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Objective: To describe the prevalence of cervical intraepithelial neoplasia (CIN), high-risk human papillomavirus (hrHPV) infection, and cervical cancer in a high-risk, underscreened incarcerated population and to evaluate the performance of current cervical cancer screening options to detect cervical precancer (CIN 2/3) in this population. Study Design: Deidentified data were obtained from all cytological, hrHPV DNA, and histopathological testing of cervical biopsies performed on people incarcerated at the North Carolina Correctional Institute for Women between January 1, 2013, and December 31, 2020. These were linked to corresponding demographic data. The proportions of histopathological diagnoses of CIN2+ and CIN3+ immediately preceded by abnormal cytology testing or hrHPV testing were determined, and prevalence differences and 95% confidence intervals were calculated. Results: A total of 15,319 individuals incarcerated at the North Carolina Correctional Institute for Women had at least one cytology result during 2013–2020. Of these, 2,829 (18%) had abnormal cervical cytology, and 3,724 (24.3%) had positive hrHPV testing. The detection of CIN2+ was 95.9% by preceding abnormal cervical cytology, 89.9% by preceding positive hrHPV testing (p = 0.03), and 96.5% by preceding positive co-testing. The detection rate of CIN3+ was 96.6% by preceding abnormal cervical cytology, 90.8% by preceding positive hrHPV testing (p = 0.12), and 96.6% by positive co-testing. Conclusion: In our sample, primary cytology and co-testing detected CIN2+ at higher rates when compared with primary hrHPV testing. This reinforces that incarcerated populations do not fall into average-risk populations for which current cervical cancer screening options are designed, which should be considered when performing screening in this population. [ABSTRACT FROM AUTHOR]

Objective Design Setting Population Methods Main outcome measures Results Conclusions To evaluate the sensitivity of human papillomavirus (HPV) tested urine to detect high‐grade cervical precancer (cervical intraepithelial neoplasia grade 2+ [CIN2+]) using two urine collection devices.Randomised controlled trial.St Mary's Hospital, Manchester, UK.Colposcopy attendees with abnormal cervical screening; a total of 480 participants were randomised. Matched urine and cervical samples were available for 235 and 230 participants using a first‐void urine (FVU)‐collection device and standard pot, respectively.Urine was self‐collected and mixed with preservative – randomised 1:1 to FVU‐collection device (Novosanis Colli‐pee® 10 mL with urine conservation medium [UCM]) or standard pot. Matched clinician‐collected cervical samples were taken before colposcopy. HPV testing used Roche cobas® 8800. A questionnaire evaluated urine self‐sampling acceptability.The primary outcome measured sensitivity of HPV‐tested urine (FVU‐collection device and standard pot) for CIN2+ detection. Secondary outcomes compared HPV‐tested cervical and urine samples for CIN2+ and evaluated the acceptability of urine self‐sampling.Urine HPV test sensitivity for CIN2+ was higher with the FVU‐collection device (90.3%, 95% CI 83.7%–94.9%, 112/124) than the standard pot (73.4%, 95% CI 64.7%–80.9%, 91/124, p = 0.0005). The relative sensitivity of FVU‐device‐collected urine was 0.92 (95% CI 0.87–0.97, pMcN = 0.004) compared with cervical, considering that all women were referred after a positive cervical HPV test. Urine‐based sampling was acceptable to colposcopy attendees.Testing of FVU‐device‐collected urine for HPV was superior to standard‐pot‐collected urine in colposcopy attendees and has promising sensitivity for CIN2+ detection. General population HPV testing of FVU‐device‐collected urine will establish its clinical performance and acceptability as an alternative to routine cervical screening. [ABSTRACT FROM AUTHOR]

Simple Summary: In situ/microinvasive adenocarcinoma of the uterine cervix represents the majority of cervical glandular lesions and can be treated conservatively. In contrast to squamous lesions, approximately 15–20% of glandular disease may be HPV-negative and therefore associated with a worse prognosis. Furthermore, up to 4% of cases may show recurrence after three years of follow-up. Given the abovementioned risk, knowing the predictive factors of disease recurrence becomes crucial for post-treatment management. In the present study, HPV testing in follow-up was the best predictor for recurrences in women with in situ/microinvasive AC undergoing conservative treatment. So, its use in clinical practice is of pivotal importance. However, attention should be paid to non-high-risk HPV women in follow-up with non-usual-type histopathology, given that it seems to represent a sub-population at increased risk of recurrences. Objective: The present study aimed to assess long-term follow-up outcomes in women with in situ/microinvasive adenocarcinoma (AC) of the uterine cervix treated conservatively. Methods: Retrospective multi-institutional study including women with early glandular lesions and 5-year follow-up undergoing fertility-sparing treatment. Independent variables associated with recurrence were evaluated. Logistic regression analysis and Kaplan–Meier survival analysis with Logrank test were performed. Results: Of 269 women diagnosed with in situ/microinvasive AC, 127 participants underwent conservative treatment. During follow-up, recurrences were found in nine women (7.1%). The only factor associated with recurrence during follow-up was positive high-risk Human Papillomavirus (hr-HPV) testing (odds ratio 6.21, confidence interval 1.47–26.08, p = 0.012). HPV positivity in follow-up showed a recurrence rate of 21.7% against 3.8% in patients who were HPV-negative (p = 0.002, Logrank test). Among women with negative high-risk HPV tests in follow-up, recurrences occurred in 20.0% of non-usual-type histology vs. 2.1% of usual-type cases (p = 0.005). Conclusion: HPV testing in follow-up is of pivotal importance in women with early glandular lesions undergoing conservative treatment, given its recurrence predictive value. However, women who are high-risk HPV-negative in follow-up with non-usual-type histopathology may represent a sub-population at increased risk of recurrences. Further studies should confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to assess long-term follow-up outcomes in women with in situ/microinvasive adenocarcinoma (AC) of the uterine cervix treated conservatively. Methods: Retrospective multi-institutional study including women with early glandular lesions and 5-year follow-up undergoing fertility-sparing treatment. Independent variables associated with recurrence were evaluated. Logistic regression analysis and Kaplan–Meier survival analysis with Logrank test were performed. Results: Of 269 women diagnosed with in situ/microinvasive AC, 127 participants underwent conservative treatment. During follow-up, recurrences were found in nine women (7.1%). The only factor associated with recurrence during follow-up was positive high-risk Human Papillomavirus (hr-HPV) testing (odds ratio 6.21, confidence interval 1.47–26.08, p = 0.012). HPV positivity in follow-up showed a recurrence rate of 21.7% against 3.8% in patients who were HPV-negative (p = 0.002, Logrank test). Among women with negative high-risk HPV tests in follow-up, recurrences occurred in 20.0% of non-usual-type histology vs. 2.1% of usual-type cases (p = 0.005). Conclusion: HPV testing in follow-up is of pivotal importance in women with early glandular lesions undergoing conservative treatment, given its recurrence predictive value. However, women who are high-risk HPV-negative in follow-up with non-usual-type histopathology may represent a sub-population at increased risk of recurrences. Further studies should confirm these findings.

