Effect of different human papillomavirus serological and DNA criteria on vaccine efficacy estimates

Am J Epidemiol. 2014 Sep 15;180(6):599-607. doi: 10.1093/aje/kwu168. Epub 2014 Aug 19.

Abstract

Two trials of clinically approved human papillomavirus (HPV) vaccines, Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE I/II) and the Papilloma Trial Against Cancer in Young Adults (PATRICIA), reported a 22% difference in vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 2 or worse in HPV-naïve subcohorts; however, serological testing methods and the HPV DNA criteria used to define HPV-unexposed women differed between the studies. We applied previously described methods to simulate these HPV-naïve subcohorts within the Costa Rica HPV16/18 Vaccine Trial and assessed how these criteria affect the estimation of VE. We applied 2 enzyme-linked immunosorbent assay (ELISA) thresholds for HPV16 and HPV18 seropositivity (8 and 7 ELISA units/mL, respectively, for PATRICIA; 54 and 65 ELISA units/mL, respectively, for FUTURE I/II (to approximate the competitive Luminex immunoassay)) and 2 criteria for HPV DNA positivity (12 oncogenic HPV types, plus HPV66 and 68/73 for PATRICIA; or plus HPV6 and 11 for FUTURE I/II). VE was computed in the 2 naïve subcohorts. Using the FUTURE I/II and PATRICIA criteria, VE estimates against cervical intraepithelial neoplasia grade 2 or worse, regardless of HPV type, were 69.0% (95% confidence interval: 40.3%, 84.9%) and 80.8% (95% confidence interval: 52.6%, 93.5%), respectively (P = 0.1). Although the application of FUTURE I/II criteria to our cohort resulted in the inclusion of more sexually experienced women, methodological differences did not fully explain the VE differences.

Trial registration: ClinicalTrials.gov NCT00128661.

Keywords: human papillomavirus; methodological differences; naïve population; vaccine efficacy.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / analysis
  • Cervical Intraepithelial Neoplasia / prevention & control*
  • DNA, Viral / analysis
  • Double-Blind Method
  • Female
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / immunology
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / immunology
  • Humans
  • Papillomaviridae / genetics*
  • Papillomaviridae / immunology*
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Vaccines / immunology*
  • Serologic Tests / methods*
  • Uterine Cervical Neoplasms / prevention & control*
  • Young Adult

Substances

  • Antibodies, Viral
  • DNA, Viral
  • Papillomavirus Vaccines

Associated data

  • ClinicalTrials.gov/NCT00128661