Evaluation of plasma Epstein‐Barr virus DNA load to distinguish nasopharyngeal carcinoma patients from healthy high‐risk populations in Southern China

BACKGROUND The utility of circulating Epstein‐Barr Virus (EBV) DNA as a tumor marker for nasopharyngeal carcinoma (NPC) detection suggests that it might improve the diagnostic performance of anti‐EBV antibody markers in NPC screening. In this study, the authors evaluated whether circulating EBV DNA load is capable of distinguishing NPC patients from high‐risk individuals who have positive anti‐EBV antibodies. METHODS In a population‐based NPC screening trial in Sihui City and Zhongshan City, Guangdong Province, China, the authors previously identified 862 high‐risk participants with 2 screening markers, immunoglobulin A (IgA) antibodies to EBV capsid antigen (VCA/IgA) and nuclear antigen‐1 (EBNA1/IgA). In the current study, real‐time polymerase chain reaction was used to measure the baseline plasma EBV DNA load among 825 participants (97%). Follow‐up was extended to the end of 2011 to evaluate the diagnostic and predictive values of plasma EBV DNA load. RESULTS By using 0 copies/mL as the cutoff value, plasma EBV DNA had a sensitivity of 86.8% (33 of 38 patients) for NPC detected within the first year of follow‐up, yielding a positive predictive value of 30% (33 of 110 participants) and a negative predictive value of 99.3% (696 of 701 participants). The patients who had early stage NPC had lower sensitivity (81.5%; 22 of 27 patients) than those who had advanced NPC (100%; 11 of 11 patients). For the 14 patients who had NPC detected after 1 year of follow‐up, only 50% (7 of 14 patients) tested positive for EBV DNA at baseline. CONCLUSIONS The plasma EBV DNA load may improve the accuracy of diagnosing NPC in high‐risk individuals, but it appears to have limited value in screening patients who have early stage NPC and predicting NPC development. Cancer 2014;120:1353–1360. © 2014 American Cancer Society. This study is the first to prospectively evaluate whether plasma Epstein‐Barr virus (EBV) DNA load may serve as a complementary screening tool to distinguish nasopharyngeal carcinoma (NPC) patients from the individuals who are positive for anti‐EBV antibodies in a population‐based NPC screening trial in endemic areas. The results provide high‐grade evidence that EBV DNA could be useful in clinical diagnosis of NPC but has limited value in screening for early stage NPC or predicting NPC development.