Jorma Paavonen1, David Jenkins2, F Xavier Bosch3, Paulo Naud4, Jorge Salmerón5, Cosette M Wheeler6, Song-Nan Chow7, Dan L Apter8, Henry C Kitchener9, Xavier Castellsague3, Newton S de Carvalho10, S Rachel Skinner11, Diane M Harper12, James A Hedrick13, Unnop Jaisamrarn14, Genara Am Limson15, Marc Dionne16, Wim Quint17, Bart Spiessens2, Pascal Peeters2, Frank Struyf2, Susan L Wieting2, Matti O Lehtinen18, Gary Dubin19. 1. University of Helsinki, Department of Obstetrics and Gynaecology, Helsinki, Finland. Electronic address: Jorma.Paavonen@hus.fi. 2. GlaxoSmithKline Biologicals, Rixensart, Belgium. 3. Institut Català d'Oncologia, Epidemiology and Cancer Registration Unit, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain. 4. University Federal of Rio Grande do Sul, Hospital de Clínica de Porto Alegre, Porto Alegre, Brazil. 5. Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social, Morelos, México. 6. University of New Mexico Health Sciences Center, Department of Molecular Genetics and Microbiology, Albuquerque, New Mexico, USA. 7. Department of Obstetrics and Gynecology, National Taiwan University Hospital, and College of Medicine, National Taiwan University, Taipei, Taiwan. 8. Family Federation of Finland, Sexual Health Clinic, Helsinki, Finland. 9. University of Manchester, Academic Unit of Obstetrics and Gynaecology, Manchester, UK. 10. Department of Obstetrics and Gynaecology, University Federal of Parana and Obstetric Gynecological and Infectious Diseases Sector, Clinic Hospital, Curitiba, Parana, Brazil. 11. TVWTelethon Institute for Child Health Research, and School of Paediatrics and Child Health, University of Western Australia, Perth, Australia. 12. Dartmouth Medical School, Hanover, NH, USA. 13. Kentucky Pediatric and Adult Research, Bardstown, KY, USA. 14. Chulalongkorn University, Department of Obstetrics and Gynaecology, Faculty of Medicine, Bangkok, Thailand. 15. University of the Philippines, College of Medicine, Philippine General Hospital, Makati Medical Center, Makati City, Philippines. 16. Centre Hospitalier Universitaire du Québec, Department of Public Health, Beauport, Québec, Canada. 17. DDL Diagnostic Laboratory, Voorburg, Netherlands. 18. University of Tampere, School of Public Health, Tampere, Finland. 19. GlaxoSmithKline Biologicals, King of Prussia, PA, USA.
Abstract
BACKGROUND: The aim of this interim analysis of a large, international phase III study was to assess the efficacy of an AS04 adjuvanted L1 virus-like-particle prophylactic candidate vaccineagainst infection with human papillomavirus (HPV) types 16 and 18 in young women. METHODS:18,644 women aged 15-25 years were randomly assigned to receive either HPV16/18 vaccine (n=9319) or hepatitis A vaccine (n=9325) at 0, 1, and 6 months. Of these women, 88 were excluded because of high-grade cytology and 31 for missing cytology results. Thus, 9258 women received theHPV16/18 vaccine and 9267 received the control vaccine in the total vaccinated cohort for efficacy, which included women who had prevalent oncogenic HPV infections, often with several HPV types, as well as low-grade cytological abnormalities at study entry and who received at least one vaccine dose. We assessed cervical cytology and subsequent biopsy for 14 oncogenic HPV types by PCR. The primary endpoint--vaccine efficacy against cervical intraepithelial neoplasia (CIN) 2+ associated with HPV16 or HPV18--was assessed in women who were seronegative and DNA negative for the corresponding vaccine type at baseline (month 0) and allowed inclusion of lesions with several oncogenic HPV types. This interim event-defined analysis was triggered when at least 23 cases of CIN2+ with HPV16 or HPV18 DNA in the lesion were detected in the total vaccinated cohort for efficacy. Analyses were done on a modified intention-to-treat basis. This trial is registered with the US National Institutes of Health clinical trial registry, number NCT00122681. FINDINGS:Mean length of follow-up for women in the primary analysis for efficacy at the time of the interim analysis was 14.8 (SD 4.9) months. Two cases of CIN2+ associated with HPV16 or HPV18 DNA were seen in the HPV16/18 vaccine group; 21 were recorded in the control group. Of the 23 cases, 14 (two in the HPV16/18 vaccine group, 12 in the control group) contained several oncogenic HPV types. Vaccine efficacy against CIN2+ containing HPV16/18 DNA was 90.4% (97.9% CI 53.4-99.3; p<0.0001). No clinically meaningful differences were noted in safety outcomes between the study groups. INTERPRETATION: The adjuvanted HPV16/18 vaccine showed prophylactic efficacy against CIN2+ associated with HPV16 or HPV18 and thus could be used for cervical cancer prevention.
