Cosette M Wheeler1, S Rachel Skinner2, M Rowena Del Rosario-Raymundo3, Suzanne M Garland4, Archana Chatterjee5, Eduardo Lazcano-Ponce6, Jorge Salmerón7, Shelly McNeil8, Jack T Stapleton9, Céline Bouchard10, Mark G Martens11, Deborah M Money12, Swee Chong Quek13, Barbara Romanowski14, Carlos S Vallejos15, Bram Ter Harmsel16, Vera Prilepskaya17, Kah Leng Fong18, Henry Kitchener19, Galina Minkina20, Yong Kuei Timothy Lim21, Tanya Stoney22, Nahida Chakhtoura23, Margaret E Cruickshank24, Alevtina Savicheva25, Daniel Pereira da Silva26, Murdo Ferguson27, Anco C Molijn28, Wim G V Quint28, Karin Hardt29, Dominique Descamps29, Pemmaraju V Suryakiran30, Naveen Karkada30, Brecht Geeraerts29, Gary Dubin31, Frank Struyf29. 1. Departments of Pathology and Obstetrics and Gynecology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. Electronic address: Cwheeler@salud.unm.edu. 2. Vaccines Trials Group, Telethon Kids Institute, Perth, WA, Australia; Sydney University Discipline of Child and Adolescent Health, Children's Hospital Westmead, Sydney, NSW, Australia. 3. Department of Obstetrics and Gynecology, San Pablo Colleges Medical Center, San Pablo City, Laguna, Philippines. 4. Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville, VIC, Australia; Department of Microbiology, The Royal Children's Hospital, Parkville, VIC, Australia; Murdoch Childrens Research Institute, Parkville, VIC, Australia; Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, VIC, Australia. 5. Department of Pediatrics, University of South Dakota, Sanford School of Medicine, Sanford Children's Specialty Clinic, Sioux Falls, SD, USA. 6. Research Centre on Public Health, National Institute of Public Health, Cuernavaca, Mexico. 7. Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social, Morelos, Mexico. 8. Canadian Center for Vaccinology, IWK Health Center and Nova Scotia Health Authority, Dalhousie University, Halifax, NS, Canada. 9. Departments of Internal Medicine and Infectious Diseases, University of Iowa, Iowa City, IA, USA. 10. Department of Obstetrics and Gynaecology, Université Laval and Clinique RSF, Québec, QC, Canada. 11. Department of Obstetrics and Gynaecology, Jersey Shore University Medical Center, Neptune, NJ, USA. 12. Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada. 13. Parkway Gynaecology Screening and Treatment Centre, Gleneagles Hospital, Singapore, Singapore. 14. Division of Infectious Diseases, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. 15. Division de Investigacion, Oncosalud-AUNA, Lima, Peru. 16. Roosevelt Kliniek, Leiden, Netherlands. 17. Outpatient Department, Scientific Center of Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation, Moscow, Russian. 18. Singapore General Hospital, Singapore, Singapore. 19. Department of Gynaecological Oncology, Women's Cancer Centre, University of Manchester, St Mary's Hospital, Manchester, UK. 20. City Clinical Hospital, Moscow, Russian. 21. Department of Gynaecologic Oncology, KK Women's and Children's Hospital, Singapore, Singapore. 22. Vaccines Trials Group, Telethon Kids Institute, University of Western Australia, Perth, WA, Australia. 23. Department of Obstetrics and Gynecology, Miler School of Medicine, University of Miami, Miami, FL, USA. 24. Department of Obstetrics and Gynaecology, University of Aberdeen, Aberdeen Maternity Hospital, Aberdeen, UK. 25. Laboratory of Microbiology, DO Ott Research Institute of Obstetrics and Gynecology, St Petersburg, Russia. 26. Departmento de Ginecologia, Instituto Português de Oncologia de Coimbra, Coimbra, Portugal. 27. Department of Family Medicine and Emergency Medicine, Colchester Research Group, Colchester Regional Hospital, Dalhousie University, Truro, NS, Canada. 28. DDL Diagnostic Laboratory, Rijswijk, Netherlands. 29. GSK Vaccines, Wavre, Belgium. 30. GSK Pharmaceuticals India Ltd, Bangalore, India. 31. GSK Vaccines, King of Prussia, PA, USA.