Abstract Background Implementation of new technologies into national health care systems requires careful capacity planning. This is sometimes informed by data from pilot studies that implement the technology on a small scale in selected areas. A critical consideration when using implementation pilot studies for capacity planning in the wider system is generalisability. We studied the feasibility of using publicly available national statistics to determine the degree to which results from a pilot might generalise for non-pilot areas, using the English human papillomavirus (HPV) cervical screening pilot as an exemplar. Methods From a publicly available source on population indicators in England (“Public Health Profiles”), we selected seven area-level indicators associated with cervical cancer incidence, to produce a framework for post-hoc pilot generalisability analysis. We supplemented these data by those from publicly available English Office for National Statistics modules. We compared pilot to non-pilot areas, and pilot regimens (pilot areas using the previous standard of care (cytology) vs. the new screening test (HPV)). For typical process indicators that inform real-world capacity planning in cancer screening, we used standardisation to re-weight the values directly observed in the pilot, to better reflect the wider population. A non-parametric quantile bootstrap was used to calculate 95% confidence intervals (CI) for differences in area-weighted means for indicators. Results The range of area-level statistics in pilot areas covered most of the spectrum observed in the wider population. Pilot areas were on average more deprived than non-pilot areas (average index of multiple deprivation 24.8 vs. 21.3; difference: 3.4, 95% CI: 0.2–6.6). Participants in HPV pilot areas were less deprived than those in cytology pilot areas, matching area-level statistics. Differences in average values of the other six indicators were less pronounced. The observed screening process indicators showed minimal change after standardisation for deprivation. Conclusions National statistical sources can be helpful in establishing the degree to which the types of areas outside pilot studies are represented, and the extent to which they match selected characteristics of the rest of the health care system ex-post. Our analysis lends support to extrapolation of process indicators from the HPV screening pilot across England.

Abstract Background High-risk human papillomavirus (hrHPV) testing has been recommended by the World Health Organization as the primary screening test in cervical screening programs. The option of self-sampling for this screening method can potentially increase women’s participation. Designing screening programs to implement this method among underscreened populations will require contextualized evidence. Methods PREvention and SCReening Innovation Project Toward Elimination of Cervical Cancer (PRESCRIP-TEC) will use a multi-method approach to investigate the feasibility of implementing a cervical cancer screening strategy with hrHPV self-testing as the primary screening test in Bangladesh, India, Slovak Republic and Uganda. The primary outcomes of study include uptake and coverage of the screening program and adherence to follow-up. These outcomes will be evaluated through a pre-post quasi-experimental study design. Secondary objectives of the study include the analysis of client-related factors and health system factors related to cervical cancer screening, a validation study of an artificial intelligence decision support system and an economic evaluation of the screening strategy. Discussion PRESCRIP-TEC aims to provide evidence regarding hrHPV self-testing and the World Health Organization’s recommendations for cervical cancer screening in a variety of settings, targeting vulnerable groups. The main quantitative findings of the project related to the impact on uptake and coverage of screening will be complemented by qualitative analyses of various determinants of successful implementation of screening. The study will also provide decision-makers with insights into economic aspects of implementing hrHPV self-testing, as well as evaluate the feasibility of using artificial intelligence for task-shifting in visual inspection with acetic acid. Trial registration ClinicalTrials.gov, NCT05234112 . Registered 10 February 2022

Background: Implementation of new technologies into national health care systems requires careful capacity planning. This is sometimes informed by data from pilot studies that implement the technology on a small scale in selected areas. A critical consideration when using implementation pilot studies for capacity planning in the wider system is generalisability. We studied the feasibility of using publicly available national statistics to determine the degree to which results from a pilot might generalise for non-pilot areas, using the English human papillomavirus (HPV) cervical screening pilot as an exemplar.Methods: From a publicly available source on population indicators in England ("Public Health Profiles"), we selected seven area-level indicators associated with cervical cancer incidence, to produce a framework for post-hoc pilot generalisability analysis. We supplemented these data by those from publicly available English Office for National Statistics modules. We compared pilot to non-pilot areas, and pilot regimens (pilot areas using the previous standard of care (cytology) vs. the new screening test (HPV)). For typical process indicators that inform real-world capacity planning in cancer screening, we used standardisation to re-weight the values directly observed in the pilot, to better reflect the wider population. A non-parametric quantile bootstrap was used to calculate 95% confidence intervals (CI) for differences in area-weighted means for indicators.Results: The range of area-level statistics in pilot areas covered most of the spectrum observed in the wider population. Pilot areas were on average more deprived than non-pilot areas (average index of multiple deprivation 24.8 vs. 21.3; difference: 3.4, 95% CI: 0.2-6.6). Participants in HPV pilot areas were less deprived than those in cytology pilot areas, matching area-level statistics. Differences in average values of the other six indicators were less pronounced. The observed screening process indicators showed minimal change after standardisation for deprivation.Conclusions: National statistical sources can be helpful in establishing the degree to which the types of areas outside pilot studies are represented, and the extent to which they match selected characteristics of the rest of the health care system ex-post. Our analysis lends support to extrapolation of process indicators from the HPV screening pilot across England. [ABSTRACT FROM AUTHOR]

ObjectiveTo determine the effectiveness of community health campaigns (CHCs) as a strategy for human papillomavirus (HPV)-based cervical cancer screening in rural western Kenya.MethodsBetween January and November 2016, a cluster-randomized trial was carried out in 12 communities in western Kenya to investigate high-risk HPV testing offered via self-collection to women aged 25-65 years in CHCs versus government health facilities. Outcome measures were the total number of women accessing cervical cancer screening and the proportion of HPV-positive women accessing treatment.ResultsIn total, 4944 women underwent HPV-based cervical cancer screening in CHCs (n=2898) or health facilities (n=2046). Screening uptake as a proportion of total eligible women in the population was greater in communities assigned to CHCs (60.0% vs 37.0%, P

Background: High-risk human papillomavirus (hrHPV) testing has been recommended by the World Health Organization as the primary screening test in cervical screening programs. The option of self-sampling for this screening method can potentially increase women's participation. Designing screening programs to implement this method among underscreened populations will require contextualized evidence.Methods: PREvention and SCReening Innovation Project Toward Elimination of Cervical Cancer (PRESCRIP-TEC) will use a multi-method approach to investigate the feasibility of implementing a cervical cancer screening strategy with hrHPV self-testing as the primary screening test in Bangladesh, India, Slovak Republic and Uganda. The primary outcomes of study include uptake and coverage of the screening program and adherence to follow-up. These outcomes will be evaluated through a pre-post quasi-experimental study design. Secondary objectives of the study include the analysis of client-related factors and health system factors related to cervical cancer screening, a validation study of an artificial intelligence decision support system and an economic evaluation of the screening strategy.Discussion: PRESCRIP-TEC aims to provide evidence regarding hrHPV self-testing and the World Health Organization's recommendations for cervical cancer screening in a variety of settings, targeting vulnerable groups. The main quantitative findings of the project related to the impact on uptake and coverage of screening will be complemented by qualitative analyses of various determinants of successful implementation of screening. The study will also provide decision-makers with insights into economic aspects of implementing hrHPV self-testing, as well as evaluate the feasibility of using artificial intelligence for task-shifting in visual inspection with acetic acid.Trial Registration: ClinicalTrials.gov, NCT05234112 . Registered 10 February 2022. [ABSTRACT FROM AUTHOR]

Cervical cancer screening in the United States has accompanied profound decreases in cancer incidence and mortality over the last half century. Two screening strategies are currently endorsed by US-based guideline groups: (1) triennial cytology for women aged 21 to 65 years, and (2) triennial cytology for women aged 21 to 29 years followed by cytology plus testing for high-risk human papillomavirus types every 5 years for women aged 30 years and older. Providing women with affordable, easily accessible screening, follow-up of abnormal tests, and timely treatment will result in the greatest impact of screening on cervical cancer incidence and mortality.

