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

Abstract

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.

Assessing the risk of cervical neoplasia in the post‐HPV vaccination era

“…26 Another fundament is that such evolutionary processes depend upon genetic diversity, which is high even for the most oncogenic hrHPVs both at species and strain level. 11,19 Therefore, it has been important to systematically examine the available community-randomized HPV vaccine trial data for possible clearance patterns of vaccine-targeted HPVs ecological niche 3 and search signs of evolutionary responses of the nonvaccine targeted lower oncogenicity hrHPV types such as type replacement. 7,23 In the postvaccination era, it will be important to explore both the ecological and epigenetic variation in infection outcome at large for HPVs.…”

“…The prevalence of vaccine‐targeted oncogenic, high‐risk (hr) HPV types is rapidly decreasing in countries with effective national vaccination programs 1–5 . Although the prevalence of nontargeted HPV types has not significantly changed the vaccination has led to changes in their relative proportions and in the overall ecological diversity of mucosal HPV types (Figure 1).…”

The impact of catch-up bivalent human papillomavirus vaccination on cervical screening outcomes: an observational study from the English HPV primary screening pilot

“…It should be noted that these women will have a lower absolute risk than prior to vaccination, due to partial herd protection [ 41 ]. Even higher levels of herd protection can be expected from the vaccination of males as well as females [ 42 , 43 ], which several countries have adopted relatively recently, including England. Nevertheless, continued monitoring of the incidence of cervical cancer, which is already being carried out [ 2 , 23 ], will remain crucial in assessing changes in relative social disparities.…”

Moral dilemma(s) in human papillomavirus vaccination – revisiting the role of the herd effect

“…The elimination of HPV-associated cancers will be accomplished by herd effect enforced eradication of these most oncogenic and prevalent HPV types. Because of both, the much lower R0, less than 4 for all other HPV types than HPV16, and the assortativeness of sexual risk-taking behaviour, it is the herd effect from moderate to high coverage gender-neutral vaccination that is the relevant factor providing protection even against HPV16 [ 5 , 6 ]. A community-randomised study has shown that the herd effect is notable in a real-life setting within less than 4 years but only after gender-neutral vaccination [ 5 , 6 ].…”

“…Because of both, the much lower R0, less than 4 for all other HPV types than HPV16, and the assortativeness of sexual risk-taking behaviour, it is the herd effect from moderate to high coverage gender-neutral vaccination that is the relevant factor providing protection even against HPV16 [ 5 , 6 ]. A community-randomised study has shown that the herd effect is notable in a real-life setting within less than 4 years but only after gender-neutral vaccination [ 5 , 6 ]. In addition, most mathematical models do not account for this, and thus their cost-efficiency estimates for the gender-neutral HPV vaccination could (should) be even better.…”