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

• Published in: Frontiers in cellular and infection microbiology 2024-09, Vol.14, p.1437704
• Main Authors: Lehtinen, Matti, Gray, Penelope, Luostarinen, Tapio, Eriksson, Tiina, Apter, Dan, Bly, Anne, Harjula, Katja, Heikkilä, Kaisa, Hokkanen, Mari, Kuortti, Marjo, Nieminen, Pekka, Nummela, Mervi, Paavonen, Jorma, Palmroth, Johanna, Petäjä, Tiina, Pimenoff, Ville N, Pukkala, Eero, Dillner, Joakim
• Format: Article
• Language: English
• Subjects: Adenocarcinoma in Situ - prevention & control; Adenocarcinoma in Situ - virology; Adolescent; Adult; Cellular and Infection Microbiology; cervical neoplasia; Female; Finland; follow-up; Follow-Up Studies; human papillomavirus; Humans; Papillomavirus Infections - prevention & control; Papillomavirus Infections - virology; Papillomavirus Vaccines - administration & dosage; Papillomavirus Vaccines - immunology; randomized trial; Treatment Outcome; Uterine Cervical Dysplasia - prevention & control; Uterine Cervical Dysplasia - virology; Uterine Cervical Neoplasms - prevention & control; Uterine Cervical Neoplasms - virology; Vaccination; vaccine efficacy; Young Adult
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2024.1437704

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. 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. 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. 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.