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Published in: BMC Infectious Diseases 1/2014

Open Access 01-12-2014 | Research article

Glutathione S-transferase L1 multiplex serology as a measure of cumulative infection with human papillomavirus

Authors: Hilary A Robbins, Yan Li, Carolina Porras, Michael Pawlita, Arpita Ghosh, Ana Cecilia Rodriguez, Mark Schiffman, Sholom Wacholder, Troy J Kemp, Paula Gonzalez, John Schiller, Douglas Lowy, Mark Esser, Katie Matys, Wim Quint, Leen-Jan van Doorn, Rolando Herrero, Ligia A Pinto, Allan Hildesheim, Tim Waterboer, Mahboobeh Safaeian

Published in: BMC Infectious Diseases | Issue 1/2014

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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.
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Metadata
Title
Glutathione S-transferase L1 multiplex serology as a measure of cumulative infection with human papillomavirus
Authors
Hilary A Robbins
Yan Li
Carolina Porras
Michael Pawlita
Arpita Ghosh
Ana Cecilia Rodriguez
Mark Schiffman
Sholom Wacholder
Troy J Kemp
Paula Gonzalez
John Schiller
Douglas Lowy
Mark Esser
Katie Matys
Wim Quint
Leen-Jan van Doorn
Rolando Herrero
Ligia A Pinto
Allan Hildesheim
Tim Waterboer
Mahboobeh Safaeian
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2014
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-14-120

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