Modeling of US Human Papillomavirus (HPV) Seroprevalence by Age and Sexual Behavior Indicates an Increasing Trend of HPV Infection Following the Sexual Revolution

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.

Keywords: cancer; cohort effect; human papillomavirus; sexual revolution.

Figure 1.

Modeling of new partner acquisition. The age-cohort model for the rate of acquisition of new sex partners is parameterized in a Bayesian framework. A. Visualization of model fit (blue: median and 95% credible interval) to mean number of lifetime sex partners (LTSPs) from 8 survey cycles in the National Health and Nutrition Examination Survey (black: point estimate and 95% confidence interval). B, Median and 95% credible interval for age-dependent partner acquisition rates in the reference birth cohort. C, Median and 95% credible interval for the cohort scaling factors of the partner-acquisition rates (relative to the reference birth cohort). Note that only limited data support the estimates for later birth cohorts, especially the 1980–1989 and 1990–1999 cohorts. D, Model-predicted age-specific median LTSPs, stratified by birth cohort.

Figure 2.

Modeling of seroprevalence. A, Model M3 (blue: median and 95% credible interval [CI] of the quasi-posterior) is fit to the mean number of serotypes in the 2005–2006 National Health and Nutrition Examination Survey (black: point estimate and 95% confidence interval). B, Histograms approximating the quasi-posterior densities of the immune waning rate and the per-partnership human papillomavirus acquisition probability for model M3. C, Comparison of the quasi-posterior density of Akaike information criteria (AIC) in the best-fitting model (M3; red) to the corresponding densities for 2 alternative models, namely the model without immune waning (M1; blue), and the model without cohort effects in the partner acquisition rate (M2). D, Comparison of the coefficient of determination (COD) between models M1, M2, and M3 (as in C).

Figure 3.

Cross-sectional seroprevalence in the US population. A, Age-stratified, cross-sectional number of detectable serotypes among US females (mean and 95% confidence interval). There was a significant decrease in mean number of serotypes between the age groups of 30–39 and 40–49 years (*P < .05), and the age groups of 40–49 and 50–59 years (**P < .01), respectively. B, The cross-sectional measure from (A) is stratified by cumulative sexual exposure as measured by self-reported number of lifetime sex partners (LTSPs) up to 50 total partners. For the strata “LTSP = 5–6” and “LTSP = 10–19,” there was a significant decrease in mean number of serotypes between the age groups of 30–39 and 40–49 years (P < .01 and P < .05, respectively), but no difference between the age groups of 40–49 and 50–59 years. In the remaining LTSP strata, no decrease in mean number of serotypes was observed after age 30–39 years.

Figure 4.

Trends in sexual behaviors and cancer incidence. Age-adjusted incidence trends for adenocarcinomas of the cervix, and carcinomas of the oropharynx and anus (1975–2013, 5-year intervals; point estimate and 95% confidence interval) are compared to the modeled mean number of lifetime sex partners (LTSPs) among females of age 25 years (1965–2015, 10-year intervals; median and 95% credible interval). The y-axis for cancer incidence is on the left (logarithmic scale), and the y-axis for mean LTSPs is on the right (linear scale logarithmic scale).