Effectiveness of various human papillomavirus vaccination strategies: A community randomized trial in Finland

Matti Lehtinen, Dan Apter, Tiina Eriksson, Katja Harjula, Mari Hokkanen, Kari Natunen, Pekka Nieminen, Jorma Paavonen, Johanna Palmroth, Tiina Petäjä, Eero Pukkala, Simopekka Vänskä, Brigitte Cheuvart, Maaria Soila, Dan Bi, Frank Struyf

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Introduction: We conducted a community-randomized trial (NCTBLINDED) in Finland to assess gender-neutral and girls-only vaccination strategies with the AS04-adjuvanted human papillomavirus (HPV)-16/18 (AS04-HPV-16/18)vaccine. Methods: Girls and boys (12−15 years) were invited. We randomized 33 communities (1:1:1 ratio): Arm A: 90% of randomly selected girls and boys received AS04-HPV-16/18 vaccine and 10% received hepatitis B vaccine (HBV); Arm B: 90% of randomly selected girls received AS04-HPV-16/18 vaccine, 10% of girls received HBV, and all boys received HBV; Arm C: all participants received HBV. Effectiveness measurements against prevalence of HPV-16/18 cervical infection were estimated in girls at 18.5 years. The main measures were: (1) overall effectiveness comparing Arms A or B, regardless of vaccination status, vs Arm C; (2) total effectiveness comparing AS04-HPV-16/18 vaccinated girls in pooled Arms A/B vs Arm C; (3) indirect effectiveness (herd effect) comparing girls receiving HBV or unvaccinated in Arm A vs Arm C. Co-primary objectives were overall effectiveness following gender-neutral or girls-only vaccination. Results: Of 80,272 adolescents invited, 34,412 were enrolled. Overall effectiveness was 23.8% (95% confidence interval: −19.0, 51.1; P = 0.232) with gender-neutral vaccination. Following girls-only vaccination, overall effectiveness was 49.6% (20.1, 68.2; P = 0.004). Total effectiveness was over 90% regardless of vaccination strategy. No herd effect was found. Immunogenicity of the AS04-HPV-16/18 vaccine was high in both sexes. Conclusions: This study illustrates the difficulty in conducting community randomized trials. It is not plausible that vaccinating boys would reduce overall effectiveness, and the apparent lack of herd effect was unexpected given findings from other studies. This analysis was likely confounded by several factors but confirms the vaccine's high total effectiveness as in clinical trials.

Original languageEnglish
JournalCancer Medicine
DOIs
Publication statusE-pub ahead of print - Sep 2021
Publication typeA1 Journal article-refereed

Keywords

  • community
  • gender-neutral
  • human papillomavirus
  • vaccination strategy

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Fingerprint

Dive into the research topics of 'Effectiveness of various human papillomavirus vaccination strategies: A community randomized trial in Finland'. Together they form a unique fingerprint.

Cite this