Abstract Background To reach non-participants, reluctant to undergo clinician-based cervical cancer screening and vaginal self-sampling, urine collection for high-risk human papillomavirus detection (hrHPV) may be valuable. Using two hrHPV DNA assays, we evaluated the concordance of hrHPV positivity in urine samples in comparison with vaginal self-samples and cervical cytology samples taken by the general practitioner (GP). We also studied women’s acceptance of urine collection and preferences towards the different sampling procedures. Methods One hundred fifty paired self-collected urine and vaginal samples and GP-collected cervical cytology samples were obtained from 30 to 59-year-old women diagnosed with ASC-US within the Danish cervical cancer screening program. After undergoing cervical cytology at the GP, the women collected first-void urine and vaginal samples at home and completed a questionnaire. Each sample was hrHPV DNA tested by the GENOMICA CLART® and COBAS® 4800 assays. Concordance in hrHPV detection between sample types was determined using Kappa (k) statistics. Sensitivity and specificity of hrHPV detection in urine was calculated using cervical sampling as reference. Results With the COBAS assay, urine showed good concordance to the vaginal (k = 0.66) self-samples and cervical samples (k = 0.66) for hrHPV detection. The corresponding concordance was moderate (k = 0.59 and k = 0.47) using CLART. Compared to cervical sampling, urinary hrHPV detection had a sensitivity of 63.9% and a specificity of 96.5% using COBAS; compared with 51.6 and 92.4% for CLART. Invalid hrHPV test rates were 1.8% for COBAS and 26.9% for CLART. Urine collection was well-accepted and 42.3% of the women ranked it as the most preferred future screening procedure. Conclusions Urine collection provides a well-accepted screening option. With COBAS, higher concordance between urine and vaginal self-sampling and cervical sampling for hrHPV detection was found compared to CLART. Urinary hrHPV detection with COBAS is feasible, but its accuracy may need to be improved before urine collection at home can be offered to non-participants reluctant to both cervical sampling and vaginal self-sampling.

The US Food and Drug Administration supports innovations to facilitate new indications for high-risk human papillomavirus testing. This report describes the retrospective testing of stored specimens and analysis of existing data to efficiently and cost-effectively support a new indication for the Onclarity human papillomavirus assay (Becton, Dickinson and Company, BD Life Sciences - Integrated Diagnostic Solutions, Sparks, MD). The performance of this index test was compared with that of a predicate test, the cobas human papillomavirus assay (Roche Diagnostics, Indianapolis, IN). Both human papillomavirus assays are based on real-time polymerase chain reaction platforms that detect the presence of 14 high-risk human papillomavirus genotypes. The predicate assay reports human papillomavirus types 16 and 18 as individual results and the other 12 human papillomavirus genotypes as 1 pooled result. The index assay reports 9 independent results (human papillomavirus types 16, 18, 31, 33/58, 35/39/68, 45, 51, 52, and 56/59/66). Both the index and predicate assays are approved by the Food and Drug Administration for cervical cancer screening, but at the time that this study was initiated, the index human papillomavirus assay was not approved for use with cervical specimens collected in PreservCyt (Hologic, Inc, San Diego, CA) liquid-based cytology media. The performance of the index human papillomavirus assay was compared with that of the predicate human papillomavirus assay for the detection of cervical intraepithelial neoplasia grades 2 or greater and 3 or greater (≥CIN2 or ≥CIN3) using PreservCyt liquid-based cytology specimens collected from women aged 21 to 65 years. In addition, the ability of the index test's extended genotyping to stratify ≥CIN2 and ≥CIN3 risks, using these specimens, was evaluated. The New Mexico HPV Pap Registry was used to select an age- and cytology-stratified random sample of 19,879 women undergoing opportunistic cervical screening and follow-up in routine clinical practice across New Mexico. A subset (n = 4820) of PreservCyt specimens was selected from 19,879 women for paired testing by the index and predicate human papillomavirus assays within age and cytology strata and included women with or without cervical biopsy follow-up. Point estimate differences and ratios were calculated for cervical disease detection and positivity rates, respectively, with 95% confidence intervals to determine statistical significance. The cumulative risk of ≥CIN2 or ≥CIN3, with up to 5-year follow-up, was estimated for the index assay using Kaplan-Meier methods. The 5-year cumulative ≥CIN3 detection rates were 5.6% for the index assay and 4.6% for the predicate assay (difference, 1.0%; 95% confidence interval, 0.5%–1.5%). The ≥CIN3 positivity rates within <1 year were 95.3% for the index assay and 94.5% for the predicate assay (ratio, 1.01; 95% confidence interval, 0.98–1.06). The ≥CIN3 cumulative positivity rates for the index and predicate assays were also similar at 5 years. Among cases of ≥CIN3, the positive agreement rates between the index and predicate assays for human papillomavirus types 16 and 18 were 100.0% (95% confidence interval, 95.0%–100.0%) and 90.9% (95% confidence interval, 62.3%–98.4%), respectively. Human papillomavirus type 16 carried the highest ≥CIN2 or ≥CIN3 risk, followed by human papillomavirus types 18/31/33/58/52/45 and human papillomavirus types 35/56/59/51/56/59/66. The index and predicate human papillomavirus assays demonstrated equivalent performance, and extended human papillomavirus genotyping, using the index assay, provided effective ≥CIN2 and ≥CIN3 risk stratification, supporting a new indication for use of the index assay with PreservCyt. [ABSTRACT FROM AUTHOR]

Background: To reach non-participants, reluctant to undergo clinician-based cervical cancer screening and vaginal self-sampling, urine collection for high-risk human papillomavirus detection (hrHPV) may be valuable. Using two hrHPV DNA assays, we evaluated the concordance of hrHPV positivity in urine samples in comparison with vaginal self-samples and cervical cytology samples taken by the general practitioner (GP). We also studied women's acceptance of urine collection and preferences towards the different sampling procedures.Methods: One hundred fifty paired self-collected urine and vaginal samples and GP-collected cervical cytology samples were obtained from 30 to 59-year-old women diagnosed with ASC-US within the Danish cervical cancer screening program. After undergoing cervical cytology at the GP, the women collected first-void urine and vaginal samples at home and completed a questionnaire. Each sample was hrHPV DNA tested by the GENOMICA CLART® and COBAS® 4800 assays. Concordance in hrHPV detection between sample types was determined using Kappa (k) statistics. Sensitivity and specificity of hrHPV detection in urine was calculated using cervical sampling as reference.Results: With the COBAS assay, urine showed good concordance to the vaginal (k = 0.66) self-samples and cervical samples (k = 0.66) for hrHPV detection. The corresponding concordance was moderate (k = 0.59 and k = 0.47) using CLART. Compared to cervical sampling, urinary hrHPV detection had a sensitivity of 63.9% and a specificity of 96.5% using COBAS; compared with 51.6 and 92.4% for CLART. Invalid hrHPV test rates were 1.8% for COBAS and 26.9% for CLART. Urine collection was well-accepted and 42.3% of the women ranked it as the most preferred future screening procedure.Conclusions: Urine collection provides a well-accepted screening option. With COBAS, higher concordance between urine and vaginal self-sampling and cervical sampling for hrHPV detection was found compared to CLART. Urinary hrHPV detection with COBAS is feasible, but its accuracy may need to be improved before urine collection at home can be offered to non-participants reluctant to both cervical sampling and vaginal self-sampling. [ABSTRACT FROM AUTHOR]

