Direct comparison of HPV16 serological assays used to define HPV-naïve women in HPV vaccine trials.

Author(s): Safaeian M,  Ghosh A,  Porras C,  Lin SW,  Rodriguez AC,  Schiffman M,  Wacholder S,  Kemp T,  Gonzalez P,  Wentzensen N,  Esser M,  Meuree A,  Matys K,  Quint W,  van Doorn LJ,  Sherman ME,  Herrero R,  Pinto LA,  Hildesheim A

Journal: Cancer Epidemiol Biomarkers Prev

Date: 2012 Sep

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

PubMed ID: 22752082

PMC ID: not available

Abstract: BACKGROUND: Two HPV serological assays, the competitive Luminex immunoassay (cLIA), and an enzyme-linked immunoassay (ELISA) against HPV16 have been used to define HPV-naïve subcohorts within large HPV vaccination trials. Some of the variation in estimated vaccine efficacies may be due to the differences in these assays used to define the HPV-naïve subgroups. To guide the interpretation of published results, we compared these assays. METHODS: Replicate enrollment sera from a stratified sample of 388 unvaccinated women from the control arm of the Costa Rica HPV 16/18 Vaccine Trial were measured for antibodies against HPV16 using cLIA and ELISA. Agreement between the assays was estimated using standard and alternative assay cutoffs. RESULTS: Using laboratory-determined seropositivity cutoffs, sampling-adjusted HPV16 seropositivity was 24.8% by ELISA and 7.2% by cLIA. Comparing cLIA and ELISA antibody levels based on the standard cutoffs, overall agreement was 53% (positive-agreement = 49%). The poor agreement was mainly driven by the higher sensitivity of the ELISA than cLIA, resulting in 30% of the ELISA-positive sample that were cLIA-negative (none of the ELISA-negatives were cLIA-positive). Increasing ELISA cutoff to 54 ELISA units (EU)/mL (the level which maximized agreement with cLIA; ELISA standard cutoff is 8 EU/mL) resulted in higher agreement (overall agreement = 91%; positive agreement = 78%). CONCLUSIONS: ELISA and cLIA are different from each other based on the laboratory-determined cutoff. Increasing ELISA cutoff increased agreement with cLIA, which could facilitate comparisons among studies that use different assays. IMPACT: Keeping cLIA at the laboratory-determined cutoff but altering ELISA cutoff for seropositivity might facilitate vaccine efficacy comparisons in the naïve cohorts defined by cLIA.