Triage performance and predictive value of the human gene methylation panel among women positive on self-collected HPV test: Results from a prospective cohort study.

Triaging of women positive for high-risk human papillomavirus (hrHPV) on self-collected samples requires a molecular reflex test to avoid recall for cytology or visual tests. We assessed triage performance and predictive value of human gene methylation panel (ZNF671/ASTN1/ITGA4/RXFP3/SOX17/DLX1) alone and with combination of HPV16/18 genotyping in a longitudinal screening study. Out of 9526 women at baseline, 1758 women positive for hrHPV on self-collected samples followed up yearly were included in the current analysis. Satisfactory risk stratification to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was demonstrated by the methylation panel with an odds ratio (OR) of 11.3 among methylation-positive women compared to methylation-negative counterparts. Triaging with methylation panel reduced colposcopy referral rate by 67.2% with sensitivity and specificity of 83.0% and 69.9% to detect CIN2+. The corresponding values for the combining methylation and HPV 16/18 were 96.6% and 58.3%. The cumulative 3-year incident CIN2+ risk was 6.8% (95% CI: 4.9%-8.6%) for hrHPV positive women, which was reduced to 4.5% (95% CI: 2.7%-6.3%) and 2.9% (95% CI: 1.2%-4.5%) for women negative on methylation triaging alone and negative on the combined strategy. The corresponding risk for women positive for both methylation and HPV 16/18 reached 33.7% (95% CI: 19.0%-45.8%). Our study demonstrated the satisfactory triage performance and predictive value of the methylation panel, especially in combination with HPV 16/18 genotyping. The substantially lower risk of CIN2+ among the triage negative women over the next 3 years suggests that the interval for repeat HPV test can be safely extended to at least 2 years.

Durability of clinical performance afforded by self-collected HPV testing: A 15-year cohort study in China.

OBJECTIVE: Self-collected HPV testing could substantially reduce disparities in cervical cancer screening, with slightly lower sensitivity compared to physician-collected specimens cross-sectionally. We aimed to evaluate the comprehensive long-term performance of self-collected HPV testing prospectively. METHODS: In 1999, 1997 women were screened by HPV testing on self-collected and physician-collected samples, cytology and visual inspection with acetic acid (VIA) and followed up in 2005, 2010 and 2014, respectively. HPV testing was performed with Hybrid Capture II. Prospective performance, baseline clinical efficiency, and 15-year cumulative risk of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were analyzed. RESULTS: Self-collected HPV testing prospectively detected 83.3% (95% CI:74.9%,89.3%), 70.3% (95% CI:62.5%,77.2%) and 63.3% (95% CI:55.7%, 70.2%) of cumulative CIN2+ at 6-year, 11-year and 15-year follow-up, respectively. Relative cumulative sensitivity of physician-collected HPV testing versus self-collected HPV testing was stable over 15 years at about 1.16. Cumulative sensitivity of self-collected HPV testing was comparable to cytology and significantly higher than VIA. Among women positive by self-collected HPV testing at baseline, 26.2% (95% CI:21.5%, 30.9%) developed CIN2+ during 6-year follow-up and no difference was observed with physician-collected HPV testing even 15 years after baseline. Negative self-collected HPV results provided greater protection against CIN2+ than VIA and ascertained CIN2+ cumulative incident rates as low as 1.1% at the 6-year follow-up. CONCLUSIONS: Self-collected HPV testing demonstrates lower sensitivity than physician-collected HPV testing but performs comparably to cytology prospectively and provides satisfactory assurance against CIN2+, indicating an alternative role in cervical cancer primary screening with five-year interval as an option especially in low-resource settings.

Clinical Performance of Self-collected Specimen HPV-DNA vs Clinician- collected Specimen HPV-mRNA to Detect High-risk HPV and High-grade Cervical Lesions and Cancer.

