Population-level prevalence and risk of oral HPV infection with or without HPV vaccination

Human papillomavirus (HPV) is the most common sexually transmitted infection in the U.S. and the primary cause of multiple anogenital and oropharyngeal cancers. Although HPV vaccination is effective, uptake remains suboptimal and disparities persist. We analyzed nationally representative data from NHANES (2009-2016) to characterize HPV vaccination trends and vaccine-targeted (VT) oral HPV prevalence among adults 18-64 y, with emphasis on vaccine-eligible adults aged 18-26. Weighted prevalence estimates and survey-weighted logistic regression assessed associations between VT oral HPV and vaccination status, sex, race/ethnicity, smoking, alcohol use, and number of lifetime oral sex partners. Latent class analysis (LCA) identified behavioral-risk profiles associated with VT oral HPV. Among 12,479 adults, the weighted prevalence of VT oral HPV infection was 1.9% (95% CI: 1.6-2.2%), higher in males and those reporting smoking, alcohol use, or multiple oral sex partners. Prevalence increased with age, from 1.4% in adults aged 18-26 y to 2.4% in those aged 45-64. Non-Hispanic White participants reported the highest vaccination uptake but the largest sex disparity. Among vaccine-eligible adults, unvaccinated individuals had significantly higher odds of VT oral HPV compared with vaccinated peers (aOR = 4.21, 95% CI: 1.14-15.56). LCA identified five behavioral-risk classes; profiles with low vaccination probability and high oral sex exposure showed the highest VT oral HPV prevalence. HPV vaccination is associated with lower odds against VT oral HPV, yet behavioral exposures remain key contributors to infection risk. Strengthening early vaccination, improving equitable access, and addressing high-risk behaviors may be important strategy components to reduce HPV-associated oropharyngeal cancers.