TOPLINE

A newly developed test strip measuring IgA antibodies to Epstein-Barr virus nuclear antigen 1 (EBNA1) yielded 85% sensitivity and more than 90% specificity in identifying individuals who developed nasopharyngeal carcinoma (NPC) within 4 years of sample collection.

METHODOLOGY

• A nested case-control study compared 20 pre-diagnostic sera collected within 4 years of NPC diagnosis to sera from 96 healthy control individuals from prospective cohorts in Singapore and Shanghai, China.
• Researchers developed EBNA1 SeroStrip-HT, a nitrocellulose strip test assay using purified EBNA1 proteins from insect and mammalian cells to detect serum IgA and IgG antibodies.
• 3 EBNA1 protein analytes were tested: mammalian-derived EBNA1 deleted for glycine alanine repeat (mamEBNA1 dGAr), insect-derived EBNA1 dGAr (insEBNA1 dGAr), and insect-derived full-length EBNA1 (insEBNA1 FL).
• Fluorescent detection and densitometry-based quantification were used for antibody levels, with standard curves prepared using purified human IgA and IgG for absolute quantification.
• Optimal cutoffs were determined, receiver operating characteristic curves were generated, and sensitivity, specificity, and area under the curve (AUC) were calculated.

TAKEAWAY

• IgA to mamEBNA1 dGAr yielded 85.0% sensitivity and 94.8% specificity (AUC, 0.939) for NPC status.
• IgA to insEBNA1 dGAr showed 85.0% sensitivity and 93.8% specificity (AUC, 0.941). IgA to insEBNA1 FL demonstrated 90.0% sensitivity but lower 91.7% specificity (AUC, 0.940).
• Technical replicates showed high correlation for each analyte: mamEBNA1 dGAr (coefficient of determination [R²], 0.9921), insEBNA1 dGAr (R², 0.9955), and insEBNA1 FL (R², 0.9895).
• The majority of serum samples collected within 4 years of diagnosis (17 out of 20) were profiled as high-risk in the strip assay, whereas only 3 from healthy controls (3 out of 96) were classified as high-risk.

IN PRACTICE

"Converting EBNA1 SeroStrip-HT into a standardized test could serve as a reflex test for existing NPC early detection programs that would prioritize test-positive individuals with unconfirmed cancer status for continued clinical follow up who remain at elevated risk for NPC. Alternatively, it may be implemented in a new risk assessment program to prioritize who should undergo routine early detection screening," the authors of the study wrote.

SOURCE

The study was led by Benjamin E. Warner, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh. It was published online on July 27 in Journal of Medical Virology.

LIMITATIONS

The 3 false-negative samples that previously tested positive with the prototype assay highlight a limitation in the lower sensitivity of the EBNA1 SeroStrip-HT. Nasal aspirates or saliva samples were not available for complementary genotyping to improve sensitivity.

DISCLOSURES

The study was supported by grants from the National Institutes of Health, the Hillman Foundation, and the Singapore Strategic Cohorts Consortium. Two authors received support from an NIH training grant and one of them was also supported by the Hillman Postdoctoral Fellowship for Innovative Cancer Research. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.