OBJECTIVE: Self- collected specimens to detect high-risk (hr) HPV and high-grade cervical lesions (CIN2+) has been introduced aiming to increase cervical cancer screening coverage. The performance of self- collected specimen  compared to clinician collected specimen is one major concern. This study aimed to compare self-sampling HPV-DNA and clinician-sampling HPV-mRNA to detect hr-HPV and high-grade cervical lesions. METHODS: Women with abnormal cervical cytology and/ or positive hr-HPV who attended the colposcopy clinics in 10 tertiary hospitals in Bangkok were enrolled. Self-collected specimens were evaluated for  HPV DNA using Cobas® 4800 HPV test prior to the clinician-collected specimens which were tested for HPV mRNA with APTIMA® HPV Assay. Subsequent colposcopy with biopsy was performed. The detection rates of hr-HPV from both HPV tests and their performance to detect high-grade lesions pathology were compared. RESULTS: Data from 497 women's specimens were analyzed. Both samplings had 86.8% concordance rate in detecting hr-HPV (Kappa 0.670; 95% confidence interval [CI] 0.599-0.746, P value < 0.001). The sensitivity (95% CI) of self-collected specimen HPV DNA and clinician- collected specimen HPV-mRNA to detect high-grade lesions were 91.8% (85.4%-96.0%) and 90.2% (83.6%-94.9%) respectively. The corresponding negative predictive values (95% CI) were 91.9% (85.6%-96.0%) and 91.7% (86.0%-95.7%) respectively. CONCLUSION: HPV DNA testing from self-collected specimen to detect HR-HPV demonstrates high concordance with HPV mRNA testing from clinician-collected specimen. The sensitivity and negative predictive value of both tests to detect high-grade lesions are comparable.

Facilitators and Barriers to Take Up Clinician-Collected and Self-Collected HPV Tests among Chinese Men Who Have Sex with Men.

Regular tests for human papillomavirus (HPV) and early treatment could represent an important strategy for preventing anal cancers among men who have sex with men (MSM). This study investigated facilitators and barriers to take up clinician-collected and self-collected HPV tests among Chinese MSM. This study was based on the baseline sample of a longitudinal study promoting HPV vaccination among 350 Chinese MSM who had never received an HPV vaccination. The baseline survey was conducted from August 2019 to April 2020. The prevalence of any HPV tests uptake in lifetime was 19.1%; 4.9% had HPV infection in anus, genital, oral cavity, and other places. Among the participants, 20% and 76.8% intended to take up self-financed and free clinician-collected HPV tests, and 76.8% intended to use free self-collected HPV tests. After adjusting for significant background characteristics, perceived risk of HPV infection, and perceived benefits, barriers, cue to action, and self-efficacy related to HPV tests in general and/or specific to self-collected HPV tests were associated with behavioral intention to take up free clinician-collected and/or self-collected HPV tests. Less than 20% of Chinese MSM reported HPV tests uptake. Modifying perceptions related to HPV tests may be useful to increase HPV tests coverage in this group.

A Novel Strategy for Cervical Cancer Prevention Using Cervical-Vaginal Self-Collected Samples Shows High Acceptability in Women Living in Low-Income Conditions from Bucaramanga, Colombia.

INTRODUCTION: Human papillomavirus molecular detection prevents cervical cancer (CC). To widen its use, cervical-vaginal self-collection devices are proposed. Our aim was to determine the acceptability of self-sampled cervical-vaginal protocol and the reproducibility of results using HPV detection brushes in a low-income Colombian population between 35 and 65 years old. METHODS: Cross-sectional study including women classified as medium to high-risk for developing CC by using a short-standardized survey. After receiving instructions, women self-collected a cervical-vaginal sample. Subsequently, a perception survey was conducted. RESULTS: Four hundred and twenty-three women performed self-collected sampling. The median age was 46.5 years (IQR 40-52), 56.5% were housewives, and 55.1% had finished elementary school. About 99% of the population (n=419) considered that they understood the instructions, 19.4% (n=82) reported having concerns about the self-collected sample, 9.2% (n=39) distrusted the results because of the self-collection, 7.3% (n=31) felt uncomfortable with the procedure, and 9.7% (n=41) reported some pain. The majority would recommend the procedure to others (99%), 88.5% of the sampled population preferred the self-collected method, 4% preferred conventional cytology, and 7.3% were not sure. The reasons behind favoring the self-collected procedure included privacy (n= 149, 40.1%), comfort (n=110, 29.7%), easiness (n=52, 14%), reliability (n=46, 12.4%), and less painful (n=110, 29.7%). The percentage of HPV detection agreement between the self-collected and the healthcare professional-collected procedures was 98.99% (Cohen's Kappa=0.9774). CONCLUSION: Women living in low-income households in Bucaramanga, Colombia preferred the self-sampling procedure because it was easy to use, convenient, and private, resulting in 98% acceptability, and positioning it as an excellent tool for CC prevention.

