection and HPV-related cancers are not routinely recommending the HPV vaccine to their patients. Reasons for providers' failure to recommend the HPV vaccine routinely are identified and possible areas for targeted interventions to increase HPV vaccination rates are discussed. PMID:24886959

HPV testing: a mixed-method approach to understand why women prefer self-collection in a middle-income country.

PubMed

Arrossi, Silvina; Ramos, Silvina; Straw, Cecilia; Thouyaret, Laura; Orellana, Liliana

2016-08-19

HPV test self-collection has been shown to reduce barriers to cervical screening and increase uptake. However, little is known about women's preferences when given the choice between self-collected and clinician-collected tests. This paper aims to describe experiences with HPV self-collection among women in Jujuy, the first Argentinean province to have introduced HPV testing as the primary screening method, provided free of cost in all public health centers. Between July and December 2012, data on acceptability of HPV self-collection and several social variables including past screening were collected from 2616 self-collection accepters and 433 non-accepters, and were analyzed using multivariate regression. In addition, in-depth interviews (n = 30) and 2 focus groups were carried out and analyzed using thematic analysis. Quantitative findings indicate that main reasons for choosing self-collection are those reducing barriers related to women's roles of responsibility for domestic work and work/family organization, and to health care services' organization. No social variables were significantly associated with acceptability. Among those who preferred clinician-collection, the main reasons were trust in health professionals and fear of hurting themselves. Qualitative findings also showed that self-collection allows women to overcome barriers related to the health system (i.e. long wait times), without sacrificing time devoted to work/domestic responsibilities. Findings have implications for self-collection recommendations, as they show it is the preferred method when women are given the choice, even if they are not screening non-attenders. Findings also highlight the importance of incorporating women's needs/preferences in HPV screening recommendations.

HPV vaccination impact on a cervical cancer screening program: methods of the FASTER-Tlalpan Study in Mexico.

PubMed

Salmerón, Jorge; Torres-Ibarra, Leticia; Bosch, F Xavier; Cuzick, Jack; Lörincz, Attila; Wheeler, Cosette M; Castle, Philip E; Robles, Claudia; Lazcano-Ponce, Eduardo

2016-04-01

To outline the design of a clinical trial to evaluate the impact of HPV vaccination as part of a hrHPV-based primary screening program to extend screening intervals. A total of 18,000 women aged 25-45 years, attending the regular cervical cancer-screening program in primary health care services in Tlalpan, Mexico City, will be invited to the study. Eligible participants will be assigned to one of three comparison groups: 1) HPV16/18 vaccine and hrHPV-based screening; 2) HPV6/11/16/18 vaccine and hrHPV-based screening; 3) Control group who will receive only hrHPV-based screening. Strict surveillance of hrHPV persistent infection and occurrence of precancerous lesions will be conducted to estimate safety profiles at different screening intervals; participants will undergo diagnosis confirmation and treatment as necessary. The FASTER-Tlalpan Study will provide insights into new approaches of cervical cancer prevention programs. It will offer valuable information on potential benefits of combining HPV vaccination and hrHPV-based screening to safety extend screening intervals.

Prevalence, Genotype Distribution and Risk Factors for Cervical Human Papillomavirus Infection in the Grand Tunis Region, Tunisia.

PubMed

Ardhaoui, Monia; Ennaifer, Emna; Letaief, Hajer; Salsabil, Rejaibi; Lassili, Thalja; Chahed, Karim; Bougatef, Souha; Bahrini, Asma; El Fehri, Emna; Ouerhani, Kaouther; Paez Jimenez, Adela; Guizani, Ikram; Boubaker, Med Samir; Ben Alaya, Nissaf Bouafif Ép

2016-01-01

Implementation of Human Papillomavirus (HPV) vaccination should be considered a key cervical cancer prevention strategy in Tunisia, where Pap smear screening is not efficient. This study aims to estimate the prevalence and to identify risk factors associated with HPV infection among women from Grand Tunis, Tunisia. We conducted a cross-sectional study, between December 2012 and May 2013. Eligible women for this study were those aged 18-65 years, sexually active, who sought medical attention at their primary health care centre or clinic in Grand Tunis, Tunisia and who gave written consent. A liquid-based Pap smear sample was obtained from all women using a cervical brush. Only women with betaglobin positive test were further analysed for HPV detection and typing. A nested-PCR of the L1 region was performed followed by reverse line blot hybridization to facilitate the specific detection of 31 HPV genotypes. Multiple logistic regression modeling was used for the analysis of associations between variables with some considered possible confounders after checking for interactions. A total of 391 women were enrolled in this study and 325 out of the 391 cervical samples were positive for the betaglobin test. Overall HPV prevalence was 13.2% [9.8%-17.5%], with the following most prevalent HPV genotypes: HPV6 (40%), HPV40 (14%), HPV16 (12%), HPV52 (9%), HPV31 and HPV59 (7%), followed by HPV68 (4%). Mean age of HPV positive women was 40.7±0.92 years. Independently associated risk factors of HPV infection were smoking (OR:2.8 [0.8-9.6]), low income (OR:9.6 [1.4-63.4), bad housing type (OR:2.5 [1-6.8]), partner with multiple sexual relationship (OR:4.5 [0.9-22.9]) and single women (widowed, divorced, separated, never married) (OR:6.9 [1.1-42.2]). This study provides the first national-based estimate of HPV prevalence in Tunisia. Our findings contribute to the evidence on the current burden of HPV infection, the critical role of sexual behaviour and socioeconomic status and call for increased support for the screening program in Tunisia to prevent cervical cancer. These results allow us to evaluate the cost-effectiveness of vaccine program implementation in Tunisia in future.

Role of Protein Biomarkers in the Detection of High-Grade Disease in Cervical Cancer Screening Programs

PubMed Central

Brown, Charlotte A.; Bogers, Johnannes; Sahebali, Shaira; Depuydt, Christophe E.; De Prins, Frans; Malinowski, Douglas P.

2012-01-01

Since the Pap test was introduced in the 1940s, there has been an approximately 70% reduction in the incidence of squamous cell cervical cancers in many developed countries by the application of organized and opportunistic screening programs. The efficacy of the Pap test, however, is hampered by high interobserver variability and high false-negative and false-positive rates. The use of biomarkers has demonstrated the ability to overcome these issues, leading to improved positive predictive value of cervical screening results. In addition, the introduction of HPV primary screening programs will necessitate the use of a follow-up test with high specificity to triage the high number of HPV-positive tests. This paper will focus on protein biomarkers currently available for use in cervical cancer screening, which appear to improve the detection of women at greatest risk for developing cervical cancer, including Ki-67, p16INK4a, BD ProEx C, and Cytoactiv HPV L1. PMID:22481919

HPV DNA test

MedlinePlus

... HPV testing in women; Cervical cancer - HPV DNA test; Cancer of cervix - HPV DNA test ... The HPV DNA test may be done during a Pap smear . You lie on a table and place your feet in stirrups. The ...

Primary surgery results in no survival benefit compared to primary radiation for oropharyngeal cancer patients stratified by high-risk human papilloma virus status.

PubMed

Lybak, Stein; Ljøkjel, Borghild; Haave, Hilde; Karlsdottir, Àsa; Vintermyr, Olav K; Aarstad, Hans Jørgen

2017-01-01

We changed the primary oropharynx squamous cell carcinoma (OPSCC) treatment recommendation from primary radiation therapy (RT) to tumor surgery and neck dissection, followed by RT around the year 2000 with apparently improved survival. However, high-risk human papilloma virus (hr-HPV)-16-caused OPSCCs have increased during this period. Furthermore, hr-HPV+ OPSCC carry a better prognosis than hr-HPV-negative patients. We have, therefore, evaluated the 5-year survival in the period from 1992 to 1999 versus 2000 to 2008 stratified by hr-HPV tumor infection status. Ninety-six OPSCC patients were treated from 1992 to 1999 compared with 136 patients from 2000 to 2008. The 5-year disease-specific survival (DDS) and overall survival (OS) were recorded, while the health-related quality of life (HRQoL) scores were obtained from some of the cured patients. Thirty-eight (40 %) in the first period and 86 OPSCCs (63 %) in the second period were hr-HPV+. In the first period, 16 versus 62 patients in the last period were treated by neck dissection, primary tumor surgery, and RT. DSS among all the hr-HPV-negative patients in the first period was 51 versus 55 % in the second period, and the corresponding OS was 33 versus 31 %, respectively. The DSS among all the hr-HPV+ patients was 78 % in the first period versus 77 % in the second period, while the OS was 71 versus 69 %, respectively. The HRQoL scores among successfully treated patients were worse following surgery, plus RT than RT only. The hr-HPV-adjusted 5-year survival in OPSCC patients was similar between the two time periods. A decreased HRQoL was associated with surgical therapy, which indicates that hr-HPV+ OPSCC patients may be treated by primary RT followed by major surgery only if RT treatment fails.

How does public policy impact cervical screening and vaccination strategies?☆

PubMed Central

Herzog, Thomas J.; Huh, Warner K.; Einstein, Mark H.

2011-01-01

Objectives To examine the current approaches to cervical screening and points to consider for improving HPV vaccination acceptance and uptake in the US. Methods An expert forum was conducted September 12–13, 2008, by the Society of Gynecologic Oncologists including 56 experts in cervical cancer and titled “Future Strategies of Cervical Cancer Prevention: What Do We Need to Do Now to Prepare?”. Results Cervical cancer prevention has primarily relied on screening paradigms but vaccination against human papillomavirus (HPV), the cause of the disease, is a primary preventative measure that has been recommended by all cervical cancer screening stakeholders. Guidelines for vaccination are developed by national advisory groups, but successful implementation requires a supportive infrastructure and the cooperation of providers, clinicians, and patients. HPV vaccination has been available in the United States (US) since 2006 and screening practices have been updated to also include HPV genotyping. However, many clinicians fail to adhere to the guidelines for HPV testing (and HPV co-testing) as part of cervical cancer screening, and vaccination coverage has been poor among females aged 11 and 12, the group for which vaccination is recommended by all organizations. Conclusions The data reviewed and presented in this session of the “Future Strategies of Cervical Cancer Prevention. What Do We Need to do Now to Prepare?”. The Forum suggests that the policies influencing HPV vaccination and screening need to be reassessed at multiple levels in order to achieve more effective implementation and regular use. PMID:20932433

Low rate of human papillomavirus vaccination among schoolgirls in Lebanon: barriers to vaccination with a focus on mothers’ knowledge about available vaccines

PubMed Central

Abou El-Ola, Maria J; Rajab, Mariam A; Abdallah, Dania I; Fawaz, Ismail A; Awad, Lyn S; Tamim, Hani M; Ibrahim, Ahmad O; Mugharbil, Anas M; Moghnieh, Rima A

2018-01-01

Background Human papillomavirus (HPV) infection is an established predisposing factor of cervical cancer. In this study, we assessed the awareness about genital warts, cervical cancer, and HPV vaccine among mothers having girls who are at the age of primary HPV vaccination attending a group of schools in Lebanon. We also assessed the rate of HPV vaccination among these girls and the barriers to vaccination in this community. Subjects and methods This is a cross-sectional, school-based survey. A 23-item, self-administered, anonymous, pretested, structured questionnaire with closed-ended questions was used to obtain data. The questionnaire was sent to the mothers through their student girls, and they were asked to return it within a week. Data were analyzed using the Statistical Package for Social Sciences version 21.0. Bivariate analysis was performed using the chi-square test to compare categorical variables, whereas continuous variables were compared using the Student’s t-test. Fisher’s exact test was used when chi-square test could not be employed. Results The response rate in our survey was 39.4%. Among the responders, the rate of awareness about HPV infection was 34%, where 72% of the mothers had heard about cervical cancer, and 34% knew that a vaccine is available to prevent cervical cancer. HPV vaccination uptake rate was 2.5%. This lack of vaccination was primarily attributed to the low rate of mothers’ awareness about the vaccine (34%). Factors significantly affecting awareness about the vaccine were the mothers’ marital age, nationality, level of education, employment, and family income. Barriers to HPV vaccination, other than awareness, were uncertainty about safety or efficacy of the vaccine, conservative ideas of mothers regarding their girls’ future sexual life, and relatively high price of the vaccine. Conclusion Vaccine uptake is low among eligible girls attending this group of schools. The barriers to vaccination are multiple; the most important one is the mothers’ lack of knowledge about HPV, cervical cancer, and the modes of prevention. Awareness campaigns along with a multimodal strategy that targets the identified barriers would be recommended to achieve higher rates of HPV vaccination. PMID:29628765

Influence of human papillomavirus on the clinical presentation of oropharyngeal carcinoma in the United States.

PubMed

Stenmark, Matthew H; Shumway, Dean; Guo, Cui; Vainshtein, Jeffrey; Mierzwa, Michelle; Jagsi, Reshma; Griggs, Jennifer J; Banerjee, Mousumi

2017-10-01

Much of what is known about the significance of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma is derived from single-institution retrospective studies, post hoc analyses of tissue specimens from clinical trials, and tissue bank studies with a small sample size. The objective of this study is to investigate the impact of HPV on the frequency and clinical presentation of oropharyngeal carcinoma in a large, national sample with information from patients who underwent HPV testing. Retrospective, cross-sectional study. We identified a comprehensive national sample of 8,359 patients with oropharyngeal carcinoma and known HPV status diagnosed between 2010 and 2011 within the National Cancer Database. Multivariable logistic regression was used to assess correlates of patient and tumor characteristics on HPV status. Among patients with oropharyngeal carcinoma, the frequency of HPV-related squamous cell carcinoma in the United States was 65.4%. HPV-related oropharyngeal carcinoma was associated with younger age, male sex, and white race (P < 0.001). Advanced primary tumor stage was associated with HPV-negative disease (P < 0.001), whereas increasing nodal burden was associated with HPV-positive disease (P < 0.001). Despite less-advanced nodal disease, HPV-negative tumors were associated with a higher likelihood of metastasis at presentation (P < 0.001). HPV now accounts for the majority of newly diagnosed oropharyngeal carcinoma in the United States and is associated with a distinct clinical profile, supporting efforts to re-evaluate the staging and treatment paradigm for HPV-associated oropharyngeal cancer. 4. Laryngoscope, 127:2270-2278, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Optimization of heterologous DNA-prime, protein boost regimens and site of vaccination to enhance therapeutic immunity against human papillomavirus-associated disease.

PubMed

Peng, Shiwen; Qiu, Jin; Yang, Andrew; Yang, Benjamin; Jeang, Jessica; Wang, Joshua W; Chang, Yung-Nien; Brayton, Cory; Roden, Richard B S; Hung, Chien-Fu; Wu, T-C

2016-01-01

Human papillomavirus (HPV) has been identified as the primary etiologic factor of cervical cancer as well as subsets of anogenital and oropharyngeal cancers. The two HPV viral oncoproteins, E6 and E7, are uniquely and consistently expressed in all HPV infected cells and are therefore promising targets for therapeutic vaccination. Both recombinant naked DNA and protein-based HPV vaccines have been demonstrated to elicit HPV-specific CD8+ T cell responses that provide therapeutic effects against HPV-associated tumor models. Here we examine the immunogenicity in a preclinical model of priming with HPV DNA vaccine followed by boosting with filterable aggregates of HPV 16 L2E6E7 fusion protein (TA-CIN). We observed that priming twice with an HPV DNA vaccine followed by a single TA-CIN booster immunization generated the strongest antigen-specific CD8+ T cell response compared to other prime-boost combinations tested in C57BL/6 mice, whether naïve or bearing the HPV16 E6/E7 transformed syngeneic tumor model, TC-1. We showed that the magnitude of antigen-specific CD8+ T cell response generated by the DNA vaccine prime, TA-CIN protein vaccine boost combinatorial strategy is dependent on the dose of TA-CIN protein vaccine. In addition, we found that a single booster immunization comprising intradermal or intramuscular administration of TA-CIN after priming twice with an HPV DNA vaccine generated a comparable boost to E7-specific CD8+ T cell responses. We also demonstrated that the immune responses elicited by the DNA vaccine prime, TA-CIN protein vaccine boost strategy translate into potent prophylactic and therapeutic antitumor effects. Finally, as seen for repeat TA-CIN protein vaccination, we showed that the heterologous DNA prime and protein boost vaccination strategy is well tolerated by mice. Our results provide rationale for future clinical testing of HPV DNA vaccine prime, TA-CIN protein vaccine boost immunization regimen for the control of HPV-associated diseases.

The role of human papilloma virus and p16 in occult primary of the head and neck: a comprehensive review of the literature.

PubMed

Fotopoulos, George; Pavlidis, Nicholas

2015-02-01

Cancer of unknown primary of the head and neck is a challenging entity for the oncologist. The role of human papilloma virus/p16 in carcinogenesis and in prognosis is well established in certain HNSCC especially in that of the oropharynx. In the case of occult primary of the head and neck the role of HPV/p16 positivity is not well defined regarding prognosis and localization of the primary. An independent review of PubMed and ScienceDirect database was performed up to May 2014 using combinations of terms such as "occult primary of the head and neck", "CUP of the head and neck" "metastatic cervical squamous cell carcinoma of unknown primary", "HPV" and "HPV and head and neck cancer". Literature review shows a strong association between HPV/p16 positivity and primary location in the oropharynx in patients with CUP of the head and neck as well as a better clinical outcome. HPV positivity and p16 overexpression could be used as surrogate markers in the search of the primary site of patients with CUP of the head and neck therefore maybe guiding treatment decisions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of a Novel Single-Tube Method for Extended Genotyping of Human Papillomavirus

PubMed Central

Serrano, I.; Wennington, H.; Graham, C.; Cubie, H.; Boland, E.; Fu, G.; Cuschieri, K.

2017-01-01

ABSTRACT The use of high-risk human papillomavirus (HPV) testing for surveillance and clinical applications is increasing globally, and it is important that tests are evaluated to ensure they are fit for this purpose. In this study, the performance of a new HPV genotyping test, the Papilloplex high-risk HPV (HR-HPV) test, was compared to two well-established genotyping tests. Preliminary clinical performance was also ascertained for the detection of CIN2+ in a disease-enriched retrospective cohort. A panel of 500 cervical liquid-based cytology samples with known clinical outcomes were tested by the Papilloplex HR-HPV test. Analytical concordance was compared to two assays: a Linear Array (LA) HPV genotyping test and an Optiplex HPV genotyping test. The initial clinical performance for the detection for CIN2+ samples was performed and compared to that of two clinically validated HPV tests: a RealTime High-Risk HPV test (RealTime) and a Hybrid Capture 2 HPV test (HC2). High agreement for HR-HPV was observed between the Papilloplex and LA and Optiplex HPV tests (97 and 95%, respectively), with kappa values for HPV16 and HPV18 being 0.90 and 0.81 compared to the LA and 0.70 and 0.82 compared to the Optiplex test. The sensitivity, specificity, positive predictive value, and negative predictive value of the Papilloplex test for the detection of CIN2+ were 92, 54, 33, and 96%, respectively, and very similar to the values observed with RealTime and HC2. The Papilloplex HR-HPV test demonstrated a analytical performance similar to those of the two HPV genotyping tests at the HR-HPV level and the type-specific level. The preliminary data on clinical performance look encouraging, although further longitudinal studies within screening populations are required to confirm these findings. PMID:29237790

Comparison of the Abbott RealTime High Risk HPV test and the Roche cobas 4800 HPV test using urine samples.

PubMed

Lim, Myong Cheol; Lee, Do-Hoon; Hwang, Sang-Hyun; Hwang, Na Rae; Lee, Bomyee; Shin, Hye Young; Jun, Jae Kwan; Yoo, Chong Woo; Lee, Dong Ock; Seo, Sang-Soo; Park, Sang-Yoon; Joo, Jungnam

2017-05-01

Human papillomavirus (HPV) testing based on cervical samples is important for use in cervical cancer screening. However, cervical sampling is invasive. Therefore, non-invasive methods for detecting HPV, such as urine samples, are needed. For HPV detection in urine samples, two real-time PCR (RQ-PCR) tests, Roche cobas 4800 test (Roche_HPV; Roche Molecular Diagnostics) and Abbott RealTime High Risk HPV test (Abbott_HPV; Abbott Laboratories) were compared to standard cervical samples. The performance of Roche_HPV and Abbott_HPV for HPV detection was evaluated at the National Cancer Center using 100 paired cervical and urine samples. The tests were also compared using urine samples stored at various temperatures and for a range of durations. The overall agreement between the Roche_HPV and Abbott_HPV tests using urine samples for any hrHPV type was substantial (86.0% with a kappa value of 0.7173), and that for HPV 16/18 was nearly perfect (99.0% with a kappa value of 0.9668). The relative sensitivities (based on cervical samples) for HPV 16/18 detection using Roche_HPV and Abbott_HPV with urine samples were 79.2% (95% CI; 57.9-92.9%) and 81.8% (95% CI; 59.7-94.8%), respectively. When the cut-off C T value for Abbott_HPV was extended to 40 for urine samples, the relative sensitivity of Abbott_HPV increased to 91.7% from 81.8% for HPV16/18 detection and to 87.0% from 68.5% for other hrHPV detection. The specificity was not affected by the change in the C T threshold. Roche_HPV and Abbott_HPV showed high concordance. However, HPV DNA detection using urine samples was inferior to HPV DNA detection using cervical samples. Interestingly, when the cut-off C T value was set to 40, Abbott_HPV using urine samples showed high sensitivity and specificity, comparable to those obtained using cervical samples. Fully automated DNA extraction and detection systems, such as Roche_HPV and Abbott_HPV, could reduce the variability in HPV detection and accelerate the standardization of HPV detection in urine. Thus, urine samples may be an effective alternative for HPV detection in women who hesitate to participate in cervical cancer screening programs. Copyright © 2017 Elsevier B.V. All rights reserved.

Pap and HPV Testing

Cancer.gov

Pap tests detect abnormal cervical cells, including precancerous cervical lesions, as well as early cervical cancers. HPV tests detect HPV infections that can cause cervical cell abnormalities. Learn how Pap and HPV tests are done, how often testing should be done, and how are HPV test results are reported.

Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

PubMed Central

Magaldi, Thomas G.; Almstead, Laura L.; Bellone, Stefania; Prevatt, Edward G.; Santin, Alessandro D.; DiMaio, Daniel

2011-01-01

Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress E6 and E7 in these cells. To enable efficient SV40 infection and E2 gene delivery, we first incubated the primary cervical cancer cells with the ganglioside GM1, a cell-surface receptor for SV40 limiting in these cells. Repression of HPV in primary cervical carcinoma cells caused them to undergo senescence, but the E2 protein had little effect on HPV-negative primary cells. These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells. PMID:22056390

Update on current care guideline: Cytological changes in the cervix, vagina and vulva.

PubMed

Annually approximately 160 new cervical cancers are diagnosed in Finland. Screening has decreased both incidence and mortality by 80%. Both primary HPV-testing and Pap smear can be used in screening. In the future HPV vaccination will decrease the number of cervical cancers. Abnormal findings in Pap smears indicate management. LSIL lesions are followed up especially among young women and HSIL lesions treated. Follow-up after treatment should be reliably arranged, because increased risk of cancer remains ever after treatment.

HPV Vaccine Effective at Multiple Anatomic Sites

Cancer.gov

A new study from NCI researchers finds that the HPV vaccine protects young women from infection with high-risk HPV types at the three primary anatomic sites where persistent HPV infections can cause cancer. The multi-site protection also was observed at l

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

Magaldi, Thomas G.; Almstead, Laura L.; Bellone, Stefania

Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress E6 and E7 in these cells. To enable efficient SV40 infection and E2 gene delivery, we first incubated the primary cervical cancer cells with the ganglioside GM1, amore » cell-surface receptor for SV40 that is limiting in these cells. Repression of HPV in primary cervical carcinoma cells caused them to undergo senescence, but the E2 protein had little effect on HPV-negative primary cells. These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells.« less

Pap smear in the prevention of HPV-related anal cancer: preliminary results of the study in a male population at risk.

PubMed

Pisano, Luigi; Tiradritti, Luana; Lorenzoni, Elisa; Zuccati, Giuliano; Matucci, Marzia; Butera, Daniela; Foxi, Prassede; Confortini, Massimo

2016-12-01

The aim of this work was to evaluate the role of human papillomavirus (HPV) testing and anal cytology, considering a population of HIV-positive and negative men who have sex with men (MSM), at high risk of sexually transmitted diseases (STD), in order to ascertain which of the methods examined is the best screening strategy for the prevention of anal cancer. In the period 06/2013-07/2014 at the "MTS Centre" of the University of Florence, 87 male patients, homo/bi-sexual, of which 46 HIV-negative and 41 HIV-positive, were recruited for anal Pap smear and HPV testing. All patients with an "abnormal" cytological result underwent anoscopy with possible biopsy. HPV testing was positive in 73 patients (83.6%). Cytology was negative in 50 patients (57.5%), inconclusive in 14 patients (16.1%), abnormal in 23 patients (26.4%): 14 ASC-US (19.2%), 4 ASC-H (5.5%), 5 L-SIL (6.8%), 0 H-SIL. Anoscopy with biopsy led to diagnosis of AIN I in 10 cases, of which 6 ASC-US+ and 4L-SIL+, AIN II in only 1 case, LS-IL+. Anal HPV testing, when used in primary screening, lead to a high number of "false positives", given the too high prevalence of HPV infection in MSM, the highest risk population targeted for screening. So we propose a screening program with anal cytology which has a high sensitivity for detection of AIN while is a poor predictor of the severity of these lesions; therefore, all patients with abnormal anal Pap smear should undergo anoscopy with biopsy.

Site-specific human papillomavirus infection in adolescent men who have sex with men (HYPER): an observational cohort study.

PubMed

Zou, Huachun; Tabrizi, Sepehr N; Grulich, Andrew E; Hocking, Jane S; Bradshaw, Catriona S; Cornall, Alyssa M; Morrow, Andrea; Prestage, Garrett; Law, Matthew G; Garland, Suzanne M; Chen, Marcus Y; Fairley, Christopher K

2015-01-01

Men who have sex with men (MSM) have an increased risk of anogenital human papilomavirus (HPV) infection, which can lead to HPV-related anogenital lesions such as warts, anal intraepithelial neoplasia, and anal cancer. Some of these HPV types are preventable with vaccines. We aimed to describe the incidence of anal, penile, and oral HPV infection, and to estimate the site-specific transmission probability per partner, for teenage MSM. In our observational cohort study, we enrolled teenage MSM (aged 16-20 years) with low sexual exposure and a low prevalence of HPV in Melbourne (VIC, Australia). At baseline, 3, 6, and 12 months, we took a swab from the anal canal, and participants self-collected a swab from the penis and an oral rinse. Our primary outcome was definite and probable incident HPV infection of the anus, penis, or mouth at any time in the 12 months from baseline, assessed through the presence of HPV DNA. We defined definite incident HPV infection as the same HPV type detected more than once from the same site in men who had a negative HPV test at baseline. We defined probable incident HPV infection as only one positive test. We estimated the probability of HPV transmission per partner using HPV prevalence in MSM with a similar age to partners of men in our cohort. This study is registered at the Australian New Zealand Clinical Trials Registry and ClinicalTrials.gov, numbers ACTRN12611000857909 and NCT01422356. We enrolled 200 MSM aged 16-20 years (median 19 years [IRQ 18-20; range 16-20]) between Sept 20, 2010, and Aug 24, 2012. Over the 12 month follow-up period, we detected 48 definite (107 possible) HPV infections in the anus, ten definite (34 possible) HPV infections on the penis, and no definite (six possible) infections in the mouth. Definite incidence rate per 100 person-years for any anal HPV infection was 57 (95% CI 46-68), and for any anal HPV type in the quadrivalent vaccine was 33 (23-44). Definite incidence rate per 100 person-years for any penile HPV was 12 (6-21) and for any HPV type in the quadrivalent vaccine was 5 (1-12). Estimated probabilities of HPV transmission from the penis to the anus were significantly higher than were those from the anus to the penis (p<0·05 for all HPV types in the quadrivalent vaccine). High incidence rates suggest that the vaccination coverage in MSM will need to be high. The transmission estimates will inform HPV modelling. Merck. Copyright © 2015 Elsevier Ltd. All rights reserved.

HPV status in patients with head and neck of carcinoma of unknown primary site: HPV, tobacco smoking, and outcome.

PubMed

Tribius, Silke; Hoffmann, Anna S; Bastrop, Sophie; Görögh, Tibor; Haag, Jochen; Röcken, Christoph; Clauditz, Till; Grob, Tobias; Wilczak, Waldemar; Tennstedt, Pierre; Borcherding, Aileen; Petersen, Cordula; Hoffmann, Markus

2012-11-01

Infection with human papillomavirus (HPV) is linked to oropharyngeal cancer. This analysis investigated possible associations between HPV status, smoking history and survival outcome in patients with neck metastasis and carcinoma of unknown primary (CUP). Registries at the Universities of Hamburg and Kiel were searched for patients with CUP diagnosed from 2002 to 2011 who had formalin-fixed and paraffin-embedded metastatic lymph node samples available. All patients underwent routine diagnostic procedures to establish the primary site and received radiotherapy (60Gy using conventional fractionation) with or without concurrent cisplatin-based chemotherapy depending on disease extent. Genotyping was performed using polymerase chain reaction; p16([INK4a]) expression was assessed using immunohistochemistry. Sixty-three patients were included; 23 (37%) had HPV DNA/p16+ samples and 40 (63%) were negative for either/both markers. A high proportion of patients had a history of tobacco smoking; significantly fewer patients with HPV+/p16+ samples were smokers than those who were negative for either/both markers (61% vs. 90%, respectively; p = 0.0067). There were no statistically significant differences between overall or recurrence-free survival in HPV+/p16+ patients vs. those negative for either/both markers. Overall survival appeared to be superior in patients with <10 pack-years smoking history and HPV+/p16+ disease. This study, the largest to date investigating HPV status in head and neck CUP, identified HPV and p16 overexpression in over one-third of patients. Tobacco smoking history appeared to affect survival in HPV+/p16+ patients. Smoking status should be considered as a prognostic factor in patients with CUP, along with HPV DNA status. Copyright © 2012 Elsevier Ltd. All rights reserved.

Can human papillomavirus DNA testing of self-collected vaginal samples compare with physician-collected cervical samples and cytology for cervical cancer screening in developing countries?

PubMed Central

Bhatla, Neerja; Dar, Lalit; Patro, A. Rajkumar; Kumar, Pankaj; Kriplani, Alka; Gulati, Arti; Iyer, Venkateswaran K.; Mathur, Sandeep R.; Sreenivas, Vishnubhatla; Shah, Keerti V.; Gravitt, Patti E.

2013-01-01

Background To determine human papillomavirus (HPV) types by polymerase chain reaction (PCR)-reverse line blot assay and examine the concordance between HPV by Hybrid Capture 2 (HC2) and PCR on self-collected vaginal and physician-collected cervical samples and cytology. Methods This was a cross-sectional study of 546 sexually active women aged ≥30 years with persistent vaginal discharge, intermenstrual or postcoital bleeding or an unhealthy cervix. Participants self-collected vaginal samples (HPV-S) and physicians collected cervical samples for conventional Pap smear and HPV DNA (HPV-P) testing and performed colposcopy, with directed biopsy, if indicated. HPV testing and genotyping was done by HC2 and PCR reverse line blot assay. Concordance between HC2 and PCR results of self- and physician-collected samples was determined using a Kappa statistic (κ) and Chi-square test. Results Complete data were available for 512 sets with 98% of women providing a satisfactory self-sample. PCR detected oncogenic HPV in 12.3% of self- and 13.0% of physician-collected samples. Overall, there was 93.8% agreement between physician-collected and self-samples (κ = 76.31%, 95% confidence interval [CI]: 64.97–82.29%, p = 0.04)—complete concordance in 473 cases (57 positive, 416 negative), partial concordance in seven pairs and discordance in 32 pairs. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of self-sampling for detection of cervical intraepithelial neoplasia (CIN)2+ disease were 82.5%, 93.6%, 52.4% and 98.4%, respectively; for physician-sampling they were 87.5%, 93.2%, 52.2% and 98.9%, respectively; and for cytology they were 77.5%, 87.3%, 34.1% and 97.9%, respectively. Concordance between HC2 and PCR was 90.9% for self-samples (κ = 63.7%, 95% CI: 55.2–72.2%) and 95.3% for physician-collected samples (κ = 80.4%, 95% CI: 71.8–89.0%). Conclusions Self-HPV sampling compares favourably with physician-sampling and cytology. A rapid, affordable, HPV self-test kit can be used as the primary method of cervical cancer screening in low-resource situations. PMID:19931499

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

PubMed Central

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

2016-01-01

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

HPV specific testing: a requirement for oropharyngeal squamous cell carcinoma patients.

PubMed

Robinson, Max; Schache, Andrew; Sloan, Philip; Thavaraj, Selvam

2012-07-01

Human papillomavirus (HPV) testing is now recommended as part of the work up for patients with oropharyngeal squamous cell carcinoma (OPSCC) and those patients with cervical lymph node metastasis of unknown origin. The laboratory testing strategy should accurately assess the presence or absence of oncogenic HPV infection in routinely collected tumour samples that are subject to standard fixation protocols, alcohol-fixed cytological preparations and formalin-fixed tissue samples. The HPV status should correlate with biologically relevant outcome measures such as overall, disease-specific and disease-free survival. Whilst increased expression of p16 by immunohistochemistry is considered to be a surrogate marker of oncogenic HPV infection and is a validated independent prognostic biomarker, only HPV specific tests provide definitive evidence of the aetiological agent. We provide an overview of HPV testing in OPSCC, justifying the use of HPV specific tests. We examine the analytical accuracy of HPV specific tests against the 'reference' test--high risk HPV mRNA in fresh tissue--and contrast this with the performance of p16 immunohistochemistry as a stand alone test. We highlight the added value of HPV specific tests in prognostication, clinical trial design, and population-based disease surveillance. We consider that HPV specific testing is the starting point for developing increasingly informative biomarker panels in the context of 'stratified medicine'. We briefly frame test information in the context of disclosure of HPV status to patients. We conclude that only a testing strategy that includes HPV specific tests can deliver more effective care for patients with OPSCC. The international head and neck oncology community should work together to clearly define the minimum requirements for assigning a diagnosis of HPV-related OPSCC in order to ensure consistent reporting of this emerging and increasingly prevalent disease.

HPV-Associated Head and Neck Cancer: Unique Features of Epidemiology and Clinical Management

PubMed Central

Maxwell, Jessica H.; Grandis, Jennifer R.; Ferris, Robert L.

2017-01-01

Human papillomavirus (HPV) is a recently identified causative agent for a subset of head and neck cancers, primarily in the oropharynx, and is largely responsible for the rising worldwide incidence of oropharyngeal cancer (OPC). Patients with HPV-positive OPC have distinct risk factor profiles and generally have a better prognosis than patients with traditional, HPV-negative, head and neck cancer. Concurrent chemotherapy and radiation is a widely accepted primary treatment modality for many patients with HPV-positive OPC. However, recent advances in surgical modalities, including transoral laser and robotic surgery, have led to the reemergence of primary surgical treatment for HPV-positive patients. Clinical trials are under way to determine optimal treatment strategies for the growing subset of patients with HPV-positive OPC. Similarly, identifying those patients with HPV-positive cancer who are at risk for recurrence and poor survival is critical in order to tailor individual treatment regimens and avoid potential undertreatment. PMID:26332002

Comparison of the cobas Human Papillomavirus (HPV) Test with the Hybrid Capture 2 and Linear Array HPV DNA Tests

PubMed Central

Sadorra, Mark; LaMere, Brandon J.; Kail, Randi; Aldrich, Carrie; Kinney, Walter; Fetterman, Barbara; Lorey, Thomas; Schiffman, Mark; Castle, Philip E.

2012-01-01

The cobas human papillomavirus (HPV) test (cobas) was recently approved by the U.S. Food and Drug Administration (FDA) and identifies HPV16 and HPV18 separately as well as detecting a pool of 11 HR-HPV genotypes (HPV31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -68) and also HPV66. We compared cobas, Linear Array (LA), and Hybrid Capture 2 (HC2) assays for detection of carcinogenic HPV DNA, and cobas and LA for detection of HPV16 and HPV18 DNA, among the first 1,852 women enrolled in the HPV Persistence and Progression Cohort (PaP Cohort) study. Specimens were tested by all 3 assays 1 year after an HC2-positive result. In 1,824 specimens with cobas results, cobas had an 85.9% agreement with HC2 and 91.0% agreement with LA for carcinogenic HPV detection. When results between cobas and HC2 disagreed, cobas tended to call more women HPV positive (P < 0.01). Categorizing cobas and LA results hierarchically according to cancer risk (HPV16, HPV18, other carcinogenic HPV genotypes, or carcinogen negative), there was a 90% agreement for all categories of HPV (n = 1,824). We found good agreement between the two U.S. FDA-approved HPV tests, with discrepancies between the two assays due to specific characteristics of the individual assays. Additional studies are needed to compare HC2 and cobas for detecting and predicting CIN3 to understand the clinical implications of the discrepant test results between the two tests. PMID:22075592

Nucleic acid tests for the detection of alpha human papillomaviruses.

PubMed

Poljak, Mario; Cuzick, Jack; Kocjan, Boštjan J; Iftner, Thomas; Dillner, Joakim; Arbyn, Marc

2012-11-20

Testing for high-risk types of alpha human papillomaviruses (HPV) is an invaluable part of clinical guidelines for cervical carcinoma screening, management and treatment. In this comprehensive inventory of commercial tests for detection of alpha-HPV, we identified at least 125 distinct HPV tests and at least 84 variants of the original tests. However, only a small subset of HPV tests has documented clinical performance for any of the standard HPV testing indications. For more than 75% of HPV tests currently on the market, no single publication in peer-reviewed literature can be identified. HPV tests that have not been validated and lack proof of reliability, reproducibility and accuracy should not be used in clinical management. Once incorporated in the lab, it is essential that the whole procedure of HPV testing is subject to continuous and rigorous quality assurance to avoid sub-optimal, potentially harmful practices. Manufacturers of HPV tests are urged to put more effort into evaluating their current and future products analytically, using international standards, and for clinical applications, using clinically validated endpoints. To assist with analytical validation, the World Health Organization is developing international standards for HPV types other than HPV16 and HPV18 and is planning development of external quality control panels specifically designed to be used for performance evaluation of current and future HPV tests. There is a need for more competitively priced HPV tests, especially for resource-poor countries, and uniform test validation criteria based on international standards should enable issuing more competitive and fair tender notices for purchasing. Automation systems allowing large-scale testing, as well as further increases in clinical performance, are the main needs in the further improvement of HPV tests. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. Copyright © 2012 Elsevier Ltd. All rights reserved.

Low Grade Peritoneal Mucinous Carcinomatosis Associated with Human Papilloma Virus Infection: Case Report

PubMed Central

Gatalica, Zoran; Foster, Jason M.; Loggie, Brian W.

2008-01-01

Pseudomyxoma peritonei is a clinical syndrome characterized by peritoneal dissemination of a mucinous tumor with mucinous ascites. The vast majority of the pseudomyxoma peritoneis are associated with mucinous neoplasms of the appendix. We describe a case of pseudomyxoma peritonei associated with mucinous adenocarcinoma of the cervix in a 60-year-old woman. The patient developed low grade mucinous peritoneal carcinomatosis 8 years after hysterectomy for cervical adenocarcinoma. No other primary mucinous tumor was identified and peritoneal carcinomatosis tested positive for high-risk human papilloma virus (HPV), showing both integrated and episomal pattern. HPV has been previously associated with development of cervical carcinomas (both squamous and mucinous) but neither has cervical adenocarcinoma nor HPV been implicated in development of pseudomyxoma peritonei. To the best of our knowledge, this is the first description of HPV-associated malignancy presenting as pseudomyxoma peritonei. PMID:18925701

Quantivirus® HPV E6/E7 RNA 3.0 assay (bDNA) is as sensitive, but less specific than Hybrid Capture 2 test.

PubMed

Shen, Yong; Gong, Jiaomei; He, Yanxia; Cheng, Guomei; Okunieff, Paul; Li, Xiaofu

2013-02-01

Human papillomavirus (HPV) infection is the primary cause of cervical cancer. The Quantivirus(®) HPV E6/E7 RNA 3.0 assay (DiaCarta, CA, USA) detects E6/E7 mRNA of 13 high risk subtypes and 6 low risk subtypes. Cervical specimens collected in PreservCyt were processed for HPV detection. Cervical biopsies were taken only from those women with abnormal colposcopy. 200 out of 272 (73.5%) cases were mRNA positive. The percentage of HPV E6/E7 mRNA positive samples increases with the severity of the cytological diagnosis, but not in histological diagnosis. In 146 patients with both tests, the E6/E7 mRNA assay had significant higher positivity rate than the Hybrid Capture 2 assay (75.3% versus 62.3%). The HPV mRNA assay and the HC2 assay had the same sensitivity of high grade cervical intraepithelial neoplasia (CIN 2+), 82.4% (14/17) (95% confidence interval [CI], 64.3, 100). However, the specificity of CIN 2+ for the HPV mRNA assay was significantly lower than HC2 assay. Receiver operating characteristic curve analysis was used to compare the diagnostic performance of the E6/E7 mRNA and HC2. E6/E7 mRNA achieved 58.8% sensitivity with 74.1% specificity, HC2, achieved 47.1% sensitivity with 70.7% specificity. The overall performance of HPV E6/E7 mRNA assay for detecting CIN 2+ was lower than HC2. This study does not support the use of this assay in screening for cervical cancer prevention alone. Copyright © 2012 Elsevier B.V. All rights reserved.

Double positivity for HPV-DNA/p16ink4a is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients.

PubMed

Mena, Marisa; Taberna, Miren; Tous, Sara; Marquez, Sandra; Clavero, Omar; Quiros, Beatriz; Lloveras, Belen; Alejo, Maria; Leon, Xavier; Quer, Miquel; Bagué, Silvia; Mesia, Ricard; Nogués, Julio; Gomà, Montserrat; Aguila, Anton; Bonfill, Teresa; Blazquez, Carmen; Guix, Marta; Hijano, Rafael; Torres, Montserrat; Holzinger, Dana; Pawlita, Michael; Pavon, Miguel Angel; Bravo, Ignacio G; de Sanjosé, Silvia; Bosch, Francesc Xavier; Alemany, Laia

2018-03-01

The etiologic role of human papillomaviruses (HPV) in oropharyngeal cancer (OPC) is well established. Nevertheless, information on survival differences by anatomic sub-site or treatment remains scarce, and it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. We conducted a retrospective cohort study of all patients diagnosed with a primary OPC in four Catalonian hospitals from 1990 to 2013. Formalin-fixed, paraffin-embedded cancer tissues were subjected to histopathological evaluation, DNA quality control, HPV-DNA detection, and p16 INK4a /pRb/p53/Cyclin-D1 immunohistochemistry. HPV-DNA positive and a random sample of HPV-DNA negative cases were subjected to HPV-E6*I mRNA detection. Demographic, tobacco/alcohol use, clinical and follow-up data were collected. Multivariate models were used to evaluate factors associated with HPV positivity as defined by four different HPV-relatedness definitions. Proportional-hazards models were used to compare the risk of death and recurrence among HPV-related and non-related OPC. 788 patients yielded a valid HPV-DNA result. The percentage of positive cases was 10.9%, 10.2%, 8.5% and 7.4% for p16 INK4a , HPV-DNA, HPV-DNA/HPV-E6*I mRNA, and HPV-DNA/p16 INK4a , respectively. Being non-smoker or non-drinker was consistently associated across HPV-relatedness definitions with HPV positivity. A suggestion of survival differences between anatomic sub-sites and treatments was observed. Double positivity for HPV-DNA/p16 INK4a showed strongest diagnostic accuracy and prognostic value. Double positivity for HPV-DNA/p16 INK4a , a test that can be easily implemented in the clinical practice, has optimal diagnostic accuracy and prognostic value. Our results have strong clinical implications for patients' classification and handling and also suggest that not all the HPV-related OPC behave similarly. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prevalence and impact on clinicopathological characteristics of human papillomavirus-16 DNA in cervical lymph node metastases of head and neck squamous cell carcinoma.

PubMed

Weiss, Daniel; Koopmann, Mario; Rudack, Claudia

2011-06-01

Human papillomavirus (HPV) is a basic risk factor for head and neck squamous cell carcinoma (HNSCC). Little knowledge exists about the impact of HPV on clinical diagnostic and therapy of patients with HNSCC. We evaluated the evidence of HPV16 in 131 retrospectively collected HNSCC and associated cervical lymph node metastases by HPV16 real-time polymerase chain reaction (PCR) and p16 immunohistochemistry and its impact on clinicopathological characteristics. HPV16-DNA and p16 overexpression were present in 27% of HNSCCs. All cervical lymph node metastases of HPV16-positive HNSCC showed HPV16-DNA. HPV16 was strongly associated with tumors arising from the oropharyngeal site (p < .000001), favorable outcome after standard therapy in univariate (p = .001) and multivariate (p = .0004) analysis, and cervical lymph node metastases before primary detection. HPV16-diagnostic in cervical lymph node metastases can predict the site of tumor origin in case of carcinoma of unknown primary (CUP) and favorable outcome and should, therefore, be included in routine diagnostic workup. Copyright © 2010 Wiley Periodicals, Inc.

Comparison of DRY and WET vaginal swabs with cervical specimens in Roche Cobas 4800 HPV and Abbott RealTime High Risk HPV tests.

PubMed

Jun, Jae Kwan; Lim, Myong Cheol; Hwang, Sang-Hyun; Shin, Hye Young; Hwang, Na Rae; Kim, Yeon-Jin; Yoo, Chong Woo; Lee, Dong Ock; Joo, Jungnam; Park, Sang-Yoon; Lee, Do-Hoon

2016-06-01

Self-collected vaginal swab samples have been proposed as an alternative specimen collection method for human papillomavirus (HPV) DNA detection. Two vaginal swabs (a cone-shaped flocked swab (DRY) and a L-shape FLOQSwab with 2mL eNAT transport medium (WET)) were compared to standard cervical samples for HPV DNA testing. Additionally, they were also compared by using Roche Cobas 4800 HPV (Roche_HPV) and Abbott Real-time High Risk HPV (Abbott_HPV) tests. Ninety-six women were prospectively enrolled from the National Cancer Center in Korea between June and August 2015. WET and DRY vaginal swabs and cervical specimens were collected. Roche_HPV and Abbott_HPV tests were performed. The Roche_HPV test on cervical specimens was used as reference. The observed agreements (kappa) of Roche_HPV and Abbott_HPV between WET and DRY swabs were 89.6% (0.790, 95% confidence interval (95% CI): 0.667-0.913) and 91.7% (0.833, 95%CI: 0.723-0.943), respectively. No statistical difference was observed between WET and DRY swabs (p>0.05 for all comparisons). For HPV16/18, the sensitivity/specificity of Roche_HPV on the DRY and WET samples presented 93.8%/96.3% and 87.5%/97.5%, respectively. For other High Risk HPV (hrHPV), the sensitivity/specificity of Roche_HPV on the DRY and WET swabs presented 91.9%/91.5% and 97.3%/98.3, respectively. The sensitivity/specificity of the Abbott_HPV on the DRY and WET swabs were 93.8%/98.8%, 87.5%/98.8% for HPV16/18, and 91.9%/93.2%, 100.0%/93.2% for other hrHPV, respectively. HPV tests performed similarly when using vaginal DRY and WET swab samples. Using DRY and WET swabs to collect vaginal specimens could be an alternative to collecting cervical samples for HPV DNA testing. Copyright © 2016 Elsevier B.V. All rights reserved.

Beral's 1974 paper: A step towards universal prevention of cervical cancer.

PubMed

Franceschi, Silvia; Vaccarella, Salvatore

2015-12-01

In 1974, Valerie Beral published a landmark paper on the sexually transmitted origin of cervical cancer (CC) using statistics routinely available in the United Kingdom (UK). Among women born between 1902 and 1947, CC mortality rates correlated remarkably well with the incidence rates of gonorrhoea when they were 20 years old and both were highest among women born after 1940. Hence, if CC prevention and treatment had remained unchanged, the youngest generations of women would have experienced a high risk of CC death as they grew older. Fortunately, progress in CC prevention has helped avoid this scenario. The adverse consequences of the "sexual revolution" were greatly mitigated in the UK and other high-resource countries by the implementation of high quality cytology-based CC screening. An age-period-cohort analysis suggests that >30,000 cases or approximately 35% of expected CC cases may have been prevented by screening programmes in the UK between 1983 and 2007 and this percentage has been steadily increasing. In addition, the discovery of the causal role of HPV is reshaping primary and secondary prevention of CC. Cheaper HPV tests are becoming available and HPV-based primary screening may at last facilitate CC screening in low-resource countries. In the long-term, however, HPV vaccination, which has already been adopted by many countries, represents the best hope for preventing CC and overcoming socio-economic differences in CC risk within and across countries. The additional elucidation of HPV cofactors to which Beral has greatly contributed may also help control HPV infection in unvaccinated women. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cervical cancer: Can it be prevented?

PubMed

Aggarwal, Pakhee

2014-10-10

Cervical cancer prevention requires a multipronged approach involving primary, secondary and tertiary prevention. The key element under primary prevention is human papilloma virus (HPV) vaccination. So far, only prophylactic HPV vaccines which prevent HPV infection by one or more subtypes are commercially available. Therapeutic HPV vaccines which aid in clearing established infection are still under trial. Secondary prevention entails early detection of precancerous lesions and its success is determined by the population coverage and the efficacy of the screening technique. A number of techniques are in use, including cytology, visual inspection (using the naked eye, magnivisualizer, acetic acid and Lugol's iodine), HPV testing and a combination of these methods. Updated screening guidelines have been advocated by the American Cancer Society in light of the role of HPV on cervical carcinogenesis. Recent research has also focussed on novel biomarkers that can predict progression to cancer in screen positive women and help to differentiate those who need treatment from those who can be left for follow-up. Last but not the least, effective treatment of precancerous lesions can help to reduce the incidence of invasive cervical cancer and this constitutes tertiary prevention. A combination of these approaches can help to prevent the burden of cervical cancer and its antecedent morbidity and mortality, but all of these are not feasible in all settings due to resource and allocation constraints. Thus, all countries, especially low and middle income ones, have to determine their own cocktail of approaches that work before we can say with certainty that yes, cervical cancer can be prevented.

Clinical Human Papillomavirus Detection Forecasts Cervical Cancer Risk in Women Over 18 Years of Follow-Up

PubMed Central

Castle, Philip E.; Glass, Andrew G.; Rush, Brenda B.; Scott, David R.; Wentzensen, Nicolas; Gage, Julia C.; Buckland, Julie; Rydzak, Greg; Lorincz, Attila T.; Wacholder, Sholom

2012-01-01

Purpose To describe the long-term (≥ 10 years) benefits of clinical human papillomavirus (HPV) DNA testing for cervical precancer and cancer risk prediction. Methods Cervicovaginal lavages collected from 19,512 women attending a health maintenance program were retrospectively tested for HPV using a clinical test. HPV positives were tested for HPV16 and HPV18 individually using a research test. A Papanicolaou (Pap) result classified as atypical squamous cells of undetermined significance (ASC-US) or more severe was considered abnormal. Women underwent follow-up prospectively with routine annual Pap testing up to 18 years. Cumulative incidence rates (CIRs) of ≥ grade 3 cervical intraepithelial neoplasia (CIN3+) or cancer for enrollment test results were calculated. Results A baseline negative HPV test provided greater reassurance against CIN3+ over the 18-year follow-up than a normal Pap (CIR, 0.90% v 1.27%). Although both baseline Pap and HPV tests predicted who would develop CIN3+ within the first 2 years of follow-up, only HPV testing predicted who would develop CIN3+ 10 to 18 years later (P = .004). HPV16- and HPV18-positive women with normal Pap were at elevated risk of CIN3+ compared with other HPV-positive women with normal Pap and were at similar risk of CIN3+ compared with women with a low-grade squamous intraepithelial Pap. Conclusion HPV testing to rule out cervical disease followed by Pap testing and possibly combined with the detection of HPV16 and HPV18 among HPV positives to identify those at immediate risk of CIN3+ would be an efficient algorithm for cervical cancer screening, especially in women age 30 years or older. PMID:22851570

Cost-effectiveness of HPV-based cervical cancer screening in the public health system in Nicaragua.

PubMed

Campos, Nicole G; Mvundura, Mercy; Jeronimo, Jose; Holme, Francesca; Vodicka, Elisabeth; Kim, Jane J

2017-06-15

To evaluate the cost-effectiveness of human papillomavirus (HPV) DNA testing (versus Papanicolaou (Pap)-based screening) for cervical cancer screening in Nicaragua. A previously developed Monte Carlo simulation model of the natural history of HPV infection and cervical cancer was calibrated to epidemiological data from Nicaragua. Cost data inputs were derived using a micro-costing approach in Carazo, Chontales and Chinandega departments; test performance data were from a demonstration project in Masaya department. Nicaragua's public health sector facilities. Women aged 30-59 years. Screening strategies included (1) Pap testing every 3 years, with referral to colposcopy for women with an atypical squamous cells of undetermined significance or worse result ('Pap'); (2) HPV testing every 5 years, with referral to cryotherapy for HPV-positive eligible women (HPV cryotherapy or 'HPV-Cryo'); (3) HPV testing every 5 years, with referral to triage with visual inspection with acetic acid (VIA) for HPV-positive women ('HPV-VIA'); and (4) HPV testing every 5 years, with referral to Pap testing for HPV-positive women ('HPV-Pap'). Reduction in lifetime risk of cancer and incremental cost-effectiveness ratios (ICER; 2015 US$ per year of life saved (YLS)). HPV-based screening strategies were more effective than Pap testing. HPV-Cryo was the least costly and most effective strategy, reducing lifetime cancer risk by 29.5% and outperforming HPV-VIA, HPV-Pap and Pap only, which reduced cancer risk by 19.4%, 12.2% and 10.8%, respectively. With an ICER of US$320/YLS, HPV-Cryo every 5 years would be very cost-effective using a threshold based on Nicaragua's per capita gross domestic product of US$2090. Findings were robust across sensitivity analyses on test performance, coverage, compliance and cost parameters. HPV testing is very cost-effective compared with Pap testing in Nicaragua, due to higher test sensitivity and the relatively lower number of visits required. Increasing compliance with recommended follow-up will further improve the health benefits and value for public health dollars. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cost-effectiveness of HPV-based cervical cancer screening in the public health system in Nicaragua

PubMed Central

Mvundura, Mercy; Jeronimo, Jose; Holme, Francesca; Vodicka, Elisabeth; Kim, Jane J

2017-01-01

Objectives To evaluate the cost-effectiveness of human papillomavirus (HPV) DNA testing (versus Papanicolaou (Pap)-based screening) for cervical cancer screening in Nicaragua. Design A previously developed Monte Carlo simulation model of the natural history of HPV infection and cervical cancer was calibrated to epidemiological data from Nicaragua. Cost data inputs were derived using a micro-costing approach in Carazo, Chontales and Chinandega departments; test performance data were from a demonstration project in Masaya department. Setting Nicaragua’s public health sector facilities. Participants Women aged 30–59 years. Interventions Screening strategies included (1) Pap testing every 3 years, with referral to colposcopy for women with an atypical squamous cells of undetermined significance or worse result (‘Pap’); (2) HPV testing every 5 years, with referral to cryotherapy for HPV-positive eligible women (HPV cryotherapy or ‘HPV-Cryo’); (3) HPV testing every 5 years, with referral to triage with visual inspection with acetic acid (VIA) for HPV-positive women (‘HPV-VIA’); and (4) HPV testing every 5 years, with referral to Pap testing for HPV-positive women (‘HPV-Pap’). Outcome measures Reduction in lifetime risk of cancer and incremental cost-effectiveness ratios (ICER; 2015 US$ per year of life saved (YLS)). Results HPV-based screening strategies were more effective than Pap testing. HPV-Cryo was the least costly and most effective strategy, reducing lifetime cancer risk by 29.5% and outperforming HPV-VIA, HPV-Pap and Pap only, which reduced cancer risk by 19.4%, 12.2% and 10.8%, respectively. With an ICER of US$320/YLS, HPV-Cryo every 5 years would be very cost-effective using a threshold based on Nicaragua’s per capita gross domestic product of US$2090. Findings were robust across sensitivity analyses on test performance, coverage, compliance and cost parameters. Conclusions HPV testing is very cost-effective compared with Pap testing in Nicaragua, due to higher test sensitivity and the relatively lower number of visits required. Increasing compliance with recommended follow-up will further improve the health benefits and value for public health dollars. PMID:28619772

Commercially available molecular tests for human papillomaviruses (HPV): 2015 update.

PubMed

Poljak, Mario; Kocjan, Boštjan J; Oštrbenk, Anja; Seme, Katja

2016-03-01

Commercial molecular tests for human papillomaviruses (HPV) are invaluable diagnostic tools in cervical carcinoma screening and management of women with cervical precancerous lesions as well as important research tools for epidemiological studies, vaccine development, and implementation and monitoring of vaccination programs. In this third inventory of commercial HPV tests, we identified 193 distinct commercial HPV tests and at least 127 test variants available on the market in 2015, which represents a 54% and 79% increase in the number of distinct HPV tests and variants, respectively, in comparison to our last inventory performed in 2012. Identified HPV tests were provisionally divided into eight main groups and several subgroups. Among the 193 commercial HPV tests, all but two target alpha-HPV types only. Although the number of commercial HPV tests with at least one published study in peer-reviewed literature has increased significantly in the last three years, several published performance evaluations are still not in line with agreed-upon standards in the HPV community. Manufacturers should invest greater effort into evaluating their products and publishing validation/evaluation results in peer-reviewed journals. To achieve this, more clinically oriented external quality-control panels and initiatives are required. For evaluating the analytical performance of the entire range of HPV tests currently on the market, more diverse and reliable external quality-control programs based on international standards for all important HPV types are indispensable. The performance of a wider range of HPV tests must be promptly evaluated on a variety of alternative clinical specimens. In addition, more complete HPV assays containing validated sample-extraction protocols and appropriate internal controls are urgently needed. Provision of a broader range of automated systems allowing large-scale HPV testing as well as the development of reliable, rapid, and affordable molecular point-of-care tests are priorities for the further improvement of HPV tests. Copyright © 2015 Elsevier B.V. All rights reserved.

Cytology and high risk HPV testing in cervical cancer screening program: Outcome of 3-year follow-up in an academic institute.

PubMed

Yang, Jack; Nolte, Fredrick S; Chajewski, Olga S; Lindsey, Kathryn G; Houser, Patricia M; Pellicier, Jalidsa; Wang, Qun; Ehsani, Laleh

2018-01-01

Combination of cervical cytology and high-risk human papillomavirus (HR-HPV) testing, co-testing, has been increasingly used in screening cervical cancers. The present study summarized the outcome of co-testing by reviewing 3-year clinical and pathological follow-up information. Patients were retrospectively identified via computerized search and were grouped based on the cytologic diagnosis and HR-HPV status as negative for intraepithelial lesion or malignancy (NILM)/HPV-, NILM/HPV+, atypical squamous cells of undetermined significance (ASC-US)/HPV-, ASC-US/HPV+, low grade squamous intraepithelial lesion (LSIL)/HPV-, LSIL/HPV+, atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H)/HPV-, ASC-H/HPV+, high grade squamous intraepithelial lesion (HSIL)/HPV-, and HSIL/HPV+. The patients' pertinent past medical history and follow-up information were analyzed. During 3-year follow-up period, histologically proven HSIL was found in 5 of 1565 (0.3%) patients with NILM/HPV-, 7 of 141 (5.0%) with NILM/HPV+, 2 of 502 (0.4%) with ASC-US/HPV-, 30 of 274 (10.9%) with ASC-US/HPV+, 1 of 81 (1.2%) with LSIL/HPV-, 28 of 159 (17.6%) with LSIL/HPV+, 3 of 18 (16.7%) with ASC-H/HPV-, 34 of 69 (49.3%) with ASC-H/HPV+, 7 of 7 (100%) with HSIL/HPV-, and 35 of 56 (62.5%) HSIL/HPV+. In reviewing 12 HSIL cases that were originally diagnosed as NILM, 7 remained as NILM, and the other 5 were reclassified as 1 HSIL, 1 ASC-H, and 3 ASC-US, respectively. In 18 HSIL cases with negative HR-HPV, 12 patients had a prior history of positive HR-HPV testing and/or positive p16 IHC stain in the follow-up cervical biopsy. HR-HPV testing plays an important role in cervical cancer screening by identifying HSIL in patients with ASC-US, LSIL, and NILM. Co-testing is an optimal method to identifying the patients with higher risk for developing cervical abnormalities. © 2017 Wiley Periodicals, Inc.

Expression of proliferation marker Ki67 correlates to occurrence of metastasis and prognosis, histological subtypes and HPV DNA detection in penile carcinomas.

PubMed

Protzel, C; Knoedel, J; Zimmermann, U; Woenckhaus, C; Poetsch, M; Giebel, J

2007-11-01

Clinical outcome of penile squamous cell carcinoma (PSCC) largely depends on the presence of lymph node metastasis. In search of a valuable marker predicting the risk for metastasis, the expression of Ki67 was investigated immunohistochemically in primary tumors and compared to presence of inguinal lymph node metastasis. As human papilloma virus (HPV) is thought to affect Ki67 expression, we evaluated whether occurrence of HPV DNA correlates to Ki67 score or metastatic potential. Samples originated from patients subjected to resection of invasive SCC of penis. Immunohistochemistry was done on paraffin-embedded sections using a monoclonal antibody against Ki67. After DNA isolation from paraffin embedded tissue the presence of HPV 6/11, HPV 16 and HPV 18 DNA was analyzed by PCR. Statistical analysis was done using two tail unpaired t test and Chi-square test. Four of 28 patients showed a weak Ki67 expression, without displaying lymph node metastasis. Among 17 patients showing an intermediate Ki67 index, eight exhibited metastases while in all seven patients with a strong expression of Ki67 lymph node metastases were found. The median Ki67 expression in metastastic lesions was significantly different (50.3%) from tumors without lymph node metastasis (31.8%) (p=0.024). Furthermore, a correlation between presence of HPV DNA and strong Ki67 expression was determined (p=0.009). Since our study demonstrated a strong Ki67 labeling index significantly associated to positive lymph nodes, we suggest Ki67 expression as a prognostic marker for lymph node metastasis in penile squamous carcinoma.

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

PubMed Central

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

2009-01-01

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

Analytic and Clinical Performance of cobas HPV Testing in Anal Specimens from HIV-Positive Men Who Have Sex with Men

PubMed Central

Follansbee, Stephen; Borgonovo, Sylvia; Tokugawa, Diane; Sahasrabuddhe, Vikrant V.; Chen, Jie; Lorey, Thomas S.; Gage, Julia C.; Fetterman, Barbara; Boyle, Sean; Sadorra, Mark; Tang, Scott Dahai; Darragh, Teresa M.; Castle, Philip E.

2014-01-01

Anal human papillomavirus (HPV) infections are common, and the incidence of anal cancer is high in HIV-infected men who have sex with men (MSM). To evaluate the performance of HPV assays in anal samples, we compared the cobas HPV test (cobas) to the Roche Linear Array HPV genotyping assay (LA) and cytology in HIV-infected MSM. Cytology and cobas and LA HPV testing were conducted for 342 subjects. We calculated agreement between the HPV assays and the clinical performance of HPV testing and HPV genotyping alone and in combination with anal cytology. We observed high agreement between cobas and LA, with cobas more likely than LA to show positive results for HPV16, HPV18, and other carcinogenic types. Specimens testing positive in cobas but not in LA were more likely to be positive for other markers of HPV-related disease compared to those testing negative in both assays, suggesting that at least some of these were true positives for HPV. cobas and LA showed high sensitivities but low specificities for the detection of anal intraepithelial neoplasia grade 2/3 (AIN2/3) in this population (100% sensitivity and 26% specificity for cobas versus 98.4% sensitivity and 28.9% specificity for LA). A combination of anal cytology and HPV genotyping provided the highest accuracy for detecting anal precancer. A higher HPV load was associated with a higher risk of AIN2/3 with HPV16 (Ptrend < 0.001), HPV18 (Ptrend = 0.07), and other carcinogenic types (Ptrend < 0.001). We demonstrate that cobas can be used for HPV detection in anal cytology specimens. Additional tests are necessary to identify men at the highest risk of anal cancer among those infected with high-risk HPV. PMID:24899025

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

PubMed

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

2006-07-01

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

Molecular characterization of late stomal recurrence following total laryngectomy.

PubMed

Stephen, Josena K; Symal, Mausumi; Chen, Kang Mei; Ghanem, Tamer; Deeb, Robert; Shah, Veena; Havard, Shaleta; Worsham, Maria J

2011-03-01

The goal was to determine recurrent or second primary status for late stomal malignancies, 16 and 17 years post-total laryngectomy in two laryngeal squamous cell carcinoma (LSCC) patients, based on DNA methylation signatures and HPV typing. Adopting a literature review based definition of late stomal recurrences as new primaries at the site of the stoma or neopharynx occurring >5 years after total laryngectomy, we employed a multi-gene candidate approach to examine promoter methylation in 24 tumor suppressor genes and PCR-based assays for HPV status offered additional insights into whether the late stomal tumors post-total laryngectomy were related or not. The primary tumor for Patient 1 was negative for HPV but had aberrant hypermethylation of APC, MLH1 and BRCA1. The stomal biopsy 17-years later showed presence of HPV-16 without any methylated genes. In Patient 2, HPV-11 and promoter methylation of APC identified in the primary tumor was also observed in the stomal malignancy 16 years post-total laryngectomy. Additional information provided by molecular typing for HPV and methylation markers underscored Patient 1's and 2's late stomal presentation as most likely a second primary and recurrence, respectively. DNA methylation markers are particularly advantageous because DNA methylation is an early event in tumorigenesis, and the epigenetic modification, 5-methylcytosine, is a stable marker. Molecular marks to discern genetic heterogeneity or relatedness of stomal malignancies several years post-total laryngectomy can provide clues to their status as either second primaries or likely recurrences. Our results support the hypothesis that a subset of stomal recurrences after total laryngectomy represents second primary tumors.

Cost-effectiveness of an HPV self-collection campaign in Uganda: comparing models for delivery of cervical cancer screening in a low-income setting

PubMed Central

Campos, Nicole G; Tsu, Vivien; Jeronimo, Jose; Njama-Meya, Denise; Mvundura, Mercy; Kim, Jane J

2017-01-01

Abstract With the availability of a low-cost HPV DNA test that can be administered by either a healthcare provider or a woman herself, programme planners require information on the costs and cost-effectiveness of implementing cervical cancer screening programmes in low-resource settings under different models of healthcare delivery. Using data from the START-UP demonstration project and a micro-costing approach, we estimated the health and economic impact of once-in-a-lifetime HPV self-collection campaign relative to clinic-based provider-collection of HPV specimens in Uganda. We used an individual-based Monte Carlo simulation model of the natural history of HPV and cervical cancer to estimate lifetime health and economic outcomes associated with screening with HPV DNA testing once in a lifetime (clinic-based provider-collection vs a self-collection campaign). Test performance and cost data were obtained from the START-UP demonstration project using a micro-costing approach. Model outcomes included lifetime risk of cervical cancer, total lifetime costs (in 2011 international dollars [I$]), and life expectancy. Cost-effectiveness ratios were expressed using incremental cost-effectiveness ratios (ICERs). When both strategies achieved 75% population coverage, ICERs were below Uganda’s per capita GDP (self-collection: I$80 per year of life saved [YLS]; provider-collection: I$120 per YLS). When the self-collection campaign achieved coverage gains of 15–20%, it was more effective than provider-collection, and had a lower ICER unless coverage with both strategies was 50% or less. Findings were sensitive to cryotherapy compliance among screen-positive women and relative HPV test performance. The primary limitation of this analysis is that self-collection costs are based on a hypothetical campaign but are based on unit costs from Uganda. Once-in-a-lifetime screening with HPV self-collection may be very cost-effective and reduce cervical cancer risk by > 20% if coverage is high. Demonstration projects will be needed to confirm the validity of our logistical, costing and compliance assumptions. PMID:28369405

Cost-effectiveness of an HPV self-collection campaign in Uganda: comparing models for delivery of cervical cancer screening in a low-income setting.

PubMed

Campos, Nicole G; Tsu, Vivien; Jeronimo, Jose; Njama-Meya, Denise; Mvundura, Mercy; Kim, Jane J

2017-09-01

With the availability of a low-cost HPV DNA test that can be administered by either a healthcare provider or a woman herself, programme planners require information on the costs and cost-effectiveness of implementing cervical cancer screening programmes in low-resource settings under different models of healthcare delivery. Using data from the START-UP demonstration project and a micro-costing approach, we estimated the health and economic impact of once-in-a-lifetime HPV self-collection campaign relative to clinic-based provider-collection of HPV specimens in Uganda. We used an individual-based Monte Carlo simulation model of the natural history of HPV and cervical cancer to estimate lifetime health and economic outcomes associated with screening with HPV DNA testing once in a lifetime (clinic-based provider-collection vs a self-collection campaign). Test performance and cost data were obtained from the START-UP demonstration project using a micro-costing approach. Model outcomes included lifetime risk of cervical cancer, total lifetime costs (in 2011 international dollars [I$]), and life expectancy. Cost-effectiveness ratios were expressed using incremental cost-effectiveness ratios (ICERs). When both strategies achieved 75% population coverage, ICERs were below Uganda's per capita GDP (self-collection: I$80 per year of life saved [YLS]; provider-collection: I$120 per YLS). When the self-collection campaign achieved coverage gains of 15-20%, it was more effective than provider-collection, and had a lower ICER unless coverage with both strategies was 50% or less. Findings were sensitive to cryotherapy compliance among screen-positive women and relative HPV test performance. The primary limitation of this analysis is that self-collection costs are based on a hypothetical campaign but are based on unit costs from Uganda. Once-in-a-lifetime screening with HPV self-collection may be very cost-effective and reduce cervical cancer risk by > 20% if coverage is high. Demonstration projects will be needed to confirm the validity of our logistical, costing and compliance assumptions. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

Automation of the linear array HPV genotyping test and its application for routine typing of human papillomaviruses in cervical specimens of women without cytological abnormalities in Switzerland.

