The importance of Epstein-Barr virus infection in the systemic treatment of patients with gastric cancer

The Epstein-Barr virus (EBV) may directly cause the development of EBV-associated gastric cancer (EBVaGC). The prevalence of EBVaGC ranges from 4% to 18%, with a 2-fold higher frequency in males, and in tumors arising in the gastric cardia or corpus and 4 times higher frequency in gastric stump carcinoma. The vast majority of EBVaGC are lymphoepithelioma-like carcinomas. Despite extensive nodal involvement and distant metastases at initial diagnosis, EBVaGC seems to be a distinct etiologic entity with a favorable prognosis. However, the lymphoepithelioma-like carcinomas subtype in EBVaGC cannot be recognized in the current molecular classifications. Neither is there an association between EBV positivity and survival of patients after curative gastrectomy if they received standard adjuvant chemotherapy, nor EBV positivity and prediction of response to neoadjuvant platinum/5-FU-based chemotherapy. Alterations in chemokines and PD-L1 provide theoretical justification for clinical evaluation of immune checkpoint therapy in EBVaGC. Moreover, a higher degree of host immune response was demonstrated in EBVaGC. The current histologic and molecular GC classification does not influence clinical practice. Further research is expected to find convenient methods to assess gastric subtypes in day-to-day practice and to tailor therapy to improve overall survival.