ROLE OF ONCOGENIC MICROORGANISMS IN THE PATHOGENESIS AND HISTOPATHOLOGICAL PROGRESSION OF HUMAN CANCERS: A SYSTEMATIC REVIEW

Abstract

Background Persistent infection with selected viruses, bacteria and parasites contributes substantially to the global burden of human cancer. Oncogenic microorganisms promote malignant transformation through microbial oncogene expression, integration into the host genome, tumour-suppressor inactivation, chronic inflammation, oxidative DNA damage, immune dysregulation, epigenetic reprogramming and sustained tissue regeneration. However, the relationship between microbial persistence and the sequential histopathological changes leading from chronic infection to precursor lesions and invasive malignancy remains incompletely integrated. Objective To systematically review the role of established and emerging oncogenic microorganisms in the molecular pathogenesis and histopathological progression of human cancers. Methods A systematic literature search was conducted in PubMed/MEDLINE, Embase, Scopus and Web of Science, supplemented by searches of the International Agency for Research on Cancer and World Health Organization repositories. Records published from database inception to January 31, 2026, were considered. Studies evaluating microbial carcinogenesis, precursor lesions, histopathological progression, microbial tissue markers and infection-associated human malignancies were eligible. Of the 2,146 records identified, 568 duplicates were removed and 1,578 records underwent title and abstract screening. A total of 219 full-text articles were assessed, of which 76 fulfilled the eligibility criteria and were included in the qualitative synthesis. Because of substantial heterogeneity in microorganisms, anatomical sites, outcomes and methodologies, meta-analysis was not performed. Results The included evidence addressed high-risk human papillomaviruses, hepatitis B, C and D viruses, Epstein–Barr virus, Kaposi sarcoma-associated herpesvirus, human T-cell lymphotropic virus type 1, Merkel cell polyomavirus, human immunodeficiency virus type 1, Helicobacter pylori, Schistosoma haematobium, Opisthorchis viverrini and Clonorchis sinensis. Distinct histopathological pathways included cervical intraepithelial neoplasia preceding HPV-associated squamous cell carcinoma; chronic atrophic gastritis, intestinal metaplasia and dysplasia preceding H. pylori-associated gastric adenocarcinoma; chronic hepatitis, cirrhosis and dysplastic nodules preceding hepatocellular carcinoma; chronic granulomatous cystitis, squamous metaplasia and dysplasia preceding schistosomiasis-associated bladder carcinoma; and chronic cholangitis, periductal fibrosis and biliary intraepithelial neoplasia preceding liver-fluke-associated cholangiocarcinoma. Other microorganisms, including Epstein–Barr virus, Kaposi sarcoma-associated herpesvirus, HTLV-1 and Merkel cell polyomavirus, promoted clonal neoplastic proliferation without a consistently recognizable conventional histological precursor. Conclusion Oncogenic microorganisms promote cancer through pathogen-specific oncogenic factors and common host pathways involving inflammation, immune evasion, genomic instability and abnormal tissue repair. Histopathology provides a temporal record of these interactions and remains essential for recognizing infection-associated precursor lesions and malignancies. Vaccination, infection eradication, antiviral suppression, parasite control and surveillance of precursor lesions offer substantial opportunities for cancer prevention.