PubMed

Dobec, Marinko; Bannwart, Fridolin; Kaeppeli, Franz; Cassinotti, Pascal

2009-05-01

There is a need for reliable, automated high throughput HPV detection and genotyping methods for pre- and post-prophylactic vaccine intervention analyses. To optimize the linear array (LA) HPV genotyping test (Roche Diagnostics, Rotkreuz) in regard to possible automation steps for the routine laboratory diagnosis of HPV infections and to analyze the HPV genotype distribution in cervical specimens of women without cytological abnormalities in Switzerland. 680 cervical cell specimens with normal cytology, obtained from women undergoing routine cervical screening by liquid-based Pap smear, were analyzed by the LA HPV genotyping test for HPV-DNA. The automation of the LA HPV genotyping test resulted in a total hands-on time reduction of 255 min (from 480 to 225 min; 53%). Any of 37 HPV genotypes were detected in 117 (17.2%) and high-risk (HR) HPV in 55 (8.1%) of 680 women with normal cytology. The highest prevalence of any HPV (28.1%) and HR-HPV (15.1%) was observed in age-group 21-30 and showed a continuous decrease in older age-groups. The most common HR-HPV genotypes were HPV-16 (12%), HPV-31 (9.4%), HPV-52 (6%), HPV-51 (5.1%), HPV-45 (4.3%), HPV-58 (4.3%) and HPV-59 (4.3%). The optimization and automation of the LA HPV genotyping test makes it suited for high throughput HPV detection and typing. The epidemiological data provides information about distribution of HPV genotypes in women without cytological abnormalities in Switzerland and may be important for determining the future impact of vaccines and potential changes in the country's epidemiological HPV profile.

Assessment of human papilloma virus infection in adult laryngeal papilloma using a screening test.

PubMed

Makiyama, Kiyoshi; Hirai, Ryoji; Matsuzaki, Hiroumi; Ikeda, Minoru

2013-03-01

Human papilloma virus (HPV) infection is involved in both juvenile and adult laryngeal papilloma. We wished to determine which types of adult laryngeal papilloma were clinically related to HPV infection. We hypothesized that multiple-site and recurrent papillomas would have a strong relationship to HPV and conducted the present study to test this hypothesis. Thirteen male patients with adult laryngeal papilloma who underwent resection of papilloma between August 2006 and September 2009 were studied. We examined the relationships between whether the tumor was solitary or multiple, presence or absence of recurrence after surgery, and HPV infection. High-risk HPV types (HPV-DNA types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) and low-risk HPV types (6, 11, 42, 43, and 44) were tested by a liquid-phase hybridization method. In addition, HPV typing was performed for patients positive for low-risk HPV types. Twenty patients with laryngeal carcinoma or laryngeal leukoplakia were enrolled as the control group. In the laryngeal papilloma group, all patients tested were negative for high-risk HPV and 69.2% were positive for low-risk HPV. Typing performed for seven of the patients who tested positive for low-risk HPV showed that one patient was positive for HPV-11, whereas the remaining six patients were positive for HPV-6. All patients with recurrent laryngeal papillomatosis (RLP) were positive for low-risk HPV. All patients who were positive for low-risk HPV had RLP. Tumor samples from repeat operations were positive for low-risk HPV in all patients tested. HPV was not detected in the control group. The relationship between RLP and low-risk HPV was strong, with all cases that were positive for low-risk HPV showing recurrence. Tumor tissue resected at the time of repeat surgery was positive for low-risk HPV in all cases tested. Copyright © 2013 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Is surgical plume developing during routine LEEPs contaminated with high-risk HPV? A pilot series of experiments.

PubMed

Neumann, Kay; Cavalar, Markus; Rody, Achim; Friemert, Luisa; Beyer, Daniel A

2018-02-01

Growing evidence shows a causal role of high-risk humane papillomavirus (HPV) infections in the development of head and neck cancer. A recent case report shows two patients suffering from tonsillar cancer without any risk factors apart from their work as gynecologists doing laser ablations and loop electrosurgical excision procedures (LEEP). The aim of the present investigation is to evaluate whether surgical plume resulting from routine LEEPs of HSIL of the cervix uteri might be contaminated with the DNA of high-risk HPV. The prospective pilot study is done at the Department of Gynecology and Obstetrics of the University of Lübeck, Germany. The primary outcome was defined as HPV subtype in resected cone and in surgical plume resulting from LEEPs of HSIL of the cervix uteri. Plume resulting from LEEPs was analyzed using a Whatman FTA Elute Indicating Card which was placed in the tube of an exhaust suction device used to remove the resulting aerosols. For detection of HPV and analysis of its subtype, the novel EUROArray HPV test was performed. Resected cones of LEEPs were evaluated separately for HPV subtypes. Four samples of surgical plume resulting from routine LEEPs indicated contamination with high-risk HPV and showed the same HPV subtype as identified in the resected cones. Surgical plume resulting from routine LEEPs for HSIL of the cervix uteri has the risk of contamination with high-risk HPV. Further investigations of infectiousness of surgical plume are necessary for evaluation of potential hazards to involved healthcare professionals.

Ten-year immune persistence and safety of the HPV-16/18 AS04-adjuvanted vaccine in females vaccinated at 15-55 years of age.

PubMed

Schwarz, Tino F; Galaj, Andrzej; Spaczynski, Marek; Wysocki, Jacek; Kaufmann, Andreas M; Poncelet, Sylviane; Suryakiran, Pemmaraju V; Folschweiller, Nicolas; Thomas, Florence; Lin, Lan; Struyf, Frank

2017-11-01

Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV-16/18 from prophylactic vaccination remains unknown. We investigated the 10-year immune response and long-term safety profile of the HPV-16/18 AS04-adjuvanted vaccine (AS04-HPV-16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04-HPV-16/18 vaccine in the primary phase-III study (NCT00196937) were invited to attend annual evaluations for long-term immunogenicity and safety. Anti-HPV-16/18 antibodies in serum and cervico-vaginal secretions (CVS) were measured using enzyme-linked immunosorbent assay (ELISA). Serious adverse events (SAEs) were recorded throughout the follow-up period. Seropositivity rates for anti-HPV-16 remained high (≥96.3%) in all age groups 10 years after first vaccination. It was found that 99.2% of 15-25-year olds remained seropositive for anti-HPV-18 compared to 93.7% and 83.8% of 26-45-year olds and 45-55-year olds, respectively. Geometric mean titers (GMT) remained above natural infection levels in all age groups. Anti-HPV-16 and anti-HPV-18 titers were at least 5.3-fold and 3.1-fold higher than titers observed after natural infection, respectively, and were predicted to persist above natural infection levels for ≥30 years in all age groups. At Year 10, anti-HPV-16/18 antibody titers in subjects aged 15-25 years remained above plateau levels observed in previous studies. Correlation coefficients for antibody titers in serum and CVS were 0.64 (anti-HPV-16) and 0.38 (anti-HPV-18). This study concluded that vaccinated females aged 15-55 years elicited sustained immunogenicity with an acceptable safety profile up to 10 years after primary vaccination, suggesting long-term protection against HPV. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

How will transitioning from cytology to HPV testing change the balance between the benefits and harms of cervical cancer screening? Estimates of the impact on cervical cancer, treatment rates and adverse obstetric outcomes in Australia, a high vaccination coverage country.

PubMed

Velentzis, Louiza S; Caruana, Michael; Simms, Kate T; Lew, Jie-Bin; Shi, Ju-Fang; Saville, Marion; Smith, Megan A; Lord, Sarah J; Tan, Jeffrey; Bateson, Deborah; Quinn, Michael; Canfell, Karen

2017-12-15

Primary HPV screening enables earlier diagnosis of cervical lesions compared to cytology, however, its effect on the risk of treatment and adverse obstetric outcomes has not been extensively investigated. We estimated the cumulative lifetime risk (CLR) of cervical cancer and excisional treatment, and change in adverse obstetric outcomes in HPV unvaccinated women and cohorts offered vaccination (>70% coverage in 12-13 years) for the Australian cervical screening program. Two-yearly cytology screening (ages 18-69 years) was compared to 5-yearly primary HPV screening with partial genotyping for HPV16/18 (ages 25-74 years). A dynamic model of HPV transmission, vaccination, cervical screening and treatment for precancerous lesions was coupled with an individual-based simulation of obstetric complications. For cytology screening, the CLR of cervical cancer diagnosis, death and treatment was estimated to be 0.649%, 0.198% and 13.4% without vaccination and 0.182%, 0.056% and 6.8%, in vaccinated women, respectively. For HPV screening, relative reductions of 33% and 22% in cancer risk for unvaccinated and vaccinated women are predicted, respectively, compared to cytology. Without the implementation of vaccination, a 4% increase in treatment risk for HPV versus cytology screening would have been expected, implying a possible increase in pre-term delivery (PTD) and low birth weight (LBW) events of 19 to 35 and 14 to 37, respectively, per 100,000 unvaccinated women. However, in vaccinated women, treatment risk will decrease by 13%, potentially leading to 4 to 41 fewer PTD events and from 2 more to 52 fewer LBW events per 100,000 vaccinated women. In unvaccinated women in cohorts offered vaccination as 12-13 year olds, no change to lifetime treatment risk is expected with HPV screening. In unvaccinated women in cohorts offered vaccination as 12-13 year olds, no change to lifetime treatment risk is expected with HPV screening. HPV screening starting at age 25 in populations with high vaccination coverage, is therefore expected to both improve the benefits (further decrease risk of cervical cancer) and reduce the harms (reduce treatments and possible obstetric complications) associated with cervical cancer screening. © 2017 UICC.

Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years.

PubMed

Romanowski, B; de Borba, P Colares; Naud, P S; Roteli-Martins, C M; De Carvalho, N S; Teixeira, J C; Aoki, F; Ramjattan, B; Shier, R M; Somani, R; Barbier, S; Blatter, M M; Chambers, C; Ferris, D; Gall, S A; Guerra, F A; Harper, D M; Hedrick, J A; Henry, D C; Korn, A P; Kroll, R; Moscicki, A-B; Rosenfeld, W D; Sullivan, B J; Thoming, C S; Tyring, S K; Wheeler, C M; Dubin, G; Schuind, A; Zahaf, T; Greenacre, Mary; Sgriobhadair, An

2009-12-12

Prophylactic human papillomavirus (HPV) vaccines have to provide sustained protection. We assessed efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. Women aged 15-25 years, with normal cervical cytology, who were HPV-16/18 seronegative and oncogenic HPV DNA-negative (14 types) at screening participated in a double-blind, randomised, placebo-controlled initial study (n=1113; 560 vaccine group vs 553 placebo group) and follow-up study (n=776; 393 vs 383). 27 sites in three countries participated in the follow-up study. Cervical samples were tested every 6 months for HPV DNA. Management of abnormal cytologies was prespecified, and HPV-16/18 antibody titres were assessed. The primary objective was to assess long-term vaccine efficacy in the prevention of incident cervical infection with HPV 16 or HPV 18, or both. We report the analyses up to 6.4 years of this follow-up study and combined with the initial study. For the primary endpoint, the efficacy analysis was done in the according-to-protocol (ATP) cohort; the analysis of cervical intraepithelial neoplasia grade 2 and above (CIN2+) was done in the total vaccinated cohort (TVC). The study is registered with ClinicalTrials.gov, number NCT00120848. For the combined analysis of the initial and follow-up studies, the ATP efficacy cohort included 465 women in the vaccine group and 454 in the placebo group; the TVC included 560 women in the vaccine group and 553 in the placebo group. Vaccine efficacy against incident infection with HPV 16/18 was 95.3% (95% CI 87.4-98.7) and against 12-month persistent infection was 100% (81.8-100). Vaccine efficacy against CIN2+ was 100% (51.3-100) for lesions associated with HPV-16/18 and 71.9% (20.6-91.9) for lesions independent of HPV DNA. Antibody concentrations by ELISA remained 12-fold or more higher than after natural infection (both antigens). Safety outcomes were similar between groups: during the follow-up study, 30 (8%) participants reported a serious adverse event in the vaccine group versus 37 (10%) in the placebo group. None was judged related or possibly related to vaccination, and no deaths occurred. Our findings show excellent long-term efficacy, high and sustained immunogenicity, and favourable safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. GlaxoSmithKline Biologicals (Belgium).

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

PubMed

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

2011-09-01

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

Assessing Acceptability of Self-Sampling Kits, Prevalence, and Risk Factors for Human Papillomavirus Infection in American Indian Women.

PubMed

Winer, Rachel L; Gonzales, Angela A; Noonan, Carolyn J; Cherne, Stephen L; Buchwald, Dedra S

2016-10-01

We evaluated the feasibility and acceptability of self-sampling for human papillomavirus (HPV) testing and calculated the prevalence of and risk factors for high-risk (hr) HPV infections in a community-based sample of American Indian women. To this end, we recruited 329 Hopi women aged 21-65 years to self-collect vaginal samples for hrHPV testing. Samples were tested by polymerase chain reaction for 14 hrHPV genotypes. We used Chi square tests to identify correlates of preference for clinician Pap testing versus HPV self-sampling, and age-adjusted Poisson regression to evaluate correlates of hrHPV prevalence. We found that satisfaction with HPV self-sampling was high, with 96 % of women reporting that the sample was easy to collect and 87 % reporting no discomfort. The majority (62 %) indicated that they preferred HPV self-sampling to receiving a Pap test from a clinician. Preference for Pap testing over HPV self-sampling was positively associated with adherence to Pap screening and employment outside the home. All samples evaluated were satisfactory for HPV testing, and 22 % were positive for hrHPV. HrHPV prevalence peaked in the late 20 s and declined with increasing age. HrHPV positivity was inversely associated with having children living the household. In conclusion, HPV self-sampling is feasible and acceptable to Hopi women, and could be effective in increasing rates of cervical cancer screening in Hopi communities. HrHPV prevalence was similar to estimates in the general United States population.

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.

Primary prevention and vaccination for penile cancer

PubMed Central

Barod, Ravi; Hegarty, Paul K.; Minhas, Suks

2013-01-01

The outcome of penile cancer is proportional to the stage at presentation. Strategies aimed at primary prevention would have a clear advantage, both for the individual and in terms of health economics. A number of preventative measures could be employed, including circumcision, smoking cessation, education on hygiene and human papillomavirus (HPV) prevention. There is a high prevalence of HPV infection associated with penile cancer worldwide. The recent development of HPV vaccines has facilitated interest in their use for the prevention of penile cancer. In this article we review the literature surrounding penile cancer prevention and HPV vaccination in men. PMID:23730331

Management of HPV-related cervical disease: role of p16INK4a immunochemistry. Review of the literature.

PubMed

Savone, Delia; Carrone, Angela; Riganelli, Lucia; Merlino, Lucia; Mancino, Pasquale; Benedetti Panici, Pierluigi

2016-10-13

This systematic review of 43 studies aims to evaluate the absolute and relative sensitivity and specificity of p16INK4a with regard to uterine cervix lesions, describing innovations and techniques for the detection of high-grade cervical dysplasia and allowing correct treatment. Studies were identified in the PubMed database up to March 2015. The keywords hrHPV, p16INK4a gene, and uterine cervical disease (MeSH terms) were used. Only English-language articles were included. We considered retrospective and prospective studies that assessed p16INK4a or p16INK4a/Ki67 staining, with or without HPV-DNA testing (HC2/PCR) as a comparator test, in cytological/histological specimens for which the diagnosis of ASCUS, LSIL or HSIL was verified with a reference standard. The primary outcome for cervical lesions was evaluation of the absolute p16INK4a immunoreactivity; the secondary outcome was evaluation of the relative p16INK4a immunoreactivity versus HPV testing in those studies where comparator tests were available. p16INK4a was more specific than HPV-DNA test (median values of 56.1% vs. 52.25% in CIN grade ≥2 lesions; 82.5% vs. 53% in negative and CIN grade ≥1 lesions). The main limitation of this study is linked to both qualitative and quantitative p16INK4a levels of expression, while the second limitation is the lack of standardized scales. p16INK4a and HPV-DNA used together increased the sensitivity and negative predictive value for CIN detection. p16INK4a can be considered a biomarker of CIN2 or CIN3, indicating a high risk of relapse or evolution to invasive carcinoma. Also p16INK4a-negative CIN should be considered and further research should be performed.

A Learning Collaborative Model to Improve Human Papillomavirus Vaccination Rates in Primary Care.

PubMed

Rand, Cynthia M; Tyrrell, Hollyce; Wallace-Brodeur, Rachel; Goldstein, Nicolas P N; Darden, Paul M; Humiston, Sharon G; Albertin, Christina S; Stratbucker, William; Schaffer, Stanley J; Davis, Wendy; Szilagyi, Peter G

2018-03-01

Human papillomavirus (HPV) vaccination rates remain low, in part because of missed opportunities (MOs) for vaccination. We used a learning collaborative quality improvement (QI) model to assess the effect of a multicomponent intervention on reducing MOs. Study design: pre-post using a QI intervention in 33 community practices and 14 pediatric continuity clinics over 9 months to reduce MOs for HPV vaccination at all visit types. outcome measures comprised baseline and postproject measures of 1) MOs (primary outcome), and 2) HPV vaccine initiation and completion. Process measures comprised monthly chart audits of MOs for HPV vaccination for performance feedback, monthly Plan-Do-Study-Act surveys and pre-post surveys about office systems. providers were trained at the start of the project on offering a strong recommendation for HPV vaccination. Practices implemented provider prompts and/or standing orders and/or reminder/recall if desired, and were provided monthly feedback on MOs to assess their progress. chi-square tests were used to assess changes in office practices, and logistic regression used to assess changes in MOs according to visit type and overall, as well as HPV vaccine initiation and completion. MOs overall decreased (from 73% to 53% in community practices and 62% to 55% in continuity clinics; P < .01, and P = .03, respectively). HPV vaccine initiation increased for both genders in community practices (from 66% to 74% for female, 57% to 65% for male; P < .01), and for male patients in continuity clinics (from 68% to 75%; P = .05). Series completion increased overall in community practices (39% to 43%; P = .04) and for male patients in continuity clinics (from 36% to 44%; P = .03). Office systems changes using a QI model and multicomponent interventions decreased rates of MO for HPV vaccination and increased initiation and completion rates among some gender subgroups. A learning collaborative model provides an effective forum for practices to improve HPV vaccine delivery. Copyright © 2018 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Screening of cervical cancer in Catalonia 2006-2012.

PubMed

de Sanjosé, Silvia; Ibáñez, Raquel; Rodríguez-Salés, Vanesa; Peris, Mercè; Roura, Esther; Diaz, Mireia; Torné, Aureli; Costa, Dolors; Canet, Yolanda; Falguera, Gemma; Alejo, Maria; Espinàs, Josep Alfons; Bosch, F Xavier

2015-01-01

The early detection of intraepithelial lesions of the cervix, through the periodic examination of cervical cells, has been fundamental for the prevention of invasive cervical cancer and its related mortality. In this report, we summarise the cervical cancer screening activities carried out in Catalonia, Spain, within the National Health System during 2008-2011. The study population covers over two million women resident in the area. The evaluation includes 758,690 cervical cytologies performed on a total of 595,868 women. The three-year coverage of cervical cytology among women aged between 25 and 65 years was 40.8%. About 50% of first screened women with negative results had not returned to the second screening round. The introduction of high-risk human papillomavirus DNA (HPV) detection, as a primary screening cotest with cytology among women over age 40 with a poor screening history, significantly improved the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), being far superior to cytology alone. Cotesting did not improve the detection of CIN2+. The use of the HPV test for the triage of atypical squamous cell undetermined significance (ASC-US) improved the selection of women at high risk of CIN2+. Sampling (both cytology and HPV test) was largely performed by midwives (66.7%), followed by obstetricians (23.8%) and nurses (7%). Over half of the centres (54.8%) had full use of online medical records. During the study period, educational activities for professionals and for women were carried out periodically. The organisation of screening as a population activity in which women are actively called to the screening visit and the introduction of HPV testing as a primary screening tool are strongly recommended to ensure the maximum population impact in the reduction of the cervical cancer burden.

Screening of cervical cancer in Catalonia 2006–2012

PubMed Central

de Sanjosé, Silvia; Ibáñez, Raquel; Rodríguez-Salés, Vanesa; Peris, Mercè; Roura, Esther; Diaz, Mireia; Torné, Aureli; Costa, Dolors; Canet, Yolanda; Falguera, Gemma; Alejo, Maria; Espinàs, Josep Alfons; Bosch, F. Xavier

2015-01-01

The early detection of intraepithelial lesions of the cervix, through the periodic examination of cervical cells, has been fundamental for the prevention of invasive cervical cancer and its related mortality. In this report, we summarise the cervical cancer screening activities carried out in Catalonia, Spain, within the National Health System during 2008–2011. The study population covers over two million women resident in the area. The evaluation includes 758,690 cervical cytologies performed on a total of 595,868 women. The three-year coverage of cervical cytology among women aged between 25 and 65 years was 40.8%. About 50% of first screened women with negative results had not returned to the second screening round. The introduction of high-risk human papillomavirus DNA (HPV) detection, as a primary screening cotest with cytology among women over age 40 with a poor screening history, significantly improved the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), being far superior to cytology alone. Cotesting did not improve the detection of CIN2+. The use of the HPV test for the triage of atypical squamous cell undetermined significance (ASC-US) improved the selection of women at high risk of CIN2+. Sampling (both cytology and HPV test) was largely performed by midwives (66.7%), followed by obstetricians (23.8%) and nurses (7%). Over half of the centres (54.8%) had full use of online medical records. During the study period, educational activities for professionals and for women were carried out periodically. The organisation of screening as a population activity in which women are actively called to the screening visit and the introduction of HPV testing as a primary screening tool are strongly recommended to ensure the maximum population impact in the reduction of the cervical cancer burden. PMID:25987901

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2017-06-01

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

[Human papillomavirus testing in cervical cancer screening at a public health service of Santiago, Chile].

PubMed

Terrazas, Solana; Ibáñez, Carolina; Lagos, Marcela; Poggi, Helena; Brañes, Jorge; Barriga, María Isabel; Cartagena, Jaime; Núñez, Felipe; González, Francisca; Cook, Paz; Van De Wyngard, Vanessa; Ferreccio, Catterina

2015-01-01

Molecular techniques for human papillomavirus (HPV) detection have a good performance as screening tests and could be included in cervical cancer early detection programs. We conducted a population-based trial comparing HPV detection and Papanicolaou as primary screening tests, in a public health service in Santiago, Chile. To describe the experience of implementing this new molecular test and present the main results of the study. Women aged 25 to 64 enrolled in three public health centers were invited to participate. In all women, samples were collected for Papanicolaou and HPV DNA testing, and naked-eye visual inspection of the cervix with acetic acid was performed. Women with any positive screening test were referred to the local area hospital for diagnostic confirmation with colposcopy and biopsy of suspicious lesions. Screening results were obtained for 8265 women, of whom 931 (11.3%) were positive to any test. The prevalence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was 1.1%; nine women had invasive cervical cancer. Sensitivities for the detection of CIN2+ were 22.1% (95% confidence interval (CI) 16.4-29.2) for Papanicolaou and 92.7% (95% CI 84.4-96.8) for HPV testing; specificities were 98.9% (95% CI 98.7-99.0) and 92.0% (95% CI 91.4-92.6) respectively. This experience showed that the implementation of a molecular test for cervical cancer screening is not a major challenge in Chile: it was well accepted by both the health team and the participants, and it may improve the effectiveness of the screening program.

Analytic and clinical performance of cobas HPV testing in anal specimens from HIV-positive men who have sex with men.

PubMed

Wentzensen, Nicolas; Follansbee, Stephen; Borgonovo, Sylvia; Tokugawa, Diane; Sahasrabuddhe, Vikrant V; Chen, Jie; Lorey, Thomas S; Gage, Julia C; Fetterman, Barbara; Boyle, Sean; Sadorra, Mark; Tang, Scott Dahai; Darragh, Teresa M; Castle, Philip E

2014-08-01

Anal human papillomavirus (HPV) infections are common, and the incidence of anal cancer is high in HIV-infected men who have sex with men (MSM). To evaluate the performance of HPV assays in anal samples, we compared the cobas HPV test (cobas) to the Roche Linear Array HPV genotyping assay (LA) and cytology in HIV-infected MSM. Cytology and cobas and LA HPV testing were conducted for 342 subjects. We calculated agreement between the HPV assays and the clinical performance of HPV testing and HPV genotyping alone and in combination with anal cytology. We observed high agreement between cobas and LA, with cobas more likely than LA to show positive results for HPV16, HPV18, and other carcinogenic types. Specimens testing positive in cobas but not in LA were more likely to be positive for other markers of HPV-related disease compared to those testing negative in both assays, suggesting that at least some of these were true positives for HPV. cobas and LA showed high sensitivities but low specificities for the detection of anal intraepithelial neoplasia grade 2/3 (AIN2/3) in this population (100% sensitivity and 26% specificity for cobas versus 98.4% sensitivity and 28.9% specificity for LA). A combination of anal cytology and HPV genotyping provided the highest accuracy for detecting anal precancer. A higher HPV load was associated with a higher risk of AIN2/3 with HPV16 (P(trend) < 0.001), HPV18 (P(trend) = 0.07), and other carcinogenic types (P(trend) < 0.001). We demonstrate that cobas can be used for HPV detection in anal cytology specimens. Additional tests are necessary to identify men at the highest risk of anal cancer among those infected with high-risk HPV. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Detection of HPV related oropharyngeal cancer in oral rinse specimens

PubMed Central

Rosenthal, Matthew; Huang, Bin; Katabi, Nora; Migliacci, Jocelyn; Bryant, Robert; Kaplan, Samuel; Blackwell, Timothy; Patel, Snehal; Yang, Liying; Pei, Zhiheng; Tang, Yi-Wei; Ganly, Ian

2017-01-01

Background The majority of patients diagnosed with oropharyngeal squamous cell cancer (OPSCC) are due to HPV infection. At present, there are no reliable tests for screening HPV in patients with OPSCC. The objective of this study was to assess the Cobas® HPV Test on oral rinse specimens as an early, non-invasive tool for HPV-related OPSCC. Methods Oral rinse specimens were collected from 187 patients (45 with OPSCC, 61 with oral cavity SCC (OCSCC) and 81 control patients who had benign or malignant thyroid nodules) treated at MSKCC. The Cobas® HPV Test was used to detect 14 high-risk HPV types in these samples. Performance of the HPV Test was correlated with p16 tumor immunohistochemistry as gold standard. Results 91.1% of the oropharynx cancer patients had p16 positive tumors compared to 3.3% of oral cavity cancer. Of the 81 control patients, 79 (97.5%) had no HPV in their oral rinse giving a specificity of the HPV test of 98%. For the combined oral cavity oropharynx cancer cohort, the sensitivity, specificity, positive predictive value and negative predictive value of the HPV Test were 79.1%, 90.5%, 85.0% and 86.4% respectively when p16 immunohistochemistry was used as the reference. Conclusion The Cobas® HPV Test on oral rinse is a highly specific and potentially sensitive test for oropharyngeal cancer and may be a potentially useful screening test for early oropharyngeal cancer. Impact We describe an oral rinse test for the detection of HPV related oropharyngeal cancer. PMID:29312616

What women want. Women's preferences for the management of low-grade abnormal cervical screening tests: a systematic review.

PubMed

Frederiksen, M E; Lynge, E; Rebolj, M

2012-01-01

If human papillomavirus (HPV) testing will replace cytology in primary cervical screening, the frequency of low-grade abnormal screening tests will double. Several available alternatives for the follow-up of low-grade abnormal screening tests have similar outcomes. In this situation, women's preferences have been proposed as a guide for management decisions. To determine women's preferences for the follow-up of low-grade cervical screening abnormalities. Using Medical Subject Headings (MeSH) terms, PubMed was searched for articles published up to December 2010. The reference lists of the retrieved studies were consulted. Studies asking women to state a preference between active follow-up and observation for the management of low-grade abnormalities on screening cytology or HPV tests. Information on study design, participants and outcomes was retrieved using a prespecified form. Studies were sorted by design. Thirteen studies were included in the review. In all five studies that surveyed women with abnormal tests before any management had started, two-thirds preferred active follow-up, predominantly as immediate colposcopy, to observation, predominantly as repeated Pap smears. In all but two studies testing other situations, women more often expressed a preference for active follow-up than for observation; however, women appeared to be somewhat more willing to accept observation if reassured of the low risk of cervical cancer. Even for low-grade abnormal cervical tests, women tend to prefer active management strategies. It may be a challenge to meet their expectations of optimal follow-up when HPV testing is used in primary screening. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

The Need for Cervical Cancer Control in HIV-Positive and HIV-Negative Women from Romania by Primary Prevention and by Early Detection Using Clinically Validated HPV/DNA Tests.

PubMed

Ursu, Ramona Gabriela; Onofriescu, Mircea; Luca, Alexandru; Prisecariu, Liviu Jany; Sălceanu, Silvia Olivia; Nemescu, Dragoş; Iancu, Luminiţa Smaranda

2015-01-01

In Romania, a country with no organized national surveillance program regarding cervical cancer, the early diagnosis of HPV (Human Papilloma Virus) infections is a major requirement, especially in HIV-infected women. The objective of this study was to determine the HPV prevalence and type distribution in young HIV-positive women and to assess the difference in the risk factors for developing cervical cancer compared to those of HIV-negative women. We conducted one cross-sectional cohort study from June 2013-September 2014, including 1,032 women: 992 HIV- women who were 36.5 years old (limits: 17 ÷ 84) and 40 HIV + women who were 22.9 years old (limits: 17 ÷ 30) with iatrogenic HIV infected. We detected HPV types with the Linear Array HPV Genotyping test (Roche, Romania). DNA/HPV was detected in 18/40 (45%) of the HIV+ patients and in 350/992 (35.2%) of the HIV- patients (OR = 1.5, 95%CI 0.76÷2.96). After age adjustment, the overall HPV prevalence was 51.6% in HIV+ versus 63.2% in HIV- women aged under 25, and 22.2% in HPV+ versus 47.2% in HIV- women aged 25-34. We detect HIV being a risk factor for acquiring multiple HPV type infections (OR = 2.30, 95% CI 0.88÷5.97). The eight most common HPV types (high-risk, and low-risk) for women below age 30, HIV+ / - were: HPV 16, 18, 31, 51, 58, 68, and 6 and 82 respectively. To assess the risk factors of HIV-positive women for acquiring HPV infection, we analyzed the CD4/μL, ARN/HIV copies/μL, the age group, the number of sexual partners, smoking, and the type of HPV infection (single versus multiple infections). We found that the number of sexual partners and smoking are statistically significant risk factors. Even though there are no significant differences regarding the prevalence of HPV infection in HIV + versus HIV - patients, multiple infections were more frequent in the first group. In our study group young HIV-infected patients under HAART therapy, high number of sexual partners (more than 3) and smoking were detected to be risk factors. Future organized screening for HPV infection using sensitive and specific methods are necessary at the national level in Romania.

Evaluation of human papilloma virus (HPV) vaccination strategies and vaccination coverage in adolescent girls worldwide.

PubMed

Owsianka, Barbara; Gańczak, Maria

2015-01-01

An analysis of HPV vaccination strategies and vaccination coverage in adolescent girls worldwide for the last eight years with regard to potential improvement of vaccination coverage rates in Poland. Literature search, covering the period 2006-2014, was performed using Medline. Comparative analysis of HPV vaccination strategies and coverage between Poland and other countries worldwide was conducted. In the last eight years, a number of countries introduced HPV vaccination for adolescent girls to their national immunization programmes. Vaccination strategies differ, consequently affecting vaccination coverage, ranging from several percent to more than 90%. Usually, there are also disparities at national level. The highest HPV vaccination coverage rates are observed in countries where vaccines are administered in school settings and funded from the national budget. Poland is one of the eight EU countries where HPV vaccination has not been introduced to mandatory immunization programme and where paid vaccination is only provided in primary health care settings. HPV vaccination coverage in adolescent girls is estimated at 7.5-10%. Disparities in HPV vaccination coverage rates in adolescent girls worldwide may be due to different strategies of vaccination implementation between countries. Having compared to other countries, the low HPV vaccination coverage in Polish adolescent girls may result from the lack of funding at national level and the fact that vaccines are administered in a primary health care setting. A multidimensional approach, involving the engagement of primary health care and school personnel as well as financial assistance of government at national and local level and the implementation of media campaigns, particularly in regions with high incidence of cervical cancer, could result in an increase of HPV vaccination coverage rates in Poland.

Health Literacy Approaches to Improving Communication between Dental Hygienists and Patients for HPV-Related Oral Cancer Prevention.

PubMed

Thompson, Erika L; Daley, Ellen M; Vamos, Cheryl A; Horowitz, Alice M; Catalanotto, Frank A; DeBate, Rita D; Merrell, Laura K; Griner, Stacey B; Vazquez-Otero, Coralia; Kline, Nolan S

2017-08-01

Purpose: Human Papillomavirus (HPV) has been identified as a causal agent for oropharyngeal cancers, suggesting a new role for dental hygienists in HPV-related cancer prevention strategies. Health literacy assessment is an approach that can be used to understand providers' informational assets and needs for educating and discussing HPV prevention with patients. This study aimed to understand dental hygienists' level of health literacy regarding HPV-related oropharyngeal cancers. Methods: Four focus group sessions with dental hygienists (n=48) were conducted at a national conference. The constant comparison method, with a priori codes for health literacy competencies (i.e., access/understand/appraise/apply), was utilized for this qualitative study. Results: Participants mentioned a variety of modes (e.g., magazines, journals) for accessing HPV-information; however, descriptions of understanding HPV and its relationship to oropharyngeal cancer varied. Participants considered patients' personal characteristics, the dental practice environment, and professional factors to appraise HPV-related information. Additionally, participants self-described themselves as being "prevention specialists." These factors influenced how dental hygienists applied primary and secondary prevention of HPV-related care issues with their patients (e.g., education and oral-cancer screenings). Conclusions: Dental hygienists recognized the importance of HPV and oropharyngeal cancer prevention efforts, including oral-cancer screenings and promotion of the HPV vaccine. The study findings identified opportunities for intervention focusing on primary prevention. Copyright © 2017 The American Dental Hygienists’ Association.

Clinical Significance of an HPV DNA Chip Test with Emphasis on HPV-16 and/or HPV-18 Detection in Korean Gynecological Patients.

PubMed

Yeo, Min-Kyung; Lee, Ahwon; Hur, Soo Young; Park, Jong Sup

2016-07-01

Human papillomavirus (HPV) is a major risk factor for cervical cancer. We evaluated the clinical significance of the HPV DNA chip genotyping assay (MyHPV chip, Mygene Co.) compared with the Hybrid Capture 2 (HC2) chemiluminescent nucleic acid hybridization kit (Digene Corp.) in 867 patients. The concordance rate between the MyHPV chip and HC2 was 79.4% (kappa coefficient, κ = 0.55). The sensitivity and specificity of both HPV tests were very similar (approximately 85% and 50%, respectively). The addition of HPV result (either MyHPV chip or HC2) to cytology improved the sensitivity (95%, each) but reduced the specificity (approximately 30%, each) compared with the HPV test or cytology alone. Based on the MyHPV chip results, the odds ratio (OR) for ≥ high-grade squamous intraepithelial lesions (HSILs) was 9.9 in the HPV-16/18 (+) group and 3.7 in the non-16/18 high-risk (HR)-HPV (+) group. Based on the HC2 results, the OR for ≥ HSILs was 5.9 in the HR-HPV (+) group. When considering only patients with cytological diagnoses of "negative for intraepithelial lesion or malignancy" and "atypical squamous cell or atypical glandular cell," based on the MyHPV chip results, the ORs for ≥ HSILs were 6.8 and 11.7, respectively, in the HPV-16/18 (+) group. The sensitivity and specificity of the MyHPV chip test are similar to the HC2. Detecting HPV-16/18 with an HPV DNA chip test, which is commonly used in many Asian countries, is useful in assessing the risk of high-grade cervical lesions.

HPV testing for cervical cancer screening appears more cost-effective than Papanicolau cytology in Mexico.

PubMed

Flores, Yvonne N; Bishai, David M; Lorincz, Attila; Shah, Keerti V; Lazcano-Ponce, Eduardo; Hernández, Mauricio; Granados-García, Víctor; Pérez, Ruth; Salmerón, Jorge

2011-02-01

To determine the incremental costs and effects of different HPV testing strategies, when compared to Papanicolau cytology (Pap), for cervical cancer screening in Mexico. A cost-effectiveness analysis (CEA) examined the specific costs and health outcomes associated with (1) no screening; (2) only the Pap test; (3) only self-administered HPV; (4) only clinician administered HPV; and (5) clinician administered HPV plus the Pap test. The costs of self- and clinician-HPV testing, as well as with the Pap test, were identified and quantified. Costs were reported in 2008 US dollars. The health outcome associated with these screening strategies was defined as the number of high-grade cervical intraepithelial neoplasia or cervical cancer cases detected. This CEA was performed using the perspective of the Mexican Institute of Social Security (IMSS) in Morelos, Mexico. Screening women between the ages of 30-80 for cervical cancer using clinical-HPV testing or the combination of clinical-HPV testing, and the Pap is always more cost-effective than using the Pap test alone. This CEA indicates that HPV testing could be a cost-effective screening alternative for a large health delivery organization such as IMSS. These results may help policy-makers implement HPV testing as part of the IMSS cervical cancer screening program.

HPV testing for cervical cancer screening appears more cost-effective than Papanicolau cytology in Mexico

PubMed Central

Bishai, David M.; Lőrincz, Attila; Shah, Keerti V.; Lazcano-Ponce, Eduardo; Hernández, Mauricio; Granados-García, Víctor; Pérez, Ruth; Salmerón, Jorge

2010-01-01

Objective To determine the incremental costs and effects of different HPV testing strategies, when compared to Papanicolau cytology (Pap), for cervical cancer screening in Mexico. Methods A cost-effectiveness analysis (CEA) examined the specific costs and health outcomes associated with (1) no screening; (2) only the Pap test; (3) only self-administered HPV; (4) only clinician administered HPV; and (5) clinician administered HPV plus the Pap test. The costs of self- and clinician-HPV testing, as well as with the Pap test, were identified and quantified. Costs were reported in 2008 US dollars. The health outcome associated with these screening strategies was defined as the number of high-grade cervical intraepithelial neoplasia or cervical cancer cases detected. This CEA was performed using the perspective of the Mexican Institute of Social Security (IMSS) in Morelos, Mexico. Results Screening women between the ages of 30–80 for cervical cancer using clinical-HPV testing or the combination of clinical-HPV testing, and the Pap is always more cost-effective than using the Pap test alone. Conclusions This CEA indicates that HPV testing could be a cost-effective screening alternative for a large health delivery organization such as IMSS. These results may help policy-makers implement HPV testing as part of the IMSS cervical cancer screening program. PMID:21170578

Impact of a quadrivalent HPV6/11/16/18 vaccine in Mexican women: public health implications for the region.

PubMed

Lazcano-Ponce, Eduardo; Pérez, Gonzalo; Cruz-Valdez, Aurelio; Zamilpa, Laura; Aranda-Flores, Carlos; Hernández-Nevarez, Pilar; Viramontes, Jose Luis; Salgado-Hernández, Joaquín; James, Margaret; Lu, Shuang; Sattler, Carlos; Haupt, Richard M; Hernández-Avila, Mauricio

2009-08-01

Recognition of human papillomavirus (HPV) as a necessary cause of cervical cancer (CC) led to new perspectives for its control and the demonstration of an effective primary prevention strategy through vaccination. We undertook this study to evaluate the safety, efficacy and immunogenicity of a quadrivalent HPV6/11/16/18 vaccine in Mexican women. A total of 679 Mexican women between 18 and 23 years old participated in two Phase III double-blind, randomized, placebo-controlled clinical trials of a quadrivalent HPV 6/11/16/18 vaccine. Women were enrolled who tested negative for pregnancy and reported having four or less sexual partners during their lifetime. Vaccine or placebo was administered at day 1, month 2 and month 6. Among Mexican women who were naïve to the respective vaccine type at enrollment, the quadrivalent vaccine was highly efficacious, preventing 100% of HPV6/11/16/18-related cervical intraepithelial neoplasia grade 2/3, adenocarcinoma in situ, condyloma and vaginal intraepithelial neoplasia. Statistical significance was not reached for every endpoint due to the limited sample size. Vaccination was generally well tolerated and immunogenic. To widely administer the vaccine, collaborative efforts should be coordinated among public, private and local community sectors. In light of the scarce knowledge of many health professionals with respect to the primary prevention of CC, it will be necessary to educate health providers on the advantages and specific recommendations of HPV vaccines and secondary prevention. Decision making should be based on scientific evidence, allowing health professionals to provide an organized social response that supports the universal right to health.

Theory-based development of an implementation intervention to increase HPV vaccination in pediatric primary care practices.

PubMed

Garbutt, Jane M; Dodd, Sherry; Walling, Emily; Lee, Amanda A; Kulka, Katharine; Lobb, Rebecca

2018-03-13

The national guideline for use of the vaccine targeting oncogenic strains of the human papillomavirus (HPV) is an evidence-based practice that is poorly implemented in primary care. Recommendations include completion of the vaccine series before the 13th birthday for girls and boys, giving the first dose at the 11- to 12-year-old check-up visit, concurrent with other recommended vaccines. Interventions to increase implementation of this guideline have had little impact, and opportunities to prevent cancer continue to be missed. We used a theory-informed approach to develop a pragmatic intervention for use in primary care settings to increase implementation of the HPV vaccine guideline recommendation. Using a concurrent mixed methods design in 10 primary care practices, we applied the Consolidated Framework for Implementation Research (CFIR) to systematically investigate and characterize factors strongly influencing vaccine use. We then used the Behavior Change Wheel (BCW) and the Theoretical Domains Framework (TDF) to analyze provider behavior and identify behaviors to target for change and behavioral change strategies to include in the intervention. We identified facilitators and barriers to guideline use across the five CFIR domains: most distinguishing factors related to provider characteristics, their perception of the intervention, and their process to deliver the vaccine. Targeted behaviors were for the provider to recommend the HPV vaccine the same way and at the same time as the other adolescent vaccines, to answer parents' questions with confidence, and to implement a vaccine delivery system. To this end, the intervention targeted improving provider's capability (knowledge, communication skills) and motivation (action planning, belief about consequences, social influences) regarding implementing guideline recommendations, and increasing their opportunity to do so (vaccine delivery system). Behavior change strategies included providing information and communication skill training with graded tasks and modeling, feedback of coverage rates, goal setting, and social support. These strategies were combined in an implementation intervention to be delivered using practice facilitation, educational outreach visits, and cyclical small tests of change. Using CFIR, the BCW and the TDF facilitated the development of a pragmatic, multi-component implementation intervention to increase use of the HPV vaccine in the primary care setting.

Expression of p16 in squamous cell carcinoma of the mobile tongue is independent of HPV infection despite presence of the HPV-receptor syndecan-1

PubMed Central

Sgaramella, N; Coates, P J; Strindlund, K; Loljung, L; Colella, G; Laurell, G; Rossiello, R; Muzio, L L; Loizou, C; Tartaro, G; Olofsson, K; Danielsson, K; Fåhraeus, R; Nylander, K

2015-01-01

Background: Tongue squamous cell carcinoma (TSCC) is increasing in incidence, especially among young patients and preferably females. Infection with human papilloma virus (HPV) has been suggested as a cause of SCC in the head and neck, and the proportion of oropharyngeal cancers caused by HPV has steadily increased. Methods: Samples from 109 patients with primary TSCC were analysed for the presence of HPV16 by in situ hybridisation and for expression of its surrogate marker p16 and the HPV receptor syndecan-1 by immunhistochemistry. Results: No evidence of HPV16 DNA was observed in the tumours, although one-third showed p16 staining. There was no difference in the expression of the primary HPV receptor, syndecan-1, between TSCC and a group of tonsil SCC. Conclusion: Whereas p16 is expressed in some TSCCs, HPV16 is undetectable, therefore, p16 cannot be used as a surrogate marker for high-risk HPV-infection in this tumour. Despite presence of the HPV-receptor syndecan-1 in TSCC, HPV prefers the tonsillar environment. Lack of p16 associates with worse prognosis primarily in patients aged ⩽40 years with tongue SCC. The improved prognosis seen in p16-positive TSCC can be due to induction of a senescent phenotype or an inherent radiosensitivity due to the ability of p16 to inhibit homologous recombination repair. PMID:26057450

New technologies in cervical cancer precursor detection.

PubMed

Soler, M E; Blumenthal, P D

2000-09-01

The current literature reflects three routes toward improving cervical cancer screening. The first is to improve the test qualities of cytology-based screening. The use of liquid-based cytology and computerized analysis of Papanicolaou tests are examples of attempts at this approach. Secondly, through various combinations of parallel or sequential tests, either the sensitivity or the specificity of a given test could be improved depending on the tests chosen and the order in which they were performed (eg, Papanicolaou test followed by human papillomavirus [HPV] or vice versa). Several excellent studies have been published this year on the use of HPV DNA testing as a primary screening modality and as an adjunct to the triage of mildly abnormal cytologic findings. The recent literature also reflects increasing interest in visual inspection of the cervix and self-collected samples for HPV testing as an equally effective and viable alternative to cytology in low-resource settings. A third possibility is to make use of advances in digital and spectroscopic techniques. In these cost-conscious times, a significant number of articles address the cost-effectiveness of these technologies and the real value of cervical cancer screening. This article reviews the current literature concerning both the advent of new cervical cancer screening technologies and the rediscovery of old ones.

Impact of pap test compliance and cervical cancer screening intervals on human papillomavirus vaccine acceptance.

PubMed

Ferris, Daron G; Waller, Jennifer; Dickinson, Ashley; McCracken, Courtney; Goebel, Angela

2012-01-01

The objective of this study was to determine the impact of Pap test compliance and cervical cancer screening intervals on human papillomavirus (HPV) vaccination acceptance. A convenience sample of 499 women 21 to 65 years old completed a 37-question survey in Augusta and Savannah, GA. The survey assessed their knowledge about HPV, cervical cancer, and the HPV vaccine. The questionnaire also determined their Pap test compliance and how longer Pap test intervals would influence their willingness to receive the HPV vaccine. Differences between categorical variables and knowledge scores were examined using χ test and unequal-variance t tests, respectively. Pap test-noncompliant women were more likely to get the HPV vaccine if they only needed a Pap test every 10 years compared with Pap test-compliant women (27.6% vs 14.6%, p = .02). A greater number (83.5%) of Pap test-noncompliant women preferred the HPV vaccine plus every 10-year Pap test option compared with Pap test-compliant women (31.3%, p < .0001). Most women (87%) responded that they would likely get the HPV vaccine if it would safely reduce the frequency of Pap testing. Women are receptive to getting the HPV vaccine in exchange for longer cervical cancer screening intervals. Moreover, Pap test-noncompliant women are more likely to get the HPV vaccine if Pap testing was needed less frequently. Increasing the Pap testing interval may be an excellent method to improving HPV vaccine acceptance in women at highest risk for cervical cancer.

Rationale and design of the HOME trial: A pragmatic randomized controlled trial of home-based human papillomavirus (HPV) self-sampling for increasing cervical cancer screening uptake and effectiveness in a U.S. healthcare system.

PubMed

Winer, Rachel L; Tiro, Jasmin A; Miglioretti, Diana L; Thayer, Chris; Beatty, Tara; Lin, John; Gao, Hongyuan; Kimbel, Kilian; Buist, Diana S M

2018-01-01

Women who delay or do not attend Papanicolaou (Pap) screening are at increased risk for cervical cancer. Trials in countries with organized screening programs have demonstrated that mailing high-risk (hr) human papillomavirus (HPV) self-sampling kits to under-screened women increases participation, but U.S. data are lacking. HOME is a pragmatic randomized controlled trial set within a U.S. integrated healthcare delivery system to compare two programmatic approaches for increasing cervical cancer screening uptake and effectiveness in under-screened women (≥3.4years since last Pap) aged 30-64years: 1) usual care (annual patient reminders and ad hoc outreach by clinics) and 2) usual care plus mailed hrHPV self-screening kits. Over 2.5years, eligible women were identified through electronic medical record (EMR) data and randomized 1:1 to the intervention or control arm. Women in the intervention arm were mailed kits with pre-paid envelopes to return samples to the central clinical laboratory for hrHPV testing. Results were documented in the EMR to notify women's primary care providers of appropriate follow-up. Primary outcomes are detection and treatment of cervical neoplasia. Secondary outcomes are cervical cancer screening uptake, abnormal screening results, and women's experiences and attitudes towards hrHPV self-sampling and follow-up of hrHPV-positive results (measured through surveys and interviews). The trial was designed to evaluate whether a programmatic strategy incorporating hrHPV self-sampling is effective in promoting adherence to the complete screening process (including follow-up of abnormal screening results and treatment). The objective of this report is to describe the rationale and design of this pragmatic trial. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessing HPV and Cervical Knowledge, Preference and HPV Status Among Urban American Indian Women.

PubMed

Cina, Kristin R; Omidpanah, Adam A; Petereit, Daniel G

2017-10-01

To evaluate whether or not an educational intervention would lead to a change in knowledge and attitudes about human papillomavirus (HPV), HPV vaccines, and cervical cancer. The HPV status was also investigated for interested participants. We provided HPV and cervical cancer education to urban American Indian (AI) women 18 and older using a pre and post-knowledge exam to assess knowledge and attitudes. Women were also given the option to perform vaginal self-tests for high risk HPV (hrHPV) analysis immediately after the education. Ninety-six women participated in our educational sessions. Improvement in performance on a knowledge exam increased from 61.6 to 84.3 percent. Ninety-three women performed the vaginal self-test with 63.1 percent of women preferring vaginal self-testing over conventional screening methods. Thirty-five out of 91 women (38.5 percent) had hrHPV types with 12 of the 35 harboring multiple hrHPV types (13 percent overall). HPV and cervical cancer education was beneficial for urban AI women with the majority of women preferring vaginal self-testing. HPV self-testing may be a strategy to improve screening rates for cervical cancer. Urban AI women had high rates of hrHPV compared to rural AI populations as reported in previous studies.

Sinonasal adenoid cystic carcinoma: Treatment outcomes and association with human papillomavirus.

PubMed

Miller, Eric D; Blakaj, Dukagjin M; Swanson, Benjamin J; Xiao, Weihong; Gillison, Maura L; Wei, Lai; Bhatt, Aashish D; Diavolitsis, Virginia M; Wobb, Jessica L; Kang, Stephen Y; Carrau, Ricardo L; Grecula, John C

2017-07-01

The purpose of this study was to review long-term outcomes of sinonasal adenoid cystic carcinoma (ACC) and to clarify its association with human papillomavirus (HPV). The medical records of 23 patients with sinonasal ACC treated with primary surgical resection between 1998 and 2013 were reviewed. Tissue specimens were available for 17 patients. The p16 testing was performed using immunohistochemistry (IHC), and HPV infection was determined using quantitative polymerase chain reaction (PCR) with primers targeting the E6/E7 region. Two of the 17 samples showed strong and diffuse p16 staining, whereas the remaining 15 cases showed p16-positivity isolated to the luminal cells. Only one of the p16-positive cases was positive for HPV. The 5-year local failure, disease-free survival (DFS), and overall survival (OS) were 51%, 52%, and 62%, respectively. Local failures are common with advanced sinonasal ACC, and the association of HPV with true sinonasal ACC is low. © 2017 Wiley Periodicals, Inc.

A randomized controlled trial in non-responders from Newcastle upon Tyne invited to return a self-sample for Human Papillomavirus testing versus repeat invitation for cervical screening.

PubMed

Cadman, Louise; Wilkes, Scott; Mansour, Diana; Austin, Janet; Ashdown-Barr, Lesley; Edwards, Rob; Kleeman, Michelle; Szarewski, Anne

2015-03-01

Non-attenders for cervical screening are at increased risk of cervical cancer. Studies offering self-sampling for high-risk Human Papillomavirus (HrHPV) testing have shown greater uptake than sending another invitation for cytology. To explore whether uptake would increase in a less diverse, more stable population than the previous English study, which demonstrated a lower response rate than other studies. The primary objective was whether non-attenders were more likely to respond to a postal invitation, including kit, to collect a self-sample compared with a further invitation for cytology screening. The secondary objective was whether women with an abnormal result would attend for follow-up. 6000 non-attenders for screening in this pragmatic, randomized (1:1) controlled trial in Newcastle-upon-Tyne were sent an HPV self-sample kit (intervention) or a further invitation for cytology screening (comparator). 411(13%) responded to the intervention, returning a self-sample (247(8%)) or attending for cytology (164(5%)), compared with 183(6%) attending for cytology, relative risk 2.25 (95% CI 1.90-2.65) (comparator arm). Of those testing hrHPV positive (32(13%)), 19(59%) subsequently attended cytology screening. Of those in the intervention group who attended for cytology screening without returning an hrHPV self-sample (n = 164), 5% (n = 8) were referred for colposcopy - all attended. In the comparator group eight of the nine referred for colposcopy attended. Persistent non-responders to invitations for cervical screening are significantly more likely to respond to a postal invitation to return a self-collected sample for HPV testing than a further invitation for cytology screening. However, just over half followed up on this positive HPV result. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Human Papilloma Virus in Melanoma Biopsy Specimens and Its Relation to Melanoma Progression

PubMed Central

Dréau, Didier; Culberson, Cathy; Wyatt, Sharon; Holder, Walter D.

2000-01-01

Objectives To evaluate melanoma biopsy specimens for human papilloma virus (HPV) and determine the relation between the presence of HPV, in vitro growth, and clinical progression of melanoma in the patients from whom the biopsy specimens were derived. Summary Background Data Ultraviolet radiation from sun exposure appears to be the primary causal agent in the development of cutaneous melanoma. However, other agents, including HPV, as observed in different epithelial carcinomas, may also play a role in melanoma development and progression. Methods Twelve melanoma biopsy specimens obtained from 12 patients with AJCC stage III and IV melanoma were stained with antibodies against gp-100 (HMB-45) and S-100 protein to confirm melanoma diagnosis and with a polyclonal HPV antibody. After mechanical dissociation, the melanoma specimen cells’ ability to grow in vitro was assessed. Patients were evaluated for melanoma progression with physical examination, complete blood count, and liver function tests every 3 months and a chest radiograph every 6 months. Results All biopsy specimens were positive for S-100, and nine (75%) were positive for gp-100. Seven of 12 (58%) were positive for HPV by immunohistochemistry. In vitro, none of the HPV-negative tumor cells grew from the tumor biopsies, whereas five of seven (71%) of the HPV-positive melanoma tumor cells grew very well. All patients with HPV-positive tumor cells had recurrences and died of melanoma progression, whereas four of five (80%) patients with HPV-negative tumor cells remained alive and without melanoma recurrence. Conclusions The presence of HPV was found in 58% of the biopsy specimens obtained from patients with stage III and IV melanoma and correlated with rapid melanoma progression. HPV may serve as a cofactor in the development of melanoma and may modulate a more aggressive phenotype in HPV-containing melanoma cells. PMID:10767787

[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.

Prevention of HPV-Related Oral Cancer by Dentists: Assessing the Opinion of Dutch Dental Students.

PubMed

Poelman, Marcella R; Brand, Henk S; Forouzanfar, Thymour; Daley, Ellen M; Jager, Derk H Jan

2017-07-24

The aim of this study is to assess dental students' opinions of the dentists' role in primary prevention of human papillomavirus (HPV)-related oral cancer using a cross-sectional web-based survey. A questionnaire, containing questions about knowledge of HPV and oral cancer, confidence in head and neck examination and role of the dentist in preventing HPV-related oral cancer, was sent to all students of the Academic Centre of Dentistry Amsterdam (n = 912). One hundred and twenty-six (n = 126) students completed the questionnaire. Significantly, more master students (75%) than bachelor students (54.3%) were aware that HPV is a causative factor for oral cancer. Master students had more knowledge of HPV than bachelor students, but knowledge about HPV vaccination was irrespective of the study phase. The majority of dental students agreed that it is important to discuss HPV vaccination with patients. Eighty-nine percent of the students think that more education about symptoms of oral cancer will increase screening for oral cancer. Development of a protocol for screening in dental practices was considered even more important. According to dental students, dentists should discuss HPV as a risk factor for oral cancer with patients. Future dentists are willing to be involved in both primary and secondary prevention of HPV-related oral cancer. Therefore, screening for oral cancer and education about HPV vaccination should be integral elements of the dental curriculum.

HPV Testing of Head and Neck Cancer in Clinical Practice.

PubMed

Robinson, Max

The pathology laboratory has a central role in providing human papillomavirus (HPV) tests for patients with head and neck cancer. There is an extensive literature around HPV testing and a large number of proprietary HPV tests, which makes the field difficult to navigate. This review provides a concise contemporary overview of the evidence around HPV testing in head and neck cancer and signposts key publications, guideline documents and the most commonly used methods in clinical practice.

Human Papilloma Virus (HPV) Oral Prevalence in Scotland (HOPSCOTCH): A Feasibility Study in Dental Settings

PubMed Central

Conway, David I.; Robertson, Chris; Gray, Heather; Young, Linda; McDaid, Lisa M.; Winter, Andrew J.; Campbell, Christine; Pan, Jiafeng; Kavanagh, Kimberley; Kean, Sharon; Bhatia, Ramya; Cubie, Heather; Clarkson, Jan E.; Bagg, Jeremy; Pollock, Kevin G.; Cuschieri, Kate

2016-01-01

The purpose of this study was to test the feasibility of undertaking a full population investigation into the prevalence, incidence, and persistence of oral Human Papilloma Virus (HPV) in Scotland via dental settings. Male and female patients aged 16–69 years were recruited by Research Nurses in 3 primary care and dental outreach teaching centres and 2 General Dental Practices (GDPs), and by Dental Care Teams in 2 further GDPs. Participants completed a questionnaire (via an online tablet computer or paper) with socioeconomic, lifestyle, and sexual history items; and were followed up at 6-months for further questionnaire through appointment or post/online. Saline oral gargle/rinse samples, collected at baseline and follow-up, were subject to molecular HPV genotyping centrally. 1213 dental patients were approached and 402 individuals consented (participation rate 33.1%). 390 completed the baseline questionnaire and 380 provided a baseline oral specimen. Follow-up rate was 61.6% at 6 months. While recruitment was no different in Research Nurse vs Dental Care Team models the Nurse model ensured more rapid recruitment. There were relatively few missing responses in the questionnaire and high levels of disclosure of risk behaviours (99% answered some of the sexual history questions). Data linkage of participant data to routine health records including HPV vaccination data was successful with 99.1% matching. Oral rinse/gargle sample collection and subsequent HPV testing was feasible. Preliminary analyses found over 95% of samples to be valid for molecular HPV detection prevalence of oral HPV infection of 5.5% (95%CI 3.7, 8.3). It is feasible to recruit and follow-up dental patients largely representative / reflective of the wider population, suggesting it would be possible to undertake a study to investigate the prevalence, incidence, and determinants of oral HPV infection in dental settings. PMID:27861508

Human Papilloma Virus (HPV) Oral Prevalence in Scotland (HOPSCOTCH): A Feasibility Study in Dental Settings.

PubMed

Conway, David I; Robertson, Chris; Gray, Heather; Young, Linda; McDaid, Lisa M; Winter, Andrew J; Campbell, Christine; Pan, Jiafeng; Kavanagh, Kimberley; Kean, Sharon; Bhatia, Ramya; Cubie, Heather; Clarkson, Jan E; Bagg, Jeremy; Pollock, Kevin G; Cuschieri, Kate

2016-01-01

The purpose of this study was to test the feasibility of undertaking a full population investigation into the prevalence, incidence, and persistence of oral Human Papilloma Virus (HPV) in Scotland via dental settings. Male and female patients aged 16-69 years were recruited by Research Nurses in 3 primary care and dental outreach teaching centres and 2 General Dental Practices (GDPs), and by Dental Care Teams in 2 further GDPs. Participants completed a questionnaire (via an online tablet computer or paper) with socioeconomic, lifestyle, and sexual history items; and were followed up at 6-months for further questionnaire through appointment or post/online. Saline oral gargle/rinse samples, collected at baseline and follow-up, were subject to molecular HPV genotyping centrally. 1213 dental patients were approached and 402 individuals consented (participation rate 33.1%). 390 completed the baseline questionnaire and 380 provided a baseline oral specimen. Follow-up rate was 61.6% at 6 months. While recruitment was no different in Research Nurse vs Dental Care Team models the Nurse model ensured more rapid recruitment. There were relatively few missing responses in the questionnaire and high levels of disclosure of risk behaviours (99% answered some of the sexual history questions). Data linkage of participant data to routine health records including HPV vaccination data was successful with 99.1% matching. Oral rinse/gargle sample collection and subsequent HPV testing was feasible. Preliminary analyses found over 95% of samples to be valid for molecular HPV detection prevalence of oral HPV infection of 5.5% (95%CI 3.7, 8.3). It is feasible to recruit and follow-up dental patients largely representative / reflective of the wider population, suggesting it would be possible to undertake a study to investigate the prevalence, incidence, and determinants of oral HPV infection in dental settings.

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

PubMed Central

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

2011-01-01

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

Performance of a New HPV Cervi-Collect Collection and Transportation Kit

PubMed Central

Chernesky, M.; Huang, S.; Jang, D.; Erickson, B.; Salituro, J.; Engel, H.; Gilchrist, J.; Neuscheler, P.; Mak, W. B.; Abravaya, K.

2012-01-01

Background. Liquid-based Pap (L-Pap) media are used for Pap and human papillomavirus (HPV) testing. Objectives. To compare RealTime High Risk (HR) HPV testing of a new collection kit (Cervi-Collect) and PreservCyt L-Pap specimens. To determine ease of use and safety of Cervi-Collect. Methods. L-Pap samples (n = 203) were tested with HC2 and RealTime HR HPV and Cervi-Collect with RealTime HR HPV. Discordant samples were genotyped. Results. L-Pap and Cervi-Collect specimens tested by RealTime HR HPV showed 93.1% agreement (Kappa 0.86). RealTime HR HPV and HC2 on L-Pap had 90.3% agreement (Kappa 0.80). RealTime HR HPV on Cervi-Collect and HC2 on L-Pap showed 88.2% agreement (Kappa 0.76). Sixteen of 21 samples which were HC2 negative and RealTime HR HPV positive on L-Pap or Cervi-Collect contained HR HPV genotypes. Eleven healthcare collectors were in strong agreement on a usability and safety questionnaire. Conclusion. Cervi-Collect samples were easy to collect and showed strong agreement with L-Pap samples tested with RealTime HR HPV or HC2. PMID:22174716

HPV Virus Transcriptional Status Assessment in a Case of Sinonasal Carcinoma.

PubMed

Ilardi, Gennaro; Russo, Daniela; Varricchio, Silvia; Salzano, Giovanni; Dell'Aversana Orabona, Giovanni; Napolitano, Virginia; Di Crescenzo, Rosa Maria; Borzillo, Alessandra; Martino, Francesco; Merolla, Francesco; Mascolo, Massimo; Staibano, Stefania

2018-03-16

Human Papilloma Virus (HPV) can play a causative role in the development of sinonasal tract malignancies. In fact, HPV may be the most significant causative agent implicated in sinonasal tumorigenesis and is implicated in as many as 21% of sinonasal carcinomas. To date, there are no definitive, reliable and cost-effective, diagnostic tests approved by the FDA for the unequivocal determination of HPV status in head and neck cancers. We followed an exhaustive algorithm to correctly test HPV infection, including a sequential approach with p16INK4a IHC, viral DNA genotyping and in situ hybridization for E6/E7 mRNA. Here, we report a case of sinonasal carcinoma with discordant results using HPV test assays. The tumor we describe showed an irregular immunoreactivity for p16INK4a, and it tested positive for HPV DNA; nevertheless, it was negative for HR-HPV mRNA. We discuss the possible meaning of this discrepancy. It would be advisable to test HPV transcriptional status of sinonasal carcinoma on a diagnostic routine basis, not only by p16INK4a IHC assay, but also by HPV DNA genotyping and HR-HPV mRNA assessment.

Tobacco use in HPV-positive advanced oropharynx cancer patients related to increased risk of distant metastases and tumor recurrence

PubMed Central

Maxwell, Jessica Hooton; Kumar, Bhavna; Feng, Felix Y.; Worden, Francis P.; Lee, Julia; Eisbruch, Avraham; Wolf, Gregory T.; Prince, Mark E.; Moyer, Jeffrey S.; Teknos, Theodoros N.; Chepeha, Douglas B.; McHugh, Jonathan B.; Urba, Susan; Stoerker, Jay; Walline, Heather; Kurnit, David; Cordell, Kitrina G.; Davis, Samantha J.; Ward, Preston D.; Bradford, Carol R.; Carey, Thomas E.

2009-01-01

Purpose The goal of this study was to examine the effect of tobacco use on disease recurrence (local/regional recurrence, distant metastasis, or second primary) among HPV-positive patients with squamous cell carcinoma of the oropharynx (SCCOP) following a complete response to chemoradiation therapy. Experimental Design Between 1999 and 2007, 124 patients with advanced SCCOP (86% with stage IV) and adequate tumor tissue for HPV analysis who were enrolled in one of two consecutive University of Michigan treatment protocols were prospectively included in this study. Patients were categorized as never, former, or current tobacco users. The primary end-points were risk of disease recurrence and time to recurrence; secondary end-points were disease-specific survival and overall survival. Results One hundred and two patients (82.3%) had HPV-positive tumors. Over two-thirds (68%) of patients with HPV-positive tumors were tobacco users. Among HPV-positive patients, current tobacco users were at significantly higher risk of disease recurrence than never-tobacco users (hazard ratio = 5.2; confidence interval [1.1-24.4]; p=0.038). Thirty-five percent of HPV-positive ever tobacco users recurred compared to only 6% of HPV-positive never users and 50% of HPV-negative patients. All HPV-negative patients were tobacco users and had significantly shorter times to recurrence (p=0.002) and reduced disease-specific survival (p=0.004) and overall survival (p<0.001) compared to HPV-positive patients. Compared to HPV-positive never-tobacco users, those with a tobacco history showed a trend for reduced disease-specific survival (p=0.064) but not overall survival (p=0.221). Conclusion Current tobacco users with advanced, HPV-positive SCCOP are at higher risk of disease recurrence compared to never-tobacco users. PMID:20145161

Molecular Pap smear: HPV genotype and DNA methylation of ADCY8, CDH8, and ZNF582 as an integrated biomarker for high-grade cervical cytology.

PubMed

Shen-Gunther, Jane; Wang, Chiou-Miin; Poage, Graham M; Lin, Chun-Lin; Perez, Luis; Banks, Nancy A; Huang, Tim Hui-Ming

2016-01-01

The Pap smear has remained the foundation for cervical cancer screening for over 70 years. With advancements in molecular diagnostics, primary high-risk human papillomavirus (hrHPV) screening has recently become an accepted stand-alone or co-test with conventional cytology. However, both diagnostic tests have distinct limitations. The aim of this study was to determine the association between HPV genotypes and cellular epigenetic modifications in three grades of cervical cytology for screening biomarker discovery. This prospective, cross-sectional study used residual liquid-based cytology samples for HPV genotyping and epigenetic analysis. Extracted DNA was subjected to parallel polymerase chain reactions using three primer sets (MY09/11, FAP59/64, E6-E7 F/B) for HPV DNA amplification. HPV+ samples were genotyped by DNA sequencing. Promoter methylation of four candidate tumor suppressor genes (adenylate cyclase 8 (ADCY8), cadherin 8, type 2 (CDH8), MGMT, and zinc finger protein 582 (ZNF582)) out of 48 genes screened was quantified by bisulfite-pyrosequencing of genomic DNA. Independent validation of methylation profiles was performed by analyzing data from cervical cancer cell lines and clinical samples from The Cancer Genome Atlas (TCGA). Two hundred seventy-seven quality cytology samples were analyzed. HPV was detected in 31/100 (31 %) negative for intraepithelial lesion or malignancy (NILM), 95/100 (95 %) low-grade squamous intraepithelial lesion (LSIL), and 71/77 (92 %) high-grade squamous intraepithelial lesion (HSIL) samples. The proportion of IARC-defined carcinogenic HPV types in sequenced samples correlated with worsening grade: NILM 7/29 (24 %), LSIL 53/92 (58 %), and HSIL 65/70 (93 %). Promoter methylation of ADCY8, CDH8, and ZNF582 was measured in 170 samples: NILM (N = 33), LSIL (N = 70), and HSIL (N = 67) also correlated with worsening grade. Similar hypermethylation patterns were found in cancer cell lines and TCGA samples. The combination of four biomarkers, i.e., HPV genotype and three-gene promoter methylation, predicted HSIL (AUC 0.89) better than HPV alone (AUC 0.74) by logistic regression and probabilistic modeling. HPV genotype and DNA methylation of ADCY8, CDH8, and ZNF582 are correlated with cytological grade. Collectively, these biomarkers may serve as a molecular classifier of Pap smears.

High risk HPV testing following treatment for cervical intraepithelial neoplasia.

PubMed

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

2016-11-01

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

The effect of a booster dose of quadrivalent or bivalent HPV vaccine when administered to girls previously vaccinated with two doses of quadrivalent HPV vaccine.

