title: Direct comparison of HPV16 serological assays used to define HPV-naïve women in HPV vaccine trials.
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.
  
  
  CONCLUSIONS
  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.
authors: Division of Cancer Epidemiology and Genetics, Infections and Immunoepidemiology Branch, National Cancer Institute, NIH, Bethesda, MD, USA. safaeianm@mail.nih.gov
authors: Mahboobeh
authors: M
authors: Safaeian
authors: Arpita
authors: A
authors: Ghosh
authors: Carolina
authors: C
authors: Porras
authors: Shih-Wen
authors: SW
authors: Lin
authors: Ana Cecilia
authors: AC
authors: Rodriguez
authors: Mark
authors: M
authors: Schiffman
authors: Sholom
authors: S
authors: Wacholder
authors: Troy
authors: T
authors: Kemp
authors: Paula
authors: P
authors: Gonzalez
authors: Nicolas
authors: N
authors: Wentzensen
authors: Mark
authors: M
authors: Esser
authors: Ariane
authors: A
authors: Meuree
authors: Katie
authors: K
authors: Matys
authors: Wim
authors: W
authors: Quint
authors: Leen-Jan
authors: LJ
authors: van Doorn
authors: Mark E
authors: ME
authors: Sherman
authors: Rolando
authors: R
authors: Herrero
authors: Ligia A
authors: LA
authors: Pinto
authors: Allan
authors: A
authors: Hildesheim
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D007118:Immunoassay; D053918:Papillomavirus Vaccines / Q000276:immunology*; D014611:Vaccination
chemical_list: D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines