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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Virus and Host
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1437704
This article is part of the Research Topic Papillomaviruses, immunity, and tumour development View all 5 articles

Head-to-head comparison of two human papillomavirus vaccines for efficacy against cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situpopulation-based follow-up of two cluster-randomized trials

Provisionally accepted
Matti Lehtinen Matti Lehtinen 1*Penelope Gray Penelope Gray 2Tapio Luostarinen Tapio Luostarinen 3Tiina Eriksson Tiina Eriksson 4Dan Apter Dan Apter 4,5Anne Bly Anne Bly 4Katja Harjula Katja Harjula 4Kaisa Heikkila Kaisa Heikkila 4Mari Hokkanen Mari Hokkanen 4Marjo Kuortti Marjo Kuortti 4Pekka Nieminen Pekka Nieminen 6Mervi Nummela Mervi Nummela 4Jorma Paavonen Jorma Paavonen 7Johanna Palmroth Johanna Palmroth 8Tiina Petaja Tiina Petaja 2,4Ville N. Pimenoff Ville N. Pimenoff 2Eero Pukkala Eero Pukkala 3Joakim Dillner Joakim Dillner 1
  • 1 Karolinska Institutet (KI), Solna, Sweden
  • 2 Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet (KI), Huddinge, Sweden
  • 3 Finnish Cancer Registry, Helsinki, Uusimaa, Finland
  • 4 University of Tampere, Tampere, Pirkanmaa, Finland
  • 5 Finnish Family Federation, Helsinki, Uusimaa, Finland
  • 6 Helsinki University Central Hospital, Helsinki, Uusimaa, Finland
  • 7 University of Helsinki, Helsinki, Uusimaa, Finland
  • 8 University of Kuopio, Kuopio, Northern Savonia, Finland

The final, formatted version of the article will be published soon.

    Human papillomavirus (HPV) vaccines protect against HPV-associated cancers. We report head-tohead comparison of the bivalent and quadrivalent HPV vaccine efficacies against immediate precursors of cervical cancer from 15 years' country-wide cancer registry follow-up of phase III trial cohorts and an age-aligned cohort of unvaccinated women. These individually and/or cluster randomized cohorts of HPV6/11/16/18 and HPV16/18 vaccinated and unvaccinated women were enrolled, respectively in 2002, 2004 and 2003/2005. The trial cohorts comprised initially 16-17 year-old HPV6/11/16/18 vaccinated FUTURE II (NCT00092534) participants (866) and HPV16/18 vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2,465), and 16,526 initially 16-19 year-old unvaccinated controls. After active 4-year clinical follow-up, passive, country-wide Finnish Cancer Registry (FCR) follow-up for cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS) was based on consented use of unique personal identifiers and started 6 months after the end of the FUTURE II and PATRICIA trials in 2007 and 2009, and ended in the end of 2019. The follow-up with altogether 229,020 follow-up years was age-aligned to ensure that similarly aged cohorts were passively followed up for 15 years post vaccination for the intention-to-treat analyses of vaccine efficacy. Overall, we identified, respectively 5 and 16 CIN3 (no AIS) cases in the HPV6/11/16/18 and HPV16/18 cohorts during the FCR-based follow-up. In the unvaccinated cohort we identified 281 CIN3 cases, 20 AIS cases and 13 cases with invasive cervical cancer. Vaccine efficacies against CIN3+ were, respectively 68.4% and 64.5% for the quadrivalent and the bivalent vaccines with overlapping confidence intervals.Long-term follow-up of randomized, initially adolescent HPV-vaccinated and unvaccinated cohorts shows, in this head-to-head setting, that the bivalent and quadrivalent HPV-vaccines are equally effective against immediate precursors of cervical cancer.

    Keywords: Cervical neoplasia, follow-up, Human papillomavirus, vaccine efficacy, randomized trial

    Received: 24 May 2024; Accepted: 29 Jul 2024.

    Copyright: © 2024 Lehtinen, Gray, Luostarinen, Eriksson, Apter, Bly, Harjula, Heikkila, Hokkanen, Kuortti, Nieminen, Nummela, Paavonen, Palmroth, Petaja, Pimenoff, Pukkala and Dillner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Matti Lehtinen, Karolinska Institutet (KI), Solna, Sweden

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