Early diagnosis of nasopharyngeal carcinoma, frequently linked to Epstein-Barr virus (EBV) infection, is critical to improve survival rates in patients. Consequently, there is a pressing need for better screening methods. A recently published stduy in the New England Journal of Medicine, identified the anti-BNLF2b total antibody (P85-Ab) as a promising novel biomarker for nasopharyngeal carcinoma screening, with higher sensitivity, specificity, and positive predictive value than the two-antibody method which is now standard of care.
Nasopharyngeal carcinoma is often associated with Epstein-Barr virus (EBV) infection, and early detection through EBV-specific antibodies or EBV DNA screening significantly raises early-stage diagnoses from 20% to over 70%. Notably, previous research indicates that individuals who undergo screening have a better long-term survival after a nasopharyngeal carcinoma diagnosis than controls. Consequently, efforts have been made to improve the performance of nasopharyngeal carcinoma screening strategies, including the combination of various biomarkers, multistep screening, and the identification of novel biomarkers. However, the advances achieved thus far remain unsatisfactory due to the low sensitivity, complex operation, or high cost. The study at hand identified and validated the anti-BNLF2b total antibody (P85-Ab) as a novel serologic biomarker for nasopharyngeal carcinoma screening, suggesting its potential superiority to previously reported antibodies against EBV proteins.
A peptide library representing highly-rated B-cell epitopes from EBV coding sequences was designed to identify novel serologic biomarkers for nasopharyngeal carcinoma. After a retrospective case–control study, the performance of the novel biomarker anti–BNLF2b total antibody (P85-Ab) was validated through a large-scale prospective screening program and compared with that of the standard two-antibody–based screening method (EBV nuclear antigen 1 [EBNA1]–IgA and EBV-specific viral capsid antigen [VCA]–IgA).
P85-Ab emerged as the most promising biomarker for nasopharyngeal carcinoma screening during the retrospective case-control study, exhibiting an excellent sensitivity of 94.4% and a remarkable specificity of 99.6%. In the prospective cohort of 24,852 eligible participants, including 47 nasopharyngeal carcinoma cases (38 at an early stage), P85-Ab demonstrated a superior sensitivity over the two-antibody method (97.9% vs. 72.3%, respectively; ratio: 1.4), together with a higher specificity (98.3% vs. 97.0%; ratio: 1.01), and a significantly improved positive predictive value (10.0% vs. 4.3%; ratio: 2.3). Notably, combining P85-Ab with the two-antibody method substantially increased the positive predictive value to 44.6%, while maintaining a sensitivity of 70.2%.
These findings suggest that P85-Ab is a promising novel biomarker for nasopharyngeal carcinoma screening, with higher sensitivity, specificity, and positive predictive value than the standard two-antibody method.
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