Real-world effectiveness and impact of human papillomavirus vaccination in males: a comprehensive review

Gender-neutral vaccination (GNV) for human papillomavirus (HPV) has increasingly been implemented worldwide. However, real-world evidence of vaccine effectiveness (VE) in males and the population-level impact of GNV remains heterogeneous. We summarized the real-world VE of HPV vaccination in males and the impact of GNV.

A comprehensive review was performed using Embase and PubMed for studies published from January 2007 to May 2024 that evaluated quadrivalent or nonavalent HPV vaccines. Eligible studies assessed VE or GNV impact on HPV infections, precancerous lesions, cancer, or anogenital warts (AGW). Risk of bias was assessed using the Risk of Bias in Non-randomized Studies of Interventions tool and the National Institutes of Health quality assessment tool.

Twenty-one geographically diverse studies were included. Most VE and vaccine impact studies were judged to have some risk of bias. In males, VE reached up to 100% against oral HPV infection and 41% for penile HPV genotypes targeted by the quadrivalent vaccine, 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%).

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.