title: Multisite HPV16/18 Vaccine Efficacy Against Cervical, Anal, and Oral HPV Infection.
abstract: BACKGROUND
  Previous Costa Rica Vaccine Trial (CVT) reports separately demonstrated vaccine efficacy against HPV16 and HPV18 (HPV16/18) infections at the cervical, anal, and oral regions; however, the combined overall multisite efficacy (protection at all three sites) and vaccine efficacy among women infected with HPV16 or HPV18 prior to vaccination are less known.
  
  
  METHODS
  Women age 18 to 25 years from the CVT were randomly assigned to the HPV16/18 vaccine (Cervarix) or a hepatitis A vaccine. Cervical, oral, and anal specimens were collected at the four-year follow-up visit from 4186 women. Multisite and single-site vaccine efficacies (VEs) and 95% confidence intervals (CIs) were computed for one-time detection of point prevalent HPV16/18 in the cervical, anal, and oral regions four years after vaccination. All statistical tests were two-sided.
  
  
  RESULTS
  The multisite woman-level vaccine efficacy was highest among "naïve" women (HPV16/18 seronegative and cervical HPV high-risk DNA negative at vaccination) (vaccine efficacy = 83.5%, 95% CI = 72.1% to 90.8%). Multisite woman-level vaccine efficacy was also demonstrated among women with evidence of a pre-enrollment HPV16 or HPV18 infection (seropositive for HPV16 and/or HPV18 but cervical HPV16/18 DNA negative at vaccination) (vaccine efficacy = 57.8%, 95% CI = 34.4% to 73.4%), but not in those with cervical HPV16 and/or HPV18 DNA at vaccination (anal/oral HPV16/18 VE = 25.3%, 95% CI = -40.4% to 61.1%). Concordant HPV16/18 infections at two or three sites were also less common in HPV16/18-infected women in the HPV vaccine vs control arm (7.4% vs 30.4%, P < .001).
  
  
  CONCLUSIONS
  This study found high multisite vaccine efficacy among "naïve" women and also suggests the vaccine may provide protection against HPV16/18 infections at one or more anatomic sites among some women infected with these types prior to HPV16/18 vaccination.
authors.affiliation: Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS). daniel.beachler@nih.gov.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Beachler
authors.affiliation: Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
authors.forename: Aimée R
authors.initials: AR
authors.lastname: Kreimer
authors.affiliation: Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.affiliation: Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.affiliation: Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.affiliation: Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
authors.forename: Ana Cecilia
authors.initials: AC
authors.lastname: Rodriguez
authors.affiliation: Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Lowy
authors.affiliation: Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
authors.forename: Carolina
authors.initials: C
authors.lastname: Porras
authors.affiliation: Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
authors.forename: John T
authors.initials: JT
authors.lastname: Schiller
authors.affiliation: Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
authors.forename: Wim
authors.initials: W
authors.lastname: Quint
authors.affiliation: Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
authors.forename: Silvia
authors.initials: S
authors.lastname: Jimenez
authors.affiliation: Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Safaeian
authors.affiliation: Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
authors.forename: Linda
authors.initials: L
authors.lastname: Struijk
authors.affiliation: Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
authors.forename: John
authors.initials: J
authors.lastname: Schussler
authors.affiliation: Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.affiliation: Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
authors.forename: Paula
authors.initials: P
authors.lastname: Gonzalez
mesh_terms: D000328:Adult; D001003:Anal Canal / Q000821:virology*; D001005:Anus Neoplasms / Q000517:prevention & control / Q000821:virology; D002584:Cervix Uteri / Q000821:virology*; D003364:Costa Rica; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000276:immunology*; D006801:Humans; D009061:Mouth Mucosa / Q000821:virology*; D009062:Mouth Neoplasms / Q000517:prevention & control / Q000821:virology; D030361:Papillomavirus Infections / Q000150:complications / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control / Q000821:virology; D014611:Vaccination
chemical_list: D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18