Cytomegalovirus and Cancer: Revisiting Oncogenic Hypotheses and Therapeutic Perspectives

Human cytomegalovirus (HCMV) has emerged as a potential oncomodulatory agent implicated in the pathogenesis of several cancers, although its precise role in tumorigenesis remains a subject of debate. This review synthesizes five decades of research examining the involvement of HCMV in cancer, with particular focus on molecular mechanisms by which the virus may contribute to tumor progression, including immune evasion, chronic inflammation, and modulation of cell cycle and signaling pathways. Evidence of HCMV detection in malignancies such as glioblastoma, breast, colorectal, and prostate cancers is critically reviewed, alongside ongoing controversies regarding its causal versus passenger role in oncogenesis.The review further explores current and emerging antiviral and immunotherapeutic strategies targeting HCMV within oncological settings, highlighting their potential translational relevance and associated challenges. By reassessing oncogenic hypotheses and therapeutic opportunities, this article aims to provide a comprehensive perspective on the complex interplay between HCMV and cancer biology, and to evaluate its potential as a novel target for cancer prevention and therapy.