RCT Entities:
BACKGROUND: The aim of this interim analysis of a large, international phase III study was to assess the efficacy of an AS04 adjuvanted L1 virus-like-particle prophylactic candidate vaccine against infection with human papillomavirus (HPV) types 16 and 18 in young women. METHODS: 18,644 women aged 15-25 years were randomly assigned to receive either HPV16/18 vaccine (n=9319) or hepatitis A vaccine (n=9325) at 0, 1, and 6 months. Of these women, 88 were excluded because of high-grade cytology and 31 for missing cytology results. Thus, 9258 women received the HPV16/18 vaccine and 9267 received the control vaccine in the total vaccinated cohort for efficacy, which included women who had prevalent oncogenic HPV infections, often with several HPV types, as well as low-grade cytological abnormalities at study entry and who received at least one vaccine dose. We assessed cervical cytology and subsequent biopsy for 14 oncogenic HPV types by PCR. The primary endpoint--vaccine efficacy against cervical intraepithelial neoplasia (CIN) 2+ associated with HPV16 or HPV18--was assessed in women who were seronegative and DNA negative for the corresponding vaccine type at baseline (month 0) and allowed inclusion of lesions with several oncogenic HPV types. This interim event-defined analysis was triggered when at least 23 cases of CIN2+ with HPV16 or HPV18 DNA in the lesion were detected in the total vaccinated cohort for efficacy. Analyses were done on a modified intention-to-treat basis. This trial is registered with the US National Institutes of Health clinical trial registry, number NCT00122681. FINDINGS: Mean length of follow-up for women in the primary analysis for efficacy at the time of the interim analysis was 14.8 (SD 4.9) months. Two cases of CIN2+ associated with HPV16 or HPV18 DNA were seen in the HPV16/18 vaccine group; 21 were recorded in the control group. Of the 23 cases, 14 (two in the HPV16/18 vaccine group, 12 in the control group) contained several oncogenic HPV types. Vaccine efficacy against CIN2+ containing HPV16/18 DNA was 90.4% (97.9% CI 53.4-99.3; p<0.0001). No clinically meaningful differences were noted in safety outcomes between the study groups. INTERPRETATION: The adjuvanted HPV16/18 vaccine showed prophylactic efficacy against CIN2+ associated with HPV16 or HPV18 and thus could be used for cervical cancer prevention.
Authors: Ratish Gambhira; Subhashini Jagu; Balasubramanyam Karanam; Patti E Gravitt; Timothy D Culp; Neil D Christensen; Richard B S Roden Journal: J Virol Date: 2007-08-22 Impact factor: 5.103
Authors: Geneviève Rail; Luisa Molino; Caroline Fusco; Moss Edward Norman; LeAnne Petherick; Jessica Polzer; Fiona Moola; Mary Bryson Journal: Can J Public Health Date: 2018-08-03