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

Author(s): Lang Kuhs KA,  Porras C,  Schiller JT,  Rodriguez AC,  Schiffman M,  Gonzalez P,  Wacholder S,  Ghosh A,  Li Y,  Lowy DR,  Kreimer AR,  Poncelet S,  Schussler J,  Quint W,  van Doorn LJ,  Sherman ME,  Sidawy M,  Herrero R,  Hildesheim A,  Safaeian M,  Costa Rica Vaccine Trial Group

Journal: Am J Epidemiol

Date: 2014 Sep 15

Major Program(s) or Research Group(s):

PubMed ID: 25139208

PMC ID: PMC4157699

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.