Abstract
BACKGROUND: The United States has experienced an increase in the incidence of human papillomavirus (HPV)-related cancers that are not screen-detectable. It has been hypothesized, but not directly demonstrated, that this is due to increasing HPV prevalence in the unvaccinated population. METHODS: Female self-reported numbers of lifetime sex partners and HPV serology from the National Health and Nutrition Examination Survey (NHANES) were used to develop mathematical models of sexual partner acquisition and antibody dynamics. Modeled trends in sexual behaviors were compared to incidence data for cervical adenocarcinoma, oropharyngeal cancer, and anal cancer. RESULTS: The age-specific HPV seroprevalence data were best explained by a partner acquisition model that explicitly accounted for cohort-dependent changes in sexual behavior. Estimates of the mean time to loss of natural antibodies varied by model, ranging from 49 to 145 years. Inferred trends in sexual behavior over the past decades paralleled the increasing incidence of HPV-related cancers in the United States. CONCLUSIONS: The findings suggest that lower HPV seroprevalence in older US women primarily reflects cohort-specific differences in sexual behaviors, and is only marginally attributable to immune waning with age. Our results emphasize the importance of continuing surveillance of sexual behaviors, alongside vaccine status, to predict future disease burden.