The 9-valent human papillomavirus vaccine was associated with a lower incidence of human papillomavirus-related cancers among males aged 9 to 26 years compared with unvaccinated peers, according to a retrospective cohort study.
Researchers used the TriNetX global database — which contained records for approximately 190 million patients across 170 health care centers as of December 2025 — to evaluate cancer incidence among vaccinated and unvaccinated males in the US. The analysis included more than 615,000 vaccinated patients and approximately 2.3 million unvaccinated patients with records from 2016 to 2024 and follow-up of up to 10 years.
Following propensity score matching to balance baseline characteristics, more than 510,000 patients were included in each group. The composite outcome — defined as diagnoses of head and neck, esophageal, penile, or anal cancer — occurred less frequently among vaccinated patients than among unvaccinated patients.
This difference corresponded to a hazard ratio of 0.54 (95% CI, 0.37–0.81), reflecting roughly a 46% lower risk of HPV-related cancer among vaccinated males.
Because of low event counts, esophageal, penile, and anal cancers could not be evaluated separately, and results were driven primarily by head and neck cancer.
Subgroup analyses showed that the association was consistent in both males aged 9 to 14 years and those aged 15 to 26 years. Sensitivity analyses using different follow-up periods and earlier vaccine versions showed similar results.
The researchers emphasized that the study shows an association rather than a causal effect, noting several limitations. Cancer diagnoses were based on administrative coding without histologic confirmation, which may have led to misclassification. In addition, vaccination records outside participating health care centers were not captured, meaning some patients categorized as unvaccinated may have received the vaccine elsewhere.
The study also could not fully account for key risk factors such as high-risk sexual behavior, and included cancers not all directly attributable to HPV, particularly within head and neck cancers.
Because of low vaccination rates outside the US cohort, findings may not be generalizable to other regions.
Despite these limitations, the researchers noted that their findings add to the growing body of evidence supporting HPV vaccination in males.
"Our findings indicate that 9-valent HPV vaccines should be administered not only to females but also to young males," wrote Taito Kitano, DrPH, of Nara Prefecture General Medical Center in Japan, and colleagues.
The findings support ongoing efforts to expand sex-neutral HPV vaccination programs, particularly where vaccination remains limited to females.
Dr. Kitano reported receiving grants from BioMérieux outside the submitted work. Co-author Sayaka Yoshida, PhD, reported receiving grants from TAUNS Laboratories and Mizuho Medy outside the submitted work.
Source: JAMA Oncology