PubMed

Gilca, Vladimir; Sauvageau, Chantal; Boulianne, Nicole; De Serres, Gatson; Crajden, Mel; Ouakki, Manale; Trevisan, Andrea; Dionne, Marc

2015-01-01

This randomized, blinded study evaluated the immunogenicity and safety of a booster dose of Gardasil (qHPV) or Cervarix (bHPV) when administered to 12-13 year-old girls who were vaccinated at the age of 9-10 with 2 doses of qHPV (0-6 months). 366 out of 416 eligible girls participated in this follow-up study. Antibody titers were measured just before and one month post-booster. A Luminex Total IgG assay was used for antibody assessment and results are presented in Liminex Units (LU). Three years post-primary vaccination, 99-100% of subjects had detectable antibodies to 4HPV genotypes included in the qHPV with GMTs varying from 50 to 322 LU depending on genotype. After a booster dose of qHPV, a ≥4 fold increase of antibody titers to genotypes included in the vaccine was observed in 88-98% of subjects. Post-booster GMTs varied from 1666 to 4536 LU depending on genotype. These GMTs were 1.1 to 1.8-fold higher when compared to those observed one month post-second dose. After a booster of bHPV, a ≥4 fold increase of antibody titers to HPV16 and HPV18 was observed in 93-99% of subjects. The anti-HPV16 and HPV18 GMTs were 5458 and 2665 LU, respectively. These GMTs were 1.2 and 1.8 higher than those observed in the qHPV group (both P < 0.01). In bHPV group a 1.4-1.6-fold increase of antibody GMTs to HPV6 and HPV11was also observed (P < 0.001). The safety profile was acceptable for both vaccines. Both qHPV and bHPV increase antibody titers when given as a booster to girls previously vaccinated with 2 doses of qHPV. The magnitude of the immune response after booster is vaccine-dependent and has the same pattern as that reported after primary vaccination with qHPV or bHPV. When given as a booster, both vaccines have an acceptable safety profile. Longer follow-up studies are warranted to assess the need of booster doses.

Rationale and design of the research project of the South Florida Center for the Reduction of Cancer Health Disparities (SUCCESS): study protocol for a randomized controlled trial.

PubMed

Carrasquillo, Olveen; McCann, Sheila; Amofah, Antony; Pierre, Larry; Rodriguez, Brendaly; Alonzo, Yisel; Ilangovan, Kumar; Gonzalez, Martha; Trevil, Dinah; Byrne, Margaret M; Koru-Sengul, Tulay; Kobetz, Erin

2014-07-23

In the United States certain minority groups, such as racial/ethnic immigrant women, are less likely than non-Hispanic White women to be screened for cervical cancer. Barriers to such care include health insurance, cost, knowledge, attitudes, health literacy, and cultural norms and practices. Among the most promising approaches to increase screening in these groups are patient navigators that can link women to sources of appropriate care. Another recent promising approach is using human papilloma virus (HPV) self-sampling. In this manuscript, we describe our National Cancer Institute-sponsored study testing such approaches among immigrant minority women. The South Florida Center for the Reduction of Cancer Health Disparities (SUCCESS) is conducting a three-arm randomized trial among Hispanic, Haitian, and African American women in Miami-Dade County. Community health workers (CHW) based in each of three communities are recruiting 200 women at each site (600 total). Eligibility criteria include women aged 30-65 years who have not had a Pap smear test in the last 3 years. Prior to randomization, all women undergo a standardized structured interview. Women randomized to public health outreach, Group 1, receive culturally tailored educational materials. Women in Group 2 receive an individualized comprehensive cervical cancer CHW-led education session followed by patient navigation to obtain the Pap smear test at community-based facilities. Women in Group 3 have the option of navigation to a Pap smear test or performing HPV self-sampling. The primary outcome is self-report of completed screening through a Pap smear test or HPV self-sampling within 6 months after enrollment. SUCCESS is one of the first trials testing HPV self-sampling as a screening strategy among underserved minority women. If successful, HPV self-sampling may be an important option in community outreach programs aimed at reducing disparities in cervical cancer. Clinical Trials.gov # NCT02121548, registered April 21, 2014.

High prevalence of human papillomavirus infection in American Indian women of the Northern Plains

PubMed Central

Bell, Maria C.; Schmidt-Grimminger, Delf; Patrick, Sarah; Ryschon, Tim; Linz, Laurie; Chauhan, Subhash C.

2008-01-01

Objectives Cervical cancer is the leading gynecological malignancy worldwide, and the incidence of this disease is very high in American Indian women. Infection with the Human Papillomavirus (HPV) is responsible for more than 95% of cervical squamous carcinomas. Therefore, the main objective of this study was to analyze oncogenic HPV infections in American Indian women residing in the Northern Plains. Methods Cervical samples were collected from 287 women attending a Northern Plains American Indian reservation outpatient clinic. DNA was extracted from the cervical samples and HPV specific DNA were amplified by polymerase chain reaction (PCR) using the L1 consensus primer sets. The PCR products were hybridized with the Roche HPV Line Blot assay for HPV genotyping to detect 27 different low and high-risk HPV genotypes. The chi-square test was performed for statistical analysis of the HPV infection and cytology diagnosis data. Results Of the total 287 patients, 61 women (21.25%) tested positive for HPV infection. Among all HPV-positive women, 41 (67.2%) were infected with high-risk HPV types. Of the HPV infected women, 41% presented with multiple HPV genotypes. Additionally, of the women infected with oncogenic HPV types, 20 (48.7%) were infected with HPV 16 and 18 and the remaining 21 (51.3%) were infected with other oncogenic types (i.e., HPV59, 39, 73). Women infected with oncogenic HPV types had significantly higher (p=0.001) abnormal Papanicolaou smear tests (Pap test) compared to women who were either HPV negative or positive for non-oncogenic HPV types. The incidence of HPV infection was inversely correlated (p<0.05) with the age of the patients, but there was no correlation (p=0.33) with seasonal variation. Conclusions In this study, we observed a high prevalence of HPV infection in American Indian women residing on Northern Plains Reservations. In addition, a significant proportion of the oncogenic HPV infections were other than HPV16 and 18. PMID:17659767

Understanding Clinic Practices for Human Papilloma Virus Vaccination Series Completion in Clinics That Provide Primary Care: Survey of Clinic Managers in Iowa.

PubMed

Askelson, Natoshia M; Edmonds, Stephanie W; Momany, Elizabeth T; Tegegne, Mesay A

2016-07-01

Rates for human papilloma virus (HPV) vaccination are low across the United States. Evidence-based-practices to increase immunization coverage have been recommended by public health organizations, yet many primary care clinics do not follow these practices. The purpose of this study was to examine if primary care clinics use these best practices to promote completion of the HPV vaccine series for their adolescent patients. Understanding the prevalence of evidence-based immunization strategies is key to increasing vaccination coverage. We mailed 914 surveys to clinic managers of clinics that provide primary care in Iowa. The survey content was based on immunization strategies related to clinic practice and policies that have been proven effective to promote the completion of the HPV vaccination series. Survey responses from 127 clinics were used in the final analysis. Most clinics always used the state's immunization information system to record HPV vaccinations (89.4%). Over a quarter of clinics (27.6%) did not use any type of reminder or recall system to alert parents or providers that an HPV vaccine was due, and 35.0% did not give the vaccine at sick visits. Clinics need to focus more on the recommended logistics and processes to ensure that patients receive the entire HPV vaccination series. Survey results indicate that clinics are not consistently implementing the recommended best practices to ensure that vaccination series are completed.

Human papillomavirus (HPV) persistence and HPV 31 predict the risk of recurrence in high-grade vaginal intraepithelial neoplasia.

PubMed

Bogani, Giorgio; Martinelli, Fabio; Ditto, Antonino; Taverna, Francesca; Lombardo, Claudia; Signorelli, Mauro; Chiappa, Valentina; Leone Roberti Maggiore, Umberto; Fontanella, Caterina; Sabatucci, Ilaria; Borghi, Chiara; Recalcati, Dario; Indini, Alice; Lorusso, Domenica; Raspagliesi, Francesco

2017-03-01

High-grade vaginal intraepithelial neoplasia (vaginal HSIL) represents an uncommon entity. Here, we sought to identify predictors for recurrence and risk factor for developing genital cancers after primary treatment for vaginal HSIL. Data of consecutive 5104 women who had human papillomavirus (HPV) DNA test were searched for identify women with histological confirmed vaginal HSIL. Disease-free interval and the risk of developing HPV-related gynecological cancers were assessed using Kaplan-Meier and Cox proportional hazard models. Overall, 77 patients were included. After a mean (SD) follow-up of 69.3 (33.0) months, 11 (14%) and 4 (5%) patients experienced vaginal HSIL recurrence and the occurrence of HPV-related gynecological cancers, respectively. Via multivariate analysis factors predicting for vaginal HSIL recurrence were infection from HPV31 at diagnosis (HR: 5.0 (95%CI:1.17, 21.3); p=0.03) and persistence of HPV infection after treatment (HR: 7.0 (95%CI:1.54, 31.6); p=0.01). Additionally, patients who had LASER ablation experienced a trend toward a lower risk of recurrence in comparison to medical treatment (HR: 0.20 (95%CI:0.03, 1.09); p=0.06). Considering the occurrence of HPV-related gynecological cancers, we observed that no factors independently correlated with this risk; while, a trend towards higher risk was observed for women with HIV infection (HR:16.4 (95%CI:0.90, 300.1); p=0.06) and persistence of HPV infection (HR: 13.3 (95%CI:0.76, 230.2); p=0.07). Patients affected by vaginal HSIL experienced a relatively high risk of recurrence. Persistence of HPV after treatment and pretreatment HPV-31 infection predicts for high-grade vaginal intraepithelial neoplasia recurrence. Further investigations are warranted in order to corroborate our data. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Therapy of Human Papillomavirus-Related Disease

PubMed Central

Stern, Peter L.; van der Burg, Sjoerd H.; Hampson, Ian N.; Broker, Thomas; Fiander, Alison; Lacey, Charles J.; Kitchener, Henry C.; Einstein, Mark H.

2014-01-01

This chapter reviews the current treatment of chronic and neoplastic HPV-associated conditions and the development of novel therapeutic approaches. Surgical excision of HPV-associated lower genital tract neoplasia is very successful but largely depends on secondary prevention programmes for identification of disease. Only high-risk HPV-driven chronic, preneoplastic lesions and some very early cancers cannot be successfully treated by surgical procedures alone. Chemoradiation therapy of cervical cancer contributes to the 66–79% cervical cancer survival at 5 years. Outlook for those patients with persistent or recurrent cervical cancer following treatment is very poor. Topical agents such as imiquimod (immune response modifier), cidofovir (inhibition of viral replication; induction apoptosis) or photodynamic therapy (direct damage of tumour and augmentation of anti-tumour immunity) have all shown some useful efficacy (~50–60%) in treatment of high grade vulvar intraepithelial neoplasia. Provider administered treatments of genital warts include cryotherapy, trichloracetic acid, or surgical removal which has the highest primary clearance rate. Patient applied therapies include podophyllotoxin and imiquimod. Recurrence after “successful” treatment is 30–40%. Further improvements could derive from a rational combination of current therapy with new drugs targeting molecular pathways mediated by HPV in cancer. Small molecule inhibitors targeting the DNA binding activities of HPV E1/E2 or the anti-apoptotic consequences of E6/E7 oncogenes are in preclinical development. Proteasome and histone deacetylase inhibitors, which can enhance apoptosis in HPV positive tumour cells, are being tested in early clinical trials. Chronic high-risk HPV infection/neoplasia is characterised by systemic and/or local immune suppressive regulatory or escape factors. Recently two E6/E7 vaccines have shown some clinical efficacy in high grade VIN patients and this correlated with strong and broad systemic HPV-specific T cell response and modulation of key local immune factors. Treatments that can shift the balance of immune effectors locally in combination with vaccination are now being tested. This article forms part of a special supplement entitled “Opportunities for comprehensive control of HPV infections and related diseases” Vaccine Volume 30, Supplement X, 2012. PMID:23199967

Barriers and facilitators to HPV vaccination in primary care practices: a mixed methods study using the Consolidated Framework for Implementation Research.

PubMed

Garbutt, Jane M; Dodd, Sherry; Walling, Emily; Lee, Amanda A; Kulka, Katharine; Lobb, Rebecca

2018-05-07

In the United States, the effective, safe huma papilloma virus (HPV) vaccine is underused and opportunities to prevent cancer continue to be missed. National guidelines recommend completing the 2-3 dose HPV vaccine series by age 13, well before exposure to the sexually transmitted virus. Accurate characterization of the facilitators and barriers to full implementation of HPV vaccine recommendations in the primary care setting could inform effective implementation strategies. We used the Consolidated Framework for Implementation Research (CFIR) to systematically investigate and characterize factors that influence HPV vaccine use in 10 primary care practices (16 providers) using a concurrent mixed methods design. The CFIR was used to guide collection and analysis of qualitative data collected through in-person semi-structured interviews with the primary care providers. We analyzed HPV vaccine use with data abstracted from medical charts. Constructs that most strongly influenced vaccine use were identified by integrating the qualitative and quantitative data. Of the 72 CFIR constructs assessed, seven strongly distinguished and seven weakly distinguished between providers with higher versus lower HPV vaccine coverage. The majority of strongly distinguishing constructs were facilitators and were related to characteristics of the providers (knowledge and beliefs; self-efficacy; readiness for change), their perception of the intervention (relative advantage of vaccinating younger vs. older adolescents), and their process to deliver the vaccine (executing). Additional weakly distinguishing constructs that were facilitators were from outer setting (peer pressure; financial incentives), inner setting (networks and communications and readiness for implementation) and process (planning; engaging, and reflecting and evaluating). Two strongly distinguishing constructs were barriers to use, one from the intervention (adaptability of the age of initiation) and the other from outer setting (patient needs and resources). Using CFIR to systematically examine the use of this vaccine in independent primary care practices enabled us to identify facilitators and barriers at the provider, interpersonal and practice level that need to be addressed in future efforts to increase vaccine use in such settings. Our findings suggest that implementation strategies that target the provider and help them to address multi-level barriers to HPV vaccine use merit further investigation.

HPV-16 E7 expression up-regulates phospholipase D activity and promotes rapamycin resistance in a pRB-dependent manner.

PubMed

Rabachini, Tatiana; Boccardo, Enrique; Andrade, Rubiana; Perez, Katia Regina; Nonogaki, Suely; Cuccovia, Iolanda Midea; Villa, Luisa Lina

2018-04-27

Human Papillomavirus (HPV) infection is the main risk factor for the development and progression of cervical cancer. HPV-16 E6 and E7 expression is essential for induction and maintenance of the transformed phenotype. These oncoproteins interfere with the function of several intracellular proteins, including those controlling the PI3K/AKT/mTOR pathway in which Phospolipase D (PLD) and Phosphatidic acid (PA) play a critical role. PLD activity was measured in primary human keratinocytes transduced with retroviruses expressing HPV-16 E6, E7 or E7 mutants. The cytostatic effect of rapamycin, a well-known mTOR inhibitor with potential clinical applications, was evaluated in monolayer and organotypic cultures. HPV-16 E7 expression in primary human keratinocytes leads to an increase in PLD expression and activity. Moreover, this activation is dependent on the ability of HPV-16 E7 to induce retinoblastoma protein (pRb) degradation. We also show that cells expressing HPV-16 E7 or silenced for pRb acquire resistance to the antiproliferative effect of rapamycin. This is the first indication that HPV oncoproteins can affect PLD activity. Since PA can interfere with the ability of rapamycin to bind mTOR, the use of combined strategies to target mTOR and PLD activity might be considered to treat HPV-related malignancies.

Validation of a Human Papillomavirus (HPV) DNA Cervical Screening Test That Provides Expanded HPV Typing.

PubMed

Demarco, Maria; Carter-Pokras, Olivia; Hyun, Noorie; Castle, Philip E; He, Xin; Dallal, Cher M; Chen, Jie; Gage, Julia C; Befano, Brian; Fetterman, Barbara; Lorey, Thomas; Poitras, Nancy; Raine-Bennett, Tina R; Wentzensen, Nicolas; Schiffman, Mark

2018-05-01

As cervical cancer screening shifts from cytology to human papillomavirus (HPV) testing, a major question is the clinical value of identifying individual HPV types. We aimed to validate Onclarity (Becton Dickinson Diagnostics, Sparks, MD), a nine-channel HPV test recently approved by the FDA, by assessing (i) the association of Onclarity types/channels with precancer/cancer; (ii) HPV type/channel agreement between the results of Onclarity and cobas (Roche Molecular Systems, Pleasanton, CA), another FDA-approved test; and (iii) Onclarity typing for all types/channels compared to typing results from a research assay (linear array [LA]; Roche). We compared Onclarity to histopathology, cobas, and LA. We tested a stratified random sample ( n = 9,701) of discarded routine clinical specimens that had tested positive by Hybrid Capture 2 (HC2; Qiagen, Germantown, MD). A subset had already been tested by cobas and LA ( n = 1,965). Cervical histopathology was ascertained from electronic health records. Hierarchical Onclarity channels showed a significant linear association with histological severity. Onclarity and cobas had excellent agreement on partial typing of HPV16, HPV18, and the other 12 types as a pool (sample-weighted kappa value of 0.83); cobas was slightly more sensitive for HPV18 and slightly less sensitive for the pooled high-risk types. Typing by Onclarity showed excellent agreement with types and groups of types identified by LA (kappa values from 0.80 for HPV39/68/35 to 0.97 for HPV16). Onclarity typing results corresponded well to histopathology and to an already validated HPV DNA test and could provide additional clinical typing if such discrimination is determined to be clinically desirable. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

HPV prevalence and HPV-related dysplasia in elderly women

PubMed Central

Hermansson, Ruth S.; Olovsson, Matts; Hoxell, Emelie

2018-01-01

Introduction In Sweden, where screening ends at the age of 60, about 30% of the cervical cancer cases occur in women older than 60. The aim of the present study was to investigate the prevalence of HPV and cervical dysplasia in women of 60 years and above. Patients and methods From September 2013 until June 2015, 1051 women aged 60–89 years (mean 68 years) were sampled for an HPV test when attending an outpatient gynecology clinic. Women with positive results had a second HPV test and liquid based cytology (LBC), after 3.5 months on average. Those with a positive second HPV test were examined by colposcopy, and biopsy and a sample for LBC was obtained. Results The prevalence of HPV was 4.1%, (95%CI 3.0–5.5, n = 43) at the first test, and at the second test 2.6% remained positive (95%CI 1.7–3.8, n = 27). The majority of women positive in both HPV tests, had dysplasia in histology, 81.5% (22/27) (4 CIN 2–0.4%, 18 CIN 1–1.7%). HPV-related dysplasia was found in 2.1%, (95%CI 1.3–3.2, n = 22) of the 1051 women. Four of the 22 women with positive HPV tests also had abnormal cytology, one ASCUS and three CIN 1. No cancer or glandular dysplasia was detected. Conclusion A significant proportion of elderly women were found to have a persistent cervical HPV infection. Among them there was a high prevalence of CIN diagnosed by histology. The HPV test showed high sensitivity and specificity in detecting CIN in elderly women, while cytology showed extremely low sensitivity. PMID:29320507

Prevalence and genotype distribution of human papillomavirus infection of the cervix in Spain: the CLEOPATRE study.

PubMed

Castellsagué, Xavier; Iftner, Thomas; Roura, Esther; Vidart, José Antonio; Kjaer, Susanne K; Bosch, F Xavier; Muñoz, Nubia; Palacios, Santiago; San Martin Rodriguez, Maria; Serradell, Laurence; Torcel-Pagnon, Laurence; Cortes, Javier

2012-06-01

Human papillomavirus (HPV) infection is a necessary cause of cervical cancer. The aim of this study was to estimate the prevalence of cervical HPV infection and HPV type-specific distribution among women attending cervical cancer screening in Spain during 2007 and 2008. Women aged 18-65 years were recruited according to an age-stratified sampling method. Liquid-based cervical samples were collected and analyzed for cytology, HPV detection, and genotyping. HPV genotyping was determined using the INNO-LiPA HPV Genotyping Extra Reverse Hybridization Line Probe Assay. Prevalence estimates were age-standardized using 2001 Spanish census data. The present study included 3,261 women. Age-standardized HC2-based HPV prevalence was 14.3% (95% CI, 13.1-15.5) among women aged 18-65 years, and 28.8% (26.6-31.1) among women aged 18-25 years. High-risk HPV types were detected in 12.2% (95% CI, 11.1-13.4) of HPV-tested women, representing 84.0% of HPV-positive samples. Multiple infections were present in 4.1% (95% CI, 3.4-4.8) of HPV-tested women (25.0% of HPV-positive samples). The most common high-risk HPV-types among HPV-tested women were 16 (2.9%), 52 (1.8%), 51 (1.6%), 31 (1.3%), and 66 (1.2%). HPV-type 16 was present in 16.9% of HPV-positive samples. One or more of the HPV vaccine types 6/11/16/18 were detected in 3.8% of HPV-tested women (22.1% of HPV-positive samples). Though not a true population-based survey, this study provides valuable baseline data for future assessment of the impact of current HPV vaccination programs in Spain. The high prevalence of HPV infection among young women may reflect recent changes in sexual behavior. Copyright © 2012 Wiley Periodicals, Inc.

HPV positive neuroendocrine cervical cancer cells are dependent on Myc but not E6/E7 viral oncogenes.

PubMed

Yuan, Hang; Krawczyk, Ewa; Blancato, Jan; Albanese, Christopher; Zhou, Dan; Wang, Naidong; Paul, Siddartha; Alkhilaiwi, Faris; Palechor-Ceron, Nancy; Dakic, Aleksandra; Fang, Shuang; Choudhary, Sujata; Hou, Tung-Wei; Zheng, Yun-Ling; Haddad, Bassem R; Usuda, Yukari; Hartmann, Dan; Symer, David; Gillison, Maura; Agarwal, Seema; Wangsa, Danny; Ried, Thomas; Liu, Xuefeng; Schlegel, Richard

2017-04-05

Using conditional cell reprogramming, we generated a stable cell culture of an extremely rare and aggressive neuroendocrine cervical cancer. The cultured cells contained HPV-16, formed colonies in soft agar and rapidly produced tumors in immunodeficient mice. The HPV-16 genome was integrated adjacent to the Myc gene, both of which were amplified 40-fold. Analysis of RNA transcripts detected fusion of the HPV/Myc genes, arising from apparent microhomologous recombination. Spectral karyotyping (SKY) and fluorescent-in-situ hybridization (FISH) demonstrated coordinate localization and translocation of the amplified Myc and HPV genes on chromosomes 8 and 21. Similar to the primary tumor, tumor cell cultures expressed very high levels of the Myc protein and, in contrast to all other HPV-positive cervical cancer cell lines, they harbored a gain-of-function mutation in p53 (R273C). Unexpectedly, viral oncogene knockdown had no effect on the growth of the cells, but it did inhibit the proliferation of a conventional HPV-16 positive cervical cancer cell line. Knockdown of Myc, but not the mutant p53, significantly inhibited tumor cell proliferation. On the basis of these data, we propose that the primary driver of transformation in this aggressive cervical cancer is not HPV oncogene expression but rather the overexpression of Myc.

EUROGIN 2011 roadmap on prevention and treatment of HPV-related disease

PubMed Central

Arbyn, Marc; de Sanjosé, Silvia; Saraiya, Mona; Sideri, Mario; Palefsky, Joel; Lacey, Charles; Gillison, Maura; Bruni, Laia; Ronco, Guglielmo; Wentzensen, Nicolas; Brotherton, Julia; Qiao, You-Lin; Denny, Lynnette; Bornstein, Jacob; Abramowitz, Laurent; Giuliano, Anna; Tommasino, Massimo; Monsonego, Joseph

2012-01-01

The EUROGIN 2011 roadmap reviews the current burden of HPV (human papillomavirus)-related morbidity, as well as the evidence and potential practice recommendations regarding primary and secondary prevention and treatment of cancers and other disease associated with HPV infection. HPV infection causes approximately 600,000 cases of cancer of the cervix, vulva, vagina, anus and oropharynx annually, as well as benign diseases such as genital warts and recurrent respiratory papillomatosis. Whereas the incidence of cervical cancer has been decreasing over recent decades, the incidence of anal and oropharyngeal carcinoma, for which there are no effective screening programs, has been rising over the last couple of decades. Randomised trials have demonstrated improved efficacy of HPV-based compared to cytology-based cervical cancer screening. Defining the best algorithms to triage HPV-positive women, age ranges and screening intervals are priorities for pooled analyses and further research, whereas feasibility questions can be addressed through screening programmes. HPV vaccination will reduce the burden of cervical precancer and probably also of invasive cervical and other HPV-related disease in women. Recent trials demonstrated that prophylactic vaccination also protects against anogenital HPV infection, ano-genital intraepithelial lesions and warts associated with vaccine types, in males; and anal HPV infection and anal intraepithelial neoplasia in MSM. HPV-related oropharyngeal cancer could be treated less aggressively because of better survival compared to cancers of the oropharynx unrelated to HPV. Key findings in the field of cervical cancer prevention should now be translated in cost-effective strategies, following an organised approach integrating primary and secondary prevention, according to scientific evidence but adapted to the local situation with particular attention to regions with the highest burden of disease. PMID:22623137

Detection of the E7 transform gene of human papilloma virus type 16 in human oral squamous cell carcinoma.

PubMed

Wang, J; Li, J; Huang, H; Fu, Y

1998-12-01

To determine, with the use of polymerase chain reaction, the prevalence of human papillomavirus (HPV) 16 in 30 patients with primary oral squamous cell carcinoma (OSCC) and 30 healthy control patients. DNA was extracted from freshly frozen tumor tissues of 30 patients with primary oral squamous cell carcinoma and from the oral mucosa of 30 controls. A pair of specific primers of the E7 early gene of HPV 16 were designed. PCR products were run by 1.5% agarose gel and the results of electrophoresis were photographed. HPV 16 was detected in 36.7% (11/30) of oral squamous cell carcinoma patients and 11.1% (4/30) of controls. HPV 16 has a significant association with oral squamous cell carcinoma. However, the role HPV 16 plays in the tumorigenesis of oral cancer and its clinical significance remain to be investigated.

Implementation of HPV-testing for cervical cancer screening in programmatic contexts: The Jujuy demonstration project in Argentina.

PubMed

Arrossi, Silvina; Thouyaret, Laura; Laudi, Rosa; Marín, Oscar; Ramírez, Josefina; Paolino, Melisa; Herrero, Rolando; Campanera, Alicia

2015-10-01

The aim of this article is to present results of programmatic introduction of HPV testing with cytologic triage among women 30 years and older in the province of Jujuy, Argentina, including description of the planning phase and results of program performance during the first year. We describe the project implementation process, and calculate key performance indicators using SITAM, the national screening information system. We also compare disease detection rates of HPV testing in 2012 with cytology as performed during the previous year. HPV testing with cytology triage was introduced through a consensus-building process. Key activities included establishment of algorithms and guidelines, creating the HPV laboratory, training of health professionals, information campaigns for women and designing the referral network. By the end of 2012, 100% (n = 270) of public health care centers were offering HPV testing and 22,834 women had been HPV tested, 98.5% (n = 22,515) were 30+. HPV positivity among women over 30 was 12.7%, 807 women were HPV+ and had abnormal cytology, and 281 CIN2+ were identified. CIN2+ detection rates was 1.25 in 2012 and 0.62 in 2011 when the program was cytology based (p = 0.0002). This project showed that effective introduction of HPV testing in programmatic contexts of low-middle income settings is feasible and detects more disease than cytology. © 2015 UICC.

Posttreatment human papillomavirus testing for residual or recurrent high-grade cervical intraepithelial neoplasia: a pooled analysis

PubMed Central

Yoshikawa, Hiroyuki

2016-01-01

Objective We conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3). Methods Source articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013. Results The pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; p<0.001). Conclusion Our findings recommend the addition of high-risk HPV testing, either alone or in conjunction with cytology, to posttreatment surveillance strategies. HPV testing can identify populations at greatest risk of posttreatment CIN 2+ lesions, especially among women with positive section margins. PMID:26463429

Assessment of HPV-mRNA test to predict recurrent disease in patients previously treated for CIN 2/3.

PubMed

Frega, Antonio; Sesti, Francesco; Lombardi, Danila; Votano, Sergio; Sopracordevole, Francesco; Catalano, Angelica; Milazzo, Giusi Natalia; Lombardo, Riccardo; Assorgi, Chiara; Olivola, Sara; Chiusuri, Valentina; Ricciardi, Enzo; French, Deborah; Moscarini, Massimo

2014-05-01

The use of HPV-mRNA test in the follow-up after LEEP is still matter of debate, with regard to its capacity of prediction relapse. The aim of the present study is to evaluate the reliability of HPV-mRNA test to predict the residual and recurrent disease, and its accuracy in the follow-up of patients treated for CIN 2/3. Multicenter prospective cohort study. Patients who underwent LEEP after a biopsy diagnosing CIN 2/3 were followed at 3, 6, 12, 24 and 36 months. Each check up included cytology, colposcopy, HPV-DNA test (LiPA) and HPV-mRNA test (PreTect HPV Proofer Kit NorChip). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), of HPV-DNA test and HPV-mRNA test to predict relapse, recurrent and residual disease. Using multiple logistic regression, the statistical significant variables as assessed in univariate analysis were entered and investigated as predictors of relapse disease. The mRNA-test in predicting a residual disease had a sensitivity of 52% and a NPV of 91%, whereas DNA-test had 100% and 100%, respectively. On the contrary in the prediction of recurrent disease mRNA-test had a sensitivity and a NPV of 73.5% and 97%, whereas DNA-test had 44% and 93%. On the multivariate analysis, age, cytology, HPV DNA and mRNA test achieved the role of independent predictors of relapse. HPV-mRNA test has a higher sensitivity and a higher NPV in predicting recurrent disease, for this reason it should be used in the follow-up of patients treated with LEEP for CIN 2/3 in order to individualize the timing of check up. Copyright © 2014 Elsevier B.V. All rights reserved.

[What should be known for the introduction of an HPV vaccine?].

PubMed

Muñoz, Nubia; Jacquard, Anne-Carole

2008-10-01

Genital human papillomavirus (HPV) infection is one of the most common sexually transmitted infections worldwide. Two HPV vaccines are now available in many countries: (i) the first vaccine is quadrivalent and indicated in the prevention of CIN 2/3, cervical cancers, VIN 2/3, VaIN 2/3 and genital warts associated with the HPV types 6, 11, 16 and 18, (ii) the second vaccine is bivalent and indicated in the prevention of CIN 2+ and cervical cancers associated with the HPV types 16 and 18. To critically review all epidemiological aspects of the HPV infection and its relation with preneoplasic lesions of the cervix and cervical cancer to assist the relevant public health authorities to make plans for the introduction of HPV vaccines that have been recently commercialized. Only articles published in English in peer reviewed journals have been selected in Date base PubMed (National Library of Medicine - National Institutes of Health) with Keywords HPV, risk factor, cervical cancer, CIN2/3, incidence, prevalence, transmission, prevention, genital cancer, HPV vaccines, screening. A critical review of most papers published during the last 10 years was made. The topics covered included: diseases caused by HPV, prevalence, incidence and transmission of HPV, risk factors for the acquisition of HPV, natural history of HPV infection, risk factors determining the progression from HPV to cancer, protective factors blocking the progression from infection to cancer (screening) and primary prevention of HPV by vaccines and other methods. The information was interpreted and summarized. It was concluded that HPV infection is one of the most common sexually transmitted infections, that it is the necessary cause of cervical cancer and the cause of other genital cancers and cancers of the upper aerodigestive tract. Fortunately most infections regress, but those infections that persist are the ones leading to cancer. Primary prevention by the introduction of prophylactic vaccines is the ideal means of preventing cervical cancer and other cancers associated to HPV. This review is to my knowledge, the most comprehensive and up-to date review to be published in French on HPV epidemiology and related diseases. It will be of great value to educate medical and paramedical personnel on HPV infection and associated diseases and it will be of great help to public health authorities and decision makers when they have to evaluate the convenience of introducing HPV vaccination in a given population.

Human Papilloma Virus Infection Does Not Predict Response to Interferon Therapy in Ocular Surface Squamous Neoplasia.

PubMed

Galor, Anat; Garg, Nisha; Nanji, Afshan; Joag, Madhura; Nuovo, Gerard; Palioura, Sotiria; Wang, Gaofeng; Karp, Carol L

2015-11-01

To identify the frequency of human papilloma virus (HPV) in ocular surface squamous neoplasia (OSSN) and to evaluate differences in clinical features and treatment response of tumors with positive versus negative HPV results. Retrospective case series. Twenty-seven patients with OSSN. Ocular surface squamous neoplasia specimens were analyzed for the presence of HPV. Clinical features and response to interferon were determined retrospectively and linked to the presence (versus absence) of HPV. Clinical characteristics of OSSN by HPV status. Twenty-one of 27 tumors (78%) demonstrated positive HPV results. The HPV genotypes identified included HPV-16 in 10 tumors (48%), HPV-31 in 5 tumors, HPV-33 in 1 tumor, HPV-35 in 2 tumors, HPV-51 in 2 tumors, and a novel HPV in 3 tumors (total of 23 tumors because 1 tumor had 3 identified genotypes). Tumors found in the superior limbus were more likely to show positive HPV results (48% vs. 0%; P=0.06, Fisher exact test). Tumors with positive HPV-16 results were larger (68 vs. 34 mm2; P=0.08, Mann-Whitney U test) and were more likely to have papillomatous morphologic features (50% vs. 12%; P=0.07, Fisher exact test) compared with tumors showing negative results for HPV-16. Human papilloma virus status was not found to be associated with response to interferon therapy (P=1.0, Fisher exact test). Metrics found to be associated with a nonfavorable response to interferon were male gender and tumors located in the superior conjunctivae. The presence of HPV in OSSN seems to be more common in lesions located in the nonexposed, superior limbus. Human papilloma virus presence does not seem to be required for a favorable response to interferon therapy. Copyright © 2015 American Academy of Ophthalmology. All rights reserved.

Triage of HR-HPV positive women with minor cytological abnormalities: a comparison of mRNA testing, HPV DNA testing, and repeat cytology using a 4-year follow-up of a population-based study.

PubMed

Persson, Maria; Elfström, K Miriam; Brismar Wendel, Sophia; Weiderpass, Elisabete; Andersson, Sonia

2014-01-01

Expression of the viral E6/E7 oncogenes of high-risk human papillomaviruses (HR-HPV) is necessary for malignant conversion and maintenance in cervical tissue. In order to determine whether HR-HPV E6/E7 mRNA testing more effectively predicts precancerous lesions and invasive cervical cancer than HR-HPV DNA testing, we aimed to compare triage using HR-HPV E6/E7 mRNA testing by APTIMA HPV Assay (APTIMA) to HPV16 DNA testing, HPV16/18 DNA testing, and repeat cytology. Liquid-based (PreservCyt) cell samples were obtained from HR-HPV-positive women diagnosed with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) within the framework of the population-based cervical cancer screening program in Stockholm, Sweden. Samples were tested for HR-HPV E6/E7 mRNA by APTIMA (Gene-Probe Inc., San Diego, CA, USA). Women were followed up for 4 years after the index cytology via medical and laboratory records, and the Stockholm Oncology Center. Nine of 25 (36%) women in the ASCUS group, and 64 of 180 (36%) women in the LSIL group developed cervical intraepithelial neoplasia (CIN) grade 2 or worse during 4 years of follow-up. 162 (74%) women were APTIMA-positive, and APTIMA had the highest sensitivity to predict CIN2 or worse and CIN3 or worse in the ASCUS (77.8% and 100%) and LSIL (78.1 and 75.8%) groups, although specificity was insufficient (<50%). HPV16 DNA testing and repeat cytology were more specific than APTIMA. The results of this population-based study with comprehensive follow-up support the use of APTIMA as a triage test for women with ASCUS. More focused investigation is required for women with LSIL.

Triage of HR-HPV Positive Women with Minor Cytological Abnormalities: A Comparison of mRNA Testing, HPV DNA Testing, and Repeat Cytology Using a 4-Year Follow-Up of a Population-Based Study

PubMed Central

Persson, Maria; Elfström, K. Miriam; Brismar Wendel, Sophia; Weiderpass, Elisabete; Andersson, Sonia

2014-01-01

Objective Expression of the viral E6/E7 oncogenes of high-risk human papillomaviruses (HR-HPV) is necessary for malignant conversion and maintenance in cervical tissue. In order to determine whether HR-HPV E6/E7 mRNA testing more effectively predicts precancerous lesions and invasive cervical cancer than HR-HPV DNA testing, we aimed to compare triage using HR-HPV E6/E7 mRNA testing by APTIMA HPV Assay (APTIMA) to HPV16 DNA testing, HPV16/18 DNA testing, and repeat cytology. Methods Liquid-based (PreservCyt) cell samples were obtained from HR-HPV-positive women diagnosed with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) within the framework of the population-based cervical cancer screening program in Stockholm, Sweden. Samples were tested for HR-HPV E6/E7 mRNA by APTIMA (Gene-Probe Inc., San Diego, CA, USA). Women were followed up for 4 years after the index cytology via medical and laboratory records, and the Stockholm Oncology Center. Results Nine of 25 (36%) women in the ASCUS group, and 64 of 180 (36%) women in the LSIL group developed cervical intraepithelial neoplasia (CIN) grade 2 or worse during 4 years of follow-up. 162 (74%) women were APTIMA-positive, and APTIMA had the highest sensitivity to predict CIN2 or worse and CIN3 or worse in the ASCUS (77.8% and 100%) and LSIL (78.1 and 75.8%) groups, although specificity was insufficient (<50%). HPV16 DNA testing and repeat cytology were more specific than APTIMA. Conclusion The results of this population-based study with comprehensive follow-up support the use of APTIMA as a triage test for women with ASCUS. More focused investigation is required for women with LSIL. PMID:24587193

Presence of koilocytosis in low-grade smears of high-risk HPV-positive women is a negative predictor for cervical intraepithelial neoplasia grade 3 or more.

PubMed

Siebers, A G; van der Linden, H; Vedder, J E M; Bekkers, R L M; Melchers, W L G; Bulten, J

2018-03-25

The Netherlands converted to high-risk (hr)HPV-based screening in 2017. An increase in referral of hrHPV-positive women with low risk for cervical intraepithelial neoplasia grade 3 or more (CIN3+) is anticipated and reduction of unjustified referrals will have priority. The relevance of koilocytosis in relation to the underlying risk of high-grade CIN in a primary HPV screening setting is unclear. The aim was to investigate whether the risk for CIN3+ differs between hrHPV-positive atypical squamous cells of undetermined significance (ASC-US)/low-grade squamous intraepithelial lesion (LSIL) with or without koilocytosis. Retrospective cohort study, using data from the Dutch national pathology database (PALGA). The population was 1201 hrHPV-positive women with cytological diagnosis of ASC-US/LSIL. Reporting of koilocytosis was assessed as well as detection rates of CIN1 or less, CIN2 and CIN3+ for ASC-US/LSIL cytology stratified by presence or absence of koilocytosis. Crude and adjusted odds ratios were determined. Koilocytosis was present in 40.1% of ASC-US and 45.9% of LSIL cases. CIN3+ is significantly less often found when koilocytosis is present (7.8% for hrHPV-positive ASC-US with- vs 15.8% without koilocytosis). For hrHPV-positive LSIL this was 11.7% vs 20.2%. The crude and adjusted odds ratios for CIN3+ was 0.45 for hrHPV-positive ASC-US and 0.52 for hrHPV-positive LSIL. The presence of koilocytosis is a negative predictor of CIN3+. The risk of hrHPV-positive ASC-US with koilocytosis is in the same range as hrHPV-positive/cytology negative cases and in a setting of primary hrHPV screening these cases could be followed conservatively by repeat cytology. The results should be confirmed by the first data from the Dutch HPV-based screening programme. © 2018 John Wiley & Sons Ltd.

Comparison of DNA testing strategies in monitoring human papillomavirus infection prevalence through simulation.

PubMed

Lin, Carol Y; Li, Ling

2016-11-07

HPV DNA diagnostic tests for epidemiology monitoring (research purpose) or cervical cancer screening (clinical purpose) have often been considered separately. Women with positive Linear Array (LA) polymerase chain reaction (PCR) research test results typically are neither informed nor referred for colposcopy. Recently, a sequential testing by using Hybrid Capture 2 (HC2) HPV clinical test as a triage before genotype by LA has been adopted for monitoring HPV infections. Also, HC2 has been reported as a more feasible screening approach for cervical cancer in low-resource countries. Thus, knowing the performance of testing strategies incorporating HPV clinical test (i.e., HC2-only or using HC2 as a triage before genotype by LA) compared with LA-only testing in measuring HPV prevalence will be informative for public health practice. We conducted a Monte Carlo simulation study. Data were generated using mathematical algorithms. We designated the reported HPV infection prevalence in the U.S. and Latin America as the "true" underlying type-specific HPV prevalence. Analytical sensitivity of HC2 for detecting 14 high-risk (oncogenic) types was considered to be less than LA. Estimated-to-true prevalence ratios and percentage reductions were calculated. When the "true" HPV prevalence was designated as the reported prevalence in the U.S., with LA genotyping sensitivity and specificity of (0.95, 0.95), estimated-to-true prevalence ratios of 14 high-risk types were 2.132, 1.056, 0.958 for LA-only, HC2-only, and sequential testing, respectively. Estimated-to-true prevalence ratios of two vaccine-associated high-risk types were 2.359 and 1.063 for LA-only and sequential testing, respectively. When designated type-specific prevalence of HPV16 and 18 were reduced by 50 %, using either LA-only or sequential testing, prevalence estimates were reduced by 18 %. Estimated-to-true HPV infection prevalence ratios using LA-only testing strategy are generally higher than using HC2-only or using HC2 as a triage before genotype by LA. HPV clinical testing can be incorporated to monitor HPV prevalence or vaccine effectiveness. Caution is needed when comparing apparent prevalence from different testing strategies.

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.

Comparison of the AdvanSure human papillomavirus screening real-time PCR, the Abbott RealTime High Risk human papillomavirus test, and the Hybrid Capture human papillomavirus DNA test for the detection of human papillomavirus.

PubMed

Hwang, Yusun; Lee, Miae

2012-05-01

We evaluated the performance of various commercial assays for the molecular detection of human papillomavirus (HPV); the recently developed AdvanSure HPV Screening real-time PCR assay (AdvanSure PCR) and the Abbott RealTime High Risk HPV PCR assay (Abbott PCR) were compared with the Hybrid Capture 2 HPV DNA Test (HC2). All 3 tests were performed on 177 samples, and any sample that showed a discrepancy in any of the 3 tests was genotyped using INNO-LiPA HPV genotyping and/or sequencing. On the basis of these results, we obtained a consensus HPV result, and the performance of each test was evaluated. We also evaluated high-risk HPV 16/18 detection by using the 2 real-time PCR assays. Among the 177 samples, 65 were negative and 75 were positive in all 3 assays; however, the results of the 3 assays with 37 samples were discrepant. Compared with the consensus HPV result, the sensitivities and specificities of HC2, AdvanSure PCR, and Abbott PCR were 97.6%, 91.7%, and 86.9% and 83.9%, 98.8%, and 100.0%, respectively. For HPV type 16/18 detection, the concordance rate between the AdvanSure PCR and Abbott PCR assays was 98.3%; however, 3 samples were discrepant (positive in AdvanSure PCR and negative in Abbott PCR) and were confirmed as HPV type 16 by INNO-LiPA genotyping and/or sequencing. For HPV detection, the AdvanSure HPV Screening real-time PCR assay and the Abbott PCR assay are less sensitive but more specific than the HC2 assay, but can simultaneously differentiate type 16/18 HPV from other types.

Prevalence of Human Papilloma Virus Infection in Young Primiparous Women During Postpartum Period: Study from a Tertiary Care Center in Northern India.

PubMed

Garg, Alpana; Suri, Vanita; Nijhawan, Raje; Aggarwal, Neelam; Aggarwal, Ritu; Guleria, Charu; Thakur, Mili

2016-10-01

Assessment of high-risk Human Papilloma Virus (HPV) prevalence is important for monitoring long-term decrease in cervical cancer after implementation of the prophylactic HPV vaccination. To determine the prevalence of high-risk HPV infection and cytological abnormalities in young primiparous women in the age group of 16-26years. In this cross-sectional study, 214 primiparous women aged 16-26years were recruited from a public tertiary health care center postpartum clinic between June 2013 and May 2014. Cytological analysis was performed by Pap smear test and patients underwent sampling with cervical brushes for HPV-DNA detection and typing by a PCR-based assay for HPV types 16, 18, 33 and 45. High-risk HPV was detected in 41 (19.2%) women. HPV 16 was found to be most prevalent with 17 (7.9%) samples testing positive, followed by HPV 18 in nine (4.2%), HPV 45 in six (2.8%) and HPV 31 in four (1.8%) women. Five women tested positive for more than one HPV types. There were no cases of intraepithelial lesions or cervical cancer. One patient who had Atypical Cells of Undetermined Significance (ASCUS) on cytology tested negative for all four HPV genotypes. This study provides a geographic baseline data of high-risk HPV prevalence in young Indian women before implementation of a vaccination program. The results are important for comparison with other global regions and monitoring the effect of HPV vaccination.

Human papillomavirus (HPV) perinatal transmission and risk of HPV persistence among children: Design, methods and preliminary results of the HERITAGE study.

PubMed

Trottier, Helen; Mayrand, Marie-Hélène; Coutlée, François; Monnier, Patricia; Laporte, Louise; Niyibizi, Joseph; Carceller, Ana-Maria; Fraser, William D; Brassard, Paul; Lacroix, Jacques; Francoeur, Diane; Bédard, Marie-Josée; Girard, Isabelle; Audibert, François

2016-12-01

Perinatal route of transmission of human papillomavirus (HPV) has been demonstrated in several small studies. We designed a large prospective cohort study (HERITAGE) to better understand perinatal HPV. The objective of this article is to present the study design and preliminary data. In the first phase of the study, we recruited 167 women in Montreal, Canada, during the first trimester of pregnancy. An additional 850 are currently being recruited in the ongoing phase. Cervicovaginal samples were obtained from mothers in the first trimester and tested for HPV DNA from 36 mucosal genotypes (and repeated in the third trimester for HPV-positive mothers). Placental samples were also taken for HPV DNA testing. Conjunctival, oral, pharyngeal and genital samples were collected for HPV DNA testing in children of HPV-positive mothers at every 3-6 months from birth until 2 years of age. Blood samples were collected in mother and children for HPV serology testing. We found a high prevalence of HPV in pregnant women (45%[95%CI:37-53%]) and in placentas (14%[8-21%]). The proportion of HPV positivity (any site) among children at birth/3-months was 11%[5-22%]. HPV was detected in children in multiple sites including the conjunctiva (5%[10-14%]). The ongoing HERITAGE cohort will help provide a better understanding of perinatal HPV. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Comparing triage algorithms using HPV DNA genotyping, HPV E7 mRNA detection and cytology in high-risk HPV DNA-positive women.

PubMed

Luttmer, Roosmarijn; Berkhof, Johannes; Dijkstra, Maaike G; van Kemenade, Folkert J; Snijders, Peter J F; Heideman, Daniëlle A M; Meijer, Chris J L M

2015-06-01

High-risk human papillomavirus (hrHPV) DNA positive women require triage testing to identify those with high-grade cervical intraepithelial neoplasia or cancer (≥CIN2). Comparing three triage algorithms (1) E7 mRNA testing following HPV16/18/31/33/45/52/58 genotyping (E7 mRNA test), (2) HPV16/18 DNA genotyping and (3) cytology, for ≥CIN2 detection in hrHPV DNA-positive women. hrHPV DNA-positive women aged 18-63 years visiting gynecology outpatient clinics were included in a prospective observational cohort study. From these women a cervical scrape and colposcopy-directed biopsies were obtained. Cervical scrapes were evaluated by cytology, HPV DNA genotyping by bead-based multiplex genotyping of GP5+6+-PCR-products, and presence of HPV16/18/31/33/45/52/58 E7 mRNA using nucleic acid sequence-based amplification (NASBA) in DNA positive women for respective HPV types. Sensitivities and specificities for ≥CIN2 were compared between E7 mRNA test and HPV16/18 DNA genotyping in the total group (n=348), and E7 mRNA test and cytology in a subgroup of women referred for non-cervix-related gynecological complaints (n=133). Sensitivity for ≥CIN2 of the E7 mRNA test was slightly higher than that of HPV16/18 DNA genotyping (66.9% versus 60.9%; ratio 1.10, 95% CI: 1.0002-1.21), at similar specificity (54.8% versus 52.3%; ratio 1.05, 95% CI: 0.93-1.18). Neither sensitivity nor specificity of the E7 mRNA test differed significantly from that of cytology (sensitivity: 68.8% versus 75.0%; ratio 0.92, 95% CI: 0.72-1.17; specificity: 59.4% versus 65.3%; ratio 0.91, 95% CI: 0.75-1.10). For detection of ≥CIN2 in hrHPV DNA-positive women, an algorithm including E7 mRNA testing following HPV16/18/31/33/45/52/58 DNA genotyping performs similar to HPV16/18 DNA genotyping or cytology. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of an HPV Educational Protocol for Adolescents

PubMed Central

Wetzel, Caitlin; Tissot, Abbigail; Kollar, Linda M.; Hillard, Paula A.; Stone, Rachel; Kahn, Jessica A.

2007-01-01

Study Objectives To develop an educational protocol about HPV and Pap tests for adolescents, to evaluate the protocol for understandability and clarity, and to evaluate the protocol for its effectiveness in increasing knowledge about HPV. Design In phase 1, investigators and adolescents developed the protocol. In phase 2, adolescents evaluated the protocol qualitatively, investigators evaluated its effectiveness in increasing HPV knowledge in a sample of adolescents, and the protocol was revised. In phase 3, investigators evaluated the effectiveness of the revised protocol in an additional adolescent sample. Setting Urban, hospital-based teen health center. Participants A total of 252 adolescent girls and boys in the three study phases. Main Outcome Measures Pre- and post-protocol knowledge about HPV, measured using a 10- or 11-item scale. Results Scores on the HPV knowledge scale increased significantly (p<.0001) among adolescents who participated in phases 2 and 3 after they received the protocol. Initial differences in scores based on race, insurance type and condom use were not noted post-protocol. Conclusion The protocol significantly increased knowledge scores about HPV in this population, regardless of sociodemographic characteristics and risk behaviors. Effective, developmentally appropriate educational protocols about HPV and Pap tests are particularly important in clinical settings as cervical cancer screening guidelines evolve, HPV DNA testing is integrated into screening protocols, and HPV vaccines become available. In-depth, one-on-one education about HPV may also prevent adverse psychosocial responses and promote healthy sexual and Pap screening behaviors in adolescents with abnormal HPV or Pap test results. Synopsis The investigators developed an educational protocol about HPV and Pap tests and evaluated its effectiveness in increasing knowledge about HPV among adolescents. PMID:17868894

Threshold cost-effectiveness analysis for a therapeutic vaccine against HPV-16/18-positive cervical intraepithelial neoplasia in the Netherlands.

PubMed

Luttjeboer, Jos; Setiawan, Didik; Cao, Qi; Cahh Daemen, Toos; Postma, Maarten J

2016-12-07

In this study, the potential price for a therapeutic vaccine against Human Papilloma Virus (HPV)-16 & 18 (pre)-malignant cervical lesions is examined. A decision tree model was built in the context of the new Dutch cervical cancer-screening program and includes a primary test for the presence of HPV. Based on data of cervical cancer screening and HPV prevalence in the Netherlands, cohorts were created with HPV-16 or 18 positive women with cervical intraepithelial neoplasia (CIN) 2 or 3 or cervical cancer stage 1A (FIGO 1A). In the base case, the vaccine price was based on equal numbers of effective treatments in the vaccine branch and the current treatments branch of the model, and parity in cost, i.e. total cost in both branches are the same. The vaccine price is calculated by subtracting the cost of the vaccine branch from cost in the standard treatment branch and divided by the total number of women in the cohort, thereby equalizing costs in both strategies. Scenario analyses were performed taking quality adjusted life years (QALYs) into account with €20,000/QALY, €50,000/QALY and €80,000/QALY as corresponding thresholds. Sensitivity analyses were specifically targeted at the characteristics of the type-specific HPV test in the screening practice and vaccine efficacy. A probabilistic sensitivity analysis (PSA) was performed to quantify the level of uncertainty of the results found in the base case. In the base case, break-even vaccine prices of €381, €568 and €1697 were found for CIN 2, CIN 3 and FIGO 1A, respectively. The PSA showed vaccine pricing below €310, €490 and €1660 will be cost saving with a likelihood of 95% for CIN 2, CIN 3 and FIGO 1A, respectively. The vaccine price proved to be very sensitive for inclusion of QALY gains, including the HPV-type specific test into the Dutch screening practice and vaccine efficacy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Human papillomavirus testing and liquid-based cytology: results at recruitment from the new technologies for cervical cancer randomized controlled trial.

PubMed

Ronco, Guglielmo; Segnan, Nereo; Giorgi-Rossi, Paolo; Zappa, Marco; Casadei, Gian Piero; Carozzi, Francesca; Dalla Palma, Paolo; Del Mistro, Annarosa; Folicaldi, Stefania; Gillio-Tos, Anna; Nardo, Gaetano; Naldoni, Carlo; Schincaglia, Patrizia; Zorzi, Manuel; Confortini, Massimo; Cuzick, Jack

2006-06-07

Although testing for human papillomavirus (HPV) has higher sensitivity and lower specificity than cytology alone for detecting cervical intraepithelial neoplasia (CIN), studies comparing conventional and liquid-based cytology have had conflicting results. In the first phase of a two-phase multicenter randomized controlled trial, women aged 35-60 years in the conventional arm (n = 16,658) were screened using conventional cytology, and women in the experimental arm (n = 16,706) had liquid-based cytology and were tested for high-risk HPV types using the Hybrid Capture 2 assay. Women in the conventional arm were referred to colposcopy with atypical cells of undetermined significance (ASCUS) or higher and those in the experimental arm were referred with ASCUS or higher cytology or with a positive (> or = 1 pg/mL) HPV test. Sensitivity and positive predictive value (PPV) for detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were calculated. The screening methods and referral criterion applied in the experimental arm had higher sensitivity than that in the conventional arm (relative sensitivity = 1.47; 95% confidence interval [CI] = 1.03 to 2.09) but a lower PPV (relative PPV = 0.40; 95% CI = 0.23 to 0.66). With HPV testing alone at > or = 1 pg/mL and at > or = 2 pg/mL, the gain in sensitivity compared with the conventional arm remained similar (relative sensitivity = 1.43, 95% CI = 1.00 to 2.04 and relative sensitivity = 1.41, 95% CI = 0.98 to 2.01, respectively) but PPV progressively improved (relative PPV = 0.58, 95% CI = 0.33 to 0.98 and relative PPV = 0.75, 95% CI = 0.45 and 1.27, respectively). Referral based on liquid-based cytology alone did not increase sensitivity compared with conventional cytology (relative sensitivity = 1.06; 95% CI = 0.72 to 1.55) but reduced PPV (relative PPV = 0.57; 95% CI = 0.39 to 0.82). HPV testing alone was more sensitive than conventional cytology among women 35-60 years old. Adding liquid-based cytology improved sensitivity only marginally but increased false-positives. HPV testing using Hybrid Capture 2 with a 2 pg/mL cutoff may be more appropriate than a 1 pg/mL cutoff for primary cervical cancer screening.

Temporal Nodal Regression and Regional Control After Primary Radiation Therapy for N2-N3 Head-and-Neck Cancer Stratified by HPV Status

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

Huang, Shao Hui; O'Sullivan, Brian; Xu, Wei

Purpose: To compare the temporal lymph node (LN) regression and regional control (RC) after primary chemoradiation therapy/radiation therapy in human papillomavirus-related [HPV(+)] versus human papillomavirus-unrelated [HPV(−)] head-and-neck cancer (HNC). Methods and Materials: All cases of N2-N3 HNC treated with radiation therapy/chemoradiation therapy between 2003 and 2009 were reviewed. Human papillomavirus status was ascertained by p16 staining on all available oropharyngeal cancers. Larynx/hypopharynx cancers were considered HPV(−). Initial radiologic complete nodal response (CR) (≤1.0 cm 8-12 weeks after treatment), ultimate LN resolution, and RC were compared between HPV(+) and HPV(−) HNC. Multivariate analysis identified outcome predictors. Results: A total of 257more » HPV(+) and 236 HPV(−) HNCs were identified. The initial LN size was larger (mean, 2.9 cm vs 2.5 cm; P<.01) with a higher proportion of cystic LNs (38% vs 6%, P<.01) in HPV(+) versus HPV(−) HNC. CR was achieved is 125 HPV(+) HNCs (49%) and 129 HPV(−) HNCs (55%) (P=.18). The mean post treatment largest LN was 36% of the original size in the HPV(+) group and 41% in the HPV(−) group (P<.01). The actuarial LN resolution was similar in the HPV(+) and HPV(−) groups at 12 weeks (42% and 43%, respectively), but it was higher in the HPV(+) group than in the HPV(−) group at 36 weeks (90% vs 77%, P<.01). The median follow-up period was 3.6 years. The 3-year RC rate was higher in the HPV(−) CR cases versus non-CR cases (92% vs 63%, P<.01) but was not different in the HPV(+) CR cases versus non-CR cases (98% vs 92%, P=.14). On multivariate analysis, HPV(+) status predicted ultimate LN resolution (odds ratio, 1.4 [95% confidence interval, 1.1-1.7]; P<.01) and RC (hazard ratio, 0.3 [95% confidence interval 0.2-0.6]; P<.01). Conclusions: HPV(+) LNs involute more quickly than HPV(−) LNs but undergo a more prolonged process to eventual CR beyond the time of initial assessment at 8 to 12 weeks after treatment. Post radiation neck dissection is advisable for all non-CR HPV(−)/non-CR N3 HPV(+) cases, but it may be avoided for selected non-CR N2 HPV(+) cases with a significant LN involution if they can undergo continued imaging surveillance. The role of positron emission tomography for response assessment should be investigated.« less

Evaluation of the clinical performance of the Abbott RealTime High-Risk HPV for carcinogenic HPV detection.

PubMed

Halfon, Philippe; Benmoura, Dominique; Agostini, Aubert; Khiri, Hacene; Penaranda, Guillaume; Martineau, Agnes; Blanc, Bernard

2010-08-01

Abbott RealTime (RT) High-Risk (HR) HPV assay is a new qualitative real-time polymerase chain reaction (PCR) based assay for the detection of 14 HR HPV DNA. The assay can differentiate between the infection by HPV 16, HPV 18 and non-HPV 16/18 types through the distinct fluorescent labels on the type specific probes. To evaluate the clinical performance of the Abbott RT HR HPV test, in comparison with biopsy, Hybrid Capture II (HCII), and Linear Array (LA), for detection of high-grade disease (CIN2+). The study population consisted of 143 women who were included in three referral gynecology clinics in Marseilles (France) between March 2007 and June 2008. The clinical performance of the RT HR HPV assay, performed on the fully automated m2000 system, was compared with HCII and LA. HR HPV positivity rate was similar for all tests (Abbott RT HR HPV and HCII, 62%, and LA 63%). All tests had high sensitivities and negative predictive values for CIN2+ detection (>90%). The agreement between HCII and Abbott RT HR HPV, and between HCII and LA were 93% (k=0.85) and 96% (k=0.91) respectively. As expected, HPV16 or HPV18 positivity was greater in advanced grades of disease, especially in CIN2+ patients: 85% in CIN2+ vs. 33% in

Quantifying the decisional satisfaction to accept or reject the Human Papillomavirus (HPV) vaccine: a preference for cervical cancer prevention.

PubMed

Harper, Diane M; Irons, Billy B; Alexander, Natalie M; Comes, Johanna C; Smith, Melissa S; Heutinck, Melinda A; Handley, Sandra M; Ahern, Debra A

2014-01-01

Only a portion of the US population is willing to consider HPV vaccination to date. The primary aim of this study is to determine the decisional satisfaction associated with HPV vaccination. This is a prospective survey conducted at an urban college where women 18-26 years old completed a decisional satisfaction survey about their HPV vaccine experience. Regardless of the decision to accept or reject HPV vaccination, the decisional satisfaction was very high (mean 5-item score = 21.2 (SD 3.8)). Women without HPV vaccination were decisionally neutral significantly more often than those already vaccinated; 22% were decisionally neutral for the option to accept HPV vaccination at that visit. Cervical cancer prevention was preferred significantly more often than genital wart prevention in all analyses. Targeting those who are decisionally neutral about HPV vaccination may result in a higher uptake of HPV vaccination.

Identification of RNA Aptamers that Internalize into HPV-16 E6/E7 Transformed Tonsillar Epithelial Cells

PubMed Central

Gourronc, Francoise A.; Rockey, William M.; Thiel, William H.; Giangrande, Paloma H.; Klingelhutz, Aloysius J.

2013-01-01

Human papillomavirus type 16 (HPV-16) associated oropharyngeal cancers are on a significant increase and better therapeutic strategies are needed. The HPV-16 oncogenes E6 and E7 are expressed in HPV-associated cancers and are able to transform human tonsillar epithelial cells (HTECs). We used cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) to select for RNA aptamers that entered into HPV-16 E6/E7-HTECs. After 12 rounds of cell-SELEX, a pool of aptamers was obtained that had significantly greater internalization capacity (~5-fold) into E6/E7-HTECs as compared to primary HTECs or fibroblasts. Analysis of individual aptamers from the pool indicated variable internalization into E6/E7-HTECs (1 to 8-fold as compared to a negative control). Most of the individual aptamers internalized into E6/E7 and primary HTECs with similar efficiency, while one aptamer exhibited ~3-fold better internalization into E6/E7-HTECs. Aptamers that internalize into cells may be useful for delivering therapeutic agents to HPV-16 associated malignancies. PMID:24074596

[New paradigms and challenges in cervical cancer prevention and control in Latin America].

PubMed

Almonte, Maribel; Murillo, Raúl; Sánchez, Gloria Inés; Jerónimo, José; Salmerón, Jorge; Ferreccio, Catterina; Lazcano-Ponce, Eduardo; Herrero, Rolando

2010-01-01

Cervical cancer continues to be a significant health problem in Latin America. The use of conventional cytology to detect precancerous cervical lesions has had almost no major impact on reducing cervical cancer incidence and mortality rates, which are still high in the region. The availability of new screening tools to detect precancerous lesions provide great opportunities for cervical cancer prevention in the region, as do highly efficacious HPV vaccines able to prevent nearly all lesions associated with HPV-16 and -18 when applied before viral exposure. This paper summarizes the scientific evidence and regional experiences related to: i) the use of HPV testing and visual inspection after the application of acetic acid (VIA) in primary screening and ii) the implementation of adolescent HPV vaccination programs. Finally, we outline a number of recommendations for different resource settings. The feasibility of implementing successful and sustainable national cervical cancer prevention programs in Latin American countries in the region will depend on health priorities and the availability of infrastructure and health personnel--as determined by rigorous local situational analysis.

Laser capture microdissection as a tool to evaluate human papillomavirus genotyping and methylation as biomarkers of persistence and progression of anal lesions

PubMed Central

Cornall, Alyssa M; Roberts, Jennifer M; Molano, Monica; Machalek, Dorothy A; Phillips, Samuel; Hillman, Richard J; Grulich, Andrew E; Jin, Fengyi; Poynten, I Mary; Templeton, David J; Garland, Suzanne M; Tabrizi, Sepehr N

2015-01-01

Introduction Anal squamous cell carcinoma is preceded by persistent infection with high-risk human papillomavirus (HPV) and the cancer precursor, high-grade squamous intraepithelial lesion (HSIL). Detection of specific HPV genotypes and HPV-related biomarkers may be an option for primary anal screening. However, more data on the natural history of HPV-related anal lesions are required. The outcomes from this study will enhance our understanding of the clinical and biological behaviour of HPV-related anal lesions and inform the development of future HPV genotype and/or biomarker screening tests. Methods and analysis HIV-negative and HIV-positive men who have sex with men, aged 35 years and over, recruited from community-based settings in Sydney, Australia, attend 6 clinic visits over 3 years. At the first 5 visits, participants undergo a digital anorectal examination, an anal swab for HPV genotyping and anal cytology, and high-resolution anoscopy with directed biopsy of any visible abnormalities that are suggestive of any abnormality suspicious of SIL. Tissue sections from participants diagnosed with histologically confirmed HSIL at the baseline clinic visit will undergo laser capture microdissection, HPV detection and genotyping, and quantitation of CpG methylation in baseline and follow-up biopsies. Histological and cytological findings in combination with HPV genotyping data will be used to identify persistent HSIL. HSIL will be stratified as non-persistent and persistent based on their status at 12 months. The performance of HPV genotype and methylation status in predicting disease persistence at 12 months will be assessed, along with associations with HIV status and other covariates such as age. Ethics and dissemination The St Vincent's Hospital Ethics Committee granted ethics approval for the study. Written informed consent is obtained from all individuals before any study-specific procedures are performed. Findings from this study will be disseminated to participants and the community through study newsletters, and through peer-reviewed publications and international conferences. PMID:26310402

Quality Improvement Initiative to Improve HPV Vaccine Initiation at Nine Years of Age,.

PubMed

Goleman, Martha J; Dolce, Millie; Morack, Jennifer

2018-05-26

Adolescent human papillomavirus (HPV) vaccine rates remain low. Early vaccination may improve the efficacy of the vaccine and immunization rates. However, clinicians have not routinely made a strong recommendation to younger adolescents. This study assessed the feasibility of routine vaccination at nine years of age. Three sequential quality improvement (QI) interventions were implemented to shift the initiation of the HPV vaccine to nine years of age in a primary care network in low-income neighborhoods in Columbus, Ohio. The first intervention changed the electronic medical record (EMR) alert for the HPV vaccine from eleven to nine years of age and focused on cancer prevention when discussing the vaccine with families. The second intervention was formation of an HPV QI team. The third intervention was a clinic incentive for HPV captured opportunity rates. Immunization rates were monitored using statistical process control charts to compare the HPV immunization rate in a sample of nine and ten-year-old children with a sample of 11 and 12-year-old children. The percentage of patients receiving an HPV vaccine before 11 years increased from 4.6% to 35.7% during the six months after the QI initiative began and to 60.8% 18 months after the project began. In comparison, the HPV vaccination rate in the sample of 11 and 12 year-olds increased from 78.7% to 82.8% 18 months later. This QI project used multiple interventions to increase HPV vaccination at nine years of age in a large primary care network serving a diverse low-income population. Copyright © 2018. Published by Elsevier Inc.

HPV DNA testing improves CIN2+ risk stratification and detection of CIN2+ in delayed triage of ASCUS and LSIL. A population-based follow-up study from Western Norway.

PubMed

Budal, Elisabeth B; Haugland, Hans K; Skar, Robert; Maehle, Bjørn O; Bjørge, Tone; Vintermyr, Olav K

2014-02-01

In Norway, Pap smears with atypical squamous cells of uncertain significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are triaged after 6 months. The aim of the study was to evaluate effects of implementing human papillomavirus (HPV) test (2005) in delayed triage of ASCUS and LSIL in a cohort of women from Western Norway. After a survey of 119,469 cervical Pap smears during 2005-2007, a total of 1055 women with an index ASCUS or LSIL were included in the study and followed up for 3-6 years with respect to progression into cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Overall sensitivity for detection of CIN2+ with HPV testing and cytology was 96% and 72%, respectively. The sensitivity for detection of CIN2+ was not affected by age, but the specificity of the HPV test increased with age. Thus, for the age groups <34 years, 34-50 years, and >50 years, the specificity of a positive HPV test to detect CIN2+ was 47%, 71%, and 82%, respectively. Positive predictive values for CIN2+ in women with positive cytology, positive HPV test, negative cytology, negative HPV test, or negative HPV and cytology tests were 52%, 41%, 8%, 1.5%, and 0.4%, respectively. HPV testing resulted in a net 22% increased detection of CIN2+. Fifty-six percent of CIN2+ was detected at an earlier time point with HPV testing in triage. Implementation of HPV testing in delayed triage of ASCUS and LSIL improved the stratification of CIN2+ risk and increased CIN2+ detection and at an earlier time point than with triage by cytology alone. © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

HPV DNA testing improves CIN2+ risk stratification and detection of CIN2+ in delayed triage of ASCUS and LSIL. A population-based follow-up study from Western Norway

PubMed Central

Budal, Elisabeth B; Haugland, Hans K; Skar, Robert; Mæhle, Bjørn O; Bjørge, Tone; Vintermyr, Olav K

2014-01-01

In Norway, Pap smears with atypical squamous cells of uncertain significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are triaged after 6 months. The aim of the study was to evaluate effects of implementing human papillomavirus (HPV) test (2005) in delayed triage of ASCUS and LSIL in a cohort of women from Western Norway. After a survey of 119,469 cervical Pap smears during 2005–2007, a total of 1055 women with an index ASCUS or LSIL were included in the study and followed up for 3–6 years with respect to progression into cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Overall sensitivity for detection of CIN2+ with HPV testing and cytology was 96% and 72%, respectively. The sensitivity for detection of CIN2+ was not affected by age, but the specificity of the HPV test increased with age. Thus, for the age groups <34 years, 34–50 years, and >50 years, the specificity of a positive HPV test to detect CIN2+ was 47%, 71%, and 82%, respectively. Positive predictive values for CIN2+ in women with positive cytology, positive HPV test, negative cytology, negative HPV test, or negative HPV and cytology tests were 52%, 41%, 8%, 1.5%, and 0.4%, respectively. HPV testing resulted in a net 22% increased detection of CIN2+. Fifty-six percent of CIN2+ was detected at an earlier time point with HPV testing in triage. Implementation of HPV testing in delayed triage of ASCUS and LSIL improved the stratification of CIN2+ risk and increased CIN2+ detection and at an earlier time point than with triage by cytology alone. PMID:24403090

De-stigmatising human papillomavirus in the context of cervical cancer: a randomised controlled trial.

