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||Glutathione S-transferase L1 multiplex serology as a measure of cumulative infection with human papillomavirus.
||Robbins HA, Li Y, Porras C, Pawlita M, Ghosh A, Rodriguez AC, Schiffman M, Wacholder S, Kemp TJ, Gonzalez P, Schiller J, Lowy D, Esser M, Matys K, Quint W, van Doorn LJ, Herrero R, Pinto LA, Hildesheim A, Waterboer T, Safaeian M
||BMC Infect Dis
||BB, CGB, HREB, IIB
||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 (nâ=â488) 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 (ORâ=â1.20 per year, 95%CI 1.03-1.40) and lifetime number of sexual partners (ORâ=â2.06 per partner, 95%CI 1.49-2.83), with similar results for HPV18. GST-L1 seropositivity did not indicate protection from incident infection over 4Â years of follow-up (HPV16 adjusted ORâ=â1.72, 95%CI 0.95-3.13; HPV18 adjusted ORâ=â0.38, 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.