Emerging salivary biomarkers for early detection of oral squamous cell carcinoma

Oral cancer, particularly oral squamous cell carcinoma (OSCC), remains a leading cause of cancer-related morbidity and mortality, with delayed diagnosis being a major contributing factor. Although salivary biomarkers have been explored for over three decades, the need for reliable, non-invasive diagnostic methods that enable early detection and continuous monitoring of OSCC remains unmet. This review aims to provide an updated overview of the latest advancements in salivary biomarker research, focusing on emerging biomarkers such as interleukin-6, interleukin-8, microRNAs and DNA methylation patterns, as well as metabolites and microbiota, all of which show significant promise for early OSCC detection. In addition to discussing well-established biomarkers, we explore recent technological developments that increase the sensitivity and specificity of these biomarkers, such as mass spectrometry, multiplex assays, and nanobiosensors. These developments are complemented by the integration of artificial intelligence for data analysis, which enables more accurate, point-of-care diagnostics that could revolutionize oral cancer screening. This review not only consolidates current knowledge but also addresses the challenges that hinder the widespread clinical adoption of salivary diagnostics, such as saliva variability and assay standardization. By overcoming these barriers, salivary biomarker-based diagnostics have the potential to transform OSCC detection, offering a non-invasive, cost-effective solution that can improve early diagnosis and patient outcomes.