Early detection and interception in hepato-pancreatic-biliary cancers: endoscopic imaging, liquid biopsy, and emerging molecular biomarkers

Early detection of hepato-pancreatic-biliary cancers requires different strategies because the populations at risk, precursor lesions, and accessible specimens vary by organ. This review examines established endoscopic imaging and tissue-acquisition pathways together with circulating and lesion-derived biomarkers. Inherited or familial pancreatic risk defines the main pancreatic surveillance population; endoscopic ultrasonography and magnetic resonance imaging are complementary, and prospective cohorts show a stage shift but also interval cancers and low-yield surgery. In pancreatic cysts, imaging features and selective tissue or cyst-fluid analysis can refine management, but no fluid marker independently identifies high-grade dysplasia with sufficient certainty. For biliary cancer, surveillance in primary sclerosing cholangitis depends on noninvasive imaging, whereas endoscopic ductal sampling, cholangioscopy-guided biopsy, and selective endoscopic ultrasonography address suspicious strictures; bile methylation and sequencing may increase diagnostic yield when an invasive procedure is already indicated. Endoscopy has a selective role in gallbladder lesions and a direct interception role in histologically confirmed ampullary adenomas. Hepatocellular carcinoma surveillance remains based on ultrasonography with alpha-fetoprotein; cell-free DNA methylation and multi-analyte blood tests are promising but have not replaced guideline-based surveillance. Across organs, case-control accuracy does not establish surveillance utility. Liquid biopsy complements rather than generally replaces histopathological diagnosis. Established adjuncts must be distinguished from investigational assays, including those with prospective diagnostic validation but no demonstrated surveillance utility. Integration requires specimen-specific analytical validation, independent testing in the intended-use population, and evidence of incremental clinical value over standard imaging and endoscopy. Interventional studies must show that this approach reduces late-stage diagnosis without excessive false-positive procedures.