Nine-Valent Human Papillomavirus Vaccination and Related Cancers in Males

Abstract

IMPORTANCE The disease burden of human papillomavirus (HPV)–related cancers is substantial, irrespective of sex. Establishing evidence on the effectiveness of the 9-valent HPV vaccine for males may support the implementation of sex-neutral HPV vaccination strategies. OBJECTIVE To evaluate the incidence of HPV-related cancers between 9-valent HPV-vaccinated and unvaccinated males using a large-scale database. DESIGN, SETTING, AND PARTICIPANTS This multicenter retrospective cohort study utilized a global database. Participants included males aged 9 to 26 years who were either unvaccinated or received at least one 9-valent HPV vaccine between January 2016 and December 2024 with outcomes followed-up for up to 10 years. MAIN OUTCOMES AND MEASURES The primary composite outcomes were HPV-related cancers, including head and neck, esophageal, anal, and penile cancers. Hazard ratios (HRs) were estimated using propensity score matching. RESULTS Before propensity score matching, 615 155 vaccinated males (mean [SD] age, 13.4 [3.5] years) and 2 290 623 unvaccinated males (mean [SD] age, 17.2 [5.5] years) were identified in the US. After propensity score matching, 510 260 participants were included in each group. Compared with those in the unvaccinated group, those in the vaccinated group had a lower risk of the primary composite outcome (HR, 0.54; 95% CI, 0.37-0.81; P = .002). Subgroup analysis demonstrated that the significantly lower incidence of the primary composite outcome in the vaccinated group was maintained among both males aged 9 to 14 years (HR, 0.58; 95% CI, 0.34-0.97; P = .04) and those aged 15 to 26 years (HR, 0.50; 95% CI, 0.27-0.93; P = .03). CONCLUSIONS AND RELEVANCE This study found a significant negative association of the 9-valent HPV vaccine with HPV-related cancers in adolescents and young adult males and contributes to the development of sex-neutral HPV vaccination.