William C Hunt

HPV vaccine impact: genotype-specific changes in cervical pre-cancer share similarities with changes in cervical screening cytology

Abstract Background After human papillomavirus (HPV) vaccine introduction, declines in the prevalence of HPV vaccine types have been observed in screening cytology, but data from the United States describing HPV type-specific changes in cervical intraepithelial neoplasia (CIN) grades 2-3 and adenocarcinoma in situ (CIN2/CIN3/AIS) are limited. Methods A statewide sample of individuals with cervical biopsies was selected for broad-spectrum HPV genotyping. CIN2/CIN3/AIS incidence and prevalence were calculated for type-specific high-risk HPV (hrHPV) among individuals aged 15-29 years. Weighted incidence rate ratios (IRR) and relative differences in prevalence (RDP) were computed to compare 3 time periods: 2006-2009 (Cohort 1 [C1], n = 4121), 2012-2015 (C2, n = 2194), and 2015-2018 (C3, n = 1481). Results When comparing C1 vs C3 among those aged 21-25 years, statistically significant reductions in hrHPV type-specific CIN2/CIN3/AIS incidence were observed for HPV16, HPV18, HPV31, and HPV33, with corresponding IRRs of 0.4 (95% confidence interval [95% CI] = 0.3 to 0.4), 0.3 (95% CI = 0.1 to 0.7), 0.6 (95% CI = 0.5 to 0.9), and 0.4 (95% CI = 0.1 to 0.8), respectively. The RDP comparing C1 vs C3 for HPV16/18-positive CIN2/CIN3/AIS was -43.8% (P < .001). When excluding HPV16/18 or HPV16/18/31/33 from all hrHPV types, the RDP was +56.6% and +92.5% (P < .001), respectively. Conclusions hrHPV type-specific CIN2/CIN3/AIS incidence decreased with statistical significance for vaccine types HPV16/18 and for HPV31 and HPV33. Although the HPV vaccine is highly beneficial and a top priority for preventing HPV-related cancer, the long-term vaccine impact in cohorts receiving the 4-valent HPV vaccine requires continued follow-up to assess genotype-specific distributions in the remaining CIN2+ lesions and cancers.

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.