Clinical utility and advances of liquid biopsy in hypopharyngeal carcinoma: a systematic review and meta-analysis

Background: Hypopharyngeal carcinoma (HPC) is an aggressive malignancy with poor prognosis due to difficult early diagnosis, frequent recurrence, and distant metastasis. Although surgery, radiotherapy, chemotherapy, and immunotherapy have progressed, accurate prognostic assessment and real-time monitoring remain limited. Liquid biopsy, a minimally invasive method detecting circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and microRNAs (miRNAs), shows promise in solid tumours, but its role in HPC is underexplored. Methods: A systematic search of PubMed, Embase, and Web of Science was conducted to September 2025 following PRISMA guidelines. Eligible studies evaluated ctDNA, CTCs, or miRNAs for diagnosis, treatment monitoring, or prognosis of HPC, reporting sensitivity, specificity, diagnostic odds ratio, or hazard ratio for meta-analysis. Results: Twenty-four studies with 933 patients were included. Pooled estimates showed sensitivity 88.3% (95% CI: 84.7-91.6) and specificity 95.9% (95% CI: 93.3-97.9), with predictive intervals sensitivity 0.74-0.98 and specificity 0.85-1.00. Heterogeneity was moderate (I² sensitivity = 52.3%; specificity = 48.5%), and no publication bias was observed. Subgroup analyses indicated ctDNA was advantageous for treatment monitoring, CTCs were consistent in prognosis, and miRNAs were strong candidates due to stability and detection sensitivity. Sensitivity analyses confirmed robustness. Conclusions: Liquid biopsy shows strong potential for diagnosis, monitoring, and prognosis in HPC. Large-scale, multicentre studies are required to validate its clinical application and integration into patient-management pathways.