Evidence for cross-protection but not type-replacement over the 11 years after human papillomavirus vaccine introduction.

Covert C, Ding L, Brown D, Franco EL, Bernstein DI, Kahn JA
Hum Vaccin Immunother in press 1-8 01/11/2019


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 cross-sectional 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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