Cytomegalovirus and Cancer: Revisiting Oncogenic Hypotheses and Therapeutic Perspectives

Human cytomegalovirus (HCMV) has emerged as a potential oncomodulatory agent implicated in several cancers, yet its precise role in oncogenesis remains debated. This review synthesizes five decades of research on the involvement of CMV in cancer, focusing on molecular mechanisms by which CMV may promote tumor progression, including immune evasion, inflammation, and modulation of cell cycle pathways. We discuss evidence of CMV presence in tumors such as glioblastoma, breast, colorectal, and prostate cancers, and critically evaluate controversies surrounding its causal role. The review further explores current and emerging antiviral and immunotherapeutic strategies targeting CMV in oncological contexts, highlighting challenges and future research priorities. By reassessing oncogenic hypotheses and therapeutic avenues, this article aims to provide a comprehensive perspective on CMV’s role in cancer biology and its potential as a target for cancer treatment.