Salivary biomarkers in oral cancer diagnosis: advancing conventional treatment strategies

Oral squamous cell carcinoma (OSCC) is a major global health challenge, with most cases being diagnosed at advanced stages. Traditional diagnostic methods are often invasive and costly, and can delay diagnosis. Saliva has emerged as a promising non-invasive source of biomarkers for OSCC detection. This highlights the need for accessible, non-invasive, and sensitive biomarkers for OSCC detection. This review critically evaluates the current status and future potential of salivary biomarkers in OSCC, with an emphasis on their diagnostic efficacy, sensitivity, specificity, clinical validation, and advantages over traditional serum- and plasma-based markers. Saliva is a promising liquid for biopsy due to its non-invasive collection and molecular richness. We summarize evidence on diverse salivary biomarkers, including microRNAs (miRNAs), proteins, metabolites, circulating tumor cells (CTCs), and circulating tumor DNA (ctDNA), highlighting their dysregulation in OSCC and diagnostic utility. Particular emphasis is placed on CTCs, ctDNA, and miRNAs, which demonstrate stability in saliva and potential for early detection. We further discuss advances in next-generation sequencing, mass spectrometry, and artificial intelligence/machine learning that enable the development of biomarker panels with improved diagnostic accuracy over single markers. Despite challenges such as sample heterogeneity and the lack of standardized protocols, salivary biomarkers hold strong potential to transform OSCC care by enabling earlier detection, guiding personalized therapies, and supporting non-invasive disease monitoring. However, achieving methodological standardization, validating biomarkers across diverse cohorts, and integrating them into clinical workflows are imperative before their routine application in practice.