title: Efficacy of human papillomavirus 16 and 18 (HPV-16/18) AS04-adjuvanted vaccine against cervical infection and precancer in young women: final event-driven analysis of the randomized, double-blind PATRICIA trial.
abstract: We report final event-driven analysis data on the immunogenicity and efficacy of the human papillomavirus 16 and 18 ((HPV-16/18) AS04-adjuvanted vaccine in young women aged 15 to 25 years from the PApilloma TRIal against Cancer In young Adults (PATRICIA). The total vaccinated cohort (TVC) included all randomized participants who received at least one vaccine dose (vaccine, n = 9,319; control, n = 9,325) at months 0, 1, and/or 6. The TVC-naive (vaccine, n = 5,822; control, n = 5,819) had no evidence of high-risk HPV infection at baseline, approximating adolescent girls targeted by most HPV vaccination programs. Mean follow-up was approximately 39 months after the first vaccine dose in each cohort. At baseline, 26% of women in the TVC had evidence of past and/or current HPV-16/18 infection. HPV-16 and HPV-18 antibody titers postvaccination tended to be higher among 15- to 17-year-olds than among 18- to 25-year-olds. In the TVC, vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 1 or greater (CIN1+), CIN2+, and CIN3+ associated with HPV-16/18 was 55.5% (96.1% confidence interval [CI], 43.2, 65.3), 52.8% (37.5, 64.7), and 33.6% (-1.1, 56.9). VE against CIN1+, CIN2+, and CIN3+ irrespective of HPV DNA was 21.7% (10.7, 31.4), 30.4% (16.4, 42.1), and 33.4% (9.1, 51.5) and was consistently significant only in 15- to 17-year-old women (27.4% [10.8, 40.9], 41.8% [22.3, 56.7], and 55.8% [19.2, 76.9]). In the TVC-naive, VE against CIN1+, CIN2+, and CIN3+ associated with HPV-16/18 was 96.5% (89.0, 99.4), 98.4% (90.4, 100), and 100% (64.7, 100), and irrespective of HPV DNA it was 50.1% (35.9, 61.4), 70.2% (54.7, 80.9), and 87.0% (54.9, 97.7). VE against 12-month persistent infection with HPV-16/18 was 89.9% (84.0, 94.0), and that against HPV-31/33/45/51 was 49.0% (34.7, 60.3). In conclusion, vaccinating adolescents before sexual debut has a substantial impact on the overall incidence of high-grade cervical abnormalities, and catch-up vaccination up to 18 years of age is most likely effective. (This study has been registered at ClinicalTrials.gov under registration no. NCT001226810.).
authors: Family Federation of Finland, Sexual Health Clinic, Helsinki, Finland dan.apter@vaestoliitto.fi.
authors: Dan
authors: D
authors: Apter
authors: Departments of Pathology and Obstetrics and Gynecology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors: Cosette M
authors: CM
authors: Wheeler
authors: Department of Obstetrics and Gynaecology, University of Helsinki, Helsinki, Finland.
authors: Jorma
authors: J
authors: Paavonen
authors: Cancer Epidemiology Research Program, Institut Català d'Oncologia (ICO), IDIBELL, Biomedical Research Centre Network for Epidemiology and Public Health (CIBER-ESP), L'Hospitalet de Llobregat, Catalonia, Spain.
authors: Xavier
authors: X
authors: Castellsagué
authors: Microbiology and Infectious Diseases Department, Royal Women's Hospital and Department of Obstetrics and Gynaecology, University of Melbourne, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia.
authors: Suzanne M
authors: SM
authors: Garland
authors: Vaccine Trials Group, Telethon Institute for Child Health Research, Perth, Western Australia, and Sydney University Discipline of Paediatrics and Child Health, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors: S Rachel
authors: SR
authors: Skinner
authors: University Federal of Rio Grande do Sul, Hospital de Clínica de Porto Alegre, Porto Alegre, Brazil.
authors: Paulo
authors: P
authors: Naud
authors: Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social, Morelos, Mexico.
authors: Jorge
authors: J
authors: Salmerón
authors: Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei, Taiwan.
authors: Song-Nan
authors: SN
authors: Chow
authors: Manchester Academic Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust, St Mary's Hospital, Manchester, United Kingdom.
authors: Henry C
authors: HC
authors: Kitchener
authors: University of Campinas, Campinas, Brazil.
authors: Julio C
authors: JC
authors: Teixeira
authors: Chulalongkorn University, Department of Obstetrics and Gynaecology, Faculty of Medicine, Bangkok, Thailand.
authors: Unnop
authors: U
authors: Jaisamrarn
authors: University of the Philippines, College of Medicine, Philippine General Hospital, Makati Medical Centre, Makati City, Philippines.
authors: Genara
authors: G
authors: Limson
authors: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.
authors: Anne
authors: A
authors: Szarewski
authors: University of Alberta, Edmonton, Alberta, Canada.
authors: Barbara
authors: B
authors: Romanowski
authors: University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Fred Y
authors: FY
authors: Aoki
authors: Central Laboratory and Vaccination Centre, Stiftung Juliusspital, Academic Teaching Hospital of the University of Wuerzburg, Wuerzburg, Germany.
authors: Tino F
authors: TF
authors: Schwarz
authors: Department of Gynaecology, University Hospital KU Leuven Gasthuisberg, Leuven, Belgium.
authors: Willy A J
authors: WA
authors: Poppe
authors: Cancer Epidemiology Research Program, Institut Català d'Oncologia (ICO), IDIBELL, Network on Cooperative Cancer Research (RTICC), L'Hospitalet de Llobregat, Catalonia, Spain.
authors: F Xavier
authors: FX
authors: Bosch
authors: Centre for AIDS Programme of Research in South Africa, Durban, South Africa.
authors: Adrian
authors: A
authors: Mindel
authors: Afdelingshoofd Gynaecologie-Oncologie, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Philippe
authors: P
authors: de Sutter
authors: GSK Vaccines, Wavre, Belgium.
authors: Karin
authors: K
authors: Hardt
authors: GSK Vaccines, Wavre, Belgium.
authors: Toufik
authors: T
authors: Zahaf
authors: GSK Vaccines, Wavre, Belgium.
authors: Dominique
authors: D
authors: Descamps
authors: GSK Vaccines, Wavre, Belgium.
authors: Frank
authors: F
authors: Struyf
authors: University of Tampere, School of Public Health, Tampere, Finland.
authors: Matti
authors: M
authors: Lehtinen
authors: GSK Vaccines, King of Prussia, Pennsylvania, USA.
authors: Gary
authors: G
authors: Dubin
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004279:DNA, Viral / Q000032:analysis / Q000302:isolation & purification; D004311:Double-Blind Method; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology* / Q000302:isolation & purification; D052161:Human papillomavirus 18 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives*; D030361:Papillomavirus Infections / Q000150:complications / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011230:Precancerous Conditions / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D055815:Young Adult
chemical_list: C532963:ASO4 mixture; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004279:DNA, Viral; D008050:Lipid A; D053918:Papillomavirus Vaccines; D000536:Aluminum Hydroxide
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