This retrospective cohort study evaluated whether HPV vaccination reduces head and neck cancer (HNC) incidence in a U.S. real-world population of 1,433,260 matched individuals (ages 9–45), comparing 716,630 vaccinated persons to 716,630 unvaccinated controls, matched on age, sex, and comorbidities, across 66 U.S. healthcare organizations.
HPV vaccination was associated with a 68% lower risk of HNC overall (40 vs. 130 cases; HR 0.315), with the strongest effect for oropharyngeal squamous cell carcinoma (HR 0.087, ~91% reduction); risk reduction was also seen in ages 9–26 (HR 0.323) and persisted 5–13 years post-vaccination.
Retrospective observational design limits causal inference; residual confounding (e.g., sexual behavior, smoking) cannot be excluded despite matching; HNC case counts are small (40 vs. 130), which may limit precision of subgroup estimates.
These real-world data strongly support HPV vaccination—especially in patients aged 9–26—as a meaningful strategy to reduce oropharyngeal and other head and neck cancers. Clinicians should prioritize timely HPV immunization and counsel patients on its long-lasting protective effect.
