Human Papillomavirus Genotype Replacement: Still Too Early to Tell?

Abstract Background Although human papillomavirus (HPV) vaccines are highly efficacious in protecting against HPV infections and related diseases, vaccination may trigger replacement by nontargeted genotypes if these compete with the vaccine-targeted types. HPV genotype replacement has been deemed unlikely, based on the lack of systematic increases in the prevalence of nonvaccine-type (NVT) infection in the first decade after vaccination, and on the presence of cross-protection for some NVTs. Methods To investigate whether type replacement can be inferred from early postvaccination surveillance, we constructed a transmission model in which a vaccine type and an NVT compete through infection-induced cross-immunity. We simulated scenarios of different levels of cross-immunity and vaccine-induced cross-protection to the NVT. We validated whether commonly used measures correctly indicate type replacement in the long run. Results Type replacement is a trade-off between cross-immunity and cross-protection; cross-immunity leads to type replacement unless cross-protection is strong enough. With weak cross-protection, NVT prevalence may initially decrease before rebounding into type replacement, exhibiting a honeymoon period. Importantly, vaccine effectiveness for NVTs is inadequate for indicating type replacement. Conclusions Although postvaccination surveillance thus far is reassuring, it is still too early to preclude type replacement. Monitoring of NVTs remains pivotal in gauging population-level impacts of HPV vaccination. It is probably still too early to preclude human papillomavirus genotype replacement after a decade of postvaccine surveillance, because replacement could occur after a honeymoon period owing to the combination of infection-induced cross-immunity and vaccine-induced cross-protection for a nonvaccine type.