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

Abstract

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.

Long‐term follow‐up of human papillomavirus type replacement among young pregnant Finnish females before and after a community‐randomised HPV vaccination trial with moderate coverage

“…Several studies have evaluated the occurrence of HPV type replacement, using differing methodologies; comparison of the HPV prevalence between the postvaccination and prevaccination era, 8‐10 between vaccinated and unvaccinated persons in the postvaccination era 11 or via individually randomised HPV vaccination trials 12 . Importantly, a recent meta‐analysis of the above‐mentioned studies found an increasing trend in the pooled nonvaccine targeted (and noncross‐protected) HPV types, 13 further to an earlier meta‐analysis which found possible increases in HPV 39 and 52 14 …”

Epidemiologic Profile of Type-Specific Human Papillomavirus Infection after Initiation of HPV Vaccination

“…However, type-specific trends of non-vaccine-type HPV are more heterogeneous without consistent signals of type replacement [ 26 ]. The likelihood of type replacement remains ambiguous, and further studies are needed to monitor for cross-protection and possible type replacement after the introduction of the HPV vaccine [ 23 , 27 , 28 , 29 ].…”

Increase of non-vaccine human papillomavirus types in a group of HPV-vaccinated Mexican women. Evidence of Pathogenic Strain Replacement

“…The vaccine offers cross protection to hpv types genetically related in the same species, so we consider the pentavalent vaccine essentially a bivalent vaccine and the 9-valent vaccine a 3-valent vaccine[8]…”

“…The authors do not discard the possibility of type replacement for non-vaccine HPV types not genetically related. [8]…”