Overcoming barriers to HPV vaccination: non-inferiority of antibody response to human papillomavirus 16/18 vaccine in adolescents vaccinated with a two-dose vs. a three-dose schedule at 21 months

Vaccine. 2014 Feb 3;32(6):725-32. doi: 10.1016/j.vaccine.2013.11.059. Epub 2013 Dec 16.


For middle and low-income countries, the cost of HPV vaccines remains challenging. We conducted an open-label nonrandomized clinical trial evaluating immune response to the HPV-16/18 AS04-adjuvanted vaccine administered on a standard (months (M) 0-1-6) versus extended schedule (M 0-6-60) at 7, 21, 60, 72 and 120 months post-vaccination. Participants were females recruited in Morelos, Mexico: 474 girls aged 9-10 years and 500 women aged 18-24 years receiving a standard schedule, and 1026 girls aged 9-10 years receiving an extended schedule (currently the girls in the extended schedule had received only the first 2 doses). This report presents the interim analysis results for non-inferiority between the regimes conducted with the current available data at 21 months after the first dose, with serum antibodies assessed by ELISA. A pre-stated margin of non-inferiority was defined by post-vaccination geometric mean titer (GMT) ratio (upper 95% confidence interval [CI]≤2.0) between the standard and the two-dose schedule in girls at month 21. Immune response to the vaccine was strongest in adolescent girls and in the 3-dose group. Statistical non-inferiority of the two-dose versus three-dose groups was demonstrated. At 21 months, comparing the adolescent 2-dose versus 3-dose groups, the GMT ratio and 95% CI were 1.66 (1.55-1.81) and 1.67 (1.51-1.86) for HPV16 and 18, respectively. The two-dose regimen was non-inferior when compared to the three-dose response in same-age girls and with women aged 18-24 years after 21 months of follow-up. The reduction in the number of doses from the current three-dose schedule may lower overall costs associated with the vaccination and increase accessibility and compliance with the recommended dosing of the HPV vaccine.

Trial registration: ClinicalTrials.gov NCT01717118.

Keywords: HPV-16/18 vaccine; Immunization schedule; Immunogenicity; Non-inferiority trial.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Viral / blood
  • Child
  • Female
  • Health Services Accessibility / economics
  • Humans
  • Immunization Schedule*
  • Mexico
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Vaccines / administration & dosage*
  • Papillomavirus Vaccines / economics
  • Uterine Cervical Neoplasms / prevention & control
  • Uterine Cervical Neoplasms / virology
  • Young Adult


  • Antibodies, Viral
  • Papillomavirus Vaccines

Associated data

  • ClinicalTrials.gov/NCT01717118