Mette Tranberg,1,2 Bodil Hammer Bech,3 Jan Blaakær,4,5 Jørgen Skov Jensen,6 Hans Svanholm,1,7 Berit Andersen1,2 1Department of Public Health Programmes, Randers Regional Hospital, Randers, Denmark; 2Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 3Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark; 4Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark; 5Department of Clinical Medicine, University of Southern Denmark, Odense, Denmark; 6Research Unit for Reproductive Microbiology, Statens Serum Institut, Copenhagen, Denmark; 7Department of Pathology, Randers Regional Hospital, Randers, Denmark Background: Participation in cervical cancer screening varies by socioeconomic status. The aims were to assess if offering human papilloma virus (HPV) self-sampling kits has an effect on screening participation among various socioeconomic groups and to determine if two invitation strategies for offering self-sampling influence the participation rate equally.Methods: The study was based on registry data that were applied to data from a randomized controlled trial (n=9,791) measuring how offering HPV self-sampling affected screening participation. The women received either 1) a self-sampling kit mailed directly to their homes (directly mailed group); 2) an invitation to order the kit (opt-in group); or 3) a standard second reminder to attend regular cytology screening (control group). The participation data were linked to registries containing socioeconomic information.Results: Women in the directly mailed group participated significantly more than women in the control group, regardless of their socioeconomic status, but the largest effects were observed in Western immigrants (participation difference [PD]=18.1%, 95% CI=10.2%–26.0%) and social welfare recipients (PD=15.2%, 95% CI=9.7%–20.6%). Compared with the control group, opt-in self-sampling only had an insignificant effect on participation among women who were immigrants, retired, or less educated. Western immigrants had a significantly higher increase in participation than native Danish women when kits were mailed directly compared with the opt-in strategy (PD=18.1%, 95% CI=10.2%–26.2% and PD=5.5%, 95% CI=2.9%–8.1%, respectively, P=0.01).Conclusion: All socioeconomic groups benefited from the directly mailed strategy in terms of higher screening participation, but Western immigrants and lower socioeconomic groups seemed to benefit the most. Immigrants and some lower socioeconomic groups only had insignificant benefits of opt-in self-sampling. The directly mailed strategy might be preferable to opt-in self-sampling because it ensures that ethnic minority groups obtain benefits of introducing HPV self-sampling in an organized cervical cancer screening program.Trial registration: Current Controlled Trials NCT02680262. Registered February 10, 2016. Keywords: self-sampling, human papillomavirus testing, cervical cancer screening, screening participation, socioeconomic status, social class, mass screening

Abstract Background Studies comparing self-samples and clinician-collected samples for high-risk human papillomavirus (HPV) detection using clinically validated PCR-based HPV DNA assays are limited. We measured the concordance of HPV detection between home-based self-sampling and general practitioner (GP) sampling using the Cobas 4800 HPV DNA test and studied women’s accept of home-based self-sampling. Methods Paired GP-collected samples and cervico-vaginal self-samples were obtained from 213 women aged 30–59 years diagnosed with ASC-US within the cervical cancer screening program. After undergoing cervical cytology at their GP, the women collected a self-sample with the Evalyn Brush at home and completed a questionnaire. Both samples were HPV-tested using the Cobas 4800 test. Histology results were available for those who tested HPV positive in GP-collected samples. Results We observed good concordance for HPV detection between self-samples and GP-collected samples (κ: 0.70, 95% CI: 0.58–0.81). No underlying CIN2+ cases were missed by self-sampling. Women evaluated that self-sampling was easy (97.2%, 95% CI: 93.9–98.9%) and comfortable (94.8%, 95% CI: 90.9–97.4%). Conclusions Home-based self-sampling using the Evalyn Brush and the Cobas 4800 test is an applicable and reliable alternative to GP-sampling.

Abstract Background Cervical cancer screening participation remains insufficient in most countries. Our aim was to evaluate whether offering a HPV self-sampling kit, either mailed directly to the woman’s home or using timely opt-in procedures for ordering the kit, increased screening participation compared with a standard second reminder. Methods In this randomized, controlled effectiveness trial, 9791 Danish women aged 30–64 who were due to receive the second reminder were equally randomized to either: 1) direct mailing of a second reminder and a self-sampling kit (directly mailed group); 2) mailing of a second reminder that offered a self-sampling kit to be ordered by e-mail, text message, phone, or webpage (opt-in group); or 3) mailing of a second reminder to attend regular cytology screening (control group). In an intention-to-treat analysis, we estimated the participation rate at 180 days post intervention, by returning a self-sample or attending regular cytology screening. We calculated the proportion of women with a positive HPV self-sample who attended for cervical cytology triage at the general practitioner within 90 days. Results Participation was significantly higher in the directly mailed group (38.0%) and in the opt-in group (30.9%) than in the control group (25.2%) (participation difference (PD): 12.8%, 95% CI: 10.6–15.0% and PD: 5.7%, 95% CI: 3.5–7.9%, respectively). Within 90 days, 107 women (90.7%, 95% CI: 83.9–95.3%) with a HPV-positive self-sample attended follow-up. Conclusions Offering the opportunity of HPV self-sampling as an alternative to regular cytology screening increased participation; the direct mailing strategy was the most effective invitation strategy. A high compliance with follow-up was seen. Trial registration Current Controlled Trials NCT02680262. Registered 10 February 2016.

Introduction: The optimal clinical management of women diagnosed with low-grade squamous intraepithelial lesions (LSIL) during cervical cancer screening remains unclear. In this prospective cohort study, we compared the clinical performance of two human papillomavirus (HPV) mRNA tests for triage of women with LSIL in Denmark.Material and Methods: In a nationwide pathology register, we identified women aged 23-65 years with LSIL during 2008-2012. We included women tested for HPV mRNA with the PreTect HPV Proofer test for five high-risk HPV types (n = 2176) or the Aptima assay for 14 high-risk HPV types (n = 426). Subsequent histological diagnoses of cervical intraepithelial neoplasia grades 2, 3 or cancer (CIN2+) were identified in the register. We calculated the sensitivity and specificity for CIN2+ at 18 and 36 months of follow up, and the cumulative incidence of CIN2+ among women testing positive and negative, overall and by age (23-29, 30-39, 40-65 years).Results: The proportion of women with a positive mRNA test at baseline was higher in women tested with Aptima (66.7%) than in women tested with Proofer (42.8%). After 18 months, Aptima had higher sensitivity for CIN2+ than Proofer (98% [95% CI 94% to 100%] vs 85% [95% CI 82% to 88%]), whereas Proofer showed higher specificity than Aptima (67% [95% CI 64% to 70%]) vs (40% [95% CI 33% to 46%]). Aptima had particularly low specificity in women aged <40 years (23-29: 19% [95% CI 5% to 36%]; 30-39: 10% [95% CI 0% to 33%]). The 36-month cumulative incidence of CIN2+ was higher in Proofer positive (54.3% [95% CI 50.9% to 57.8%]) than in Aptima positive women (37.6% [95% CI 31.2% to 44.8%]). In women with a negative mRNA test, the 36-month cumulative incidences of CIN2+ were 13.1% (95% CI 10.8% to 15.8%) and 5.9% (95% CI 1.7% to 19.0%) for Proofer and Aptima, respectively.Conclusions: In women with LSIL, Aptima had high sensitivity for CIN2+, but low specificity, especially in women aged <40 years. The Proofer test may be useful to limit immediate colposcopy referrals in younger women with LSIL, but given its low sensitivity and negative predictive value, Proofer negative women must be followed with repeat cytology. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to compare the cost and benefit of four different cervical cancer screening strategies involving primary HPV 16/18 genotyping, hrHPV testing alone and cytology for detecting CIN2+. Methods: Economical analysis using Markov modeling approach to combine the epidemiological data from current population-based study of The National Cancer Institute of Thailand. A cohort of 100,000 hypothetical female population age 30–65 years was simulated in each strategy. The compared strategies are HPV 16/18 genotyping with reflexed cytology, hrHPV testing alone followed by colposcopy, Papanicolaou standard cytology and liquid based cytology followed by colposcopy. The interval of screening was 5 years' interval. The main outcomes were defined as a number of CIN2+ cases and cost per 100,000 women screening over 35 years. Results: Model predictions indicated that, the most cost-effectiveness strategy is hrHPV testing alone by reducing cost and also increase CIN2+ detection rate. It identify an additional 130 cases and decrease cost by 46,950,840 THB (1,394,441 USD) per 100,000 women screened when compared to HPV 16/18 genotyping. Compared with cytology, hrHPV testing decrease cost by 51,279,781 THB (1,523,011 USD) and detected more 506 cases of CIN2+. From sensitivity analysis, the cost of HPV testing, cost of colposcopy, incidence of HPV infection and sensitivity of cytology may affect the results. (1 USD = 33.67 Baht). Conclusion: The results of this cost-effectiveness analysis support the full scale implementation of HPV testing as a primary cervical cancer screening in Thailand.

