Journal article
Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 4-year interim follow-up of the phase 3, double-blind, randomised controlled VIVIANE study
The Lancet (British edition), Vol.384(9961), pp.2213-2227
12/20/2014
DOI: 10.1016/S0140-6736(14)60920-X
PMID: 25189358
Abstract
Although adolescent girls are the main population for prophylactic human papillomavirus (HPV) vaccines, adult women who remain at risk of cervical cancer can also be vaccinated. We report data from the interim analysis of the ongoing VIVIANE study, the aim of which is to assess the efficacy, safety, and immunogenicity of the HPV 16/18 AS04-adjuvanted vaccine in adult women.
In this phase 3, multinational, double-blind, randomised controlled trial, we randomly assigned healthy women older than 25 years to the HPV 16/18 vaccine or control (1:1), via an internet-based system with an algorithm process that accounted for region, age stratum, baseline HPV DNA status, HPV 16/18 serostatus, and cytology. Enrolment was age-stratified, with about 45% of participants in each of the 26-35 and 36-45 years age strata and 10% in the 46 years and older stratum. Up to 15% of women in each age stratum could have a history of HPV infection or disease. The primary endpoint was vaccine efficacy against 6-month persistent infection or cervical intraepithelial neoplasia grade 1 or higher (CIN1+) associated with HPV 16/18. The primary analysis was done in the according-to-protocol cohort for efficacy, which consists of women who received all three vaccine or control doses, had negative or low-grade cytology at baseline, and had no history of HPV disease. Secondary analyses included vaccine efficacy against non-vaccine oncogenic HPV types. Mean follow-up time was 40·3 months. This study is registered with ClinicalTrials.gov, number NCT00294047.
The first participant was enrolled on Feb 16, 2006, and the last study visit for the present analysis took place on Dec 10, 2010; 5752 women were included in the total vaccinated cohort (n=2881 vaccine, n=2871 control), and 4505 in the according-to-protocol cohort for efficacy (n=2264 vaccine, n=2241 control). Vaccine efficacy against HPV 16/18-related 6-month persistent infection or CIN1+ was significant in all age groups combined (81·1%, 97·7% CI 52·1-94·0), in the 26-35 years age group (83·5%, 45·0-96·8), and in the 36-45 years age group (77·2%, 2·8-96·9); no cases were seen in women aged 46 years and older. Vaccine efficacy against atypical squamous cells of undetermined significance or greater associated with HPV 16/18 was also significant. We also noted significant cross-protective vaccine efficacy against 6-month persistent infection with HPV 31 (79·1%, 97·7% CI 27·6-95·9) and HPV 45 (76·9%, 18·5-95·6]) Serious adverse events occurred in 285 (10%) of 2881 women in the vaccine group and 267 (9%) of 2871 in the control group; five (<1%) and eight (<1%) of these events, respectively, were believed to be related to vaccination.
In women older than 25 years, the HPV 16/18 vaccine is efficacious against infections and cervical abnormalities associated with the vaccine types, as well as infections with the non-vaccine HPV types 31 and 45.
GlaxoSmithKline Biologicals SA.
Details
- Title: Subtitle
- Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 4-year interim follow-up of the phase 3, double-blind, randomised controlled VIVIANE study
- Creators
- S Rachel Skinner - Vaccines Trials Group, Telethon Institute for Child Health Research, Perth, WA, Australia; Sydney University Discipline of Paediatrics and Child Health, Children's Hospital Westmead, Sydney, NSW, Australia. Electronic address: rachel.skinner@health.nsw.gov.auAnne Szarewski - Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UKBarbara Romanowski - Division of Infectious Diseases, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, CanadaSuzanne M Garland - 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, AustraliaEduardo Lazcano-Ponce - Avenida Universidad S/N Jojutla, Morelos, MexicoJorge Salmerón - Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social, Morelos, MexicoM Rowena Del Rosario-Raymundo - Department of Obstetrics and Gynecology, San Pablo Colleges Medical Center, San Pablo City, Laguna, PhilippinesRené H M Verheijen - Gynaecological Oncology and HumVac Research Group, University Medical Center Utrecht, Utrecht, NetherlandsSwee Chong Quek - Parkway Gynaecology Screening & Treatment Centre, Gleneagles Hospital, SingaporeDaniel P da Silva - Departmento de Ginecologia, Instituto Português de Oncologia de Coimbra, Coimbra, PortugalHenry Kitchener - Women's Cancer Centre, Institute of Cancer Sciences, University of Manchester, St Mary's Hospital, Manchester, UKKah Leng Fong - Department of Obstetrics and Gynaecology, Singapore General Hospital, SingaporeCéline Bouchard - Clinique RSF, Québec, QC, CanadaDeborah M Money - Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada; The Women's Health Research Institute, Vancouver, BC, CanadaArunachalam Ilancheran - Division of Gynecologic Oncology, National University Hospital, SingaporeMargaret E Cruickshank - Division of Medical Education, University of Aberdeen, Aberdeen, UKMyron J Levin - University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USAArchana Chatterjee - Department of Pediatrics, University of South Dakota Sanford School of Medicine, and Sanford Children's Specialty Clinics, Sioux Falls, SD, USAJack T Stapleton - Department of Internal Medicine, University of Iowa, Iowa City, IA, USAMark Martens - Jersey Shore University Medical Center, Neptune, NJ, USAWim Quint - DDL Diagnostic Laboratory, Rijswijk, NetherlandsMarie-Pierre David - GSK Vaccines, Wavre, BelgiumDorothée Meric - GSK Vaccines, Wavre, BelgiumKarin Hardt - GSK Vaccines, Wavre, BelgiumDominique Descamps - GSK Vaccines, Wavre, BelgiumBrecht Geeraerts - GSK Vaccines, Wavre, BelgiumFrank Struyf - GSK Vaccines, Wavre, BelgiumGary Dubin - GSK Vaccines, King of Prussia, PA, USAVIVIANE Study Group
- Resource Type
- Journal article
- Publication Details
- The Lancet (British edition), Vol.384(9961), pp.2213-2227
- DOI
- 10.1016/S0140-6736(14)60920-X
- PMID
- 25189358
- ISSN
- 0140-6736
- eISSN
- 1474-547X
- Language
- English
- Date published
- 12/20/2014
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Internal Medicine
- Record Identifier
- 9984094403302771
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