Background The quadrivalent human papillomavirus (HPV) vaccine was shown to prevent infections and lesions related to HPV6, 11, 16, and 18 in a randomised, placebo-controlled study in men aged 16-26 years. We assessed the incidences of external genital warts related to HPV6 or 11, and external genital lesions and anal dysplasia related to HPV6, 11, 16, or 18, over 10 years of follow-up. Methods The 3-year base study was an international, multicentre, double-blind, randomised, placebo-controlled trial done at 71 sites in 18 countries. Eligible participants were heterosexual men (aged 16-23 years) or men who have sex with men (MSM; aged 16-26 years). Men who had clinically detectable anogenital warts or genital lesions at screening that were suggestive of infection with non-HPV sexually transmitted diseases, or who had a history of such findings, were excluded. Eligible participants were randomly assigned (1:1) to receive three doses of either quadrivalent HPV vaccine or placebo on day 1, month 2, and month 6, administered as a 0.5-mL injection into the deltoid muscle. The 7-year, open-label, long-term follow-up extension study was done at 46 centres in 16 countries. Participants who received one or more doses of the quadrivalent HPV vaccine in the base study were eligible for enrolment into the long-term follow-up study (early vaccination group). Placebo recipients were offered the three-dose quadrivalent HPV vaccine at the end of the base study; those who received one or more quadrivalent HPV vaccine doses were eligible for enrolment into the long-term follow-up study (catch-up vaccination group). The primary efficacy endpoints were the incidence of external genital warts related to HPV6 or 11 and the incidence of external genital lesions related to HPV6, 11, 16, or 18 in all participants and the incidence of anal intraepithelial neoplasia (including anal warts and flat lesions) or anal cancer related to HPV6, 11, 16, or 18 in MSM only. The primary efficacy analysis was done in the per-protocol population for the early vaccination group, which included participants who received all three vaccine doses, were seronegative at day 1 and PCR-negative from day 1 through month 7 of the base study for the HPV type being analysed, had no protocol violations that could affect evaluation of vaccine efficacy, and had attended at least one visit during the long-term follow-up study. For the catch-up vaccination group, efficacy was assessed in the modified intention-to-treat population, which included participants who had received at least one vaccine dose, were seronegative and PCR-negative for HPV types analysed from day 1 of the base study to the final follow-up visit before receiving the quadrivalent HPV vaccine, and had at least one long-term follow-up visit. Safety was assessed in all randomised participants who received at least one vaccine dose. This study is registered with ClinicalTrials.gov, NCT00090285. Findings Between Aug 10, 2010, and April 3, 2017, 1803 participants were enrolled in the long-term follow-up study, of whom 936 (827 heterosexual men and 109 MSM) were included in the early vaccination group and 867 (739 heterosexual men and 128 MSM) were included in the catch-up vaccination group. Participants in the early vaccination group were followed up for a median of 9.5 years (range 0.1-11.5) after receiving the third dose of the quadrivalent HPV vaccine, and participants in the catch-up vaccination group were followed up for a median of 4.7 years (0.0-6.6) after receiving the third dose. In early vaccine group participants during long-term follow-up compared with the placebo group in the base study, the incidence per 10 000 person-years of external genital warts related to HPV6 or 11 was 0.0 (95% CI 0.0-8.7) versus 137.3 (83.9-212.1), of external genital lesions related to HPV6, 11, 16, or 18 was 0.0 (0.0-7.7) versus 140.4 (89.0-210.7), and of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 in MSM only was 20.5 (0.5-114.4) versus 906.2 (553.5-1399.5). Compared with during the base study (ie, before quadrivalent HPV vaccine administration), during the long-term follow-up period, participants in the catch-up vaccination group had no new reported cases of external genital warts related to HPV6 or 11 (149.6 cases per 10 000 person-years [95% CI 101.6-212.3] vs 0 cases per 10 000 person-years [0.0-13.5]) or external genital lesions related to HPV6, 11, 16, or 18 (155.1 cases per 10 000 person-years [108.0-215.7] vs 0 cases per 10 000 person-years [0.0-10.2]), and a lower incidence of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 (886.0 cases per 10 000 person-years [583.9-1289.1] vs 101.3 cases per 10 000 person-years [32.9-236.3]). No vaccinerelated serious adverse events were reported. Interpretation The quadrivalent HPV vaccine provides durable protection against anogenital disease related to HPV6, 11, 16, and 18. The results support quadrivalent HPV vaccination in men, including catch-up vaccination. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.

Background: A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV) vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV) vaccine. Methods: Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16-26 years, and an immunogenicity and safety study in girls and boys aged 9-15 years. Participants (N= 5312) received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs) were also monitored in all participants. Results: The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6). Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (> 99%) 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden.

Background: The 9-valent HPV (9vHPV) vaccine was developed to prevent infection and disease related to 9 HPV types (HPV6/11 /16/18/31/33/45/52/58) which cause approximately 90% of cervical cancers, HPVrelated vulvar, vaginal and anal cancers, and genital warts worldwide. In a pivotal efficacy study, the 9vHPV vaccine prevented infection and disease due to the 9 vaccine types. Duration of protection remains to be determined. Vaccines that induce long-term protection are generally characterized by the generation of immune memory. The purpose of this report is to assess the persistence of HPV antibody response and existence of immune memory at 5 years post-vaccination. Methods: A subset of subjects (N = 150) who received 3 doses of 9vHPV vaccine at day 1, month 2 and month 6 in the pivotal efficacy study continued in a study extension and received a fourth dose of 9vHPV vaccine at month 60. Serum HPV antibody levels were measured pre-dose 4 and at 7 and 28 days post-dose 4 by competitive Luminex immunoassay. Adverse events were assessed using a vaccination report card. Results: HPV antibodies induced following the 3-dose series of 9vHPV vaccine in the base study persisted through month 60 with seropositivity rates ranging from 77.5% to 100%. Geometric mean titers at 1 week and 1 month post-dose 4 were 1.25-4.10 and 1.65-4.88-fold higher, respectively, than levels observed 1 month following the completion of the three-dose primary series. Seropositivity rates were >99% and 100% at 1 week and 1 month post-dose 4, respectively. The fourth dose of 9vHPV vaccine was generally well tolerated. Conclusions: A three-dose regimen of the 9vHPV vaccine induced persistent HPV antibody response through 5 years post-vaccination. Administration of a fourth dose resulted in a strong anamnestic response to all 9 vaccine types. These findings suggest that the efficacy of the 9vHPV vaccine will be long lasting. Conclusions: Clinical Trials.gov Identifier: NCT00543543. (C) 2017 Elsevier Ltd. All rights reserved.