Are Salivary Biomarkers Ready for Clinical Dentistry?

By Ayesha Khan, MBA

Saliva is increasingly being recognized as more than a protective oral fluid. It contains proteins, nucleic acids, metabolites, antibodies, microbial components, and extracellular vesicles that can reflect both local oral conditions and broader systemic biological processes.

That potential was a central theme of the American Dental Association (ADA) Salivary Diagnostics Summit, held in Chicago in June 2026. Researchers, clinicians, diagnostic scientists, and other stakeholders examined what is required to move salivary diagnostics from promising research into reliable clinical dentistry. The more important question is which salivary biomarkers can provide sufficiently accurate and reproducible information to change patient care?

Saliva as a Medium and Biomarker

Saliva offers several practical advantages over conventional biological specimens. Collection is noninvasive, inexpensive, repeatable, and generally well tolerated. Unlike venipuncture, saliva collection can potentially be performed chairside or outside traditional laboratory environments.

The ADA summit specifically identified periodontal disease, caries, xerostomia, diabetes, cardiovascular disease, and Alzheimer's disease among areas warranting further clinical investigation.

The strongest evidence currently exists in several oral diseases such as:

• Periodontal Disease: Periodontology is currently one of the strongest areas for salivary biomarker research. Matrix metalloproteinase-8 (MMP-8) has received considerable attention because of its relationship with collagen degradation and periodontal tissue destruction. A 2024 systematic meta-analysis of salivary MMP-8 found significantly higher concentrations in patients with gingivitis and periodontitis than in healthy individuals. Across 10 studies involving 704 participants, patients with gingivitis had substantially higher MMP-8 concentrations than healthy controls, while concentrations were also higher in periodontitis than gingivitis. The authors concluded that salivary MMP-8 has potential to distinguish periodontal health from disease and differentiate gingivitis from periodontitis. The evidence extends beyond MMP-8. A 2025 systematic meta-analysis examining salivary interleukin-1β (IL-1β), MMP-8, and MMP-9 found significantly elevated levels of all three biomarkers among patients with periodontitis compared with healthy controls.
• Dental Caries: Salivary diagnostics may also help characterize caries activity and susceptibility. A 2024 systematic review incorporating 50 studies found that individuals with dental caries demonstrated altered salivary profiles, including significantly higher salivary interleukin-6 and tumor necrosis factor-alpha concentrations compared with caries-free individuals. More recently, a systematic review evaluating salivary alpha-amylase found an association between higher salivary alpha-amylase activity and an increased likelihood of dental caries, further supporting investigation of salivary biochemical markers for caries assessment.
• Xerostomia: Medication-associated dry mouth is particularly relevant in an aging population and among patients taking multiple medications. At the 2026 ADA summit, researchers highlighted medication use as a major contributor to hyposalivation and reported that more than 42% of medications may have dry mouth listed as a potential adverse effect. Instead of identifying xerostomia only after symptoms become clinically significant, quantitative salivary assessment could potentially support earlier preventive intervention.
• Oral Cancer: Oral squamous cell carcinoma (OSCC) represents another area in which salivary biomarkers have attracted substantial attention. A 2025 systematic review of 28 studies involving 3,507 patients with oral squamous cell carcinoma (OSCC) and 3,501 controls evaluated 37 salivary protein biomarkers. The evidence suggests that multimarker panels may offer greater clinical value than any single biomarker alone. Among the candidates demonstrating relatively strong evidence were TNF-α, IL-1β, IL-6, IL-8, lactate dehydrogenase (LDH), and matrix metalloproteinase-9 (MMP-9). An estimated 59,660 Americans were diagnosed with oral cancer in 2025, with approximately 12,770 deaths. Overall five-year relative survival for oral cancer was approximately 69.5% in the most recent 2015–2021 SEER data, while outcomes are substantially better when disease is diagnosed at a localized stage. These numbers explain why a noninvasive tool that can identify cancer-associated molecular changes has enormous appeal.

Beyond the Mouth and Into Systemic Diseases

The systemic implications are particularly intriguing for dentistry.

