title: Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial.
abstract: OBJECTIVE
  Global use of human papillomavirus (HPV) vaccines to prevent cervical cancer is impeded by cost. A 2-dose schedule for girls may be possible.
  
  
  OBJECTIVE
  To determine whether mean antibody levels to HPV-16 and HPV-18 among girls receiving 2 doses was noninferior to women receiving 3 doses.
  
  
  METHODS
  Randomized, phase 3, postlicensure, multicenter, age-stratified, noninferiority immunogenicity study of 830 Canadian females from August 2007 through February 2011. Follow-up blood samples were provided by 675 participants (81%).
  
  
  METHODS
  Girls (9-13 years) were randomized 1:1 to receive 3 doses of quadrivalent HPV vaccine at 0, 2, and 6 months (n = 261) or 2 doses at 0 and 6 months (n = 259). Young women (16-26 years) received 3 doses at 0, 2, and 6 months (n = 310). Antibody levels were measured at 0, 7, 18, 24, and 36 months.
  
  
  METHODS
  Primary outcome was noninferiority (95% CI, lower bound >0.5) of geometric mean titer (GMT) ratios for HPV-16 and HPV-18 for girls (2 doses) compared with young women (3 doses) 1 month after last dose. Secondary outcomes were noninferiority of GMT ratios of girls receiving 2 vs 3 doses of vaccine; and durability of noninferiority to 36 months.
  
  
  RESULTS
  The GMT ratios were noninferior for girls (2 doses) to women (3 doses): 2.07 (95% CI, 1.62-2.65) for HPV-16 and 1.76 (95% CI, 1.41-2.19) for HPV-18. Girls (3 doses) had GMT responses 1 month after last vaccination for HPV-16 of 7736 milli-Merck units per mL (mMU/mL) (95% CI, 6651-8999) and HPV-18 of 1730 mMU/mL (95% CI, 1512-1980). The GMT ratios were noninferior for girls (2 doses) to girls (3 doses): 0.95 (95% CI, 0.73-1.23) for HPV-16 and 0.68 (95% CI, 0.54-0.85) for HPV-18. The GMT ratios for girls (2 doses) to women (3 doses) remained noninferior for all genotypes to 36 months. Antibody responses in girls were noninferior after 2 doses vs 3 doses for all 4 vaccine genotypes at month 7, but not for HPV-18 by month 24 or HPV-6 by month 36.
  
  
  CONCLUSIONS
  Among girls who received 2 doses of HPV vaccine 6 months apart, responses to HPV-16 and HPV-18 one month after the last dose were noninferior to those among young women who received 3 doses of the vaccine within 6 months. Because of the loss of noninferiority to some genotypes at 24 to 36 months in girls given 2 doses vs 3 doses, more data on the duration of protection are needed before reduced-dose schedules can be recommended.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00501137.
authors: Department of Pediatrics, University of British Columbia, Vancouver, Canada. sdobson@cw.bc.ca
authors: Simon R M
authors: SR
authors: Dobson
authors: Shelly
authors: S
authors: McNeil
authors: Marc
authors: M
authors: Dionne
authors: Meena
authors: M
authors: Dawar
authors: Gina
authors: G
authors: Ogilvie
authors: Mel
authors: M
authors: Krajden
authors: Chantal
authors: C
authors: Sauvageau
authors: David W
authors: DW
authors: Scheifele
authors: Tobias R
authors: TR
authors: Kollmann
authors: Scott A
authors: SA
authors: Halperin
authors: Joanne M
authors: JM
authors: Langley
authors: Julie A
authors: JA
authors: Bettinger
authors: Joel
authors: J
authors: Singer
authors: Deborah
authors: D
authors: Money
authors: Dianne
authors: D
authors: Miller
authors: Monika
authors: M
authors: Naus
authors: Fawziah
authors: F
authors: Marra
authors: Eric
authors: E
authors: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation; D002648:Child; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control* / Q000821:virology; D055815:Young Adult
chemical_list: D053918:Papillomavirus Vaccines