Sex differences in human papillomavirus vaccination among Japanese university students and associated factors: a cross-sectional study examining the mediating effect of knowledge and interactions

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Background Human papillomavirus (HPV) vaccination rates among Japanese university students, especially among males, remain low. Following the suspension of active recommendations in 2013, vaccination rates have not improved since their resumption in 2022; male vaccination has not been established as a routine. Objectives To describe sex-specific HPV vaccination status and associated factors, examine sex differences in associated patterns, and examine the potential mediating role of HPV-related knowledge. Methods This web-based cross-sectional survey was conducted among undergraduates at a Japanese university in April 2025. The data of 3203 participants (1760 males, 1443 females) were analyzed. Self-reported vaccination history was the primary outcome. Multivariable logistic regression, bootstrap-based mediation analysis, and interaction analysis were performed. Results The vaccination rate was 30.1% (3.2% among males vs. 62.9% among females; P < 0.001). Male sex was strongly negatively associated with vaccination (OR = 0.024; 95% confidence interval [CI]: 0.017–0.034). Knowledge of free vaccination (OR = 3.477) and HPV-related diseases (OR = 1.758) showed positive associations. In females, only knowledge variables were significant, whereas in males, lifestyle variables were also associated. The indirect effect of sex on vaccination via HPV-related knowledge was statistically significant (indirect effect β = −0.263; 95% CI: −0.383 to −0.141), indicating partial mediation. Among unvaccinated males, 81.1% reported not needing the vaccine; 50.4% of unvaccinated females cited concerns about adverse effects. Conclusions Legislation mandating routine vaccination for males, subsidized costs, parental education, and sex-specific university-based programs are needed.