title: Cross-protection of the Bivalent Human Papillomavirus (HPV) Vaccine Against Variants of Genetically Related High-Risk HPV Infections.
abstract: BACKGROUND
  Results from the Costa Rica Vaccine Trial (CVT) demonstrated partial cross-protection by the bivalent human papillomavirus (HPV) vaccine, which targets HPV-16 and HPV-18, against HPV-31, -33, and -45 infection and an increased incidence of HPV-51 infection.
  
  
  METHODS
  A study nested within the CVT intention-to-treat cohort was designed to assess high-risk HPV variant lineage-specific vaccine efficacy (VE). The 2 main end points were (1) long-term incident infections persisting for ≥2 years and/or progression to high-grade squamous intraepithelial lesions (ie, cervical intraepithelial neoplasia grade 2/3 [CIN 2/3]) and (2) incident transient infections lasting for <2 years. For efficiency, incident infections due to HPV-16, -18, -31, -33, -35, -45, and -51 resulting in persistent infection and/or CIN 2/3 were matched (ratio, 1:2) to the more-frequent transient viral infections, by HPV type. Variant lineages were determined by sequencing the upstream regulatory region and/or E6 region.
  
  
  RESULTS
  VEs against persistent or transient infections with HPV-16, -18, -33, -35, -45, and -51 did not differ significantly by variant lineage. As the possible exception, VEs against persistent infection and/or CIN 2/3 due to HPV-31 A/B and HPV-31C variants were -7.1% (95% confidence interval [CI], -33.9% to 0%) and 86.4% (95% CI, 65.1%-97.1%), respectively (P = .02 for test of equal VE). No difference in VE was observed by variant among transient HPV-31 infections (P = .68).
  
  
  CONCLUSIONS
  Overall, sequence variation at the variant level does not appear to explain partial cross-protection by the bivalent HPV vaccine.
authors.affiliation: Department of Microbiology and Immunology.
authors.forename: Ariana
authors.initials: A
authors.lastname: Harari
authors.affiliation: Department of Pediatrics.
authors.forename: Zigui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, San José, Costa Rica.
authors.forename: Ana Cecilia
authors.initials: AC
authors.lastname: Rodríguez
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville.
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.affiliation: Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, San José, Costa Rica.
authors.forename: Carolina
authors.initials: C
authors.lastname: Porras
authors.affiliation: Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, San José, Costa Rica International Agency for Research on Cancer, World Health Organization, Lyon, France.
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville.
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville.
authors.forename: Orestis A
authors.initials: OA
authors.lastname: Panagiotou
authors.affiliation: Information Management Services, Silver Spring, Maryland.
authors.forename: Brian
authors.initials: B
authors.lastname: Befano
authors.affiliation: Department of Microbiology and Immunology Department of Pediatrics Department of Obstetrics and Gynecology and Women's Health Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burk
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville.
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
mesh_terms: D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D014644:Genetic Variation; D006801:Humans; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000276:immunology*; D055815:Young Adult
chemical_list: D053918:Papillomavirus Vaccines
keywords: HPV vaccine; HPV variants; cross-protection