PubMed

Kwan, Tracy T C; Tam, Kar-Fai; Lee, Peter W H; Lo, Sue S T; Chan, Karen K L; Ngan, Hextan Y S

2010-12-01

To identify the components of a human papillomavirus (HPV) message contributing to reducing the stigma of HPV in cervical cancer. 294 ethnic Chinese women attending a community-based clinic in Hong Kong were randomly allocated to read one of three written HPV messages: Group 'lr+hrHPV': low-risk and high-risk HPVs facts, Group 'hrHPV': high-risk HPV facts only and Group 'ds+hrHPV': high-risk HPV facts and de-stigmatising components, namely being anti-stereotypical, motivational and low in complexity. Main outcome measures were high-risk HPV-related sexual stigma, knowledge, attitude towards message, and intention to be HPV-tested measured by self-administered questionnaires immediately before and after reading. Message allocation had a significant effect on sexual stigma (F = 5.219, p = 0.006). Participants who read message ds+hrHPV showed the least stigma, and were significantly less likely to believe that high-risk HPV infection implicated promiscuity, non-monogamy or that monogamy offered complete protection against high-risk HPV. The genital HPV-focused message was more stigmatising than cervical cancer-focused messages. Of all participants, 93% (237/254) and 97% (260/269) indicated a positive intention to be HPV-tested before and after reading, respectively. There were no between-group differences noted in terms of knowledge and intention to be HPV-tested before or after reading. Our findings show that an HPV message containing specific de-stigmatising components may reduce public stigma towards high-risk HPV. Also, focusing solely on high-risk HPV in the context of cervical cancer helps to avoid the stigmatising effect of genital warts from tainting perceptions about high-risk HPV infection. Copyright © 2010 John Wiley & Sons, Ltd.

A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women.

PubMed

Joura, Elmar A; Giuliano, Anna R; Iversen, Ole-Erik; Bouchard, Celine; Mao, Constance; Mehlsen, Jesper; Moreira, Edson D; Ngan, Yuen; Petersen, Lone Kjeld; Lazcano-Ponce, Eduardo; Pitisuttithum, Punnee; Restrepo, Jaime Alberto; Stuart, Gavin; Woelber, Linn; Yang, Yuh Cheng; Cuzick, Jack; Garland, Suzanne M; Huh, Warner; Kjaer, Susanne K; Bautista, Oliver M; Chan, Ivan S F; Chen, Joshua; Gesser, Richard; Moeller, Erin; Ritter, Michael; Vuocolo, Scott; Luxembourg, Alain

2015-02-19

The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age. We performed a randomized, international, double-blind, phase 2b-3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV. The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group. The 9vHPV vaccine prevented infection and disease related to HPV-31, 33, 45, 52, and 58 in a susceptible population and generated an antibody response to HPV-6, 11, 16, and 18 that was noninferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine. (Funded by Merck; ClinicalTrials.gov number, NCT00543543).

Prevalence of High-Risk Genotypes of Human Papillomavirus: Women Diagnosed with Premalignant and Malignant Pap Smear Tests in Southern Ecuador.

PubMed

Dalgo Aguilar, Paola; Loján González, Cisne; Córdova Rodríguez, Ana; Acurio Páez, Katherine; Arévalo, Ana Paulina; Bobokova, Jana

2017-01-01

Human papillomavirus (HPV) is the primary infectious agent for the development of cervical cancer, although the presence of the virus alone is insufficient for viral development and proliferation; this can be attributed to the increase in potential oncogenic risk, along with other risk factors. In the present investigation, the prevalence of high-risk HPV was determined from samples of premalignant or malignant cervical cytology in women from the southern region of Ecuador. The kit we used was able to detect genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. In addition, 64.5% of the analyzed samples were positive for HPV, with genotypes 16 and 18 being the most prevalent (16 was detected in 148 samples and 18 in 108). Genotypes 58 and 51 were the third most frequent simple and multiple infections, respectively. The data are very similar to those obtained worldwide, suggesting that the strategy of sex education, and the use of vaccines as primary prevention agents, could significantly decrease the incidence and mortality rate of cervical cancer in the southern region of Ecuador.

Prevalence of High-Risk Genotypes of Human Papillomavirus: Women Diagnosed with Premalignant and Malignant Pap Smear Tests in Southern Ecuador

PubMed Central

Loján González, Cisne; Córdova Rodríguez, Ana; Acurio Páez, Katherine; Arévalo, Ana Paulina; Bobokova, Jana

2017-01-01

Human papillomavirus (HPV) is the primary infectious agent for the development of cervical cancer, although the presence of the virus alone is insufficient for viral development and proliferation; this can be attributed to the increase in potential oncogenic risk, along with other risk factors. In the present investigation, the prevalence of high-risk HPV was determined from samples of premalignant or malignant cervical cytology in women from the southern region of Ecuador. The kit we used was able to detect genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. In addition, 64.5% of the analyzed samples were positive for HPV, with genotypes 16 and 18 being the most prevalent (16 was detected in 148 samples and 18 in 108). Genotypes 58 and 51 were the third most frequent simple and multiple infections, respectively. The data are very similar to those obtained worldwide, suggesting that the strategy of sex education, and the use of vaccines as primary prevention agents, could significantly decrease the incidence and mortality rate of cervical cancer in the southern region of Ecuador. PMID:28717342

[Cervical screening: toward a new paradigm?].

PubMed

Lavoué, V; Bergeron, C; Riethmuller, D; Daraï, E; Mergui, J-L; Baldauf, J-J; Gondry, J; Douvier, S; Lopès, P; de Reilhac, P; Quéreux, C; Letombe, B; Marchetta, J; Boulanger, J-C; Levêque, J

2010-04-01

Analysis of the trials which compare the virologic testing (HPV testing) and the cytology in the cervical screening. The MedLine database was consulted using the Keywords: "cervical screening", "pap smear", "liquid based cytology", "HPV testing", "adults", "adolescents", "cervical intraepithelial neoplasia (CIN)", "uterine cervix cancer". Articles were selected according their concern about the debate of the uterine cervix cancer screening in France. The HPV testing seems interesting allowing a decreasing delay in the diagnosis of CIN (more diagnosis of CIN2+ in the first round and less during the second one). But, when the two rounds are added, the number of CIN2+ are identical in the two arms (cytology and HPV testing) in all the trials (except the Italian NTCC trial). A negative HPV testing protects the women much longer than cytology can do: a delay of five years between two rounds seems ideal. The HPV testing alone increases the detection rate of cervical lesions, which could regress spontaneously and may induce an overtreatment, especially in the youngest population: a triage is necessary and the cytology appears to be the best way to select the candidates for colposcopy in case of positive HPV testing and cytology. The HPV infection presents some particularities in adolescent females: for this reason, the HPV testing should not be used in this special population. In vaccinated women, a consensus for the screening is necessary. The health care providers in France have to understand the characteristics of the HPV testing: its advantages compared to the cytologic screening are only evident in case of an organization of the screening in France and even in Europe. (c) 2010 Elsevier Masson SAS. All rights reserved.

HPV-testing versus HPV-cytology co-testing to predict the outcome after conization.

PubMed

Bruhn, Laerke Valsøe; Andersen, Sisse Josephine; Hariri, Jalil

2018-06-01

The purpose of this study was to determine the feasibility of human Papillomavirus (HPV) testing alone as a prognostic tool to predict recurrent disease within a three-year follow-up period after treatment for cervical intraepithelial neoplasia (CIN)2 + . Retrospectively, 128 women with histologically verified CIN2 + who had a conization performed at Southern Jutland Hospital in Denmark between 1 January 2013 and 31 December 2013 were included. Histology, cytology and HPV test results were obtained for a three-year follow-up period. 4.7% (6/128) of the cases developed recurrent disease during follow-up. Of the cases without free margins, recurrent dysplasia was detected normal in 10.4% (5/48), whereas in the group with free margins it was 1.3% (1/80). The post-conization HPV test was negative in 67.2% (86/128) and Pap smear normal in 93.7% (120/128). Combining resection margins, cytology and HPV had sensitivity for prediction of recurrent dysplasia of 100%. Specificity was 45.8%, positive predictive value (PPV) 8.5% and negative predictive value (NPV) 100%. Using HPV test alone as a predictor of recurrent dysplasia gave a sensitivity of 83.3%, specificity 69.7%, PPV 11.9% and NPV 98.8%. Combining resection margin and HPV test had a sensitivity of 100%, specificity 45.9%, PPV 8.3% and NPV 100%. HPV test at six months control post-conization gave an NPV of 98.8% and can be used as a solitary test to identify women at risk for recurrent disease three years after treatment for precursor lesions. Using both resection margin and HPV test had a sensitivity of 100% and NPV 100%. Adding cytology did not increase the predictive value. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

The human papillomavirus type 58 E7 oncoprotein modulates cell cycle regulatory proteins and abrogates cell cycle checkpoints

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

Zhang Weifang; Department of Microbiology, School of Medicine, Shandong University, Jinan, Shandong; Li Jing

2010-02-05

HPV type 58 (HPV-58) is the third most common HPV type in cervical cancer from Eastern Asia, yet little is known about how it promotes carcinogenesis. In this study, we demonstrate that HPV-58 E7 significantly promoted the proliferation and extended the lifespan of primary human keratinocytes (PHKs). HPV-58 E7 abrogated the G1 and the postmitotic checkpoints, although less efficiently than HPV-16 E7. Consistent with these observations, HPV-58 E7 down-regulated the cellular tumor suppressor pRb to a lesser extent than HPV-16 E7. Similar to HPV-16 E7 expressing PHKs, Cdk2 remained active in HPV-58 E7 expressing PHKs despite the presence of elevatedmore » levels of p53 and p21. Interestingly, HPV-58 E7 down-regulated p130 more efficiently than HPV-16 E7. Our study demonstrates a correlation between the ability of down-regulating pRb/p130 and abrogating cell cycle checkpoints by HPV-58 E7, which also correlates with the biological risks of cervical cancer progression associated with HPV-58 infection.« less

Persistence of type-specific human papillomavirus infection and increased long-term risk of cervical cancer.

PubMed

Chen, Hui-Chi; Schiffman, Mark; Lin, Ching-Yu; Pan, Mei-Hung; You, San-Lin; Chuang, Li-Chung; Hsieh, Chang-Yao; Liaw, Kai-Li; Hsing, Ann W; Chen, Chien-Jen

2011-09-21

Human papillomavirus (HPV) persistence is the pivotal event in cervical carcinogenesis. We followed a large-scale community-based cohort for 16 years to investigate the role of genotype-specific HPV persistence in predicting cervical cancer including invasive and in situ carcinoma. At the baseline examination in 1991-1992, 11,923 participants (aged 30-65 years) consented to HPV testing and cytology; 6923 participants were reexamined in 1993-1995. For HPV testing, we used a polymerase chain reaction-based assay that detected 39 HPV types. Women who developed cervical cancer were identified from cancer and death registries. Cumulative risks for developing cervical cancer among infected and persistently infected women were calculated by the Kaplan-Meier method. Of 10,123 women who were initially cytologically normal, 68 developed cervical cancer. The 16-year cumulative risks of subsequent cervical cancer for women with HPV16, HPV58 (without HPV16), or other carcinogenic HPV types (without HPV16 or HPV58) were 13.5%, 10.3%, and 4.0%, respectively, compared with 0.26% for HPV-negative women. Women with type-specific persistence of any carcinogenic HPV had greatly increased risk compared with women who were HPV-negative at both visits (hazard ratio = 75.4, 95% confidence interval = 31.8 to 178.9). The cumulative cervical cancer risks following persistent carcinogenic HPV infections increased with age: The risks were 5.5%, 14.4%, and 18.1% for women aged 30-44 years, 45-54 years, and 55 years and older, respectively. However, newly acquired infections were associated with a low risk of cervical cancer regardless of age. HPV negativity was associated with a very low long-term risk of cervical cancer. Persistent detection of HPV among cytologically normal women greatly increased risk. Thus, it is useful to perform repeated HPV testing following an initial positive test.

Options in human papillomavirus (HPV) detection for cervical cancer screening: comparison between full genotyping and a rapid qualitative HPV-DNA assay in Ghana.

PubMed

Obiri-Yeboah, Dorcas; Adu-Sarkodie, Yaw; Djigma, Florencia; Akakpo, Kafui; Aniakwa-Bonsu, Ebenezer; Amoako-Sakyi, Daniel; Jacques, Simpore; Mayaud, Philippe

2017-01-01

Modern cervical cancer screening increasingly relies on the use of molecular techniques detecting high-risk oncogenic human papillomavirus (hr-HPV). A major challenge for developing countries like Ghana has been the unavailability and costs of HPV DNA-based testing. This study compares the performance of care HPV, a semi-rapid and affordable qualitative detection assay for 14 hr-HPV genotypes, with HPV genotyping, for the detection of cytological cervical squamous intraepithelial lesions (SIL). A study comparing between frequency matched HIV-1 seropositive and HIV-seronegative women was conducted in the Cape Coast Teaching Hospital, Ghana. A systematic sampling method was used to select women attending clinics in the hospital. Cervical samples were tested for HPV by care HPV and Anyplex-II HPV28 genotyping assay, and by conventional cytology. A total of 175 paired results (94 from HIV-1 seropositive and 81 from HIV-seronegative women) were analyzed based on the ability of both tests to detect the 14 hr-HPV types included in the care HPV assay. The inter-assay concordance was 94.3% (95%CI: 89.7-97.2%, kappa = 0.88), similar by HIV serostatus. The care HPV assay was equally sensitive among HIV-1 seropositive and seronegative women (97.3% vs. 95.7%, p  = 0.50) and slightly more specific among HIV-seronegative women (85.0% vs. 93.1%, p  = 0.10). care HPV had good sensitivity (87.5%) but low specificity (52.1%) for the detection of low SIL or greater lesions, but its performance was superior to genotyping (87.5 and 38.8%, respectively). Reproducibility of care HPV, tested on 97 samples by the same individual was 82.5% (95%CI: 73.4-89.4%). The performance characteristics of care HPV compared to genotyping suggest that this simpler and cheaper HPV detection assay could offer a suitable alternative for HPV screening in Ghana.

Determinants of women's likelihood of vaginal self-sampling for human papillomavirus to screen for cervical cancer in Taiwan: a cross-sectional study.

PubMed

Chen, Shu-Ling; Hsieh, Pao-Chun; Chou, Chia-Hui; Tzeng, Ya-Ling

2014-11-25

Many Taiwanese women (43.8%) did not participate in regular cervical screening in 2011. An alternative to cervical screening, self-sampling for human papillomavirus (HPV), has been available at no cost under Taiwan's National Health Insurance since 2010, but the extent and likelihood of HPV self-sampling were unknown. A cross-sectional study was performed to explore determinants of women's likelihood of HPV self-sampling. Data were collected by questionnaire from a convenience sample of 500 women attending hospital gynecologic clinics in central Taiwan from June to October 2012. Data were analyzed by descriptive statistics, chi-square test, and logistic regression. Of 500 respondents, 297 (59.4%) had heard of HPV; of these 297 women, 69 (23%) had self-sampled for HPV. Among the 297 women who had heard of HPV, 234 (78.8%) considered cost a priority for HPV self-sampling. Likelihood of HPV self-sampling was determined by previous Pap testing, high perceived risk of cervical cancer, willingness to self-sample for HPV, high HPV knowledge, and cost as a priority consideration. Outreach efforts to increase the acceptability of self-sampling for HPV testing rates should target women who have had a Pap test, perceive themselves at high risk for cervical cancer, are willing to self-sample for HPV, have a high level of HPV knowledge, and for whom the cost of self-sampling covered by health insurance is a priority.

Management algorithms for cervical cancer screening and precancer treatment for resource-limited settings.

PubMed

Basu, Partha; Meheus, Filip; Chami, Youssef; Hariprasad, Roopa; Zhao, Fanghui; Sankaranarayanan, Rengaswamy

2017-07-01

Management algorithms for screen-positive women in cervical cancer prevention programs have undergone substantial changes in recent years. The WHO strongly recommends human papillomavirus (HPV) testing for primary screening, if affordable, or if not, then visual inspection with acetic acid (VIA), and promotes treatment directly following screening through the screen-and-treat approach (one or two clinic visits). While VIA-positive women can be offered immediate ablative treatment based on certain eligibility criteria, HPV-positive women need to undergo subsequent VIA to determine their eligibility. Simpler ablative methods of treatment such as cryotherapy and thermal coagulation have been demonstrated to be effective and to have excellent safety profiles, and these have become integral parts of new management algorithms. The challenges faced by low-resource countries are many and include, from the management perspective, identifying an affordable point-of-care HPV detection test, minimizing over-treatment, and installing an effective information system to ensure high compliance to treatment and follow-up. © 2017 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.

Stability Study of Cervical Specimens Collected by Swab and Stored Dry Followed by Human Papillomavirus DNA Detection Using the cobas 4800 Test.

PubMed

Lin, Chun-Qing; Zeng, Xi; Cui, Jian-Feng; Liao, Guang-Dong; Wu, Ze-Ni; Gao, Qian-Qian; Zhang, Xun; Yu, Xiu-Zhang; Chen, Wen; Xi, Ming-Rong; Qiao, You-Lin

2017-02-01

Safer, more convenient methods for cervical sample collection and storage are necessary to facilitate human papillomavirus (HPV) DNA testing in low-resource settings. Our study aimed to evaluate the stability of cervical specimens collected with dry swabs and stored dry, compared to liquid-based cytology (LBC) samples, as detected by HPV DNA testing. Women with abnormal cytological findings or HPV-positive results at colposcopy were recruited from the West China Second University Hospital, Sichuan University, between October 2013 and March 2014. From each woman, physicians collected cervical specimens with a swab placed into a Sarstedt tube and a CytoBrush placed into LBC medium. Samples were randomly assigned to be stored at uncontrolled ambient temperature for 2, 7, 14, or 28 days and then were tested for 14 high-risk HPV (HR-HPV) types using the cobas HPV test. The rates of agreement between dry swab and LBC samples for any HR-HPV type, HPV16, HPV18, and the 12 pooled HR-HPV types were 93.8%, 97.8%, 99.4%, and 93.2%, respectively, with kappa values of 0.87 (95% confidence interval [CI], 0.83 to 0.91), 0.94 (95% CI, 0.91 to 0.97), 0.94 (95% CI, 0.87 to 1.00), and 0.86 (95% CI, 0.82 to 0.90). The performance of swab samples for detection of cervical precancerous lesions by means of cobas HPV testing was equal to that of LBC samples, even with stratification by storage time. Dry storage of swab-collected cervical samples can last for 1 month without loss of test performance by cobas HPV testing, compared to LBC samples, which may offer a simple inexpensive approach for cervical cancer screening in low-resource settings. Copyright © 2017 American Society for Microbiology.

The EVVA Cohort Study: Anal and Cervical Type-Specific Human Papillomavirus Prevalence, Persistence, and Cytologic Findings in Women Living With HIV.

PubMed

de Pokomandy, Alexandra; Kaufman, Elaina; de Castro, Christina; Mayrand, Marie-Hélène; Burchell, Ann N; Klein, Marina; Charest, Louise; Auger, Manon; Rodrigues-Coutlée, Sophie; Coutlée, François

2017-08-15

The risk of anal cancer due to high-risk human papillomavirus (HR-HPV) is higher in women living with human immunodeficiency virus (HIV) than in the general population. We present findings of cervical and anal HPV and cytologic tests at baseline in the EVVA cohort study and HPV persistence data 6 months after baseline. Semiannual visits included questionnaires, chart reviews, cervical/anal cytologic and cervical/anal HPV testing for 2 years. Genotyping for 36 HPV genotypes was performed using the Roche Linear Array HPV genotyping test. A total of 151 women living with HIV were recruited. At baseline, 75% had anal HPV, 51% had anal HR-HPV, 50% had cervical HPV, and 29% had cervical HR-HPV. Anal HPV-16 and HPV-51 were more frequent in women born in Canada (31% and 29%, respectively, compared with ≤16% for other women). Most anal HR-HPV types detected at 6 months (57%-93%) were persistent from baseline. Findings of anal cytologic tests were abnormal for 37% of women. Anal HPV is highly prevalent in women living with HIV, and type distribution varies by place of birth. High-resolution anoscopy was indicated in more than one third of results. As anal cancer is potentially preventable, these important findings need to be considered when selecting the best approach for anal cancer screening programs. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Human papillomavirus reduces the prognostic value of nodal involvement in tonsillar squamous cell carcinomas.

PubMed

Straetmans, Jos M J A A; Olthof, Nadine; Mooren, Jeroen J; de Jong, Jos; Speel, Ernst-Jan M; Kremer, Bernd

2009-10-01

Assessment of the prognostic value of nodal status in relation to human papillomavirus (HPV) status and the various treatment modalities in tonsillar squamous cell carcinomas (TSCC). Retrospective 5-year survival analysis. A 5-year follow-up of disease-free, disease-specific, and overall survival in a group of 81 patients with TSCC was conducted. The nodal status and integration of HPV-DNA in the genome (detected with fluorescence in situ hybridization) as prognostic indicators were examined while correcting for other clinical parameters (smoking habits, alcohol consumption, treatment modality, differentiation, TNM classification). Of TSCCs, 41% were positive for HPV type 16. In these TSCCs, the primary tumor was significantly smaller when compared to HVP-negative TSCCs (P = .04), whereas the percentage of cases with cervical metastases was identical. In the total population, it was not nodal involvement, but rather HPV manifestation, which was related to patient prognosis. Within the treatment modalities (surgery combined with radiotherapy and radiotherapy alone), neither nodal status nor HPV were prognostic indicators. Since a substantial percentage of TSCCs are HPV-positive and metastasizes to cervical lymph nodes in less advanced primary tumors, the N status is an unreliable prognostic indicator in TSCCs. HPV is only prognostically relevant in the total tumor population, but loses its value within patient groups receiving a single treatment modality. The value of HPV for prognosis of patients with TSCC requires further study.

HPV test results and histological follow-up results of patients with LSIL Cervical Cytology from the Largest CAP-certified laboratory in China.

PubMed

Zheng, Baowen; Yang, Huaitao; Li, Zaibo; Wei, Guijian; You, Jia; Liang, Xiaoman; Zhao, Chengquan

2017-01-01

Age-adjusted evaluations have explored the possible utility of (HPV test results in women with LSIL Pap. We investigated HPV test results and histopathologic follow-up results of LSIL patients from China's largest CAP-certified laboratory. Patients with LSIL between 2011 and 2015 from the Guangzhou Kingmed Diagnostics were retrospectively retrieved and their hrHPV test results and histological follow-up results were collected and analyzed. LSIL result was identified in 37,895 cases from 2,206,588 Pap tests (1.7%) including 1,513,265 liquid-based cytology and 693,323 conventional Pap tests. The average of these women was 38.4 years (15-88). The LSIL reporting rate in women <30 years was significantly higher than that in women > 30 years (2.1% vs 1.7%). The age specific reporting LSIL rates declined with increased age. 8,014 of 37,895 (21.2%) women with LSIL cytology also had HC2 HPV test results. 75.8% of women with LSIL Pap tests were hrHPV+ and the HPV+ rates declined with increased age except in patients older than 60 years. Overall histopathologic diagnoses within 6 months after LSIL were identified in 5,987 of 37,895 patients at Guangzhou Kingmed Diagnostics. CIN2/3 was identified in 15.2% patients, CIN1 in 66.9%, negative in 14.9% patients. No invasive carcinoma was found in all patients. Of 8014 patients with LSIL Pap test and HPV testing results, 1727 patients had histological follow-up within 6 months after Pap cytology test and HPV testing. The detection rate of CIN2/3 was significantly higher in patients with positive HPV testing result than that in patients with negative HPV testing result (17.8% vs. 8.1%). Among patients with LSIL/HPV negative tests, CIN2/3 was detected in 1 of 30 (3.3%) women aged 50 years and above, appearing lower than those in women less than 50 years (8.0%, 28/351, P=0.357). This is the largest histological follow-up study in women with LSIL Pap from China and the data are helpful in establishing a baseline for better understanding the status of cervical screening in China. The 85.1% positive predict value of LSIL Pap cytology for follow-up CIN lesion was within currently recognized benchmark ranges.

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

The Effect of History of Abnormal Pap Smear or Preceding HPV infection on the Humoral Immune Response to Quadrivalent Human Papilloma virus (qHPV) Vaccine in Women with Systemic Lupus Erythematosus.

PubMed

Dhar, J Patricia; Essenmacher, Lynnette; Dhar, Renee; Magee, Ardella; Ager, Joel; Sokol, Robert J

2018-04-30

To determine if natural human papillomavirus (HPV) infection would induce an anamnestic response to quadrivalent (qHPV) vaccine in women with Systemic Lupus Erythematosus (SLE). Thirty four women (19-50 years) with mild to moderate and minimally active or inactive SLE received standard qHPV vaccine. Neutralizing antibody titers to HPV 6, 11, 16 and18 were evaluated pre- and post- vaccine using HPV competitive Luminex Immunoassay. For each HPV type, logistic regressions were performed to explore the relationship between a positive titer at baseline with their final geometric mean titer and with the rise in titer. Fisher's Exact Test was used to assess the association of at least one positive HPV antibody test at baseline and history of abnormal pap. History of abnormal pap smear/cervical neoplasia occurred in 52.9%. Baseline anti HPV antibody titers: 21% = negative for all 4 HPV types, 79% = positive for ≥1 of the HPV types. Statistical analysis showed: those with a history of abnormal pap smear/cervical neoplasia were likely to have a positive anti-HPV antibody result pre-vaccine to ≥ 1 of the 4 types, p = 0.035 Fisher's Exact Test. In general, HPV exposed women showed higher post vaccine GMTs than HPV unexposed women with higher point estimates. However, when examining the rise in titers using logistic regression, there was no evidence of an anamnestic response. Prior HPV infection and cervical neoplasia in SLE are linked with no anamnestic response to HPV vaccine. This supports not checking HPV-antibodies pre-vaccine. Women with SLE should be vaccinated for HPV.

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

PubMed

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

2018-05-16

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

HPV-Testing in Follow-up of Patients Treated for CIN2+ Lesions

PubMed Central

Mariani, Luciano; Sandri, Maria Teresa; Preti, Mario; Origoni, Massimo; Costa, Silvano; Cristoforoni, Paolo; Bottari, Fabio; Sideri, Mario

2016-01-01

Persistent positivity of HPV-DNA testing is considered a prognostic index of recurrent disease in patients treated for CIN2+. HPV detection, and particularly genotyping, has an adequate high rate of sensitivity and specificity (along with an optimal reproducibility), for accurately predicting treatment failure, allowing for an intensified monitoring activity. Conversely, women with a negative HPV-test 6 months after therapy have a very low risk for residual/recurrent disease, which leads to a more individualized follow-up schedule, allowing for a gradual return to the normal screening scheme. HPV testing should be routinely included (with or without cytology) in post-treatment follow-up of CIN2+ patients for early detection of recurrence and cancer progression. HPV genotyping methods, as a biological indicator of persistent disease, could be more suitable for a predictive role and risk stratification (particularly in the case of HPV 16/18 persistence) than pooled HPV-based testing. However, it is necessary to be aware of the performance of the system, adhering to strict standardization of the process and quality assurance criteria. PMID:26722366

Development of culturally tailored educational brochures on HPV and pap tests for American Indian women.

PubMed

Sharpe, Patricia A; Brandt, Heather M; McCree, Donna H; Owl-Myers, Elizabeth; Taylor, Betty; Mullins, Glenda

2013-07-01

Participatory formative research guided the creation of a culturally tailored educational brochure about human papillomavirus (HPV) at an American Indian women's clinic. A review of existing educational materials and in-depth interviews were conducted. Nine steps for creating health communications messages that were patterned after National Cancer Institute guidelines guided the brochure development process. Of 95 women tested for HPV, 41% were positive, 32 (34%) agreed to the in-depth interview, and 9 agreed to the pretesting interview. Mean age was 41 years. Interviews revealed key themes concerning emotional reactions to abnormal Pap test results and HPV; need for basic information about HPV, Pap tests, and results; concerns about HPV stigma, sexual transmission, and communication with sexual partner; and the preferred source and format for HPV educational materials. A literature review revealed 12 areas of basic HPV content. A participatory process successfully engaged nursing staff and patients in creating culturally appropriate brochures for clinic use. This article provides specific steps for creating culturally tailored patient education materials.

Oropharyngeal cancer and human papilloma virus: evolving diagnostic and management paradigms.

PubMed

Buckley, Lisa; Gupta, Ruta; Ashford, Bruce; Jabbour, Joe; Clark, Jonathan R

2016-06-01

The significant increase in human papilloma virus (HPV)-associated oropharyngeal carcinoma (OPC) over recent years has lead to a surge in research and an improved understanding of the disease. Most patients with HPV-associated OPC present with cystic nodal metastases with a small primary tumour, and respond well to all treatment modalities including primary surgery and primary chemoradiotherapy. Current research is evaluating treatment de-escalation to reduce long-term treatment-associated morbidities. Transoral robotic surgery (TORS) is particularly relevant as the transoral approach allows small primary tumours to be removed with lower morbidity than traditional surgical approaches. The current American Joint Committee on Cancer staging system for oropharyngeal cancer does not appropriately stratify HPV-associated OPC; hence, alternative risk stratification and staging classifications are being proposed. © 2015 Royal Australasian College of Surgeons.

Relative Performance of HPV and Cytology Components of Cotesting in Cervical Screening.

PubMed

Schiffman, Mark; Kinney, Walter K; Cheung, Li C; Gage, Julia C; Fetterman, Barbara; Poitras, Nancy E; Lorey, Thomas S; Wentzensen, Nicolas; Befano, Brian; Schussler, John; Katki, Hormuzd A; Castle, Philip E

2018-05-01

The main goal of cervical screening programs is to detect and treat precancer before cancer develops. Human papillomavirus (HPV) testing is more sensitive than cytology for detecting precancer. However, reports of rare HPV-negative, cytology-positive cancers are motivating continued use of both tests (cotesting) despite increased testing costs. We quantified the detection of cervical precancer and cancer by cotesting compared with HPV testing alone at Kaiser Permanente Northern California (KPNC), where 1 208 710 women age 30 years and older have undergone triennial cervical cotesting since 2003. Screening histories preceding cervical cancers (n = 623) and precancers (n = 5369) were examined to assess the relative contribution of the cytology and HPV test components in identifying cases. The performances of HPV testing and cytology were compared using contingency table methods, general estimating equation models, and nonparametric statistics; all statistical tests were two-sided. HPV testing identified more women subsequently diagnosed with cancer (P < .001) and precancer (P < .001) than cytology. HPV testing was statistically significantly more likely to be positive for cancer at any time point (P < .001), except within 12 months (P = .10). HPV-negative/cytology-positive results preceded only small fractions of cases of precancer (3.5%) and cancer (5.9%); these cancers were more likely to be regional or distant stage with squamous histopathology than other cases. Given the rarity of cancers among screened women, the contribution of cytology to screening translated to earlier detection of at most five cases per million women per year. Two-thirds (67.9%) of women found to have cancer during 10 years of follow-up at KPNC were detected by the first cotest performed. The added sensitivity of cotesting vs HPV alone for detection of treatable cancer affected extremely few women.

[Distribution and associated factors of high-risk HPV genotypes infection among HPV-positive women who participated cervical screening test in Shenzhen, 2014-2016, China].

PubMed

Wang, Y Y; Lin, W; Wu, B; Yuan, S X; Yao, J L; Zhao, X S; Chen, B; Qiao, Y L; Zhao, F H; Chen, W; Hu, S Y; Liu, Z H

2018-05-06

Objective: To analyze the distribution and associated factors of high-risk genotypes of HPV in cervical infection among women in Shenzhen. Methods: The information on sociodemographic characteristics and HPV genotypes of HPV-positive women who participated cervical screening test from January 2014 to December 2016 was downloaded from Shenzhen Maternity and Child Healthcare Management Information System. According to the pathogenicity, the high-risk HPV genotypes were divided into 15 types including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68; and there were 6 low-risk genotypes including HPV 6, 11, 42, 43, 44, and 81. Chi-square tests were applied to compare the proportions of high-risk HPV infection among women who had different sociodemographic characteristics. A non-conditional logistic regression model was used to analyze the associated factors for high-risk HPV infection. Results: In total, all HIV positives received HPV genotyping, with an average age of (38.08±9.38) years old. There were 9 979 (93.9%) high-risk and 645 (6.1%) low-risk HPV infections. The proportions of HPV infections for high-risk type in each year were 91.5%, 93.8%, and 95.6%, increasing with the screening years (χ(2)=54.79, P< 0.001). Multivariate logistic regression analysis showed that compared with women younger than 25 years old, women in other age groups (at age 26 to 30 years, 31 to 35 years, 36 to 40 years, 41 to 45 years, and 50 years or older) had increased risks of high-risk HPV infection, with OR (95 %CI ) of 1.67 (1.20-2.31), 1.49 (1.09-2.03), 1.71 (1.23-2.37), 1.65 (1.19-2.31), and 1.84 (1.26-2.67), respectively; compared with the married, single women had a decreased risk of high-risk HPV infection ( OR (95 %CI ): 0.71 (0.50-1.00)); women received HPV testing in 2015 and 2016 showed higher risk of high-risk HPV infection than those in 2014 ( OR (95 %CI ): 1.43 (1.17-1.74) and 2.03 (1.68-2.46)). The 5 most common HPV genotypes were HPV52 (25.1%, 2 670 cases), followed by HPV16 (19.2%, 2 041 cases), HPV58 (13.3%, 1 413 cases), HPV18 (9.9%, 1 048 cases), and HPV51 (9.3%, 993 cases). Conclusion: Age, marital status, and screening year were associated with high-risk HPV infections. Besides HPV16 and HPV18, the prevention and control on HPV infections for HPV52, HPV58, and HPV51 should be prioritized in Shenzhen area.

The role of human papillomavirus vaccines in cervical cancer: Prevention and treatment.

PubMed

Bogani, Giorgio; Leone Roberti Maggiore, Umberto; Signorelli, Mauro; Martinelli, Fabio; Ditto, Antonino; Sabatucci, Ilaria; Mosca, Lavinia; Lorusso, Domenica; Raspagliesi, Francesco

2018-02-01

Human papillomavirus (HPV) is the most common sexually transmitted disease, worldwide. Primary prevention thorough vaccination si able to reduce the burden of HPV-related lesions. Ten years ago the Food and drug Administration (FDA) approved the first vaccine against HPV. In the last decades, growing data on safety and effectiveness have been collected. In the present review we report the current knowledge on vaccine against HPV, highlighting the current value and prospective regarding the widespread diffusion of HPV vaccines. The role of emerging therapeutic vaccines is reviewed. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevalence and clinical utility of human papilloma virus genotyping in patients with cervical lesions.

PubMed

Kaur, Parminder; Aggarwal, Aruna; Nagpal, Madhu; Oberoi, Loveena; Sharma, Swati

2014-08-01

Cervical cancer is the commonest cancer among Indian women. High-risk human papilloma virus (HPV) detection holds the potential to be used as a tool to identify women, at risk of subsequent development of cervical cancer. There is a pressing need to identify prevalence of asymptomatic cervical HPV infection in local population. In our study, we explored the prevalence of HPV genotypes and their distribution in women with cervical lesions. Scrape specimens were obtained from 100 women (study group) with cervical abnormalities. HPV was detected with amplicor HPV tests, and the individual genotypes in these specimens were identified by Hybribio Genoarray test kit. Fifty specimens were also collected from females with healthy cervix (control group). The present study also aimed to determine the status of HPV prevalence and its association with different sociodemographic factors. Out of the total number of 100 samples, 10 (10 %) women tested positive for HPV DNA. Among them, HPV 18 was observed in 6, HPV 16 in 2, HPV 52 and HPV 39 in one each. Fifty specimens collected from patients with healthy cervix were not infected with any of the HPV genotype. Our study generates data of HPV prevalence in patients with cervical lesions visiting tertiary care institute. The data generated will be useful for laying guidelines for mass screening of HPV detection, treatment, and prophylaxis.

HPV genotypes and associated cervical cytological abnormalities in women from the Pearl River Delta region of Guangdong province, China: a cross-sectional study

PubMed Central

2014-01-01

Background It is important to understand the specific HPV genotype distribution in screen-detected lesions. HPV Genotype is helpful for separating HPV-positive women at greater risk of cancer from those who can regress spontaneously and for preventing cervical cancer at early stage. The aim of this study was to investigate the high-risk HPV genotype distribution among cervical cytology abnormality in Pearl River Delta Region, Southern China Methods 5585 HPV-infected women were screened from 77069 women in Pearl River Delta Region. Information was obtained from 3226 screened subjects through questionnaires and personal interviews. Exfoliated cervical cells were collected by doctors for HPV test with MassARRAY (Sequenom, Sandiego, CA) technique based on the matrix-assisted laser desorption/ionization time-of flight (MALDI-TOF) mass spectrometry (MS). The ThinPrep cytology test was performed to screen for cervical cancer. Unconditional logistic was used to determine the most common HPV carcinogenic types. Results Of the 3226 HPV-positive samples tested, 1744 (54.1%) with normal cervical cytology, 1482 (45.9%) with abnormal cytology. The five most common HPV types in this study were HPV16 (20.2%), HPV52 (17.1%), HPV58 (13.2%), HPV18 (9.5%), HPV6 (7.6%). Overall, HPV16 (OR = 10.5, 95% CI: 3.7 ~ 29.6), HPV33 (OR = 9.1, 95% CI: 2.8 ~ 29.2), HPV58 (OR = 6.3, 95% CI: 2.1 ~ 18.6), HPV31 (OR = 4.5, 95% CI: 1.3 ~ 15.5), multiple genotype infection (OR = 3.0, 95% CI: 1.7 ~ 14.7), especially HPV16 and HPV33, increased the risk of cytology abnormalities. Conclusions HPV16, HPV31, HPV33, HPV58, and multiple HPV genotype infection increased the risk of cytology abnormalities in Pearl River Delta Region and might be useful for the screening, preventing, treating, and monitoring of pre-cancer lesions in southern China. PMID:25016305

Cost-effectiveness analysis of different types of human papillomavirus vaccination combined with a cervical cancer screening program in mainland China.

PubMed

Mo, Xiuting; Gai Tobe, Ruoyan; Wang, Lijie; Liu, Xianchen; Wu, Bin; Luo, Huiwen; Nagata, Chie; Mori, Rintaro; Nakayama, Takeo

2017-07-18

China has a high prevalence of human papillomavirus (HPV) and a consequently high burden of disease with respect to cervical cancer. The HPV vaccine has proved to be effective in preventing cervical cancer and is now a part of routine immunization programs worldwide. It has also proved to be cost effective. This study aimed to assess the cost-effectiveness of 2-, 4-, and 9-valent HPV vaccines (hereafter, HPV2, 4 or 9) combined with current screening strategies in China. A Markov model was developed for a cohort of 100,000 HPV-free girls to simulate the natural history to HPV infection. Three recommended screening methods (1. liquid-based cytology test + HPV DNA test; 2. pap smear cytology test + HPV DNA test; 3. visual inspection with acetic acid) and three types of HPV vaccination program (HPV2/4/9) were incorporated into 15 intervention options, and the incremental cost-effectiveness ratio (ICER) was calculated to determine the dominant strategies. Costs, transition probabilities and utilities were obtained from a review of the literature and national databases. One-way sensitivity analyses and threshold analyses were performed for key variables in different vaccination scenarios. HPV9 combined with screening showed the highest health impact in terms of reducing HPV-related diseases and increasing the number of quality-adjusted life years (QALYs). Under the current thresholds of willingness to pay (WTP, 3 times the per capita GDP or USD$ 23,880), HPV4/9 proved highly cost effective, while HPV2 combined with screening cost more and was less cost effective. Only when screening coverage increased to 60% ~ 70% did the HPV2 and screening combination strategy become economically feasible. The combination of the HPV4/9 vaccine with current screening strategies for adolescent girls was highly cost-effective and had a significant impact on reducing the HPV infection-related disease burden in Mainland China.

Brief research report: uncertainty-inducing and reassuring facts about HPV: a descriptive study of French Canadian women.

PubMed

Rosen, Natalie O; Knäuper, Bärbel; Pagé, Gabrielle; Di Dio, Pasqualina; Morrison, Eleshia; Mayrand, Marie-Hélène; Franco, Eduardo L; Rosberger, Zeev

2009-10-01

We sought to describe information that makes women feel (1) uncertain and (2) reassured about their human papillomavirus (HPV) status and the potential health implications of an HPV DNA test result and (3) to examine information seeking after receiving their result. Thirty women (previously tested HPV negative) read factual information on HPV and cervical cancer and were asked which facts were uncertainty inducing and which were reassuring. Twenty-four facts reassured women of their HPV negative status, 11 facts made women feel uncertain, and 10 facts made them feel both. The most common reason for seeking information in the future was receiving a positive test result. The authors outline what specific facts about HPV health providers can emphasize to alleviate anxiety and encourage women to feel reassured of their low cancer risk following a negative test result.

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

PubMed

Ronco, Guglielmo; Confortini, Massimo; Maccallini, Vincenzo; Naldoni, Carlo; Segnan, Nereo; Sideri, Mario; Zappa, Marco; Zorzi, Manuel; Calvia, Maria; Giorgi Rossi, Paolo

2012-01-01

OBJECTIVE OF THE PROJECT: Purpose of this Report is to evaluate the impact of the introduction of liquid-based cytology (LBC) in cervical cancer screening in terms of efficacy, undesired effects, costs and implications for organisation. EFFICACY AND UNDESIRED EFFECTS: LBC WITH MANUAL INTERPRETATION: The estimates of cross-sectional accuracy for high-grade intraepithelial neoplasia (CIN2 or more severe and CIN3 or more severe) obtained by a systematic review and meta-analysis published in 2008 were used. This review considered only studies in which all women underwent colposcopy or randomised controlled trials (RCTs) with complete verification of test positives. A systematic search of RCTs published thereafter was performed. Three RCTs were identified. One of these studies was conducted in 6 Italian regions and was of large size (45,174 women randomised); a second one was conducted in another Italian region (Abruzzo) and was of smaller size (8,654 women randomised); a third RCT was conducted in the Netherlands and was of large size (89,784 women randomised). No longitudinal study was available. There is currently no clear evidence that LBC increases the sensitivity of cytology and even less that its introduction increases the efficacy of cervical screening in preventing invasive cancers. The Italian randomised study NTCC showed a decrease in specificity, which was not observed in the other two RCTs available. In addition, the 2008 meta-analysis observed a reduction - even if minimal - in specificity just at the ASC-US cytological cut-off, but also a remarkable heterogeneity between studies. These results suggest that the effect of LBC on specificity is variable and plausibly related to the local style of cytology interpretation. There is evidence that LBC reduces the proportion of unsatisfactory slides, although the size of this effect varies remarkably. LBC WITH COMPUTER-ASSISTED INTERPRETATION: An Australian study, based on double testing, showed a statistically significant increase of the sensitivity for CIN2 or more of LBC with computer-assisted interpretation vs. conventional cytology with manual interpretation. However, an English RCT estimated that LBC with computer-assisted interpretation has a lower sensitivity than LBC with manual interpretation. COST AND ECONOMIC EVALUATION: In the current Italian situation the use of liquid-based cytology for primary screening is estimated to increase the costs of cytological screening. Liquid-based cytology needs shorter time for interpretation than conventional cytology. However, in the Italian situation, savings obtained from this time reduction and from the decreased number of repeats due to unsatisfactory slides are not currently sufficient to compensate the cost increase due to the prices currently applied by producers and to a possible greater number of colposcopies caused by LBC. In any case, at current prices, cost is estimated to increase even when assuming a referral rate to colposcopy with LBC similar or slightly lower than that with conventional cytology. For the costs of computer-assisted interpretation of liquid-based cytology, readers are referred to the relative HTA report (Epidemiol Prev 2012;36(5) Suppl 3:e1-43). ORGANISATIONAL AND ETHICAL ASPECTS: Ethical, legal and communication problems are judged to remain unchanged when compared to screening with conventional cytology. After having used the test for some time, interpreters prefer liquid-based to conventional cytology. Reduced time for interpretation makes the adoption of LBC a possible approach to deal with shortenings of cytology interpreters which is happening in Italy. However, alternative solutions, such as computer-assisted interpretation of cytology and the use of HPV as primary screening test, should be considered. Liquid-based cytology allows performing molecular tests, in particular the HPV test. This property allows triaging women with borderline or mild cytology by "reflex" molecular or immunocytochemical tests with no need to recall them. LBC sampling can be used also if HPV is applied as the primary screening test, allowing "reflex" triaging of HPV positive women by cytology with no need to recall them nor to take two samples, one for HPV testing and one for conventional cytology. This represents a remarkable advantage in terms of organization. However, costs are high because only 5-7% of women screened with this approach need interpretation of cytology. In addition, HPV testing with the Hybrid Capture assay on material preserved in LBC transport media needs a preliminary conversion phase, which limits the use of LBC for triaging HPV positive women. It is advisable that in the near future industry develops sampling/transport systems that allow performing both the HPV test and cytology or other validated triage tests without additional manipulations and at sustainable costs.

Sensitivity and specificity of oral HPV detection for HPV-positive head and neck cancer.

PubMed

Gipson, Brooke J; Robbins, Hilary A; Fakhry, Carole; D'Souza, Gypsyamber

2018-02-01

The incidence of HPV-related head and neck squamous cell carcinoma (HPV-HNSCC) is increasing. Oral samples are easy and non-invasive to collect, but the diagnostic accuracy of oral HPV detection methods for classifying HPV-positive HNSCC tumors has not been well explored. In a systematic review, we identified eight studies of HNSCC patients meeting our eligibility criteria of having: (1) HPV detection in oral rinse or oral swab samples, (2) tumor HPV or p16 testing, (3) a publication date within the last 10 years (January 2007-May 2017, as laboratory methods change), and (4) at least 15 HNSCC cases. Data were abstracted from each study and a meta-analysis performed to calculate sensitivity and specificity. Eight articles meeting inclusion criteria were identified. Among people diagnosed with HNSCC, oral HPV detection has good specificity (92%, 95% CI = 82-97%) and moderate sensitivity (72%, 95% CI = 45-89%) for HPV-positive HNSCC tumor. Results were similar when restricted to studies with only oropharyngeal cancer cases, with oral rinse samples, or testing for HPV16 DNA (instead of any oncogenic HPV) in the oral samples. Among those who already have HNSCC, oral HPV detection has few false-positives but may miss one-half to one-quarter of HPV-related cases (false-negatives). Given these findings in cancer patients, the utility of oral rinses and swabs as screening tests for HPV-HNSCC among healthy populations is probably limited. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human Papillomavirus Prevalence and Herd Immunity after Introduction of Vaccination Program, Scotland, 2009–2013

PubMed Central

Kavanagh, Kimberley; Pan, Jiafeng; Love, John; Cuschieri, Kate; Robertson, Chris; Ahmed, Syed; Palmer, Timothy; Pollock, Kevin G.J.

2016-01-01

In 2008, a national human papillomavirus (HPV) immunization program using a bivalent vaccine against HPV types 16 and 18 was implemented in Scotland along with a national surveillance program designed to determine the longitudinal effects of vaccination on HPV infection at the population level. Each year during 2009–2013, the surveillance program conducted HPV testing on a proportion of liquid-based cytology samples from women undergoing their first cervical screening test for precancerous cervical disease. By linking vaccination, cervical screening, and HPV testing data, over the study period we found a decline in HPV types 16 and 18, significant decreases in HPV types 31, 33, and 45 (suggesting cross-protection), and a nonsignificant increase in HPV 51. In addition, among nonvaccinated women, HPV types 16 and 18 infections were significantly lower in 2013 than in 2009. Our results preliminarily indicate herd immunity and sustained effectiveness of the bivalent vaccine on virologic outcomes at the population level. PMID:26692336

Human Papillomavirus Prevalence and Herd Immunity after Introduction of Vaccination Program, Scotland, 2009-2013.

PubMed

Cameron, Ross L; Kavanagh, Kimberley; Pan, Jiafeng; Love, John; Cuschieri, Kate; Robertson, Chris; Ahmed, Syed; Palmer, Timothy; Pollock, Kevin G J

2016-01-01

In 2008, a national human papillomavirus (HPV) immunization program using a bivalent vaccine against HPV types 16 and 18 was implemented in Scotland along with a national surveillance program designed to determine the longitudinal effects of vaccination on HPV infection at the population level. Each year during 2009-2013, the surveillance program conducted HPV testing on a proportion of liquid-based cytology samples from women undergoing their first cervical screening test for precancerous cervical disease. By linking vaccination, cervical screening, and HPV testing data, over the study period we found a decline in HPV types 16 and 18, significant decreases in HPV types 31, 33, and 45 (suggesting cross-protection), and a nonsignificant increase in HPV 51. In addition, among nonvaccinated women, HPV types 16 and 18 infections were significantly lower in 2013 than in 2009. Our results preliminarily indicate herd immunity and sustained effectiveness of the bivalent vaccine on virologic outcomes at the population level.

Comparison of the clinical performances of the AdvanSure HPV Screening Real-Time PCR, the Abbott Real-Time High-Risk HPV Test, and the Hybrid Capture High-Risk HPV DNA Test for Cervical Cancer Screening.

PubMed

Chung, Hae-Sun; Hahm, Chorong; Lee, Miae

2014-09-01

The clinical performance of three human papillomavirus (HPV) DNA commercial assays for cervical cancer screening was evaluated; the AdvanSure HPV Screening Real-Time PCR (AdvanSure PCR; LG Life Sciences) that was developed recently for the detection of both high-risk and low-risk genotypes, the Abbott RealTime High-Risk HPV Test (Abbott PCR; Abbott Molecular) and the Hybrid Capture High-Risk HPV DNA test (HC2; Qiagen). The three different HPV DNA tests were compared using cytology samples obtained from 619 women who underwent routine cervical cancer screening. The gold-standard assay was histopathological confirmation of cervical intraepithelial neoplasia of grade 2 or worse. The clinical sensitivities of the AdvanSure PCR, the Abbott PCR and the HC2 for the detection of cervical intraepithelial neoplasia of grade 2 or worse were 95.5%, 95.5% and 100%, respectively, while the clinical specificities were 61.6%, 86.4% and 83.3%, respectively. There were no significant differences in the clinical sensitivities of the Abbott PCR and the AdvanSure PCR compared to the HC2. The clinical specificities of the Abbott PCR and the AdvanSure PCR for the detection of HPV types 16/18 were 97.8% and 98.5%, respectively. For cervical cancer screening, all three tests showed relatively good clinical sensitivities, but the AdvanSure PCR had lower clinical specificity than the Abbott PCR and the HC2. The AdvanSure PCR and the Abbott PCR assays have the advantage of being automated and the ability to distinguish between HPV types 16/18 and other HPV types. The two real-time PCR assays could be useful tools in HPV testing for cervical cancer screening. Copyright © 2014 Elsevier B.V. All rights reserved.

Accuracy of urinary human papillomavirus testing for presence of cervical HPV: systematic review and meta-analysis

PubMed Central

Pathak, Neha; Dodds, Julie; Khan, Khalid

2014-01-01

Objective To determine the accuracy of testing for human papillomavirus (HPV) DNA in urine in detecting cervical HPV in sexually active women. Design Systematic review and meta-analysis. Data sources Searches of electronic databases from inception until December 2013, checks of reference lists, manual searches of recent issues of relevant journals, and contact with experts. Eligibility criteria Test accuracy studies in sexually active women that compared detection of urine HPV DNA with detection of cervical HPV DNA. Data extraction and synthesis Data relating to patient characteristics, study context, risk of bias, and test accuracy. 2×2 tables were constructed and synthesised by bivariate mixed effects meta-analysis. Results 16 articles reporting on 14 studies (1443 women) were eligible for meta-analysis. Most used commercial polymerase chain reaction methods on first void urine samples. Urine detection of any HPV had a pooled sensitivity of 87% (95% confidence interval 78% to 92%) and specificity of 94% (95% confidence interval 82% to 98%). Urine detection of high risk HPV had a pooled sensitivity of 77% (68% to 84%) and specificity of 88% (58% to 97%). Urine detection of HPV 16 and 18 had a pooled sensitivity of 73% (56% to 86%) and specificity of 98% (91% to 100%). Metaregression revealed an increase in sensitivity when urine samples were collected as first void compared with random or midstream (P=0.004). Limitations The major limitations of this review are the lack of a strictly uniform method for the detection of HPV in urine and the variation in accuracy between individual studies. Conclusions Testing urine for HPV seems to have good accuracy for the detection of cervical HPV, and testing first void urine samples is more accurate than random or midstream sampling. When cervical HPV detection is considered difficult in particular subgroups, urine testing should be regarded as an acceptable alternative. PMID:25232064

The prevention of infection-associated cancers

PubMed Central

De Flora, Silvio; Bonanni, Paolo

2011-01-01

Collectively, chronic viral and bacterial infections and trematode infestations have been estimated to be associated with approximately one of five human cancers worldwide. The fraction attributable to each one of the chronic infections caused by hepatitis B and C viruses (HBV and HCV), human papillomaviruses (HPV) and Helicobacter pylori, is ∼5%. These infections are the most important causes of major types of cancer, including hepatocellular carcinoma, cervical cancer and stomach cancer, respectively. Taking into account the mechanisms of infection-related carcinogenesis, integrated approaches are addressed to the control of the associated infection as well as to avoidance of cancer occurrence and progression. Large-scale interventions have been implemented, such as the anti-HBV and anti-HPV routine vaccination programs. The latter has been designed with the specific goal of preventing HPV-associated cancers, which is an outstanding breakthrough in cancer prevention. Intriguingly, not only prevention but even therapy of an infectious disease and eradication of a pathogen become a crucial tool for the primary prevention of these cancers. An important role is also played by secondary prevention (e.g. Pap test and DNA testing for HPV-associated cervical cancers) and by tertiary prevention (e.g. antiangiogenesis in Kaposi's sarcoma). The present article reviews the microbial and parasitic diseases that have been associated so far with human cancers, draws an overview of their burden in cancer epidemiology, deals with applicable prevention strategies and provides examples of co-ordinated approaches to the control of cancers associated with HBV, HCV, HPV, human immunodeficiency virus and H.pylori infections. PMID:21436188

[Results of the first human papilloma virus center in Hungary (2007-2011)].

PubMed

Galamb, Adám; Pajor, Attila; Langmár, Zoltán; Sobel, Gábor

2011-11-06

Human papilloma virus (HPV) is the most common sexually transmitted infection in the 21st century. It has been established that infections with specific HPV types are contributing factors to cervical cancer. Approximately 99.7% of cervical cancers are associated with high risk HPV types. HPV testing plays an important role in the prevention, by decreasing the prevalence and the mortality of cervical cancer. There are 16 HPV-centers operating in Hungary, in which patients undergo HPV screening, cervical exams, and treatment based on standardized guidelines. The first HPV-center was founded in 2007 in Budapest, at the 2nd Department of Obstetrics and Gynecology, Semmelweis University. This study aimed to define the presence and prevalence of HPV-DNA in the cervical swab samples obtained from patients in our center. Authors conducted to assess the age-specific-prevalence, and HPV type distribution, the associated cervical abnormalities, comparing our results with international data. Overall 1155 woman underwent HPV-testing and genotyping, using polymerase chain reaction. Overall, 55.5% of patients had positive test for HPV DNA types, in which 38.5% for high-risk HPV DNA. Overall prevalence was the highest among females aged 15 to 25 years (62.9%). The most common HPV type found was the high risk type 16 (19.5% among the patients with positive HPV testing). Presence of high risk HPV with concurrent cervical cytological abnormality was in 32%. More than two-thirds of woman with cytological atypia (70.6%) were infected with two or more high risk HPV types. HPV 16 was detected in 32% of patients with cytological abnormalities. The results suggest that the prevalence of HPV in this study population exceeds the international data. The results attracts the attention the peak prevalence of the high risk types in the youngest age-group, and the higher risk of cervical abnormality in case of presence of two or more HPV types. The dominance of type 16 and 18 was predictable, but the strong attendance of type 51 and 31 among patients who had cytological atypia, was slightly surprising.

Community-Based Screening for Cervical Cancer: A Feasibility Study of Rural Appalachian Women

PubMed Central

Crosby, Richard A.; Hagensee, Michael E.; Vanderpool, Robin; Nelson, Nia; Parrish, Adam; Collins, Tom; Jones, Nebraska

2015-01-01

Objectives To describe women’s comfort levels and perceptions about their experience self-collecting cervico-vaginal swabs for HPV testing; to determine whether nurse-guided patient navigation increases the odds of women receiving a traditional Pap test after HPV screening; and to test the hypothesis that women testing positive for oncogenic HPV would be more likely to have a subsequent Pap test than those testing negative. Methods 400 women were recruited from eight rural Appalachian counties, in 2013 and 2014. After completing a survey, women were provided instructions for self-collecting a cervico-vaginal swab. Specimens were tested for 13 oncogenic HPV types. Simultaneously, women were notified of their test results and offered initial navigation for Pap testing. Chart-verified Pap testing within the next six months served as the endpoint. Results Comfort levels with self-collection were high: 89.2% indicated they would be more likely to self-collect a specimen for testing, on a regular basis, compared to Pap testing. Thirty women (7.5%) had a follow-up Pap test. Women receiving added nurse-guided navigation efforts were significantly less likely to have a subsequent test (P = .01). Women testing positive for oncogenic HPV were no more likely than those testing negative to have a subsequent Pap test (P = .27). Data were analyzed in 2014. Conclusions Rural Appalachian women are comfortable self-collecting cervico-vaginal swabs for HPV testing. Further, efforts to re-contact women who have received an oncogenic HPV test result and an initial navigation contact may not be useful. Finally, testing positive for oncogenic HPV may not be a motivational factor for subsequent Pap testing. PMID:26462184

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

PubMed

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

2016-11-01

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

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

PubMed Central

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

2016-01-01

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

Experience of Combined Liquid Based Cervical Cytology and High-Risk HPV mRNA for Cervical Cancer Screening in Thammasat University Hospital.

PubMed

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

2016-01-01

Cervical cancer is the second most common of malignancy found in Thai women. Human papillomavirus (HPV) infection is a major cause. The objective of the present study was to evaluate the prevalence of HPV infection and association with abnormal cervical cytology in Thai women. This study was conducted at the Gynecologic Clinic, Thammasat University, Pathum Thani, Thailand. A total of 2,144 cases who underwent annual cervical cancer screening by co-testing (liquid based cytology and HPV testing, DNA versus mRNA) during the priod from July 2013 to June 2016 were recruited in this study. Prevalence of positive high risk (HR) HPV DNA and mRNA test were 19.7 and 8.4%, respectively with a statistically significant difference. Majority of cases of abnormal cytology in this study were atypical squamous cells of undetermined significance (ASC-US). In patients with ASC-US, positive HR HPV DNA was greater than in the mRNA group (10.1 and 4.5%, p<0.001). Nonetheless, there was no significant difference in participants with cervical intraepithelial neoplasia (CIN). HPV mRNA test had slightly lower sensitivity but higher negative predictive value (NPV) than the DNA test to detect abnormal cytology during cervical cancer screening (p<0.001). Both HPV test (DNA and mRNA) had equally efficacy to detect high grade precancerous lesion or higher (CIN 2+). Prevalence of HR HPV DNA and mRNA were 19.7 and 8.4 percent, respectively. NPV of HPV mRNA was higher than DNA test. Both tests had equal efficacy to detect CIN 2+ with sensitivity and specificity of 63% vs 55.7% and 83% vs 92%, respectively.

Progress toward implementation of human papillomavirus vaccination--the Americas, 2006-2010.

PubMed

2011-10-14

Cervical cancer is a major cause of morbidity and mortality in the Americas, where an estimated 80,574 new cases and 36,058 deaths were reported in 2008, with 85% of this burden occurring in Latin America and the Caribbean. Two oncogenic human papillomavirus (HPV) types (16 and 18) cause approximately 70% of cervical cancers and a substantial proportion of other HPV-related cancers. HPV vaccination provides an opportunity to greatly reduce cervical cancer burden through primary prevention of HPV infection. This report summarizes the progress toward HPV vaccine introduction in the Americas, focusing on countries that have introduced the vaccine in national or regional immunization programs. As of January 2011, four countries in the Americas had introduced HPV vaccine. Overcoming issues related to financing and delivery of HPV vaccine remains a key public health challenge to more widespread implementation of HPV vaccination in the Americas.

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

PubMed

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

2014-01-01

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

HPV test by Hybrid Capture II for the diagnosis of HR-HPV persistent infection.

PubMed

Serour, Y; Bendahmane, M; Abbou Baker, F; Medles, M; Moueddene, B; Kraiba, R

2017-11-01

Persistent high-risk HPV (HR-HPV) infection is associated with a greater risk of cervical cancer. Statistical data on the prevalence of HR-HPV infections in the Algerian population is lacking. We conducted a prospective study of 300 women aged between 25 and 50 years, screened for cervical cancer from 2012 to 2015 in Sidi Bel Abbès, a western region of Algeria. We aimed to assess the reliability of the repeated use of the HC II test (three longitudinal HPV tests 9 months apart from each other) in diagnosing the persistence of HR-HPV infection. The prevalence of HR-HPV infection was 7.33% and infected women were aged 37.9±3years. For 90.9% of HR-HPV-positive patients, the infection persisted for a mean of 18.5months [95% CI: 16.9-22.1months]. Among these patients, 55.55% developed CIN1 and 11.11% developed CIN2. The sensitivity of the HC II test was 81.74% [95% CI: 71.3-89.6] and its positive predictive value associated with abnormal cervical biopsy was 27.49% [95% CI: 16.0-33.33]. Repeating the HC II test is a good predictor for identifying women at high risk of cervical cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Human papillomavirus genotypes in genital warts in Latin America: a cross-sectional study in Bogota, Colombia.

PubMed

Hernandez-Suarez, G; Pineros, M; Vargas, J C; Orjuela, L; Hernandez, F; Peroza, C; Torres, D; Escobar, A; Perez, G

2013-07-01

Epidemiological studies on benign lesions related to human papillomavirus (HPV) infection are scarce in Latin America. We enrolled 342 consecutive patients with lesions suspected of being genital warts (GW). All patients underwent confirmatory biopsy and GP5+/GP6+/- Reverse Line Blot HPV testing on frozen tissue. In 261 (81%) cases, the diagnosis was confirmed by histopathology and HPV was detected in 90.6% of men and 87.7% of women. HPV 6 was by far the most common type in both women (62%) and men (56%), followed by HPV 11 (∼20%). Co-infection with these two types occurred in 7% and 12% of women and men, respectively. HPV16 ranked third in prevalence, with 16% of patients testing positive. Twenty-five percent of cases tested positive for multiple HPV genotypes. Although HPV 6 and HPV 11 were the main types detected and no differences between men and women were observed, we found HPV 11 contributed more to GW aetiology compared with previous reports, showing a variability of HPV type distribution in GW across populations. This information is valuable baseline data in Latin America for future estimations of the burden of GW in men and women and shows the potential benefit obtainable by prophylactic vaccination against HPV types 6 and 11.

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

PubMed

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

2015-10-01

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

Assessment of the presence of mucosal human papillomaviruses in malignant melanomas using combined fluorescent in situ hybridization and chemiluminescent immunohistochemistry.

PubMed

Ambretti, S; Venturoli, S; Mirasoli, M; La Placa, M; Bonvicini, F; Cricca, M; Zerbini, M; Roda, A; Musiani, M

2007-01-01

The vast majority of studies aimed at detecting human papillomavirus (HPV) DNA in skin cancer have used sensitive polymerase chain reaction (PCR) methods but the PCR technique, despite its high sensitivity, is not suitable to ascertain whether (i) the presence of HPV can be related only to few cells harbouring the virus, (ii) the presence of HPV is due to a tumour surface contamination and (iii) the presence of HPV is localized in cancer cells, rather than in normal keratinocytes present in the tumour biopsy. In a recent work we have found mucosal high-risk (HR) HPV genotypes in primary melanoma by PCR. To localize mucosal HR-HPV nucleic acids and tumoural melanocytic marker in the same sections of primary melanoma samples in order to understand the relationship between HPVs and melanoma cells. We have developed a very sensitive method that combines an enzyme-amplified fluorescent in situ hybridization (ISH) for the detection of HPV nucleic acids (types 16 and 18) with a chemiluminescent immunohistochemistry (IHC) method for the detection of the tumoural melanocytic marker HMB-45 sequentially in the same section. Digital images of fluorescent ISH and chemiluminescent IHC were separately recorded, assigned different colours and merged using specific software for image analysis. The combined fluorescent ISH and chemiluminescent IHC demonstrated a sharp colocalization (in the range 60-80%) of HPV nucleic acids and melanoma marker inside the same sections of melanoma biopsies, with a strong specificity and sensitivity. The strong colocalization of mucosal HR-HPV nucleic acids and HMB-45 melanocytic marker emphasized that viral nucleic acids were specifically present in melanoma cells and supported a possible active role of HPV in malignant melanoma.

Maternal support for human papillomavirus vaccination in Honduras.

PubMed

Perkins, Rebecca B; Langrish, Sarah M; Cotton, Deborah J; Simon, Carol J

2011-01-01

Cervical cancer is a leading cause of cancer death for women in Latin America, and vaccinating against human papillomavirus (HPV) has the potential to limit this disease. We sought to determine Honduran women's awareness of HPV vaccination and interest in vaccinating their daughters against HPV. We interviewed mothers aged ≥17 at primary care clinics in Honduras. First, we collected demographic information and assessed knowledge related to cervical cancer prevention and awareness of HPV and HPV vaccination. Because most participants were not familiar with HPV, education about the relationships among HPV, sexual activity, and cervical cancer was provided before we asked participants if they would accept HPV vaccination for a 9-year-old daughter. We used multivariable logistic regression to determine predictors of vaccine acceptance. We interviewed 632 mothers. Only 13% had heard of HPV vaccination before the interview. After education, 91% would accept HPV vaccination for a 9-year-old daughter. Mothers who intended to vaccinate knew more at baseline about cervical cancer prevention than did those who did not endorse vaccination. Demographic characteristics did not predict vaccine acceptance. Few Honduran mothers were aware of HPV or HPV vaccination. However, most Honduran mothers would accept HPV vaccination for their daughters after receiving education about the relationship between HPV infection and cervical cancer. Baseline cervical cancer knowledge was associated with vaccine acceptance.

Accuracy of human papillomavirus testing on self-collected versus clinician-collected samples: a meta-analysis.

PubMed

Arbyn, Marc; Verdoodt, Freija; Snijders, Peter J F; Verhoef, Viola M J; Suonio, Eero; Dillner, Lena; Minozzi, Silvia; Bellisario, Cristina; Banzi, Rita; Zhao, Fang-Hui; Hillemanns, Peter; Anttila, Ahti

2014-02-01

Screening for human papillomavirus (HPV) infection is more effective in reducing the incidence of cervical cancer than screening using Pap smears. Moreover, HPV testing can be done on a vaginal sample self-taken by a woman, which offers an opportunity to improve screening coverage. However, the clinical accuracy of HPV testing on self-samples is not well-known. We assessed whether HPV testing on self-collected samples is equivalent to HPV testing on samples collected by clinicians. We identified relevant studies through a search of PubMed, Embase, and CENTRAL. Studies were eligible for inclusion if they fulfilled all of the following selection criteria: a cervical cell sample was self-collected by a woman followed by a sample taken by a clinician; a high-risk HPV test was done on the self-sample (index test) and HPV-testing or cytological interpretation was done on the specimen collected by the clinician (comparator tests); and the presence or absence of cervical intraepithelial neoplasia grade 2 (CIN2) or worse was verified by colposcopy and biopsy in all enrolled women or in women with one or more positive tests. The absolute accuracy for finding CIN2 or worse, or CIN grade 3 (CIN3) or worse of the index and comparator tests as well as the relative accuracy of the index versus the comparator tests were pooled using bivariate normal models and random effect models. We included data from 36 studies, which altogether enrolled 154 556 women. The absolute accuracy varied by clinical setting. In the context of screening, HPV testing on self-samples detected, on average, 76% (95% CI 69-82) of CIN2 or worse and 84% (72-92) of CIN3 or worse. The pooled absolute specificity to exclude CIN2 or worse was 86% (83-89) and 87% (84-90) to exclude CIN3 or worse. The variation of the relative accuracy of HPV testing on self-samples compared with tests on clinician-taken samples was low across settings, enabling pooling of the relative accuracy over all studies. The pooled sensitivity of HPV testing on self-samples was lower than HPV testing on a clinician-taken sample (ratio 0·88 [95% CI 0·85-0·91] for CIN2 or worse and 0·89 [0·83-0·96] for CIN3 or worse). Also specificity was lower in self-samples versus clinician-taken samples (ratio 0·96 [0·95-0·97] for CIN2 or worse and 0·96 [0·93-0·99] for CIN3 or worse). HPV testing with signal-based assays on self-samples was less sensitive and specific than testing on clinician-based samples. By contrast, some PCR-based HPV tests generally showed similar sensitivity on both self-samples and clinician-based samples. In screening programmes using signal-based assays, sampling by a clinician should be recommended. However, HPV testing on a self-sample can be suggested as an additional strategy to reach women not participating in the regular screening programme. Some PCR-based HPV tests could be considered for routine screening after careful piloting assessing feasibility, logistics, population compliance, and costs. The 7th Framework Programme of the European Commission, the Belgian Foundation against Cancer, the International Agency for Research on Cancer, and the German Guideline Program in Oncology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Presenting symptoms and clinical findings in HPV-positive and HPV-negative oropharyngeal cancer patients.

