Real-World Effectiveness and Impact of Human Papillomavirus Vaccination in Males: A Comprehensive Review.

BACKGROUND: Gender-neutral vaccination (GNV) for human papillomavirus (HPV) has increasingly been implemented worldwide. However, real-world evidence on vaccine effectiveness (VE) in males and the population-level impact of GNV remains heterogeneous. We summarized real-world VE of HPV vaccination in males and the impact of GNV. METHODS: A comprehensive review was performed using Embase and PubMed from January 2007 to May 2024, for studies evaluating quadrivalent (4vHPV) or nonavalent (9vHPV) vaccines. Eligible studies assessed VE or GNV impact on HPV infections, precancerous lesions, cancer, or anogenital warts (AGW). Risk of bias was assessed using ROBINS-I and the National Institute of Health quality assessment tool. RESULTS: Twenty-one geographically diverse studies were included. Most VE and VI studies demonstrated risk of bias. In males, VE reached up to 100% against oral HPV infection and 41% for penile HPV (4vHPV genotypes), with higher VE among adolescents and those vaccinated before age 23. Among men who have sex with men, VE was higher for penile HPV infection (85%), AGW (55%), and anal infection (60%). CONCLUSIONS: Real-world evidence indicates that HPV vaccination substantially reduces anogenital and oral HPV infections and AGW in males. GNV programs further reduce HPV-related disease burden, reinforcing the public health significance of universal HPV vaccination programs worldwide.