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.

Penelope Gray,Simopekka Vänskä,Joakim Dillner,Helena Faust,Ville N Pimenoff,Tiina Eriksson,Hanna Kann,Heljä‐Marja Surcel,Indira Adhikari,Matti Lehtinen

doi:10.1002/ijc.33169

Abstract

Large scale human papillomavirus (HPV) vaccination against the most oncogenic high-risk human papillomavirus (HPV) types 16/18 is rapidly reducing their incidence. However, attempts at assessing if this leads to an increase of nonvaccine targeted HPV types have been hampered by several limitations, such as the inability to differentiate secular trends. We performed a population-based serological survey of unvaccinated young women over 12 years. The women were under 23-years-old, residents from 33 communities which participated in a community-randomised trial (CRT) with approximately 50% vaccination coverage. Serum samples were retrieved pre-CRT and post-CRT implementation. Seropositivity to 17 HPV types was assessed. HPV seroprevalence ratios (PR) comparing the postvaccination to prevaccination era were estimated by trial arm. This was also assessed among the sexual risk-taking core group, where type replacement may occur more rapidly. In total, 8022 serum samples from the population-based Finnish Maternity Cohort were retrieved. HPV types 16/18 showed decreased seroprevalence among the unvaccinated in communities only after gender-neutral vaccination (PR16/18A = 0.8, 95% CI 0.7-0.9). HPV6/11 and HPV73 were decreased after gender-neutral vaccination (PR6/11A = 0.8, 95% CI 0.7-0.9, PR73A = 0.7, 95% CI 0.6-0.9, respectively) and girls-only vaccination (PR6/11B = 0.8, 95% CI 0.7-0.9, PR73B = 0.9, 95% CI 0.8-1.0). HPV68 alone was increased but only after girls-only vaccination (PR68B = 1.3, 95% CI 1.0-1.7, PRcore68B = 2.8, 95% CI 1.2-6.3). A large-scale, long-term follow-up found no type replacement in the communities with the strongest reduction of vaccine HPV types. Limited evidence for an increase in HPV68 was restricted to girls-only vaccinated communities and may have been due to secular trends (ClinicalTrials.gov number: NCT00534638).

Highlights

Oncogenic human papillomavirus (HPV), the necessary cause of cervical cancer,[1] is a well-established causal agent of several anogenital and oropharyngeal cancers
There are a total of 12 high-risk HPV types which are classified by the International Agency for Research on Cancer (IARC) as carcinogenic to humans, HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59, with a further eight types classified as possibly carcinogenic, HPV26, 53, 66, 68, 67, 70, 73 and 83.4 As such, concern has been flagged over a decade ago, whether such selective vaccination could induce HPV type replacement to occur.[5]
We evaluate the occurrence of HPV type replacement in a decade following a large population-based community-randomised HPV vaccination trial with close to 50% vaccination coverage, by conducting a survey of HPV seroprevalence in unvaccinated Finnish female community residents over the pretrial and posttrial era

Summary

| INTRODUCTION

Oncogenic human papillomavirus (HPV), the necessary cause of cervical cancer,[1] is a well-established causal agent of several anogenital and oropharyngeal cancers. Several studies have evaluated the occurrence of HPV type replacement, using differing methodologies; comparison of the HPV prevalence between the postvaccination and prevaccination era,[8,9,10] 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 noncrossprotected) HPV types,[13] further to an earlier meta-analysis which found possible increases in HPV 39 and 52.14. We evaluate the occurrence of HPV type replacement in a decade following a large population-based community-randomised HPV vaccination trial with close to 50% vaccination coverage (beginning in October 2007), by conducting a survey of HPV seroprevalence in unvaccinated Finnish female community residents over the pretrial and posttrial era. Herpes simplex virus type II (HSV-2) serology is an established marker of sexual risk taking, thereby we utilise this as a proxy of core group membership,[19] to further investigate the occurrence of type replacement within the core-group (the assortative subgroup of the population with high sexual contact rates), as it has been suggested that HPV type replacement may first manifest within this group.[20]

| Study design and materials

| RESULTS

B Vaccine targeted hr lr Postvaccination vs prevaccination vaccination era

Findings

| DISCUSSION