Molecular Prognostic Value of Circulating Epstein-Barr Viral DNA in Nasopharyngeal Carcinoma: A Meta-Analysis of 27,235 Cases in the Endemic Area of Southeast Asia

Abstract

Aims:

This meta-analysis evaluated the value of using Epstein-Barr virus (EBV) DNA titers as a predictive factor in assessing the clinical course of nasopharyngeal carcinoma (NPC) patients in Southeast Asia.

Methods:

A systematic search was performed using PubMed, the Cochrane Library, and Embase online databases. Eligible studies with complete baseline information and extractable hazard ratios (HRs), 95% confidence intervals (CIs), and other details were included in this analysis. All pooled statistics were calculated using RevMan 5.3 software with inverse variance methods, forest plots, or funnel plots directly; the results were analyzed both in toto and by subgroups using meta-regression and sensitivity analyses.

Results:

Forty studies involving 27,235 subjects were included in this meta-analysis. When the recommended EBV DNA viral cutoff values of 2,000, 0, and 0 copies/mL were used for the pretreatment, mid treatment, and post treatment groups, respectively, all values above these cutoffs were associated with at least a 2.5-fold increased risk of death compared with patients with lower levels of EBV DNA (HRs and 95% CIs were 2.47 [2.10-2.89], 2.67 [1.50-4.75], and 5.25 [3.58-7.71], respectively, p < 0.05). This finding could also explain heterogeneities among the studies.

Conclusion:

Higher pretreatment, mid-treatment, and post-treatment EBV DNA levels were all significantly correlated with poor outcomes for patients afflicted with NPCs. Further investigations of EBV DNA levels, combined with addressing tumor size, lymph nodes, metastases stages, are needed to determine whether they can be used as clinical guidelines for diagnosis and treatment.