PubMed

Carpén, Timo; Sjöblom, Anni; Lundberg, Marie; Haglund, Caj; Markkola, Antti; Syrjänen, Stina; Tarkkanen, Jussi; Mäkitie, Antti; Hagström, Jaana; Mattila, Petri

2018-05-01

Oropharyngeal squamous cell carcinoma (OPSCC) is divided in two different disease entities depending on HPV involvement. We investigated differences in presenting symptoms and clinical findings in patients with HPV-positive and -negative OPSCC tumors. Altogether 118 consecutive patients diagnosed with primary OPSCC between 2012 and 2014 at the Helsinki University Hospital were included. HPV-status of the tumors was assessed by PCR detection of HPV DNA and immunostaining with p16-INK4a antibody. Fifty-one (47.7%) of the patients had HPV-positive and 56 (52.3%) HPV-negative tumors. Forty-nine (49/51, 96.1%) of the HPV+ tumors were also p16+ showing high concordance. The most common presenting symptom among HPV+/p16+ patients was a neck mass (53.1%), whereas any sort of pain in the head and neck area was more frequently related to the HPV-/p16- (60.0%) group. HPV+/p16+ tumors had a tendency to locate in the tonsillar complex and more likely had already spread into regional lymph nodes compared with HPV-/p16- tumors. Smoking and heavy alcohol consumption were significantly more common among HPV-/p16- patients but also rather common among HPV+/p16+ patients. This analysis of symptoms and signs confirm that OPSCC can be dichotomized in two distinct disease entities as defined by HPV status.

Knowledge of HPV and HPV Vaccine among Women Ages 19 to 26.

PubMed

Unger, Zoe; Maitra, Abby; Kohn, Julia; Devaskar, Sangita; Stern, Lisa; Patel, Ashlesha

2015-01-01

To describe knowledge about human papillomavirus (HPV) and HPV vaccination among women ages 19 to 26 seeking a variety of services at reproductive health centers. A secondary objective was to identify common sources of HPV information. Ten reproductive health centers enrolled 365 women ages 19 to 26 in a randomized, controlled trial to determine the effect of automated reminder messages on HPV vaccine completion. Using responses from a 61-item self-administered baseline questionnaire completed before initiating the HPV vaccine, this subanalysis assessed participants' knowledge regarding HPV and the HPV vaccine. Knowledge of HPV prevention, transmission, and disease outcomes among the study population was highly variable. The mean HPV knowledge score was 11.0 of a possible 19 (SD = 3.8). Most participants (77%) had heard of the HPV vaccine before completing the questionnaire and indicated that their primary sources of information about the vaccine were television ads (61%), health care providers (52%), and friends (45%). Despite a relatively high awareness of the vaccine, specific knowledge regarding HPV and the HPV vaccine varied substantially and participant scores highlighted knowledge gaps among vaccine-eligible young women. Media, health care providers, and friends were identified by participants as sources of information and may influence their knowledge of HPV and the HPV vaccine. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Primary Care Provider Practices and Perceptions Regarding HPV Vaccination and Anal Cancer Screening at a Boston Community Health Center.

PubMed

Apaydin, Kaan Z; Fontenot, Holly B; Shtasel, Derri L; Mayer, Kenneth H; Keuroghlian, Alex S

2018-02-26

Human papillomavirus (HPV) vaccination and anal cancer screening are valuable, yet underutilized, tools in prevention of HPV-related cancers among sexual and gender minority (SGM) populations. The aim of this study was to characterize primary care providers' (PCPs) practices and perceptions pertaining to HPV vaccination and anal cancer screening. A survey assessing self-reported practice characteristics related to HPV vaccination and anal cancer screening, as well as perceived barriers to vaccination and anal cancer screening at the patient-, provider-, and system-level was distributed to PCPs at a Federally-Qualified Health Center that specializes in care for SGM populations in the greater Boston area. A total of 33 PCPs completed the survey. All PCPs strongly recommended HPV vaccination to their patients by emphasizing that the vaccine is extremely important or very important. Most PCPs told their patients that the HPV vaccine prevents cervical cancer (96.9%), anal cancer (96.9%), oropharyngeal cancer (72.7%), penile cancer (57.5%), and genital warts (63.6%). There is substantial variability among providers regarding recommendations for anal cancer screening and follow-up. Most PCPs perceived that patient-level factors such as poverty, mental illness, and substance use disorders were barriers to HPV vaccination and anal cancer screening. Systems-level barriers such as lack of clinical time with each patient and lack of staffing were also described as barriers to vaccination and screening. Patient-, provider- and systems-level improvements are important to increase HPV vaccination and anal cancer screening rates.

Study protocol of the CHOiCE trial: a three-armed, randomized, controlled trial of home-based HPV self-sampling for non-participants in an organized cervical cancer screening program.

PubMed

Tranberg, Mette; Bech, Bodil Hammer; Blaakær, Jan; Jensen, Jørgen Skov; Svanholm, Hans; Andersen, Berit

2016-11-03

The effectiveness of cervical cancer screening programs is challenged by suboptimal participation and coverage. Offering cervico-vaginal self-sampling for human papillomavirus testing (HPV self-sampling) to non-participants can increase screening participation. However, the effect varies substantially among studies, especially depending on the approach used to offer HPV self-sampling. The present trial evaluates the effect on participation in an organized screening program of a HPV self-sampling kit mailed directly to the home of the woman or mailed to the woman's home on demand only, compared with the standard second reminder for regular screening. The CHOiCE trial is a parallel, randomized, controlled, open-label trial. It will include 9327 women aged 30-64 years who are living in the Central Denmark Region and who have not participated in cervical cancer screening after an invitation and one reminder. The women will be equally randomized into three arms: 1) Directly mailed a second reminder including a HPV self-sampling kit; 2) Mailed a second reminder offering a HPV self-sampling kit, to be ordered by e-mail, text message, phone, or through a webpage; and 3) Mailed a second reminder for a practitioner-collected sample (control group). The primary outcome will be the proportion of women in the intervention groups who participate by returning their HPV self-sampling kit or have a practitioner-collected sample compared with the proportion of women who have a practitioner-collected sample in the control group at 90 and 180 days after mail out of the second reminders. Per-protocol and intention-to-treat analyses will be performed. The secondary outcome will be the proportion of women with a positive HPV self-collected sample who attend follow-up testing at 30, 60, or 90 days after mail out of the results. The CHOiCE trial will provide strong and important evidence allowing us to determine if and how HPV self-sampling can be used to increase participation in cervical cancer screening. This trial therefore has the potential to improve prevention and reduce the number of deaths caused by cervical cancer. Current Controlled Trials NCT02680262 . Registered 10 February 2016.

Evaluation of the immunogenicity of the quadrivalent HPV vaccine using 2 versus 3 doses at month 21: An epidemiological surveillance mechanism for alternate vaccination schemes

PubMed Central

Hernández-Ávila, Mauricio; Torres-Ibarra, Leticia; Stanley, Margaret; Salmerón, Jorge; Cruz-Valdez, Aurelio; Muñoz, Nubia; Herrero, Rolando; Villaseñor-Ruíz, Ignacio F; Lazcano-Ponce, Eduardo

2016-01-01

The cost of HPV vaccines and the need for 3 doses remains a barrier for their inclusion in routine vaccination schedules for girls in low and middle income countries. In a non-inferiority study, we aimed to compare the immunogenicity of a standard 3 doses and a 2 doses schedule. We enrolled 450 participants in an open-label non-randomized clinical trial to evaluate the immunogenicity induced at different ages by the licensed HPV6/11/16/18 quadrivalent vaccine in a 2 doses schedule (0–6 months, n = 150 girls aged 9–10 y) and 3 doses schedule (0, 2, and 6 months; n = 150 girls aged 9–10 y and n=150 women aged 18 to 24 years). To assess the antibody response, blood samples were obtained at Month 7 and 21 after the first vaccination from participants in all study groups. cLIA testing was performed at Merck Research Laboratories. Antibody levels were expressed as milli-Merck units (mMU) per ml. Primary outcome was non-inferiority (95% CI, lower bound >0.5) of the geometric mean titers (GMT) ratios for HPV6, HPV11, HPV16 and HPV18 antibodies 7 and 21 months after the first dose among girls receiving 2 doses compared with young women and girls receiving 3 doses. All vaccinees were seropositive for both HPV16 and HPV18 antibodies at month 7. At month 21, 98.5 and 56.6% of women 18–24 y old were seropositive for HPV16 and 18, respectively. For girls in the three doses group, seropositivity rates were 99.3 and 86.3% for HPV16 and 18, respectively. For girls in the two doses group rates were 99.3 and 70.2% for HPV16 and 18, respectively. The two doses schedule was non-inferior compared to the 3 doses schedule in same-age girls and to the group of adult women after 21 months of the first vaccine dose. Our results are in agreement with similar trials evaluating the immune response of a 2 doses schedule of both HPV vaccines, supporting the recent WHO recommendation as well as the Mexican policy to incorporate the 2 doses schedule for girls aged 9–11 y. PMID:26211489

Cervical Dysplasia and High-Risk Human Papillomavirus Infections among HIV-Infected and HIV-Uninfected Adolescent Females in South Africa

PubMed Central

Mrubata, Megan; Williamson, Anna-Lise; Bekker, Linda-Gail

2014-01-01

Background. HIV-infected adolescents may be at higher risk for high-grade cervical lesions than HIV-uninfected adolescents. The purpose of this study was to compare the prevalence of high-risk HPV (HR-HPV) infections and Pap smear abnormalities between these two groups. Methods. In this cross-sectional study, we compared the HPV DNA and Pap smear results between 35 HIV-infected and 50 HIV-uninfected adolescents in order to determine the prevalence of HR-HPV genotypes and cervical cytological abnormalities. Comparisons were made using Pearson χ 2 and independent-samples t-tests analyses, and associations between demographic and behavioral characteristics and HPV infections were examined. Results. HIV-infected participants were more likely to be infected with any HPV (88.6% versus 48.0%; P < 0.001) and with at least one HR-HPV (60.0% versus 24.0%; P = 0.001), and to have multiple concurrent HPV infections (68.6% versus 22.0%; P < 0.001). HPV 16 and 18 were relatively underrepresented among HR-HPV infections. Abnormal Pap test results were more common among HIV-infected participants (28.8% versus 12.0%; P = 0.054). A history of smoking was associated with HR-HPV infection. Conclusions. HIV-infected adolescents have an increased risk of infection with HR-HPV and of Pap test abnormalities. The majority of HR-HPV infections among our participants would not be prevented by the currently available vaccinations against HPV. PMID:25389377

Estimation of HPV prevalence in young women in Scotland; monitoring of future vaccine impact

PubMed Central

2013-01-01

Background Estimation of pre-immunisation prevalence of HPV and distribution of HPV types is fundamental to understanding the subsequent impact of HPV vaccination. We describe the type specific prevalence of HPV in females aged 20–21 in Scotland who attended or defaulted from cervical screening using three specimen types; from attenders liquid based cytology and from defaulters urine or self-taken swabs. Methods Residual liquid based cytology samples (n = 2148), collected from women aged 20–21 attending for their first smear were genotyped for HPV. A sample (n = 709) from women who had defaulted from screening was also made available for HPV testing through the use of postal testing kits (either urine samples (n = 378) or self-taken swabs (n = 331)). Estimates of prevalence weighted by deprivation, and for the postal testing kit, also by reminder status and specimen type were calculated for each HPV type. The distribution of HPV types were compared between specimen types and the occurrence of multiple high-risk infections examined. The influence of demographic factors on high-risk HPV positivity and multiple infections was examined via logistic regression. Results The prevalence of any HPV in young women aged 20–21 was 32.2% for urine, 39.5% for self-taken swab, and 49.4% for LBC specimens. Infection with vaccine specific types (HPV 16, 18) or those associated with cross-protection (HPV 31, 33, 45, 51) was common. Individuals were more likely to test positive for high-risk HPV if they resided in an area of high deprivation or in a rural area. The overall distribution of HPV types did not vary between defaulters and attenders. Multiple infections occurred in 48.1% of high-risk HPV positive individuals. Excluding vaccine types the most common pairing was HPV 56 and 66. Conclusions Understanding of the pre-immunisation prevalence of HPV in young women puts Scotland in a prime position to assess the early effect of vaccination as the first highly vaccinated cohorts of individuals enter the screening programme. Differences in results with different specimen types must be taken into account when monitoring the impact of vaccination programmes. PMID:24188790

Estimation of HPV prevalence in young women in Scotland; monitoring of future vaccine impact.

PubMed

Kavanagh, Kimberley; Sinka, Katy; Cuschieri, Kate; Love, John; Potts, Alison; Pollock, Kevin G J; Cubie, Heather; Donaghy, Martin; Robertson, Chris

2013-11-05

Estimation of pre-immunisation prevalence of HPV and distribution of HPV types is fundamental to understanding the subsequent impact of HPV vaccination. We describe the type specific prevalence of HPV in females aged 20-21 in Scotland who attended or defaulted from cervical screening using three specimen types; from attenders liquid based cytology and from defaulters urine or self-taken swabs. Residual liquid based cytology samples (n = 2148), collected from women aged 20-21 attending for their first smear were genotyped for HPV. A sample (n = 709) from women who had defaulted from screening was also made available for HPV testing through the use of postal testing kits (either urine samples (n = 378) or self-taken swabs (n = 331)). Estimates of prevalence weighted by deprivation, and for the postal testing kit, also by reminder status and specimen type were calculated for each HPV type. The distribution of HPV types were compared between specimen types and the occurrence of multiple high-risk infections examined. The influence of demographic factors on high-risk HPV positivity and multiple infections was examined via logistic regression. The prevalence of any HPV in young women aged 20-21 was 32.2% for urine, 39.5% for self-taken swab, and 49.4% for LBC specimens. Infection with vaccine specific types (HPV 16, 18) or those associated with cross-protection (HPV 31, 33, 45, 51) was common. Individuals were more likely to test positive for high-risk HPV if they resided in an area of high deprivation or in a rural area. The overall distribution of HPV types did not vary between defaulters and attenders. Multiple infections occurred in 48.1% of high-risk HPV positive individuals. Excluding vaccine types the most common pairing was HPV 56 and 66. Understanding of the pre-immunisation prevalence of HPV in young women puts Scotland in a prime position to assess the early effect of vaccination as the first highly vaccinated cohorts of individuals enter the screening programme. Differences in results with different specimen types must be taken into account when monitoring the impact of vaccination programmes.

Comprehensive mapping of the human papillomavirus (HPV) DNA integration sites in cervical carcinomas by HPV capture technology.

PubMed

Liu, Ying; Lu, Zheming; Xu, Ruiping; Ke, Yang

2016-02-02

Integration of human papillomavirus (HPV) DNA into the host genome can be a driver mutation in cervical carcinoma. Identification of HPV integration at base resolution has been a longstanding technical challenge, largely due to sensitivity masking by HPV in episomes or concatenated forms. The aim was to enhance the understanding of the precise localization of HPV integration sites using an innovative strategy. Using HPV capture technology combined with next generation sequencing, HPV prevalence and the exact integration sites of the HPV DNA in 47 primary cervical cancer samples and 2 cell lines were investigated. A total of 117 unique HPV integration sites were identified, including HPV16 (n = 101), HPV18 (n = 7), and HPV58 (n = 9). We observed that the HPV16 integration sites were broadly located across the whole viral genome. In addition, either single or multiple integration events could occur frequently for HPV16, ranging from 1 to 19 per sample. The viral integration sites were distributed across almost all the chromosomes, except chromosome 22. All the cervical cancer cases harboring more than four HPV16 integration sites showed clinical diagnosis of stage III carcinoma. A significant enrichment of overlapping nucleotides shared between the human genome and HPV genome at integration breakpoints was observed, indicating that it may play an important role in the HPV integration process. The results expand on knowledge from previous findings on HPV16 and HPV18 integration sites and allow a better understanding of the molecular basis of the pathogenesis of cervical carcinoma.

Prevalence of oral and oropharyngeal human papillomavirus in a sample of South African men: a pilot study.

PubMed

Davidson, Christy Lana; Richter, Karin Louise; Van der Linde, Mike; Coetsee, Judy; Boy, Sonja Catharina

2014-03-26

Human papillomavirus (HPV) infection is well known to be associated with head and neck cancers (HNCs). HPV-associated HNCs are related to sexual behaviour, particularly the lifetime number of oral sex partners, but the epidemiology of oral and oropharyngeal HPV in South African men has not yet been studied. To determine the oral and oropharyngeal HPV strain prevalence and associated factors in a selected male population in Pretoria, South Africa (SA). Male factory workers were recruited. Oral rinse and gargle samples were tested for 37 HPV types using the Linear Array HPV Genotyping Test (Roche Molecular Systems). A questionnaire was used to obtain information regarding age, medical conditions, substance and alcohol use and sexual behaviour. HIV testing was optional. The HPV prevalence was 5.6% among men (N=125) aged 17 - 64 years. High-risk HPV (hrHPV) types 16 and 68 were found in two men. Oral sex seemed to be an uncommon practice in the majority of respondents, but the two respondents with hrHPV did practise oral sex. There was a statistically significant association between HPV infection and an increased number of sexual partners (p=0.027), but not between HPV and substance use, HIV status or clinical mucosal pathology. The prevalence of oral and oropharyngeal HPV was lower than reported in other countries. An association between oral HPV and having multiple sexual partners was found. A larger nationwide study would give a more representative view of the burden of oral and oropharyngeal HPV infection in SA.

Triage of women with low-grade cervical lesions--HPV mRNA testing versus repeat cytology.

PubMed

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

2011-01-01

In Norway, women with low-grade squamous intraepithelial lesions (LSIL) are followed up after six months in order to decide whether they should undergo further follow-up or be referred back to the screening interval of three years. A high specificity and positive predictive value (PPV) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures. At the University Hospital of North Norway, repeat cytology and the HPV mRNA test PreTect HPV-Proofer, detecting E6/E7 mRNA from HPV types 16, 18, 31, 33 and 45, are used in triage of women with ASC-US and LSIL. In this study, women with LSIL cytology in the period 2005-2008 were included (n = 522). Two triage methods were evaluated in two separate groups: repeat cytology only (n = 225) and HPV mRNA testing in addition to repeat cytology (n = 297). Histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) was used as the study endpoint. Of 522 women with LSIL, 207 had biopsies and 125 of them had CIN2+. The sensitivity and specificity of repeat cytology (ASC-US or worse) were 85.7% (95% confidence interval (CI): 72.1, 92.2) and 54.4 % (95% CI: 46.9, 61.9), respectively. The sensitivity and specificity of the HPV mRNA test were 94.2% (95% CI: 88.7, 99.7) and 86.0% (95% CI: 81.5, 90.5), respectively. The PPV of repeat cytology was 38.4% (95% CI: 29.9, 46.9) compared to 67.0% (95% CI: 57.7, 76.4) of the HPV mRNA test. HPV mRNA testing was more sensitive and specific than repeat cytology in triage of women with LSIL cytology. In addition, the HPV mRNA test showed higher PPV. These data indicate that the HPV mRNA test is a better triage test for women with LSIL than repeat cytology.

Cervical Cancer Screening (Pap Testing) Behaviours and Acceptability of Human Papillomavirus Self-Testing among Lesbian and Bisexual Women Aged 21–26 Years in the USA

PubMed Central

Reiter, Paul L.; McRee, Annie-Laurie

2017-01-01

Objective Lesbian and bisexual women are at risk for human papillomavirus (HPV) infection and cervical disease. We examined Pap testing among these women and their acceptability of HPV self-testing at home, a potential cervical cancer screening strategy. Methods We analyzed data from a national sample of lesbian and bisexual women ages 21–26 who completed our online survey during Fall 2013 (n=418). Logistic regression identified correlates of: 1) receipt of a Pap test in the last three years; and 2) willingness to use an HPV self-test at home. Results About 70% of women had received a Pap test in the last three years. Pap testing was more common among women who had disclosed their sexual orientation to their healthcare provider (OR=2.01, 95% CI: 1.02–3.95) and less common among women who self-identified as lesbian (OR=0.48, 95% CI: 0.25–0.93). Just over half of women (51%) were willing to use an HPV self-test at home. Women were more willing to use an HPV self-test at home if they were older (OR=1.16, 95% CI: 1.03–1.30) or reported higher levels of worry about getting an HPV-related disease (OR=1.28, 95% CI: 1.01–1.63). The most common concerns about HPV self-testing at home were using the test incorrectly (70%) and test accuracy (64%). Conclusions Many young lesbian and bisexual women have not received a recent Pap test. HPV self-testing at home may be a promising future strategy for reaching and screening these women. Findings highlight beliefs and concerns that could be addressed by self-test programs. PMID:25385868

Comparison of clinical performances among Roche Cobas HPV, RFMP HPV PapilloTyper and Hybrid Capture 2 assays for detection of high-risk types of human papillomavirus.

PubMed

Yu, Shinae; Kwon, Min-Jung; Lee, Eun Hee; Park, Hyosoon; Woo, Hee-Yeon

2015-09-01

The cervical cancer screening guidelines suggest that early detection of HPV16 and HPV18 is helpful for identifying women with cervical intraepithelial neoplasia (CIN) grade two or higher. We comparatively evaluated three HPV DNA assays, Roche Cobas HPV, RFMP HPV PapilloTyper, and Hybrid Capture 2 (HC2). A total of 861 cervical swab samples from women over 30 years of age were classified into two groups, that is, high grade squamous intraepithelial lesion (HSIL) and non-HSIL, according to cervical cytology results and analyzed by three assays. The results of direct sequencing or Linear array HPV genotyping test were considered true when the three assays presented discrepancies. The concordance rates between Roche Cobas HPV versus RFMP HPV PapilloTyper, RFMP HPV PapilloTyper versus HC2, and Roche Cobas versus HC2 were 94.5%, 94.3%, and 95.9%, respectively. For detection of HPV16 and HPV18, Roche Cobas HPV showed the concordance rates of 98.3% (κ = 0.73) and 99.4% (κ = 0.40) with the confirmation tests, respectively; and RFMP HPV PapilloTyper showed the concordance rates of 99.5% (κ = 0.92) and 100.0% (κ = 1.00), respectively. In conclusion, Roche Cobas HPV, RFMP HPV PapilloTyper, and HC2 showed high agreement rates. Roche Cobas HPV and RFMP HPV PapilloTyper are particularly useful, since both provide HPV specific genotypes, HPV16 and HPV18. © 2015 Wiley Periodicals, Inc.

Self-collection based HPV testing for cervical cancer screening among women living with HIV in Uganda: a descriptive analysis of knowledge, intentions to screen and factors associated with HPV positivity.

PubMed

Mitchell, Sheona M; Pedersen, Heather N; Eng Stime, Evelyn; Sekikubo, Musa; Moses, Erin; Mwesigwa, David; Biryabarema, Christine; Christilaw, Jan; Byamugisha, Josaphat K; Money, Deborah M; Ogilvie, Gina S

2017-01-13

Women living with HIV (WHIV) are disproportionately impacted by cervical dysplasia and cancer. The burden is greatest in low-income countries where limited or no access to screening exists. The goal of this study was to describe knowledge and intentions of WHIV towards HPV self-collection for cervical cancer screening, and to report on factors related to HPV positivity among women who participated in testing. A validated survey was administered to 87 HIV positive women attending the Kisenyi Health Unit aged 30-69 years old, and data was abstracted from chart review. At a later date, self-collection based HPV testing was offered to all women. Specimens were tested for high risk HPV genotypes, and women were contacted with results and referred for care. Descriptive statistics, Chi Square and Fischer-exact statistical tests were performed. The vast majority of WHIV (98.9%) women did not think it necessary to be screened for cervical cancer and the majority of women had never heard of HPV (96.4%). However, almost all WHIV found self-collection for cervical cancer screening to be acceptable. Of the 87 WHIV offered self-collection, 40 women agreed to provide a sample at the HIV clinic. Among women tested, 45% were oncogenic HPV positive, where HPV 16 or 18 positivity was 15% overall. In this group of WHIV engaged in HIV care, there was a high prevalence of oncogenic HPV, a large proportion of which were HPV genotypes 16 or 18, in addition to low knowledge of HPV and cervical cancer screening. Improved education and cervical cancer screening for WHIV are sorely needed; self-collection based screening has the potential to be integrated with routine HIV care in this setting.

Outcomes in Women With Cytology Showing Atypical Squamous Cells of Undetermined Significance With vs Without Human Papillomavirus Testing.

PubMed

Cuzick, Jack; Myers, Orrin; Lee, Ji-Hyun; Shi, Yang; Gage, Julia C; Hunt, William C; Robertson, Michael; Wheeler, Cosette M

2017-10-01

Little is known about the long-term yield of high-grade cervical intraepithelial neoplasia (CIN) and the influence on biopsy and treatment rates of human papillomavirus (HPV) triage of cytology showing atypical squamous cells of undetermined significance (hereafter ASC-US cytology). To examine 5-year outcomes after ASC-US cytology with vs without HPV testing. In this observational study, all cervical cytology and HPV testing reports from January 1, 2007, to December 31, 2012, were obtained for women throughout New Mexico and linked to pathology reports. The dates of the analysis were May 4, 2015, to January 13, 2017. Influence of HPV testing on disease yield, time to histologically confirmed disease, and biopsy or loop electrosurgical excision procedure rates. A total of 457 317 women (mean [SD] age, 39.8 [12.5] years) with a screening test were recorded between 2008 and 2012, and 20 677 (4.5%) of the first cytology results per woman were reported as ASC-US. CIN grade 3 or more severe (CIN3+) lesions were detected in 2.49% of women with HPV testing vs 2.15% of women without HPV testing (P = .23). Time to CIN3+ detection was much shorter in those with HPV testing vs those without testing (median, 103 vs 393 days; P < .001). CIN grade 1 was detected in 11.6% of women with HPV testing vs 6.6% without testing (relative risk, 1.76; 95% CI, 1.56-2.00; P < .001). Loop electrosurgical excision procedure rates within 5 years were 20.0% higher in those who underwent HPV testing, resulting in more CIN2+ and CIN3+ detection. Human papillomavirus testing led to faster and more complete diagnosis of cervical disease, but 55.8% more biopsies and 20.0% more loop electrosurgical excision procedures were performed. In those tested, virtually all high-grade disease occurred in the 43.1% of women who were HPV positive, allowing clinical resources to be focused on women who need them most. These data provide essential information for cervical screening guidelines and public health policy.

Oncogenic Human Papillomavirus (HPV) Type Distribution and HPV Type 16 E6 Variants in Two Spanish Population Groups with Different Levels of HPV Infection Risk

PubMed Central

Ortiz, M.; Torres, M.; Muñoz, L.; Fernández-García, E.; Canals, J.; Cabornero, A. I.; Aguilar, E.; Ballesteros, J.; del Amo, J.; García-Sáiz, A.

2006-01-01

The aim of this study is to determine oncogenic human papillomavirus (HPV) types and HPV type 16 (HPV16) variant distribution in two Spanish population groups, commercial sex workers and imprisoned women (CSW/IPW) and the general population. A multicenter cross-sectional study of 1,889 women from five clinical settings in two Spanish cities was conducted from May to November 2004. Oncogenic HPV infection was tested by an Hybrid Capture II (HC2) test, and positive samples were genotyped by direct sequencing using three different primer sets in L1 (MY09/11 and GP5+/GP6+) and E6/E7. HPV16 variants were identified by sequencing the E6, E2, and L1 regions. Four hundred twenty-five samples were positive for the HC2 test, 31.5% from CSW/IPW and 10.7% from the general population. HPV16 was the most frequent type. Distinct profiles of oncogenic HPV type prevalence were observed across the two populations. In order of decreasing frequency, HPV types 16, 31, 58, 66, 56, and 18 were most frequent in CSW/IPW women, and types 16, 31, 52, 68, 51, and 53 were most frequent in the general population. We analyzed HPV16 intratype variants, and a large majority (78.7%) belonged to the European lineage. AA variants were detected in 16.0% of cases. African variants belonging to classes Af1 (4.0%) and Af2 (1.3%) were detected. Different HPV types and HPV16 intratype variants are involved in oncogenic HPV infections in our population. These results suggest that HPV type distribution differs in CSW/IPW women and in the general population, although further analysis is necessary. PMID:16597872

Screening for human papillomavirus, cervical cytological abnormalities and associated risk factors in HIV-positive and HIV-negative women in Rwanda.

PubMed

Mukanyangezi, M F; Sengpiel, V; Manzi, O; Tobin, G; Rulisa, S; Bienvenu, E; Giglio, D

2018-02-01

Cervical cancer is the major cause of death from cancer in Africa. We wanted to assess the prevalence of human papillomavirus (HPV) infections and associated risk factors and to determine whether HPV testing could serve as a screening method for squamous intraepithelial lesions (SILs) in Rwanda. We also wanted to obtain a broader understanding of the underlying risk factors for the establishment of HPV infection in Rwanda. A total of 206 HIV-positive women, 172 HIV-negative women and 22 women with unknown HIV status were recruited at the University Teaching Hospitals of Kigali (UTHK) and of Butare (UTHB) in Rwanda. Participants underwent an interview, cervical sampling for a Thinprep Pap test and a screening test analysing 37 HPV strains. Only 27% of HIV-positive women and 7% of HIV-negative women had been screened for cervical cancer before. HPV16 and HPV52 were the most common HPV strains. HIV-positive women were more commonly infected with high-risk (HR) HPV and multitype HPV than HIV-negative women. The sensitivity was 78% and the specificity 87% to detect high-grade SIL (HSIL) with HPV screening. Among HIV-negative women, being divorced was positively associated with HR-HPV infection, while hepatitis B, Trichomonas vaginalis infection and HR-HPV infection were factors positively associated with SILs. Ever having had gonorrhoea was positively associated with HR-HPV infection among HIV-positive women. HR-HPV infection and the number of live births were positively associated with SILs. The currently used quadrivalent vaccine may be insufficient to give satisfactory HPV coverage in Rwanda. HPV Screening may be effective to identify women at risk of developing cervical cancer, particularly if provided to high-risk patients. © 2017 British HIV Association.

Oncogenic human papillomavirus (HPV) type distribution and HPV type 16 E6 variants in two Spanish population groups with different levels of HPV infection risk.

PubMed

Ortiz, M; Torres, M; Muñoz, L; Fernández-García, E; Canals, J; Cabornero, A I; Aguilar, E; Ballesteros, J; Del Amo, J; García-Sáiz, A

2006-04-01

The aim of this study is to determine oncogenic human papillomavirus (HPV) types and HPV type 16 (HPV16) variant distribution in two Spanish population groups, commercial sex workers and imprisoned women (CSW/IPW) and the general population. A multicenter cross-sectional study of 1,889 women from five clinical settings in two Spanish cities was conducted from May to November 2004. Oncogenic HPV infection was tested by an Hybrid Capture II (HC2) test, and positive samples were genotyped by direct sequencing using three different primer sets in L1 (MY09/11 and GP5+/GP6+) and E6/E7. HPV16 variants were identified by sequencing the E6, E2, and L1 regions. Four hundred twenty-five samples were positive for the HC2 test, 31.5% from CSW/IPW and 10.7% from the general population. HPV16 was the most frequent type. Distinct profiles of oncogenic HPV type prevalence were observed across the two populations. In order of decreasing frequency, HPV types 16, 31, 58, 66, 56, and 18 were most frequent in CSW/IPW women, and types 16, 31, 52, 68, 51, and 53 were most frequent in the general population. We analyzed HPV16 intratype variants, and a large majority (78.7%) belonged to the European lineage. AA variants were detected in 16.0% of cases. African variants belonging to classes Af1 (4.0%) and Af2 (1.3%) were detected. Different HPV types and HPV16 intratype variants are involved in oncogenic HPV infections in our population. These results suggest that HPV type distribution differs in CSW/IPW women and in the general population, although further analysis is necessary.

Natural immune responses against eight oncogenic human papillomaviruses in the ASCUS-LSIL triage study

PubMed Central

Wilson, Lauren E.; Pawlita, Michael; Castle, Phillip E.; Waterboer, Tim; Sahasrabuddhe, Vikrant; Gravitt, Patti E.; Schiffman, Mark; Wentzensen, Nicolas

2014-01-01

Only a subset of women with human papillomavirus (HPV) infections will become seropositive, and the factors influencing seroconversion are not well-understood. We used a multiplex serology assay in women with mildly abnormal cytology results to examine seroreactivity to oncogenic HPV genotypes. An unbiased subset of women in the atypical squamous cell of undetermined significance /low-grade squamous intraepithelial lesion Triage Study (ALTS) provided blood samples at trial enrollment for serological testing. A Luminex assay based on GST-L1 fusion proteins as antigens was used to test seroreactivity against eight carcinogenic HPV genotypes (16, 18, 31, 33, 35, 45, 52, 58). We analyzed the relationship between seroprevalence in women free of precancer (N=2464) and HPV DNA status, age, sexual behavior, and other HPV-related risk factors. The overall seroprevalence was 24.5% for HPV16 L1 and ~ 20% for 18L1 and 31L1. Among women free of precancer, seroprevalence peaked in women less than 29 years and decreased with age. Type-specific seroprevalence was associated with baseline DNA detection for HPV16 (OR= 1.36, 95%CI: 1.04–1.79) and HPV18 (OR= 2.31, 95%CI: 1.61–3.32), as well as for HPV52 and HPV58. Correlates of sexual exposure were associated with increased seroprevalence across most genotypes. Women who were current or former smokers were less likely to be seropositive for all eight of the tested oncogenic genotypes. The multiplex assay showed associations between seroprevalence and known risk factors for HPV infection across nearly all tested HPV genotypes but associations between DNA- and serostatus were weak, suggesting possible misclassification of the participants’ HPV serostatus. PMID:23588935

Screening for cervical cancer among HIV-positive and HIV-negative women in Cameroon using simultaneous co-testing with careHPV DNA testing and visual inspection enhanced by digital cervicography: Findings of initial screening and one-year follow-up.

PubMed

Cholli, Preetam; Bradford, Leslie; Manga, Simon; Nulah, Kathleen; Kiyang, Edith; Manjuh, Florence; DeGregorio, Geneva; Ogembo, Rebecca K; Orock, Enow; Liu, Yuxin; Wamai, Richard G; Sheldon, Lisa Kennedy; Gona, Philimon N; Sando, Zacharie; Welty, Thomas; Welty, Edith; Ogembo, Javier Gordon

2018-01-01

The World Health Organization (WHO)'s cervical cancer screening guidelines for limited-resource settings recommend sequential screening followed by same-day treatment under a "screen-and-treat" approach. We aimed to (1) assess feasibility and clinical outcomes of screening HIV-positive and HIV-negative Cameroonian women by pairing visual inspection with acetic acid and Lugol's iodine enhanced by digital cervicography (VIA/VILI-DC) with careHPV, a high-risk human papillomavirus (HR-HPV) nucleic acid test designed for low-resource settings; and (2) determine persistence of HR-HPV infection after one-year follow-up to inform optimal screening, treatment, and follow-up algorithms. We co-tested 913 previously unscreened women aged ≥30years and applied WHO-recommended treatment for all VIA/VILI-DC-positive women. Baseline prevalence of HR-HPV and HIV were 24% and 42%, respectively. On initial screen, 44 (5%) women were VIA/VILI-DC-positive, of whom 22 had HR-HPV infection, indicating 50% of women screened false-positive and would have been triaged for unnecessary same-day treatment. VIA/VILI-DC-positive women with HIV infection were three times more likely to be HR-HPV-positive than HIV-negative women (65% vs. 20%). All women positive for either VIA/VILI-DC or HR-HPV (n=245) were invited for repeat co-testing after one year, of which 136 (56%) returned for follow-up. Of 122 women who were HR-HPV-positive on initial screen, 60 (49%) re-tested negative, of whom 6 had received treatment after initial screen, indicating that 44% of initially HR-HPV-positive women spontaneously cleared infection after one year without treatment. Women with HIV were more likely to remain HR-HPV-positive on follow-up than HIV-negative women (61% vs. 22%, p<0.001). Treatment was offered to all VIA/VILI-DC positive women on initial screen, and to all women screening VIA/VILI-DC or HR-HPV positive on follow-up. We found careHPV co-testing with VIA/VILI-DC to be feasible and valuable in identifying false-positives, but careHPV screening-to-result time was too long to inform same-day treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of oncogenic human papillomavirus determination for diagnosis of high-grade anal intraepithelial neoplasia in HIV-infected MSM.

PubMed

Burgos, Joaquin; Hernández-Losa, Javier; Landolfi, Stefania; Guelar, Ana; Dinares, MªCarmen; Villar, Judith; Navarro, Jordi; Ribera, Esteve; Falcó, Vicenç; Curran, Adria

2017-10-23

To assess the oncogenic human papillomavirus (HPV) determination and the cotesting HPV and anal cytology value to detect high-grade anal intraepithelial neoplasia (HGAIN) in a cohort of HIV-MSM. Prospective study of HIV-infected MSM who underwent screening for anal dysplasia. Screening program includes anal cytology, HPV testing, and high-resolution anoscopy (HRA) at each visit. Histological samples were obtained if suspicious lesions were revealed by HRA. Sensitivity and specificity of the different tests were calculated by using histological results of HRA-guided biopsy as the reference test for HGAIN diagnosis. From May 2009 to August 2016, 692 HIV-infected MSM underwent 1827 anal cytologies, 1841 HRA examinations, and 1607 HPV testing. At first screening visit, anal cytology results were abnormal in 418 (60.4%) of 692 patients, and oncogenic HPV genotypes were found in 482 (79.5%) of 606 patients. Anal cytology showed a sensitivity of 89.2% [95% confidence interval (CI); 80.7-94.2] and a specificity of 44.2% (95% CI; 40.2-48.2) to detect HGAIN. Oncogenic HPV testing had 90.4% sensitivity (95% CI; 82-86.8) and 24.4% specificity (95% CI; 20.8-28.3). Cotesting showed a 97.4% sensitivity (95% CI; 91-99.3) and 14% specificity (95% CI; 11.2-17.3). In patients with atypical squamous cells of uncertain significance on cytology, oncogenic HPV testing had 91.3% sensitivity and 28.3% specificity to detect HGAIN. Abnormal cytology and oncogenic HPV determination showed similar sensitivity for detecting HGAIN. The two tests used together improved the sensitivity but with lowered specificity. In our opinion, HPV testing does not improve HGAIN detection and should not replace anal cytology as a standard screening test for HIV-infected MSM.

High Risk Human Papillomavirus Persistence Among HIV-infected Young Women in South Africa

PubMed Central

Adler, David; Wallace, Melissa; Bennie, Thola; Abar, Beau; Sadeghi, Rokhsanna; Meiring, Tracy; Williamson, Anna-Lise; Bekker, Linda-Gail

2015-01-01

Objectives Persistence of infection with high-risk Human papillomaviruses (HR-HPV) increases the risk of incident and progressive precancerous lesions of the cervix. Rates of HR-HPV persistence have been shown to be increased among HIV-infected adult women, however there is a paucity of literature addressing HPV persistence in the young HIV-infected population. We compared rates of HR-HPV persistence between HIV-infected and HIV-uninfected young women. Methods We obtained self-collected vaginal swabs at six-month intervals from 50 HIV-uninfected and 33 HIV-infected young women recruited through a community youth center (age 17-21 years) and compared rates of HR-HPV persistence. HR-HPV testing was conducted using the Roche’s Linear Array® HPV Test. Results Eighty-three prevalent (upon baseline testing) and incident (upon subsequent testing) individual HR-HPV infections were identified among 43 members of the cohort (23 HIV-uninfected and 20 HIV-infected). At twelve months, 19% of baseline HR-HPV infections continued to be present with a statistically significant difference between HIV-uninfected and HIV-infected participants (4% versus 31%; p=0.01). Conclusions HIV-infected young women in our cohort had a seven-fold increased rate of persistence of HR-HPV overall at 12 months indicating an increased risk for incident and progressive precancerous lesions. Identification of persistent infection with HR-HPV may complement cytological findings in determining the need for colposcopy. PMID:25697074

[Utilization of self-sampling kits for HPV testing in cervical cancer screening - pilot study].

PubMed

Ondryášová, H; Koudeláková, V; Drábek, J; Vaněk, P; Slavkovský, R; Hajdúch, M

2015-12-01

To get initial experience with alternative sampling (self-sampling) for HPV testing as the means of cervical cancer screening program. Original work. Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc. Based on expression of interest, 215 self-sampling kits were posted to women. Evalyn(®) Brush Vaginal swabs obtained by self-sampling were analyzed for the presence of HPV infection by Cobas 4800 HPV (Roche) followed by genotyping using PapilloCheck(®) HPV-Screening (Greiner Bio-One). Sixty women randomly chosen from our sample were sent a questionnaire focused on their experience with self-sampling. One hundred seventy-four of 215 (81%) distributed self-sampling devices have been delivered to analysis. All cervicovaginal swabs were sampled correctly and it was possible to analyze them by Cobas 4800 HPV test. Similarly, 98% (171/174) samples were analyzable by PapilloCheck(®) HPV-Screening.One hundred twenty-five (72%) of 174 tested samples were HPV negative. Low risk HPV infection was detected only in 7 samples (4%), and high risk HPV (hrHPV) infection was present in 42 samples (24%). The most frequently detected hrHPV genotypes were HPV16 (11/42; 26%) and HPV53 (6/42; 14%). HrHPV co-infection was detected in 10 cases, in 5 of them lrHPV infection was find also.Of the 60 questionnaires, 48 (80%) were returned. From this group, 47 (98%) women rated their experience with self-sampling device as good to excellent. User manual of self-sampling device was considered good to excellent by all women (100%). All women also rated the convenience of self-sampling device using as good to excellent. As expected, most of the women (n = 42 [88%]) preferred self-sampling to physician sampling. Cervicovaginal self-sampling leads to valid results of HPV screening using two molecular genetics methods and was accepted by Czech women very well. The self-sampling as an opportunity to participate in cervical cancer screening could increase the attendance of the screening program and would help to reduce the incidence and mortality for this disease in the Czech population.

[Counseling for HPV detection when used to screen for cervical cancer: a qualitative study on the needs of women from Michoacan, Mexico].

PubMed

León-Maldonado, Leith; Allen-Leigh, Betania; Lazcano-Ponce, Eduardo

2014-01-01

To explore the information and counseling needs of a group of Mexican women during use of the HPV test. In 2011, 24 semistructured interviews were done with women upon receiving HPV test results in two municipalities in the state of Michoacan. Qualitative analysis of the interviews was done using constant comparison techniques. During their use of screening services women received limited counseling; they felt anguish and confusion. Women were interested in receiving information and advice on HPV and cervical cancer, the meaning of test result, next steps to be taken in their healthcare use as well as information and emotional support related to the sexual transmission of HPV. The design and implementation of policies are needed which instigate health education and counseling in conjunction with HPV testing.

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

Eight Nucleotide Substitutions Inhibit Splicing to HPV-16 3′-Splice Site SA3358 and Reduce the Efficiency by which HPV-16 Increases the Life Span of Primary Human Keratinocytes

PubMed Central

Li, Xiaoze; Johansson, Cecilia; Cardoso Palacios, Carlos; Mossberg, Anki; Dhanjal, Soniya; Bergvall, Monika; Schwartz, Stefan

2013-01-01

The most commonly used 3′-splice site on the human papillomavirus type 16 (HPV-16) genome named SA3358 is used to produce HPV-16 early mRNAs encoding E4, E5, E6 and E7, and late mRNAs encoding L1 and L2. We have previously shown that SA3358 is suboptimal and is totally dependent on a downstream splicing enhancer containingmultiple potential ASF/SF2 binding sites. Here weshow that only one of the predicted ASF/SF2 sites accounts for the majority of the enhancer activity. We demonstrate that single nucleotide substitutions in this predicted ASF/SF2 site impair enhancer function and that this correlates with less efficient binding to ASF/SF2 in vitro. We provide evidence that HPV-16 mRNAs that arespliced to SA3358 interact with ASF/SF2 in living cells. In addition,mutational inactivation of the ASF/SF2 site weakened the enhancer at SA3358 in episomal forms of the HPV-16 genome, indicating that the enhancer is active in the context of the full HPV-16 genome.This resulted in induction of HPV-16 late gene expression as a result of competition from late splice site SA5639. Furthermore, inactivation of the ASF/SF2 site of the SA3358 splicing enhancer reduced the ability of E6- and E7-encoding HPV-16 plasmids to increase the life span of primary keratinocytes in vitro, demonstrating arequirement for an intact splicing enhancer of SA3358 forefficient production of the E6 and E7 mRNAs. These results link the strength of the HPV-16 SA3358 splicing enhancer to expression of E6 and E7 and to the pathogenic properties of HPV-16. PMID:24039800

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.

Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa: a cross-sectional study.

PubMed

Moodley, Jennifer R; Constant, Deborah; Hoffman, Margaret; Salimo, Anna; Allan, Bruce; Rybicki, Ed; Hitzeroth, Inga; Williamson, Anna-Lise

2009-08-07

Cervical cancer and infection with human immunodeficiency virus (HIV) are both important public health problems in South Africa (SA). The aim of this study was to determine the prevalence of cervical squamous intraepithelial lesions (SILs), high-risk human papillomavirus (HR-HPV), HPV viral load and HPV genotypes in HIV positive women initiating anti-retroviral (ARV) therapy. A cross-sectional survey was conducted at an anti-retroviral (ARV) treatment clinic in Cape Town, SA in 2007. Cervical specimens were taken for cytological analysis and HPV testing. The Digene Hybrid Capture 2 (HC2) test was used to detect HR-HPV. Relative light units (RLU) were used as a measure of HPV viral load. HPV types were determined using the Roche Linear Array HPV Genotyping test. Crude associations with abnormal cytology were tested and multiple logistic regression was used to determine independent risk factors for abnormal cytology. The median age of the 109 participants was 31 years, the median CD4 count was 125/mm3, 66.3% had an abnormal Pap smear, the HR-HPV prevalence was 78.9% (Digene), the median HPV viral load was 181.1 RLU (HC2 positive samples only) and 78.4% had multiple genotypes. Among women with abnormal smears the most prevalent HR-HPV types were HPV types 16, 58 and 51, all with a prevalence of 28.5%. On univariate analysis HR-HPV, multiple HPV types and HPV viral load were significantly associated with the presence of low and high-grade SILs (LSIL/HSIL). The multivariate logistic regression showed that HPV viral load was associated with an increased odds of LSIL/HSIL, odds ratio of 10.7 (95% CI 2.0 - 57.7) for those that were HC2 positive and had a viral load of 181.1 RLU. Women initiating ARVs have a high prevalence of abnormal Pap smears and HR-HPV. Our results underscore the need for locally relevant, rigorous screening protocols for the increasing numbers of women accessing ARV therapy so that the benefits of ARVs are not partially offset by an excess risk in cervical cancer.

Cytology and human papillomavirus testing 6 to 12 months after ASCUS or LSIL cytology in organized screening to predict high-grade cervical neoplasia between screening rounds.

PubMed

Tropé, Ameli; Sjøborg, Katrine D; Nygård, Mari; Røysland, Kjetil; Campbell, Suzanne; Alfsen, G Cecilie; Jonassen, Christine M

2012-06-01

We carried out a prospective study comparing the performance of human papillomavirus (HPV) E6/E7 mRNA (PreTect HPV-Proofer; NorChip, Klokkarstua, Norway) and DNA (Amplicor HPV test; Roche Diagnostics, Basel, Switzerland) triage testing of women 6 to 12 months after atypical-squamous-cells-of-undetermined-significance (ASCUS) or low-grade-squamous-intraepithelial-lesion (LSIL) cytology in organized screening to predict high-grade cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) between screening rounds. Between January 2005 and April 2008, 692 study women with screening-detected ASCUS/LSIL cytology 6 to 12 months earlier returned for HPV mRNA and DNA testing and repeat cytology. The median follow-up time was 3 years, using existing health care facilities. Follow-up test results were available for 625 women. Of the 145 CIN2+ cases detected during the study period, 95 (65.5%) were HPV mRNA positive 6 to 12 months after screening-detected ASCUS/LSIL, 44 (30.4%) were HPV mRNA negative, and 6 (4.1%) were invalid. The corresponding HPV DNA results were 139 (95.9%), 5 (3.4%), and 1 (0.7%), respectively. The cumulative incidences of CIN2+ 3 years after a negative HPV mRNA and DNA test were 10.3% (95% confidence interval [CI], 7.2 to 13.3%) and 1.8% (95% CI, 0.0 to 3.6%), respectively. The cumulative incidences of CIN2+ 3 years after positive HPV mRNA and DNA tests were 52.8% (95% CI, 40.1 to 60.1%) and 41.3% (95% CI, 35.5 to 46.6%), respectively. In conclusion, both positive HPV mRNA and DNA test results have a high enough long-term prediction of CIN2+ risk to consider referral to colposcopy as good practice when performed in delayed triage of women with ASCUS/LSIL cytology. In addition, the low CIN2+ risk among women with a negative Amplicor HPV test in our study confirms its safe use in a clinical setting.

Cytology and Human Papillomavirus Testing 6 to 12 Months after ASCUS or LSIL Cytology in Organized Screening To Predict High-Grade Cervical Neoplasia between Screening Rounds

PubMed Central

Sjøborg, Katrine D.; Nygård, Mari; Røysland, Kjetil; Campbell, Suzanne; Alfsen, G. Cecilie; Jonassen, Christine M.

2012-01-01

We carried out a prospective study comparing the performance of human papillomavirus (HPV) E6/E7 mRNA (PreTect HPV-Proofer; NorChip, Klokkarstua, Norway) and DNA (Amplicor HPV test; Roche Diagnostics, Basel, Switzerland) triage testing of women 6 to 12 months after atypical-squamous-cells-of-undetermined-significance (ASCUS) or low-grade-squamous-intraepithelial-lesion (LSIL) cytology in organized screening to predict high-grade cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) between screening rounds. Between January 2005 and April 2008, 692 study women with screening-detected ASCUS/LSIL cytology 6 to 12 months earlier returned for HPV mRNA and DNA testing and repeat cytology. The median follow-up time was 3 years, using existing health care facilities. Follow-up test results were available for 625 women. Of the 145 CIN2+ cases detected during the study period, 95 (65.5%) were HPV mRNA positive 6 to 12 months after screening-detected ASCUS/LSIL, 44 (30.4%) were HPV mRNA negative, and 6 (4.1%) were invalid. The corresponding HPV DNA results were 139 (95.9%), 5 (3.4%), and 1 (0.7%), respectively. The cumulative incidences of CIN2+ 3 years after a negative HPV mRNA and DNA test were 10.3% (95% confidence interval [CI], 7.2 to 13.3%) and 1.8% (95% CI, 0.0 to 3.6%), respectively. The cumulative incidences of CIN2+ 3 years after positive HPV mRNA and DNA tests were 52.8% (95% CI, 40.1 to 60.1%) and 41.3% (95% CI, 35.5 to 46.6%), respectively. In conclusion, both positive HPV mRNA and DNA test results have a high enough long-term prediction of CIN2+ risk to consider referral to colposcopy as good practice when performed in delayed triage of women with ASCUS/LSIL cytology. In addition, the low CIN2+ risk among women with a negative Amplicor HPV test in our study confirms its safe use in a clinical setting. PMID:22518869

Human Papillomavirus (HPV) infection in pregnant women and mother-to-child transmission of genital HPV genotypes: a prospective study in Spain

PubMed Central

2009-01-01

Background Studies on HPV infection in pregnant women and HPV transmission to the child have yielded inconsistent results. Methods To estimate mother-to-child HPV transmission we carried out a prospective cohort study that included 66 HPV-positive and 77 HPV-negative pregnant women and their offspring attending a maternity hospital in Barcelona. To estimate HPV prevalence and genotype distribution in pregnancy we also carried out a related screening survey of cervical HPV-DNA detection among 828 pregnant women. Cervical cells from the mother were collected at pregnancy (mean of 31 weeks) and at the 6-week post-partum visit. Exfoliated cells from the mouth and external genitalia of the infants were collected around birth, at the 6-week post-partum visit, and around 3, 6, 12, and 24 months of age. All samples were tested for HPV using PCR. Associations between potential determinants of HPV infection in pregnant women and of HPV positivity in infants were also explored by logistic regression modelling. Results Overall cervical HPV-DNA detection in pregnant women recruited in the HPV screening survey was 6.5% (54/828). Sexual behavior-related variables, previous histories of genital warts or sexually transmitted infections, and presence of cytological abnormalities were statistically significantly and positively associated with HPV DNA detection in pregnant women recruited in the cohort. At 418 infant visits and a mean follow-up time of 14 months, 19.7% of infants born to HPV-positive mothers and 16.9% of those born to HPV-negative mothers tested HPV positive at some point during infants' follow-up. The most frequently detected genotype both in infants and mothers was HPV-16, after excluding untyped HPV infections. We found a strong and statistically significant association between mother's and child's HPV status at the 6-week post-partum visit. Thus, children of mothers' who were HPV-positive at the post-partum visit were about 5 times more likely to test HPV-positive than children of corresponding HPV-negative mothers (p = 0.02). Conclusion This study confirms that the risk of vertical transmission of HPV genotypes is relatively low. HPV persistence in infants is a rare event. These data also indicate that vertical transmission may not be the sole source of HPV infections in infants and provides partial evidence for horizontal mother-to-child HPV transmission. PMID:19473489

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

PubMed Central

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

2015-01-01

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

Human papillomavirus infection and anxiety: analyses in women with low-grade cervical cytological abnormalities unaware of their infection status.

PubMed

Johnson, Candice Y; Sharp, Linda; Cotton, Seonaidh C; Harris, Cheryl A; Gray, Nicola M; Little, Julian

2011-01-01

Women testing positive for human papillomavirus (HPV) infection experience increased levels of anxiety that have been attributed to fears of stigmatization and developing cervical cancer. The objective of this study was to investigate the association between HPV infection and anxiety in women who were unaware they had been tested specifically for HPV, to determine if any anxiety experienced by HPV-positive women could be due to causes other than learning of test results. This study was nested within a randomised controlled trial of management of women with abnormal cervical cytology conducted in the United Kingdom with recruitment between 1999 and 2002. At baseline, prior to having a sample taken for HPV testing, the results of which were not disclosed, women were assessed for anxiety using the Hospital Anxiety and Depression Scale and asked about fears of developing cervical cancer ("cancer worries"); this assessment was repeated at 12, 18, 24, and 30 months of follow-up. Logistic regression and generalized estimating equations were used for the cross-sectional (baseline) and longitudinal analyses, respectively. Among the 2842 participants, there was no association between HPV status and anxiety among white women. Among non-white women, however, anxiety was less common among HPV-positive than HPV-negative women (adjusted odds ratio 0.41, 95% confidence interval 0.22 to 0.77). Among non-smokers, cancer worry was more common in HPV-positive than HPV-negative women; the opposite association was observed among ex-smokers. Associations between HPV status and anxiety may be explained by factors other than learning of test results and may vary by ethnicity and lifestyle factors.

Impact of 6-month frozen storage of cervical specimens in alkaline buffer conditions on human papillomavirus genotyping.

PubMed

LaMere, Brandon J; Howell, Renee; Fetterman, Barbara; Shieh, Jen; Castle, Philip E

2008-08-01

The impact of 6-month storage of cervical specimens under alkaline conditions that occurs as the result of Hybrid Capture 2 testing on human papillomavirus (HPV) genotyping is not well documented. To examine this issue, 143 frozen hc2-positive specimens in specimen transport medium were selected at random from each of the following groups: specimens stored for 6 months, 4 months, and 2.5 months under alkaline pH (pH 12-13) and specimens stored 1 month at neutral pH (pH 6-7) as controls. Specimens were tested in a masked fashion for 20 HPV genotypes (HPV6, 11, 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, and 82) using a prototype, research-use-only GP5+/6+ L1 consensus PCR method and multiplex hybridization using Luminex xMAP for detection of specific HPV genotypes One control specimen had missing test results. There were no statistical differences in the number of HPV genotypes detected, number of carcinogenic HPV genotypes detected, or in the signal strength among HPV-positive results across groups. Six-month frozen storage of cervical specimens at alkaline pH had little impact on testing for HPV genotypes among hc2-positive women using this HPV genotyping method.

[Preinvasive vulvar and cervical cancer in a 32-year-old woman, DNA HPV 16 positive with mtDNA mutation--case study].

PubMed

Kedzia, Witold; Malkowska-Walczak, Blanka; Józefiak, Agata; Wadowicka, Alicja; Guglas, Bogna; Pruski, Dominik; Kedzia, Helena; Spaczyński, Marek

2009-07-01

Coincidence of preinvasive vulvar and cervical cancer in young women is very rare. Lesions like VIN 3/preinvasive vulvar cancer and CIN 3/preinvasive cervical cancer are strictly connected with viral infection and are multilocular. In the presented case the following tests have been performed: HPV DNA test for the presence of 13 oncogenic HPV types, mRNA HPV test for the presence of transcripts for HPV 16, 18, 31, 33, 45 and the analysis of mtDNA D-Loop region. In the examined patient HPV 16 infection, as well as the presence of transcripts for HPV 16 E6/7 were diagnosed. The analysis of mtDNA D-Loop region showed nucleotide lesions like: T>C 16.192, T>C 16.223, T>C 16.292, C>T 16.325, C>T 16.579.

Maternal Support for Human Papillomavirus Vaccination in Honduras

PubMed Central

Langrish, Sarah M.; Cotton, Deborah J.; Simon, Carol J.

2011-01-01

Abstract Background Cervical cancer is a leading cause of cancer death for women in Latin America, and vaccinating against human papillomavirus (HPV) has the potential to limit this disease. We sought to determine Honduran women's awareness of HPV vaccination and interest in vaccinating their daughters against HPV. Methods We interviewed mothers aged ≥17 at primary care clinics in Honduras. First, we collected demographic information and assessed knowledge related to cervical cancer prevention and awareness of HPV and HPV vaccination. Because most participants were not familiar with HPV, education about the relationships among HPV, sexual activity, and cervical cancer was provided before we asked participants if they would accept HPV vaccination for a 9-year-old daughter. We used multivariable logistic regression to determine predictors of vaccine acceptance. Results We interviewed 632 mothers. Only 13% had heard of HPV vaccination before the interview. After education, 91% would accept HPV vaccination for a 9-year-old daughter. Mothers who intended to vaccinate knew more at baseline about cervical cancer prevention than did those who did not endorse vaccination. Demographic characteristics did not predict vaccine acceptance. Conclusions Few Honduran mothers were aware of HPV or HPV vaccination. However, most Honduran mothers would accept HPV vaccination for their daughters after receiving education about the relationship between HPV infection and cervical cancer. Baseline cervical cancer knowledge was associated with vaccine acceptance. PMID:21091226

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.

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

PubMed

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

2016-04-01

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

Prevalence of and risk factors for anal human papillomavirus infection in heterosexual men.

PubMed

Nyitray, Alan; Nielson, Carrie M; Harris, Robin B; Flores, Roberto; Abrahamsen, Martha; Dunne, Eileen F; Giuliano, Anna R

2008-06-15

In US men, the incidence of anal cancer, the primary cause of which is human papillomavirus (HPV) infection, has increased almost 3-fold in 3 decades; however, little is known about the epidemiology of anal HPV infection, especially in heterosexual men. In 2 US cities, behavioral data and anal biological specimens were collected from 253 men who acknowledged having engaged in sexual intercourse with a woman during the preceding year. On the basis of DNA analysis, overall prevalence of anal HPV infection was found to be 24.8% in 222 men who acknowledged having had no prior sexual intercourse with men. Of the men with anal HPV infection, 33.3% had an oncogenic HPV type. Risk factors independently associated with anal HPV were lifetime number of female sex partners and frequency of sex with females during the preceding month. These results suggest that anal HPV infection may be common in heterosexual men.

Refractory Genital HPV Infection and Adult-Onset Still Disease: A Case Report and Literature Review.

PubMed

Yu, Xin; Zheng, Heyi

2016-04-01

Adult-onset Still disease (AOSD) is a systemic autoimmune disease (AIID) that can develop after exposure to infectious agents. Genital human papillomavirus (HPV) infection has been reported to induce or exacerbate AIIDs, such as systemic lupus erythematosus (SLE). No guidelines are available for the management of genital warts in AOSD. Case report and literature review. We report a patient who was diagnosed AOSD in the setting of refractory and recurrent genital HPV infection, demonstrating a possible link between HPV infection and AOSD. In addition, we also discuss the management of genital warts in patients with AOSD. To the best of our knowledge, no previous cases of AOSD with genital HPV infection have been reported in literature. We then conclude that the patient AOSD may be triggered by primary HPV infection. Larger number of patient samples is needed to confirm whether HPV could trigger AOSD.

Association of both consistency and strength of self-reported clinician recommendation for HPV vaccination and HPV vaccine uptake among 11- to 12-year-old children.

PubMed

Finney Rutten, Lila J; St Sauver, Jennifer L; Beebe, Timothy J; Wilson, Patrick M; Jacobson, Debra J; Fan, Chun; Breitkopf, Carmen Radecki; Vadaparampil, Susan T; MacLaughlin, Kathy L; Jacobson, Robert M

2017-10-27

We tested the hypotheses that consistency and strength of clinician recommendation of the human papillomavirus (HPV) vaccination would be associated with vaccine delivery rates. From October 2015 through January 2016, we conducted a survey of primary care clinicians (n=227) in Southeastern Minnesota to evaluate clinician behaviors regarding HPV vaccination. The survey response rate was 41.0% (51 clinical sites). We used the Rochester Epidemiology Project, a clinical data linkage infrastructure, to ascertain clinical site-level HPV vaccination rates. We examined associations of clinician self-reports of both the consistency and strength of their recommendations for HPV vaccination for patients aged 11-12years (n=14,406) with site-level vaccination rates. The majority of clinicians reported consistently (always or usually) recommending the HPV vaccine to females (79.0%) and to males (62.2%); 71.9% of clinicians reported strongly recommending the vaccine to females while 58.6% reported strongly recommending to males. Consistency and strength of recommending the HPV vaccine was significantly higher among those practicing in pediatrics and board certified in pediatrics compared to family medicine. Higher rates of initiation (1 dose) [Incidence Rate Ratio (IRR)=1.05; 95% CI (1.01-1.09)] and completion (3 doses) [IRR=1.08; 95% CI (1.02-1.13)] were observed among clinical sites where, on average, clinicians more frequently reported always or usually recommending the vaccine for females compared to sites where, on average, clinicians reported recommending the vaccine less frequently. Similarly, higher rates of initiation [IRR=1.03; 95% CI (1.00-1.06)] and completion [IRR=1.04; CI (1.00, 1.08)] were observed among sites where clinicians reported strongly recommending the vaccine to females more frequently compared to sites where, on average, clinicians reported strongly recommending the HPV vaccine less frequently; similar associations were observed for male initiation [IRR=1.05; CI (1.02,1.08)] and completion [IRR=1.05; 95% CI (1.01, 1.09)]. Consistency and strength of HPV vaccination recommendation was associated with higher vaccination rates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Findings of multiple HPV genotypes in cervical carcinoma are associated with poor cancer-specific survival in a Swedish cohort of cervical cancer primarily treated with radiotherapy.

PubMed

Kaliff, Malin; Sorbe, Bengt; Mordhorst, Louise Bohr; Helenius, Gisela; Karlsson, Mats G; Lillsunde-Larsson, Gabriella

2018-04-10

Cervical cancer (CC) is one of the most common cancers in women and virtually all cases of CC are a result of a persistent infection of human papillomavirus (HPV). For disease detected in early stages there is curing treatment but when diagnosed late with recurring disease and metastasis there are limited possibilities. Here we evaluate HPV impact on treatment resistance and metastatic disease progression. Prevalence and distribution of HPV genotypes and HPV16 variants in a Swedish CC patient cohort (n=209) was evaluated, as well as HPV influence on patient prognosis. Tumor samples suitable for analysis (n=204) were genotyped using two different real-time PCR methods. HPV16 variant analysis was made using pyrosequencing. Results showed that HPV prevalence in the total series was 93%. Of the HPV-positive samples, 13% contained multiple infections, typically with two high-risk HPV together. Primary cure rate for the complete series was 95%. Recurrence rate of the complete series was 28% and distant recurrences were most frequent (20%). Patients with tumors containing multiple HPV-strains and particularly HPV genotypes belonging to the alpha 7 and 9 species together had a significantly higher rate of distant tumor recurrences and worse cancer-specific survival rate.

Detection of human papillomavirus in pterygium and conjunctival papilloma by hybrid capture II and PCR assays.

PubMed

Takamura, Y; Kubo, E; Tsuzuki, S; Akagi, Y

2008-11-01

To elucidate the putative role of human papillomavirus (HPV) infection in pterygium and conjunctival papilloma. Hybrid capture II (HC-II) and polymerase chain reaction (PCR) assays were performed to detect HPV in pterygium (42 samples obtained from 40 patients) and conjunctival papilloma (8 samples from 6 patients). The amount of HPV DNA was evaluated by measurement of relative light units (RLUs) on a luminometer. All papilloma samples were positive for HPV DNA by PCR and HC-II. The RLU values for specimens of recurrent and re-recurrent papilloma were markedly higher than those for specimens of primary lesions. HPV was detected by PCR in 2 of 42 (4.8%) beta-globin-positive pterygium specimens, whereas HC-II showed that HPV was negative in all pterygium samples. Our results support the hypothesis that HPV DNA is associated with the pathogenesis of conjunctival papilloma, but not pterygium. RLU measurement by HC-II may serve as a marker for evaluating the activity of HPV in conjunctival tumours.

Locoregional Recurrent or Second Primary Head and Neck Cancer: Management Strategies and Challenges.

PubMed

Wong, Stuart J; Heron, Dwight E; Stenson, Kerstin; Ling, Diane C; Vargo, John A

2016-01-01

Treatment of patients with locoregional recurrent or second primary head and neck squamous cell cancer (HNSCC) has been guided by well-reasoned principles and informed by carefully tested chemotherapy and radiation regimens. However, clinical decision making for this population is complicated by many factors. Although surgery is generally considered the treatment of choice for patients with HNSCC with recurrent disease or new second primary disease in a previously irradiated field, operability of cases is not always straightforward. Postoperative treatment is frequently warranted but carries significant risk. In addition, the rapid rise in the incidence of HPV-associated HNSCC raises the question of whether established treatment paradigms should be re-examined in this population of patients with a much better prognosis than the non-HPV population. Furthermore, new radiation techniques and new systemic agents show early promising results in recent clinical studies, suggesting potential for practice-changing effects in the future management of this disease. This article examines each of the treatment modalities used in the care of patients with HNSCC with recurrent or new second primary disease and provides a perspective to aid clinicians in the management of this disease.

Repeat Cytology and Human Papillomavirus Screening Strategies in Detecting Preinvasive Cervical Lesions

PubMed Central

Li, Kemin; Yin, Rutie

2015-01-01

Abstract The aim of the present study was to determine the value of human papillomavirus (HPV) testing in screening patients with preinvasive cervical lesions. Seven hundred thirty-four women diagnosed with atypical squamous cells of undetermined significance (ASCUS+) cervical cytology during routine screening had additional cytologic testing and HPV DNA testing within 6 months of their diagnosis, after which all women who tested positive were referred for colposcopy and biopsy. The test findings were then used to determine the screening value of HPV for diagnosing preinvasive cervical lesions. Cytology and HPV testing were compared by conventional cytology. The odds ratio (OR) of sensitivity using ASCUS+ or low-grade squamous intraepithelial neoplasia (LSIL+) as a cutoff for detecting cervical intraepithelial neoplasia (CIN) II+ was, respectively, 0.78 (0.72, 0.85) and 0.82 (0.70, 0.95) (P < 0.01). The cytology for triage and conventional cytology had different sensitivities using ASCUS+ or LSIL+ as the cutoff (P < 0.01). The cytology or HPV testing and conventional cytology had a difference in sensitivity using ASCUS+, LSIL+, or high-grade squamous intraepithelial neoplasia (HSIL+) as the cutoff (P < 0.01). Cytology and HPV testing were also compared with conventional cytology. The OR of specificity using ASCUS+ or LSIL+ as the cutoff for the detection of CIN II+ was 1.97 (1.68, 2.31) and 1.10 (1.02, 1.18), respectively (P < 0.01). The cytology for triage and conventional cytology had a difference in specificity when ASCUS+ or LSIL+ was used as the cutoff (P < 0.01). Finally, the cytology or HPV testing and conventional cytology had a difference in specificity when ASCUS+, LSIL+, or HSIL+ was used as the cutoff (P < 0.01). Cytology and HPV testing and cytology for triage improved the specificity of detecting CIN II+, but this did not improve the sensitivity. Additionally, cytology or HPV testing improved the sensitivity of detecting CIN II+ but not the specificity. PMID:25654377

An appraisal of theoretical approaches to examining behaviours in relation to Human Papillomavirus (HPV) vaccination of young women

PubMed Central

Batista Ferrer, Harriet; Audrey, Suzanne; Trotter, Caroline; Hickman, Matthew

2015-01-01

Background Interventions to increase uptake of Human Papillomavirus (HPV) vaccination by young women may be more effective if they are underpinned by an appropriate theoretical model or framework. The aims of this review were: to describe the theoretical models or frameworks used to explain behaviours in relation to HPV vaccination of young women, and: to consider the appropriateness of the theoretical models or frameworks used for informing the development of interventions to increase uptake. Methods Primary studies were identified through a comprehensive search of databases from inception to December 2013. Results Thirty-four relevant studies were identified, of which 31 incorporated psychological health behaviour models or frameworks and three used socio-cultural models or theories. The primary studies used a variety of approaches to measure a diverse range of outcomes in relation to behaviours of professionals, parents, and young women. The majority appeared to use theory appropriately throughout. About half of the quantitative studies presented data in relation to goodness of fit tests and the proportion of the variability in the data. Conclusion Due to diverse approaches and inconsistent findings across studies, the current contribution of theory to understanding and promoting HPV vaccination uptake is difficult to assess. Ecological frameworks encourage the integration of individual and social approaches by encouraging exploration of the intrapersonal, interpersonal, organisational, community and policy levels when examining public health issues. Given the small number of studies using such approach, combined with the importance of these factors in predicting behaviour, more research in this area is warranted. PMID:26314783

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.