Objective: To evaluate two usages of the folate receptor-mediated staining solution (FRD) for detecting high-grade cervical lesions and invasive cancer, and compared with cytology test (TCT) and human papillomavirus (HPV) testing.Methods: FRD sampling and FRD direct staining methods were used for detecting high-grade cervical lesions and invasive cancer. As a comparison, TCT and HPV testing were also applied for screening high-grade cervical lesions and invasive cancer. The sensitivity and specificity of TCT, HPV testing, and staining results of FRD were analyzed by the SPSS software.Results: In this study, 317 patients with biopsy were collected. The positive rate of FRD sampling method was 35.33% (112/317), and positive rate of FRD direct staining was 48.90% (155/317). Area under the curve (AUC) of TCT, HPV testing, FRD sampling and FRD direct staining were 0.53, 0.55, 0.58, and 0.75, respectively. The sensitivity of TCT, HPV, FRD sampling and FRD direct staining was 69.72%, 97.25%, 64.22% and 81.65%, respectively, and the specificity was 37.98%, 12.98%, 79.81% and 68.27%, respectively.Conclusion: Compared with TCT and HPV testing, two usages of FRD methods have compatible sensitivity and high specificity to detect high-grade cervical lesions and invasive cancer. FRD direct staining may be comfortable for routine cervical cancer screening. [ABSTRACT FROM AUTHOR]

Objectives One reason that women over age 50 report avoiding cervical screening is increased discomfort postmenopause. This study aimed to explore the acceptability of human papillomavirus testing on clinician-collected vaginal samples without a speculum ('non-speculum') for cervical screening among older women. Methods Thirty-eight women in England aged 50–64 with a range of cervical screening experience ('up-to-date' n = 17, 'overdue screening' n = 18, 'never screened' n = 3) were identified via a recruitment agency. Women participated in focus groups or interviews about the potential for using clinician-collected samples without a speculum. Discussions were analysed using Framework Analysis. Results The two main themes identified were women's perceptions of the speculum and attitudes towards non-speculum screening. Many women reported negative experiences with the speculum, including increased pain after the menopause. Women generally had positive attitudes towards non-speculum clinician sampling and felt it would be a less intrusive option, but expressed concern that it could be less accurate than screening with a speculum. Women who were 'up-to-date' preferred conventional screening, while overdue and never screened women welcomed the option to be screened without a speculum. Conclusions Human papillomavirus testing on non-speculum clinician-collected vaginal samples could be an acceptable alternative cervical screening method for older women. Offering this approach could increase screening uptake in older women who find conventional cervical screening to be less acceptable with ageing or the menopause. [ABSTRACT FROM AUTHOR]

Introduction: 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. Methods: This study enrolled 7584 women aged ≥25 years who were undergoing routine screening. All women underwent LBC 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Introduction: Human papillomavirus (HPV) testing is a suitable tool for primary cervical cancer (CC) screening and follow-up in low-resource settings. Vaginal samples taken by women themselves (Self-HPV) are an interesting alternative to physician-performed sampling (Dr-HPV). Our aim was to assess the performance of Self-HPV and Dr-HPV at 6 and 12 months following a CC screening campaign. Methods: This study was carried out at the Dschang District Hospital, Cameroon. Women aged 30-49 years were recruited in a CC screening campaign. HPV-positive women, of whom 2/3 were treated with thermoablation because of abnormal results at baseline screening, were invited to participate in a follow-up study. Self- and Dr-HPV, as well as cytology, were performed at 6 and 12 months. HPV samples were analyzed using the Xpert HPV assay. Sensitivity and specificity for the detection of low-grade squamous intraepithelial lesion or worse and of high-grade squamous intraepithelial lesion or worse were calculated for Self-HPV and Dr-HPV, using cytology as the reference diagnosis. Results: Overall, 188 HPV-positive women were invited to attend follow-up. The obtained follow-up visits' attendance was 154 (81.9%) and 131 (69.7%) at 6 and 12 months, respectively. While the overall performance of Dr-HPV at 6 months was slightly superior, Self-HPV showed an improved sensitivity for HSIL+ detection at 12 months when compared with Dr-HPV (83.3% [95% CI 41.8-98.9] versus 71.4% [95% CI 21.5-95.8], respectively). The overall HPV positivity agreement between Self- and Dr-HPV at 6 and 12 months corresponded to a κ value of 0.62 and 0.52, respectively. Among women treated with thermoablation (n=121) at baseline screening, Self-HPV was as sensitive as Dr-HPV, although less specific (P=0.003). Conclusion: Self-HPV is a valuable tool for the follow-up of HPV-positive women in lowresource settings. Larger, randomized trials are needed to confirm the validity of our findings. [ABSTRACT FROM AUTHOR]

As explained by Kitchener in a previous issue of Cytopathology (2015; 26:4-6), primary human papillomavirus ( HPV) testing is likely to be introduced in the UK for all women aged 25-64 years following pilot site studies already in place. This will be necessary when the prevalence of cervical cancer and its precursors declines when vaccination takes effect but there is a risk in abandoning cytology as a primary test: a risk that would be most apparent in the present unvaccinated population in which the prevalence of cervical cancer and its precursors is exceptionally high. HPV testing is more sensitive than cytology but has a significant false-negative rate that could be detrimental to a successful screening programme if introduced without cytology backup. Accurate cytology would be needed for triage and could be compromised if HPV-negative tests were excluded from examination. This article proposes a compromise: cytology and HPV co-testing for the first two screening tests to optimise the sensitivity of the test as a whole. Registrations of invasive and in situ carcinoma of the uterine cervix in England indicate that the prevalence of the disease is highest in young women in the early rounds of screening. Calculations of the likely impact on the workload of this proposal have been based on a service evaluation of 295 cytology tests received at St Thomas' Hospital, which suggests that the volume of cytology tests would be reduced by approximately 60% compared with 80% for primary HPV testing alone. This proposal should be debated openly before irrevocable changes are made to a skilled workforce. [ABSTRACT FROM AUTHOR]

Background: 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. Methods/design: 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. Discussion: 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. Trial registration: Current Controlled Trials NCT02680262. Registered 10 February 2016. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Two transport media, PreservCyt and SurePath, are widely used for cervical cytology screening. There are concerns that they may perform differently for HPV testing. Objectives A comparison of the performance of six different HPV tests in SurePath and PreservCyt in a referral population using two samples from each woman. The primary goal was to compare the performance of each test in the two media. Comparisons between assays and viral load comparisons between media were secondary aims. Study design Two cervical samples were collected in random order at the same visit in women with abnormal cytology. One sample was placed in 20 ml of PreservCyt and the other in 10 ml of SurePath. Aliquots were taken for 4 DNA based tests: digene HC2 High-Risk HPV DNA Test, Abbott Realti m e, BD Onclarity and Genera PapType, an RNA based test—: Hologic Aptima and a protein test: OncoHealth. Results 630 sample pairs were included in the analyses. For all tests except the protein test sensitivities were in excess of 90% for CIN2+ and 95% for CIN3+ for both media and with no significant differences except for a lower sensitivity for CIN2+ of Aptima in SurePath (93% vs 98%, P = 0.005). Specificity for

