Bivalent Human Papillomavirus (HPV) Vaccine Effectiveness Correlates With Phylogenetic Distance From HPV Vaccine Types 16 and 18

Abstract To substantiate cross-protection reported across AS04-adjuvanted bivalent human papillomavirus (HPV) vaccine (2vHPV) studies, we reevaluated vaccine effectiveness against type-specific HPV positivity as a function of phylogenetic distance to vaccine target types HPV-16 and -18. We provide evidence of sustained cross-protection up to 8 years postvaccination in a high-risk population in the Netherlands. Moreover, our findings suggest that genomic distance better explains cross-protection than distance measures based on capsid antigens only. Taken together, 2vHPV is predicted to provide partial cross-protection against HPV-31, -33, -35, -45, -52, and possibly -58, that is, acknowledged oncogenic types with close phylogenetic relationships to HPV-16 or -18. Ongoing surveillance in Dutch sexual health centers demonstrates sustained effectiveness of the bivalent human papillomavirus (HPV) vaccine against vaccine-targeted types and nontargeted but phylogenetically related types, supporting the hypothesis that vaccine-induced cross-protection is due to genomic similarities between HPV genotypes.