title: Glutathione S-transferase L1 multiplex serology as a measure of cumulative infection with human papillomavirus.
abstract: BACKGROUND
  Several assays are used to measure type-specific serological responses to human papillomavirus (HPV), including the bead-based glutathione S-transferase (GST)-L1 multiplex serology assay and virus-like particle (VLP)-based ELISA. We evaluated the high-throughput GST-L1, which is increasingly used in epidemiologic research, as a measure of cumulative HPV infection and future immune protection among HPV-unvaccinated women.
  
  
  METHODS
  We tested enrollment sera from participants in the control arm of the Costa Rica Vaccine Trial (n = 488) for HPV16 and HPV18 using GST-L1, VLP-ELISA, and two assays that measure neutralizing antibodies (cLIA and SEAP-NA). With statistical adjustment for sampling, we compared GST-L1 serostatus to established HPV seropositivity correlates and incident cervical HPV infection using odds ratios. We further compared GST-L1 to VLP-ELISA using pair-wise agreement statistics and by defining alternate assay cutoffs.
  
  
  RESULTS
  Odds of HPV16 GST-L1 seropositivity increased with enrollment age (OR = 1.20 per year, 95%CI 1.03-1.40) and lifetime number of sexual partners (OR = 2.06 per partner, 95%CI 1.49-2.83), with similar results for HPV18. GST-L1 seropositivity did not indicate protection from incident infection over 4 years of follow-up (HPV16 adjusted OR = 1.72, 95%CI 0.95-3.13; HPV18 adjusted OR = 0.38, 95%CI 0.12-1.23). Seroprevalence by GST-L1 (HPV16 and HPV18, respectively) was 5.0% and 5.2%, compared to 19.4% and 23.8% by VLP-ELISA, giving positive agreement of 39.2% and 20.8%. Lowering GST-L1 seropositivity cutoffs improved GST-L1/VLP-ELISA positive agreement to 68.6% (HPV16) and 61.5% (HPV18).
  
  
  CONCLUSIONS
  Our data support GST-L1 as a marker of cumulative HPV infection, but not immune protection. At lower seropositivity cutoffs, GST-L1 better approximates VLP-ELISA.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland, USA. hilary.robbins@nih.gov.
authors.forename: Hilary A
authors.initials: HA
authors.lastname: Robbins
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Carolina
authors.initials: C
authors.lastname: Porras
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.forename: Arpita
authors.initials: A
authors.lastname: Ghosh
authors.forename: Ana Cecilia
authors.initials: AC
authors.lastname: Rodriguez
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: Troy J
authors.initials: TJ
authors.lastname: Kemp
authors.forename: Paula
authors.initials: P
authors.lastname: Gonzalez
authors.forename: John
authors.initials: J
authors.lastname: Schiller
authors.forename: Douglas
authors.initials: D
authors.lastname: Lowy
authors.forename: Mark
authors.initials: M
authors.lastname: Esser
authors.forename: Katie
authors.initials: K
authors.lastname: Matys
authors.forename: Wim
authors.initials: W
authors.lastname: Quint
authors.forename: Leen-Jan
authors.initials: LJ
authors.lastname: van Doorn
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Tim
authors.initials: T
authors.lastname: Waterboer
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Safaeian
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D003364:Costa Rica; D004279:DNA, Viral / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D016021:Epidemiologic Studies; D005260:Female; D005982:Glutathione Transferase / Q000097:blood*; D052162:Human papillomavirus 16; D052161:Human papillomavirus 18; D006801:Humans; D016017:Odds Ratio; D030361:Papillomavirus Infections / Q000097:blood / Q000175:diagnosis*; D053918:Papillomavirus Vaccines / Q000627:therapeutic use; D016036:Seroepidemiologic Studies; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004279:DNA, Viral; D053918:Papillomavirus Vaccines; D005982:Glutathione Transferase