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Background Gay and bisexual men (GBM) are at increased risk of human papillomavirus (HPV)–associated anal high-grade squamous intraepithelial lesions (HSILs). Understanding the fractions of HSILs attributable to HPV genotypes is important to inform potential impacts of screening and vaccination strategies. However, multiple infections are common, making attribution of causative types difficult. Algorithms developed for predicting HSIL-causative genotype fractions have never been compared with a reference standard in GBM. Method Samples were from the Study of the Prevention of Anal Cancer. Baseline HPV genotypes detected in anal swab samples (160 participants) were compared with HPV genotypes in anal HSILs (222 lesions) determined by laser capture microdissection (LCM). Five algorithms were compared: proportional, hierarchical, maximum, minimum, and maximum likelihood estimation. Results All algorithms predicted HPV-16 as the most common HSIL-causative genotype, and proportions differed from LCM detection (37.8%) by algorithm (with differences of −6.1%, +20.9%, −20.4%, +2.9%, and +2.2% respectively). Fractions predicted using the proportional method showed a strong positive correlation with LCM, overall (R = 0.73 and P =.002), and by human immunodeficiency virus (HIV) status (HIV positive, R = 0.74 and P =.001; HIV-negative, R = 0.68 and P =.005). Conclusions Algorithms produced a range of inaccurate estimates of HSIL attribution, with the proportional algorithm performing best. The high occurrence of multiple HPV infections means that these algorithms may be of limited use in GBM. [ABSTRACT FROM AUTHOR]

Background Australia introduced a school-based gender-neutral human papillomavirus (HPV) vaccination program for girls and boys aged 12–13 years in 2013. We examined HPV type–specific antibody levels in unvaccinated young men who have sex with men (MSM) with natural infection and compared these with levels in those vaccinated against HPV. Methods Serum specimens at baseline were collected from MSM aged 16–20 years in the HYPER1 (Human Papillomavirus in Young People Epidemiological Research) and HYPER2 studies, conducted in 2010–2013 and 2017–2019, respectively. Merck's 4-plex HPV competitive Luminex Immunoassay was used to quantify HPV6-, HPV11-, HPV16-, and HPV18-specific antibodies. We compared antibody levels for each HPV genotype between unvaccinated men (HYPER1) and vaccinated men (HYPER2) using the Mann-Whitney U test. Results There were 200 unvaccinated men and 127 vaccinated men included in the analysis. Median antibody levels among vaccinated men were significantly higher than levels among unvaccinated men for HPV6 (223 milli-Merck units per milliliter [mMU/mL] vs 48 mMU/mL, P  < .0001), HPV11 (163 mMU/mL vs 21 mMU/mL, P  < .0001), HPV16 (888 mMU/mL vs 72 mMU/mL, P  < .0001), and HPV18 (161 mMU/mL vs 20 mMU/mL, P  < .0001). Antibody levels did not change over time for up to 66 months for all 4 genotypes among vaccinated men. Conclusions Among young MSM vaccinated with the quadrivalent HPV vaccine, antibody levels for HPV6, HPV11, HPV16, and HPV18 were significantly higher than those in unvaccinated MSM following natural infection. Antibody levels following vaccination appeared to remain stable over time. Clinical Trials Registration NCT01422356 for HYPER1 and NCT03000933 for HYPER2. [ABSTRACT FROM AUTHOR]

Background Gay and bisexual men (GBM) are disproportionately affected by anal cancer. Prevention is hindered by incomplete understanding of the natural history of its precursor, anal high-grade squamous intraepithelial lesions (HSIL). Methods The Study of the Prevention of Anal Cancer, conducted between 2010 and 2018, enrolled human immunodeficiency virus (HIV)-positive and HIV-negative GBM aged ≥35 years. Anal cytology and high-resolution anoscopy (HRA) were performed at baseline and 3 annual visits. A composite HSIL diagnosis (cytology ± histology) was used. Cytological high-grade squamous intraepithelial lesions (cHSIL) incidence and clearance rates were calculated with 95% confidence intervals (CIs). Predictors were calculated using Cox regression with hazard ratios (HRs) and 95% CIs. Results Among 617 men, 220 (35.7%) were HIV-positive, median age 49 years. And 124 incident cHSIL cases occurred over 1097.3 person-years (PY) follow-up (11.3, 95% CI 9.5–13.5 per 100 PY). Significant bivariate predictors of higher incidence included age <45 years (HR 1.64, 95% CI 1.11–2.41), HIV positivity (HR 1.43, 95% CI.99–2.06), prior SIL diagnosis (P -trend <.001) and human papillomavirus (HPV)16 (HR 3.39, 2.38–4.84). Over 695.3 PY follow-up, 153 HSIL cleared (clearance 22.0, 95% CI 18.8–25.8 per 100 PY). Predictors were age < 45 years (HR 1.52, 1.08–2.16), anal intraepithelial neoplasia (AIN)2 rather than AIN3 (HR 1.79, 1.29–2.49), smaller lesions (HR 1.62, 1.11–2.36) and no persistent HPV16 (HR 1.72, 1.23–2.41). There was 1 progression to cancer (incidence 0.224, 95% CI.006–1.25 per 100 PY). Conclusion These data strongly suggest that not all anal HSIL detected in screening requires treatment. Men with persistent HPV16 were less likely to clear HSIL and are more likely to benefit from effective HSIL treatments. Clinical Trials Registration Australia New Zealand Clinical Trials Registry (ANZCTR365383). [ABSTRACT FROM AUTHOR]

