Saliva as a Source of Noninvasive Biomarkers for Systemic and Oral Diseases

Saliva contains host proteins, metabolites, nucleic acids, microbial products and extracellular vesicles that can be sampled repeatedly without venipuncture. These properties make it attractive for screening and monitoring, but analytical accessibility does not by itself establish diagnostic utility. Evidence on salivary biomarkers was assessed across periodontal disease, oral cancer, dental caries, diabetes, cardiovascular disease and Sjögren disease. Emerging salivary liquid-biopsy approaches also include extracellular vesicles and circulating tumor DNA. Across these applications, the strongest methodological requirements are standardized collection, control of oral inflammation, separation of discovery from validation, and comparison with an appropriate clinical reference standard. A biomarker may be useful for a local oral disorder while remaining nonspecific for a systemic condition. High discrimination in a small case-control sample can also overestimate performance in screening populations. The evidence supports further development of selected multimarker panels, particularly when saliva is biologically close to the disease process. Broad replacement of established diagnostic pathways is not justified by exploratory studies alone.