BACKGROUND: Clinical trials of the 4-valent human papillomavirus (HPV) vaccine demonstrate high efficacy, but surveillance studies are essential to examine the long-term impact of vaccine introduction on HPV prevalence in community settings. The aims of this study were to determine during the 11 years after vaccine introduction the prevalence of (1) vaccinetype HPV in adolescent and young adult women who were vaccinated (to assess vaccine effectiveness) and (2) vaccine-type HPV in women who were unvaccinated (to assess herd protection). METHODS: Young women 13 to 26 years of age were recruited from hospital-based and community health clinics for 4 surveillance studies from 2006 to 2017. We determined the proportion of vaccinated and unvaccinated women who were positive for vaccine-type HPV across the studies, and the odds of positivity for vaccine-type HPV using logistic regression; all analyses were propensity score-adjusted to control for between-wave differences in participant characteristics. RESULTS: Vaccination rates increased from 0% to 84.3% (97% of study participants received the 4-valent vaccine). Among women who were vaccinated, 4-valent vaccine-type HPV detection decreased from 35% to 6.7% (80.9% decline; odds ratio 0.13, 95% confidence interval 0.08 to 0.22). Among women who were unvaccinated, 4-valent vaccine-type HPV detection decreased from 32.4% to 19.4% (40% decline; odds ratio 0.50, 95% confidence interval 0.26 to 0.97). Estimated vaccine effectiveness was 90.6% in wave 3 and 80.1% in wave 4. CONCLUSIONS: In this study in which trends in HPV in a US community >10 years after 4-valent HPV vaccine introduction and after 9-valent vaccine introduction were examined, we found evidence of vaccine effectiveness and herd protection. Further research is needed to examine trends in 9-valent vaccine-type HPV after higher rates of vaccination are achieved.

Examination of cross-protection and type replacement after human papillomavirus (HPV) vaccine introduction is essential to guide vaccination recommendations and policies. The aims of this study were to examine trends in non-vaccine-type HPV: 1) genetically related to vaccine types (to assess for cross-protection) and 2) genetically unrelated to vaccine types (to assess for type replacement), among young women 13-26 years of age during the 11 years after HPV vaccine introduction. Participants were recruited from a hospital-based teen health center and a community health department for four crosssectional surveillance studies between 2006 and 2017. Participants completed a survey that assessed sociodemographic characteristics and behaviors, and cervicovaginal swabs were collected and tested for 36 HPV genotypes. We determined changes in proportions of non-vaccine-type HPV prevalence and conducted logistic regression to determine the odds of infection across the surveillance studies, propensity-score adjusted to control for selection bias. Analyses were stratified by vaccination status. Among vaccinated women who received only the 4-valent vaccine (n = 1,540), the adjusted prevalence of HPV types genetically related to HPV16 decreased significantly by 45.8% (adjusted odds ratio [AOR] = 0.48, 95% confidence interval [CI] = 0.31-0.74) from 2006-2017, demonstrating evidence of cross-protection. The adjusted prevalence of HPV types genetically related to HPV18 did not change significantly (14.2% decrease, AOR = 0.83, 95% CI = 0.56-1.21). The adjusted prevalence of HPV types genetically unrelated to vaccine types did not change significantly (4.2% increase, AOR = 1.09, CI = 0.80-1.48), demonstrating no evidence of type replacement. Further studies are needed to monitor for cross-protection and possible type replacement after introduction of the 9-valent HPV vaccine.

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