Abstract
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. 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). 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. ClinicalTrials.gov number NCT00534638, https://clinicaltrials.gov/ct2/show/NCT00534638.
Highlights
The World Health Organization has called for the elimination of cervical cancer as a public health problem [1]
With only moderate vaccination coverage, a gender-neutral vaccination strategy can facilitate the control of even HPV16
We evaluated the herd effect created by the different vaccination strategies by measuring the cumulative incidence of vaccine-protected human papillomavirus (HPV) types in 8,022 young unvaccinated pregnant females, comparing the time periods 2005–2010 and 2011–2016
Summary
The World Health Organization has called for the elimination of cervical cancer as a public health problem [1] To this end, the WHO has developed a global strategy requiring every country globally to achieve 90% human papillomavirus (HPV) vaccination of girls by the age of 15 years by the year 2030 [2]. In populations implementing girls-only vaccination, notable herd effect against HPV16 (the most oncogenic and most common HPV type) has only been observed when the vaccination coverage was high [15,16,17]. 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
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