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

Matti Lehtinen; Penelope Gray; Tapio Luostarinen; Tiina Eriksson; Dan Apter; Anne Bly; Katja Harjula; Kaisa Heikkilä; Mari Hokkanen; Marjo Kuortti; Pekka Nieminen; Mervi Nummela; Jorma Paavonen; Johanna Palmroth; Tiina Petäjä; Ville N. Pimenoff; Eero Pukkala; Joakim Dillner

doi:10.3389/fcimb.2024.1437704

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

Matti Lehtinen, Penelope Gray, Tapio Luostarinen, Tiina Eriksson, Dan Apter, Anne Bly, Katja Harjula, Kaisa Heikkilä, Mari Hokkanen, Marjo Kuortti, Pekka Nieminen, Mervi Nummela, Jorma Paavonen, Johanna Palmroth, Tiina Petäjä, Ville N. Pimenoff, Eero Pukkala, Joakim Dillner

Research output: Contribution to journal › Article › Scientific › peer-review

Abstract

Introduction: We report head-to-head 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. Methods: These individually and/or clusterrandomized 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- to 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- to 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 at 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. Results: Overall, we identified 5 and 16 CIN3 (no AIS) cases in the HPV6/11/16/18 and HPV16/18 cohorts, respectively, 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 68.4% and 64.5% for the quadrivalent and the bivalent vaccines, respectively, with overlapping confidence intervals. Discussion: 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.

Original language	English
Article number	1437704
Number of pages	7
Journal	Frontiers in Cellular And Infection Microbiology
Volume	14
DOIs	https://doi.org/10.3389/fcimb.2024.1437704
Publication status	Published - 2024
Publication type	A1 Journal article-refereed

Funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Finnish Cancer Society, Swedish Cancer Society, and Nordic Cancer Union. The RISCC grant number 847845. Acknowledgments This work was supported by Swedish Cancerfonden, EU-RISCC network.

Funders	Funder number
Cancerfonden
Swedish Cancerfonden
EU-RISCC network
Finnish Cancer Society
Nordic Cancer Union	847845

Keywords

cervical neoplasia
follow-up
human papillomavirus
randomized trial
vaccine efficacy

Publication forum classification

Publication forum level 1

ASJC Scopus subject areas

Microbiology
Immunology
Microbiology (medical)
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3389/fcimb.2024.1437704Licence: CC BY

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https://urn.fi/URN:NBN:fi:tuni-202411059899Licence: CC BY

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Lehtinen, M., Gray, P., Luostarinen, T., Eriksson, T., Apter, D., Bly, A., Harjula, K., Heikkilä, K., Hokkanen, M., Kuortti, M., Nieminen, P., Nummela, M., Paavonen, J., Palmroth, J., Petäjä, T., Pimenoff, V. N., Pukkala, E., & Dillner, J. (2024). Head-to-head comparison of two human papillomavirus vaccines for efficacy against cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ: population-based follow-up of two cluster-randomized trials. Frontiers in Cellular And Infection Microbiology, 14, Article 1437704. https://doi.org/10.3389/fcimb.2024.1437704

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abstract = "Introduction: We report head-to-head comparison of the bivalent and quadrivalent HPV vaccine efficacies against immediate precursors of cervical cancer from 15 years{\textquoteright} country-wide cancer registry follow-up of phase III trial cohorts and an age-aligned cohort of unvaccinated women. Methods: These individually and/or clusterrandomized 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- to 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- to 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 at 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. Results: Overall, we identified 5 and 16 CIN3 (no AIS) cases in the HPV6/11/16/18 and HPV16/18 cohorts, respectively, 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 68.4% and 64.5% for the quadrivalent and the bivalent vaccines, respectively, with overlapping confidence intervals. Discussion: 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.",

