Saliva-based liquid biopsy for precision diagnosis of oral diseases: a review

Saliva has emerged as a valuable medium for liquid biopsy due to its non-invasive accessibility and molecular diversity. Advances in analytical technologies have enabled the detection of a wide range of salivary biomarkers, expanding its diagnostic potential of saliva beyond conventional oral health assessment. This review study aimed to overview the biological basis of salivary biomarkers and recent progress in saliva-based diagnostics for major oral and oral mucosal diseases, including periodontal diseases, dental caries, Sjögren’s syndrome, oral lichen planus, and oral squamous cell carcinoma. Particular emphasis is placed on salivaomics, which combines genomic, transcriptomic, proteomic, metabolomic, and microbiomics data to improve diagnostic accuracy and address the limitations of single-biomarker strategies. The incorporation of artificial intelligence and machine learning techniques is discussed as an important advancement for managing complex salivary datasets, enabling automated biomarker selection, disease classification, and risk stratification. Emerging biosensor platforms are also highlighted for their potential to enable rapid and point-of-care detection of salivary biomarkers, although most remain in early stages of clinical translation. Despite significant technological improvement, clinical translation remains challenged by biological variability, low biomarker abundance, and the lack of standardized protocols. This review outlines these challenges and discusses practical strategies to improve clinical outcomes. Overall, saliva-based liquid biopsy represents a promising component of precision dentistry, with future developments expected to focus on optimized multiomics integration, point-of-care biosensing platforms, and large-scale clinical validation.