Open Access Research article

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

Hilary A Robbins1*, Yan Li12, Carolina Porras3, Michael Pawlita4, Arpita Ghosh5, Ana Cecilia Rodriguez3, Mark Schiffman1, Sholom Wacholder1, Troy J Kemp6, Paula Gonzalez37, John Schiller8, Douglas Lowy8, Mark Esser9, Katie Matys10, Wim Quint11, Leen-Jan van Doorn11, Rolando Herrero37, Ligia A Pinto6, Allan Hildesheim1, Tim Waterboer4 and Mahboobeh Safaeian1

Author Affiliations

1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland, USA

2 Joint Program for Survey Methodology, University of Maryland, College Park, Maryland, USA

3 Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Guanacaste, Costa Rica

4 German Cancer Research Center (DKFZ), Heidelberg, Germany

5 Public Health Foundation of India, New Delhi, India

6 HPV Immunology Laboratory, SAIC-Frederick Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA

7 International Agency for Research on Cancer, Lyon, France

8 Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA

9 MedImmune, Gaithersburg, Maryland, USA

10 PPD Vaccines and Biologics Center of Excellence, Wayne, Pennsylvania, USA

11 DDL Diagnostic Laboratory, Rijswijk, Netherlands

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BMC Infectious Diseases 2014, 14:120  doi:10.1186/1471-2334-14-120

Published: 3 March 2014



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.


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.


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).


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.