Effect of human papillomavirus (HPV) vaccine on HPV type replacement and sexual behaviors in the post-vaccine era: A cross-sectional study

Human Papillomavirus (HPV) vaccination has been implemented for more than 15 years to prevent HPV infection and associated precancerous lesions. However, limited data are available regarding the long-term impacts of HPV vaccination, particularly concerning cross-protection and type replacement. Using data from the 2007-2016 National Health and Nutrition Examination Survey (NHANES), we employed the survey-weighted Student's t-tests, chi-square tests, and logistic regression models to examine the association between vaccine effectiveness and timing of vaccination. Among 9040 females aged 18 years and over, vaccination showed great effectiveness against both vaccine-targeted and non-vaccine-targeted high-risk HPV (hrHPV) among those vaccinated before sexual debut. After full adjustment, participants vaccinated after sex had a 48% increased risk of hrHPV infection (OR (95% CI) = 1.48 (1.16, 1.88)) compared to unvaccinated participants, and their sexual behaviors were more active as well. The most prevalent HPV subtypes were HPV 16/51/52/66, and the prevalence of subtypes 18/35/52/66/68 differed significantly across racial groups. Despite the prevalence of most hrHPV subtypes declined continuously or fluctuated over time, it is noteworthy that the infection rate of HPV 66 increased by 59% compared to the unvaccinated (95% CI: 0.18-0.92). Continuous surveillance is warranted for hrHPV types antigenically distant from vaccine strains, as early type replacement may be emerging. Given the notable difference in effectiveness based on vaccination timing, public-health education should emphasize both the benefits and limitations of HPV vaccination in the context of sexual health.