# Epstein-Barr virus EBNA1 IgA as a biomarker in nasopharyngeal carcinoma risk prediction

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $198,750

## Abstract

ABSTRACT
Southeast Asian and immigrant Chinese communities across the globe have disproportionately high NPC
incidence, averaging 25-30 times higher than the general population in neighboring areas. EBV infection is
extremely common and more than 95% of adults have seroconverted, but only a subset of chronic carriers will
develop EBV-associated nasopharyngeal carcinoma (NPC). Latent and clonal EBV infection occurs in the tumor
cells, and a variant of a key EBV protein (EBNA1 Val487) required for co-infection with the host has been
identified as a cancer risk-variant because it is found in nearly all (98.8%) NPC tumors from NPC-endemic areas.
Both EBV serology and EBV DNA sequencing are informative. Early detection screening programs by one of
two screening methods (IgA serology, or next-gen sequencing of plasma cell-free EBV DNA) have been
recommended for NPC-endemic populations. However, the screening time-interval for routine early detection is
not known. A biomarker that can identify high-risk individuals several years before clinical onset would greatly
benefit from an early detection screening program.
Antibodies to EBV proteins rise several years before NPC onset. IgA serology is a sentinel for aberrant EBV
infection at mucosal sites. We previously surveyed EBV IgA/IgG/IgM serology from the serum of incident NPC
cases in a Singapore prospective cohort (discovery cohort) and tested the leading biomarker (EBNA1 IgA) in an
additional validation cohort from Shanghai, China. The sojourn time for the custom EBNA1 IgA assay was 4
years before NPC diagnosis (100% sensitivity, 100% specificity in 20 case-controls). False-positives emerged
in the expanded control samples which is likely attributed to periodic EBV reactivation but background signal
could be minimized by removing cross-reactive epitopes yielding a satisfactory EBNA1 IgA assay (93.7%
specificity at 100% sensitivity). Following on from the case-control study performed on a low-throughput but
highly accurate multiplex immunoblot assay, the goal of this proposal is to develop a high-throughput EBNA1
IgA assay using a prototypic slot blot assay and applying the principles from EBNA1 mapping studies. By
leveraging EBV serology, this work is expected to produce a high-throughput assay for NPC risk assessment.
Identified high-risk individuals would benefit from an NPC early detection screening program and/or clinical
follow-up.

## Key facts

- **NIH application ID:** 10987599
- **Project number:** 1R21DE033551-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Kathy Shair
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $198,750
- **Award type:** 1
- **Project period:** 2024-07-03 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10987599

## Citation

> US National Institutes of Health, RePORTER application 10987599, Epstein-Barr virus EBNA1 IgA as a biomarker in nasopharyngeal carcinoma risk prediction (1R21DE033551-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10987599. Licensed CC0.

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