Virus infections and cancers: from mechanisms to therapeutics

Abstract

Viral infections are a major contributor to global cancer incidence and mortality. However, integrative reviews that connect viral classification, carcinogenic mechanisms, tumor microenvironment remodeling, and translational strategies remain limited. This review summarizes the classification and epidemiological characteristics of major oncogenic viruses, including human papillomavirus (HPV), Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), Merkel cell polyomavirus (MCPyV), human T-lymphotropic virus type 1 (HTLV-1), Kaposi’s sarcoma-associated herpesvirus (KSHV), and human immunodeficiency virus (HIV), as well as emerging viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We then discuss the molecular basis of virus-associated carcinogenesis, including viral oncogenes, viral DNA integration, epigenetic remodeling, aberrant host signaling, and metabolic dysregulation. We further examine how chronic inflammation and fibrosis create oncogenic niches within the tumor microenvironment (TME), how viruses promote tumor progression through immune evasion and immune exhaustion, and how infected cells interact with stromal and immune components of the TME. At the preventive and therapeutic levels, we discuss antiviral therapies, vaccines, biomarker-based precision diagnostics, and prognostic strategies, with particular attention to the synergistic potential of emerging therapeutic approaches such as immune checkpoint inhibitors (ICIs), CAR-T therapy, and oncolytic viruses (OVs). Finally, we highlight how multi-omics approaches, single-cell transcriptomics, spatial transcriptomics, organoid models, and artificial intelligence can advance mechanistic studies and translational innovation in virus-associated cancers. Overall, this review provides an integrated framework for understanding, preventing, and treating virus-associated tumorigenesis.