University of Oulu

Gray P, Kann H, Pimenoff VN, Eriksson T, Luostarinen T, Vänskä S, et al. (2021) 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 18(6): e1003588.

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

Saved in:
Author: Gray, Penelope1; Kann, Hanna2; Pimenoff, Ville N.2,3,4;
Organizations: 1Faculty of Social Sciences, Tampere University, Tampere, Finland
2Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
3Oncology Data Analytics Program, Bellvitge Biomedical Research Institute (IDIBELL), Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Hospitalet de Llobregat, Barcelona, Spain
4FICAN Mid, Tampere, Finland
5Department of Research and Development, Tampere University Hospital, Tampere, Finland
6Finnish Cancer Registry, Helsinki, Finland
7Department of Infectious Disease Control and Vaccination, Finnish Institute for Health and Welfare, Helsinki, Finland
8Faculty of Medicine, University of Oulu, Oulu, Finland
9Biobank Borealis of Northern Finland, Oulu University Hospital, Oulu, Finland
10Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.3 MB)
Persistent link:
Language: English
Published: Public Library of Science, 2021
Publish Date: 2021-09-21


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.

see all

Series: PLoS medicine
ISSN: 1549-1277
ISSN-E: 1549-1676
ISSN-L: 1549-1277
Volume: 18
Issue: 6
Article number: e1003588
DOI: 10.1371/journal.pmed.1003588
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
3123 Gynaecology and paediatrics
Funding: The study was also supported by grants from the Swedish Cancer Society (CAN 2015/399 and CAN 2017/459,, from the Swedish Foundation for Strategic Research (grant number RB13-0011, and from Karolinska Institutet (Dnr. 2019-01523, ML received funding from KI for his Professorship (Dnr. 2-3698/2017, PG received personal working grants from the Cancer Society of Finland (pink ribbon fund, and the City of Tampere Science Fund ( GlaxoSmithKline Biologicals SA funded the community-randomized HPV-040 trial (NCT00534638, however was not in any way involved in the conduct of this study.
Dataset Reference: All the pertinent summary-level data are contained within the manuscript and supplementary files. All other relevant underlying individual-level data will be returned to Northern Finland Biobank Borealis in accordance with the signed Material Transfer Agreement. Biobank Borealis will subsequently make this individual-level data available researchers in accordance with their data access policies (contact via:
Copyright information: © 2021 Gray et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.