MicroRNA networks shaping the future of diagnosis, prognosis, and therapy in head and neck cancer

Head and neck cancer (HNC) remains a major global health challenge, characterized by high morbidity, mortality, and clinical heterogeneity. MicroRNAs (miRNAs), a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level, have emerged as critical regulators of HNC development and progression. This review summarizes current evidence on miRNA biogenesis, dysregulation patterns, molecular mechanisms, and their clinical relevance in HNC. This narrative review is based on literature published between 2009 and 2026 identified through searches of PubMed, PubMed Central, Scopus, Web of Science, and Google Scholar, with emphasis on clinically relevant and translational studies in HNC. Aberrant expression of oncogenic and tumor-suppressive miRNAs influences key biological processes, including cell proliferation, apoptosis, epithelial–mesenchymal transition, invasion, metastasis, and resistance to chemotherapy and radiotherapy. Several miRNAs, including miR-21, miR-155, miR-375, and members of the miR-99 family, have demonstrated significant diagnostic and prognostic value across oral, laryngeal, and pharyngeal cancers. Their remarkable stability in saliva, plasma, and other body fluids supports their application as minimally invasive biomarkers for early detection, disease monitoring, and liquid biopsy-based approaches. Furthermore, emerging therapeutic strategies, such as miRNA replacement therapy, miRNA inhibition, nanotechnology-assisted delivery systems, and CRISPR-mediated gene modulation, highlight the translational potential of miRNA-based interventions. Despite their considerable promise, the clinical translation of miRNA-based diagnostics and therapeutics remains constrained by limited biomarker validation, variability in liquid biopsy workflows, delivery barriers, tumor heterogeneity, and lack of standardization. Nevertheless, ongoing advances in molecular profiling, RNA delivery systems, and precision oncology are expected to accelerate the future clinical integration of miRNA-based strategies in HNC.