Non-invasive Diagnostics in the Focus: The Importance of Salivary Biomarkers in Detecting Oral Cancer

Oral squamous cell carcinoma (OSCC) is a global health challenge, often diagnosed at advanced stages due to the invasiveness and limited accessibility of current methods like tissue biopsies. Salivary biomarkers have emerged as a transformative alternative, offering a non-invasive, cost-effective, and patient-friendly approach for early detection, prognosis, and treatment monitoring. This review highlights the mechanistic roles of salivary biomolecules, including microRNAs (miRNAs) (e.g., miR-31, miR-200a), proteins (interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9)), circulating tumor DNA (ctDNA), and metabolites, in OSCC pathogenesis. We discuss advancements in salivaomics (genomics, proteomics, metabolomics) and technologies (biosensors, AI-driven multi-marker panels) that enhance diagnostic accuracy. Published data from validation studies indicate that several salivary biomarkers demonstrate strong diagnostic potential for OSCC detection. Despite ongoing advances, significant challenges such as biomarker variability, lack of standardized collection protocols, and the need for robust clinical validation currently limit the widespread adoption of salivary diagnostics in OSCC. Future research is focusing on integrated multi-omics strategies, the development of wearable real-time monitoring devices, and establishing regulatory frameworks to better facilitate clinical implementation. Addressing these issues may improve the reliability and accessibility of saliva-based diagnostics for OSCC, particularly in low-resource and high-risk populations.