Chow EPF, Tabrizi SN, Fairley CK, Wigan R, Machalek DA, Garland SM, Cornall AM, Atchison S, Hocking JS, Bradshaw CS, Balgovind P, Murray GL, and Chen MY
Background: Anal infection with high-risk human papillomavirus (HPV) genotypes 16 and 18 and anal cancer are overrepresented in men who have sex with men (MSM). This study investigated HPV prevalence in young MSM before and after the implementation of a school-based quadrivalent HPV (genotypes 6, 11, 16, and 18) vaccination programme for boys in Australia in 2013., Methods: In this repeated cross-sectional study, MSM aged 16-20 years were recruited from two successive birth cohorts via sexual health clinics and the community in Melbourne, Australia. The first cohort was before the implementation of gender-neutral vaccination (HYPER1 study, done in 2010-12, NCT01422356), and the second was the post-vaccination cohort (HYPER2 study, done in 2017-18, NCT03000933). Men who self-identified as being same-sex attracted were enrolled, and those recruited via the HYPER2 study had to be resident in Australia since 2013 to ensure eligibility. Study procedures were done in the Melbourne Sexual Health Centre. A clinician-collected anal swab and self-collected penile swab and oral rinse were tested for 28 HPV genotypes, and data on demographics and sexual health practices were collected via questionnaires. Only assessable samples were included in the analyses. We compared anatomical site-specific prevalence of HPV genotypes between cohorts by calculating the prevalence ratio, adjusting for age, circumcision, and sex with women. Herd protection was also assessed, by calculating the adjusted prevalence ratios by vaccination status., Findings: 400 MSM, 200 per cohort, were included in the study. In both cohorts, the median number of lifetime male partners was ten (IQR 5-25). The prevalence of any anal quadrivalent vaccine-preventable HPV genotype was higher in the pre-vaccination cohort (54 [28%] of 193) than in the post-vaccination cohort (14 [7%] of 193; adjusted prevalence ratio [PR] 0·24, 95% CI 0·14-0·42), largely driven by decreases in HPV6, followed by HPV11, 16, and 18. Nevertheless, there was also a significant reduction in anal HPV16 and 18 in the post-vaccination cohort from the pre-vaccination cohort (0·31, 0·14-0·68). The prevalence of any penile quadrivalent vaccine-preventable HPV genotype was also higher in the pre-vaccination cohort (21 [12%] of 177) than in the post-vaccination cohort (11 [6%] of 179; 0·48, 0·24-0·97), driven by decreases in HPV 6 and 11, but not by 16 and 18. The prevalence of any oral quadrivalent vaccine-preventable HPV genotype was higher in the pre-vaccination cohort (seven [4%] of 200) than in the post-vaccination cohort (one [1%] of 199; 0·10, 0·01-0·97); there were no cases of oral HPV6 or 11 detected in HYPER2. Comparing the pre-vaccinated cohort with the 149 confirmed vaccinated men from HYPER2 showed a reduction in any quadrivalent vaccine-preventable HPV genotype for anal (0·09, 0·03-0·25) and penile (0·18, 0·05-0·59) infection but not for oral infection (0·17, 0·03-1·08)., Interpretation: A reduction in anal, penile, and oral quadrivalent vaccine-targeted genotypes occurred in young MSM following the implementation of a school-based gender-neutral HPV vaccination programme. The fall in anal HPV16 and 18 may lead to a reduction in the incidence of anal cancer., Funding: Merck and the Australian Government Department of Health., Competing Interests: Declaration of interests EPFC is supported by an Australian National Health and Medical Research Council (NHMRC) Emerging Leadership Investigator Grant (GNT1172873). CKF and CSB are supported by an Australian NHMRC Leadership Investigator Grant (GNT1172900 and GNT1173361, respectively). EPFC and AMC have received educational grants from Seqirus Australia and bioCSL to assist with education, training, and academic purposes in the area of HPV, outside the submitted work. CKF has received research funding from CSL Biotherapies and owns shares in CSL Biotherapies. SMG has received advisory board fees and lecture fees from Merck for work in private time and through her institution (Royal Women's Hospital) funding for an investigator initiated grant from Merck for a young women's study on HPV, and is a member of the Merck Global Advisory Board for HPV vaccination. DAM reports educational grants from Seqirus to assist with education, training, and academic purposes in the area of HPV, and travel funding and honoraria to her institute from Merck, outside of the submitted work. She is also an investigator on a genital warts surveillance grant funded by Seqirus. She also reports grants from Commonwealth Department of Health during the conduct of the study. AMC reports grants from Australian Government of Health National HPV Monitoring Program during the conduct of the study. CSB reports grants from SpeeDx outside the submitted work. EPFC, MYC, CKF, SNT, SMG, and AMC received the investigator initiated grant to conduct the HYPER2 study from Merck. All other authors have no competing interests to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)