Comparison of initial stream urine samples and cervical samples for detection of human papillomavirus.

PubMed

Hagihara, Mao; Yamagishi, Yuka; Izumi, Koji; Miyazaki, Narimi; Suzuki, Takayoshi; Kato, Hideo; Nishiyama, Naoya; Koizumi, Yusuke; Suematsu, Hiroyuki; Mikamo, Hiroshige

2016-08-01

Uterine cervical cancer is a treatable and preventable cancer. Medical efforts to reduce rates of cervical cancer focus on the promotion of human papillomavirus (HPV) vaccination and the promotion of routine cervical cancer screening done by cervical cytology and cervical HPV testing. Urine-based HPV testing would be simple and noninvasive approach to screen for cervical cancer. Two biospecimens (clinician-taken sample from cervix and initial stream urine sample) were provided from a total of 240 healthy women attending for cancer screening provided for HPV testing. We have assessed the HPV detection rates among cervical samples and pellet fraction of urine samples using HPV test (Anyplex™ II HPV28 Detection kit, Seegene, Korea). Among 240 samples screened, HPV prevalence was 42.9% in pellet fractions of urine samples. The agreement between the two kinds of samples was 98.4%, k = 0.792. Discordant results were observed in 27 cases; 5 were positive only by urine samples and 22 were positive only by smear samples. Sensitivity and specificity for all HPV DNA in pellet fractions of urine using cervical samples as reference was 68.4% and 99.9%. Comparing methodologies of collection of samples for HPV detection, they showed the higher agreements for almost genotypes between cervical samples and pellet fractions of urine samples. These results suggest that urine could be a good noninvasive tool to monitor HPV infection in women. Additional research in a larger and general screening population would be needed. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

An automated quantitative DNA image cytometry system detects abnormal cells in cervical cytology with high sensitivity.

PubMed

Wong, O G; Ho, M W; Tsun, O K; Ng, A K; Tsui, E Y; Chow, J N; Ip, P P; Cheung, A N

2018-03-26

To evaluate the performance of an automated DNA-image-cytometry system as a tool to detect cervical carcinoma. Of 384 liquid-based cervical cytology samples with available biopsy follow-up were analyzed by both the Imager System and a high-risk HPV test (Cobas). The sensitivity and specificity of Imager System for detecting biopsy proven high-grade squamous intraepithelial lesion (HSIL, cervical intraepithelial neoplasia [CIN]2-3) and carcinoma were 89.58% and 56.25%, respectively, compared to 97.22% and 23.33% of HPV test but additional HPV 16/18 genotyping increased the specificity to 69.58%. The sensitivity and specificity of the Imager System for predicting HSIL+ (CIN2-3+) lesions among atypical squamous cells of undetermined significance samples were 80.00% and 70.53%, respectively, compared to 100% and 11.58% of HPV test whilst the HPV 16/18 genotyping increased the specificity to 77.89%. Among atypical squamous cells-cannot exclude HSIL, the sensitivity and specificity of Imager System for predicting HSIL+ (CIN2-3+) lesions upon follow up were 82.86% and 33.33%%, respectively, compared to 97.14% and 4.76% of HPV test and the HPV 16/18 genotyping increased the specificity to 19.05%. Among low-grade squamous intraepithelial lesion cases, the sensitivity and specificity of the Imager System for predicting HSIL+ (CIN2-3+) lesions were 66.67% and 35.71%%, respectively, compared to 66.67% and 29.76% of HPV test while HPV 16/18 genotyping increased the specificity to 79.76%. The overall results of imager and high-risk HPV test agreed in 69.43% (268) of all samples. The automated imager system and HPV 16/18 genotyping can enhance the specificity of detecting HSIL+ (CIN2-3+) lesions. © 2018 John Wiley & Sons Ltd.

Molecular epidemiology and genotype distribution of Human Papillomavirus (HPV) among Arab women in the State of Qatar.

PubMed

Bansal, Devendra; Elmi, Asha A; Skariah, Sini; Haddad, Pascale; Abu-Raddad, Laith J; Al Hamadi, Aysha H; Mohamed-Nady, Nady; Affifi, Nahla M; Ghedira, Randa; Hassen, Elham; Al-Thani, Asma A J; Al-Ansari, Afaf A H M; Sultan, Ali A

2014-11-26

Human Papilloma Virus (HPV) infection is the major cause of cervical cancer worldwide. With limited data available on HPV prevalence in the Arab countries, this study aimed to identify the prevalence and genotypic distribution of HPV in the State of Qatar. 3008 cervical samples, exclusively of women with Arabic origin residing in Qatar were collected from the Women's Hospital and Primary Health Care Corporation in Doha, State of Qatar. HPV DNA detection was done using GP5+/6+ primers based real time-polymerase chain reaction (RT-PCR) assay followed by the usage of HPV type specific primers based RT- PCR reactions and Sanger sequencing for genotype identification. Similar prevalence rates of HPV infection was identified in both Qatari and non-Qatari women at 6.2% and 5.9% respectively. HPV prevalence rate of 5.8% and 18.4% was identified in women with normal cytology and in women with abnormal cytology respectively. HPV 81, 11 and 16, in decreasing order were the most commonly identified genotypes. HPV 81 was the most frequent low-risk genotype among women with both normal (74.0%) and abnormal (33.3%) cytology. HPV 16 (4.6%) was identified as the predominant high-risk HPV genotype among women with normal cytology and HPV 16, HPV 18, and HPV 56 (22.2% each) were the most common identified high-risk genotypes in women with abnormal cytology. The overall HPV prevalence in Arab women in Qatar was identified as 6.1% with an increased HPV prevalence seen in women with abnormal cytology results and no significant trends seen with age. In contrast to Western countries, we report a varied genotypic profile of HPV with a high prevalence of low-risk HPV genotype 81 among the Arab women residing in Qatar.

Impact and Cost-effectiveness of 3 Doses of 9-Valent Human Papillomavirus (HPV) Vaccine Among US Females Previously Vaccinated With 4-Valent HPV Vaccine.

PubMed

Chesson, Harrell W; Laprise, Jean-François; Brisson, Marc; Markowitz, Lauri E

2016-06-01

We estimated the potential impact and cost-effectiveness of providing 3-doses of nonavalent human papillomavirus (HPV) vaccine (9vHPV) to females aged 13-18 years who had previously completed a series of quadrivalent HPV vaccine (4vHPV), a strategy we refer to as "additional 9vHPV vaccination." We used 2 distinct models: (1) the simplified model, which is among the most basic of the published dynamic HPV models, and (2) the US HPV-ADVISE model, a complex, stochastic, individual-based transmission-dynamic model. When assuming no 4vHPV cross-protection, the incremental cost per quality-adjusted life-year (QALY) gained by additional 9vHPV vaccination was $146 200 in the simplified model and $108 200 in the US HPV-ADVISE model ($191 800 when assuming 4vHPV cross-protection). In 1-way sensitivity analyses in the scenario of no 4vHPV cross-protection, the simplified model results ranged from $70 300 to $182 000, and the US HPV-ADVISE model results ranged from $97 600 to $118 900. The average cost per QALY gained by additional 9vHPV vaccination exceeded $100 000 in both models. However, the results varied considerably in sensitivity and uncertainty analyses. Additional 9vHPV vaccination is likely not as efficient as many other potential HPV vaccination strategies, such as increasing primary 9vHPV vaccine coverage. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Awareness and Knowledge About HPV and HPV Vaccine Among Romanian Women.

PubMed

Grigore, Mihaela; Teleman, Sergiu Iuliu; Pristavu, Anda; Matei, Mioara

2018-02-01

Cervical cancer is one of the most prevalent gynecological malignancies worldwide. Romania has the highest incidence of this type of cancer in Europe. A successful prevention strategy has to consider the primary prevention measures (including health education on human papilloma virus (HPV) infection but also vaccination). The aim of this study was to assess the knowledge and attitudes of Romanian women about HPV and HPV vaccine. We conducted a cross-sectional study survey of 454 women using an anonymously completed questionnaire covering the awareness and knowledge of HPV infection and attitudes to vaccination. We also analyzed the discussions and conclusion from a focus group of healthcare professionals regarding (1) HPV and HPV awareness and attitude, and (2) suggestions for improving HPV vaccine knowledge and acceptance. 69.2% of women were aware about HPV but their knowledge was minimal and incomplete. While 62.3% had heard about HPV vaccine, only 50.7% had a positive attitude toward it. The main barriers to vaccination were the fear of side effects, the perception that is risky, and the financial concerns. Deficiencies in knowledge were noted for vaccine, genital warts, or risks factors for HPV infection like the early onset of sexual life. The information regarding HPV and vaccine is not always accurate and complete, and only 50.7% of women have a positive attitude toward the vaccine. More educational programs and clearer communication are needed to raise awareness and knowledge regarding HPV and HPV vaccine.

Human papillomavirus-related diseases: oropharynx cancers and potential implications for adolescent HPV vaccination.

PubMed

Gillison, Maura L

2008-10-01

Molecular and epidemiological data now support an etiologic role for oncogenic human papillomavirus (HPV) in oral cancers in women and men. Recent studies have demonstrated an increase in the incidence of HPV-associated oral cancers in the United States. Moreover, the incidence rates for these cancers are higher in men than women. Oral HPV infections acquired through oral sex appear to be the principal risk factor for HPV-associated oral cancers. Despite reports in the popular press that the prevalence of oral sexual behaviors is increasing in the adolescent population, trends in these behaviors over time are largely unavailable. However, data indicate that oral-genital contact is frequently practiced among adolescents; adolescents do not typically consider this a risky behavior. The majority of oral cancers (approximately 90%) caused by HPV are identified as HPV 16 positive. Therefore, HPV-associated oral cancers could be prevented by a prophylactic vaccine if the vaccine were demonstrated to be capable of preventing oral HPV 16 infection. These findings have created new potential opportunities for the primary prevention of oral cancers.

HPV Carcinomas in Immunocompromised Patients

PubMed Central

Reusser, Nicole M.; Downing, Christopher; Guidry, Jacqueline; Tyring, Stephen K.

2015-01-01

Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide and can result in pre-malignancies or overt malignancies of the skin and mucosal surfaces. HPV-related illnesses are an important personal and public health problem causing physical, mental, sexual and financial detriments. Moreover, this set of malignancies severely affects the immunosuppressed population, particularly HIV-positive patients and organ-transplant recipients. There is growing incidence of HPV-associated anogenital malignancies as well as a decrease in the average age of affected patients, likely related to the rising number of high-risk individuals. Squamous cell carcinoma is the most common type of HPV-related malignancy. Current treatment options for HPV infection and subsequent disease manifestations include imiquimod, retinoids, intralesional bleomycin, and cidofovir; however, primary prevention with HPV vaccination remains the most effective strategy. This review will discuss anogenital lesions in immunocompromised patients, cutaneous warts at nongenital sites, the association of HPV with skin cancer in immunocompromised patients, warts and carcinomas in organ-transplant patients, HIV-positive patients with HPV infections, and the management of cutaneous disease in the immunocompromised patient. PMID:26239127

Urine human papillomavirus prevalence in women with high-grade cervical lesions.

PubMed

Nicolau, P; Mancebo, G; Agramunt, S; Solé-Sedeño, J M; Bellosillo, B; Muset, M M; Lloveras, B; Alameda, F; Carreras, R

2014-12-01

To determine the prevalence of human papillomavirus (HPV) in urine samples from women with high-grade cervical lesions. Secondary objectives are to identify the influence of socio-demographic factors and the different genotypes with urinary HPV positivity. 75 women with a positive biopsy for CIN2+ were included in the study from October 2010 to July 2011. A sample of urine was collected immediately before conization at the outpatient clinic. We analyzed the presence of HPV using a PCR technique. The mean age of the patients was 34.8 years (range 24 to 61). All patients had histological CIN2+, of whom 54.67% had CIN3. The prevalence of HPV in urine test was 58.82% in CIN2 population versus 78.05% in CIN3 patients (p 0.072). 31 different genotypes were found. The most frequent HPV genotype was 16-HPV, which was identified in 58% of women with positive HPV-DNA in urine samples. No demographic characteristics were significantly associated to urinary HPV prevalence. Most of the patients with CIN2+ showed positive results for urine HPV test. The prevalence of positive urinary HPV test was higher for patients with CIN3. HPV urine detection could be considered as an acceptable option for high-risk population who skip regular screening programs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The role of high-risk HPV-DNA testing in the male sexual partners of women with HPV-induced lesions.

PubMed

Giraldo, Paulo C; Eleutério, Jose; Cavalcante, Diane Isabelle M; Gonçalves, Ana Katherine S; Romão, Juliana A A; Eleutério, Renata M N

2008-03-01

The objectives were to assess the prevalence of high-risk HPV in the male sexual partners of women with HPV-induced lesions, and correlate it with biopsies guided by peniscopy. Fifty-four asymptomatic male sexual partners of women with low-grade squamous intra-epithelial lesions (LSIL) associated with high-risk HPV were examined between April 2003 and June 2005. The DNA-HPV was tested using a second-generation hybrid capture technique in scraped penile samples. Peniscopy identified acetowhite lesions leading to biopsy. High-risk HPV was present in 25.9% (14 out of 54) of the cases. Peniscopy led to 13 biopsies (24.07%), which resulted in two cases of condyloma, two cases of intra-epithelial neoplasia (PIN) I, one case of PIN II, and eight cases of normal tissue. The high-risk HPV test demonstrated 80% sensitivity, 100% specificity, 100% positive predictive value, and 88.9% negative predictive value for the identification of penile lesions. There was a greater chance of finding HPV lesions in the biopsy in the positive cases of high-risk HPV with abnormal peniscopy (p=0.007); OR=51 (CI 1.7-1527.1). Among asymptomatic male sexual partners of women with low-grade intra-epithelial squamous lesions, those infected by high-risk HPV have a higher chance of having abnormal penile tissue compared with male partners without that infection.

Clinical management of HPV-related disease of the lower genital tract.

PubMed

Kyrgiou, M; Valasoulis, G; Founta, C; Koliopoulos, G; Karakitsos, P; Nasioutziki, M; Navrozoglou, I; Dalkalitsis, N; Paraskevaidis, E

2010-09-01

Cytology remains the mainstay for cervical screening. The need to achieve effective management, limit complications, and preserve reproductive function led to the popularity of local treatment. Although the cure rates for ablative and excisional methods are similar, the excisional method provides a more reliable histopathological diagnosis. Recent evidence revealed increased perinatal morbidity after treatment that appears to be related to the proportion of cervix removed. The human papillomavirus (HPV) DNA test appears to enhance the detection of disease in primary screening, in the triage of minor cytological abnormalities, and in follow-up. Further research on the clinical application of a scoring system is ongoing. The vaccines are now available and appear to be safe, well tolerated, and highly efficacious in HPV naive women. A synergy of vaccination and screening will be required. Treatment for early cervical cancer is increasingly shifting toward more fertility-sparing surgical techniques. Careful selection of patients is essential. © 2010 New York Academy of Sciences.

The low risk of precancer after a screening result of human papillomavirus-negative/atypical squamous cells of undetermined significance papanicolaou and implications for clinical management.

PubMed

Gage, Julia C; Katki, Hormuzd A; Schiffman, Mark; Castle, Philip E; Fetterman, Barbara; Poitras, Nancy E; Lorey, Thomas; Cheung, Li C; Behrens, Catherine; Sharma, Abha; Zhao, Fang-Hui; Cuzick, Jack; Yang, Zi Hua; Kinney, Walter K

2014-11-01

Different US practice guidelines have conflicting recommendations for when women should return after a screening result of human papillomavirus (HPV)-negative with an equivocal Papanicolaou (Pap) result of atypical squamous cells of undetermined significance (ASC-US) (ie, return in either 3 or 5 years). One way to determine management is to compare the risk of precancer/cancer after an HPV-negative/ASC-US result with the risks after other negative screening results. For example, if the risk after an HPV-negative/ASC-US result was similar to the risk after a negative Pap test, a 3-year return would be preferred because guidelines agree that women with negative Pap test results should return in 3 years. Alternatively, if the risk after an HPV-negative/ASC-US result is similar to that after a cotest-negative result (HPV negative/Pap test negative), a 5-year return would be preferred because guidelines agree that women testing cotest negative should return in 5 years. The authors compared risks of cervical intraepithelial neoplasia of grade 3 or higher (CIN3+) and cervical cancer among women aged 30 years to 64 years at Kaiser Permanente Northern California with the following test results from 2003 through 2012: 17,191 women testing HPV negative/ASC-US; 980,268 women testing Pap test negative (regardless of HPV result); and 892,882 women testing cotest negative. The 5-year CIN3+ and cancer risks after an HPV-negative/ASC-US result were closer to the risks after a negative Pap test result (CIN3+: 0.48% vs 0.31% [P =.0019]; and cancer: 0.043% vs 0.031% [P =.4]) than after a negative cotest (CIN3+: 0.48% vs 0.11% [P<.0001]; and cancer: 0.043% vs 0.014% [P =.016]). Women testing HPV negative/ASC-US were found to have precancer/cancer risks that were more closely aligned with women with negative Pap test results, suggesting that women testing HPV negative/ASC-US should be managed similarly to women testing negative on Pap tests with a 3-year return for screening. © 2014 American Cancer Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Sociodemographic characteristics and sexual behavior as risk factors for human papillomavirus infection in Saudi Arabia.

PubMed

Alhamlan, F S; Khayat, H H; Ramisetty-Mikler, S; Al-Muammar, T A; Tulbah, A M; Al-Badawi, I A; Kurdi, W I; Tulbah, M I; Alkhenizan, A A; Hussain, A N; Ahmed, M; Al-Ahdal, M N

2016-05-01

To determine the prevalence and the sociodemographic characteristics and sexual behavior risk factors for human papillomavirus (HPV) infection in a hospital-based cohort of women in Saudi Arabia. Cervical specimens and questionnaire data were collected from women attending clinics in Riyadh, Saudi Arabia. Cervical specimens were examined for abnormal cytology using a standard Pap test and for the presence of HPV-DNA using PCR and reverse line blot hybridization tests. Approximately 73% of the 400 women tested were Saudi nationals. Nearly 50% were under 40 years old (range 22-80 years, mean±standard deviation 41.20±10.43 years). Approximately 17% of the women were HPV-positive. The most commonly detected HPV types were HPV-18 (34%) and HPV-16 (19%), with multiple infections detected in 10% of positive specimens. Multivariate analyses revealed that smoking and multiple partners were significant risk factors for HPV infection (p<0.01). Because of societal challenges and an unsubstantiated assumption of low HPV prevalence, few studies have examined sociodemographic characteristics or sexual behaviors associated with HPV in Saudi women. However, a high prevalence of HPV infection was found, with smoking and multiple partners as significant risk factors, in this hospital-based cohort of predominantly Saudi women. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

High rates of incident and prevalent anal human papillomavirus infection among young men who have sex with men.

PubMed

Glick, Sara Nelson; Feng, Qinghua; Popov, Viorica; Koutsky, Laura A; Golden, Matthew R

2014-02-01

There are few published estimates of anal human papillomavirus (HPV) infection rates among young men who have sex with men (YMSM). We estimated incidence and prevalence of type-specific anal HPV infection using clinician-collected anal swabs for HPV DNA testing obtained during a 1-year prospective study of 94 YMSM (mean age, 21 years) in Seattle. Seventy percent of YMSM had any HPV infection detected during the study, and HPV-16 and/or -18 were detected in 37%. The incidence rate for any new HPV infection was 38.5 per 1000 person-months and 15.3 per 1000 person-months for HPV-16/18; 19% had persistent HPV-16/18 infection. No participant tested positive for all 4 HPV types in the quadrivalent vaccine. The number of lifetime male receptive anal sex partners was significantly associated with HPV infection. The prevalence of HPV-16/18 was 6% among YMSM with a history of 1 receptive anal sex partner and 31% among YMSM with ≥ 2 partners. Although the high prevalence of HPV among YMSM highlights the desirability of vaccinating all boys as a strategy to avert the morbidity of HPV infection, most YMSM appear to remain naive to either HPV-16 or -18 well into their sexual lives and would benefit from HPV immunization.

Human papillomavirus (HPV) information needs: a theoretical framework

PubMed Central

Marlow, Laura A V; Wardle, Jane; Waller, Jo; Grant, Nina

2009-01-01

Background With the introduction of human papillomavirus (HPV) testing and vaccination in the UK, health professionals will start to receive questions about the virus from their patients. This study aimed to identify the key questions about HPV that British women will ask when considering having an HPV test or vaccination. Methods Face-to-face interviews were carried out with 21 women to discover what they wanted to know about HPV. A thematic framework approach was used to analyse the data and identify key themes in women's HPV knowledge requirements. Results Women's questions about HPV fell into six areas: identity (e.g. What are the symptoms?), cause (e.g. How do you get HPV?), timeline (e.g. How long does it last?), consequences (e.g. Does it always cause cervical cancer?) and control-cure (e.g. Can you prevent infection?). In addition, they asked procedural questions about testing and vaccination (e.g. Where do I get an HPV test?). These mapped well onto the dimensions identified in Leventhal's description of lay models of illness, called the 'Common Sense Model' (CSM). Discussion and conclusions These results indicated that the majority of the questions women asked about HPV fitted well into the CSM, which therefore provides a structure for women's information needs. The findings could help health professionals understand what questions they may be expected to answer. Framing educational materials using the CSM themes may also help health educators achieve a good fit with what the public want to know. PMID:19126314

Differential uptake of recent Papanicolaou testing by HPV vaccination status among young women in the United States, 2008-2013.

PubMed

Sauer, Ann Goding; Jemal, Ahmedin; Simard, Edgar P; Fedewa, Stacey A

2015-08-01

A positive association between recent Papanicolaou (Pap) test uptake and initiation of HPV vaccination among U.S. women has been reported. However, it is unknown whether recent Pap testing by HPV vaccination status varies by race/ethnicity. Discerning racial/ethnic variations is important given the higher prevalence of HPV types other than 16 and 18 in some racial/ethnic groups. We assessed whether uptake of recent Pap testing differed among women aged 21-30 years who had not initiated the HPV vaccination series versus those who had and whether this pattern differed by sociodemographic factors. 2008, 2010, and 2013 National Health Interview Survey data were used to generate weighted prevalence estimates and 95% confidence intervals (CIs) (n=7095). Adjusted predicted marginal models were used to generate adjusted prevalence ratios (aPRs) to assess the relationship between recent Pap test uptake and HPV vaccination series initiation by race/ethnicity. The uptake of recent Pap testing among those who had not initiated the HPV vaccination series was significantly lower (81.0%) compared to those who had initiated vaccination (90.5%) (aPR=0.93, 95% CI: 0.90-0.96). This finding was consistent across most sociodemographic factors, though not statistically significant for Blacks, Hispanics, those with lower levels of education, or those with higher levels of income. Young women who had not initiated HPV vaccination were less likely to have had a recent Pap test compared to women who had initiated vaccination. Concerted efforts are needed to increase uptake of recommended cervical cancer screening and HPV vaccination among young women. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparative effectiveness study on human papillomavirus detection methods used in the cervical cancer screening programme

PubMed Central

Nygård, Mari; Røysland, Kjetil; Campbell, Suzanne; Dillner, Joakim

2014-01-01

Objectives To compare the short-term and long-term effectiveness of human papillomavirus (HPV) tests in Norwegian Cervical Cancer Screening Programme (NCCSP). Design Nationwide register-based prospective follow-up study. Setting In 2005, the NCCSP implemented HPV testing in follow-up of unsatisfactory, atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) cytology. Participants 19 065 women with repeat cytology and HPV test after unsatisfactory ASC-US or LSIL screening result in 2005–2009. Interventions Through individual registry linkages we observed how women were treated in the regular medical care. Main outcome measures We estimated cumulative incidence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in 6 months and 3 years after repeat cytology and HPV test. Patients diagnosed with CIN2+ in 6 months and 3 years were assessed for initial HPV positivity. Results 5392 had ASC-US/LSIL and 13 673 had normal/unsatisfactory repeat cytology; for HPV detection 4715 used AMPLICOR HPV Test (Roche Diagnostics, Basel, Switzerland), 9162 Hybrid Capture 2 (HC2) High-Risk HPV DNA Test (QIAGEN, Gaithersburg, Maryland, USA) and 5188 PreTect HPV-Proofer (NorChip, Klokkarstua, Norway). Among those with ASC-US/LSIL repeat cytology, 3-year risk of CIN2+ was 15-fold in Amplicor/HC2-positives compared with Amplicor/HC2-negatives and sevenfold in Proofer-positives compared with Proofer-negatives; a 3-year risk of CIN2+ was 2.1% (95% CI 0.7% to 3.4%) in Amplicor-negatives and 7.2% (95% CI 5.4% to 8.9%) in Proofer-negatives. Close to 100% of patients with CIN2+ diagnosed within 6 months tested positive to HPV (all methods). Considering all patients diagnosed with CIN2+ in 3-year follow-up, 97% were initially positive in the Amplicor group and more than 94% in the HC2 group, compared with less than 80% in the Proofer group. Conclusions While the long-term evaluation of new screening routines showed a good overall performance of triage-HPV DNA testing, the management of HPV-negative women with persistent ASC-US/LSIL was suboptimal. PMID:24401720

HPV E6/E7 mRNA versus HPV DNA biomarker in cervical cancer screening of a group of Macedonian women.

PubMed

Duvlis, Sotirija; Popovska-Jankovic, Katerina; Arsova, Zorica Sarafinovska; Memeti, Shaban; Popeska, Zaneta; Plaseska-Karanfilska, Dijana

2015-09-01

High risk types of human papillomaviruses E6/E7 oncogenes and their association with tumor suppressor genes products are the key factors of cervical carcinogenesis. This study proposed them as specific markers for cervical dysplasia screening. The aim of the study is to compare the clinical and prognostic significance of HPV E6/E7 mRNA as an early biomarker versus HPV DNA detection and cytology in triage of woman for cervical cancer. The study group consists of 413 women: 258 NILM, 26 ASC-US, 81 LSIL, 41 HSIL, and 7 unsatisfactory cytology. HPV4AACE screening, real-time multiplex PCR and MY09/11 consensus PCR primers methods were used for the HPV DNA detection. The real-time multiplex nucleic acid sequence-based assay (NucliSENS EasyQ HPV assay) was used for HPV E6/E7 mRNA detection of the five most common high risk HPV types in cervical cancer (16, 18, 31, 33, and 45). The results show that HPV E6/E7 mRNA testing had a higher specificity 50% (95% CI 32-67) and positive predictive value (PPV) 62% (95% CI 46-76) for CIN2+ compared to HPV DNA testing that had specificity of 18% (95% CI 7-37) and PPV 52% (95% CI 39-76) respectively. The higher specificity and PPV of HPV E6/E7 mRNA testing are valuable in predicting insignificant HPV DNA infection among cases with borderline cytological finding. It can help in avoiding aggressive procedures (biopsies and over-referral of transient HPV infections) as well as lowering patient's anxiety and follow up period. © 2015 Wiley Periodicals, Inc.

Comparison between Urine and Cervical Samples for HPV DNA Detection and Typing in Young Women in Colombia.

PubMed

Cómbita, Alba Lucía; Gheit, Tarik; González, Paula; Puerto, Devi; Murillo, Raúl Hernando; Montoya, Luisa; Vorsters, Alex; Van Keer, Severien; Van Damme, Pierre; Tommasino, Massimo; Hernández-Suárez, Gustavo; Sánchez, Laura; Herrero, Rolando; Wiesner, Carolina

2016-09-01

Urine sampling for HPV DNA detection has been proposed as an effective method for monitoring the impact of HPV vaccination programs; however, conflicting results have been reported. The goal of this study was to evaluate the performance of optimized urine HPV DNA testing in women aged 19 to 25 years. Optimization process included the use of first void urine, immediate mixing of urine with DNA preservative, and the concentration of all HPV DNA, including cell-free DNA fragments. Urine and cervical samples were collected from 535 young women attending cervical screening at health centers from two Colombian cities. HPV DNA detection and genotyping was performed using an HPV type-specific multiplex genotyping assay, which combines multiplex polymerase chain reaction with bead-based Luminex technology. Concordance between HPV DNA detection in urine and cervical samples was determined using kappa statistics and McNemar tests. The accuracy of HPV DNA testing in urine samples was evaluated measuring sensitivity and specificity using as reference the results obtained from cervical samples. Statistical analysis was performed using STATA11.2 software. The findings revealed an overall HPV prevalence of 60.00% in cervical samples and 64.72% in urine samples, HPV-16 being the most frequent HPV type detected in both specimens. Moreover, our results indicate that detection of HPV DNA in first void urine provides similar results to those obtained with cervical samples and can be used to monitor HPV vaccination trials and programs as evidenced by the substantial concordance found for the detection of the four vaccine types. Cancer Prev Res; 9(9); 766-71. ©2016 AACR. ©2016 American Association for Cancer Research.

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.

Cost-effectiveness of human papillomavirus DNA testing in the United Kingdom, The Netherlands, France, and Italy.

PubMed

Kim, Jane J; Wright, Thomas C; Goldie, Sue J

2005-06-15

European countries with established cytology-based screening programs for cervical cancer will soon face decisions about whether to incorporate human papillomavirus (HPV) DNA testing and what strategies will be most cost-effective. We assessed the cost-effectiveness of incorporating HPV DNA testing into existing cervical cancer screening programs in the United Kingdom, The Netherlands, France, and Italy. We created a computer-based model of the natural history of cervical carcinogenesis for each using country-specific data on cervical cancer risk and compared each country's current screening policy with two new strategies: 1) cytology throughout a woman's lifetime, using HPV DNA testing as a triage strategy for equivocal cytology results ("HPV triage"), as well as 2) cytology until age 30 years and HPV DNA testing in combination with cytology in women more than 30 years of age ("combination testing"). Outcomes included reduction in lifetime cervical cancer risk, increase in life expectancy, lifetime costs, and incremental cost-effectiveness ratios, expressed as cost per year of life saved. We explored alternative protocols and conducted sensitivity analysis on key parameters of the model over a relevant range of values to identify the most cost-effective options for each country. Both HPV DNA testing strategies, HPV triage and combination testing, were more effective than each country's status quo screening policy. Incremental cost-effectiveness ratios for HPV triage were less than $13,000 per year of life saved, whereas those for combination testing ranged from $9800 to $75,900 per year of life saved, depending on screening interval. We identified options that would be very cost-effective (i.e., cost-effectiveness ratio less than the gross domestic product per capita) in each of the four countries. HPV DNA testing has the potential to improve health benefits at a reasonable cost compared with current screening policies in four European countries.

Triage of Women with Low-Grade Cervical Lesions - HPV mRNA Testing versus Repeat Cytology

PubMed Central

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

2011-01-01

Background In Norway, women with low-grade squamous intraepithelial lesions (LSIL) are followed up after six months in order to decide whether they should undergo further follow-up or be referred back to the screening interval of three years. A high specificity and positive predictive value (PPV) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures. Materials and Methods At the University Hospital of North Norway, repeat cytology and the HPV mRNA test PreTect HPV-Proofer, detecting E6/E7 mRNA from HPV types 16, 18, 31, 33 and 45, are used in triage of women with ASC-US and LSIL. In this study, women with LSIL cytology in the period 2005–2008 were included (n = 522). Two triage methods were evaluated in two separate groups: repeat cytology only (n = 225) and HPV mRNA testing in addition to repeat cytology (n = 297). Histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) was used as the study endpoint. Results Of 522 women with LSIL, 207 had biopsies and 125 of them had CIN2+. The sensitivity and specificity of repeat cytology (ASC-US or worse) were 85.7% (95% confidence interval (CI): 72.1, 92.2) and 54.4 % (95% CI: 46.9, 61.9), respectively. The sensitivity and specificity of the HPV mRNA test were 94.2% (95% CI: 88.7, 99.7) and 86.0% (95% CI: 81.5, 90.5), respectively. The PPV of repeat cytology was 38.4% (95% CI: 29.9, 46.9) compared to 67.0% (95% CI: 57.7, 76.4) of the HPV mRNA test. Conclusion HPV mRNA testing was more sensitive and specific than repeat cytology in triage of women with LSIL cytology. In addition, the HPV mRNA test showed higher PPV. These data indicate that the HPV mRNA test is a better triage test for women with LSIL than repeat cytology. PMID:21918682

Prevalence and type distribution of human papillomavirus (HPV) in Malaysian women with and without cervical cancer: an updated estimate.

PubMed

Tan, Shing Cheng; Ismail, Mohd Pazudin; Duski, Daniel Roza; Othman, Nor Hayati; Ankathil, Ravindran

2018-04-27

Information on the prevalence and type distribution of human papillomavirus (HPV) among Malaysian women is currently limited. The present study therefore aimed to provide an updated estimate on the prevalence and type distribution of HPV among Malaysian women with and without cervical cancer. Total DNA was isolated from the cervical cell specimens of 185 histopathologically confirmed cervical cancer patients and 209 cancer-free healthy females who were tested negative in a recent Pap test. Viral-specific DNA was subsequently amplified with biotinylated primers and hybridized to HPV type-specific probes via a proprietary "flow-through hybridization" process for determination of HPV genotype. It was demonstrated that 83.2% of the cervical cancer patients and none (0.0%) of the cancer-free females were positive for HPV infection. Among HPV-positive subjects, 14 different viral genotypes were observed, namely HPV16, 18, 31, 33, 35, 45, 52, 53, 58, 66/68, 73, 81, 82, and 84/26. A total of 91.6% of the HPV-positive subjects had single-type HPV infections and the remaining 8.4% were simultaneously infected by two HPV genotypes. The most common HPV infections found were HPV16 (35.7%), HPV18 (26.0%), HPV58 (9.1%), and HPV33 (7.1%) single-type infections, followed by HPV16 + HPV18 co-infections (5.2%). The study has successfully provided an updated estimate on the prevalence and type distribution of HPV among Malaysian women with and without cervical cancer. These findings could contribute valuable information for appraisal of the impact and cost-effectiveness of prophylactic HPV vaccines in the Malaysian population. © 2018 The Author(s).

Has Their Son Been Vaccinated? Beliefs About Other Parents Matter for Human Papillomavirus Vaccine.

PubMed

Schuler, Christine L; Coyne-Beasley, Tamera

2016-07-01

The goal of this study was to determine if parents' beliefs about social norms of human papillomavirus (HPV) vaccination for sons were associated with knowledge of HPV, intention to vaccinate sons, or beliefs about side effects. A cross-sectional, survey-based study of parents with sons was performed in 2010. Fisher's exact tests were used to examine associations between demographics and responses about social norms. Multivariate logistic regression models examined beliefs about social norms of male HPV vaccination and primary outcomes. Few parents agreed that others were vaccinating sons (n = 31/267, 12%), including 1% responding strongly agree and 11% responding agree. Most parents, 52%, disagreed that others were vaccinating (40% disagree, 11% strongly disagree), and 37% chose prefer not to answer regarding others' vaccination practices. Hispanic parents and those with a high school education or less were significantly more likely to choose prefer not to answer than their respective counterparts regarding vaccination norms. In multivariate models, parents agreeing others were vaccinating sons had greater odds of having high knowledge of HPV (adjusted odds ratio [aOR] high vs low knowledge 3.15, 95% confidence interval [CI] 1.13, 8.77) and increased intention to vaccinate sons (n = 243, aOR = 4.41, 95% CI = 1.51, 12.89). Beliefs about side effects were not significantly associated with beliefs about social norms. Parents' beliefs about others' vaccination practices are important with regard to knowledge of HPV and intention to vaccinate sons. Studying how various public messages about HPV vaccine may influence normative beliefs could be relevant to improving vaccination coverage. © The Author(s) 2015.

Completing the cervical screening pathway: Factors that facilitate the increase of self-collection uptake among under-screened and never-screened women, an Australian pilot study.

PubMed

McLachlan, E; Anderson, S; Hawkes, D; Saville, M; Arabena, K

2018-02-01

To examine factors that enhance under-screened and never-screened women's completion of the self-collection alternative pathway of the Renewed National Cervical Screening Program (ncsp) in Victoria, Australia. With the Australian ncsp changing, starting on 1 December 2017, the Medical Services Advisory Committee (msac) recommended implementing human papillomavirus (hpv) testing using a self-collected sample for under-screened and never-screened populations. In response, a multi-agency group implemented an hpv self-collection pilot project to trial self-collection screening pathways for eligible women. Quantitative data were collected on participation rates and compliance rates with follow-up procedures across three primary health care settings. Forty women who self-collected were interviewed in a semi-structured format, and seven agency staff completed in-depth interviews. Qualitative data were used to identify and understand clinical and personal enablers that assisted women to complete self-collection cervical screening pathways successfully. Eighty-five per cent (10 women) of participants who tested positive for hpv successfully received their results and completed follow-up procedures as required. Two remaining participants also received hpv-positive results. However, agencies were unable to engage them in follow-up services and procedures. The overall participation rate in screening (self-collection or Pap test) was 85.7% (84 women), with 79 women self-collecting. Qualitative data indicated that clear explanations on self-collection, development of trusting, empathetic relationships with health professionals, and recognition of participants' past experiences were critical to the successful completion of the self-collection pathway. When asked about possible inhibitors to screening and to following up on results and appointments, women cited poor physical and mental health, as well as financial and other structural barriers. A well-implemented process, led by trusted, knowledgeable, and engaged health care professionals who can provide appropriate support and information, can assist under-screened and never-screened women to complete the hpv self-collection pathway successfully.

Comprehensive T-cell immunophenotyping and next-generation sequencing of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinomas.

PubMed

Poropatich, Kate; Fontanarosa, Joel; Swaminathan, Suchitra; Dittmann, Dave; Chen, Siqi; Samant, Sandeep; Zhang, Bin

2017-11-01

The success of programmed cell death 1 (PD-1) inhibition in achieving a clinical response in a subset of head and neck squamous cell carcinoma (HNSCC) patients emphasizes the need to better understand the immunobiology of HNSCC. Immunophenotyping was performed for 30 HCSCC patients [16 human papillomavirus (HPV)-positive; 14 HPV-negative] on matched tissue from the primary tumour site, locally metastatic cervical lymph nodes (LNs), uninvolved local cervical LNs, and peripheral blood. CD4 + and CD8 + T-cell lymphocytes obtained from tissue were analysed for expression levels of the inhibitory receptors PD-1, TIM-3 and CTLA-4. Next-generation sequencing of the T-cell receptor (TCR) β chain was performed on patients (n = 9) to determine receptor repertoire diversity and for clonality analysis. HPV-negative HNSCC patients, particularly those with stage IV disease, had significantly higher proportions of CD8 + T cells expressing CTLA-4 in tumour tissue (P = 0.0013) and in peripheral blood (P = 0.0344) than HPV-positive patients, as well as higher expression levels of TIM-3 + PD-1 + CD8 + T cells (P = 0.0072) than controls. For all patients, PD-1 expression on CD8 + T cells - particularly in HPV-negative HNSCC cases - strongly correlated (r = 0.63, P = 0.013) with tumour size at the primary site. The top CD8 + TCR clones from tumour tissue significantly overlapped with circulating peripheral blood TCR clones (r = 0.946), and HPV-positive patients had frequently expanded TCR clones that were more hydrophobic - and potentially more immunogenic - than those from HPV-negative patients. Collectively, our findings demonstrate, for the first time, that high-stage HPV-negative HNSCC patients with primary tumours at different sites in the head and neck have elevated peripheral CTLA-4 + CD8 + T-cell levels, that tumour-familiar CD8 + T cells are detectable in peripheral blood from HNSCC patients, and that TCRs from HPV-positive HNSCC patients potentially recognize distinctly immunogenic cognate antigens. However, our findings are preliminary, and need to be further confirmed in a larger patient cohort; also, how these factors affect patient response to immunotherapy needs to be determined. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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

PubMed

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

2007-10-01

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

Outcomes in Women With Cytology Showing Atypical Squamous Cells of Undetermined Significance With vs Without Human Papillomavirus Testing

PubMed Central

Cuzick, Jack; Myers, Orrin; Lee, Ji-Hyun; Shi, Yang; Gage, Julia C.; Hunt, William C.; Robertson, Michael

2017-01-01

Importance Little is known about the long-term yield of high-grade cervical intraepithelial neoplasia (CIN) and the influence on biopsy and treatment rates of human papillomavirus (HPV) triage of cytology showing atypical squamous cells of undetermined significance (hereafter ASC-US cytology). Objective To examine 5-year outcomes after ASC-US cytology with vs without HPV testing. Design, Setting, and Participants In this observational study, all cervical cytology and HPV testing reports from January 1, 2007, to December 31, 2012, were obtained for women throughout New Mexico and linked to pathology reports. The dates of the analysis were May 4, 2015, to January 13, 2017. Main Outcomes and Measures Influence of HPV testing on disease yield, time to histologically confirmed disease, and biopsy or loop electrosurgical excision procedure rates. Results A total of 457 317 women (mean [SD] age, 39.8 [12.5] years) with a screening test were recorded between 2008 and 2012, and 20 677 (4.5%) of the first cytology results per woman were reported as ASC-US. CIN grade 3 or more severe (CIN3+) lesions were detected in 2.49% of women with HPV testing vs 2.15% of women without HPV testing (P = .23). Time to CIN3+ detection was much shorter in those with HPV testing vs those without testing (median, 103 vs 393 days; P < .001). CIN grade 1 was detected in 11.6% of women with HPV testing vs 6.6% without testing (relative risk, 1.76; 95% CI, 1.56-2.00; P < .001). Loop electrosurgical excision procedure rates within 5 years were 20.0% higher in those who underwent HPV testing, resulting in more CIN2+ and CIN3+ detection. Conclusions and Relevance Human papillomavirus testing led to faster and more complete diagnosis of cervical disease, but 55.8% more biopsies and 20.0% more loop electrosurgical excision procedures were performed. In those tested, virtually all high-grade disease occurred in the 43.1% of women who were HPV positive, allowing clinical resources to be focused on women who need them most. These data provide essential information for cervical screening guidelines and public health policy. PMID:28655061

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion: review of ancillary testing modalities and implications for follow-up.

PubMed

Davey, Diane Davis; Greenspan, David L; Kurtycz, Daniel F I; Husain, Mujtaba; Austin, R Marshall

2010-07-01

To review the cytology category atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), with human papillomavirus (HPV) and other ancillary testing results and according to age group. A literature search was performed on the ASC-H category, and studies analyzing ASC-H according to ancillary testing modalities or patient age groups during the past 4 years were emphasized. The ASC-H category accounts for less than 1% of cytology reports, and 33% to 84% will test positive for oncogenic HPV. The number of patients with cervical intraepithelial neoplasia 2/3 and cancer on biopsy is quite variable, from about 12% to more than 70%, averaging about 40%. The variation reflects patient population as well as local laboratory practices, but older subgroups are more likely to have negative HPV results and negative follow-up. Both the sensitivity of HPV testing for cervical intraepithelial neoplasia 2/3 detection and the negative predictive value for a patient with ASC-H and negative HPV testing average more than 95%. Additional studies evaluating other types of ancillary testing for the ASC-H category are needed. Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion, is an uncommon cytology result, and HPV testing results and biopsy follow-up show variation according to patient age group and local laboratory practices. A negative HPV result in ASC-H offers a high negative predictive value and could be considered as a management strategy in mature women as well as women 30 years and older receiving combined cytology and HPV screening.

Primary cutaneous adenosquamous carcinoma of the penis: the first characterization of HPV status in this rare and diagnostically challenging entity with review of glandular carcinomas of the penis.

PubMed

Rush, P S; Shiau, J M; Hibler, B P; Longley, B J; Downs, T M; Bennett, D D

2016-12-01

Glandular and pseudoglandular tumors of the penile skin are extremely uncommon and can present diagnostic challenges. Primary adenosquamous carcinoma of the penis is an extremely rare tumor, composed of distinct areas of malignant squamous and glandular cells, making it a diagnostically challenging entity. The World Health Organization (WHO) recognizes several subtypes of squamous cell carcinoma (SCC), each with its own distinctive pathologic appearance, clinical associations and prognosis. Among these variants is the exceedingly uncommon adenosquamous carcinoma (ASC), representing 1%-2% of all SCC of the penis. Recent large studies have interrogated the presence of human papillomavirus (HPV) in malignant penile tumors and have shown specific morphologic patterns and clinical presentations to associate with HPV status. However, given the rarity of the adenosquamous variant of SCC, it has largely been excluded from these studies. The glandular components of these lesions can present a confusing appearance, particularly when a large tumor is represented on a small biopsy. Here we describe a difficult histologic presentation of this rare tumor, with the first published characterization of the HPV status of this subtype. This case represents a distinctly unusual case of metastatic HPV-positive primary cutaneous adenosquamous carcinoma of the penis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

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

2016-01-01

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

Assessing the performance of a Loop Mediated Isothermal Amplification (LAMP) assay for the detection and subtyping of high-risk suptypes of Human Papilloma Virus (HPV) for Oropharyngeal Squamous Cell Carcinoma (OPSCC) without DNA purification.

PubMed

Rohatensky, Mitchell G; Livingstone, Devon M; Mintchev, Paul; Barnes, Heather K; Nakoneshny, Steven C; Demetrick, Douglas J; Dort, Joseph C; van Marle, Guido

2018-02-08

Oropharyngeal Squamous Cell Carcinoma (OPSCC) is increasing in incidence despite a decline in traditional risk factors. Human Papilloma Virus (HPV), specifically subtypes 16, 18, 31 and 35, has been implicated as the high-risk etiologic agent. HPV positive cancers have a significantly better prognosis than HPV negative cancers of comparable stage, and may benefit from different treatment regimens. Currently, HPV related carcinogenesis is established indirectly through Immunohistochemistry (IHC) staining for p16, a tumour suppressor gene, or polymerase chain reaction (PCR) that directly tests for HPV DNA in biopsied tissue. Loop mediated isothermal amplification (LAMP) is more accurate than IHC, more rapid than PCR and is significantly less costly. In previous work we showed that a subtype specific HPV LAMP assay performed similar to PCR on purified DNA. In this study we examined the performance of this LAMP assay without DNA purification. We used LAMP assays using established primers for HPV 16 and 18, and new primers for HPV 31 and 35. LAMP reaction conditions were tested on serial dilutions of plasmid HPV DNA to confirm minimum viral copy number detection thresholds. LAMP was then performed directly on different human cell line samples without DNA purification. Our LAMP assays could detect 10 5 , 10 3 , 10 4 , and 10 5 copies of plasmid DNA for HPV 16, 18, 31, and 35, respectively. All primer sets were subtype specific, with no cross-amplification. Our LAMP assays also reliably amplified subtype specific HPV DNA from samples without requiring DNA isolation and purification. The high risk OPSCC HPV subtype specific LAMP primer sets demonstrated, excellent clinically relevant, minimum copy number detection thresholds with an easy readout system. Amplification directly from samples without purification illustrated the robust nature of the assay, and the primers used. This lends further support HPV type specific LAMP assays, and these specific primer sets and assays can be further developed to test for HPV in OPSCC in resource and lab limited settings, or even bedside testing.

Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women.

PubMed

Paavonen, J; Naud, P; Salmerón, J; Wheeler, C M; Chow, S-N; Apter, D; Kitchener, H; Castellsague, X; Teixeira, J C; Skinner, S R; Hedrick, J; Jaisamrarn, U; Limson, G; Garland, S; Szarewski, A; Romanowski, B; Aoki, F Y; Schwarz, T F; Poppe, W A J; Bosch, F X; Jenkins, D; Hardt, K; Zahaf, T; Descamps, D; Struyf, F; Lehtinen, M; Dubin, G

2009-07-25

The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections, and associated precancerous lesions in an event-triggered interim analysis of the phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in the final event-driven analysis. Women (15-25 years) were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC, included all women receiving at least one vaccine dose, regardless of their baseline HPV status; represents the general population, including those who are sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut; vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and DNA negative at baseline and month 6 for the corresponding type (ATP-E). This trial is registered with ClinicalTrials.gov, number NCT00122681. Mean follow-up was 34.9 months (SD 6.4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92.9% (96.1% CI 79.9-98.3) in the primary analysis and 98.1% (88.4-100) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types (ATP-E cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was 30.4% (16.4-42.1) in the TVC and 70.2% (54.7-80.9) in the TVC-naive. Corresponding values against CIN3+ were 33.4% (9.1-51.5) in the TVC and 87.0% (54.9-97.7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54.0% (34.0-68.4; ATP-E). Individual cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in the TVC. The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes. GlaxoSmithKline Biologicals.

An evaluation of clinical performance of FTA cards for HPV 16/18 detection using cobas 4800 HPV Test compared to dry swab and liquid medium.

PubMed

Dong, Li; Lin, Chunqing; Li, Li; Wang, Margaret; Cui, Jianfeng; Feng, Ruimei; Liu, Bin; Wu, Zeni; Lian, Jia; Liao, Guangdong; Chen, Wen; Qiao, Youlin

2017-09-01

Effective dry storage and transport media as an alternative to conventional liquid-based medium would facilitate the accessibility of women in the low-resource settings to human papillomavirus (HPV)- based cervical cancer screening. To evaluate analytical and clinical performance of indicating FTA™ Elute Cartridge (FTA card) for the detection of HPV16/18 and cervical precancerous lesions and cancer compared to dry swab and liquid medium. Ninety patients with abnormal cytology and/or HPV infection were included for analysis. Three specimens of cervical exfoliated cells from each woman were randomly collected by FTA card, dry swab or liquid-based medium prior to colposcopy examination. The subsequent HPV DNA tests were performed on cobas 4800 HPV platform. High-risk HPV (hrHPV) positivity rate was 63.3%, 62.2% and 65.6% for samples collected by FTA card, dry swab and liquid medium, respectively. The overall agreements and kappa values for the detection of hrHPV, HPV 16 and HPV 18 between FTA card and liquid-based medium were 88.9% (κ=0.76), 97.8% (κ=0.94) and 100% (κ=1.0),respectively; between FTA card and dry swab were 92.1% (κ=0.83), 94.5% (κ=0.87) and 100% (κ=1.0), respectively. The performances of hrHPV tested by FTA card, dry swab, and liquid-based medium for detecting CIN2+ were comparable in terms of the sensitivity and specificity. The specificity of detection of CIN2+ by HPV16/18 increased by approximately 40% compared to hrHPV for any medium albeit at cost of a moderate loss of sensitivity. Dry medium might offer an alternative to conventional liquid-based medium in the HPV-based cervical cancer screening program especially in low-resource settings but still needs further evaluation. Copyright © 2017. Published by Elsevier B.V.

HPV genotypes in high grade cervical lesions and invasive cervical carcinoma as detected by two commercial DNA assays, North Carolina, 2001-2006.

PubMed

Hariri, Susan; Steinau, Martin; Rinas, Allen; Gargano, Julia W; Ludema, Christina; Unger, Elizabeth R; Carter, Alicia L; Grant, Kathy L; Bamberg, Melanie; McDermott, James E; Markowitz, Lauri E; Brewer, Noel T; Smith, Jennifer S

2012-01-01

HPV typing using formalin fixed paraffin embedded (FFPE) cervical tissue is used to evaluate HPV vaccine impact, but DNA yield and quality in FFPE specimens can negatively affect test results. This study aimed to evaluate 2 commercial assays for HPV detection and typing using FFPE cervical specimens. Four large North Carolina pathology laboratories provided FFPE specimens from 299 women ages18 and older diagnosed with cervical disease from 2001 to 2006. For each woman, one diagnostic block was selected and unstained serial sections were prepared for DNA typing. Extracts from samples with residual lesion were used to detect and type HPV using parallel and serial testing algorithms with the Linear Array and LiPA HPV genotyping assays. LA and LiPA concordance was 0.61 for detecting any high-risk (HR) and 0.20 for detecting any low-risk (LR) types, with significant differences in marginal proportions for HPV16, 51, 52, and any HR types. Discordant results were most often LiPA-positive, LA-negative. The parallel algorithm yielded the highest prevalence of any HPV type (95.7%). HR type prevalence was similar using parallel (93.1%) and serial (92.1%) approaches. HPV16, 33, and 52 prevalence was slightly lower using the serial algorithm, but the median number of HR types per woman (1) did not differ by algorithm. Using the serial algorithm, HPV DNA was detected in >85% of invasive and >95% of pre-invasive lesions. The most common type was HPV16, followed by 52, 18, 31, 33, and 35; HPV16/18 was detected in 56.5% of specimens. Multiple HPV types were more common in lower grade lesions. We developed an efficient algorithm for testing and reporting results of two commercial assays for HPV detection and typing in FFPE specimens, and describe HPV type distribution in pre-invasive and invasive cervical lesions in a state-based sample prior to HPV vaccine introduction.

[Prevalence of human papilloma virus isolated from cervix lesions in a female population from Transilvania].

PubMed

Feticu, Lucia; Bocşan, I S; Bondor, Cosmina loana; Boboş, Cecilia

2012-01-01

Between the years 2008-2011 reverse hibridisation (INNO-LiPA HPV Genotyping Extra test) and genotyping 1a Roche (the kit: Linear array HPV genotyping test) were used for detection of Human Papilloma Virus (HPV) in the cervix secretions of 182 female patients aged 16-63 years, predominantly of urban origin. 99 patients (54.4%) were identified as being infected with various types of HPV, prevalent in urban (53 single infections and 46 multiple infections). HPV infection was not detected in 83 (45.6%) patients. Only 7 females from rural areas were tested (5 females had single or multiple HPV infections). 32 types of HPV were identificated: 15 HPV types with high risk (51, 82, 56, 18, 39, 45, 59, 68, 16, 31, 33, 35, 52, 58, 73), 14 types with low risk (42, 61, 62, 72, 81, 83, 84, CP6108, 70, 6, 11, 55, 74, 54), and 3 types with possible high risk (26, 53, 66). The type of HPV could not be identified in other two cases. The most frecvent types of HPV with high risk isolated were: the type 16. The types 51 and 58 of HPV with high risk and the type 84 with low risk are detected in single infections in urban and in rural. HPV clades involved in single infections are: 1 (1 case), 3 (5 cases), 5 (4 cases), 6 (5 cases), 7 (5 cases), 9 (21 cases), 10 (7 cases). The clades 11 (7 cases) and 13 (6 cases) were involved only in multiple infections detected in urban. The types 35, 39, 59, 68 of HPV with high risk were isolated from multple infections. In rural, multiple infections with two HPV were detected. The citological screening by Babe-Papanicolaou examination was made only in 9 cases: HPV was not detected in 4 cases (one female had ASC-US: atypical squamous cells of "undetermined significance"); in 5 positive cases were detected HPV 16, 31, 58, 6.

Six years genotype distribution of Human Papillomavirus in Calabria Region, Southern Italy: a retrospective study.

PubMed

Galati, Luisa; Peronace, Cinzia; Fiorillo, Maria Teresa; Masciari, Rosanna; Giraldi, Cristina; Nisticò, Salvatore; Minchella, Pasquale; Maiolo, Vincenzo; Barreca, Giorgio Settimo; Marascio, Nadia; Lamberti, Angelo Giuseppe; Giancotti, Aida; Lepore, Maria Gabriella; Greco, Francesca; Mauro, Maria Vittoria; Borelli, Annelisa; Bocchiaro, Giuseppa Lo; Surace, Giovanni; Liberto, Maria Carla; Focà, Alfredo

2017-01-01

Although analysis of the Human papillomavirus (HPV) genotype spread in a particular area has a crucial impact on public health and prevention programmes, there is a lack of epidemiological data regarding HPV in the Calabria region of Italy. We therefore update information on HPV age/genotype distribution by retrospectively analysing a cohort of women, with and without cervical lesions, living in Calabria, who underwent HPV DNA testing; moreover, we also evaluated HPV age/genotype distribution in a subset of patients with cervical lesions. Cervical scrape specimens obtained from 9590 women (age range 20-75 years) from January 2010 to December 2015 were tested for HPV DNA. Viral types were genotyped by Linear Array HPV Genotyping® test (Roche, USA) at the Clinical Microbiology Operative Unit of six hospitals located in four provinces of the Calabria region. Cervical scrape specimens were also used to perform Pap smears for cytological analysis in a subset of 405 women; cytological classification of the samples was performed according to the Bethesda classification system. A total of 2974 women (31%) (C.I. 95% 30.09-31.94) were found to be HPV DNA positive for at least one (57.3%) or several (42.7%) HPV genotypes. Of single genotype HPV infections, 46.5% and 36.4 % were classed as high-risk (HR, Group 1) and low-risk (LR, Group 3) respectively, while 16.9% were classed as probably/possibly carcinogenic and 0.2% undetermined risk. Stratified by age, total HPV distribution, showed the highest prevalence within the range 30-39 years (37.2%), while single genotype infection distribution displayed a peak in women from the age range 20-29 years (37.5%). The most common high-risk HPV type was HPV 16 (19.1%), followed by HPV 31 (9.1%). We provide epidemiological data on HPV age/genotype distribution in women living in the Calabria region with or without cytological abnormalities, further to the enhancement of HPV screening/prevention programmes for the local population.

HPV prevalence at enrollment and baseline results from the Carolina Women’s Care Study, a longitudinal study of HPV persistence in women of college age

PubMed Central

Banister, Carolyn E; Messersmith, Amy R; Chakraborty, Hrishikesh; Wang, Yinding; Spiryda, Lisa B; Glover, Saundra H; Pirisi, Lucia; Creek, Kim E

2013-01-01

Background Cervical cancer, a rare outcome of high-risk human papillomavirus (HPV) infection, disproportionately affects African American women, who are about twice more likely than European American women to die of the disease. Most cervical HPV infections clear in about one year. However, in some women HPV persists, posing a greater risk for cervical dysplasia and cancer. The Carolina Women’s Care Study (CWCS) was conducted to explore the biological, genetic, and lifestyle determinants of persistent HPV infection in college-aged European American and African American women. This paper presents the initial results of the CWCS, based upon data obtained at enrollment. Methods Freshman female students attending the University of South Carolina were enrolled in the CWCS and followed until graduation with biannual visits, including two Papanicolaou tests, cervical mucus collection, and a questionnaire assessing lifestyle factors. We recruited 467 women, 293 of whom completed four or more visits for a total of 2274 visits. Results and conclusion CWCS participants were 70% European American, 24% African American, 3% Latina/Hispanic, and 3% Asian. At enrollment, 32% tested positive for any HPV. HPV16 infection was the most common (18% of infections). Together, HPV16, 66, 51, 52, and 18 accounted for 58% of all HPV infections. Sixty-four percent of all HPV-positive samples contained more than one HPV type, with an average of 2.2 HPV types per HPV-positive participant. We found differences between African American and European American women in the prevalence of HPV infection (38.1% African American, 30.7% European American) and abnormal Papanicolaou test results (9.8% African-American, 5.8% European American). While these differences did not reach statistical significance at enrollment, as the longitudinal data of this cohort are analyzed, the sample size will allow us to confirm these results and compare the natural history of HPV infection in college-aged African American and European American women. PMID:23861602

Human Papillomavirus Genotyping Using an Automated Film-Based Chip Array

PubMed Central

Erali, Maria; Pattison, David C.; Wittwer, Carl T.; Petti, Cathy A.

2009-01-01

The INFINITI HPV-QUAD assay is a commercially available genotyping platform for human papillomavirus (HPV) that uses multiplex PCR, followed by automated processing for primer extension, hybridization, and detection. The analytical performance of the HPV-QUAD assay was evaluated using liquid cervical cytology specimens, and the results were compared with those results obtained using the digene High-Risk HPV hc2 Test (HC2). The specimen types included Surepath and PreservCyt transport media, as well as residual SurePath and HC2 transport media from the HC2 assay. The overall concordance of positive and negative results following the resolution of indeterminate and intermediate results was 83% among the 197 specimens tested. HC2 positive (+) and HPV-QUAD negative (−) results were noted in 24 specimens that were shown by real-time PCR and sequence analysis to contain no HPV, HPV types that were cross-reactive in the HC2 assay, or low virus levels. Conversely, HC2 (−) and HPV-QUAD (+) results were noted in four specimens and were subsequently attributed to cross-contamination. The most common HPV types to be identified in this study were HPV16, HPV18, HPV52/58, and HPV39/56. We show that the HPV-QUAD assay is a user friendly, automated system for the identification of distinct HPV genotypes. Based on its analytical performance, future studies with this platform are warranted to assess its clinical utility for HPV detection and genotyping. PMID:19644025

Human papillomavirus genotyping using an automated film-based chip array.

PubMed

Erali, Maria; Pattison, David C; Wittwer, Carl T; Petti, Cathy A

2009-09-01

The INFINITI HPV-QUAD assay is a commercially available genotyping platform for human papillomavirus (HPV) that uses multiplex PCR, followed by automated processing for primer extension, hybridization, and detection. The analytical performance of the HPV-QUAD assay was evaluated using liquid cervical cytology specimens, and the results were compared with those results obtained using the digene High-Risk HPV hc2 Test (HC2). The specimen types included Surepath and PreservCyt transport media, as well as residual SurePath and HC2 transport media from the HC2 assay. The overall concordance of positive and negative results following the resolution of indeterminate and intermediate results was 83% among the 197 specimens tested. HC2 positive (+) and HPV-QUAD negative (-) results were noted in 24 specimens that were shown by real-time PCR and sequence analysis to contain no HPV, HPV types that were cross-reactive in the HC2 assay, or low virus levels. Conversely, HC2 (-) and HPV-QUAD (+) results were noted in four specimens and were subsequently attributed to cross-contamination. The most common HPV types to be identified in this study were HPV16, HPV18, HPV52/58, and HPV39/56. We show that the HPV-QUAD assay is a user friendly, automated system for the identification of distinct HPV genotypes. Based on its analytical performance, future studies with this platform are warranted to assess its clinical utility for HPV detection and genotyping.

Understanding Cervical Changes: A Health Guide for Women

Cancer.gov

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

Human papillomavirus E6 protein enriches the CD55(+) population in cervical cancer cells, promoting radioresistance and cancer aggressiveness.

PubMed

Leung, Thomas Ho-Yin; Tang, Hermit Wai-Man; Siu, Michelle Kwan-Yee; Chan, David Wai; Chan, Karen Kar-Loen; Cheung, Annie Nga-Yin; Ngan, Hextan Yuen-Sheung

2018-02-01

Accumulating evidence indicates that the human papillomavirus (HPV) E6 protein plays a crucial role in the development of cervical cancer. Subpopulations of cells that reside within tumours are responsible for tumour resistance to cancer therapy and recurrence. However, the identity of such cells residing in cervical cancer and their relationship with the HPV-E6 protein have not been identified. Here, we isolated sphere-forming cells, which showed self-renewal ability, from primary cervical tumours. Gene expression profiling revealed that cluster of differentiation (CD) 55 was upregulated in primary cervical cancer sphere cells. Flow-cytometric analysis detected abundant CD55(+) populations among a panel of HPV-positive cervical cancer cell lines, whereas few CD55(+) cells were found in HPV-negative cervical cancer and normal cervical epithelial cell lines. The CD55(+) subpopulation isolated from the C33A cell line showed significant sphere-forming ability and enhanced tumourigenicity, cell migration, and radioresistance. In contrast, the suppression of CD55 in HPV-positive CaSki cells inhibited tumourigenicity both in vitro and in vivo, and sensitized cells to radiation treatment. In addition, ectopic expression of the HPV-E6 protein in HPV-negative cervical cancer cells dramatically enriched the CD55(+) subpopulation. CRISPR/Cas9 knockout of CD55 in an HPV-E6-overexpressing stable clone abolished the tumourigenic effects of the HPV-E6 protein. Taken together, our data suggest that HPV-E6 protein expression enriches the CD55(+) population, which contributes to tumourigenicity and radioresistance in cervical cancer cells. Targeting CD55 via CRISPR/Cas9 may represent a novel avenue for developing new strategies and effective therapies for the treatment of cervical cancer. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Knowledge on HPV Vaccine and Cervical Cancer Facilitates Vaccine Acceptability among School Teachers in Kitui County, Kenya

PubMed Central

Masika, Moses Muia; Ogembo, Javier Gordon; Chabeda, Sophie Vusha; Wamai, Richard G.; Mugo, Nelly

2015-01-01

Background Vaccines against human papillomavirus (HPV) infection have the potential to reduce the burden of cervical cancer. School-based delivery of HPV vaccines is cost-effective and successful uptake depends on school teachers’ knowledge and acceptability of the vaccine. The aim of this study is to assess primary school teachers’ knowledge and acceptability of HPV vaccine and to explore facilitators and barriers of an ongoing Gavi Alliance-supported vaccination program in Kitui County, Kenya. Methods This was a cross-sectional, mixed methods study in Central Division of Kitui County where the Ministry of Health is offering the quadrivalent HPV vaccine to grade four girls. Data on primary school teachers’ awareness, knowledge and acceptability of HPV vaccine as well as facilitators and barriers to the project was collected through self-administered questionnaires and two focus group discussions. Results 339 teachers (60% female) completed the survey (62% response rate) and 13 participated in 2 focus group discussions. Vaccine awareness among teachers was high (90%), the level of knowledge about HPV and cervical cancer among teachers was moderate (48%, SD = 10.9) and females scored higher than males (50% vs. 46%, p = 0.002). Most teachers (89%) would recommend the vaccine to their daughter or close relatives. Those who would recommend the vaccine had more knowledge than those who would not (p = <0.001). The main barriers were insufficient information about the vaccine, poor accessibility of schools, absenteeism of girls on vaccine days, and fear of side effects. Conclusions Despite low to moderate levels of knowledge about HPV vaccine among school teachers, vaccine acceptability is high. Teachers with little knowledge on HPV vaccine are less likely to accept the vaccine than those who know more; this may affect uptake if not addressed. Empowering teachers to be vaccine champions in their community may be a feasible way of disseminating information about HPV vaccine and cervical cancer. PMID:26266949

Knowledge on HPV Vaccine and Cervical Cancer Facilitates Vaccine Acceptability among School Teachers in Kitui County, Kenya.

PubMed

Masika, Moses Muia; Ogembo, Javier Gordon; Chabeda, Sophie Vusha; Wamai, Richard G; Mugo, Nelly

2015-01-01

Vaccines against human papillomavirus (HPV) infection have the potential to reduce the burden of cervical cancer. School-based delivery of HPV vaccines is cost-effective and successful uptake depends on school teachers' knowledge and acceptability of the vaccine. The aim of this study is to assess primary school teachers' knowledge and acceptability of HPV vaccine and to explore facilitators and barriers of an ongoing Gavi Alliance-supported vaccination program in Kitui County, Kenya. This was a cross-sectional, mixed methods study in Central Division of Kitui County where the Ministry of Health is offering the quadrivalent HPV vaccine to grade four girls. Data on primary school teachers' awareness, knowledge and acceptability of HPV vaccine as well as facilitators and barriers to the project was collected through self-administered questionnaires and two focus group discussions. 339 teachers (60% female) completed the survey (62% response rate) and 13 participated in 2 focus group discussions. Vaccine awareness among teachers was high (90%), the level of knowledge about HPV and cervical cancer among teachers was moderate (48%, SD = 10.9) and females scored higher than males (50% vs. 46%, p = 0.002). Most teachers (89%) would recommend the vaccine to their daughter or close relatives. Those who would recommend the vaccine had more knowledge than those who would not (p = <0.001). The main barriers were insufficient information about the vaccine, poor accessibility of schools, absenteeism of girls on vaccine days, and fear of side effects. Despite low to moderate levels of knowledge about HPV vaccine among school teachers, vaccine acceptability is high. Teachers with little knowledge on HPV vaccine are less likely to accept the vaccine than those who know more; this may affect uptake if not addressed. Empowering teachers to be vaccine champions in their community may be a feasible way of disseminating information about HPV vaccine and cervical cancer.

Improved survival with HPV among African Americans with oropharyngeal cancer.

PubMed

Worsham, Maria J; Stephen, Josena K; Chen, Kang Mei; Mahan, Meredith; Schweitzer, Vanessa; Havard, Shaleta; Divine, George

2013-05-01

A major limitation of studies reporting a lower prevalence rate of human papilloma virus (HPV) in African American patients with oropharyngeal squamous cell cancer (OPSCC) than Caucasian Americans, with corresponding worse outcomes, was adequate representation of HPV-positive African American patients. This study examined survival outcomes in HPV-positive and HPV-negative African Americans with OPSCC. The study cohort of 121 patients with primary OPSCC had 42% African Americans. Variables of interest included age, race, gender, HPV status, stage, marital status, smoking, treatment, and date of diagnosis. Caucasian Americans are more likely to be HPV positive (OR = 3.28; P = 0.035), as are younger age (age < 50 OR = 7.14; P = 0.023 compared with age > 65) or being married (OR = 3.44; P = 0.016). HPV positivity and being unmarried were associated with being late stage (OR = 3.10; P = 0.047 and OR = 3.23; P = 0.038, respectively). HPV-negative patients had 2.7 times the risk of death as HPV-positive patients (P = 0.004). Overall, the HPV-race groups differed (log-rank P < 0.001), with significantly worse survival for HPV-negative African Americans versus (i) HPV-positive African Americans (HR = 3.44; P = 0.0012); (ii) HPV-positive Caucasian Americans (HR = 3.11; P = < 0.049); and (iii) HPV-negative Caucasian Americans (HR = 2.21; P = 0.049). HPV has a substantial impact on overall survival in African American patients with OPSCC. Among African American patients with OPSCC, HPV-positive patients had better survival than HPV negative. HPV-negative African Americans also did worse than both HPV-positive Caucasian Americans and HPV-negative Caucasian Americans. This study adds to the mounting evidence of HPV as a racially linked sexual behavior life style risk factor impacting survival outcomes for both African American and Caucasian American patients with OPSCC. ©2013 AACR.