Abstract
BACKGROUND: Although the risk of human papillomavirus (HPV) infection is greatest in young women, women older than 25 years remain at risk. We present data from the VIVIANE study of the HPV 16/18 AS04-adjuvanted vaccine in adult women after 7 years of follow-up. METHODS: In this phase 3, double-blind, randomised controlled trial, healthy women older than 25 years were enrolled (age stratified: 26-35 years, 36-45 years, and ≥46 years). Up to 15% in each age stratum had a history of HPV infection or disease. Women were randomly assigned (1:1) to receive HPV 16/18 vaccine or aluminium hydroxide control, with an internet-based system. The primary endpoint was vaccine efficacy against 6-month persistent infection or cervical intraepithelial neoplasia grade 1 or greater (CIN1+) associated with HPV 16/18. We did analyses in the according-to-protocol cohort for efficacy and total vaccinated cohort. Data for the combined primary endpoint in the according-to-protocol cohort for efficacy were considered significant when the lower limit of the 96·2% CI around the point estimate was greater than 30%. For all other endpoints and cohorts, data were considered significant when the lower limit of the 96·2% CI was greater than 0%. This study is registered with ClinicalTrials.gov, number NCT00294047. FINDINGS: The first participant was enrolled on Feb 16, 2006, and the last study visit took place on Jan 29, 2014. 4407 women were in the according-to-protocol cohort for efficacy (n=2209 vaccine, n=2198 control) and 5747 women in the total vaccinated cohort (n=2877 vaccine, n=2870 control). At month 84, in women seronegative for the corresponding HPV type in the according-to-protocol cohort for efficacy, vaccine efficacy against 6-month persistent infection or CIN1+ associated with HPV 16/18 was significant in all age groups combined (90·5%, 96·2% CI 78·6-96·5). Vaccine efficacy against HPV 16/18-related cytological abnormalities (atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion) and CIN1+ was also significant. We also noted significant cross-protective efficacy against 6-month persistent infection with HPV 31 (65·8%, 96·2% CI 24·9-85·8) and HPV 45 (70·7%, 96·2% CI 34·2-88·4). In the total vaccinated cohort, vaccine efficacy against CIN1+ irrespective of HPV was significant (22·9%, 96·2% CI 4·8-37·7). Serious adverse events related to vaccination occurred in five (0·2%) of 2877 women in the vaccine group and eight (0·3%) of 2870 women in the control group. INTERPRETATION: In women older than 25 years, the HPV 16/18 vaccine continues to protect against infections, cytological abnormalities, and lesions associated with HPV 16/18 and CIN1+ irrespective of HPV type, and infection with non-vaccine types HPV 31 and HPV 45 over 7 years of follow-up. FUNDING: GlaxoSmithKline Biologicals SA.
BACKGROUND: Although the risk of human papillomavirus (HPV) infection is greatest in young women, women older than 25 years remain at risk. We present data from the VIVIANE study of the HPV 16/18 AS04-adjuvanted vaccine in adult women after 7 years of follow-up. METHODS: In this phase 3, double-blind, randomised controlled trial, healthy women older than 25 years were enrolled (age stratified: 26-35 years, 36-45 years, and ≥46 years). Up to 15% in each age stratum had a history of HPV infection or disease. Women were randomly assigned (1:1) to receive HPV 16/18 vaccine or aluminium hydroxide control, with an internet-based system. The primary endpoint was vaccine efficacy against 6-month persistent infection or cervical intraepithelial neoplasia grade 1 or greater (CIN1+) associated with HPV 16/18. We did analyses in the according-to-protocol cohort for efficacy and total vaccinated cohort. Data for the combined primary endpoint in the according-to-protocol cohort for efficacy were considered significant when the lower limit of the 96·2% CI around the point estimate was greater than 30%. For all other endpoints and cohorts, data were considered significant when the lower limit of the 96·2% CI was greater than 0%. This study is registered with ClinicalTrials.gov, number NCT00294047. FINDINGS: The first participant was enrolled on Feb 16, 2006, and the last study visit took place on Jan 29, 2014. 4407 women were in the according-to-protocol cohort for efficacy (n=2209 vaccine, n=2198 control) and 5747 women in the total vaccinated cohort (n=2877 vaccine, n=2870 control). At month 84, in women seronegative for the corresponding HPV type in the according-to-protocol cohort for efficacy, vaccine efficacy against 6-month persistent infection or CIN1+ associated with HPV 16/18 was significant in all age groups combined (90·5%, 96·2% CI 78·6-96·5). Vaccine efficacy against HPV 16/18-related cytological abnormalities (atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion) and CIN1+ was also significant. We also noted significant cross-protective efficacy against 6-month persistent infection with HPV 31 (65·8%, 96·2% CI 24·9-85·8) and HPV 45 (70·7%, 96·2% CI 34·2-88·4). In the total vaccinated cohort, vaccine efficacy against CIN1+ irrespective of HPV was significant (22·9%, 96·2% CI 4·8-37·7). Serious adverse events related to vaccination occurred in five (0·2%) of 2877 women in the vaccine group and eight (0·3%) of 2870 women in the control group. INTERPRETATION: In women older than 25 years, the HPV 16/18 vaccine continues to protect against infections, cytological abnormalities, and lesions associated with HPV 16/18 and CIN1+ irrespective of HPV type, and infection with non-vaccine types HPV 31 and HPV 45 over 7 years of follow-up. FUNDING: GlaxoSmithKline Biologicals SA.
Authors: Maarten F Schim van der Loeff; Alex Vorsters; Elske Marra; Pierre Van Damme; Arjan Hogewoning Journal: Hum Vaccin Immunother Date: 2019-05-07 Impact factor: 3.452
Authors: Peter H Goff; Tomoko Hayashi; Wenqian He; Shiyin Yao; Howard B Cottam; Gene S Tan; Brian Crain; Florian Krammer; Karen Messer; Minya Pu; Dennis A Carson; Peter Palese; Maripat Corr Journal: J Virol Date: 2017-09-12 Impact factor: 5.103