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

PLoS Med. 2021 Jun 7;18(6):e1003588. doi: 10.1371/journal.pmed.1003588. eCollection 2021 Jun.

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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alphapapillomavirus* / immunology
  • Antibodies, Viral* / blood
  • Child
  • Cross-Sectional Studies
  • Female
  • Finland / epidemiology
  • Human papillomavirus 16 / immunology
  • Human papillomavirus 18 / immunology
  • Humans
  • Immunity, Herd*
  • Immunogenicity, Vaccine*
  • Papillomavirus Infections* / epidemiology
  • Papillomavirus Infections* / immunology
  • Papillomavirus Infections* / prevention & control
  • Papillomavirus Infections* / virology
  • Papillomavirus Vaccines* / administration & dosage
  • Pregnancy
  • Randomized Controlled Trials as Topic
  • Seroepidemiologic Studies
  • Serologic Tests
  • Uterine Cervical Neoplasms* / immunology
  • Uterine Cervical Neoplasms* / prevention & control
  • Uterine Cervical Neoplasms* / virology
  • Vaccination*
  • Young Adult

Substances

  • Antibodies, Viral
  • Papillomavirus Vaccines

Associated data

  • ClinicalTrials.gov/NCT00534638

Grants and funding

The study was also supported by grants from the Swedish Cancer Society (CAN 2015/399 and CAN 2017/459, https://www.cancerfonden.se/), from the Swedish Foundation for Strategic Research (grant number RB13-0011, https://strategiska.se/en/) and from Karolinska Institutet (Dnr. 2019-01523, https://ki.se/). ML received funding from KI for his Professorship (Dnr. 2-3698/2017, https://ki.se/). PG received personal working grants from the Cancer Society of Finland (pink ribbon fund, https://www.cancersociety.fi/) and the City of Tampere Science Fund (https://www.tampere.fi/). GlaxoSmithKline Biologicals SA funded the community-randomized HPV-040 trial (NCT00534638, https://www.gsk.com/) however was not in any way involved in the conduct of this study. The authors are solely responsible for the final content and interpretation.