ONCOGENIC MICROORGANISMS IN HUMAN CANCER: MECHANISMS OF CARCINOGENESIS AND HISTOPATHOLOGICAL PROGRESSION-A SYSTEMATIC REVIEW

Abstract

Background: Persistent infection with selected viruses, bacteria, and parasites contributes substantially to the global cancer burden. Oncogenic microorganisms promote malignant transformation through direct expression of microbial oncogenes, integration of microbial genetic material into the host genome, chronic inflammation, oxidative stress, immune evasion, genomic instability, epigenetic reprogramming, disruption of cellular signalling pathways, and alteration of the local tissue microenvironment. These molecular events are accompanied by characteristic histopathological changes that may progress from persistent infection and chronic inflammation to metaplasia, dysplasia, invasive malignancy, and metastatic disease. Objective: This systematic review aimed to synthesize the available evidence regarding the major oncogenic microorganisms associated with human cancers, their molecular and immunopathological mechanisms of carcinogenesis, and the corresponding histopathological progression from infection-associated precursor lesions to invasive malignancy. Methods: A systematic search of PubMed/MEDLINE, Embase, Scopus, and Web of Science was conducted from database inception to January 31, 2026. Additional literature was identified through Google Scholar, International Agency for Research on Cancer resources, World Health Organization documents, and manual screening of reference lists. Studies examining recognised or suspected oncogenic microorganisms in relation to molecular carcinogenesis, precancerous lesions, tumour histopathology, malignant transformation, or cancer progression were eligible. Two reviewers independently screened the literature, extracted relevant data, and evaluated methodological quality. Owing to substantial heterogeneity in microorganisms, tumour types, study designs, detection techniques, and reported outcomes, a narrative synthesis was performed. Results: A total of 1,842 records were identified. After removal of 466 duplicates, 1,376 records underwent title and abstract screening. Of these, 118 full-text articles were assessed for eligibility, and 30 studies were included in the final qualitative synthesis. The strongest and most consistently demonstrated associations were observed between high-risk human papillomavirus and cervical, anogenital, and oropharyngeal cancers; Epstein–Barr virus and lymphoid, nasopharyngeal, and gastric malignancies; hepatitis B and C viruses and hepatocellular carcinoma; Helicobacter pylori and gastric adenocarcinoma or gastric mucosa-associated lymphoid tissue lymphoma; human T-cell lymphotropic virus type 1 and adult T-cell leukaemia/lymphoma; Kaposi sarcoma-associated herpesvirus and Kaposi sarcoma; Merkel cell polyomavirus and Merkel cell carcinoma; Schistosoma haematobium and urinary bladder squamous cell carcinoma; and Opisthorchis viverrini or Clonorchis sinensis and cholangiocarcinoma. Commonly affected pathways included p53, retinoblastoma protein, nuclear factor-κB, Janus kinase/signal transducer and activator of transcription, phosphatidylinositol-3-kinase/AKT, Wnt/β-catenin, transforming growth factor-β, telomerase, apoptosis, and DNA-repair pathways. Conclusions: Oncogenic microorganisms promote human carcinogenesis through interacting direct and indirect mechanisms. Their effects are reflected in recognisable histopathological continua, including cervical intraepithelial neoplasia, chronic atrophic gastritis–intestinal metaplasia–dysplasia, chronic hepatitis–cirrhosis–hepatocellular carcinoma, chronic schistosomal cystitis–squamous metaplasia–bladder carcinoma, and chronic cholangitis–biliary dysplasia–cholangiocarcinoma. Integration of histomorphology with validated microbial, immunohistochemical, and molecular tests can improve tumour classification and risk assessment. Vaccination, infection prevention, antimicrobial treatment, screening, and surveillance of high-risk populations provide major opportunities for reducing the burden of microorganism-associated cancers.