Association between Epstein-Barr virus and Thymic epithelial tumors: a systematic review

The possible role of Epstein-Barr virus (EBV) in the pathogenesis of thymic epithelial tumors (TET) remains controversial. This study aimed to determine the prevalence of EBV in TET. We conducted a systematic review of relevant English-language studies published between January 1980 and December 2013. Effect size was calculated as event rates (95% confidence interval [CI]) by homogeneity testing using Cochran's Q and I² statistics for benign TET, benign TET with myasthenia gravis (MG), and thymic carcinoma (TC). Among 136 potentially relevant studies, 22 met the inclusion criteria. Despite a considerable degree of heterogeneity, the pooled estimated incidences were 9% (95% CI, 1-23%), 20% (95% CI, 0-54%), and 6% (95% CI, 0-21%) for benign TET, benign TET with MG, and TC, respectively. There was significant heterogeneity among studies that used in situ hybridization (ISH) for both benign TET and benign TET with MG. According to the random-effects model, studies employing ISH yielded lower point estimates of EBV prevalence (5%) than those employing other methods (33%). Using the random-effects model, we found a lack of significant heterogeneity among studies from different geographic regions (p = 0.0848). Further, 12 of 23 lymphoepithelioma-like carcinoma (LELC) cases tested EBV-positive. The prevalence of EBV in benign TET with or without MG was lower than in nasopharyngeal carcinoma, suggesting that EBV plays a minor role in TET pathogenesis. Although the prevalence of EBV in TC was also low, EBV may play an important causal role in LELC. Further research is needed to clarify these associations.