title: Randomized trial of an alternate human papillomavirus vaccine administration schedule in college-aged women.
abstract: BACKGROUND
  Human papillomavirus (HPV) vaccine is effective against HPV types 16 and 18, which cause 70% of cervical cancers. The three-dose vaccination schedule at 0, 2, and 6 months may be inconvenient for college-aged women. This study assessed noninferiority of the immune response to an alternate vaccination schedule at 0, 2, and 12 months.
  
  
  METHODS
  Two hundred nonpregnant women, aged 18-23 years, with <5 sexual partners were randomized into standard and alternate schedules. Blood samples were drawn before dose 1 and 2-6 weeks after dose 3 and analyzed with the competitive Luminex immunoassay. Seropositives at baseline were eliminated from analyses by HPV type. Log-transformed titers were used to calculate HPV type-specific geometric mean titers (GMTs) and 95% confidence intervals (CI) for each group. Noninferiority was tested against a one-sided null hypothesis that the post-dose 3 GMT ratio of the alternate to standard schedule was < or =0.5 for each HPV type.
  
  
  RESULTS
  One hundred eighty-eight women completed the study, with all 12 dropouts in the alternate schedule group (p < 0.001). Antibody responses in the alternate schedule were noninferior to the standard schedule for all vaccine types (p < 0.0001). Among the per-protocol population, GMTs (95% CI) for the alternate schedule were 4,440 (3,080-5,696), 5,688 (3,960-7,291), 12,443 (8,611-15,977), and 2,129 (1,183-3,063) for HPV types 6, 11, 16, and 18, respectively, vs. 2,153 (1,794-2,478), 1,966 (1,401-2,491), 6,218 (4,367-7,946), and 1,370 (1,167-1,553) for the standard schedule. Time between doses 2 and 3 significantly predicted final titer for all virus types (p < 0.005).
  
  
  CONCLUSIONS
  For all HPV vaccine types, the GMT ratios indicated noninferiority of the alternate vaccine administration schedule at 0, 2, and 12 months. The alternate schedule may be used to expand options for the timing of the third dose in the HPV vaccine schedule.
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. zimmer@pitt.edu
authors.forename: Richard K
authors.initials: RK
authors.lastname: Zimmerman
authors.forename: Mary Patricia
authors.initials: MP
authors.lastname: Nowalk
authors.forename: Chyongchiou J
authors.initials: CJ
authors.lastname: Lin
authors.forename: Dwight E
authors.initials: DE
authors.lastname: Fox
authors.forename: Feng-Shou
authors.initials: FS
authors.lastname: Ko
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wettick
authors.forename: Gaye
authors.initials: G
authors.lastname: Cost
authors.forename: Linda
authors.initials: L
authors.lastname: Hand
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hayes
authors.forename: Marian
authors.initials: M
authors.lastname: Michaels
mesh_terms: D000293:Adolescent; D052685:Alphapapillomavirus / Q000276:immunology / Q000302:isolation & purification; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D007118:Immunoassay / Q000379:methods; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D014495:Universities; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines