The role of saliva in risk assessments and disease prevention
The burgeoning science on the use of saliva for diagnostic purposes makes it difficult to keep up with what this means for clinical dental practice. This article is designed to provide background to dentists about saliva as a diagnostic aid, for both microbial challenges and chemicopharmaceutical monitoring and evaluation.
The Surgeon General's "Report on Oral Health" re-emphasized that the oral cavity is one of the most important portals into the body. As the first line of defense against many foreign pathogens and overpopulation of resident microorganisms, understanding the role of saliva can be an important adjunct in careful treatment planning. We know that saliva contains a variety of enzymes and proteins that have demonstrated antibacterial, antifungal, and/or antiviral activities. For example, certain substances in saliva — such as lysozymes, lactoferrin, peroxidase, and histatins — can directly kill or inhibit a variety of microorganisms.
The protective substances in saliva have broad-based activity and specificity. While histatins are potent antifungal agents, other salivary proteins exhibit antiviral properties. For example, secretory leukocyte protease inhibitor (SLPI) is known to have the ability to inhibit human immunodeficiency virus (HIV) from invading cells. Mucins protect the oral tissues against drying and physical and chemical irritants. The epidermal growth factor (EGF) in saliva promotes wound healing. The flow of saliva contributes to constant cleansing of soft and hard intraoral tissues. The lubricating action of saliva helps with the digestive process and protects the intraoral tissues against microbial colonization. Saliva also contributes minerals that facilitate the balance between remineralization and demineralization in the dentition.
Saliva as a screening/diagnostic aid
Within the last few years, saliva has become an important screening aid due to ease of collection, advances in laboratory microdetection methods, and discovery of new substances in saliva. Unlike blood and urine, saliva is easy to collect in a noninvasive manner. Therefore, in recent years, saliva has attracted much attention as a potential diagnostic aid for the detection of systemic diseases and response to chemotherapeutic agents. Keeping up with the literature could be a challenge. Between 1994 and 2004 alone, more than 1,586 citations in the scientific literature have focused on the diagnostic potential of oral fluids! With these advances, we are likely to see many more uses of oral fluids for diagnostic purposes for a range of conditions, including testing for common disorders and conditions such as diabetes, compliance with pharmaceutical drug therapies, and testing for illicit drug use.
Salivary flow may impact our treatment planning for the placement of new restorations and for maintenance of current oral health. A variety of exogenous and endogenous factors affect salivary flow rates. Dehydration, medical conditions, xerogenic medications, and irradiation therapy are some examples. Baseline levels of saliva have been established:
- Unstimulated whole saliva ≤0.1 gm/min and chewing stimulated whole saliva ≤0.7 gm/min (men), ≤0.5 gm/min (women) are considered abnormal, indicative of salivary gland hypofunction.
- Whole unstimulated saliva ≤0.1 ml/min is currently used as a criterion for the diagnosis of primary Sjogren's syndrome.
Various conditions and diseases may impact salivary gland function. Advancing age per se is not a major contributing factor in the onset of salivary gland hypofunction. Women may be more at risk for salivary gland hypofunction than men, because they have a higher life expectancy and are more susceptible to systemic conditions such as Sjogren's syndrome, connective tissue disorders, systemic lupus erythematous, Hashimoto's disease, type 1 diabetes, and depression that are known to be associated with salivary gland hypofunction. Polypharmacy is also common among geriatric female patients and is the most common cause of salivary gland hypofunction in this age group.
Since salivary gland hypofunction is associated with increased susceptibility to dental caries and oral fungal infection, the flow rate determination (sialometric evaluation) will help to identify patients who are at risk for these conditions.
Whole saliva can be collected under unstimulated or stimulated conditions. Patients are asked to fast for 90 minutes before the test session. For unstimulated saliva collection, saliva is collected in a graduated or preweighted test tube attached to a funnel. The collection period is usually five minutes. The patient is instructed to lean head forward, minimize orofacial movements, and allow saliva to pool in the mouth and drip over the lower lip in the test tube attached to the funnel (draining method).
