title: Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA Trials.
abstract: BACKGROUND
  There is some evidence to suggest that one or two doses of the HPV vaccine provides similar protection to the three-dose regimen. The main aim of the study was to ascertain HPV-16/18 vaccine efficacy in both full and naive cohorts and to explore protection conferred against non-vaccine HPV types, by number of doses received.
  
  
  METHODS
  Summary data from the Costa Rica Vaccine Trial (CVT; NCT00128661) and ~the PATRICIA trial (NCT001226810), two phase 3, double-blind, randomised controlled clinical trials of the HPV-16/18 AS04-adjuvanted vaccine in young women, were combined in a post-hoc analysis (GlaxoSmithKline [GSK] e-track number 202142) to investigate the efficacy of fewer than three doses of the HPV-16/18 vaccine after 4 years of follow-up. Women were randomly assigned to receive three doses of the HPV-16/18 vaccine or to a control vaccine; yet, some received fewer doses. After exclusion of women with less than 12 months of follow-up or those who were HPV-16/18 DNA-positive at enrolment (for the HPV-16/18 endpoint), we calculated vaccine efficacy against one-time detection of incident HPV infections after three, two, and one dose(s). The primary study endpoint was one-time detection of first incident HPV-16/18 infections accumulated during the follow-up phase.
  
  
  RESULTS
  We assessed vaccine efficacy against incident HPV-16/18 infection in the modified total vaccinated cohort (22 327 received three doses, 1185 two doses, 543 one dose). Vaccine efficacy against incident HPV-16/18 infections for three doses was 77·0% (95% CI 74·7-79·1), two doses was 76·0% (62·0-85·3), and one dose was 85·7% (70·7-93·7). Vaccine efficacy against incident HPV-31/33/45 infections for three doses was 59·7% (56·0-63·0), two doses was 37·7% (12·4-55·9), and one dose was 36·6% (-5·4 to 62·2). Vaccine efficacy against incident HPV-16/18 infection for two-dose women who received their second dose at 1 month was 75·3% (54·2-87·5) and 82·6% (42·3-96·1) for those who received the second dose at 6 months (CVT data only). Vaccine efficacy against HPV-31/33/45 for two-dose women who received their second dose at 6 months (68·1%, 27·0-87·0; CVT data only), but not those receiving it at one month (10·1%, -42·0 to 43·3), was similar to the three-dose group.
  
  
  CONCLUSIONS
  4 years after vaccination of women aged 15-25 years, one and two doses of the HPV-16/18 vaccine seem to protect against cervical HPV-16/18 infections, similar to the protection provided by the three-dose schedule. Two doses separated by 6 months additionally provided some cross-protection. These data argue for a direct assessment of one-dose efficacy of the HPV-16/18 vaccine.
  
  
  BACKGROUND
  US National Cancer Institute, National Institutes of Health Office of Research on Women's Health, and Ministry of Health of Costa Rica (CVT); GlaxoSmithKline Biologicals SA (PATRICIA).
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: kreimera@mail.nih.gov.
authors.forename: Aimée R
authors.initials: AR
authors.lastname: Kreimer
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Struyf
authors.affiliation: Department of Obstetrics and Gynecology, San Pablo Colleges Medical Center, San Pablo City, Philippines.
authors.forename: Maria Rowena
authors.initials: MR
authors.lastname: Del Rosario-Raymundo
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.affiliation: Vaccine Trials Group, Telethon Institute for Child Health Research, Perth, WA, Australia; Sydney University Discipline of Paediatrics and Child Health, Children's Hospital at Westmead, Sydney, NSW, Australia.
authors.forename: S Rachel
authors.initials: SR
authors.lastname: Skinner
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.affiliation: Microbiology and Infectious Diseases Department, Royal Women's Hospital and Department of Obstetrics and Gynaecology, University of Melbourne, Murdoch Childrens Research Institute Melbourne, VIC, Australia.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Garland
authors.affiliation: Proyecto Epidemiologico Guanacaste, San José, Costa Rica; Section of Early Detection and Prevention, International Agency for Research on Cancer, Lyon, France.
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: David
authors.affiliation: Departments of Pathology and Obstetrics and Gynecology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. Electronic address: cwheeler@salud.unm.edu.
authors.forename: Cosette M
authors.initials: CM
authors.lastname: Wheeler
authors.forename: Paula
authors.initials: P
authors.lastname: González
authors.forename: Silvia
authors.initials: S
authors.lastname: Jiménez
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Lowy
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
authors.forename: Caroline
authors.initials: C
authors.lastname: Porras
authors.forename: Ana Cecilia
authors.initials: AC
authors.lastname: Rodriguez
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Safaeian
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: John T
authors.initials: JT
authors.lastname: Schiller
authors.forename: John
authors.initials: J
authors.lastname: Schussler
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Bosch
authors.forename: Xavier
authors.initials: X
authors.lastname: Castellsague
authors.forename: Archana
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Song-Nan
authors.initials: SN
authors.lastname: Chow
authors.forename: Dominique
authors.initials: D
authors.lastname: Descamps
authors.forename: Francisco
authors.initials: F
authors.lastname: Diaz-Mitoma
authors.forename: Gary
authors.initials: G
authors.lastname: Dubin
authors.forename: Maria Julieta
authors.initials: MJ
authors.lastname: Germar
authors.forename: Diane M
authors.initials: DM
authors.lastname: Harper
authors.forename: David J M
authors.initials: DJ
authors.lastname: Lewis
authors.forename: Genara
authors.initials: G
authors.lastname: Limson
authors.forename: Paulo
authors.initials: P
authors.lastname: Naud
authors.forename: Klaus
authors.initials: K
authors.lastname: Peters
authors.forename: Willy A J
authors.initials: WA
authors.lastname: Poppe
authors.forename: Brian
authors.initials: B
authors.lastname: Ramjattan
authors.forename: Barbara
authors.initials: B
authors.lastname: Romanowski
authors.forename: Jorge
authors.initials: J
authors.lastname: Salmeron
authors.forename: Tino F
authors.initials: TF
authors.lastname: Schwarz
authors.forename: Julio C
authors.initials: JC
authors.lastname: Teixeira
authors.forename: Wiebren A A
authors.initials: WA
authors.lastname: Tjalma
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D003364:Costa Rica; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D052162:Human papillomavirus 16 / Q000276:immunology / Q000302:isolation & purification; D052161:Human papillomavirus 18 / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage*; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014611:Vaccination / Q000379:methods; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000517:prevention & control* / Q000821:virology*
chemical_list: D000276:Adjuvants, Immunologic; D053918:Papillomavirus Vaccines