Objectives The VACCINE [Vaccine Against Cervical Cancer Impact and Effectiveness] study evaluated the prevalence of quadrivalent vaccine-targeted human papillomavirus (HPV) genotypes (HPV 6, 11, 16, 18) amongst young women of vaccine-eligible age. Methods Between October 2011 – June 2015, women aged 18–25 years from Victoria, Australia, were recruited through targeted advertising on the social networking website Facebook. Participants completed an online questionnaire and provided a self-collected vaginal swab for HPV DNA detection and genotyping (Linear Array HPV genotyping assay). Self-reported HPV vaccination details were verified with the National HPV Vaccination Program Register (NHVPR). Results Of 1223 who agreed to participate, 916 (74.9%) completed the survey and, for 1007 (82.3%) sexually-active participants, 744 (73.9%) returned the self-collected swab, of which 737 contained detectable DNA. 184/737 (25.0%) were positive for HPV. Vaccine-targeted HPV genotypes were detected in only 13 (1.7%) women: 11 HPV 16 (six vaccinated after sexual debut, five unvaccinated) and two HPV 6. Prevalence of any of HPV 31/33/45 collectively was 2.9%, varying significantly by vaccination status (fully 2.0%, unvaccinated 6.8%; p = 0.01). Vaccination rates among the sexually-active cohort were high, with 65.6%, 71.6% and 74.2% of participants having received three, at least two or at least one dose of vaccine, respectively. Of women self-reporting HPV vaccination, the NHVPR confirmed one or more doses were received in 90%. Strong associations were observed between vaccination status, age, language spoken at home and country of birth, as well as between HPV detection and the number of male sexual partners. Conclusion Surveillance five to eight years’ post-initiation of a national HPV vaccination program demonstrated a consistent and very low prevalence of vaccine-related HPV genotypes and some evidence of cross protection against related types amongst vaccine-eligible women from Victoria, Australia. [ABSTRACT FROM AUTHOR]

Background: Persistent high-risk human papillomavirus (HPV) infection is a necessary prerequisite for development of cervical cancer and its precursor lesion, high-grade squamous intraepithelial lesion (HSIL). However, HPV infection is not sufficient to drive this process, and genetic and environmental factors may also play a role.Methods/design: The Cervical Cancer, Genetics and Environment Twin Study was established to investigate the environmental and genetic influences on variation in susceptibility to cervical pre-cancer in 25- to 69-year-old monozygotic (MZ) and dizygotic (DZ) twins recruited through the Australian Twin Registry. Reviews of Papanicolaou (Pap) screening histories were undertaken to identify individual women with a history of an abnormal Pap test. This was followed by detection of HPV in archival Pap smears of selected twin pairs to determine HPV persistence. Selected twin pairs also completed a detailed questionnaire on socio-demographic characteristics, sexual behavior, and HPV knowledge. In future analyses, under the assumptions of the classical twin design, case-wise concordance for persistent HPV infection and HSIL will be calculated for MZ and DZ twin pairs, and twin pairs (both MZ and DZ) who are discordant for the above outcomes will be used to assess the contributions of measured environmental risk factors.Discussion: The study examines factors related to HPV persistence and development of HSIL among female MZ and DZ twins. The results will contribute to our understanding of the natural history of cervical HPV infection and the relative contributions of genetic and environmental factors in disease progression. [ABSTRACT FROM AUTHOR]

Background: In Australia, high uptake of the quadrivalent human papillomavirus (4vHPV) vaccine has led to reductions in the prevalence of human papillomavirus (HPV) genotypes 6, 11, 16, and 18 in women and girls aged ≤25 years. We evaluated the impact of the program impact on HPV prevalence in unvaccinated male subjects.Methods: Sexually active heterosexual male subjects aged 16-35 years were recruited in 2014-2016. Participants provided a self-collected penile swab sample for HPV genotyping (Roche Linear Array) and completed a demographic and risk factor questionnaire.Results: The prevalence of 4vHPV genotypes among 511 unvaccinated male subjects was significantly lower in those aged ≤25 than in those aged >25 years: 3.1% (95% confidence interval, 1.5%-5.7%) versus 13.7% (8.9%-20.1%), respectively (P < .001); adjusted prevalence ratio, 0.22 (.09-.51; P < .001). By contrast, the prevalence of high-risk HPV genotypes other than 16 and 18 remained the same across age groups: 16.8% (95% confidence interval, 12.6%-21.9%) in men aged ≤25 years and 17.9% (12.4%-25.0%) in those aged >25 years (P = .76); adjusted prevalence ratio, 0.98, (.57-1.37; P = .58).Conclusions: A 78% lower prevalence of 4vHPV genotypes was observed among younger male subjects. These data suggest that unvaccinated men may have benefited from herd protection as much as women from a female-only HPV vaccination program with high coverage. [ABSTRACT FROM AUTHOR]

