BACKGROUND: Following 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 state-wide 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 three 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, 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 significantly for vaccine types HPV16/18 and for HPV31 and HPV33. While 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.