Human Papillomavirus Seroprevalence In Pregnant Women Following Gender-Neutral And Girls-Only Vaccination Programs In Finland: A Cross-Sectional Cohort Analysis Following A Cluster Randomized Trial

Background Cervical cancer elimination through human papillomavirus (HPV) vaccination programs requires the attainment of herd effect. Due to its uniquely high basic reproduction number, the vaccination coverage required to achieve herd effect against HPV type 16 exceeds what is attainable in most populations. We have compared how gender-neutral and girls-only vaccination strategies create herd effect against HPV16 under moderate vaccination coverage achieved in a population-based, community-randomized trial.Methods and findings In 2007-2010, the 1992-1995 birth cohorts of 33 Finnish communities were randomized to receive gender-neutral HPV vaccination (Arm A), girls-only HPV vaccination (Arm B), or no HPV vaccination (Arm C) (11 communities per trial arm). HPV16/18/31/33/35/45 seroprevalence differences between the pre-vaccination era (2005-2010) and post-vaccination era (2011-2016) were compared between all 8,022 unvaccinated women <23 years old and resident in the 33 communities during 2005-2016 (2,657, 2,691, and 2,674 in Arms A, B, and C, respectively). Post- versus pre-vaccination-era HPV seroprevalence ratios (PRs) were compared by arm. Possible outcome misclassification was quantified via probabilistic bias analysis. An HPV16 and HPV18 seroprevalence reduction was observed post-vaccination in the gender-neutral vaccination arm in the entire study population (PR16 = 0.64, 95% CI 0.10-0.85; PR18 = 0.72, 95% CI 0.22-0.96) and for HPV16 also in the herpes simplex virus type 2 seropositive core group (PR16 = 0.64, 95% CI 0.50-0.81). Observed reductions in HPV31/33/35/45 seroprevalence (PR31/33/35/45 = 0.88, 95% CI 0.81-0.97) were replicated in Arm C (PR31/33/35/45 = 0.79, 95% CI 0.69-0.90).Conclusions In this study we only observed herd effect against HPV16/18 after gender-neutral vaccination with moderate vaccination coverage. With only moderate vaccination coverage, a gender-neutral vaccination strategy can facilitate the control of even HPV16. Our findings may have limited transportability to other vaccination coverage levels.Trial registration ClinicalTrials.gov number NCT00534638, https://clinicaltrials.gov/ct2/show/NCT00534638.Author summaryWhy was this study done?High-risk human papillomavirus (HPV) infection is a necessary cause of cervical cancer in females. HPV vaccination targeting high-risk HPV types 16 and 18 has been implemented internationally. Achieving herd protection for HPV16 may require greater than 80% girls-only vaccination coverage, a level that has not been achievable in many countries. We evaluate whether gender-neutral or girls-only HPV vaccination results in HPV16 and HPV18 herd protection when the vaccination coverage is only moderate (40%-50%).What did the researchers do and find?We implemented a community-randomized trial of gender-neutral versus girls-only versus no HPV vaccination of young adolescents in 2007-2010, with 11 communities in each arm. Vaccination coverage was implemented with moderate coverage (40%-50%) at the community level. We evaluated the herd effect created by the different vaccination strategies by measuring the cumulative incidence of vaccine-protected HPV types in 8,022 young unvaccinated pregnant females (under 23 years old), comparing the time periods 2005-2010 (pre-vaccination) and 2011-2016 (post-vaccination). An HPV16 herd effect, that is, a reduction in cumulative incidence among the unvaccinated females, was only observed in communities where gender-neutral vaccination had been implemented.What do these findings mean?Achieving a vaccination coverage of above 80%, which is required to achieve herd effect against HPV16, may be unrealistic in some populations. Implementing gender-neutral HPV vaccination provides a solution to this problem as the vaccination coverage threshold required to provide herd effect to unvaccinated females is lower. Our study finds that gender-neutral vaccination provides stronger herd effect than girls-only vaccination in the setting of moderate vaccination coverage. However, these findings are limited to this setting and are not readily generalizable to settings with high (>80%) vaccination coverage.