Comparison of detection rate of high risk HPV infection between self-collected HPV testing and clinician-collected HPV testing in cervical cancer screening.

OBJECTIVE: to correlate the detection rate of high risk HPV (HR-HPV) DNA between self-collected and clinician-collected testing. MATERIALS AND METHODS: A cross-sectional analytic study was conducted in 400 women undergoing cervical cancer screening program during February and May 2015. The procedure began with self-collected method and then clinician-collected method. Then, the specimens were processed and interpreted with the same technique. If the results from either methods were positive for HPV genotype 16 or 18, colposcopy was performed. We also conducted cytology testing for the participants. If the results were abnormal (ASC-US+), colposcopy was also performed. RESULTS: The detection rate of HR-HPV DNA was 10.0% and 7.5% by self-collected and clinician-collected specimen, respectively (kappa = 0.73). HR-HPV positive rate in cytology ASC-US+ was no significantly different between groups. HR-HPV DNAs were positive in every HSIL (100% detection rate). HPV DNA test positive for detection CIN+ was not significantly different between self-collected and clinician-collected testing. CONCLUSION: self-collected HPV testing can be used as an alternative option for primary cervical screening program. Detection rate of high grade lesion is similar to clinician-collected test.

Community-based HPV self-collection versus visual inspection with acetic acid in Uganda: a cost-effectiveness analysis of the ASPIRE trial.

BACKGROUND: Cervical cancer is the leading cause of cancer death for women in Uganda, despite the potential for prevention through organised screening. Community-based self-collected human papillomavirus (HPV) testing has been proposed to reduce barriers to screening. OBJECTIVE: Our objective was to evaluate the cost-effectiveness of the Advances in Screening and Prevention of Reproductive Cancers (ASPIRE) trial, conducted in Kisenyi, Uganda in April 2014 (n=500). The trial compared screening uptake and compliance with follow-up in two arms: (1) community-based (ie, home or workplace) self-collected HPV testing (facilitated by community health workers) with clinic-based visual inspection with acetic acid (VIA) triage of HPV-positive women ('HPV-VIA') and (2) clinic-based VIA ('VIA'). In both arms, VIA was performed at the local health unit by midwives with VIA-positive women receiving immediate treatment with cryotherapy. DESIGN: We informed a Monte Carlo simulation model of HPV infection and cervical cancer with screening uptake, compliance and retrospective cost data from the ASPIRE trial; additional cost, test performance and treatment effectiveness data were drawn from observational studies. The model was used to assess the cost-effectiveness of each arm of ASPIRE, as well as an HPV screen-and-treat strategy ('HPV-ST') involving community-based self-collected HPV testing followed by treatment for all HPV-positive women at the clinic. OUTCOME MEASURES: The primary outcomes were reductions in cervical cancer risk and incremental cost-effectiveness ratios (ICERs), expressed in dollars per year of life saved (YLS). RESULTS: HPV-ST was the most effective and cost-effective screening strategy, reducing the lifetime absolute risk of cervical cancer from 4.2% (range: 3.8%-4.7%) to 3.5% (range: 3.2%-4%), 2.8% (range: 2.4%-3.1%) and 2.4% (range: 2.1%-2.7%) with ICERs of US$130 (US$110-US$150) per YLS, US$240 (US$210-US$280) per YLS, and US$470 (US$410-US$550) per YLS when performed one, three and five times per lifetime, respectively. Findings were robust across sensitivity analyses, unless HPV costs were more than quadrupled. CONCLUSIONS: Community-based self-collected HPV testing followed by treatment for HPV-positive women has the potential to be an effective and cost-effective screening strategy.