A Randomized Controlled Trial on Evaluation of Plasma Epstein-Barr Virus Biomarker for Early Diagnosis in Patients With Nasopharyngeal Carcinoma.

Early diagnosis of nasopharyngeal carcinoma (NPC) remains a major problem in Southern China. Epstein-Barr virus (EBV) biomarkers have been widely used in NPC screening. This study aims to evaluate the early diagnostic performances of individual EBV biomarkers in NPC. The levels of EBV biomarkers-IgA antibodies against EBV nuclear antigen 1 (EBNA1-IgA), EBV capsid antigen (VCA-IgA), EBV early antigen (EA-IgA), EBV BZLF1 transcription activator protein (Zta-IgA) and IgG antibodies against EBV BRLF1 transcription activator protein (Rta-IgG)-from 106 NPC patients (stage I and II) and 150 normal subjects were measured. VCA-IgA and EA-IgA were detected by immunofluorescence assay (IFA), EBNA1-IgA, Rta-IgG and Zta-IgA were measure by enzyme-linked immunosorbent assay (ELISA), and EBV DNA was detected by qPCR. Statistical analyses of a single index were conducted to evaluate the significance of NPC early diagnosis and TNM classification. The level of EBNA1-IgA, EBV DNA, VCA-IgA, EA-IgA, Rta-IgG and Zta-IgA in early-stage NPC was significantly higher than in healthy controls (all P < 0.001). EBNA1-IgA yielded the biggest area under the curve (AUC) of 0.962 in distinguishing early-stage NPC patients from the normal subjects, with a sensitivity of 91.5% and a specificity of 98.7%. However, EBV biomarker levels were not associated with tumor size (all P > 0.050), whereas four biomarker levels (EBNA1-IgA, EBV DNA, VCA-IgA, EA-IgA) were related to lymph node metastasis (N0 and N1-2), among which EBNA1-IgA and EBV DNA showed good performance. Finally, high correlation was found between VCA-IgA and EA-IgA (r > 0.800). A single EBNA1-IgA exhibits excellent discrimination performance in early diagnosis of NPC and could become a promising marker for NPC screening.