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

Cancer Epidemiol Biomarkers Prev. 2012 Sep;21(9):1547-54. doi: 10.1158/1055-9965.EPI-12-0558. Epub 2012 Jul 2.

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Antibodies, Viral / blood*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Human papillomavirus 16 / immunology*
  • Humans
  • Immunoassay
  • Papillomavirus Vaccines / immunology*
  • Vaccination*

Substances

  • Antibodies, Viral
  • Papillomavirus Vaccines