Human papillomavirus genotype-specific prevalence and infection risks: a 10-year population-based study from the United States

Abstract

Background: Various studies have reported on the impact of human papillomavirus (HPV) vaccines. Here we present the largest population-based investigation of genotype-specific distributions over the decade following implementation of the quadrivalent HPV vaccine (HPV-6/11/16/18) in the United States.

Methods: Liquid-based cervical cytology samples from individuals aged 15-30 years undergoing cervical screening throughout New Mexico were tested by broad-spectrum HPV genotyping. Weighted relative differences in HPV type-specific prevalence and 95% confidence intervals (CIs) were calculated by comparing individuals screened between 2007 and 2009 (n = 95 915) with individuals screened between 2013 and 2016 (n = 103 371). Weighted logistic regression was used to estimate relative risk of type-specific HPV infections. Tests of significance were 2-sided.

Results: Genotype-specific prevalence fell with statistical signficance for HPV-16 (relative difference = ‒52.6%, 95% CI = ‒56.9 to ‒48.3), HPV-18 (relative difference = ‒62.1%, 95% CI = ‒68.5 to ‒55.8), HPV-31 (relative difference = ‒34.2%, 95% CI = ‒42.1 to ‒26.3), and HPV-33 (relative difference = ‒31.8%, 95% CI = ‒48.4 to ‒15.1). The relative difference increased for other carcinogenic HPV types by 19.5% (95% CI = 14.3 to 24.6) when excluding HPV-16/18. Large reductions in HPV-6/11 relative differences were observed, but overall, noncarcinogenic, nonvaccine types increased. Comparing female individuals born in 1996 with female individuals born in 1989, risk of infection with HPV-6, 11, 16, and 18 decreased by 80.0% among individuals aged 21-25 years. High-grade squamous intraepithelial lesions or worse decreased by 49.4% when extending the evaluation from 2007 to 2018.

Conclusion: The incidence of high-grade squamous intraepithelial lesions or worse is decreasing, with large reductions in the prevalence of quadrivalent HPV vaccine types and nonvaccine types HPV-31 and HPV-33, reflecting vaccine cross-protection. Increases in nonvaccine HPV genotypes may attenuate anticipated reductions in HPV-related abnormalities, including cancers, but the benefits of HPV vaccination remain substantial.

Figure 1.

Prevalence (%) of human papillomavirus (HPV) types 16, 18, 31, and 33 in cohort 1 (December 2007-April 2009) and cohort 2 (September 2013-September 2016), by age. Line graphs show the trend in HPV prevalence across individuals aged 15-60 years. Separate lines for cohort 1 and cohort 2 allow comparing before and after HPV vaccine uptake. Graphs are plotted for HPV types 16, 18, 31, and 33 separately, with different scales used for different type-specific HPV incidence. Estimated prevalence data points and lines used Epanechnikov kernel smoothing.

Figure 2.

Relative difference (%) in human papillomavirus (HPV) prevalence between cohorts 1 and 2, with 95% confidence intervals (CIs), are shown for individual and groups of HPV genotypes among individuals aged 15-20, 21-25, and 26-30 years. Data weighted to the statewide screening population. Carcinogenic HPVs include HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52 (detectable only in the absence of HPV33, HPV35, or HPV58), 56, 58, 59, and 68. Noncarcinogenic HPVs include HPV types 6, 11, 26, 40, 42, 53, 54, 55, 61, 62, 64, 66, 67, 69, 70, 71, 72, 73 (MM9), 81, 82 (MM4), 83 (MM7), 84 (MM8), IS39, and CP6108. Histograms show the relative difference in prevalence for type-specific HPV and groups of HPV genotypes between cohort 1 and cohort 2. Individual HPV types include HPV types 6, 16, 18, 31, and 33. Groups include quadrivalent HPV vaccine types, carcinogenic types, and noncarcinogenic types with and without exclusions. Histogram bars were computed for all 3 age groups—15-20, 21-25, and 26-30 years—and plotted next to each other to show trends in relative prevalence differences, with 95% CIs shown for each relative difference.

Figure 3.

Relative risk (%) of detecting groups of human papillomavirus (HPV) infections (quadrivalent types 6, 11, 16, and 18; HPV-16/18; HPV-31/33; and HPV-6/11), by birth cohort, adjusted for age at screening in cohort 2. Quadrivalent HPV types include 6, 11, 16, and 18. Data weighted to the statewide screening population. Line graphs were plotted separately for quadrivalent HPV types—HPV-16/18, HPV-31/33, and HPV-6/11—to show the relative reduction in risk of being HPV positive, by birth cohort in 2007, when HPV vaccines were first introduced. Individuals born in 1989 were compared with individuals born subsequently across 1-year (age) intervals through 1996. Relative reductions were calculated from logistic regression models.

Figure 4.

Overall population incidence of high-grade squamous intraepithelial lesions or worse, by year (2007-2018), for individuals aged 15-20, 21-25, and 26-30 years. Line graphs were plotted showing the trend in incidence of high-grade squamous intraepithelial lesions or worse cytology results between 2007 and 2018 for individuals aged 15-20, 21-25, and 26-30 years. Exact data estimates of incidence were plotted, as were local polynomial regression curves to smooth trends.