Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 7-year follow-up of the phase 3, double-blind, randomised controlled VIVIANE study

被引:145
作者
Wheeler, Cosette M. [1 ,2 ]
Skinner, S. Rachel [3 ,4 ]
Rowena Del Rosario-Raymundo, M. [5 ]
Garland, Suzanne M. [6 ,7 ,8 ,9 ]
Chatterjee, Archana [10 ]
Lazcano-Ponce, Eduardo [11 ]
Salmeron, Jorge [12 ]
McNeil, Shelly [13 ,14 ]
Stapleton, Jack T. [15 ,16 ]
Bouchard, Celine [17 ,18 ]
Martens, Mark G. [19 ]
Money, Deborah M. [20 ]
Quek, Swee Chong [21 ]
Romanowski, Barbara [22 ]
Vallejos, Carlos S. [23 ]
ter Harmsel, Bram [24 ]
Prilepskaya, Vera [25 ]
Fong, Kah Leng [26 ]
Kitchener, Henry [27 ]
Minkina, Galina [28 ]
Lim, Yong Kuei Timothy [29 ]
Stoney, Tanya [30 ]
Chakhtoura, Nahida [31 ]
Cruickshank, Margaret E. [32 ]
Savicheva, Alevtina [33 ]
da Silva, Daniel Pereira [34 ]
Ferguson, Murdo [35 ]
Molijn, Anco C. [36 ]
Quint, Wim G. V. [36 ]
Hardt, Karin [37 ]
Descamps, Dominique [37 ]
Suryakiran, Pemmaraju V. [38 ]
Karkada, Naveen [38 ]
Geeraerts, Brecht [37 ]
Dubin, Gary [39 ]
Struyf, Frank [37 ]
机构
[1] Univ New Mexico, Dept Pathol, Hlth Sci Ctr, Albuquerque, NM 87131 USA
[2] Univ New Mexico, Dept Obstet & Gynecol, Hlth Sci Ctr, Albuquerque, NM 87131 USA
[3] Telethon Kids Inst, Vaccines Trials Grp, Perth, WA, Australia
[4] Univ Sydney, Discipline Child & Adolescent Hlth, Childrens Hosp Westmead, Sydney, NSW, Australia
[5] San Pablo Coll Med Ctr, Dept Obstet & Gynecol, San Pablo City, Laguna, Philippines
[6] Royal Womens Hosp, Dept Microbiol & Infect Dis, Parkville, Vic, Australia
[7] Royal Childrens Hosp, Dept Microbiol, Parkville, Vic, Australia
[8] Murdoch Childrens Res Inst, Parkville, Vic, Australia
[9] Univ Melbourne, Dept Obstet & Gynaecol, Parkville, Vic, Australia
[10] Univ South Dakota, Dept Pediat, Sanford Sch Med, Sanford Childrens Specialty Clin, Sioux Falls, SD USA
[11] Natl Inst Publ Hlth, Res Ctr Publ Hlth, Cuernavaca, Morelos, Mexico
[12] Inst Mexicano Seguro Social, Unidad Invest Epidemiol & Serv Salud, Cuernavaca, Morelos, Mexico
[13] Dalhousie Univ, Canadian Ctr Vaccinol, IWK Hlth Ctr, Halifax, NS, Canada
[14] Dalhousie Univ, Nova Scotia Hlth Author, Halifax, NS, Canada
[15] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA
[16] Univ Iowa, Dept Infect Dis, Iowa City, IA USA
[17] Univ Laval, Dept Obstet & Gynaecol, Quebec City, PQ, Canada
[18] Clin RSF, Quebec City, PQ, Canada
[19] Jersey Shore Univ, Med Ctr, Dept Obstet & Gynaecol, Neptune, NJ USA
[20] Univ British Columbia, Dept Obstet & Gynaecol, Vancouver, BC, Canada
[21] Gleneagles Hosp, Pkwy Gynaecol Screening & Treatment Ctr, Singapore, Singapore
[22] Univ Alberta, Div Infect Dis, Dept Med, Fac Med & Dent, Edmonton, AB, Canada
[23] Oncosalud AUNA, Div Invest, Lima, Peru
[24] Roosevelt Klin, Leiden, Netherlands
[25] Minist Hlth Russian Federat, Outpatient Dept, Sci Ctr Obstet Gynecol & Perinatol, Moscow, Russia
[26] Singapore Gen Hosp, Singapore, Singapore
[27] Univ Manchester, St Marys Hosp, Dept Gynaecol Oncol, Womens Canc Ctr, Manchester, Lancs, England
[28] City Clin Hosp, Moscow, Russia
[29] KK Womens & Childrens Hosp, Dept Gynaecol Oncol, Singapore, Singapore
[30] Univ Western Australia, Telethon Kids Inst, Vaccines Trials Grp, Perth, WA, Australia
[31] Univ Miami, Miler Sch Med, Dept Obstet & Gynecol, Miami, FL USA
[32] Univ Aberdeen, Aberdeen Matern Hosp, Dept Obstet & Gynaecol, Aberdeen, Scotland
[33] DO Ott Res Inst Obstet & Gynecol, Microbiol Lab, St Petersburg, Russia
[34] Inst Portugues Oncol Coimbra, Dept Ginecol, Coimbra, Portugal
[35] Dalhousie Univ, Dept Family Med & Emergency Med, Colchester Reg Hosp, Colchester Res Grp, Truro, NS, Canada
[36] DDL Diagnost Lab, Rijswijk, Netherlands
[37] GSK Vaccines, Wavre, Belgium
[38] GSK Pharmaceut India Ltd, Bangalore, Karnataka, India
[39] GSK Vaccines, King Of Prussia, PA USA
关键词
OF-STUDY ANALYSIS; INTRAEPITHELIAL NEOPLASIA; QUADRIVALENT VACCINE; SUSTAINED EFFICACY; CONTROLLED-TRIAL; HPV VACCINATION; CERVICAL-CANCER; PATRICIA TRIAL; BROAD-SPECTRUM; YOUNG-WOMEN;
D O I
10.1016/S1473-3099(16)30120-7
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
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 signifi cant 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 signifi cant 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 signifi cance and low-grade squamous intraepithelial lesion) and CIN1+ was also signifi cant. We also noted signifi cant 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 signifi cant (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.
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页码:1154 / 1168
页数:15
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