Diagnostic and prognostic potential of salivary microRNA in oral and head and neck squamous cell carcinomas: a systematic review

Abstract

Oral squamous cell carcinoma (OSCC) and head and neck squamous cell carcinoma (HNSCC) are aggressive malignancies with poor survival rates, largely attributable to late diagnosis. Salivary microRNAs (miRNAs), particularly exosome-derived miRNAs, have emerged as promising non-invasive biomarkers for early detection and prognostic assessment. This systematic review evaluated the diagnostic and prognostic value of free and exosomal salivary miRNAs in OSCC and HNSCC. A comprehensive search of PubMed, Scopus, Web of Science, and Google Scholar was conducted for studies published between January 2008 and May 2025. Studies assessing salivary miRNAs in histologically confirmed OSCC/HNSCC using validated molecular techniques were included, with quality assessed using QUADAS-2. Forty-two studies encompassing 2577 patients/samples were analyzed. Several miRNAs, including miR-21, miR-31, miR-1307-5p, and miR-486-5p, demonstrated high diagnostic accuracy (AUC > 0.85), while others were significantly associated with lymph node metastasis, treatment response, and survival outcomes. Exosomal miRNAs generally showed superior stability and predictive performance compared with free miRNAs. However, substantial methodological heterogeneity was observed. Overall, salivary miRNAs-particularly exosomal-represent promising biomarkers for OSCC and HNSCC, although standardized protocols and large-scale validation studies are required for clinical translation.

Keywords: Biomarkers; Early diagnosis; Exosomes; MicroRNAs; Prognosis; Saliva; Squamous cell carcinoma of head and neck.