Complementary Test of Antibodies to EBNA-1 and EA for NPC

Abstract

Problem This hospital-based cohort study evaluated the efficacy of three Epstein-Barr virus (EBV) - associated assays for nasopharyngeal carcinoma (NPC) primary screening and monitoring treatment outcome. Methods Five hundred seventeen consecutive subjects, including 156 NPC patients, 264 healthy volunteers and ninety-seven patients with head-and-neck squamous cell carcinoma (HNSCC) were enrolled. The sensitivity and specificity of EBV IgAs to viral capsid antigen (VCA), complementary EBV IgAs to early antigen and nuclear antigen-1 (EA+EBNA-1), and EBV DNA load were examined by immunofluorecent assays, enzyme-linked immunosorbent assays, and quantitative real-time PCR, respectively. Results After constructing the receiver operating characteristics to demonstrate screening efficacy, EBV EA+EBNA-1 IgA (AUC: 0.952; 95% CI, 0.930–0.974) was proved superior to EBV VCA IgA (AUC: 0.888; 95% CI, 0.854–0.922) or EBV DNA load (AUC: 0.893; 95% CI, 0.854–0.932) in differentiating NPC patients from controls. Comparison of screening efficacy between NPC patients and HNSCC patients revealed EBV EA+EBNA-1 IgA (AUC: 0.964; 95% CI, 0.943–0.985) still outperformed EBV VCA IgA (AUC: 0.884; 95% CI, 0.845–0.923). In subjects with higher serum titer or level equal to or above 1:80 and 6 EU/ml for EBV VCA IgA and EA+EBNA-1 IgA, the specificity reached as high as 99.2% and 95.1%, respectively, in the control groups. However, correlation of these three assays with clinicopathological manifestations of NPC, revealed only EBV DNA load significantly associated with N stage and overall stage in NPC patients. Additionally, EBV DNA load could be used to further raise the specificity of EBV EA+EBNA-1 IgA assays and was also the only assay to be consistently predictive of tumor relapse in post-treatment patients according to serial test results by time frame. Conclusion The EBV EA+EBNA-1 IgA-based protocol is recommended for mass screening, but EBV DNA load should be used solely for post-treatment monitoring for NPC in endemic areas. Significance A possible alternative for primary screening of NPC. Support NSC of Taiwan, ROC. (NSC92-2314-B-182A-207) and CGU (CMRPG32090 and CMRPG360211).