The research progress of the synergistic effect of Epstein-Barr virus and Helicobacter pylori infection in the occurrence and development of gastric cancer

Gastric cancer (GC) is a malignant tumor characterized by high morbidity and mortality rates worldwide. The development of GC is a complex process influenced by various factors. Helicobacter pylori (HP) and Epstein-Barr virus (EBV) are recognized as pivotal contributors to this malignancy. HP instigates chronic inflammation, disrupts the gastric mucosal barrier, and triggers epigenetic modifications and aberrant cell signaling pathways, thereby facilitating GC progression. Conversely, EBV infection is specifically associated with Epstein-Barr virus-associated gastric cancer (EBVaGC), a distinct subtype of GC. EBV contributes to tumorigenesis by expressing latent membrane proteins, EBV nuclear antigens, and non-coding RNA, resulting in the hypermethylation of tumor suppressor genes in host cells and the rewiring of cellular metabolism. Historically, HP and EBV infections were considered distinct risk factors for gastric cancer. Nevertheless, recent research indicates a synergistic relationship between these pathogens in gastric cancer development, wherein they collaboratively influence key signaling pathways, bolster gastric cancer stem cell characteristics, and remodel the tumor microenvironment to expedite tumor advancement. The inflammatory milieu induced by HP infection fosters EBV colonization and reactivation. Consequently, comprehending the combined mechanism of gastric cancer initiation by EBV and HP infections holds paramount importance for gastric cancer treatment and prevention. This review comprehensively examines the synergistic interplay of HP and EBV in gastric cancer onset and progression, consolidates recent advancements in relevant research models and therapeutic approaches, and outlines prospective research avenues in this domain.