• Cosette M Wheeler, S Rachel Skinner, M Rowena Del Rosario-Raymundo, Suzanne M Garland, Archana Chatterjee, Eduardo Lazcano-Ponce, Jorge Salmerón, Shelly McNeil, Jack T Stapleton, Céline Bouchard, Mark G Martens, Deborah M Money, Swee Chong Quek, Barbara Romanowski, Carlos S Vallejos, Bram Ter Harmsel, Vera Prilepskaya, Kah Leng Fong, Henry Kitchener, Galina Minkina, Lim Yong Kuei Timothy YKT Department of Gynaecologic Oncology, KK Women's and Children's Hospital, Singapore, Singapore., Tanya Stoney, Nahida Chakhtoura, Margaret E Cruickshank, Alevtina Savicheva, Daniel Pereira da Silva, Murdo Ferguson, Anco C Molijn, Quint Wim G V WGV DDL Diagnostic Laboratory, Rijswijk, Netherlands., Karin Hardt, Dominique Descamps, Suryakiran Pemmaraju V PV GSK Pharmaceuticals India Ltd, Bangalore, India., Naveen Karkada, Brecht Geeraerts, Gary Dubin, Frank Struyf, and VIVIANE Study Group.
• Departments of Pathology and Obstetrics and Gynecology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. Electronic address: Cwheeler@salud.unm.edu.
• Lancet Infect Dis. 2016 Oct 1; 16 (10): 1154-1168.

BackgroundAlthough 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.MethodsIn 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.FindingsThe 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.InterpretationIn 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.FundingGlaxoSmithKline Biologicals SA.Copyright © 2016 Elsevier Ltd. All rights reserved.

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