Health and economic impact of HPV 16/18 vaccination and cervical cancer screening in Eastern Africa.

PubMed

Campos, Nicole G; Kim, Jane J; Castle, Philip E; Ortendahl, Jesse D; O'Shea, Meredith; Diaz, Mireia; Goldie, Sue J

2012-06-01

Eastern Africa has the world's highest cervical cancer incidence and mortality rates. We used epidemiologic data from Kenya, Mozambique, Tanzania, Uganda, and Zimbabwe to develop models of HPV-related infection and disease. For each country, we assessed HPV vaccination of girls before age 12 followed by screening with HPV DNA testing once, twice, or three times per lifetime (at ages 35, 40, 45). For women over age 30, we assessed only screening (with HPV DNA testing up to three times per lifetime or VIA at age 35). Assuming no waning immunity, mean reduction in lifetime cancer risk associated with vaccination ranged from 36 to 45%, and vaccination followed by screening once per lifetime at age 35 with HPV DNA testing ranged from 43 to 51%. For both younger and older women, the most effective screening strategy was HPV DNA testing three times per lifetime. Provided the cost per vaccinated girl was less than I$10 (I$2 per dose), vaccination had an incremental cost-effectiveness ratio [I$ (international dollars)/year of life saved (YLS)] less than the country-specific per capita GDP, a commonly cited heuristic for "very cost-effective" interventions. If the cost per vaccinated girl was between I$10 (I$2 per dose) and I$25 (I$5 per dose), vaccination followed by HPV DNA testing would save the most lives and would be considered good value for public health dollars. These results should be used to catalyze design and evaluation of HPV vaccine delivery and screening programs, and contribute to a dialogue on financing HPV vaccination in poor countries. Copyright © 2011 UICC.

Identification of human papillomavirus (HPV) subtype in oral cancer patients through microarray technology.

PubMed

Kim, Soung Min; Kwon, Ik Jae; Myoung, Hoon; Lee, Jong Ho; Lee, Suk Keun

2018-02-01

Human papilloma virus (HPV) is the main source of cervical cancer. Many recent studies have revealed the prevalence and prognosis of HPV associated with oropharyngeal squamous cell carcinoma, but fewer reports have evaluated HPV in oral squamous cell carcinoma (OSCC). The purpose of this study was to determine the prevalence and prognosis of HPV associated with OSCC according to HPV and tumor types. We used a DNA chip kit (MY-HPV chip kit ® , Mygene Co., Korea) to detect high-risk HPV subtypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 54, 56, 58) and low-risk subtypes (6, 11, 34, 40, 42, 43, 44) among 187 patients. The prevalence was determined by Chi-square and Fisher's exact tests, and the prognosis was calculated by the Kaplan-Meier method and the log-rank test. The overall prevalence of HPV in OSCC was 7.0% for all HPV positives and 4.3% for high-risk HPV positives. The prevalence of HPV was significantly higher in individuals under 65 years old and in those with tumors in the tongue and gum regions. The prognosis did not differ between the HPV-positive and -negative groups. Although the prevalence of HPV-positive cases in OSCC was low (7.0, 4.3%) and the prognosis did not depend on HPV positivity, HPV-associated OSCC should be considered in the evaluation and treatment of oral cancer patients. In addition, separating high- and low-risk groups based on the HPV status of other body parts might not be appropriate. The DNA microarray method can accurately detect known HPV subtypes simultaneously, but has limitations in detecting new subtypes. Vaccines can also be used to prevent HPV-associated OSCC in patients, so further studies on the prognosis and efficacy of vaccines should be undertaken.

A systematic review of the prevalence and attribution of human papillomavirus types among cervical, vaginal, and vulvar precancers and cancers in the United States.

PubMed

Insinga, Ralph P; Liaw, Kai-Li; Johnson, Lisa G; Madeleine, Margaret M

2008-07-01

To describe prevalence and estimated attribution of human papillomavirus (HPV) types in U.S. cervical, vaginal, and vulvar precancers and cancers. U.S. studies reporting HPV typing for cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), and vaginal intraepithelial neoplasia (VaIN) and/or invasive cancers of those sites were gathered from the PubMed database (http://www.ncbi.nlm.nih.gov/sites/entrez/). Selected studies had PCR testing data for > or =10 cases for a disease endpoint. Analytic methods augmented prior reviews of cervical disease with an updated and expanded analysis (including vulvar and vaginal disease), new selection criteria for specimens, and adjustment for histologic type, where possible, among pooled cancer cases. In addition, for analyses of estimated attribution of HPV types, we incorporated accounting methods for lesions infected with multiple HPV types. Data from 22 U.S. studies meeting review eligibility criteria were tabulated. Following adjustment for the presence of multiple HPV types in a single specimen, the top two HPV types contributing to disease were CIN 1 (HPV 16/66; 15.3%), CIN 2/3 (HPV 16/31; 61.9%), cervical cancer (HPV 16/18; 79.2%), VIN 1 (HPV 6/11; 41.7%), VIN 3 (HPV 16/18; 84.0%), vulvar cancer (HPV 16/33; 55.5%), VaIN 3 (HPV 16/18; 65.1%), and vaginal cancer (HPV 16/18; 72.7%). The HPV type distribution and proportion of cases testing positive for any HPV type were observed to vary among U.S. cervical, vulvar, and vaginal neoplasias and by grade of disease. Adjustment for the presence of multitype HPV infections can have an important effect on the estimated attribution of HPV types to disease, particularly for types other than HPV 16.

Impact of HPV vaccination with Gardasil® in Switzerland.

PubMed

Jacot-Guillarmod, Martine; Pasquier, Jérôme; Greub, Gilbert; Bongiovanni, Massimo; Achtari, Chahin; Sahli, Roland

2017-12-22

Gardasil®, a quadrivalent vaccine targeting low-risk (6, 11) and high-risk (16, 18) human papillomaviruses (HPV), has been offered to 11-14 year-old schoolgirls in Switzerland since 2008. To evaluate its success and its potential impact on cervical cancer screening, HPV genotypes were examined in 18-year-old girls five years later (sub-study 1) and in outpatients participating to cervical cancer screening before and after vaccine implementation (sub-study 2). For sub-study 1, 3726 females aged 18 in 2013 were invited to fill a questionnaire on personal demographics and HPV risk factors and to provide a self-collected cervicovaginal sample for HPV genotyping and Chlamydia trachomatis PCR. Personal data were evaluated by univariable and multivariable statistics. In sub-study 2, the proportion of the vaccine-type HPV among anogenital HPV was examined with archived genotyping data of 8039 outpatients participating to cervical cancer screening from 1999 till 2015. The yearly evolution of this proportion was evaluated by segmented logistic regression. 690 (18.5%) women participated to sub-study 1 and 327 (8.8%) provided a self-collected sample. Prevalence of Chlamydia trachomatis (4.6%) and demographics confirmed that the subjects were representative of sexually-active Swiss young women. Vaccine (five-year coverage: 77.5%) was preferentially accepted by contraceptive-pill users (P = 0.001) and samples were mainly provided by sexually-active subjects (P < 0.001). The proportion (4%) of the vaccine-type HPV in this population was lower than in sub-study 2 outpatients (n = 849, <26 years old) in the pre-vaccine era (25.7%). The proportion of the high-risk vaccine-type HPV decreased significantly (59%, P = 0.0048) in the outpatients during the post-vaccine era, yet this decrease was restricted to those aged less than 26 years (n = 673, P < 0.0001). The low proportion of vaccine-type HPV in 18-year-old females and its rapid decrease in young women participating to cervical cancer screening extend the success of HPV vaccination to Switzerland. Our data suggest that cervical cancer screening is now entering a stage of reduced proportion of HPV16 and/or 18 in samples reported positive by cytology. In view of the high likelihood of reduced clinical specificity of cytology, primary screening modalities involving HPV testing and cytology should now be re-evaluated in Switzerland.

Receipt of human papillomavirus vaccine among privately insured adult women in a U.S. Midwestern Health Maintenance Organization.

PubMed

Kharbanda, Elyse Olshen; Parker, Emily; Nordin, James D; Hedblom, Brita; Rolnick, Sharon J

2013-11-01

To describe human papillomavirus (HPV) vaccine coverage among adult privately insured women including variation in coverage by race/ethnicity. This cross-sectional, observational study included women 18-26 years of age with continuous enrollment in a U.S. Midwestern health insurance plan and at least one visit to a plan affiliated practice. Vaccination data came from insurance claims and the electronic medical record. Primary outcomes were: receipt of at least 1 HPV vaccine (HPV1) and completion of the 3-dose HPV vaccine series (HPV3). Coverage was described for the entire cohort and stratified by race/ethnicity. For a subset of women, automated data was compared to personal recall. As of June 2010, among 2546 privately insured women 18-26 years, 72.7% had received their first HPV vaccine and 57.9% completed the 3-dose series. Compared to white women, African American and Asian women had significantly lower coverage for HPV1 and HPV3. There was 94.5% (95% CI: 88.5-100%) agreement between personal recall and claims/EMR for receiving HPV1. In this cohort of privately insured women, a majority received HPV1 and more than half completed the 3-dose vaccine series. Marked disparities in receipt of HPV vaccine by race/ethnicity were observed. © 2013.

Parental acceptance of HPV vaccines in Chiang Mai, Thailand.

PubMed

Juntasopeepun, Phanida; Thana, Kanjana

2018-06-01

To identify variables associated with the acceptance of HPV vaccination among Thai parents/primary caregivers. The present prospective cross-sectional study recruited the parents/caregivers of female adolescents aged 12-18 years from schools in Chiang Mai, Thailand, between January 1 and February 29, 2016. A four-part questionnaire was distributed to assess demographics, HPV vaccine acceptance, knowledge, and beliefs toward HPV and cervical cancer. Predictors of HPV vaccine acceptance were determined by logistic regression analysis. The study enrolled 331 parents; more than half (195 [61.1%]) had heard of HPV vaccines. Their knowledge related to HPV and cervical cancer was moderate. A majority of parents (266/313 [85.0%]) indicated they would accept HPV vaccination if the costs were subsidized by the government. Acceptance of HPV vaccines was associated with perceived benefits of HPV vaccination (odds ratio [OR] 1.49; 95% confidence interval [CI] 1.18-1.88), perceived susceptibility to disease (OR 1.42; 95% CI 1.11-1.81), and household income (OR 1.35; 95% CI 1.02-1.78). Parental beliefs have an important role in their acceptance to vaccinate their daughters. These potentially modifiable beliefs offer strategies for future interventions designed to increase uptake for future HPV vaccination campaigns. © 2018 International Federation of Gynecology and Obstetrics.

Influence of smoking history on imaging characteristics among patients with human papillomavirus-positive oropharyngeal cancer: a blinded matched-pair analysis.

PubMed

Cantrell, Sarah C; Reid, Holly H; Li, Guojun; Wei, Qingyi; Sturgis, Erich M; Ginsberg, Lawrence E

2014-01-01

Human papillomavirus (HPV)-positive oropharyngeal cancers represent a distinct clinical entity with more favorable prognosis than do HPV-negative oropharyngeal cancers. However, among patients with HPV-positive oropharyngeal carcinomas, those with a significant smoking history have a much worse prognosis. Recently, imaging characteristics of oropharyngeal cancers were identified as markers of poor prognosis. The purpose of this study was to determine whether nodal imaging characteristics differ between smokers and never/light smokers with HPV-positive oropharyngeal cancer. A review of 130 pretreatment computed tomographic examinations of HPV-positive oropharyngeal cancers in smokers (>10 pack-years) and never/light smokers (10 pack-years) matched for T stage and tumor subsite was performed, with the reviewing radiologist blinded to the HPV status, smoking history, and clinical stage. Additionally 24 pretreatment computed tomographic examinations of patients with HPV-negative oropharyngeal cancers were also reviewed in a blinded fashion. Imaging characteristics of metastatic nodal disease were compared using the testing (Fisher exact testing where appropriate) and McNemar testing for the matched-pair analysis. As expected, those with HPV-positive oropharyngeal cancer were more likely to be younger, male, non-Hispanic white, never/former smokers, and never drinkers than were those with HPV-negative oropharyngeal cancer. Furthermore, the HPV-positive oropharyngeal cancers were more likely to be in the tonsil, smaller T category, higher N category, poorly differentiated, than were the HPV-negative oropharyngeal cancers. However, among the HPV-positive oropharyngeal cancers, we could identify no obvious difference in the pretreatment imaging characteristics of paired smokers and never/light smokers. Among the patients with HPV-positive oropharyngeal cancer, no imaging characteristics were identified to correlate with the critical prognostic feature smoking status. Cystic and necrotic nodal metastases, as described previously, were more common among the patients with HPV-positive than those with HPV-negative oropharyngeal cancers. Although cystic nodal metastases were more common among the never/light smokers with HPV-positive oropharyngeal cancer than among smokers with HPV-positive oropharyngeal cancer, however, because these results did not reach statistical significance, we concluded that the imaging results cannot serve as a surrogate for an HPV-driven phenotype.

Cervical cancer screening programs in Latin America and the Caribbean.

PubMed

Murillo, Raul; Almonte, Maribel; Pereira, Ana; Ferrer, Elena; Gamboa, Oscar A; Jerónimo, José; Lazcano-Ponce, Eduardo

2008-08-19

Latin America and the Caribbean (LAC) have a significant burden of cervical cancer. Prophylactic human papillomavirus (HPV) vaccines are an opportunity for primary prevention and new screening methods, such as new HPV DNA testing, are promising alternatives to cytology screening that should be analyzed in the context of regional preventive programs. Cytology-based screening programs have not fulfilled their expectations and coverage does not sufficiently explain the lack of impact on screening in LAC. While improved evaluation of screening programs is necessary to increase the impact of screening on the reduction of incidence and mortality, other programmatic aspects will need to be addressed such as follow-up of positive tests and quality control. The implementation of new technologies might enhance screening performance and reduce mortality in the region. The characteristics, performance and impact of cervical cancer screening programs in LAC are reviewed in this article.

Public awareness of human papillomavirus.

PubMed

Cuschieri, K S; Horne, A W; Szarewski, A; Cubie, H A

2006-01-01

The main objective of this study was to review the evidence relating to the level of awareness of human papillomavirus (HPV) in the general population and the implications for the potential introduction of HPV vaccination and HPV testing as part of screening. PubMed search performed on terms: 'HPV education', 'HPV awareness' 'Genital Warts Awareness' Results: Public awareness of HPV is generally very low, particularly with respect to its relation to abnormal smears and cervical cancer although knowledge levels vary to some extent according to sociodemographic characteristics. There is also much confusion around which types cause warts and the types that can cause cancer. The sexually transmissible nature of the infection is of major concern and confusion to women. Due to the lack of current awareness of HPV, significant education initiatives will be necessary should HPV vaccination and/or HPV testing be introduced. Organized edification of health-care workers and the media, who constitute the two most preferred sources of information, will be crucial.

Evaluation of the Clinical Performance of the HPV-Risk Assay Using the VALGENT-3 Panel.

PubMed

Polman, N J; Oštrbenk, A; Xu, L; Snijders, P J F; Meijer, C J L M; Poljak, M; Heideman, D A M; Arbyn, M

2017-12-01

Human papillomavirus (HPV) testing is increasingly being incorporated into cervical cancer screening. The Validation of HPV Genotyping Tests (VALGENT) is a framework designed to evaluate the clinical performance of various HPV tests relative to that of the validated and accepted comparator test in a formalized and uniform manner. The aim of this study was to evaluate the clinical performance of the HPV-Risk assay with samples from the VALGENT-3 panel and to compare its performance to that of the clinically validated Hybrid Capture 2 assay (HC2). The VALGENT-3 panel comprises 1,300 consecutive samples from women participating in routine cervical cancer screening and is enriched with 300 samples from women with abnormal cytology. DNA was extracted from original ThinPrep PreservCyt medium aliquots, and HPV testing was performed using the HPV-Risk assay by investigators blind to the clinical data. HPV prevalence was analyzed, and the clinical performance of the HPV-Risk assay for the detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) and CIN2 or worse (CIN2+) relative to the performance of HC2 was assessed. The sensitivity of the HPV-Risk assay for the detection of CIN3+ was similar to that of HC2 (relative sensitivity, 1.00; 95% confidence interval [CI], 0.95 to 1.05; P = 1.000), but the specificity of the HPV-Risk assay was significantly higher than that of HC2 (relative specificity, 1.02; 95% CI, 1.01 to 1.04; P < 0.001). For the detection of CIN2+, similar results were obtained, with the relative sensitivity being 0.98 (95% CI, 0.93 to 1.02; P = 0.257) and the relative specificity being 1.02 (95% CI, 1.01 to 1.03; P < 0.001). The performance of the HPV-Risk assay for the detection of CIN3+ and CIN2+ was noninferior to that of HC2, with all P values being ≤0.006. In conclusion, the HPV-Risk assay demonstrated noninferiority to the clinically validated HC2 by the use of samples from the VALGENT-3 panel for test validation and comparison. Copyright © 2017 Polman et al.

A head-to-head comparison of hydrogen peroxide vapor and aerosol room decontamination systems.

PubMed

Holmdahl, T; Lanbeck, P; Wullt, M; Walder, M H

2011-09-01

New technologies have emerged in recent years for the disinfection of hospital rooms and equipment that may not be disinfected adequately using conventional methods. There are several hydrogen peroxide-based area decontamination technologies on the market, but no head-to-head studies have been performed. We conducted a head-to-head in vitro comparison of a hydrogen peroxide vapor (HPV) system (Bioquell) and an aerosolized hydrogen peroxide (aHP) system (Sterinis). The tests were conducted in a purpose-built 136-m(3) test room. One HPV generator and 2 aHP machines were used, following recommendations of the manufacturers. Three repeated tests were performed for each system. The microbiological efficacy of the 2 systems was tested using 6-log Tyvek-pouched Geobacillus stearothermophilus biological indicators (BIs). The indicators were placed at 20 locations in the first test and 14 locations in the subsequent 2 tests for each system. All BIs were inactivated for the 3 HPV tests, compared with only 10% in the first aHP test and 79% in the other 2 aHP tests. The peak hydrogen peroxide concentration was 338 ppm for HPV and 160 ppm for aHP. The total cycle time (including aeration) was 3 and 3.5 hours for the 3 HPV tests and the 3 aHP tests, respectively. Monitoring around the perimeter of the enclosure with a handheld sensor during tests of both systems did not identify leakage. One HPV generator was more effective than 2 aHP machines for the inactivation of G. stearothermophilus BIs, and cycle times were faster for the HPV system.

Genital warts

MedlinePlus

Condylomata acuminata; Penile warts; Human papillomavirus (HPV); Venereal warts; Condyloma; HPV DNA test; Sexually transmitted disease (STD) - warts; Sexually transmitted infection (STI) - warts; LSIL-HPV; ...

Clinical Validation of Anyplex II HPV HR Detection Test for Cervical Cancer Screening in Korea.

PubMed

Jung, Sunkyung; Lee, Byungdoo; Lee, Kap No; Kim, Yonggoo; Oh, Eun-Jee

2016-03-01

The Anyplex II HPV HR detection kit (Seegene Inc, Seoul, Korea) is a new, multiplex, real-time polymerase chain reaction assay to detect individual 14 high-risk (HR) human papillomavirus (HPV) types in a single tube. To evaluate the clinical performance of the HPV HR kit in predicting high-grade squamous intraepithelial lesions and cervical intraepithelial lesions grade 2 or worse in cervical cancer screening. We analyzed 1137 cervical samples in Huro Path medium (CelltraZone, Seoul, Korea) from Korean women. The clinical performance of the HPV HR kit was compared with Hybrid Capture 2 (Qiagen, Valencia, California) using the noninferiority score test in a routine cervical cancer screening setting. The intralaboratory and interlaboratory agreements of HPV HR were also evaluated. Overall agreement between the 2 assays was 92.4% (1051 of 1137) with a κ value of 0.787. Clinical sensitivity of HPV HR for high-grade squamous intraepithelial lesions and cervical intraepithelial lesions grade 2 or worse was 94.4% (95% confidence interval [CI], 89.2-99.7) and 92.5% (95% CI, 84.3-100.0), respectively. The respective values for Hybrid Capture 2 were 93.1% (95% CI, 87.2-98.9) and 87.5% (95% CI, 77.3-99.7). Clinical sensitivity and specificity of HPV HR were not inferior to those of Hybrid Capture 2 (P = .005 and P = .04, respectively). The HPV HR showed good intralaboratory and interlaboratory reproducibility at 98.0% (κ = 0.953) and 97.4% (κ = 0.940), respectively. The HPV HR demonstrates comparable performance to the Hybrid Capture 2 test and can be useful for HPV-based cervical cancer screening testing.

Human papillomavirus-related carcinoma with adenoid cystic-like features: a series of five cases expanding the pathological spectrum.

PubMed

Hang, Jen-Fan; Hsieh, Min-Shu; Li, Wing-Yin; Chen, Jo-Yu; Lin, Shih-Yao; Liu, Shih-Hao; Pan, Chin-Chen; Kuo, Ying-Ju

2017-12-01

Human papillomavirus (HPV)-related carcinoma with adenoid cystic-like features is a newly described entity of the sinonasal tract. In this study, we evaluated histomorphology, immunophenotype and molecular testing to identify potentially helpful features in distinguishing it from classic adenoid cystic carcinoma (AdCC). We retrospectively collected five HPV-related carcinomas with adenoid cystic-like features and 14 AdCCs of the sinonasal tract. All histological slides were retrieved for morphological evaluation. As comparing with AdCC, HPV-related carcinomas with adenoid cystic-like features were associated with squamous dysplasia of surface epithelium (80% versus 0%, P < 0.01) and the presence of a solid growth pattern (100% versus 29%, P = 0.01), but less densely hyalinized tumour stroma (20% versus 86%, P = 0.02). Squamous differentiation in the invasive tumour was seen in three HPV-related carcinomas with adenoid cystic-like features, two of them showing abrupt keratinization and one with scattered non-keratinizing squamous nests. Diffuse p16 staining in ≥75% of tumour cells was noted in all HPV-related carcinomas with adenoid cystic-like features but in only one AdCC (100% versus 7%, P < 0.01). High-risk HPV testing gave positive results in all HPV-related carcinomas with adenoid cystic-like features (four associated with type 33 and one associated with type 16) but not in AdCCs. MYB rearrangement was tested in four HPV-related carcinomas with adenoid cystic-like features, and all were negative. This study has further clarified the histological spectrum of this tumour type, and reports the first HPV type 16-related case. Diffuse p16 staining followed by HPV molecular testing is useful in distinguishing HPV-related carcinomas with adenoid cystic features from classic AdCCs. © 2017 John Wiley & Sons Ltd.

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

PubMed

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

1990-01-01

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

Comparison of the Roche Cobas(®) 4800 HPV assay to Digene Hybrid Capture 2, Roche Linear Array and Roche Amplicor for Detection of High-Risk Human Papillomavirus Genotypes in Women undergoing treatment for cervical dysplasia.

PubMed

Phillips, Samuel; Garland, Suzanne M; Tan, Jeffery H; Quinn, Michael A; Tabrizi, Sepehr N

2015-01-01

The recently FDA (U.S. food and drug administration) approved Roche Cobas(®) 4800 (Cobas) human papillomavirus (HPV) has limited performance data compared to current HPV detection methods for test of cure in women undergoing treatment for high grade lesions. Evaluation of Cobas HPV assay using historical samples from women undergoing treatment for cervical dysplasia. A selection of 407 samples was tested on the Cobas assay and compared to previous results from Hybrid Capture 2, HPV Amplicor and Roche Linear Array. Overall, a correlation between high-risk HPV positivity and high grade histological diagnosis was 90.6% by the Cobas, 86.1% by Hybrid Capture 2, 92.9% by HPV Amplicor and 91.8% by Roche Linear Array. The Cobas HPV assay is comparative to both the HPV Amplicor and Roche Linear Array assays and better than Hybrid capture 2 assay in the detection of High-Risk HPV in women undergoing treatment for cervical dysplasia. Copyright © 2014 Elsevier B.V. All rights reserved.

Prevalence and genotype distribution of human papillomavirus infection among women in northeastern Guangdong Province of China.

PubMed

Zhao, Pingsen; Liu, Sudong; Zhong, Zhixiong; Hou, Jingyuan; Lin, Lifang; Weng, Ruiqiang; Su, Luxian; Lei, Nanxiang; Hou, Tao; Yang, Haikun

2018-05-03

Human papillomavirus (HPV) DNA testing is an important method in cervical cancer screening. However, the studies on prevalence and genotype distribution of HPV among women in northeastern Guangdong Province of China are very limited. A total of 28,730 women attending the Department of Gynecology of Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University between January 1st, 2013 and June 1st, 2015 were enrolled in this study. HPV type-specific distribution was tested using flow-through hybridization and gene chip. The overall prevalence of HPV infection was 19.81%, among which 79.09% were infected with high-risk HPV subtypes in the subjects. The 5 most predominant genotypes were HPV16, 52, 58, 18 and 81. Most HPV infections were observed in women aged 41-50 and women aged 30-59 accounted for a proportion of over 80%. Our findings suggested a high burden of HPV infection among women in northeastern Guangdong Province of China. We identified the top 5 HPV genotypes as well as the age-specific distribution of HPV infections in this area.

Prediction of cervical intraepithelial neoplasia grade 2+ (CIN2+) using HPV DNA testing after a diagnosis of atypical squamous cell of undetermined significance (ASC-US) in Catalonia, Spain.

PubMed

Ibáñez, Raquel; Moreno-Crespi, Judit; Sardà, Montserrat; Autonell, Josefina; Fibla, Montserrat; Gutiérrez, Cristina; Lloveras, Belen; Alejo, María; Català, Isabel; Alameda, Francesc; Casas, Miquel; Bosch, F Xavier; de Sanjosé, Silvia

2012-01-26

A protocol for cervical cancer screening among sexually active women 25 to 65 years of age was introduced in 2006 in Catalonia, Spain to increase coverage and to recommend a 3-year-interval between screening cytology. In addition, Human Papillomavirus (HPV) was offered as a triage test for women with a diagnosis of atypical squamous cells of undetermined significance (ASC-US). HPV testing was recommended within 3 months of ASC-US diagnosis. According to protocol, HPV negative women were referred to regular screening including a cytological exam every 3 years while HPV positive women were referred to colposcopy and closer follow-up. We evaluated the implementation of the protocol and the prediction of HPV testing as a triage tool for cervical intraepithelial lesions grade two or worse (CIN2+) in women with a cytological diagnosis of ASC-US. During 2007-08 a total of 611 women from five reference laboratories in Catalonia with a novel diagnosis of ASC-US were referred for high risk HPV (hrHPV) triage using high risk Hybrid Capture version 2. Using routine record linkage data, women were followed for 3 years to evaluate hrHPV testing efficacy for predicting CIN2+ cases. Logistic regression analysis was used to estimate the odds ratio for CIN2 +. Among the 611 women diagnosed with ASC-US, 493 (80.7%) had at least one follow-up visit during the study period. hrHPV was detected in 48.3% of the women at study entry (mean age 35.2 years). hrHPV positivity decreased with increasing age from 72.6% among women younger than 25 years to 31.6% in women older than 54 years (p < 0.01). At the end of the 3 years follow-up period, 37 women with a diagnosis of CIN2+ (18 CIN2, 16 CIN3, 2 cancers, and 1 with high squamous intraepithelial lesions--HSIL) were identified and all but one had a hrHPV positive test at study entry. Sensitivity to detect CIN2+ of hrHPV was 97.2% (95%confidence interval (CI) = 85.5-99.9) and specificity was 68.3% (95%CI = 63.1-73.2). The odds ratio for CIN2+ was 45.3 (95% CI: 6.2-333.0), when among ASC-US hrHPV positive women were compared to ASC-US hrHPV negative women. Triage of ASC-US with hrHPV testing showed a high sensitivity for the detection of CIN2+ and a high negative predictive value after 3 years of follow-up. The results of this study are in line with the current guidelines for triage of women with ASC-US in the target age range of 25-65. Non adherence to guidelines will lead to unnecessary medical interventions. Further investigation is needed to improve specificity of ASC-US triage.

Laboratory and clinical aspects of human papillomavirus testing

PubMed Central

Chan, Paul K.S.; Picconi, María Alejandra; Cheung, Tak Hong; Giovannelli, Lucia; Park, Jong Sup

2012-01-01

Human papillomavirus (HPV) infection is associated with a wide spectrum of disease that ranges from self-limited skin warts to life-threatening cancers. Since HPV plays a necessary etiological role in cervical cancer, it is logical to use HPV as a marker for early detection of cervical cancer and precancer. Recent advances in technology enable the development of high-throughput HPV assays of different formats, including DNA-based, mRNA-based, high-risk group-specific and type-specific methods. The ultimate goal of these assays is to improve the accuracy and cost-effiectiveness of cervical screening programs. HPV testing has several potential advantages compared to cytology-based screening. However, since the cancer to transient infection ratio is always low in the general population, HPV test results are bound to have a low positive predictive value that may subject women to unnecessary follow-up investigations. The wide-spread administration of prophylactic HPV vaccine will substantially decrease the incidence of cancer and precancer. This poses a number of challenges to cytology-based screening, and the role of HPV testing is expected to increase. Finally, apart from technical and cost-effiectiveness considerations, one should also keep in mind the psycho-social impact of using sexually-transmitted agents as a marker for cancer screening. PMID:22913405

Impact of age on the false negative rate of human papillomavirus DNA test in patients with atypical squamous cells of undetermined significance.

PubMed

Won, Kyu-Hee; Lee, Jae Yeon; Cho, Hye-Yon; Suh, Dong Hoon; No, Jae Hong; Kim, Yong-Beom

2015-03-01

Human papillomavirus (HPV) test was incorporated into the triage of lesser abnormal cervical cytologies: atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL). This study aimed to evaluate the impact of age on the efficacy of HPV testing in patients with lesser abnormal cervical cytologies. A total of 439 patients with ASCUS or LSIL were included. The association between age groups and the diagnostic performances of HPV test for high-grade cervical intraepithelial neoplasia (CIN2+) was evaluated. Median age was 44 years (range, 17 to 75 years). ASCUS was more frequently observed in older patients while LSIL was more common in younger patients (P=0.002). CIN2+ was found in 11.3% (32/284) of the ASCUS patients and 12.9% (20/155) of patients with LSIL. Older patients with ASCUS showed lower HPV infection rates (P=0.025), but not LSIL (P=0.114). However, the prevalence of CIN2+ was similar between the age groups with ASCUS or LSIL. In patients with ASCUS, the false negative rate of HPV test for CIN2+ was 6.2%. The false negative rate of the HPV test became higher with increasing of the age after the age of 50 (P=0.034). Our findings suggest that false negative rate of the HPV test for CIN2+ in ASCUS patients older than 50 years might become higher with increasing of the age. Negative HPV results in patients of the age >50 years with ASCUS should be carefully interpreted.

U.S. Navy Womens Experience with Cervical Cancer Screening and Follow-up Care

DTIC Science & Technology

2015-07-15

encounters, non- adherence to HPV vaccines , and increased rates of sexually transmitted infections. The screening process is an excellent...167. 16. Shen-Gunther J, Shank JJ, Ta V. Gardasil HPV vaccination : Surveillance of vaccine usage and adherence in a military population. Gynecol Oneal...upsetting as it describes the primary cause of an abnormal CCS having an HPV etiology. Information that had not been disclosed to them by the provider

Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial.

PubMed

Posner, M R; Lorch, J H; Goloubeva, O; Tan, M; Schumaker, L M; Sarlis, N J; Haddad, R I; Cullen, K J

2011-05-01

The association between human papillomavirus (HPV) and overall survival (OS) in oropharynx cancer (OPC) was retrospectively examined in TAX 324, a phase III trial of sequential therapy for locally advanced head and neck cancer. Accrual for TAX 324 was completed in 2003 and data updated through 2008. Pretherapy tumor biopsies were studied by PCR for human papillomavirus type 16 and linked to OS, progression-free survival (PFS) and demographics. Of 264 patients with OPC, 111 (42%) had evaluable biopsies; 56 (50%) were HPV+ and 55 (50%) were HPV-. HPV+ patients were significantly younger (54 versus 58 years, P = 0.02), had T1/T2 primary cancers (49% versus 20%, P = 0.001), and had a performance status of zero (77% versus 49%, P = 0.003). OS and PFS were better for HPV+ patients (OS, hazard ratio = 0.20, P < 0.0001). Local-regional failure was less in HPV+ patients (13% versus 42%, P = 0.0006); at 5 years, 82% of HPV+ patients were alive compared with 35% of HPV- patients (P < 0.0001). HPV+ OPC has a different biology compared with HPV- OPC; 5-year OS, PFS, and local-regional control are unprecedented. These results support the possibility of selectively reducing therapy and long-term morbidity in HPV+ OPC while preserving survival and approaching HPV- disease with more aggressive treatment.

Human Papillomavirus (HPV) Infection: Molecular Epidemiology, Genotyping, Seroprevalence and Associated Risk Factors among Arab Women in Qatar

PubMed Central

Acharya, Anushree; Skariah, Sini; Dargham, Soha R.; Abu-Raddad, Laith J.; Mohamed-Nady, Nady; Amuna, Paul; Al-Thani, Asma A. J.; Sultan, Ali A.

2017-01-01

Human Papillomavirus (HPV) infections are known to cause cervical cancer worldwide, however, limited information is currently available on prevalence, types distribution and risk factors for HPV infection in the Arab countries. We conducted a cross-sectional observational study exclusively of women of Arabic origin residing in Qatar (n = 406) who were selected from the Women’s Hospital at Hamad Medical Corporation (HMC) and Health Centers of the Primary Health Care Corporation in Doha, Qatar over the period March 2013 to August 2014. Socio-demographic, behavioral and clinical data were collected. Four hundred and six cervical smears and 292 blood samples were included in the study. HPV typing was done using HPV type-specific primers-based real-time PCR, and Sanger sequencing. HPV-IgG and IgM were quantified using ELISA assays. The prevalence of HPV infection amongst Qatari and non-Qatari Arab women were 9.8% and 6.1%, respectively and 7.6% and 16.7% in women with normal and abnormal cytology, respectively. HPV 81 was the most commonly found genotype in women with normal cytology (34.5%), whereas HPV 81, 16 and 59 in women with abnormal cytology (25.0% each). All the HPV DNA positive women were seronegative and HPV-IgG prevalence was higher in Qatari women than in non-Qatari Arab women. None of the studied factors had any significant association with HPV-DNA positivity or HPV-IgG seropositivity. The overall identified HPV DNA prevalence and HPV seroprevalence among Arab women in Qatar were on the low side compared to global levels. PMID:28046025

Human Papillomavirus (HPV) Infection: Molecular Epidemiology, Genotyping, Seroprevalence and Associated Risk Factors among Arab Women in Qatar.

PubMed

Elmi, Asha A; Bansal, Devendra; Acharya, Anushree; Skariah, Sini; Dargham, Soha R; Abu-Raddad, Laith J; Mohamed-Nady, Nady; Amuna, Paul; Al-Thani, Asma A J; Sultan, Ali A

2017-01-01

Human Papillomavirus (HPV) infections are known to cause cervical cancer worldwide, however, limited information is currently available on prevalence, types distribution and risk factors for HPV infection in the Arab countries. We conducted a cross-sectional observational study exclusively of women of Arabic origin residing in Qatar (n = 406) who were selected from the Women's Hospital at Hamad Medical Corporation (HMC) and Health Centers of the Primary Health Care Corporation in Doha, Qatar over the period March 2013 to August 2014. Socio-demographic, behavioral and clinical data were collected. Four hundred and six cervical smears and 292 blood samples were included in the study. HPV typing was done using HPV type-specific primers-based real-time PCR, and Sanger sequencing. HPV-IgG and IgM were quantified using ELISA assays. The prevalence of HPV infection amongst Qatari and non-Qatari Arab women were 9.8% and 6.1%, respectively and 7.6% and 16.7% in women with normal and abnormal cytology, respectively. HPV 81 was the most commonly found genotype in women with normal cytology (34.5%), whereas HPV 81, 16 and 59 in women with abnormal cytology (25.0% each). All the HPV DNA positive women were seronegative and HPV-IgG prevalence was higher in Qatari women than in non-Qatari Arab women. None of the studied factors had any significant association with HPV-DNA positivity or HPV-IgG seropositivity. The overall identified HPV DNA prevalence and HPV seroprevalence among Arab women in Qatar were on the low side compared to global levels.

Human Papillomavirus DNA Methylation as a Biomarker for Cervical Precancer: Consistency across 12 Genotypes and Potential Impact on Management of HPV-Positive Women.

PubMed

Clarke, Megan A; Gradissimo, Ana; Schiffman, Mark; Lam, Jessica; Sollecito, Christopher C; Fetterman, Barbara; Lorey, Thomas; Poitras, Nancy; Raine-Bennett, Tina R; Castle, Philip E; Wentzensen, Nicolas; Burk, Robert D

2018-05-01

Purpose: Human papillomavirus (HPV) DNA methylation testing is a promising triage option for women testing HPV positive during cervical cancer screening. However, the extent to which methylation indicates precancer for all 12 carcinogenic HPV types has not been evaluated. Experimental Design: In this nested case-control study, we tested up to 30 cases of precancer [cervical intraepithelial neoplasia grade 3 (CIN3)/adenocarcinoma in situ (AIS)] and 30 normal controls for each carcinogenic type (single infections with 16/18/31/33/35/39/45/51/52/56/58/59). Next-generation bisulfite sequencing was performed on CpG sites within the L1 and L2 genes. We calculated differences in methylation, ORs, and AUC. Using a fixed sensitivity of 80%, we evaluated the specificity and the risk of CIN3/AIS for best performing CpG sites, and compared the performance of an explorative multi-type methylation assay with current triage strategies. Results: Methylation was positively associated with CIN3/AIS across all 12 types. AUCs for the top sites ranged from 0.71 (HPV51 and HPV56) to 0.86 (HPV18). A combined 12-type methylation assay had the highest Youden index (0.46), compared with cytology (0.31) and a 5-type methylation assay, including only previously described types (0.26). The 12-type methylation assay had higher sensitivity (80% vs. 76.6%) and lower test positivity compared with cytology (38.5% vs. 48.7%). The risk of CIN3/AIS was highest for methylation positives and lowest for cytology or HPV16/18 positives. Conclusions: HPV DNA methylation is a general phenomenon marking the transition from HPV infection to precancer for all 12 carcinogenic types. Development of a combined multitype methylation assay may serve as a triage test for HPV-positive women. Clin Cancer Res; 24(9); 2194-202. ©2018 AACR . ©2018 American Association for Cancer Research.

Rapid identification of HPV 16 and 18 by multiplex nested PCR-immunochromatographic test.

PubMed

Kuo, Yung-Bin; Li, Yi-Shuan; Chan, Err-Cheng

2015-02-01

Human papillomavirus (HPV) types 16 and 18 are known to be high-risk viruses that cause cervical cancer. An HPV rapid testing kit that could help physicians to make early and more informed decisions regarding patient care is needed urgently but not yet available. This study aimed to develop a multiplex nested polymerase chain reaction-immunochromatographic test (PCR-ICT) for the rapid identification of HPV 16 and 18. A multiplex nested PCR was constructed to amplify the HPV 16 and 18 genotype-specific L1 gene fragments and followed by ICT which coated with antibodies to identify rapidly the different PCR products. The type-specific gene regions of high-risk HPV 16 and 18 could be amplified successfully by multiplex nested PCR at molecular sizes of approximately 99 and 101bp, respectively. The capture antibodies raised specifically against the moleculars labeled on the PCR products could be detected simultaneously both HPV 16 and 18 in one strip. Under optimal conditions, this PCR-ICT assay had the capability to detect HPV in a sample with as low as 100 copies of HPV viral DNA. The PCR-ICT system has the advantage of direct and simultaneous detection of two high-risk HPV 16 and 18 DNA targets in one sample, which suggested a significant potential of this assay for clinical application. Copyright © 2014. Published by Elsevier B.V.

Human Papillomavirus (HPV) Genotyping: Automation and Application in Routine Laboratory Testing

PubMed Central

Torres, M; Fraile, L; Echevarria, JM; Hernandez Novoa, B; Ortiz, M

2012-01-01

A large number of assays designed for genotyping human papillomaviruses (HPV) have been developed in the last years. They perform within a wide range of analytical sensitivity and specificity values for the different viral types, and are used either for diagnosis, epidemiological studies, evaluation of vaccines and implementing and monitoring of vaccination programs. Methods for specific genotyping of HPV-16 and HPV-18 are also useful for the prevention of cervical cancer in screening programs. Some commercial tests are, in addition, fully or partially automated. Automation of HPV genotyping presents advantages such as the simplicity of the testing procedure for the operator, the ability to process a large number of samples in a short time, and the reduction of human errors from manual operations, allowing a better quality assurance and a reduction of cost. The present review collects information about the current HPV genotyping tests, with special attention to practical aspects influencing their use in clinical laboratories. PMID:23248734

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.

Detection of human papillomavirus 16, 18, and 45 in women with ASC-US cytology and the risk of cervical precancer: results from the CLEAR HPV study.

PubMed

Castle, Phillip E; Cuzick, Jack; Stoler, Mark H; Wright, Thomas C; Reid, Jennifer L; Dockter, Janel; Giachetti, Cristina; Getman, Damon

2015-02-01

The Aptima human papillomavirus (HPV) 16 18/45 Genotype (GT) assay (AHPV-GT) is a qualitative E6/ E7 oncogene messenger RNA test that detects HPV 16 and a pool of HPV 18 and 45. The CLEAR (Clinical Evaluation of APTIMA mRNA) study was the pivotal, prospective, multicenter US clinical study to validate the Aptima HPV (AHPV) assays. In this analysis, we evaluated the clinical performance of AHPV and AHPV-GT assays for detection of cervical intraepithelial neoplasia grade 2 or more severe (CIN2 +) and grade 3 (CIN3) or adenocarcinoma in situ in 912 women with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou result. The AHPV-GT assay was performed on high-risk HPV (hrHPV) positives as determined by the AHPV assay. Overall, the percent positive for hrHPV was 38.8% (354/912), of which 34.2% (121/354) were GT positive. Among hrHPV-positive women, the risks of CIN2 + were 37.0% for HPV 16 positives, 15.9% for HPV 18/45 positives, 14.3% for other hrHPV positives, and 2.2% for AHPV negatives. The risks of CIN3 + were 20.5% for HPV 16 positives, 9.1% for HPV 18/45 positives, 4.3% for other hrHPV positives, and 0.7% for HPV negatives. We demonstrated that AHPV-GT is a reliable and effective test for cervical cancer risk stratification in women with an ASC-US cytology diagnosis. Copyright© by the American Society for Clinical Pathology.

Perceptions of Nigerian Women about Human Papilloma Virus, Cervical Cancer, and HPV Vaccine

PubMed Central

Akanbi, Olusola Anuoluwapo; Iyanda, Abiodun; Osundare, Folakemi; Opaleye, Oluyinka Oladele

2015-01-01

Background. Cervical cancer caused by human papilloma virus (HPV) though preventable has claimed the lives of many women worldwide. This study was embarked upon to evaluate the general knowledge and perceptions of Nigerian women on HPV, cervical cancer, and HPV vaccine. Methods. Structured questionnaires were administered to a cross section of 737 women randomly selected from the general population in two southwestern States of Nigeria. Statistical analysis was done using SPSS computer software version 16. A P value >0.05 was considered statistically significant. Results. One hundred and seventy-six (23.9%) of the respondents had knowledge of HPV; 474 (64.3%) are aware of cervical cancer but only 136 (18.5%) know that HPV causes cervical cancer. 200 (27.1%) are aware that there is an HPV vaccine while 300 (40.7%) had knowledge of Pap smear test. Two hundred and sixty (35.3%) of the respondents know that early detection of HPV can prevent cervical cancer and in spite of this, only 110 (14.9%) have taken the Pap smear test before while 151 (20.5%) are not willing to go for the test at all. Conclusions. There is therefore the need to create proper awareness on the HPV and its possible consequence of cervical carcinoma. PMID:26550522

Public knowledge and attitudes towards Human Papilloma Virus (HPV) vaccination

PubMed Central

Walsh, Charlotte Devereaux; Gera, Aradhana; Shah, Meeraj; Sharma, Amit; Powell, Judy E; Wilson, Sue

2008-01-01

Background Human Papilloma Virus (HPV) vaccine has undergone successful trials and has recently been approved for use for the primary prevention of cervical cancer. The aim of this study was to determine knowledge and attitudes towards HPV vaccination. Methods Semi-structured interview and questionnaire delivered in a street survey. Standardised HPV-related statements used to measure HPV knowledge and attitudes to vaccination. The setting was three different areas of Birmingham, to target a mix of social class and ethnicity. The sample population was composed of 16–54 year olds. Results A total of 420 participants were recruited. Poor knowledge of HPV and its links with cervical cancer were observed. 81% had a knowledge score of zero. Knowledge about HPV was associated with different ethnic group and socio-economic group. The majority (88%) of participants were in favour of vaccination, with 83.6% indicating that they would allow a child under their care to be vaccinated. Conclusion Initial responses to the proposed HPV vaccination within the UK public are favourable. However, knowledge levels are poor and media and health professional promotion are required to raise awareness. PMID:18947430

Diagnosing women with HPV: the impact of diagnosis disclosure methods.

PubMed

Harvey-Knowles, Jacquelyn A; Kosenko, Kami A

2012-07-01

Little data exists on women's HPV diagnosis encounters. This research focuses on impacts of the communicative medium used to inform women of their HPV status. We conducted a qualitative study to identify the mediums used to communicate HPV diagnoses and the impact of each medium on the diagnosis experience. Twenty-five women with HPV completed semi-structured interviews, which we recorded and transcribed. We relied on grounded theory techniques in both data collection and analysis. There are three primary mediums health care providers use to inform women of their HPV diagnosis: phone calls, mailed letters/email, and face-to-face interactions. Implications regarding each medium are identified and discussed. There are drawbacks associated with the use of each medium that healthcare practitioners should be aware of and seek to avoid. Healthcare providers can utilize descriptions of diagnosis encounters and the recommendations accompanying them to understand and modify ways they choose to inform individuals of an HPV diagnosis. Published by Elsevier Ireland Ltd.

Roscovitine strongly enhances the effect of olaparib on radiosensitivity for HPV neg. but not for HPV pos. HNSCC cell lines.

PubMed

Ziemann, Frank; Seltzsam, Steve; Dreffke, Kristin; Preising, Stefanie; Arenz, Andrea; Subtil, Florentine S B; Rieckmann, Thorsten; Engenhart-Cabillic, Rita; Dikomey, Ekkehard; Wittig, Andrea

2017-12-01

At present, advanced stage human Papillomavirus (HPV) negative and positive head and neck squamous cell carcinoma (HNSCC) are treated by intense multimodal therapy that includes radiochemotherapy, which are associated with relevant side effects. Patients with HPV positive tumors possess a far better prognosis than those with HPV negative cancers. Therefore, new therapeutic strategies are needed to improve the outcome especially of the latter one as well as quality of life for all HNSCC patients. Here we tested whether roscovitine, an inhibitor of cyclin-dependent kinases (CDKs), which hereby also blocks homologous recombination (HR), can be used to enhance the radiation sensitivity of HNSCC cell lines. In all five HPV negative and HPV positive cell lines tested, roscovitine caused inhibition of CDK1 and 2. Surprisingly, all HPV positive cell lines were found to be defective in HR. In contrast, HPV negative strains demonstrated efficient HR, which was completely suppressed by roscovitine. In line with this, for HPV negative but not for HPV positive cell lines, treatment with roscovitine resulted in a pronounced enhancement of the radiation-induced G2 arrest as well as a significant increase in radiosensitivity. Due to a defect in HR, all HPV positive cell lines were efficiently radiosensitized by the PARP-1 inhibitor olaparib. In contrast, in HPV negative cell lines a significant radiosensitization by olaparib was only achieved when combined with roscovitine.

Dual expression of Epstein-Barr virus, latent membrane protein-1 and human papillomavirus-16 E6 transform primary mouse embryonic fibroblasts through NF-κB signaling.

PubMed

Shimabuku, Tetsuya; Tamanaha, Ayumi; Kitamura, Bunta; Tanabe, Yasuka; Tawata, Natsumi; Ikehara, Fukino; Arakaki, Kazunari; Kinjo, Takao

2014-01-01

The prevalence of Epstein-Barr virus (EBV) and high-risk human papilloma virus (HPV) infections in patients with oral cancer in Okinawa, southwest islands of Japan, has led to the hypothesis that carcinogenesis is related to EBV and HPV co-infection. To explore the mechanisms of transformation induced by EBV and HPV co-infection, we analyzed the transformation of primary mouse embryonic fibroblasts (MEFs) expressing EBV and HPV-16 genes, alone or in combination. Expression of EBV latent membrane protein-1 (LMP-1) alone or in combination with HPV-16 E6 increased cell proliferation and decreased apoptosis, whereas single expression of EBV nuclear antigen-1 (EBNA-1), or HPV-16 E6 did not. Co-expression of LMP-1 and E6 induced anchorage-independent growth and tumor formation in nude mice, whereas expression of LMP-1 alone did not. Although the singular expression of these viral genes showed increased DNA damage and DNA damage response (DDR), co-expression of LMP-1 and E6 did not induce DDR, which is frequently seen in cancer cells. Furthermore, co-expression of LMP-1 with E6 increased NF-κB signaling, and the knockdown of LMP-1 or E6 in co-expressing cells decreased cell proliferation, anchorage independent growth, and NF-κB activation. These data suggested that expression of individual viral genes is insufficient for inducing transformation and that co-expression of LMP-1 and E6, which is associated with suppression of DDR and increased NF-κB activity, lead to transformation. Our findings demonstrate the synergistic effect by the interaction of oncogenes from different viruses on the transformation of primary MEFs.

Reduction in HPV 16/18 prevalence in sexually active young women following the introduction of HPV immunisation in England.

PubMed

Mesher, D; Soldan, K; Howell-Jones, R; Panwar, K; Manyenga, P; Jit, M; Beddows, S; Gill, O N

2013-12-17

Reduction in the prevalence of vaccine type HPV infection in young women is an early indication of the impact of the HPV immunisation programme and a necessary outcome if the subsequent impact on cervical cancer is to be realised. Residual vulva-vaginal swab (VVS) specimens from young women aged 16-24 years undergoing chlamydia screening in community sexual health services (formerly known as family planning clinics), general practice (GP), and youth clinics in 2010-2012 were submitted from 10 laboratories in seven regions around England. These specimens were linked to demographic and sexual behaviour data reported with the chlamydia test, anonymised, and tested for type-specific HPV DNA using a multiplex PCR and Luminex-based genotyping test. Estimated immunisation coverage was calculated and findings were compared to a baseline survey conducted prior to the introduction of HPV immunisation in 2008. A total of 4664 eligible specimens were collected and 4178 had a valid test result. The post-immunisation prevalence of HPV 16/18 infection was lowest in this youngest age group (16-18 years) and increased with age. This increase with age was a reversal of the pattern seen prior to immunisation and was inversely associated with estimates of age-specific immunisation coverage (65% for 16-18 year olds). The prevalence of HPV 16/18 infection in the post-immunisation survey was 6.5% amongst 16-18 year olds, compared to 19.1% in the similar survey conducted prior to the introduction of HPV immunisation. These findings are the first indication that the national HPV immunisation programme is successfully preventing HPV 16/18 infection in sexually active young women in England. The reductions seen suggest, for the estimated coverage, high vaccine effectiveness and some herd-protection benefits. Continued surveillance is needed to determine the effects of immunisation on non-vaccine HPV types. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

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.

Hybrid capture-II and LCR-E7 PCR assays for HPV typing in cervical cytologic samples.

PubMed

Yamazaki, H; Sasagawa, T; Basha, W; Segawa, T; Inoue, M

2001-10-15

As part of an ongoing cohort study in the Hokuriku region of Japan, cervical cell samples from histologically confirmed normal (n = 114) or abnormal (n = 286) women were examined for the presence of HPV DNA using a second-generation hybrid capture assay (HCA-II) and LCR-E7 PCR. HCA-II detected low-risk (HPV-6, -11, -42, 43 and -44) and high-risk (HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59 and -68) HPV types, while LCR-E7 PCR detected an additional 7 HPV types and some uncharacterized types. In screening of high-grade squamous intraepithelial lesions (HSILs) and invasive cervical cancer, the sensitivities of HCA-II and LCR-E7 PCR testing the high-risk HPV types were 83% and 81%, respectively, while the specificity of both assays was 93%. The sensitivity of LCR-E7 PCR increased to 87%, which was significantly higher than that in HCA-II, when testing both high-risk and other HPV types. Sixty-eight inconsistent results (17% of total tested) from HCA-II and LCR-E7 PCR were due to (i) low copy number of HPV genome (false-negative for HCA-II, 5.3% and for LCR-E7 PCR, 1.3%), (ii) infection with HPV types undetectable by HCA-II (4.8%), (iii) multiple HPV infections (5%) or (iv) unknown reasons (0.8%). LCR-E7 PCR revealed that infections with HPV-16, -18, -31, -33, -35, -51, -52, -56, -58 or -67 was a high risk for cancer since these types predominated in HSIL and invasive cervical cancer. Samples showing high relative light units (>20) with a high-risk probe in HCA-II also gave positive results in LCR-E7 PCR and were generally associated with abnormal cervical lesions. Thus, we propose that both HCA-II and LCR-E7 PCR are valuable screening tests for premalignant and malignant cervical lesions. Copyright 2001 Wiley-Liss, Inc.

Establishment and characterization of a human papillomavirus type 16-positive tonsillar carcinoma xenograft in BALB/c nude mice.

PubMed

Letsolo, Boitelo T; Faust, Helena; Ekblad, Lars; Wennerberg, Johan; Forslund, Ola

2016-03-01

Among head and neck cancers, human papillomavirus type 16 (HPV16) is associated with tonsillar carcinomas. Despite this, no HPV16-positive tonsillar cancer cell line has been established in nude mice. Fresh tonsillar carcinoma biopsies were obtained from 23 patients and implanted subcutaneously into nude mice (BALB/c, nu/nu). After 7 months, one xenograft was established. The primary tumor harbored 2.7 copies (95% confidence interval = 2.4-2.9) of HPV16/cell and displayed 99.9% (7904/7906) nucleotide identity to HPV16 (EU118173.1). The xenograft showed increased methylation in two E2-binding sites of the HPV16 genome. Both episomal and integrated HPV16 were detected in the original tumor and in 14 xenografts from the second passage. From this passage, a viral load of 6.4 copies/cell (range = 4.6-9.6) and 3.7 (range = 1.0-5.5) E7-mRNA transcripts/HPV16-genome were detected. This xenograft represents the first established HPV16-positive tonsillar tumor in nude mice and could provide an experimental system of HPV16-positive tonsillar cancers. © 2015 Wiley Periodicals, Inc.

Radiomic analysis in prediction of Human Papilloma Virus status.

PubMed

Yu, Kaixian; Zhang, Youyi; Yu, Yang; Huang, Chao; Liu, Rongjie; Li, Tengfei; Yang, Liuqing; Morris, Jeffrey S; Baladandayuthapani, Veerabhadran; Zhu, Hongtu

2017-12-01

Human Papilloma Virus (HPV) has been associated with oropharyngeal cancer prognosis. Traditionally the HPV status is tested through invasive lab test. Recently, the rapid development of statistical image analysis techniques has enabled precise quantitative analysis of medical images. The quantitative analysis of Computed Tomography (CT) provides a non-invasive way to assess HPV status for oropharynx cancer patients. We designed a statistical radiomics approach analyzing CT images to predict HPV status. Various radiomics features were extracted from CT scans, and analyzed using statistical feature selection and prediction methods. Our approach ranked the highest in the 2016 Medical Image Computing and Computer Assisted Intervention (MICCAI) grand challenge: Oropharynx Cancer (OPC) Radiomics Challenge, Human Papilloma Virus (HPV) Status Prediction. Further analysis on the most relevant radiomic features distinguishing HPV positive and negative subjects suggested that HPV positive patients usually have smaller and simpler tumors.

Molecular characterization, tissue tropism, and genetic variability of the novel Mupapillomavirus type HPV204 and phylogenetically related types HPV1 and HPV63

PubMed Central

Šterbenc, Anja; Hošnjak, Lea; Chouhy, Diego; Bolatti, Elisa M.; Oštrbenk, Anja; Seme, Katja; Kocjan, Boštjan J.; Luzar, Boštjan; Giri, Adriana A.; Poljak, Mario

2017-01-01

HPV204 is the only newly identified Mupapillomavirus (Mu-PV) type in more than a decade. To comprehensively characterize HPV204, we performed a detailed molecular analysis of the viral genome and evaluated its clinical relevance in comparison to the other Mu-PVs, HPV1 and HPV63. The 7,227-bp long genome of HPV204 exhibits typical genomic organization of Mu-PVs with eight open reading frames (ORFs) (E6, E7, E1, E2, E8, E4, L2, and L1). We developed three type-specific quantitative real-time PCRs and used them to test a representative collection (n = 1,006) of various HPV-associated benign and malignant neoplasms, as well as samples of clinically normal cutaneous, mucosal, and mucocutaneous origins. HPV204, HPV1, and HPV63 were detected in 1.1%, 2.7%, and 1.9% of samples tested, respectively, and were present in skin and mucosa, suggesting dual tissue tropism of all Mu-PVs. To evaluate the etiological role of Mu-PVs in the development of HPV-associated neoplasms, Mu-PV viral loads per single cell were estimated. HPV1 and HPV63 were present in high viral copy numbers in 3/43 and 1/43 cutaneous warts, respectively, and were identified as the most likely causative agents of these warts. HPV204 viral load was extremely low in a single HPV204-positive cutaneous wart (7.4 × 10−7 viral copies/cell). Hence, etiological association between HPV204 and the development of cutaneous warts could not be established. To the best of our knowledge, this is the first study to evaluate the genetic variability of Mu-PVs by sequencing complete LCR genomic regions of HPV204, HPV1, and HPV63. We detected several nucleotide substitutions and deletions within the LCR genomic regions of Mu-PVs and identified two genetic variants of HPV204 and HPV63 and five genetic variants of HPV1. PMID:28426749

Natural history of anal human papillomavirus infection in heterosexual women and risks associated with persistence.

PubMed

Moscicki, Anna-Barbara; Ma, Yifei; Farhat, Sepideh; Jay, Julie; Hanson, Evelyn; Benningfield, Susanna; Jonte, Janet; Godwin-Medina, Cheryl; Wilson, Robert; Shiboski, Stephen

2014-03-01

Anal cancer is more common in women than in men, yet little is known about the natural history of human papillomavirus (HPV) in women. The objective was to examine the natural history of anal HPV in heterosexual women. Young women participating in an HPV cohort study were seen at 4-month intervals for cervical and anal HPV testing. Time to clearance was estimated using the Kaplan-Meier approach; risks for persistence were assessed using Cox regression models. Seventy-five women (mean age, 23.5 ± 4.1 years) who tested positive for anal HPV were followed for a mean of 84.5 ± 44.9 months. By 3 years, 82.5% of anal non-16 high-risk (HR) HPV, 82.6% of low-risk (LR) HPV, and 76.2% of HPV-16 infections had cleared. By 3 years, only 36.4% of women had become negative for all HPV types. In the multivariable model, concurrent cervical HPV-16 (P < .001), weekly alcohol use (P = .015), anal touching during sex (P = .045), recent anal sex (P = .04), and no condom use during anal sex (P = .04) were associated with HPV-16 persistence. Greater number of new sex partners (P = .024) and condom use during vaginal sex (P = .003) were associated with clearance. Similar associations were found for clearance in all HR-HPV infections. Only concomitant cervical HPV was associated with non-16 HR-HPV persistence. The majority of anal HPV infections cleared within 3 years. HPV-16 infections were slower to clear than other HR-HPV infections, consistent with its role in anal cancer. Specific sexual behaviors were associated with persistence, suggesting that education and behavioral interventions may decrease persistence.

Natural History of Anal Human Papillomavirus Infection in Heterosexual Women and Risks Associated With Persistence

PubMed Central

Moscicki, Anna-Barbara; Ma, Yifei; Farhat, Sepideh; Jay, Julie; Hanson, Evelyn; Benningfield, Susanna; Jonte, Janet; Godwin-Medina, Cheryl; Wilson, Robert; Shiboski, Stephen

2014-01-01

Background. Anal cancer is more common in women than in men, yet little is known about the natural history of human papillomavirus (HPV) in women. The objective was to examine the natural history of anal HPV in heterosexual women. Methods. Young women participating in an HPV cohort study were seen at 4-month intervals for cervical and anal HPV testing. Time to clearance was estimated using the Kaplan-Meier approach; risks for persistence were assessed using Cox regression models. Results. Seventy-five women (mean age, 23.5 ± 4.1 years) who tested positive for anal HPV were followed for a mean of 84.5 ± 44.9 months. By 3 years, 82.5% of anal non-16 high-risk (HR) HPV, 82.6% of low-risk (LR) HPV, and 76.2% of HPV-16 infections had cleared. By 3 years, only 36.4% of women had become negative for all HPV types. In the multivariable model, concurrent cervical HPV-16 (P < .001), weekly alcohol use (P = .015), anal touching during sex (P = .045), recent anal sex (P = .04), and no condom use during anal sex (P = .04) were associated with HPV-16 persistence. Greater number of new sex partners (P = .024) and condom use during vaginal sex (P = .003) were associated with clearance. Similar associations were found for clearance in all HR-HPV infections. Only concomitant cervical HPV was associated with non-16 HR-HPV persistence. Conclusions. The majority of anal HPV infections cleared within 3 years. HPV-16 infections were slower to clear than other HR-HPV infections, consistent with its role in anal cancer. Specific sexual behaviors were associated with persistence, suggesting that education and behavioral interventions may decrease persistence. PMID:24368624

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

PubMed

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

2016-01-01

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

Overall human papilloma virus and types 16/18 prevalence in women with normal cervical cytology in Serbia: is it time for human papillomavirus testing and/or vaccination?

PubMed

Malisic, Emina; Brotto, Ksenija; Krivokuca, Ana; Cavic, Milena; Jankovic, Radmila

2014-01-01

Infection with high-risk human papilloma viruses (HR-HPV), especially types 16/18, is the main factor in cervical carcinogenesis. Although the incidence of cervical cancer in Serbia is among the highest ones in Europe, data about HPV infection are insufficient. The aim of this study was to investigate the presence of overall and HPV16/18 infections in women with healthy appearance and cytologically (Pap) normal cervix. The study was performed on women who participated in this cervical cancer screening pilot study. Cervical HPV infection was detected by GP5+/6+ PCR. HPV16/18 were detected by amplification of E7/E1 viral gene, respectively. In 350 women we got the following results: cytological abnormalities (10.3%); visible cervical changes (20.3%); previous precancerous lesion (2.3%); normal Pap and speculum finding without history of precancerous lesion (67.1%). In the last group overall HPV prevalence was 41.3%, with 10.5% HPV16 and 23.7% HPV18. The rate of multiple HPV16 plus HPV18 infections was 2.6%. HR-HPV16/18 comprised 31.6% of the total HPV positive participants. Owing to the high prevalence of overall and HPV16/18 infections in women with healthy appearance and cytologically normal cervix, we postulate that testing/ prophylaxis for these HR-HPV types could be introduced in cervical cancer screening and preventive programmes in Serbia.

HPV Testing from Dried Urine Spots as a Tool for Cervical Cancer Screening in Low-Income Countries.

PubMed

Frati, Elena Rosanna; Martinelli, Marianna; Fasoli, Ester; Colzani, Daniela; Bianchi, Silvia; Binda, Sandro; Olivani, Pierfranco; Tanzi, Elisabetta

2015-01-01

Nowadays, several screening strategies are available to prevent cervical cancer, but inadequate resources, sociocultural barriers, and sampling issues impede their success in low-income countries. To overcome these issues, this study aimed to evaluate the performance of human papillomavirus (HPV) testing from dried urine spots (DUS). Eighty-eight urine samples (including 56 HPV DNA positive specimens) were spotted on filter paper, dried, and stored in paper-bags. HPV DNA was detected from the DUS after 1 week and 4 weeks of storage using a polymerase chain reaction (PCR) assay. The sensitivity, specificity, and concordance of the DUS-based HPV test were evaluated by comparing the results with those of HPV testing on fresh urine samples as the gold standard. The sensitivity of the test was 98.21% (95% CI: 90.56-99.68) for DUS stored for 1 week and 96.42% (95% CI: 87.88-99.01) for DUS stored for 4 weeks. The specificity was 100% (95% CI: 89.28-100) at both time points. The concordance between DUS and fresh urine HPV testing was "almost perfect" using the κ statistic. These preliminary data suggest that a DUS-based assay could bypass sociocultural barriers and sampling issues and therefore could be a suitable, effective tool for epidemiological surveillance and screening programs, especially in low-income countries.

HPV Testing from Dried Urine Spots as a Tool for Cervical Cancer Screening in Low-Income Countries

PubMed Central

Olivani, Pierfranco

2015-01-01

Nowadays, several screening strategies are available to prevent cervical cancer, but inadequate resources, sociocultural barriers, and sampling issues impede their success in low-income countries. To overcome these issues, this study aimed to evaluate the performance of human papillomavirus (HPV) testing from dried urine spots (DUS). Eighty-eight urine samples (including 56 HPV DNA positive specimens) were spotted on filter paper, dried, and stored in paper-bags. HPV DNA was detected from the DUS after 1 week and 4 weeks of storage using a polymerase chain reaction (PCR) assay. The sensitivity, specificity, and concordance of the DUS-based HPV test were evaluated by comparing the results with those of HPV testing on fresh urine samples as the gold standard. The sensitivity of the test was 98.21% (95% CI: 90.56–99.68) for DUS stored for 1 week and 96.42% (95% CI: 87.88–99.01) for DUS stored for 4 weeks. The specificity was 100% (95% CI: 89.28–100) at both time points. The concordance between DUS and fresh urine HPV testing was “almost perfect” using the κ statistic. These preliminary data suggest that a DUS-based assay could bypass sociocultural barriers and sampling issues and therefore could be a suitable, effective tool for epidemiological surveillance and screening programs, especially in low-income countries. PMID:26180790

Human papilloma virus testing in oropharyngeal squamous cell carcinoma: what the clinician should know.

PubMed

Mirghani, Haïtham; Amen, Furrat; Moreau, Frederique; Guigay, Joel; Ferchiou, Malek; Melkane, Antoine E; Hartl, Dana M; Lacau St Guily, Jean

2014-01-01

High risk Human Papilloma virus (HR-HPV) associated oropharyngeal cancers are on the increase. Although, the scientific community is aware of the importance of Human Papilloma Virus (HPV) testing, there is no consensus on the assays that are required to reliably identify HR-HPV related tumors. A wide range of methods have been developed. The most widely used techniques include viral DNA detection, with polymerase chain reaction (PCR) or In Situ Hybridization, and p16 detected by immunohistochemistry. However, these tests provide different information and have their own specific limitations. In this review, we summarize these different techniques, in light of the recent literature. p16 Overexpression, which is an indirect marker of HPV infection, is considered by many head and neck oncologists to be the most important marker for patient stratification. We describe the frequent lack of concordance of this marker with other assays and the possible reasons for this. The latest developments in HPV testing are also reported, such as the RNAscope™ HPV test, and how they fit into the existing framework of techniques. HPV testing must not be considered in isolation, as there are important interactions with other parameters, such as tobacco exposure. This is an important and rapidly evolving field and is likely to become pivotal to staging and choice of treatment of oropharyngeal carcinoma in the future. Copyright © 2013 Elsevier Ltd. All rights reserved.

Human Papillomavirus Genotyping After Denaturation of Specimens for Hybrid Capture 2 Testing: Feasibility Study for the HPV Persistence and Progression Cohort†

PubMed Central

LaMere, Brandon J.; Kornegay, Janet; Fetterman, Barbara; Sadorra, Mark; Shieh, Jen; Castle, Philip E.

2009-01-01

Human papillomavirus (HPV) genotyping could be clinically useful, depending on the results of large, prospective studies like the HPV Persistence and Progression cohort. The cohort is based on genotyping and follow-up of Hybrid Capture-positive women at Kaiser Permanente, Northern California. HPV DNA testing by Hybrid Capture 2 requires denaturation with alkali, possibly damaging the DNA for optimal PCR-based genotyping. A feasibility study was conducted on paired aliquots of anonymized specimens from 100 women with low-grade intraepithelial lesion cytology. Test aliquots were left in denaturant for 10 or 18 hours at 4°C and then neutralized; comparison aliquots were not denatured but diluted to match the timing, temperature, concentration and salt conditions of the treated specimens. The masked aliquots were tested using a commercialized PCR-based assay that detects of 37 HPV genotypes. There was no overall effect of treatment on test positivity or number of types. HPV16 was marginally more likely to be detected in untreated versus treated aliquots (P = 0.09) but HPV45 was marginally more likely to be detected in treated than untreated aliquots (P = 0.07), suggesting that these differences represented chance (intra-test variability). It can be concluded that residual Hybrid Capture-positive specimens can be accurately genotyped by PCR after Hybrid Capture 2 processing. PMID:17673302

Beta-test Results for an HPV Information Web site: GoHealthyGirls.org – Increasing HPV Vaccine Uptake in the United States

PubMed Central

Nodulman, Jessica A.; Kong, Alberta S.; Wheeler, Cosette M.; Buller, David B.; Woodall, W. Gill

2014-01-01

A web site, GoHealthyGirls, was developed to educate and inform parents and their adolescent daughters about human papillomavirus (HPV) and HPV vaccines. This article provides an overview of web site development and content followed by the results of a beta-test of the web site. 63 New Mexican parents of adolescent girls tested the site. Results indicated that GoHealthyGirls was a functioning and appealing web site. During this brief educational intervention, findings suggest that the web site has the potential to increase HPV vaccine uptake. This research supports the Internet as a valuable channel to disseminate health education and information to diverse populations. PMID:25221442

Clinician and Parent Perspectives on Educational Needs for Increasing Adolescent HPV Vaccination.