• Diabetes is one of the conditions most frequently investigated in salivary biomarker research because alterations in glucose metabolism can be reflected in saliva. Earlier meta-analytic evidence demonstrated higher salivary glucose concentrations among individuals with type 2 diabetes and a significant relationship between salivary glucose, blood glucose, and HbA1c.
• Neurodegenerative Disease: Researchers have examined salivary amyloid-beta, tau proteins, lactoferrin, acetylcholinesterase, and other molecular signals associated with neurodegeneration. A 2026 systematic review incorporating 30 studies found significant alterations in salivary beta-amyloid 42 and phosphorylated tau among patients with Alzheimer's disease, while total tau and lactoferrin showed borderline decreases.

Turning Biomarkers into Clinical Decisions

The greatest barrier to widespread adoption may not be technology. It may be clinical standardization. The ADA summit emphasized several requirements before salivary diagnostics can become routine:

• Standardized saliva collection and processing protocols.
• Clearly defined reference ranges and clinical cutoffs.
• Large, prospective, multicenter validation studies.
• Demonstrated sensitivity and specificity.
• Evidence that testing improves clinical outcomes.
• Defined pathways for interpreting abnormal results.
• Regulatory approval for specific intended uses.
• Integration with, not replacement of clinical examination.

The Future Is Likely to Be Multimodal

The most realistic future for salivary diagnostics is not a dental appointment in which a saliva test produces a definitive diagnosis for every disease. Instead, saliva is more likely to become one component of a multimodal diagnostic framework, including clinical examination, radiography, periodontal measurements, medical history, microbiological assessment, imaging, and salivary biomarkers. Salivary diagnostics could add another layer: molecular information about what is happening biologically before, during, and after visible disease.

The ADA summit therefore represents more than a discussion of emerging technology. It signals a broader shift toward precision dentistry, where prevention and treatment decisions may increasingly be informed by measurable biological signals rather than clinical appearance alone.

If you're further interested in this topic, DOCS Education and Dr. Thomas Larkin present Salivary Diagnostics in Dentistry – an insightful course demonstrating why it’s time to pivot from the restorative model of dentistry to more preventative protocols.

The course takes a deeper look at the pathway to helping patients become more independently healthy. Participants can earn 1.5 CE credits upon completion.

Author: Ayesha Khan, MBA, is a registered physician, former research fellow, and award-winning author. With a wide range of articles published in renowned newspapers and scientific journals, she covers topics such as nutrition, wellness, supplements, medical research, and alternative medicine. Currently serving as the Vice President of Social Communications and Strategy at Renaissance, Ayesha brings her expertise and strategic mindset to drive impactful initiatives. Follow her blog for insightful content on healthcare advancements and empower yourself with knowledge.

References:

1. International Association for Dental Research. (2026). Position and policy statement on salivary biology and diagnostics.
2. Moraes, S. M., Ferrari, C. R., & Buzalaf, M. A. R. (2026). Salivary biomarkers in oral diseases: From caries to cancer—Advances, challenges, and future directions. Advances in Clinical Chemistry, 132, 57–124.
3. Priyadarsini, S. S., Kumar, P. G. N., Khairnar, M. R., Akram, Z., Ghodela, R., Jadhav, S. K., & Shukla, N. (2025). Salivary alpha amylase as a diagnostic biomarker for dental caries: A systematic review and meta-analysis. Archives of Oral Biology, 170, 106136.
4. Domokos, Z., Simon, F., Uhrin, E., Szabó, B., Váncsa, S., Hegyi, P., Kerémi, B., & Németh, O. (2024). Evaluating salivary MMP-8 as a biomarker for periodontal diseases: A systematic review and meta-analysis. Heliyon, 10(22), e40402.
5. Borelli, P. V., Machado, L., Carello-Collar, G., Ferreira, P. C. L., Domingues Lourenço de Lima, A. M., Bellaver, B., Pascoal, T. A., Benedet, A. L., Ashton, N. J., Zimmer, E. R., & Borelli, W. V. (2026). Diagnostic performance of salivary markers of Alzheimer's disease: A systematic review. Alzheimer's & Dementia, 22(4), e71248.
6. Beladiya, J., Mehta, D., Patel, Y., Patel, S., Parmar, D., Dholakia, S., Sheth, D., Mahalakshmi, B., Patel, C. A., & Boddu, S. H. S. (2025). Salivary protein biomarkers for the diagnosis of oral squamous cell carcinoma: A systematic review and meta-analysis. Diagnosis.
7. Deng, Q., Wong, H. M., & Peng, S. (2024). Alterations in salivary profile in individuals with dental caries and/or obesity: A systematic review and meta-analysis. Journal of Dentistry, 151, 105451.