Cervical cancer screening involves a complex process of cytology, human papillomavirus (HPV) testing, colposcopy, and a multitude of algorithms for the identification of preinvasive disease and prevention of invasive disease. High-risk HPV is a prerequisite for the development of almost all types of cervical cancer; therefore, a test for high-risk HPV has become an integral part of new screening strategies. Major changes to screening guidelines in the last decade include initiation of screening at age 21 years, conservative management of young women with abnormal cytology, extended screening intervals for women age ≥30 years, and cessation of screening in low-risk women at age 65 years. This review will focus on the evidence that has led to the current evidence-based guidelines. Evidence regarding primary HPV testing as well as postvaccine-based screening strategies will also be reviewed. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical value of human papillomavirus (HPV) DNA testing (Hybrid Capture II) in predicting which women with mild cervical cytologic abnormality (atypical squamous cells of undetermined significance [ASCUS] or low-grade squamous intraepithelial lesions [LSIL]) are most likely to have high-grade cervical intraepithelial neoplasia (CIN). Materials and Methods: A total of 266 women with mildly abnormal Papanicolaou (Pap) smear results (160 with ASCUS and 106 with LSIL) concurrently underwent Hybrid Capture II testing, repeat Pap smear, and colposcopy-directed biopsies. Results: Overall, the underlying prevalence of histologically confirmed CIN2/3 was 16.9% (27/160) in women with ASCUS and 29.2% (31/106) in those with LSIL. High-risk HPV DNA was detected in 55% and 88.7%, respectively. The sensitivity of CIN2/3 detection by HPV DNA was 96.3% (26/27) and 100% (31/31) among women with ASCUS and LSIL, respectively. Conclusion: A positive baseline HPV test in women with ASCUS or LSIL is clinically equivalent, requiring colposcopic examination and denoting an approximately one-third chance of having CIN2/3. Among women with ASCUS, a negative HPV test strongly indicates that the patient is free of CIN2/3, which should minimize a patient's anxiety and unnecessary colposcopic examinations.

BACKGROUND Cervical cancer screening and follow-up guidelines have changed considerably in recent years, but to the authors' knowledge few published reports exist to estimate the impact of these changes in community-based settings. The authors examined the patterns and results of cervical cancer testing and follow-up over a decade in 4 geographically diverse US health care systems to inform the future evaluation of changes resulting from increased uptake of the human papillomavirus (HPV) vaccination. METHODS The authors studied women aged 21 to 65 years who were members of one of these health systems at any time between 1998 and 2007. Data were collected and standardized across sites, based on receipt of Papanicolaou (Pap) and HPV tests, HPV vaccination, cervical biopsies, and treatment of cervical dysplasia. Annual rates (per 1000 person-years) of Pap testing, HPV testing, and cervical biopsy and treatment procedures were calculated. Screening intervals and trends in the results of screening Pap tests and cervical biopsies also were examined. RESULTS Pap testing rates decreased (from 483 per 1000 person-years in 2000 to 412 per 1000 person-years in 2007) and HPV testing rates increased over the study period. Screening frequency varied across health care systems, and many women continued to receive annual testing. All 4 sites moved to less frequent screening over the study period without marked changes in the overall use of cervical biopsy or treatment. CONCLUSIONS Despite differences over time and across health plans in rates of cervical cancer testing and follow-up cervical procedures, the authors found no notable differences in Pap test results, diagnostic or treatment procedure rates, or pathological outcomes. This finding suggests that the longer screening intervals did not lead to more procedures or more cancer diagnoses. Cancer 2015;121:2976-2983. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objective: To estimate the proportion of cervical screening non-attenders presenting to general practice (GP) primary care over one year. Setting: 137 practices in East London, UK. Methods: Anonymous primary care records were downloaded using EMIS web (clinical software). Cervical screening nonattendance was defined as no recorded smear in the last 3.5 years (women aged 25-49) or 5.5 years (women aged 50-64). The last three consultation entries were used to estimate the proportion of non-attenders who consulted in GP over 3 months and 1 year using the Kaplan-Meier method. Newly registered women were assessed separately. Results were calculated for each practice and the median and interquartile range (IQR) across practices are presented. Heterogeneity was assessed using funnel plots. Results: Of 261,810 women, 224,313 (86%) had been registered for >1 year. The proportion classified as non-attenders differed between those registered for >1 year (30%, IQR 27%-35%) and within the last year (49%, IQR 40%-57%), suggesting that screening records were less up-to-date in newly registered women. A median of 32% (IQR: 27%-37%) of non-attenders presented over 3 months, and 60% (IQR: 52%-67%) over 1 year. Funnel plots of the proportion of non-attenders presenting by the number of non-attenders showed substantial variation between practices. Conclusions: Over half of cervical screening non-attenders present to their GP at least once a year, in over 75% of practices. This represents a good opportunity for improving coverage by offering an alternative form of screening, such as self-sampling for human papillomavirus testing. [ABSTRACT FROM AUTHOR]

Submission of vaginal samples collected at home could remove barriers that women face in getting screened for cervical cancer. From December 2013 to January 2014, women aged 21-30 years were recruited online to participate in either (1) self-collected testing for human papillomavirus (HPV) infection and an online survey, or (2) an online survey regarding their perceptions of self-collected testing for HPV infection. Demographics, risk factors, testing perceptions, and satisfaction with self-collected testing were assessed with online questionnaires. Women who performed self-collection were sent a home sampling kit by US mail, which was returned via US mail for HPV testing. A total of 197 women were enrolled, with 130 completing the online survey and 67 participating in both the survey and self-collection. Of the 67 women who were sent kits, 62 (92.5 %) were returned for testing. Sixty kits contained a sample sufficient for testing. The overall prevalence of HPV infection was 17.8 %, however 6 women (9.7 %) were infected with >1 type of HPV. Women who self-collected a sample reported more favorable attributes of self-collection compared to women who only participated in the online survey, including ease of sampling (87.1 vs. 18.9 %), no pain during sampling (72.6 vs. 5.6 %), and lack of embarrassment (67.7 vs. 12.9 %). A high prevalence of HPV infection was demonstrated among women recruited via the internet. Online recruitment and at home screening methods have the potential to engage women in screening by offering an approach that might be more acceptable to women of different backgrounds. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) DNA testing is replacing cervical cytology as a primary cervical cancer screening tool. The aim of this study was to determine the frequency of occurrence of HPV types 16 and 18 in liquid-based cytology (LBC) cervical samples in our set-up. This study comprised of 302 LBC cervical samples. HPV 16 and HPV 18 were detected by polymerase chain reaction (PCR), and the results were compared between normal ( n = 155), inflammatory ( n = 99), squamous ( n = 37) and glandular abnormalities ( n = 11). Of our patient cohort, 73.8 % was ≤40 years old. We found HPV 16 DNA in 91/302 (30.1 %) cases and HPV 18 DNA in 21/302 (6.95 %). HPV types 16 and 18 were detected in 25.8 and 4.5 % cytologically normal samples, respectively. HPV 16 was positive in 29.3 % of inflammatory samples. Squamous cervical abnormalities were more often HPV positive (HPV 16 in 48.6 %; HPV 18 in 29.7 %) than glandular abnormalities (36.4 and 18.2 %, respectively). We found high-risk HPV DNA in more than one third of the tested women. A good number of these HPV-positive cases were negative in cervical cytology. [ABSTRACT FROM AUTHOR]

