The New Liquid Biopsy

Saliva aids in digestion, reduces the adhesion of microorganisms to the tooth surface, and buffers dietary acids within foods and drinks. Pertinent minerals are present in saliva that facilitate the demineralization/ remineralization process. Saliva is also a reliable indicator of the plasma and serum levels of myriad substances, such as hormones and medications. The study of saliva has made significant advancements in the past 20 years. The National Institute of Dental and Craniofacial Research has emphasized the need for further research into the use of saliva as a noninvasive diagnostic tool.¹

SALIVAOMICS

Salivaomics, or salivary diagnostics, focuses on the biological molecules, or biomarkers, in saliva that may be able to detect disease.² Biomarkers—which include body temperature to determine presence of fever; blood pressure to determine risk of stroke; cholesterol levels to indicate coronary and vascular disease risk; and C-reactive protein to note the presence of inflammation—play a major role in early diagnosis, disease prevention, and drug response and target identification. They are useful in detecting disease, measuring the progress of disease, and evaluating the most effective therapeutic treatment, as well as in establishing long-term susceptibility to disease or its recurrence.³

The diagnostic testing of blood, urine, perspiration, and saliva all use biomarkers. A blood chemistry panel and complete blood work are typically the most accurate source of health information. They provide a quick snapshot of overall health and measure the quality of platelets, red blood cells, and white blood cells. However, the testing of blood and serum is invasive.

Other types of diagnostic methods are used to test for specific health problems. For instance, urine is typically used to test for diabetes and kidney dysfunction because the presence of protein indicates kidney damage. Pregnancy tests use urine analysis, as it provides a noninvasive measurement of hormone levels. A sweat test that measures the amount of sodium and chloride found in perspiration is used to detect cystic fibrosis, as these substances are highly elevated among individuals with this genetic disorder.⁴ 

SALIVARY BIOMARKERS

To further the study of salivary biomarkers, David T.W. Wong, DMD, DMSc, of the University of California, Los Angeles (UCLA), created the Salivaomics Knowledge Base in 2008.⁵ It is a high-tech database that enables the submission and sharing of data that support the discovery of salivary biomarkers. It is the first database of its kind dedicated to the study of saliva and contains the information needed to explore the diagnostic potential of human saliva. This information can be used to develop health care interventions that are specific to an individual’s DNA makeup.⁵

Researchers at UCLA’s Salivaomics Knowledge Base have identified five saliva diagnostic alphabets for translational and clinical applications in the detection of systemic diseases.⁵ The diagnostic alphabets are the biomarkers that enable researchers to discover, develop, and validate biomarkers for early disease detection.² These diagnostic alphabets are proteome, transcriptomes, MicroRNA (MiRNA), metabolome, and microbiome.

Human salivary proteome analysis is important in understanding oral health and disease pathogenesis. Several US research groups have defined and cataloged 1,166 proteins in saliva. Out of these salivary proteins, five have been found to be highly discriminatory biomarkers for oral cancer, with greater than 90% clinical accuracy.^6–8 

Approximately 3,000 mRNA species have been discovered in saliva. A core amount of salivary transcriptome has been identified in healthy subjects, thereby suggesting the use of transcriptome levels for disease detection.⁹

SALIVA TESTING

Saliva testing can be used to detect many oral diseases, such as periodontitis, caries, oral cancer, and salivary gland disorders. Research demonstrates that a variation in one of the saliva alphabets may be a detector for early signs of pancreatic cancer. The use of salivary markers to detect breast, ovarian, and lung cancer, as well as diabetes, neurological disorders, tuberculosis, stroke risk, Alzheimer’s disease, cardiovascular disease, and certain autoimmune diseases is also being studied.² Additionally, new salivary biomarkers are being investigated for Sjögren syndrome.²

Currently, the most comprehensive analysis conducted of RNA molecules in human saliva reveals that saliva contains many of the same disease-revealing molecules found in blood.⁵ Saliva diagnostics, in some instances, is equivalent in accuracy to blood testing.⁵

The collection of saliva has many advantages over collecting serum and tissues. For one, it is a noninvasive procedure. Saliva samples are easy to collect and do not require the need for fasting before collection. Saliva sampling requires no special equipment for collection and reduces the number of manipulations required for biochemical analysis because it does not clot like blood. Saliva can be stored and shipped in a less complicated manner than blood and serum. The ability to treat or refer a patient immediately is a definite advantage.⁹ These benefits make saliva collection less costly, as well.

FUTURE CLINICAL APPLICATIONS FOR SALIVA

The valuable data that saliva can provide position saliva diagnostics as a convenient, noninvasive tool that allows clinicians to provide personalized care. Benefits of saliva used as a diagnostic tool include: ease of collection, eliminating the need for needle sticks, reduced cost of collection, simplicity of storing and shipping, large sample volumes, and decreased risk of percutaneous injury.¹⁰ The major roadblock to widely implementing saliva diagnostic testing is reimbursement and manufacturing.¹¹

CONCLUSION

As salivary diagnostic testing gains validation, preventive medicine can be carried out in the dental office. Dental hygienists are the most likely oral health care team members to administer such testing. Now is the time for oral health professionals to welcome salivary diagnostics into clinical practice, thereby advancing dentistry into preventive medicine and primary health care.

References

1. National Institute of Dental and Craniofacial Research. Panel on Genomics and Proteomics Of Oral, Dental and Craniofacial Diseases. Available at: nidcr.nih.gov/research/ResearchPriorities/ExpertPanelsOnScientificOpportunities/PanelOnGenomicsAndProteomics.htm?_ga=1.86526619.2026248495.1447710073. Accessed December 27, 2016.
2. Wong DT. Salivaomics. J Am Dent Assoc. 2012;143(10 Suppl):19s–24s.
3. Giannobile, WV, Wong, DT. Salivary diagnostic: oral health and beyond! J Dent Res. 2011;90:1153–1154.
4. Cystic Fibrosis Foundation. Sweat Test. Available at: cff.org/What-is-CF/Testing/Sweat-Test. Accessed December 27, 2016.
5. Jiye A, Smith B, Wong TD. Saliva ontology: an ontology-based framework for a Salivaomics Knowledge Base. BMC Bioinformatics. 2010;1:302–309.
6. Wolpert S. Treasure in Saliva May Reveal Deadly Diseases Early Enough to Treat Them, UCLA Scientists Report. Available at: newsroom.ucla.edu/ releases/treasure-in-saliva-may-reveal-deadly-diseases-early-enough-to-treat-them-ucla-scientists-report. Accessed December 27, 2016.
7. Henson B, Zents R, Wong DT. A Primer on Salivary Diagnostics. American Dental Association. Available at: ada.org/~/media/ADA/Science%20and%20 Research/Files/saliva_diagnostics.ashx. Accessed December 27, 2016.
8. Wong DT. Salivary proteomic and genomic targets for translational application. J Dent Res. 2007;86:190.
9. Suneetha K, Rambabu T. Salivaomics–a promising future in early diagnosis of dental diseases. J Dent Res. 2014;11:11–15.
10. Forsyth Center for Salivary Diagnostics. Salivary Diagnostics. Available at: forsyth.org/salivary-diagnostic. Accessed December 27, 2016.
11. Greenberg BL, Glick M, Frantsve-Hawley J, Kantor ML. Dentists’ attitudes toward chairside screening for medical conditions. J Am Dent Assoc. 2010;141:52–62.

From Dimensions of Dental Hygiene. January 2017;15(1):22-23.