title: Effect of different human papillomavirus serological and DNA criteria on vaccine efficacy estimates.
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.
authors.forename: Krystle A
authors.initials: KA
authors.lastname: Lang Kuhs
authors.forename: Carolina
authors.initials: C
authors.lastname: Porras
authors.forename: John T
authors.initials: JT
authors.lastname: Schiller
authors.forename: Ana Cecilia
authors.initials: AC
authors.lastname: Rodriguez
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Paula
authors.initials: P
authors.lastname: Gonzalez
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: Arpita
authors.initials: A
authors.lastname: Ghosh
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Lowy
authors.forename: Aimée R
authors.initials: AR
authors.lastname: Kreimer
authors.forename: Sylviane
authors.initials: S
authors.lastname: Poncelet
authors.forename: John
authors.initials: J
authors.lastname: Schussler
authors.forename: Wim
authors.initials: W
authors.lastname: Quint
authors.forename: Leen-Jan
authors.initials: LJ
authors.lastname: van Doorn
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: Mary
authors.initials: M
authors.lastname: Sidawy
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Safaeian
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology; D052161:Human papillomavirus 18 / Q000235:genetics / Q000276:immunology; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics* / Q000276:immunology*; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000276:immunology*; D012698:Serologic Tests / Q000379:methods*; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000517:prevention & control*
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D053918:Papillomavirus Vaccines
keywords: human papillomavirus; methodological differences; naïve population; vaccine efficacy