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author = "Matti Lehtinen and Penelope Gray and Tapio Luostarinen and Tiina Eriksson and Dan Apter and Anne Bly and Katja Harjula and Kaisa Heikkil{\"a} and Mari Hokkanen and Marjo Kuortti and Pekka Nieminen and Mervi Nummela and Jorma Paavonen and Johanna Palmroth and Tiina Pet{\"a}j{\"a} and Pimenoff, {Ville N.} and Eero Pukkala and Joakim Dillner",

note = "Publisher Copyright: Copyright {\textcopyright} 2024 Lehtinen, Gray, Luostarinen, Eriksson, Apter, Bly, Harjula, Heikkil{\"a}, Hokkanen, Kuortti, Nieminen, Nummela, Paavonen, Palmroth, Pet{\"a}j{\"a}, Pimenoff, Pukkala and Dillner.",

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Lehtinen, M, Gray, P, Luostarinen, T, Eriksson, T, Apter, D, Bly, A , Harjula, K, Heikkilä, K, Hokkanen, M, Kuortti, M, Nieminen, P, Nummela, M, Paavonen, J, Palmroth, J, Petäjä, T, Pimenoff, VN, Pukkala, E & Dillner, J 2024, 'Head-to-head comparison of two human papillomavirus vaccines for efficacy against cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ: population-based follow-up of two cluster-randomized trials', Frontiers in Cellular And Infection Microbiology, vol. 14, 1437704. https://doi.org/10.3389/fcimb.2024.1437704

Head-to-head comparison of two human papillomavirus vaccines for efficacy against cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ: population-based follow-up of two cluster-randomized trials. / Lehtinen, Matti; Gray, Penelope; Luostarinen, Tapio et al.
In: Frontiers in Cellular And Infection Microbiology, Vol. 14, 1437704, 2024.

Research output: Contribution to journal › Article › Scientific › peer-review

TY - JOUR

T1 - Head-to-head comparison of two human papillomavirus vaccines for efficacy against cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ

T2 - population-based follow-up of two cluster-randomized trials

AU - Lehtinen, Matti

AU - Gray, Penelope

AU - Luostarinen, Tapio

AU - Eriksson, Tiina

AU - Apter, Dan

AU - Bly, Anne

AU - Harjula, Katja

AU - Heikkilä, Kaisa

AU - Hokkanen, Mari

AU - Kuortti, Marjo

AU - Nieminen, Pekka

AU - Nummela, Mervi

AU - Paavonen, Jorma

AU - Palmroth, Johanna

AU - Petäjä, Tiina

AU - Pimenoff, Ville N.

AU - Pukkala, Eero

AU - Dillner, Joakim

N1 - Publisher Copyright: Copyright © 2024 Lehtinen, Gray, Luostarinen, Eriksson, Apter, Bly, Harjula, Heikkilä, Hokkanen, Kuortti, Nieminen, Nummela, Paavonen, Palmroth, Petäjä, Pimenoff, Pukkala and Dillner.

PY - 2024

Y1 - 2024

N2 - Introduction: We report head-to-head 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. Methods: These individually and/or clusterrandomized 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- to 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- to 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 at 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. Results: Overall, we identified 5 and 16 CIN3 (no AIS) cases in the HPV6/11/16/18 and HPV16/18 cohorts, respectively, 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 68.4% and 64.5% for the quadrivalent and the bivalent vaccines, respectively, with overlapping confidence intervals. Discussion: 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.

AB - Introduction: We report head-to-head 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. Methods: These individually and/or clusterrandomized 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- to 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- to 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 at 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. Results: Overall, we identified 5 and 16 CIN3 (no AIS) cases in the HPV6/11/16/18 and HPV16/18 cohorts, respectively, 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 68.4% and 64.5% for the quadrivalent and the bivalent vaccines, respectively, with overlapping confidence intervals. Discussion: 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.

KW - cervical neoplasia

KW - follow-up

KW - human papillomavirus

KW - randomized trial

KW - vaccine efficacy

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DO - 10.3389/fcimb.2024.1437704

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SN - 2235-2988

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JO - Frontiers in Cellular And Infection Microbiology

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Lehtinen M, Gray P, Luostarinen T, Eriksson T, Apter D, Bly A et al. Head-to-head comparison of two human papillomavirus vaccines for efficacy against cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ: population-based follow-up of two cluster-randomized trials. Frontiers in Cellular And Infection Microbiology. 2024;14:1437704. doi: 10.3389/fcimb.2024.1437704