Detection of Epstein-Barr Virus DNA in the Peripheral-Blood Cells of Patients With Nasopharyngeal Carcinoma: Relationship to Distant Metastasis and Survival

Abstract

PURPOSE: Nasopharyngeal carcinoma (NPC) has been proved to be an Epstein-Barr virus (EBV)-associated cancer. By use of nested polymerase chain reactions (PCRs), we examined whether the presence of EBV DNA in the peripheral-blood cells (PBC) can serve as a prognostic indicator for NPC.PATIENTS AND METHODS: Peripheral blood from 124 patients with NPC who had no evidence of distant metastasis and 114 healthy volunteers with serologically positive findings for EBV infection was collected prospectively. Plasma and erythrocytes were separated. DNA was extracted from PBCs and analyzed by a nested PCR using primers specific to Epstein-Barr virus nuclear antigen 1 (EBNA-1). All patients were treated by radiotherapy with or without chemotherapy. Clinical parameters and status of EBNA-1 in PBCs were used for survival analysis using the Kaplan-Meier method and the Cox proportional hazards model.RESULTS: Positive rates of EBNA-1 DNA in PBCs of NPC patients and healthy volunteers are 71% and 14%, respectively (P = .001). No significant difference was observed with regard to the clinical characteristics of patients who were EBNA-1–positive (n = 88) and those who were EBNA-1–negative (n = 36). After a median follow-up period of 38 months (range, 24 to 56 months), 29 of 88 EBNA-1–positive patients and only one of 36 EBNA-1–negative patients developed distant metastases (P = .00015). Kaplan-Meier estimates of overall survival (P = .0010), metastasis-free survival (P = .0004), and progression-free survival (P = .0004) were significantly lower for the patients in the EBNA-1–positive group than for those in the EBNA-1–negative group. Multivariate Cox analysis confirmed the same results.CONCLUSION: The presence of EBNA-1 DNA in PBCs is a novel, important risk factor for patients with NPC that indicates a significantly higher risk of developing distant metastasis as well as a lower survival rate.