PubMed

Widman, Christy A; Rodriguez, Elisa M; Saad-Harfouche, Frances; Twarozek, Annamaria Masucci; Erwin, Deborah O; Mahoney, Martin C

2018-04-01

Human papillomavirus (HPV)-related morbidity and mortality remain a significant public health burden despite the availability of HPV vaccines for cancer prevention. We engaged clinicians and parents to identify barriers and opportunities related to adolescent HPV vaccination within a focused geographic region. This mixed-method study design used an interviewer-administered semi-structured interview with clinicians (n = 52) and a written self-administered survey with similar items completed by parents (n = 54). Items focused on experiences, opinions, and ideas about HPV vaccine utilization in the clinical setting, family, and patient perceptions about HPV vaccination and potential future efforts to increase vaccine utilization. Quantitative items were analyzed using descriptive statistics, while qualitative content was analyzed thematically. Suggested solutions for achieving higher rates of HPV vaccination noted by clinicians included public health education, the removal of stigma associated with vaccines, media endorsements, and targeting parents as the primary focus of educational messages. Parents expressed the need for more information about HPV-related disease, HPV vaccines, vaccine safety, sexual concerns, and countering misinformation on social media. Results from this mixed-method study affirm that educational campaigns targeting both health care professionals and parents represent a key facilitator for promoting HPV vaccination; disease burden and cancer prevention emerged as key themes for this messaging.

Human papillomavirus DNA detected in breast milk.

PubMed

Sarkola, Marja; Rintala, Marjut; Grénman, Seija; Syrjänen, Stina

2008-06-01

Human papillomavirus (HPV) testing of 223 breast milk samples 3 days postpartum was performed with polymerase chain reaction, hybridization, and sequencing. HPV-16-DNA was detected in 4.0% of the samples. HPV carriage in the breast milk was not correlated with mother's oral or cervical HPV-status or the demographic data. Oral HPV-infection of the spouse at month 6 and 12 postpartum was statistically significantly associated with HPV carriage in the breast milk.

National HPV immunisation programme: knowledge and acceptance of mothers attending an obstetrics clinic at a teaching hospital, Kuala Lumpur.

PubMed

Ezat, Sharifa Wan Puteh; Hod, Rozita; Mustafa, Jamsiah; Mohd Dali, Ahmad Zailani Hatta; Sulaiman, Aqmar Suraya; Azman, Azlin

2013-01-01

Introduction of the HPV vaccine is a forefront primary prevention method in reducing the incidence of carcinogenic human papillomavirus (HPV) and cervical cancer. The Malaysia government has implemented the National HPV immunisation programme since 2010, supplying HPV vaccine free to targeted 13 year olds. This study aimed to explore the level of knowledge among mothers on cervical cancer, HPV, HPV vaccine and National HPV (NHPV) immunisation programme since its' implementation. It also assessed acceptance of mothers towards HPV vaccine being administered to their daughter, son or themselves. A cross sectional study was conducted on 155 respondents using self-administered questionnaires; conducted in December 2012 at the Obstetrics and Gynaecology Clinic in a teaching hospital in Kuala Lumpur. Respondents were selected using a multistage sampling technique. A response rate of 100% was obtained. Overall, 51.0% of mothers had good knowledge, with 55% having good knowledge of cervical cancer, 54.2% for both HPV and the National HPV immunisation programme and 51.0% for the HPV vaccine. Regression analyses showed that ethnicity was associated with knowledge on cervical cancer (p=0.003) while education was associated with knowledge on HPV (p=0.049). Three factors are associated with knowledge of the National HPV immunisation programme; ethnicity (p=0.017), mothers' education (p=0.0005) and number of children (p=0.020). The acceptance of HPV vaccine to be administered among daughter was the highest at 87.1%, followed by for mothers themselves at 73.5%, and the least is for sons 62.6%. This study found that the overall level of knowledge was moderate. Adequate information on cervical cancer, HPV, HPV vaccination and the National HPV immunisation programme should be provided to mothers in order to increase acceptance of the HPV vaccine which can reduce the disease burden in the future.

Testing for HPV as an objective measure for quality assurance in gynecologic cytology: positive rates in equivocal and abnormal specimens and comparison with the ASCUS to SIL ratio.

PubMed

Ko, Vincent; Nanji, Shabin; Tambouret, Rosemary H; Wilbur, David C

2007-04-25

Inappropriate use of the category of atypical squamous cells of undetermined significance (ASCUS) can result in overtreatment or undertreatment of patients, which may decrease the cost effectiveness of screening. Quality assurance tools, such as the ASCUS to squamous intraepithelial lesion ratio (ASCUS:SIL) and case review, are imperfect. High-risk HPV (hrHPV) testing is an objective test for a known viral carcinogen, and hrHPV may be more useful in monitoring the quality of ASCUS interpretations. hrHPV rates for cytologic diagnoses and patient age groups were calculated for a 2-year period. All hrHPV results for ASCUS and SIL over a 17-month period were analyzed by patient age group, over time, and by individual cytopathologist to compare hrHPV rates with the corresponding ASCUS:SIL. The hrHPV positive rate for SIL was >90%, and it was 32.6% for ASCUS. Stratification by patient age showed that approximately 50% of patients younger than 30 years and older than 70 years of age were hrHPV positive, whereas other patients had a lower rate ranging from 14% to 34%. The overall ASCUS:SIL was 1.42, and the overall hrHPV positive rate was 39.9%. Over time and by individual cytopathologist, the hrHPV rate performed similarly to the ASCUS:SIL. The analysis by patient age showed a high statistical correlation (R(2) = 0.9772) between the 2 methods. Despite differences between these techniques, the hrHPV rate closely recapitulates the ASCUS:SIL. When used together, the 2 methods can complement each other. The desirable hrHPV-positive range appears to be 40% to 50%; however, this may vary based on the patient population. The hrHPV rate is as quick and cost effective as determining the ASCUS:SIL. (c) 2007 American Cancer Society.

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

PubMed

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

2015-02-01

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

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

PubMed Central

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

2015-01-01

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

Is self-sampling to test for high-risk papillomavirus an acceptable option among women who have been treated for high-grade cervical intraepithelial neoplasia?

PubMed

Andersson, Sonia; Belkić, Karen; Mints, Miriam; Östensson, Ellinor

2018-01-01

Self-sampling to test for high risk human papilloma virus (HPV) is becoming an increasingly important component of cervical cancer screening. The aim of this observational study is to examine how women treated for high-grade cervical intraepithelial neoplasia (CIN) view HPV self-sampling. Invited to participate in the present study were patients who had undergone treatment of high-grade CIN (grade 2 or higher) and were followed-up at 6-months at the Karolinska University Hospital, Stockholm. The participants were instructed as to how to perform HPV self-sampling. Thereafter, the participants completed a questionnaire about HPV self-sampling and other cervical cancer screening methods, as well as about self-perceived risk of cervical cancer without regular gynecologic follow-up and about specific knowledge regarding HPV, CIN and cervical cancer. Altogether 479 women enrolled in this study. The participation rate was 96.6%. Nearly 75% of the participants stated they would consider performing the HPV self-sampling prior to their next gynecologic follow-up. Confidence in HPV self-sampling was a significant independent predictor of willingness to perform HPV self-sampling. However, confidence in HPV self-sampling was significantly lower than confidence in Papanicolaou smears and in HPV testing with samples collected by health professionals. Higher specific knowledge about HPV, CIN and cervical cancer was also a significant independent predictor of willingness to perform HPV self-sampling, as was having travelled longer distance to attend gynecologic follow-up. Participants with lower income and without completed university education expressed significantly higher confidence in HPV self-sampling and lower confidence in Papanicolaou smears than the other women. To the best of our knowledge, this is the first study to examine the views of women treated for high-grade CIN vis-à-vis HPV self-sampling. The latter is an acceptable option for the vast majority of this cohort of women.

Clinical progress of human papillomavirus genotypes and their persistent infection in subjects with atypical squamous cells of undetermined significance cytology: Statistical and latent Dirichlet allocation analysis

PubMed Central

Kim, Yee Suk; Lee, Sungin; Zong, Nansu; Kahng, Jimin

2017-01-01

The present study aimed to investigate differences in prognosis based on human papillomavirus (HPV) infection, persistent infection and genotype variations for patients exhibiting atypical squamous cells of undetermined significance (ASCUS) in their initial Papanicolaou (PAP) test results. A latent Dirichlet allocation (LDA)-based tool was developed that may offer a facilitated means of communication to be employed during patient-doctor consultations. The present study assessed 491 patients (139 HPV-positive and 352 HPV-negative cases) with a PAP test result of ASCUS with a follow-up period ≥2 years. Patients underwent PAP and HPV DNA chip tests between January 2006 and January 2009. The HPV-positive subjects were followed up with at least 2 instances of PAP and HPV DNA chip tests. The most common genotypes observed were HPV-16 (25.9%, 36/139), HPV-52 (14.4%, 20/139), HPV-58 (13.7%, 19/139), HPV-56 (11.5%, 16/139), HPV-51 (9.4%, 13/139) and HPV-18 (8.6%, 12/139). A total of 33.3% (12/36) patients positive for HPV-16 had cervical intraepithelial neoplasia (CIN)2 or a worse result, which was significantly higher than the prevalence of CIN2 of 1.8% (8/455) in patients negative for HPV-16 (P<0.001), while no significant association was identified for other genotypes in terms of genotype and clinical progress. There was a significant association between clearance and good prognosis (P<0.001). Persistent infection was higher in patients aged ≥51 years (38.7%) than in those aged ≤50 years (20.4%; P=0.036). Progression from persistent infection to CIN2 or worse (19/34, 55.9%) was higher than clearance (0/105, 0.0%; P<0.001). In the LDA analysis, using symmetric Dirichlet priors α=0.1 and β=0.01, and clusters (k)=5 or 10 provided the most meaningful groupings. Statistical and LDA analyses produced consistent results regarding the association between persistent infection of HPV-16, old age and long infection period with a clinical progression of CIN2 or worse. Therefore, LDA results may be presented as explanatory evidence during time-constrained patient-doctor consultations in order to deliver information regarding the patient's status. PMID:28587376

[Cervical cancer screening: Is active recruitment worth the effort?].

PubMed

Morales Martínez, Ángeles; Blanco Rodríguez, Lorena; Morales Martínez, Cristina; Tejuca Somoano, Sonia

2015-12-01

To determine the percentage of women who have had a Pap smear in the last 5 years, and the place where it was carried out. To detect cytological abnormalities and precursors of cervical cancer in un-screened or inadequately screened women and the prevalence of HPV-positive determinations. Cross sectional study. Natahoyo Health Centre, Gijón (Spain). Women aged 40-50 years living in the area and assigned to the Health Centre. The information was collected from databases, telephone and home surveys. There was active recruitment of unscreened women or inadequately screened in Primary Care as well as offering to perform cytology and HPV determination. Of the 1420 women aged 40 to 50 years, 1236 (87%) had cytology in the last 5 years, and 184 women (13%) had no screening or it was inadequate. Of these 184 women, 108 (58.7%) agreed to have cytology and HPV test performed. No high-grade cervical dysplasia was diagnosed. The prevalence of HPV-positive was 8.3%. In our population there is a high coverage of opportunistic screening for cervical cancer. The active recruitment of women who were not in the screening program was not useful. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

An Examination of HPV16 Natural Immunity in Men Who Have Sex with Men (MSM) in the HPV in Men (HIM) Study.

PubMed

Beachler, Daniel C; Pinto, Ligia A; Kemp, Troy J; Nyitray, Alan G; Hildesheim, Allan; Viscidi, Raphael; Schussler, John; Kreimer, Aimée R; Giuliano, Anna R

2018-04-01

Background: Evidence suggests that natural antibodies developed after HPV16 infection may protect some women but not men against subsequent HPV16 reacquisition. Less is known whether antibodies developed following HPV16 infection are protective among men who have sex with men (MSM). Methods: Four hundred seventy-five MSM from the Human Papillomavirus Infection in Men (HIM) study were tested for serum antibodies to HPV16 L1 using enzyme-linked immunosorbent assays, and for anal and genital HPV16 DNA using PCR consensus primer system (PGMY 09/11). Adjusted Cox regression was used to evaluate whether baseline HPV16 seropositivity impacts subsequent genital or anal HPV16 DNA. Results: The risk of subsequent genital HPV16 [aHR = 1.05, 95% confidence interval (CI) = 0.66-1.68] and anal HPV16 infections among MSM (aHR = 2.34, 95% CI = 0.92-5.98) was similar or nonsignificantly higher in HPV16-seropositive than HPV16-seronegative MSM. The risk of genital HPV16 was also similar between HPV16-seronegative and HPV16-seropositive MSM in the highest tertile of HPV16 antibody levels and when restricting to those with new sex partners during follow-up ( P > 0.20). Among the 118 MSM who were HPV16 seropositive, 90% remained HPV16 seropositive up to 4 years later. When tested together, MSM with the highest antibody titers (top tertile) had similar levels to females (mean = 130.3 vs. 134.5 EU/mL, P = 0.84). Conclusions: Despite years of HPV16 seropositivity persistence and antibody titers comparable with females, this study suggested no evidence of HPV16 natural antibodies protecting against subsequent genital or anal HPV16 infection in MSM. Impact: This could help partially explain the high incidence of genital and anal HPV16 infection and related anal cancer seen in middle-aged and older MSM. Cancer Epidemiol Biomarkers Prev; 27(4); 496-502. ©2018 AACR . ©2018 American Association for Cancer Research.

Head and neck second primary cancer rates in the human papillomavirus era: A population-based analysis.

PubMed

Diaz, Dayssy Alexandra; Reis, Isildinha M; Weed, Donald T; Elsayyad, Nagy; Samuels, Michael; Abramowitz, Matthew C

2016-04-01

Patients with head and neck cancer are at high risk for second primary malignancies. Human papillomavirus (HPV)-driven tumors are generally high-grade oropharyngeal cancers. We analyzed the incidence of second primary malignancy of the head and neck in patients with primary squamous cell carcinoma (SCC) of the head and neck and temporal trends in the HPV era. The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with SCC of the head and neck (range, 1973-2008). Cumulative incidence rates of second primary malignancy of the head and neck were compared based on competing risk analysis. A total of 104,639 cases were included in this study, of which 4616 patients had second primary malignancy of the head and neck. Oropharyngeal cancer incidence increased over time. Estimated incidence rate/10,000 person-years (105.5, 80.6, and 50.2 for 1973-1989, 1990-1999, and 2000-2008, respectively) and cumulative incidence rates (10-year rates of 6.68%, 5.72%, and 4.59% for 1973-1989, 1990-1999, and 2000-2008, respectively) of second primary malignancies of the head and neck for patients with oropharyngeal cancer decreased over time (p < .001). The second primary malignancy of the head and neck incidence rate was significantly lower in patients with high-grade oropharyngeal cancer from 2000 to 2008 (30.3 vs 65.5 and 54.6 from 1973-1989 and 1990-1999, respectively; p < .001). The incidence of second primary malignancy of the head and neck in patients with head and neck cancer has decreased over time. This is driven by lower rates in patients with high-grade oropharyngeal cancer, is temporally related with increases in HPV-associated oropharyngeal cancer, and suggests that incidence rates of second primary malignancy of the head and neck may be lower for HPV-associated cancer. © 2015 Wiley Periodicals, Inc. Head Neck 38: E873-E883, 2016. © 2015 Wiley Periodicals, Inc.

Eurogin 2016 Roadmap: how HPV knowledge is changing screening practice.

PubMed

Wentzensen, Nicolas; Arbyn, Marc; Berkhof, Johannes; Bower, Mark; Canfell, Karen; Einstein, Mark; Farley, Christopher; Monsonego, Joseph; Franceschi, Silvia

2017-05-15

Human papillomaviruses (HPVs) are the necessary cause of most cervical cancers, a large proportion of other anogenital cancers, and a subset of oropharyngeal cancers. The knowledge about HPV has led to development of novel HPV-based prevention strategies with important impact on clinical and public health practice. Two complementary reviews have been prepared following the 2015 Eurogin Conference to evaluate how knowledge about HPV is changing practice in HPV infection and disease control through vaccination and screening. This review focuses on screening for cervical and anal cancers in increasingly vaccinated populations. The introduction of HPV vaccines a decade ago has led to reductions in HPV infections and early cancer precursors in countries with wide vaccination coverage. Despite the high efficacy of HPV vaccines, cervical cancer screening will remain important for many decades. Many healthcare systems are considering switching to primary HPV screening, which has higher sensitivity for cervical precancers and allows extending screening intervals. We describe different approaches to implementing HPV-based screening efforts in different healthcare systems with a focus in high-income countries. While the population prevalence for other anogenital cancers is too low for population-based screening, anal cancer incidence is very high in HIV-infected men who have sex with men, warranting consideration of early detection approaches. We summarize the current evidence on HPV-based prevention of anal cancers and highlight important evidence gaps. © 2016 UICC.

The psychosocial burden of human papillomavirus related disease and screening interventions.

PubMed

Pirotta, M; Ung, L; Stein, A; Conway, E L; Mast, T C; Fairley, C K; Garland, S

2009-12-01

(i) To assess the psychosocial burden of testing for human papillomavirus (HPV) related genital disease or of a HPV-related diagnosis; (ii) to compare an instrument specifically designed to measure HPV-related psychosocial burden with other generic quality of life (QoL) instruments. A cross-sectional design. Researchers recruited women from outpatient clinics at a major tertiary women's hospital and a sexual health centre who completed surveys within 3 months of receiving 331 women, 18-45 years, who had experienced a normal cervical Papanicolaou (Pap) result, an abnormal Pap result, biopsy confirmed cervical intraepithelial neoplasia (CIN) or external genital warts (EGW). The HPV impact profile (HIP) designed to assess the psychosocial impact of HPV; two general health-related QoL surveys-the EuroQoL VAS and the Sheehan disability scale; and a HPV knowledge survey. Response rate was 78%. Significant psychosocial impacts were found for women screened for, or having a diagnosis of, HPV-related genital disease. The largest impact was in women with CIN 2/3 and EGW. This HPV-related psychosocial impact was most sensitively detected with the HIP. Relative to generic measures of QoL, the HIP provided insight into the full range of psychosocial impacts of HPV testing and diagnoses. Clinicians need to be aware of the potential psychosocial impact of testing for or diagnosing HPV-related genital disease, in particular CIN 2/3 and EGW. The HIP survey is a more sensitive measure of the psychosocial impact of HPV-related genital disease than generic QoL surveys.

Differences between African-American adolescent females with and without human papillomavirus infection.

PubMed

Seth, Puja; Wingood, Gina M; Diclemente, Ralph J; Crosby, Richard A; Salazar, Laura F; Rose, Eve S; Sales, Jessica M

2011-03-01

An important policy question is whether high-risk populations can be identified and prioritised for human papillomavirus (HPV) immunisation. Data collection included an audio computer-assisted survey interview and testing of Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, and HPV among 295 African-American adolescent females. The results indicated that 43.1% tested positive for HPV. Logistic regression analyses indicated that HPV prevalence was not associated with other sexually transmissible infections (prevalence ratio (PR)=0.85, 95% confidence interval (CI)=0.51-1.41), unprotected vaginal sex (PR=1.04, 95% CI=0.56-1.92), having sex with an older male partner (PR=1.12, 95% CI=0.64-1.96), and having a casual partner (PR=0.89, 95% CI=0.54-1.48). Additionally, t-tests indicated that HPV prevalence was not associated with frequency of vaginal sex (t=0.17, P=0.87), protected sex (t=-0.16, P=0.87), number of recent (t=0.40, P=0.69) or lifetime (t=1.45, P=0.15) sexual partners. However, those testing positive for HPV were younger (t=1.97, P=0.05) and reported current use of birth control pills (PR=2.38, 95% CI=1.00-5.63). It may not be possible to identify those with elevated risk of HPV acquisition. Thus, HPV vaccination, regardless of risk indicators, may be the most efficacious public health strategy.

HPV, Cervical Cancer and Pap Test Related Knowledge Among a Sample of Female Dental Students in India.

PubMed

Doshi, Dolar; Reddy, B Srikanth; Karunakar, P; Deshpande, Kopparesh

2015-01-01

The present study was designed to ascertain knowledge about HPV, cervical cancer (CC) and the Pap test among female dental students of Panineeya Institute of Dental Sciences and Hospital, Hyderabad, India. A self-administered questionnaire covering demographic details, knowledge relating to human papilloma virus (HPV) (8 items), cervical cancer (4 items) and the Pap smear (6 items) was employed. Responses were coded as "True, False and Don't Know". Mean and standard deviation (SD) for correct answers and levels of knowledge were determined. Based on the year of study, significant differences in knowledge of HPV were noted for questions on symptoms (p=0.01); transmission from asymptomatic partners (p=0.002); treatment with antibiotics (p=0.002); start of sexual activity (p=0.004); and recommended age for HPV vaccination (p=0.01). For knowledge regarding CC, significance was observed for the age group being affected (p=0.008) and symptoms of the disease in early stages (p=0.001). Indications for Pap smear tests like symptoms' of vaginal discharge (p=0.002), marital status (p=0.01) and women with children (p=0.02) had significant difference based on the year of study. Based on religion, transmission of HPV via pregnancy, HPV related diseases except CC and preventive measures except condom use and oral contraceptives showed significant differences. However, significant variation with religion was observed only for two preventive measures of CC (Pap test; p=0.004) and HPV vaccination (p=0.003). Likewise, only the frequency of Pap test showed a significant difference for religion (p=0.001). This study emphasizes the lack of awareness with regard to HPV, CC and screening with pap smear even among health professionals. Hence, regular health campaigns are essential to reduce the disease burden.

Immunization effects of a communication intervention to promote preteen HPV vaccination in primary care practices.

PubMed

Cates, Joan R; Crandell, Jamie L; Diehl, Sandra J; Coyne-Beasley, Tamera

2018-01-02

HPV vaccination at the recommended ages of 11-12 is highly effective yet has stalled well below the goal of 80% of the population. We evaluated a statewide practice-based communication intervention (tools: brochures, posters, online training for providers and resources for parents, video game for preteens) to persuade parents, preteens and providers to vaccinate against HPV. The 9-month intervention started May 1, 2015. We compared vaccine initiation and completion rates over three 9-month periods (baseline, intervention, post-intervention) between practices enrolled in the intervention and a comparable comparison group. All practices reported to the North Carolina Immunization Registry (NCIR) and had at least 100 11- and 12-year-olds who had not completed the HPV vaccine series. Of 175 eligible practices, the 14 intervention practices included 19,398 individuals and the 161 comparison practices included 127,896 individuals. An extended Cox model was used to test the intervention effect. The intervention had a significant effect on both initiation and completion during the intervention and post-intervention periods; the estimated hazard ratio (HR) for initiation was 1.17 (p = .004) during the intervention and 1.11 (p = .005) post-intervention. Likewise, completion during the intervention period was 17% higher in intervention practices, after controlling for baseline differences. This effect increased in the post-intervention period to 30% higher (p = .03). Individuals in the intervention practices were 17% more likely to initiate and complete HPV vaccination than in the comparison practices during the intervention period and the effect was sustained post-intervention. This intervention is promising for increasing rates of HPV vaccination at ages 11-12. Copyright © 2017 Elsevier Ltd. All rights reserved.

SurePath Specimens Versus ThinPrep Specimen Types on the COBAS 4800 Platform: High-Risk HPV Status and Cytology Correlation in an Ethnically Diverse Bronx Population.

PubMed

Naeem, R C; Goldstein, D Y; Einstein, Mark H; Ramos Rivera, G; Schlesinger, K; Khader, S N; Suhrland, M; Fox, A S

2017-08-01

To compare the cytologic preparations of 130 cervical specimens (from women of various ethnicities at high risk for human papillomavirus [HPV] infection) using the SurePath (SP) collection system with specimens gathered using the ThinPrep (TP) system, as processed on the Cobas 4800 analyzer, to determine which collection method more accurately identifies HPV infection. In our prospective study, specimens were collected from 130 women of various ethnicities residing in or near Bronx County, NY. The SP-collected specimen was first processed for cytologic findings; if clinical HPV testing was requested on that specimen, it was tested using Hybrid Capture II (HC2) methodology. We tested the remnant SP-collected cell concentrate using the Cobas analyzer. Then, the TP-collected and SP-collected specimens were tested in the same run on that analyzer, and the results were compared. We also compared the results with the concurrent cytologic findings. The results were concordant for overall HR-HPV status in 93.8% of cases. Also, a statistically significant lower cycle threshold value was observed with Cobas testing of specimen concentrates tested via the BD SurePath Pap Test (P = .001), suggesting higher sensitivity compared with specimens tested via the ThinPrep Pap Test. Cobas 4800 HPV testing of SP-collected specimen concentrates yields comparable results to TP-collected specimen concentrates. Based on the limited data that we derived, SP collection may be a more favorable methodology than TP collection for HPV testing of individuals at high risk in our ethnically diverse, urban patient population. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Artificial intelligence estimates the impact of human papillomavirus types in influencing the risk of cervical dysplasia recurrence: progress toward a more personalized approach.

PubMed

Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Leone Roberti Maggiore, Umberto; Taverna, Francesca; Lombardo, Claudia; Borghi, Chiara; Scaffa, Cono; Lorusso, Domenica; Raspagliesi, Francesco

2018-01-22

The objective of this study was to determine whether the pretreatment human papillomavirus (HPV) genotype might predict the risk of cervical dysplasia persistence/recurrence. Retrospective analysis of prospectively collected data of consecutive 5104 women who underwent the HPV-DNA test were matched with retrospective data of women undergoing either follow-up or medical/surgical treatment(s) for genital HPV-related infection(s). Artificial neuronal network (ANN) analysis was used in order to weight the importance of different HPV genotypes in predicting cervical dysplasia persistence/recurrence. ANN simulates a biological neuronal system from both the structural and functional points of view: like neurons, ANN acquires knowledge through a learning-phase process and allows weighting the importance of covariates, thus establishing how much a variable influences a multifactor phenomenon. Overall, 5104 women were tested for HPV. Among them, 1273 (25%) patients underwent treatment for HPV-related disorders. LASER conization and cervical vaporization were performed in 807 (59%) and 386 (30%) patients, respectively, and secondary cervical conization in 45 (5.5%). ANN technology showed that the most important genotypes predicting cervical dysplasia persistence/recurrence were HPV-16 (normalized importance: 100%), HPV-59 (normalized importance: 51.2%), HPV-52 (normalized importance: 47.7%), HPV-18 (normalized importance: 32.8%) and HPV-45 (normalized importance: 30.2%). The pretreatment diagnosis of all of those genotypes, except HPV-45, correlated with an increased risk of cervical dysplasia persistence/recurrence; the pretreatment diagnosis was also arrived at using standard univariate and multivariable models (P<0.01). Pretreatment positivity for HPV-16, HPV-18, HPV-52 and HPV-59 might correlate with an increased risk of cervical dysplasia persistence/recurrence after treatment. These data might be helpful during patients' counseling and to implement new vaccination programs.

HPV Prevalence in Multiple Anatomical Sites among Men Who Have Sex with Men in Peru

PubMed Central

Blas, Magaly M.; Brown, Brandon; Menacho, Luis; Alva, Isaac E.; Silva-Santisteban, Alfonso; Carcamo, Cesar

2015-01-01

Background Human Papilloma Virus (HPV) infection is the most common sexually transmitted viral infection worldwide. HPV is highly prevalent in sexually active men who have sex with men (MSM) and has been associated with anal cancer, penile cancer, and oropharyngeal cancer. Methods From March to September 2011, we conducted a cross-sectional study of HPV prevalence among MSM above age 18 years. Participants were recruited using respondent driven sampling at Clinica Cayetano Heredia. All participants provided anal, genital, and oral samples for HPV DNA testing, and blood for HIV and HPV antibody testing. Results A total of 200 MSM were recruited in the study. The mean age was 34 years (range 18–59 years, SD = 9.4) and101 participants were HIV negative (99 HIV positive). HPV 6/11/16/18 or quadrivalent HPV vaccine (HPV4) genotype seroprevalence among HIV negative and positive MSM was 64.3% (55%-75.9%) and 93.8% (87.6%-99.2%) respectively (p<0.001). HIV positivity was associated with a higher prevalence of HPV4 and HPV 16/18 DNA at external genital sites and the anal canal. HPV4 DNA prevalence at external genital sites among HIV negative and positive MSM was 14.9% and 28.7% (p = 0.02) respectively, at anal canal was 50.9% and 79.0% (p = 0.001), and at the oral cavity was 9.9% and 8.5% (p = 0.6). Conclusions HPV4 seroprevalence was high in our study among both HIV positives and negatives, with HPV DNA prevalence much lower, and the anal canal being the anatomical site with the highest HPV DNA prevalence. HPV prevention interventions are needed among MSM at high-risk for HIV infection. PMID:26437318

HPV Prevalence in Multiple Anatomical Sites among Men Who Have Sex with Men in Peru.

PubMed

Blas, Magaly M; Brown, Brandon; Menacho, Luis; Alva, Isaac E; Silva-Santisteban, Alfonso; Carcamo, Cesar

2015-01-01

Human Papilloma Virus (HPV) infection is the most common sexually transmitted viral infection worldwide. HPV is highly prevalent in sexually active men who have sex with men (MSM) and has been associated with anal cancer, penile cancer, and oropharyngeal cancer. From March to September 2011, we conducted a cross-sectional study of HPV prevalence among MSM above age 18 years. Participants were recruited using respondent driven sampling at Clinica Cayetano Heredia. All participants provided anal, genital, and oral samples for HPV DNA testing, and blood for HIV and HPV antibody testing. A total of 200 MSM were recruited in the study. The mean age was 34 years (range 18-59 years, SD = 9.4) and101 participants were HIV negative (99 HIV positive). HPV 6/11/16/18 or quadrivalent HPV vaccine (HPV4) genotype seroprevalence among HIV negative and positive MSM was 64.3% (55%-75.9%) and 93.8% (87.6%-99.2%) respectively (p<0.001). HIV positivity was associated with a higher prevalence of HPV4 and HPV 16/18 DNA at external genital sites and the anal canal. HPV4 DNA prevalence at external genital sites among HIV negative and positive MSM was 14.9% and 28.7% (p = 0.02) respectively, at anal canal was 50.9% and 79.0% (p = 0.001), and at the oral cavity was 9.9% and 8.5% (p = 0.6). HPV4 seroprevalence was high in our study among both HIV positives and negatives, with HPV DNA prevalence much lower, and the anal canal being the anatomical site with the highest HPV DNA prevalence. HPV prevention interventions are needed among MSM at high-risk for HIV infection.

Case-control study of genus-beta human papillomaviruses in plucked eyebrow hairs and cutaneous squamous cell carcinoma.

PubMed

Iannacone, Michelle R; Gheit, Tarik; Pfister, Herbert; Giuliano, Anna R; Messina, Jane L; Fenske, Neil A; Cherpelis, Basil S; Sondak, Vernon K; Roetzheim, Richard G; Silling, Steffi; Pawlita, Michael; Tommasino, Massimo; Rollison, Dana E

2014-05-01

Cutaneous human papillomaviruses (HPV) have been reported in cutaneous squamous cell carcinoma (SCC). We conducted a clinic-based case-control study to investigate the association between genus-beta HPV DNA in eyebrow hairs (EBH) and SCC. EBH from 168 SCC cases and 290 controls were genotyped for genus-beta HPV DNA. SCC tumors from a subset of cases (n = 142) were also genotyped. Viral load was determined in a subset of specimens positive for a single HPV type. Associations with SCC were estimated by odds ratios (OR) and 95% confidence intervals (CI) adjusted for age and sex using logistic regression. Statistical tests were two-sided. EBH DNA prevalence was greater in cases (87%) than controls (73%) (p < 0.05), and the association with SCC increased with the number of HPV types present, (≥ 4 types vs. HPV-negative: OR = 2.02, 95% CI = 1.07-3.80; p(trend) = 0.02). Type-specific associations were observed between SCC and DNA in EBH for HPV23 (OR = 1.90, 95% CI = 1.10-3.30) and HPV38 (OR = 1.84, 95% CI = 1.04-3.24). Additionally, when compared with the controls, the DNA prevalence in EBH was significantly higher among cases for 11 of the 25 genus-beta types tested, when accounting for DNA for the same HPV type in the tumor (ORs = 3.44-76.50). Compared to controls, the mean viral DNA load in EBH among the selected cases was greater for HPV5, HPV8 and HPV24, but lower for HPV38. SCC cases were more likely than controls to have HPV DNA+ EBH for single and multiple HPV types, providing additional support for the potential role of genus-beta HPV infections in SCC development. © 2013 UICC.

High Prevalence of Anal Canal High-Risk Human Papillomavirus Infection in Patients With Crohn's Disease.

PubMed

Vuitton, Lucine; Jacquin, Elise; Parmentier, Anne-Laure; Crochet, Elise; Fein, Francine; Dupont-Gossart, Anne-Claire; Plastaras, Laurianne; Bretagne, Charles-Henri; Mauny, Frédéric; Koch, Stéphane; Prétet, Jean-Luc; Mougin, Christiane; Valmary-Degano, Séverine

2018-03-15

The increasing incidence of anal canal carcinomas requires better knowledge on anal human papillomavirus (HPV) infection. We aimed to assess anal canal HPV infection prevalence and risk factors among patients seen at a gastroenterology department in France. We analyzed anal tissue samples collected from 469 consecutive patients (median age 54 years, 52% women), including 112 who received immunosuppressant therapies and 101 with inflammatory bowel disease (70 with Crohn's disease), who underwent colonoscopy examinations from April 1, 2012 to April 30, 2015. HPV was detected and genotyped using the INNO-LiPA assay, and we collected medical and demographic data from all subjects. Risk factors for any HPV, high-risk HPV (HR-HPV) and HPV16 infection were assessed by bivariate and multivariate analysis. The primary outcomes association of HR-HPV or HPV16 with medical and demographic features. We detected HPV DNA in anal tissues from 34% of the subjects and HR-HPV in 18%. HPV16 was the most prevalent genotype (detected in 7%), followed by HPV51, HPV52, and HPV39. HR-HPV was detected in a significantly higher proportion of samples from women (23.1%) than men (12.8%) (P = .0035); HR-HPV and HPV16 were detected in a significantly higher proportion of patients with Crohn's disease (30.0%) than without (18.1%) (P = .005). Female sex, history of sexually transmitted disease, lifetime and past year-number of sexual partners, active smoking, and immunosuppressive therapies were independent risk factors for anal HR-HPV infection in multivariate analysis. One third of patients who underwent colonoscopy at a gastroenterology department were found to have anal canal HPV infection. We detected HR-HPV infection in almost 20% of patients and in a significantly higher proportion of patients with Crohn's disease than without. Increasing our knowledge of HPV infection of anal tissues could help physicians identify populations at risk and promote prophylaxis with vaccination and adequate screening. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Differential effects of human papillomavirus type 6, 16, and 18 DNAs on immortalization and transformation of human cervical epithelial cells

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

Pecoraro, G.; Morgan, D.; Defendi, V.

1989-01-01

The human papillomaviruses (HPVs) are associated with specific benign and malignant lesions of the skin and mucosal epithelia. Cloned viral DNAs from HPV types 6b, 16, and 18 associated with different pathological manifestations of genital neoplasia in vivo were introduced into primary human cervical epithelial cells by electroporation. Cells transfected with HPV16 or HPV18 DNA acquired indefinite lifespans, distinct morphological alterations, and anchorage-independent growth (HPV18), and contain integrated transcriptionally active viral genomes. HPV6b or plasmid electroporated cells senesced at low passage. The alterations in growth and differentiation of the cells appear to reflect the progressive oncogenic processes that result inmore » cervical carcinoma in vivo.« less

Age-Specific Prevalence of and Risk Factors for Anal Human Papillomavirus (HPV) among Men Who Have Sex with Women and Men Who Have Sex with Men: The HPV in Men (HIM) Study

PubMed Central

Carvalho da Silva, Roberto J.; Baggio, Maria Luiza; Lu, Beibei; Smith, Danélle; Abrahamsen, Martha; Papenfuss, Mary; Villa, Luisa L.; Lazcano-Ponce, Eduardo; Giuliano, Anna R.

2011-01-01

Background. An increasing incidence of anal cancer among men suggests a need to better understand anal canal human papillomavirus (HPV) infection among human immunodeficiency virus–negative men. Methods. Genotyping for HPV was conducted on cells from the anal canal among men who have sex with women (MSW) and men who have sex with men (MSM), aged 18–70 years, from Brazil, Mexico, and the United States. Factors associated with anal HPV infection were assessed using multivariable logistic regression. Results. The prevalence of any HPV type and oncogenic HPV types did not differ by city. Anal canal HPV prevalence was 12.2% among 1305 MSW and 47.2% among 176 MSM. Among MSW, reporting a lifetime number of ≥10 female sex partners, a primary sexual relationship <1 year in duration, and a prior hepatitis B diagnosis were independently associated with detection of any anal HPV in multivariable analysis. Among MSM, a younger age, reporting ≥2 male anal sex partners in the past 3 months, and never using a condom for anal sex in the past 6 months were independently associated with detection of any anal HPV in multivariable analysis. Conclusions. Number of sex partners was associated with anal HPV infection in both MSW and MSM. Anal HPV infection in men may be mediated by age, duration of sexual relationship, and condom use. PMID:21148496

Combined effects of smoking and HPV16 in oropharyngeal cancer

PubMed Central

Anantharaman, Devasena; Muller, David C; Lagiou, Pagona; Ahrens, Wolfgang; Holcátová, Ivana; Merletti, Franco; Kjærheim, Kristina; Polesel, Jerry; Simonato, Lorenzo; Canova, Cristina; Castellsague, Xavier; Macfarlane, Tatiana V; Znaor, Ariana; Thomson, Peter; Robinson, Max; Conway, David I; Healy, Claire M; Tjønneland, Anne; Westin, Ulla; Ekström, Johanna; Chang-Claude, Jenny; Kaaks, Rudolf; Overvad, Kim; Drogan, Dagmar; Hallmans, Göran; Laurell, Göran; Bueno-de-Mesquita, HB; Peeters, Petra H; Agudo, Antonio; Larrañaga, Nerea; Travis, Ruth C; Palli, Domenico; Barricarte, Aurelio; Trichopoulou, Antonia; George, Saitakis; Trichopoulos, Dimitrios; Quirós, J Ramón; Grioni, Sara; Sacerdote, Carlotta; Navarro, Carmen; Sánchez, María-José; Tumino, Rosario; Severi, Gianluca; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Francoise; Panico, Salvatore; Weiderpass, Elisabete; Lund, Eiliv; Gram, Inger T; Riboli, Elio; Pawlita, Michael; Waterboer, Tim; Kreimer, Aimée R; Johansson, Mattias; Brennan, Paul

2016-01-01

Abstract Background: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood. Methods: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multi-centre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression. Results: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer. Conclusions: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer. PMID:27197530

Natural history of progression of HPV infection to cervical lesion or clearance: analysis of the control arm of the large, randomised PATRICIA study.

PubMed

Jaisamrarn, Unnop; Castellsagué, Xavier; Garland, Suzanne M; Naud, Paulo; Palmroth, Johanna; Del Rosario-Raymundo, Maria Rowena; Wheeler, Cosette M; Salmerón, Jorge; Chow, Song-Nan; Apter, Dan; Teixeira, Julio C; Skinner, S Rachel; Hedrick, James; Szarewski, Anne; Romanowski, Barbara; Aoki, Fred Y; Schwarz, Tino F; Poppe, Willy A J; Bosch, F Xavier; de Carvalho, Newton S; Germar, Maria Julieta; Peters, Klaus; Paavonen, Jorma; Bozonnat, Marie-Cecile; Descamps, Dominique; Struyf, Frank; Dubin, Gary O; Rosillon, Dominique; Baril, Laurence

2013-01-01

The control arm of PATRICIA (PApilloma TRIal against Cancer In young Adults, NCT00122681) was used to investigate the risk of progression from cervical HPV infection to cervical intraepithelial neoplasia (CIN) or clearance of infection, and associated determinants. Women aged 15-25 years were enrolled. A 6-month persistent HPV infection (6MPI) was defined as detection of the same HPV type at two consecutive evaluations over 6 months and clearance as ≥2 type-specific HPV negative samples taken at two consecutive intervals of approximately 6 months following a positive sample. The primary endpoint was CIN grade 2 or greater (CIN2+) associated with the same HPV type as a 6MPI. Secondary endpoints were CIN1+/CIN3+ associated with the same HPV type as a 6MPI; CIN1+/CIN2+/CIN3+ associated with an infection of any duration; and clearance of infection. The analyses included 4825 women with 16,785 infections (3363 women with 6902 6MPIs). Risk of developing a CIN1+/CIN2+/CIN3+ associated with same HPV type as a 6MPI varied with HPV type and was significantly higher for oncogenic versus non-oncogenic types. Hazard ratios for development of CIN2+ were 10.44 (95% CI: 6.96-15.65), 9.65 (5.97-15.60), 5.68 (3.50-9.21), 5.38 (2.87-10.06) and 3.87 (2.38-6.30) for HPV-16, HPV-33, HPV-31, HPV-45 and HPV-18, respectively. HPV-16 or HPV-33 6MPIs had ~25-fold higher risk for progression to CIN3+. Previous or concomitant HPV infection or CIN1+ associated with a different HPV type increased risk. Of the different oncogenic HPV types, HPV-16 and HPV-31 infections were least likely to clear. Cervical infections with oncogenic HPV types increased the risk of CIN2+ and CIN3+. Previous or concomitant infection or CIN1+ also increased the risk. HPV-16 and HPV-33 have by far the highest risk of progression to CIN3+, and HPV-16 and HPV-31 have the lowest chance of clearance.

Natural History of Progression of HPV Infection to Cervical Lesion or Clearance: Analysis of the Control Arm of the Large, Randomised PATRICIA Study

PubMed Central

Jaisamrarn, Unnop; Castellsagué, Xavier; Garland, Suzanne M.; Naud, Paulo; Palmroth, Johanna; Del Rosario-Raymundo, Maria Rowena; Wheeler, Cosette M.; Salmerón, Jorge; Chow, Song-Nan; Apter, Dan; Teixeira, Julio C.; Skinner, S. Rachel; Hedrick, James; Szarewski, Anne; Romanowski, Barbara; Aoki, Fred Y.; Schwarz, Tino F.; Poppe, Willy A. J.; Bosch, F. Xavier; de Carvalho, Newton S.; Germar, Maria Julieta; Peters, Klaus; Paavonen, Jorma; Bozonnat, Marie-Cecile; Descamps, Dominique; Struyf, Frank; Dubin, Gary O.; Rosillon, Dominique; Baril, Laurence

2013-01-01

Background The control arm of PATRICIA (PApillomaTRIal against Cancer In young Adults, NCT00122681) was used to investigate the risk of progression from cervical HPV infection to cervical intraepithelial neoplasia (CIN) or clearance of infection, and associated determinants. Methods and Findings Women aged 15-25 years were enrolled. A 6-month persistent HPV infection (6MPI) was defined as detection of the same HPV type at two consecutive evaluations over 6 months and clearance as ≥2 type-specific HPV negative samples taken at two consecutive intervals of approximately 6 months following a positive sample. The primary endpoint was CIN grade 2 or greater (CIN2+) associated with the same HPV type as a 6MPI. Secondary endpoints were CIN1+/CIN3+ associated with the same HPV type as a 6MPI; CIN1+/CIN2+/CIN3+ associated with an infection of any duration; and clearance of infection. The analyses included 4825 women with 16,785 infections (3363 womenwith 6902 6MPIs). Risk of developing a CIN1+/CIN2+/CIN3+ associated with same HPV type as a 6MPI varied with HPV type and was significantly higher for oncogenic versus non-oncogenic types. Hazard ratios for development of CIN2+ were 10.44 (95% CI: 6.96-15.65), 9.65 (5.97-15.60), 5.68 (3.50-9.21), 5.38 (2.87-10.06) and 3.87 (2.38-6.30) for HPV-16, HPV-33, HPV-31, HPV-45 and HPV-18, respectively. HPV-16 or HPV-33 6MPIs had ~25-fold higher risk for progression to CIN3+. Previous or concomitant HPV infection or CIN1+ associated with a different HPV type increased risk. Of the different oncogenic HPV types, HPV-16 and HPV-31 infections were least likely to clear. Conclusions Cervical infections with oncogenic HPV types increased the risk of CIN2+ and CIN3+. Previous or concomitant infection or CIN1+ also increased the risk. HPV-16 and HPV-33 have by far the highest risk of progression to CIN3+, and HPV-16 and HPV-31 have the lowest chance of clearance. PMID:24260180

Human papilloma virus (HPV) genotypes prevalence in a region of South Italy (Apulia).

PubMed

Coscia, Maria Franca; Monno, Rosa; Ballini, Andrea; Mirgaldi, Rosanna; Dipalma, Gianna; Pettini, Francesco; Cristallo, Vincenzo; Inchingolo, Francesco; Foti, Caterina; de Vito, Danila

2015-01-01

Since human papillomavirus (HPV) is the central casual factor in cervical cancer, understanding the epidemiology and geographical area distribution of the most prevalent HPV genotypes constitutes an important step towards development of strategies of prevention. The aim of this study was to investigate the prevalence of HPV infection and to determine HPV types distribution among 822 HPV positive women and some sexual male partners in Apulia (Italy). HPV DNA detection and genotyping was performed by nested-PCR for the L1 region and reverse line blot hybridization allowing the specific detection of 24 HPV genotyping both high risk (HR) and low risk (LR). The most prevalent HPV genotypes were HPV 16 (35%), HPV 31 (16%) HPV 6 (9%), HPV 58 and 66 (7%), followed by HPV 33 (6%), HPV 18 and 56 (4%), HPV 70 and 45 (3%), HPV 53 and 11 (2%). Currently 1.5% of tested specimens remained unclassified. Multiple infections with at last two different high- risk HPV genotypes were observed in 10% of specimens. This finding adds knowledge to HPV epidemiological investigation, and addresses further studies aimed to consider public health for identifying groups at risk for cervical cancer.

Impact of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle vaccine in a sexually active population of North American women.

PubMed

Barr, Eliav; Gause, Christine K; Bautista, Oliver M; Railkar, Radha A; Lupinacci, Lisa C; Insinga, Ralph P; Sings, Heather L; Haupt, Richard M

2008-03-01

The purpose of this study was to inform policy regarding human papillomavirus (HPV) vaccination in North America. We measured the clinical impact of HPV-6/-11/-16/-18 vaccination in North American women. The study enrolled 21,954 women, the majority aged 16-25, across 5 studies of a quadrivalent HPV vaccine or its HPV-16 vaccine prototype. The North American subjects (n = 5996) were pooled from these trials, and the prevalence of HPV-6/-11/-16/-18 exposure was measured. The impact of vaccination on the burden of anogenital HPV lesions in an intention-to-treat population (regardless of enrollment HPV status) was calculated. At enrollment, the median age was 20 years; 13% of the women had had a Papanicolaou test abnormality, and 76% of the women had negative tests results for all 4 vaccine HPV types. With approximately 3 years of follow-up evaluations in the intention-to-treat population (regardless of enrollment HPV status), vaccination reduced the rate of HPV-16- and -18-related precancers and HPV-6/-11/-16/-18-related genital lesions by 66.4% (95% CI, 42.7%-81.1%) and 57.7% (95% CI, 27.3%-76.3%), respectively. The administration of HPV vaccine to sexually active North American women reduced the burden of HPV-6/-11/-16/-18-related disease. Catch-up vaccination programs in this population are warranted.

Prevalence of human papillomavirus infection among Iranian women using COBAS HPV DNA testing.

PubMed

Jamdar, Farzane; Farzaneh, Farah; Navidpour, Fariba; Younesi, Sarang; Balvayeh, Payam; Hosseini, Maryamsadat; Ghodssi-Ghasemabadi, Robabeh

2018-01-01

Persistent infection with High Risk Human Papillomavirus (HR HPV) typesplaysamajor role in the development of cervical cancer. Therefore, the detection of HR HPV types is an essential part of cervical cancer screening. The aim of this study was to estimate the prevalence of HR HPV infection among healthy women undergoing routine cervical cancer screening in Iran. In this cross-sectional study,the results of HPV DNA typing in 2453 normal Iranian womenwhowere referred for routine cervical cancer screening from September 2015 to March 2017 were analyzed. Participants were screened using COBAS assay for HPV DNA typing and liquid based cytology. A total of 2453 healthy sexually active women were included in this study. The mean age was 35.1 ± 8.08 years. The overall prevalence of HR HPV infection was 10.3%. HPV16 was found in 73 (3%) women. The prevalence of HPV18 and other HR HPV typeswere 16(0.7%) and166 (8.2%),respectively. Approximately, 5% of the study population had an abnormal cervical cytology (ASCUS or worse), of whom 34% were infected by HR HPV. The prevalence of HR HPV infection among Iranian women has increased in the recent years which indicates the need for public education and health planning toprevent this cancer through vaccination and early diagnosis using screening tests.HPV DNA typing, diagnosisand the distribution of prevalent genotypes should be considered in the development of comprehensive cervical cancer prevention programs in Iran.

Dynamics of HPV viral loads reflect the treatment effect of photodynamic therapy in genital warts.

PubMed

Hu, Zhili; Liu, Lishi; Zhang, Wenjing; Liu, Hui; Li, Junpeng; Jiang, Lifen; Zeng, Kang

2018-03-01

Photodynamic therapy (PDT) has demonstrated good clinical cure rates and low recurrence rates in the treatment of genital warts. Human papillomavirus (HPV) genotypes and viral load assays can reflect the status of persistent or latent infection and serve as a predictor of infection clearance. Specimens from 41 patients with HPV infection were obtained, and the HPV genotypes and viral load were analyzed using real-time polymerase chain reaction (PCR) assays. Traditional treatment, such as radiofrequency, microwave, or surgical therapy, was used to remove the visible lesions, and then PDT treatment was performed every week. HPV DNA testing was performed at every patient visit and the frequency of PDT treatment was determined by changes in HPV viral loads. HPV viral loads decreased significantly after PDT treatment. There were significant differences in HPV viral loads between pretherapy and three or six rounds of PDT treatment. Significant differences were also observed between single and multiple type HPV infection after six rounds of PDT treatment. Patients with single type HPV infection had significantly higher rates of negative HPV DNA test results, as compared with patients with multiple infections after six rounds of PDT treatment; however, there was no difference in recurrence rates between the two groups. Dynamic monitoring of HPV genotypes and viral loads can be used to guide PDT treatment and indicate PDT treatment efficacy in eliminating HPV. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevalence of and risk factors for oral human papillomavirus among young women in Costa Rica.

PubMed

Lang Kuhs, Krystle A; Gonzalez, Paula; Struijk, Linda; Castro, Felipe; Hildesheim, Allan; van Doorn, Leen-Jan; Rodriguez, Ana Cecilia; Schiffman, Mark; Quint, Wim; Lowy, Douglas R; Porras, Carolina; Delvecchio, Corey; Katki, Hormuzd A; Jimenez, Silvia; Safaeian, Mahboobeh; Schiller, John; Solomon, Diane; Wacholder, Sholom; Herrero, Rolando; Kreimer, Aimée R

2013-11-15

Little is known about the epidemiology of oral human papillomavirus (HPV) in Latin America. Women (N = 5838) aged 22-29 in the control and vaccine arms of an HPV-16/18 vaccine trial in Costa Rica had oral, cervical, and anal specimens collected. Samples were tested for alpha mucosal HPV types (SPF10/LiPA25 version 1); a subset of oral samples (n = 500) was tested for cutaneous HPV types in the genera alpha, beta, gamma, mu, and nu. In the control arm (n = 2926), 1.9% of women had an oral alpha mucosal HPV detected, 1.3% had carcinogenic HPV, and 0.4% had HPV-16; similar patterns for non-16/18 HPV types were observed in the vaccine arm. Independent risk factors for any oral alpha mucosal HPV among women in the control arm included marital status (adjusted odds ratio [AOR], 3.2; 95% confidence interval [CI], 1.8-5.7 for single compared to married/living as married), number of sexual partners (AOR, 2.4; 95% CI, 1.0-6.1 for ≥4 partners compared to 0-1 partners), chronic sinusitis (AOR, 3.1; 95% CI, 1.5-6.7), and cervical HPV infection (AOR, 2.6; 95% CI, 1.4-4.6). Detection of beta HPV was common (18.6%) and not associated with sexual activity. Unlike cutaneous HPV types, alpha mucosal HPV types were uncommon in the oral region and were predominately associated with sexual behavior. Clinical Trials Registration. NCT00128661.

Incarcerated women's HPV awareness, beliefs, and experiences.

PubMed

Pankey, Tyson; Ramaswamy, Megha

2015-01-01

The purpose of this paper is to explore incarcerated women's awareness, beliefs, and experiences with human papillomavirus (HPV) infection and vaccination. Researchers conducted focus groups with 45 incarcerated women in an urban Midwestern US jail to assess how women talked about their Papanicolaou (Pap) test screening and abnormal Pap test follow-up experiences. Some focus group questions specifically assessed individual awareness, beliefs, and experiences with HPV infection and vaccination. Based on these data, the authors described participants' awareness of HPV, as well as used open coding to ultimately extract themes related to beliefs and experiences with HPV infection and vaccine. While all 45 participants reported experiencing an abnormal Pap test event within the last five years, only two-thirds of participants (n=30) reported having heard of the HPV infection. Several themes emerged from the analysis of the data: the women's beliefs about cause and severity of HPV; frustration with age requirements of the vaccine; varied experiences with vaccinations for themselves and their children; the impact of media exposure on knowledge; and desire for more HPV infection and vaccine information. Incarcerated women's awareness and limited experiences with HPV infection and vaccination may be a barrier to adequate screening and cervical cancer prevention. This study has implications for the development of cervical health education for this high-risk group of women, who are four to five times as likely to have cervical cancer as non-incarcerated women.

Correlation of human papilloma virus with oral squamous cell carcinoma in Chinese population.

PubMed

Zhou, Jingping; Tao, Detao; Tang, Daofang; Gao, Zhenlin

2015-01-01

Previous studies indicated that oral squamous cell carcinomas (OSCC) might be related to human papilloma virus (HPV) infection. However, the relationship between OSCC in a Chinese population and oral HPV infection is still unclear. In this study, we evaluate the relationship of OSCC with HPV infection in a Chinese population via a meta-analysis. The reports on HPV and OSCC in a Chinese population published between January, 1994, and October, 2015 were retrieved via CNKI/WANFANG/pubmed databases. According to the inclusion criteria, we selected 26 eligible case-control studies. After testing the heterogeneity of the studies by the Cochran Q test, the meta-analyses for HPV and HPV16 were performed using the random effects model. Quantitative meta-analyses showed that, compared with normal oral mucosa the combined odds ratio of OSCC with HPV infection were 1.98 (95% CI: 1.34-2.92). The test for overall effect showed that the P value was less than 0.05 (Z = 3.46). Forest plot analyses were seen in Figures 2 and 3. Publication bias and bias risk analysis using RevMan 5.3 software were measured indicators of the graphics of the basic symmetry. High incidences of HPV infection were found in the samples of Chinese OSCC. For the Chinese population, HPV infection elevates the risk of OSCC tumorigenesis.

Human papillomavirus mRNA and DNA testing in women with atypical squamous cells of undetermined significance: A prospective cohort study.

PubMed

Thomsen, Louise T; Dehlendorff, Christian; Junge, Jette; Waldstrøm, Marianne; Schledermann, Doris; Frederiksen, Kirsten; Kjaer, Susanne K

2016-10-15

In this prospective cohort study, we compared the performance of human papillomavirus (HPV) mRNA and DNA testing of women with atypical squamous cells of undetermined significance (ASC-US) during cervical cancer screening. Using a nationwide Danish pathology register, we identified women aged 30-65 years with ASC-US during 2005-2011 who were tested for HPV16/18/31/33/45 mRNA using PreTect HPV-Proofer (n = 3,226) or for high-risk HPV (hrHPV) DNA using Hybrid Capture 2 (HC2) (n = 9,405) or Linear Array HPV-Genotyping test (LA) (n = 1,533). Women with ≥1 subsequent examination in the register (n = 13,729) were followed for up to 9.5 years for high-grade cervical intraepithelial neoplasia (CIN) or cancer. After 3 years' follow-up, mRNA testing had higher specificity for CIN3 or worse (CIN3+) than HC2 testing (88.1% [95% confidence interval (CI): 86.8-89.6%] versus 59.3% [95% CI: 58.1-60.4%]) and higher positive predictive value (PPV) (38.2% [95% CI: 33.8%-43.1%] versus 19.5% [95% CI: 17.8-20.9%]). However, the sensitivity of mRNA testing was lower than that of HC2 testing (66.7% [95% CI: 59.3-74.5%] versus 97.0% [95% CI: 95.5-98.4%]), and women testing mRNA negative had higher 3-year risk for CIN3+ than those testing HC2 negative (3.2% [95% CI: 2.2-4.2%] versus 0.5% [95% CI: 0.3-0.7%]). Patterns were similar after 18 months and 5 years'; follow-up; for CIN2+ and cancer as outcomes; across all age groups; and when comparing mRNA testing to hrHPV DNA testing using LA. In conclusion, the HPV16/18/31/33/45 mRNA test is not optimal for ASC-US triage due to its low sensitivity and the substantial risk for precancer following a negative test. © 2016 UICC.

A patient-centered approach to counseling patients with head and neck cancer undergoing human papillomavirus testing: a clinician's guide.

PubMed

Chu, Amy; Genden, Eric; Posner, Marshall; Sikora, Andrew

2013-01-01

The International Agency for Research on Cancer and the National Cancer Institute have acknowledged human papillomavirus (HPV)-16 as an independent risk factor for oropharyngeal cancer (OPC). HPV-positive oropharyngeal cancer (HPVOPC) is a sexually transmitted entity that is on the rise; within the next 10 years, the annual number of HPV-associated OPC cases is projected to exceed the annual number of cervical cancer cases in the United States. Recognition of HPV status in OPC has broad implications beyond the traditional oncological concerns of timely diagnosis, accurate staging, and appropriate treatment of cancer patients. The National Comprehensive Cancer Network recommends testing the tumor site for HPV-status during OPC management; it is likely this will become a standard component of care for patients with high-probability tumors of the oropharynx. As the practice of HPV testing becomes more common, it behooves providers to be able to adequately address the concerns of patients with HPVOPC. Although there are currently few relevant studies focusing on this population, existing literature on HPV-infected women and patients with cervical cancer strongly supports the concept that patients with HPVOPC need education to optimally address concerns such as self-blame, guilt, intimacy, and interpersonal relationships. When HPV testing is done, it should be accompanied by evidence-driven and patient-centered counseling to best minimize negative psychosocial outcomes and ensure optimum health promotion. Based on the current state of the literature, this article is intended to be a reference for physicians to effectively manage psychosocial outcomes when diagnosing patients with HPV-associated OPC.

Incidence and Human Papillomavirus (HPV) Type Distribution of Genital Warts in a Multinational Cohort of Men: The HPV in Men Study

PubMed Central

Anic, Gabriella M.; Lee, Ji–Hyun; Stockwell, Heather; Rollison, Dana E.; Wu, Yougui; Papenfuss, Mary R.; Villa, Luisa L.; Lazcano-Ponce, Eduardo; Gage, Christine; Silva, Roberto José C.; Baggio, Maria L.; Quiterio, Manuel; Salmerón, Jorge; Abrahamsen, Martha

2011-01-01

Background. Data on the natural history of human papillomavirus (HPV)–related genital warts (GWs) in men are sparse. We described the distribution of HPV types in incident GWs and estimated GW incidence and time from type-specific incident HPV infections to GW detection in a multinational cohort of men aged 18–70 years. Methods. Participants included 2487 men examined for GWs and tested for HPV every 6 months and followed up for a median of 17.9 months. Samples were taken from 112 men with incident GWs to test for HPV DNA by polymerase chain reaction. Results. Incidence of GWs was 2.35 cases per 1000 person-years, with highest incidence among men aged 18–30 years (3.43 cases per 1000 person-years). HPV 6 (43.8%), HPV 11 (10.7%), and HPV 16 (9.8%) were the genotypes most commonly detected in GWs. The 24-month cumulative incidence of GWs among men with incident HPV 6/11 infections was 14.6% (95% confidence interval [CI], 7.5%–21.1%). Median time to GW detection was 17.1 months (95% CI, 12.4–19.3 months), with shortest time to detection among men with incident infections with HPV 6/11 only (6.2 months; 95% CI, 5.6–24.2 months). Conclusions. HPV 6/11 plays an important role in GW development, with the highest incidence and shortest time to detection among men with incident HPV 6/11 infection. PMID:22013227

Accuracy and Cost-Effectiveness of Cervical Cancer Screening by High-Risk HPV DNA Testing of Self-Collected Vaginal Samples

PubMed Central

Balasubramanian, Akhila; Kulasingam, Shalini L.; Baer, Atar; Hughes, James P.; Myers, Evan R.; Mao, Constance; Kiviat, Nancy B.; Koutsky, Laura A.

2010-01-01

Objective Estimate the accuracy and cost-effectiveness of cervical cancer screening strategies based on high-risk HPV DNA testing of self-collected vaginal samples. Materials and Methods A subset of 1,665 women (18-50 years of age) participating in a cervical cancer screening study were screened by liquid-based cytology and by high-risk HPV DNA testing of both self-collected vaginal swab samples and clinician-collected cervical samples. Women with positive/abnormal screening test results and a subset of women with negative screening test results were triaged to colposcopy. Based on individual and combined test results, five screening strategies were defined. Estimates of sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or worse were calculated and a Markov model was used to estimate the incremental cost-effectiveness ratios (ICERs) for each strategy. Results Compared to cytology-based screening, high-risk HPV DNA testing of self-collected vaginal samples was more sensitive (68%, 95%CI=58%-78% versus 85%, 95%CI=76%-94%) but less specific (89%, 95%CI=86%-91% versus 73%, 95%CI=67%-79%). A strategy of high-risk HPV DNA testing of self-collected vaginal samples followed by cytology triage of HPV positive women, was comparably sensitive (75%, 95%CI=64%-86%) and specific (88%, 95%CI=85%-92%) to cytology-based screening. In-home self-collection for high-risk HPV DNA detection followed by in-clinic cytology triage had a slightly lower lifetime cost and a slightly higher quality-adjusted life expectancy than did cytology-based screening (ICER of triennial screening compared to no screening was $9,871/QALY and $12,878/QALY, respectively). Conclusions Triennial screening by high-risk HPV DNA testing of in-home, self-collected vaginal samples followed by in-clinic cytology triage was cost-effective. PMID:20592553

Impact of variations in triage cytology interpretation on human papillomavirus-based cervical screening and implications for screening algorithms.

PubMed

Ronco, Guglielmo; Zappa, Marco; Franceschi, Silvia; Tunesi, Sara; Caprioglio, Adele; Confortini, Massimo; Del Mistro, Annarosa; Carozzi, Francesca; Segnan, Nereo; Zorzi, Manuel; Giorgi-Rossi, Paolo

2016-11-01

Women positive to human papillomavirus (HPV+) testing at cervical screening need triage, typically cytology and immediate colposcopy in case of atypical squamous cells of undetermined significance (ASCUS) or worse (ASCUS+) or, in cytology-normal HPV+ women, HPV test repeat after 1 year and colposcopy referral if still HPV+. Our hypothesis was that substantial variations in triage positivity and sensitivity may produce little variation in overall referral to colposcopy and on sensitivity of the entire screening process. Centre- and age-aggregated data from 72,869 women aged 35-64 years were derived from 10 organised screening programmes which have piloted HPV screening in Italy since 2012. Overall colposcopy referral was evaluated as a function of immediate colposcopy referral and overall CIN2+ detection as a function of the proportion of all CIN2+ detected by immediate referral (a proxy of cytology's sensitivity). We fitted additive regression models, adjusted for centre, age, compliance to HPV retesting and to colposcopy, by generalised estimation equations. The proportion of HPV+ women directly referred to colposcopy varied across programmes (20-57%; average 37%) and so did CIN2+ detection (49-94%; average 77%). Overall, 63% (range 41-75%) of HPV+ were referred to colposcopy either immediately or at HPV repeat. An absolute 10% increase in immediate colposcopy referral resulted in 4.2% (95% CI: 3.3-5.1%) increase in overall referral. An absolute 10% increase in cytology's sensitivity resulted in a 1.1% (95% CI: 0.1-2.0%) increase in overall CIN2+ detection. Repeat HPV testing limits the effect of subjectivity of cytology interpretation on overall referral and sensitivity. These will change only slightly when replacing cytology with another test if the interval to HPV repeat remains unchanged. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Human papillomavirus genotyping by Linear Array and Next-Generation Sequencing in cervical samples from Western Mexico.

PubMed

Flores-Miramontes, María Guadalupe; Torres-Reyes, Luis Alberto; Alvarado-Ruíz, Liliana; Romero-Martínez, Salvador Angel; Ramírez-Rodríguez, Verenice; Balderas-Peña, Luz María Adriana; Vallejo-Ruíz, Verónica; Piña-Sánchez, Patricia; Cortés-Gutiérrez, Elva Irene; Jave-Suárez, Luis Felipe; Aguilar-Lemarroy, Adriana

2015-10-06

The Linear Array® (LA) genotyping test is one of the most used methodologies for Human papillomavirus (HPV) genotyping, in that it is able to detect 37 HPV genotypes and co-infections in the same sample. However, the assay is limited to a restricted number of HPV, and sequence variations in the detection region of the HPV probes could give false negatives results. Recently, 454 Next-Generation sequencing (NGS) technology has been efficiently used also for HPV genotyping; this methodology is based on massive sequencing of HPV fragments and is expected to be highly specific and sensitive. In this work, we studied HPV prevalence in cervixes of women in Western Mexico by LA and confirmed the genotypes found by NGS. Two hundred thirty three cervical samples from women Without cervical lesions (WCL, n = 48), with Cervical intraepithelial neoplasia grade 1 (CIN I, n = 98), or with Cervical cancer (CC, n = 87) were recruited, DNA was extracted, and HPV positivity was determined by PCR amplification using PGMY09/11 primers. All HPV- positive samples were genotyped individually by LA. Additionally, pools of amplicons from the PGMY-PCR products were sequenced using 454 NGS technology. Results obtained by NGS were compared with those of LA for each group of samples. We identified 35 HPV genotypes, among which 30 were identified by both technologies; in addition, the HPV genotypes 32, 44, 74, 102 and 114 were detected by NGS. These latter genotypes, to our knowledge, have not been previously reported in Mexican population. Furthermore, we found that LA did not detect, in some diagnosis groups, certain HPV genotypes included in the test, such as 6, 11, 16, 26, 35, 51, 58, 68, 73, and 89, which indicates possible variations at the species level. There are HPV genotypes in Mexican population that cannot be detected by LA, which is, at present, the most complete commercial genotyping test. More studies are necessary to determine the impact of HPV-44, 74, 102 and 114 on the risk of developing CC. A greater number of samples must be analyzed by NGS for the most accurate determination of Mexican HPV variants.

Prevalence and predictors of human papillomavirus infection in women in Ontario, Canada

PubMed Central

Sellors, John W.; Mahony, James B.; Kaczorowski, Janusz; Lytwyn, Alice; Bangura, Helen; Chong, Sylvia; Lorincz, Attila; Dalby, Dawn M.; Janjusevic, Vladan; Keller, Jana L

2000-01-01

Background Human papillomavirus (HPV) is thought to be the primary cause of cervical intraepithelial neoplasia and cervical cancer. We determined the age-specific prevalence of HPV infection and its risk factors in Ontario women. Methods We obtained 2 cervical specimens from randomly selected women (in 5-year age categories, from 15 to 49 years) who were being seen in 32 family practices for cytologic screening. The specimens were tested for carcinogenic HPV by the hybrid capture II assay (Digene Corp., Silver Spring, Md.) and by polymerase chain reaction (PCR) and genotyping. Results Of 1004 women eligible to participate, samples were obtained from 955 (95.1%). The prevalence of HPV (as determined by the hybrid capture II method) was highest, at 24.0% (95% confidence interval [CI] 16.5% to 31.5%), among women 20 to 24 years of age and was progressively lower in older age groups, reaching 3.4% (95% CI 0.1% to 6.7%) in women 45 to 49 years old. The prevalence of HPV (any type) as determined by PCR showed a similar pattern but was significantly higher (p = 0.01) among women 45 to 49 years old than among those 40 to 44 years old (13.0% [95% CI 6.4% to 19.6%] v. 3.3% [95% CI 0.1% to 6.5%]). Risk factors for positivity with the hybrid capture II method were never-married status, divorced or separated status, more than 3 lifetime partners, more than 1 partner in the preceding year, cigarette smoking and current use of oral contraceptives. The presence of squamous intraepithelial lesions on cytologic examination was strongly associated with positivity with the hybrid capture II assay (odds ratio 96.0, 95% CI 22.3 to 413.4; p < 0.01). Interpretation The highest prevalence of HPV was 24.0%, in women 20 to 24 years old. Risk factors supported a sexual mode of transmission, and there was a strong association between HPV and abnormal cervical cytologic result PMID:11006760