For stimulated saliva collection, unflavored gum base, paraffin, or parafilm could be used as stimulants. The patient is instructed to chew on the stimuli and spit the generated saliva into the container every one minute. The rate of chewing may be self-paced or controlled by a metronome.
Microbiota and biomarkers
Saliva can be used to detect oral fungal and periodontal infections, to assess susceptibility to dental caries, and to screen for oral neoplasms. Salivary fungal colony-forming units can be used for detection of oral candidiasis. The salivary levels of pathogens such as Porphyromonas gingivalis, Streptococcus mutans, and Lactobacillus acidophilus can be utilized in risk assessments for periodontal diseases and dental caries. Elevated levels of some salivary proteins have also been associated with oral squamous cell carcinoma. The association of oral cancer with high salivary levels of nitrate and nitrite has also been reported. Salivary levels of these two factors are significantly associated with the levels of dietary intake. Salivary steroid hormones have been used to assess ovarian function and the risk for preterm labor, to evaluate child health and development, and to study mood and cognitive emotional behavior.
New diagnostic tests with saliva collection are becoming available. The Food and Drug Administration (FDA) recently approved the use of saliva-based testing for HIV rapid tests, with results within 20 minutes through easier laboratory techniques, unlike traditional testing. This is one of the best recent examples of the use of saliva as a diagnostic aid. Saliva is also used to measure the presence of antibodies or antigens in a variety of other viral pathogens, such as hepatitis C, a leading cause of liver cirrhosis; hepatitis B surface antigen; cytomegalovirus; herpes simplex viruses 6, 7, and 8; and epidemiological studies of Epstein-Barr virus in schoolchildren. Saliva has received much attention in recent years for its potential role in the diagnosis of Helicobacter pylori, the pathogen associated with peptic ulcers. Elevated levels of some salivary markers have been associated with ovarian and breast cancer. The potential value of saliva as a diagnostic aid for breast cancer detection is under evaluation by the FDA.
Chemotherapeutic and toxicologic aid
Saliva can be used for monitoring the systemic (plasma) levels of medications as well as therapeutic responses to medications. For example, saliva can be used to monitor a patient's compliance with insulin therapy, psychotherapy, and anticancer medications. It can also be used for evaluation of illicit drug use, ethanol consumption, recreational drug use, and tobacco consumption. Currently, there are FDA-approved saliva tests for the detection of cocaine, cotinine, methamphetamine, opiates, PCP, ethanol, HIV antibody, and estriol. The value of saliva as a diagnostic aid will expand during the coming years as more scholars, educators, health-care providers, and policymakers explore the fascinating world of saliva and the explosion of scientific information about saliva. Women dentists should continue to update their knowledge about this rapidly expanding topic through continuing education, reading, and news reports to determine its appropriate role in the delivery of oral health care and treatment.
For more information about saliva
- www.sjogrens.org
- www.oralcancer.org
- www.nidcr.nih.gov
- www.salivatest.com
- www.nlm.nih.gov/medlineplus
Additional resources
- Tabak LA. A revolution in biomedical assessment: the development of salivary diagnostics. J Dent Educ 2001; 65(12):1335-9.
- Kaufman K, Lamster IB. The diagnostic applications of saliva – a review. Crit Rev Oral Biol Med 2002; 13(2):197-212.
- Streckfus CF, Bigler LR. Saliva as a diagnostic fluid. Oral Diseases 2002; 8:69-76.
- Navazesh M. Methods for collecting saliva: saliva as a diagnostic fluid. Ann NY Acad Sci 1993; 694:72-77.
Mahvash Navazesh, DMD
Dr. Navazesh is an associate professor at the University of Southern California School of Dentistry. She has been chair of the Division of Diagnostic Sciences at USC since 2001. You may contact Dr. Navazesh by email at [email protected].