In populations where the prevalence of vaccine-targeted HPV types has been reduced significantly due to widespread vaccination of the target population, the sensitivity of some consensus PCR-based assays to detect remaining HPV types may be altered, leading to misrepresentations of prevalence. Importantly, this may lead to false indications of type replacement in vaccinated populations. To assess whether excess vaccine-targeted HPV DNA resulted in reduced detection of other genotypes on the Roche HPV linear array genotype assay, simulated samples containing 1000 copies of one or two high-risk HPV DNA genomes in the presence and the absence of 10,000 copies of the HPV16 genome were tested. HPV16 alone did not affect detection of other high-risk genotypes; however when HPV16 and an additional genotype were present, detection of HPV31, 33, 51 or 59 was impeded, indicating potential for misrepresentation of population-based prevalence of these genotypes and false evidence for type replacement following vaccination. [ABSTRACT FROM AUTHOR]

Background. Anogenital human papillomavirus (HPV) is common among men who have sex with men (MSM) and causes anal cancer. This study examined the determinants of initial anogenital HPV infection among teenage MSM.Methods. Two hundred MSM aged 16 to 20 years were recruited via community and other sources. Men were tested for HPV DNA from the anus and penis.Results. The proportion of men with anal HPV of any type increased from 10.0% in men reporting no prior receptive anal sex to 47.3% in men reporting ≥4 receptive anal sex partners (P < .001).A similar pattern was also seen with HPV type 16 (P = .044). The proportion of men with penile HPV increased from 3.7% in men reporting no prior insertive anal sex to 14.8% in men reporting ≥4 insertive anal sex partners (P = .014). Overall, 39.0% (95% confidence interval (CI), 32.2%−46.1%) of men had at least 1 HPV type: 23.0% (95% CI, 17.4%−29.5%) had a vaccine-preventable type (6, 11, 16 or 18).Conclusions. Early and high per partner transmission of HPV occurred between men soon after their first sexual experiences. HPV vaccination needs to commence early for maximal prevention of HPV among MSM. [ABSTRACT FROM AUTHOR]

Abstract: An automated blotter was evaluated for detection of the HPV SPF10-LiPA25 RHA for HPV genotyping with 63 FFPE tissue and 45 WHO proficiency panel samples. The results showed that 10–20% more types were detected and bands were of significantly stronger intensity (p <0.0001) compared to manual processing. Therefore it was concluded that automated detection of HPV genotypes using the HPV SPF10-LiPA25 is more sensitive for low copy number and mixed-type HPV samples. [Copyright &y& Elsevier]

Australia introduced a school-based human papillomavirus (HPV) vaccination program for females aged 12–13 years in 2007, with a three-year catch-up to age 26; and for boys aged 12–13 from 2013, with a two-year catch-up to age 15. This study aimed to compare the prevalence of penile HPV between teenage heterosexual males in cohorts eligible or non-eligible for the school-based male vaccination program. Between 2014 and 2017, sexually active heterosexual males aged 17–19 were recruited from sexual health centres and community sources across Australia. Males provided a self-collected penile swab for 37 HPV genotypes using Roche Linear Array and completed a questionnaire. We calculated adjusted prevalence ratios (aPR) of HPV between males in two periods: 2014–2015 (preceding implementation of school-based male vaccination) and 2016–2017 (eligible for school-based male vaccination). Self-reported vaccine doses were confirmed with doses reported to the National HPV Vaccination Program Register. Overall, 152 males were recruited in 2014–2015 and 146 in 2016–2017. Numbers of female sex partners and condom use did not differ between the two periods. The prevalence of quadrivalent vaccine-preventable [4vHPV] genotypes (6/11/16/18) was low in both periods (2.6% [2014–15] versus 0.7% [2016–17]; p = 0.371; aPR 0.28 [95% CI: 0.03–2.62]). Compared with men in 2014–2015, men in 2016–2017 had a lower prevalence of any of the 37 HPV genotypes tested (21.7% versus 11.6%; aPR 0.62 [95% CI: 0.36–1.07]) and any of the 13 high-risk genotypes tested (15.8% versus 7.5%; aPR 0.59 [95% CI: 0.30–1.19]). Prevalence of low-risk HPV genotypes did not differ between the two periods. Of the males recruited in 2016–2017, 55% had received ≥1 vaccine dose. The prevalence of 4vHPV genotypes among teenage heterosexual males in both cohorts was low, presumably due to herd protection from the female-only vaccination program. Further studies are required to determine the impact of universal HPV vaccination on HPV prevalence in males. [ABSTRACT FROM AUTHOR]