Objectives　The purpose of the study is to compare the results of doctor sampling and self-collection of specimens in the same examinee for cervical cytopathology and human papillomavirus (HPV) testing.Methods　Patients who have undergone cervical cancer screening at the four clinics affiliated with the Association for Preventive Medicine of Japan and who consented to participate were included in the study. Approximately one month after undergoing cervical cancer screening at the clinic, we tested a method of self-collection by mailing a Kato-type self-collection container to the participants. We evaluated the results of cytopathology and HPV testing obtained by self-collection and doctor sampling in the same patients. We used the χ 2 test and κ analysis for the evaluation of the results.Results　A total of 134 health checkup participants each underwent both doctor sampling and self-collection. The positive rate of cytology was 6.0% in doctor sampling and 2.2% for self-collection, but there was no evidence in statistical significance (P>0.05). However, cervical duct lining membrane cells could not be detected by self-collection. The positive rate of HPV testing in both doctor sampling and self-collection was the same at 14.2%. However, HPV18 type was positive only in one case by self-collection.Conclusion　The results of this study suggest that it is necessary to proceed with studies by self-collection, and introduce the applications of liquid cytopathology and its combined uses with HPV testing.

Cervical cancer (CC) represents the most common cancer among women in developing countries. Present confirmation suggests that human papillomavirus (HPV) testing is more efficient than cytology for CC screening. Even if implementing a high-quality cytology programme in these countries is probable, it would only be fairly effective. This is because the presently used Pap test misses approximately 50% of high-grade precursor lesions and cancers with a single screening. Several screening alternatives have been planned for areas with incomplete resources. Amid these, visual inspection with acetic acid (VIA) includes the application to the cervix of 5% diluted acetic acid (vinegar), making the dysplastic epithelium turn white (acetowhitening). Screening with HPV testing and VIA have been verified to be effective and potentially cost-effective in low-resource settings, allowing for fewer follow-up visits (e.g., screen-and-treat approaches) and, in the case of HPV testing, automated processing of laboratory specimens that reduces resource and quality control necessities. [ABSTRACT FROM AUTHOR]

Objective To explore emotional responses, and predictors of negative reactions, among women undergoing human papillomavirus ( HPV) tests in routine clinical practice. Design Exploratory qualitative interview study. Setting A large busy colposcopy clinic in a Dublin hospital. Sample Twenty-seven women who had had an HPV DNA test in the previous 6 months following one or more low-grade cytology tests or treatment for cervical intraepithelial neoplasia ( CIN). Methods In-depth semi-structured interviews were conducted. Interview transcripts were analysed using a thematic approach (Framework Analysis). Main outcome measures Women's emotional responses and predictors of negative emotional reactions. Results For most women, having a test for high-risk HPV types generated little negative or positive emotional impact. Adverse emotional responses related to HPV infection rather than testing. Factors that influenced whether women experienced negative emotional responses were: concerns over abnormal cytology or diagnosis of CIN; HPV knowledge; awareness of HPV being sexually transmitted; awareness of HPV prevalence; and HPV information needs. Women's concerns about abnormal cytology/ CIN dominated all other issues. Conclusions These qualitative data suggest that in the context of follow up of abnormal cytology or treatment for CIN, the emotional impact of HPV testing may be modest: women's primary concerns at this time relate to abnormal cytology/ CIN. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Visual inspection with 5% Acetic acid (VIA) as a low cost screening method has good sensitivity with the limitation of low specificity and low positive predictive values. The present study therefore evaluates the performance of secondary testing by human papillomavirus (HPV) test and Colposcopy in a single-visit screening approach to increase program effectiveness in limited health-care resources settings. MATERIALS AND METHODS: In a cross-sectional cervical cancer screening trial, 3629 women (30-65 years) were screened by primary screening test VIA. VIA test positive women were subsequently tested for the presence of oncogenic HPV types by hybrid capture II and with colposcopy. The reference investigation histopathology was performed for all primary screen positive women. RESULTS: Data for 3613 evaluable women showed 352 (9.7%) women positive on primary screening by VIA. VIA had a sensitivity of 93% (95% confidence interval (CI): 0.76-0.99) and specificity of 91% (95% CI: 0.90-0.92) respectively to detect the cervical intraepithelial neoplasia grade 2+ . HPV DNA and colposcopy as secondary tests to triage VIA positive women had a sensitivity of 61% (95% CI: 0.41-0.78), 43% (95% CI: 0.24-0.63) and specificity of 99% (95% CI: 0.99-1.00), 99% (95% CI: 0.99-0.99) respectively for detecting CIN2+ lesions. CONCLUSION: Two step screening model combining highly sensitive low cost test like VIA for primary screening followed by more specific HPV DNA test as triage test for primary screen positive can be a cost-effective cervical screening strategy in resource constrained settings. [ABSTRACT FROM AUTHOR]

Aim The purpose of our study was to evaluate the efficacy of laser ablation as a conservative treatment for cervical intraepithelial neoplasia 3 ( CIN3) and assess whether the human papillomavirus ( HPV) test is useful to predict recurrence after treatment. Materials and Methods A total of 134 patients who received laser ablation for treatment of CIN3 were enrolled in this study. During the follow-up period, patients were followed with cytological and colposcopic evaluations. Recurrence of CIN3 was regarded as the primary end-point. HPV genotype was tested before and after treatment. Post-treatment cumulative recurrence rates were estimated and comparisons by both patient age and HPV genotype were performed. Results Overall cumulative recurrence rate of CIN3 in the first year after treatment was 22.6% for all patients. No significant correlation was shown between patient age and recurrence. Patients infected by specific genotypes (16, 18, 31, 33, 52, and 58) frequently failed to clear the infection after treatment. The 1-year recurrence-free survival in those positive after treatment for eight high-risk genotypes (16, 18, 31, 33, 35, 45, 52, and 58) was significantly lower (66.7%), compared to that in those positive for other high-risk types (78.6%). The recurrence-free survival of those who remained HPV-positive after treatment was significantly lower than those who turned negative. Conclusion Laser ablation should be performed prudently with appropriate patient counseling about recurrence rate. Considering its minimal invasiveness, laser ablation is effective, especially for young patients who are negative for eight high-risk genotypes. With regard to HPV testing, although genotyping has significant value for predicting recurrence, screening for all genotypes warrants further evaluation. [ABSTRACT FROM AUTHOR]

