Seropositivity to non-vaccine incorporated genotypes induced by the bivalent and quadrivalent HPV vaccines: A systematic review and meta-analysis

Background Human papillomavirus vaccines have demonstrated remarkable efficacy against persistent infection and disease associated with vaccine-incorporated genotypes and a degree of efficacy against some genetically related, non-vaccine-incorporated genotypes. The vaccines differ in the extent of cross-protection against these non-vaccine genotypes. Data supporting the role for neutralizing antibodies as a correlate or surrogate of cross-protection are lacking, as is a robust assessment of the seroconversion rates against these non-vaccine genotypes. Methods We performed a systematic review and meta-analysis of available data on vaccine-induced neutralizing antibody seropositivity to non-vaccine incorporated HPV genotypes. Results Of 304 articles screened, 9 were included in the analysis representing ca. 700 individuals. The pooled estimate for seropositivity against HPV31 for the bivalent vaccine (86%; 95%CI 78–91%) was higher than that for the quadrivalent vaccine (61%; 39–79%; p = 0.011). The pooled estimate for seropositivity against HPV45 for the bivalent vaccine (50%; 37–64%) was also higher than that for the quadrivalent vaccine (16%; 6–36%; p = 0.007). Seropositivity against HPV33, HPV52 and HPV58 were similar between the vaccines. Mean seropositivity rates across non-vaccine genotypes were positively associated with the corresponding vaccine efficacy data reported from vaccine trials. Conclusions These data improve our understanding of vaccine-induced functional antibody specificity against non-vaccine incorporated genotypes and may help to parameterize vaccine-impact models and improve patient management in a post-vaccine setting.