By Daniel Malamud, PhD
Professor of Basic Science and Craniofacial Biology and
Director of the HIV/AIDS Research Program NYU College of Dentistry
As the role of the dentist continues to evolve, a unique opportunity exists for dental professionals to become leaders in the emerging field of oralbased diagnostics. The key to both prevention and therapy is diagnostics. Through early detection of drug abuse, infectious diseases, or environmental toxins, prevention becomes feasible and targeted, and therapy can be designed based on the identification of the lesion, the infectious agent, a metabolic disturbance, or demonstration of an abnormal growth. Diagnostic methods can also impact economics by preventing work interruptions and fostering a healthy lifestyle.
The realization that the oral cavity influences, and is influenced by, events occurring in the rest of the body has generated a great deal of interest in "oralsystemic links." Much of this attention has focused on how the oral cavity affects a wide range of systemic conditions, such as the link between periodontal diseases and preterm birth, cardiovascular diseases, stroke, and diabetes.1,2 It is also well known that systemic diseases can have profound effects on the oral cavity, for example in the cases of untreated diabetes mellitus, HIV/AIDS, malnutrition, osteoporosis, pregnancy, druginduced xerostomia and bulimia.
An equally important, but less appreciated, connection between the oral cavity and the rest of the body involves the ability to use saliva and other types of oral samples for the diagnosis of both local and systemic diseases. The mouth has served as a readily accessible window to the rest of the body dating back to the origin of medical practice, and investigators have utilized samples from the oral cavity to monitor a variety of systemic conditions. Oralbased diagnostics has evolved to include a range of approaches from merely visual inspection of the oral cavity to collecting a fluid or tissue sample and analyzing it using modern micro or nanobased technologies.
The rationale for developing an oral diagnostic platform, as compared to existing bloodbased tests, is simple. A noninvasive test is inherently more acceptable to the patient. Given a choice between providing either saliva or a blood sample, the majority of people will select the former. Salivary testing is also more economical since it does not require a trained phlebotomist and it is clearly safer in terms of potential adverse events, such as the possibility of transmitting infectious agents or infection. In addition, for special populations including pediatric, geriatric, and field studies in geographically remote areas, blood draws can be complicated when compared to the collection of an oral sample.
We are all familiar with the practice whereby a physician, a dentist or a veterinarian looks into the mouth for telltale signs of infectious disease. Here the clinician may take note of color, presence or absence of lesions, or visible signs of inflammation. One of the first and most successful oralbased diagnostic devices designed to inform about systemic health was the oral thermometer. With this device, in less than one minute the body temperature can be measured and used to monitor fever or even predict ovulation. The development and acceptance of the oral thermometer, when compared to its predecessor the rectal thermometer, suggests that once it is demonstrated that an oral test has equivalent sensitivity and specificity to a blood test, the oral test will be preferred.
While one initially thinks of saliva as the vehicle for an oral diagnostic system, there are multiple types of samples that can be obtained from the oral cavity. Table 1 summarizes the types of oral samples that have been utilized for analysis of local and systemic conditions. Some of these require specific collection devices such as paper points for gingival crevicular fluid or different bioprobes to detect oral volatile substances while others employ saliva collected in various ways. Ductal saliva (collected directly from Wharton’s or Stensen’s ducts) has played a key role in determining the origins of salivary analytes, but in general this fluid is too difficult to collect for a commercial oral diagnostic device, where a simpler type of collection (e.g. oral swab or expectorate into a tube) is preferred.
Many therapeutic and recreational drugs can be monitored via salivary sampling and a partial list of the types of molecules detected in oral samples is shown in Table 2. Oral testing has potential for both home and workplace use and commercially available salivary tests are currently used to monitor steroid hormones 3 and also systemic antibodies to bacterial and viral pathogens.4 In this latter category, the FDA approved tests for antibodies to HIV are increasingly being used in hospital settings, community health centers and anonymous testing sites in most major cities to screen for HIV+ individuals. The use of saliva or buccal swabs to collect DNA is an established technique that is used in forensics, and recently there have been several reports demonstrating the presence of messenger RNA in the "salivary transcriptome" for diagnosis of oral cancer.5
Research funding from the NIH/NIDCR supports several groups developing pointofcare devices for detection of periodontal diseases, infectious diseases, oral cancer and cardiovascular biomarkers (http://www.nidcr.nih.gov/NewsAndReports/ENewsletters/Salivary DiagnosticsGroup.htm). In addition, a wide variety of diagnostic tests using saliva and other oral samples have already been developed (Table 3). This list is certain to grow as results from the salivary proteome become available. The proteomic studies, also funded by NIDCR, are designed to identify all of the proteins produced by the parotid and submandibular salivary glands. The data from these studies will identify potential markers secreted by the major salivary glands that can be linked to specific diseases such as Sjogrens syndrome, diabetes mellitus, breast cancer, etc.
There are many reasons why oralbased testing can be considered an appropriate replacement for blood tests, and interest in this field is increasing as biotechnology companies recognize that FDA approval for oral tests is possible and that the public is interested in noninvasive alternatives to tests that require blood. That said, I want to make two observations, which strike me as curious; (1) although oral samples are the basis of these new tests, relatively few have been developed for local oral diseases. Instead, most of the studies have focused on using oral samples to detect or monitor systemic conditions; and (2) notwithstanding the fact that these tests utilize oral samples, the dental community has not yet embraced the use of oralbased diagnostics.
I propose that dental professionals seize the opportunity to become involved, and indeed take the lead, in the emerging field of oral diagnostics. Oralbased diagnostics should be part of the dental professional’s regimen because dentists, dental hygienists and dental assistants are experts in the study of the oral cavity. Their knowledge of oral anatomy, physiology, biochemistry and pathology defines them as "clinicians of the mouth." Patients expect the dental professional to know about oralbased diagnostics and generally find the collection of saliva, buccal cells, and gingival crevicular fluid or even oral volatiles an acceptable procedure. The time is now ideal for the dental community to come forward and claim the field of oral diagnostics as its domain.
- Whole Saliva (stimulated/unstimulated)
- Duct Saliva
- Gingival Crevicular Fluid
- Buccal Swabs
ANALYTES DETECTED IN ORAL SAMPLES
- Steroid Hormones
Widely used oral tests
- Oral thermometer
- HIV antibody testing
- Blood alcohol levels
- Drugs of abuse
- Steroid hormones
- Strep throat swabs
- DNA from buccal swab
- Oral and Whole Body Health, 2006. A custom publication of Scientific American Presents, Scientific American Inc, NY, NY.
- The OralSystemic Disease Connection, 2006. JADA Special Supplement 137: 1S40S
- Hibel, LC, Granger, DA, Kivlighan, KT, and Blair C. 2006. Individual differences in salivary cortisol: Association with common overthecounter and prescription medication status in infants and their mothers. Hormone Behavior 50:293300.
- Malamud, D., Bau, H., Niedbala, S. and Corstjens, P. 2005. Point detection of pathogens in oral samples. Adv Dental Res 18:1216.
- Wong, DT 2006. Salivary diagnostics for oral cancer. J Calif Dent Assoc 34:303308.