BACKGROUND High-risk human papillomavirus (hrHPV) DNA detection is generally accepted for the triage of women with a cytologic diagnosis of atypical squamous cells of undetermined significance (ASC-US). However, no consensus has been reached on the optimal management of low-grade squamous intraepithelial lesions (LSIL). METHODS In this meta-analysis, the diagnostic accuracy of nucleic acid sequence-based amplification (NASBA) detection of messenger ribonucleic acid (mRNA) of 5 hrHPV types (the PreTect HPV-Proofer and NucliSENS EasyQ tests) for detecting grade 2 cervical intraepithelial neoplasia or worse (CIN2+) and CIN3+ was assessed in women who had a diagnosis of ASC-US and LSIL. The results were compared with the Hybrid Capture-2 (HC2) assay, which detects the DNA of 13 hrHPV types. A bivariate random-effect model that incorporated the intrinsic correlation between the true-positive and false-positive rates was used for a pooled meta-analysis. RESULTS Considering underlying CIN2+, the pooled absolute sensitivity of the 10 included studies was 75.4% (95% confidence interval [CI], 68.1%-82.7%) and 76.2% (95% CI, 68.3%-76.9%) for the triage of ASC-US and LSIL, respectively. The pooled absolute specificity to exclude CIN2+ was 77.9% (95% CI, 70.1%-85.7%) and 74.2% (95% CI, 69.5%-78.8%) in women with ASC-US and LSIL, respectively. Five studies allowed direct comparison of the mRNA assays with HC2. Considering CIN2+ in women with ASC-US and LSIL, mRNA testing was substantially more specific than the HC2 assay (ratio: 1.98 and 3.36, respectively; P < .001) but was less sensitive (ratio: 0.80 and 0.74, respectively; P < .001). CONCLUSIONS HPV assays for detecting the mRNA of 5 hrHPV types may reduce the over-diagnosis of women who have minor cytologic abnormalities. However, given the lower sensitivity, women with negative mRNA test results cannot be considered free of CIN2+ and require further surveillance. Cancer (Cancer Cytopathol) 2013;121:675-687. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

J. Bowring, R. Albrow, A. Fisher, G. Downey, J. Cullimore, J. Patnick, P.G. Walker and H.C. Kitchener A prospective study of human papillomavirus (HPV) testing to resolve uncertainty in colposcopy Objective: UK colposcopy services are seeing increased workloads, a large proportion of which are follow-up appointments. The English Cervical Screening Programme HPV Special Interest Group identified five subcategories of colposcopy clinic patients who often require prolonged follow-up regimes for low-grade abnormalities. Human papillomavirus (HPV) testing has a high negative predictive value, meaning that HPV-negative women are at very low risk of underlying disease. Our objectives were to quantify the number of HPV-negative women in each study subcategory and to evaluate the number who could potentially be discharged from colposcopy on the basis of their results. Methods: Four colposcopy clinics prospectively identified women according to five categories over 12 months. All women underwent cytological testing and high-risk HPV (hrHPV) testing using the Hybrid Capture 2 test. Management outcomes and decisions based on a knowledge of the HPV status were recorded. Results: Data available on 755 women showed that 422/755 (55.9%) and 260/755 (34.4%) had persistent cervical intraepithelial neoplasia grade 1 (CIN1) (Category 1) or a minor abnormality following treatment (Category 2), respectively. In Categories 1 and 2, 51.7% and 60.2%, respectively, were hrHPV negative. The rates with biopsies of CIN2 or worse (CIN2+) across the two categories were 3/355 (0.8%) and 21/291 (7.0%) for hrHPV-negative and hrHPV-positive women, respectively. Conclusion: The incorporation of hrHPV testing within organized cervical screening programmes has been widely accepted. hrHPV testing for the clinical scenarios outlined in this study detects women who are hrHPV negative and therefore at low risk of underlying disease, potentially reducing anxiety and inconvenience for women and costs to colposcopy services. [ABSTRACT FROM AUTHOR]

Human papillomavirus testing has been shown to be far more sensitive and robust in detecting cervical intraepithelial neoplasia 2 and above (and cervical intraepithelial neoplasia 3 and above) for cervical screening than approaches based on either cytology or visual inspection; however, there are a number of issues that need to be overcome if it is to substantially reduce the morbidity and mortality associated with cervical cancer at the population level. The two main issues are coverage (increasing the number of women who participate in screening) and the management of women who test positive for high-risk human papillomavirus. This article will review the potential for vaginal self-collection to improve coverage and the options for triage of high-risk human papillomavirus-positive women in high-resource and low-resource settings. [ABSTRACT FROM AUTHOR]

Persistence of human papillomavirus (HPV) infection is necessary for the development of cervical cancer. Additionally, infection with HPV is implicated in the majority of cases of other genital tract malignancies including vulvar, penile, and vaginal cancer. HPV testing and vaccination are a routine part of obstetrical/gynecological clinical practice. With an enhanced public awareness of HPV infections, many patients turn to their obstetricians/gynecologists with questions about transmission, testing, and prevention. In this review, we will discuss the biology of HPV, epidemiology of disease, methods and indications for testing, and vaccination strategies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

J. H. F. Smith ABC3 Part I: a review of the guidelines for terminology, classification and management of cervical cytology in England The provision of guidance on cytology reporting and evaluation, first outlined in 1995 with the publication of Achievable Standards, Benchmarks for Reporting, and Criteria for Evaluating Cervical Cytopathology (ABC), and subsequently revised and expanded in a second edition in 2000, has been pivotal to the success of the National Health Service Cervical Screening Programme (NHSCSP), ensuring that standards are upheld, and that rigorous evaluation and quality assurance take place. In the last decade, major changes to the NHSCSP, notably the adoption of revised age ranges and screening intervals for all women in England, implementation of liquid-based cytology and, most recently, the decision to introduce high-risk human papillomavirus (HR-HPV) testing for triage of low-grade and borderline (equivalent to 'atypical') cytological abnormalities and test of cure after treatment of cervical intraepithelial neoplasia (CIN) determined that an updated version of ABC was required. The third edition of ABC recommends adoption, with minor modification, of the revised British Society for Clinical Cytology terminology and provides guidance on the management of abnormal cytology results linked to this terminology taking account of HR-HPV testing. To accommodate these changes, expanded result codes, which are electronic codes used to transfer management information to central computers for follow-up, call and recall of individual women, have been developed. Further guidance on specimen adequacy is also provided. Revised performance indicators are described and explained in a separate article by R. Blanks in this issue of Cytopathology. All the changes in ABC3 are designed to support the mission statement of the NHSCSP that 'the objective of cervical screening is to reduce cervical cancer incidence and mortality by screening with a high sensitivity for the detection of CIN2 or worse, whilst maintaining a high specificity'. [ABSTRACT FROM AUTHOR]

The best method for identifying women who have minor cervical lesions that require diagnostic workup remains unclear. The authors of this report performed a meta-analysis to assess the accuracy of cyclin-dependent kinase inhibitor 2A (p16INK4a) immunocytochemistry compared with high-risk human papillomavirus DNA testing with Hybrid Capture 2 (HC2) to detect grade 2 or greater cervical intraepithelial neoplasia (CIN2+) and CIN3+ among women who had cervical cytology indicating atypical squamous cells of undetermined significance (ASC-US) or low-grade cervical lesions (LSIL). A literature search was performed in 3 electronic databases to identify studies that were eligible for this meta-analysis. Seventeen studies were included in the meta-analysis. The pooled sensitivity of p16INK4a to detect CIN2+ was 83.2% (95% confidence interval [CI], 76.8%-88.2%) and 83.8% (95% CI, 73.5%-90.6%) in ASC-US and LSIL cervical cytology, respectively, and the pooled specificities were 71% (95% CI, 65%-76.4%) and 65.7% (95% CI, 54.2%-75.6%), respectively. Eight studies provided both HC2 and p16INK4a triage data. p16INK4a and HC2 had similar sensitivity, and p16INK4a has significantly higher specificity in the triage of women with ASC-US (relative sensitivity, 0.95 [95% CI, 0.89-1.01]; relative specificity, 1.82 [95% CI, 1.57-2.12]). In the triage of LSIL, p16INK4a had significantly lower sensitivity but higher specificity compared with HC2 (relative sensitivity, 0.87 [95% CI, 0.81-0.94]; relative specificity, 2.74 [95% CI, 1.99-3.76]). The published literature indicated the improved accuracy of p16INK4a compared with HC2 testing in the triage of women with ASC-US. In LSIL triage, p16INK4a was more specific but less sensitive. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]