Efficacy of the bivalent HPV vaccine against HPV 16/18-associated precancer: long-term follow-up results from the Costa Rica Vaccine Trial

• Published in: The lancet oncology 2020-12, Vol.21 (12), p.1643-1652
• Main Authors: Porras, Carolina, Tsang, Sabrina H, Herrero, Rolando, Guillén, Diego, Darragh, Teresa M, Stoler, Mark H, Hildesheim, Allan, Wagner, Sarah, Boland, Joseph, Lowy, Douglas R, Schiller, John T, Schiffman, Mark, Schussler, John, Gail, Mitchell H, Quint, Wim, Ocampo, Rebeca, Morales, Jorge, Rodríguez, Ana C, Hu, Shangying, Sampson, Joshua N, Kreimer, Aimée R, Cortés, Bernal, González, Paula, Jiménez, Silvia E, Rodríguez, Ana Cecilia, Sherman, Mark, Pinto, Ligia A, Kemp, Troy J, Sidawy, Mary K, Van Doorn, Leen-Jan, Struijk, Linda, Palefsky, Joel M
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biopsy; Cellular biology; Cervical cancer; Clinical trials; Colposcopy; Costa Rica; Cytology; Deoxyribonucleic acid; DNA; DNA vaccines; Double-Blind Method; Female; Hepatitis; Hepatitis A; Human papillomavirus; Human papillomavirus 16 - immunology; Human papillomavirus 18 - immunology; Humans; Immunization; Infections; Informed consent; Invasiveness; Neoplasm Grading; Papillomavirus Infections - diagnosis; Papillomavirus Infections - prevention & control; Papillomavirus Infections - virology; Papillomavirus Vaccines - administration & dosage; Papillomavirus Vaccines - adverse effects; Pregnancy; Puerperium; Time Factors; Treatment Outcome; Uterine Cervical Dysplasia - pathology; Uterine Cervical Dysplasia - prevention & control; Uterine Cervical Dysplasia - virology; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - prevention & control; Uterine Cervical Neoplasms - virology; Vaccine efficacy; Vaccines; Vaccines, Combined - administration & dosage; Vaccines, Combined - adverse effects; Womens health; Young Adult
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(20)30524-6

Oncogenic human papillomavirus (HPV) infections cause most cases of cervical cancer. Here, we report long-term follow-up results for the Costa Rica Vaccine Trial (publicly funded and initiated before licensure of the HPV vaccines), with the aim of assessing the efficacy of the bivalent HPV vaccine for preventing HPV 16/18-associated cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Women aged 18–25 years were enrolled in a randomised, double-blind, controlled trial in Costa Rica, between June 28, 2004, and Dec 21, 2005, designed to assess the efficacy of a bivalent vaccine for the prevention of infection with HPV 16/18 and associated precancerous lesions at the cervix. Participants were randomly assigned (1:1) to receive an HPV 16/18 AS04-adjuvanted vaccine or control hepatitis A vaccine. Vaccines were administered intramuscularly in three 0·5 mL doses at 0, 1, and 6 months and participants were followed up annually for 4 years. After the blinded phase, women in the HPV vaccine group were invited to enrol in the long-term follow-up study, which extended follow-up for 7 additional years. The control group received HPV vaccine and was replaced with a new unvaccinated control group. Women were followed up every 2 years until year 11. Investigators and patients were aware of treatment allocation for the follow-up phase. At each visit, clinicians collected cervical cells from sexually active women for cytology and HPV testing. Women with abnormal cytology were referred to colposcopy, biopsy, and treatment as needed. Women with negative results at the last screening visit (year 11) exited the long-term follow-up study. The analytical cohort for vaccine efficacy included women who were HPV 16/18 DNA-negative at vaccination. The primary outcome of this analysis was defined as histopathologically confirmed CIN2+ or cervical intraepithelial neoplasia grade 3 or worse associated with HPV 16/18 cervical infection detected at colposcopy referral. We calculated vaccine efficacy by year and cumulatively. This long-term follow-up study is registered with ClinicalTrials.gov, NCT00867464. 7466 women were enrolled in the Costa Rica Vaccine Trial; 3727 received the HPV vaccine and 3739 received the control vaccine. Between March 30, 2009, and July 5, 2012, 2635 women in the HPV vaccine group and 2836 women in the new unvaccinated control group were enrolled in the long-term follow-up study. 2635 women in the HPV vaccine group and 2677 women in the control group wer