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J Am Dent Assoc, Vol 137, No 3, 284-286.
© 2006 American Dental Association |
COMMENTARY |
The future is now
After many years of predicting that saliva might replace blood and thus provide a noninvasive diagnostic matrix, it appears that the future is now. Point-of-care (POC) diagnostics is the holy grail for health care in the 21st century. Coupling this with methods being developed in nanotechnology, we are about to realize portable devices that can diagnose a wide variety of disease conditions on site using an oral sample.
As health care providers attempt to create new approaches to handle increased patient loads with decreased resources, the ability to diagnose a condition on site and make clinical decisions before a patient leaves the office is an attractive goal. Within the discipline of POC diagnostics, the use of saliva and other oral samples (buccal swabs, gingival crevicular fluid, volatiles) as the source of biomarkers is particularly appealing since their collection is relatively noninvasive and well-tolerated by the patient. The high profile of the field is reflected by a number of upcoming conferences on this topic, including a workshop sponsored by the National Institutes of Health and the National Science Foundation on "Improving Health Care Accessibility Through Point-of-Care Technologies" (Arlington, Va., April 11–12), "Oral-Based Diagnostics" sponsored by the New York Academy of Sciences (Lake Lanier, Ga., Oct. 10–13), and "Salivary Diagnostics" sponsored by the American Dental Association (Las Vegas, Oct. 17).
Articles in this issue by Wong1 and by Miller and colleagues2 demonstrate two different applications of salivary testing, looking at systemic disease. These articles focus on how new technologies can amplify the signals present in oral samples so that new diagnostic tests can reliably confirm the presence of clinical disease and, it is hoped, help clinicians diagnose it at an earlier stage than is currently possible. By combining emerging techniques for POC testing with a noninvasive fluid such as saliva, one can envision a major paradigm shift in the rapid diagnosis of both oral and systemic diseases.
Dr. Miller has shown that one can simultaneously detect multiple periodontitis markers so that inflammation, collagen degradation and bone turnover can be analyzed together. Another project being carried out by Dr. Anup Singh (Sandia National Laboratories, Albuquerque, N.M.) and Dr. William Giannobile (University of Michigan, Ann Arbor) involves the development of a self-contained saliva test kit that can detect periodontal markers at the point of care.
Studies by Dr. Wong’s group at the University of California Los Angeles (UCLA) have identified messenger RNA markers in the saliva of patients that are correlated with oral cancer. Along with colleagues in the UCLA School of Engineering (led by Dr. Chih-Ming Ho), Dr. Wong is developing a real-time system for detecting these tumor markers and other salivary analytes.
As Dr. Wong points out, the National Institute of Dental and Craniofacial Research (NIDCR) has spearheaded this renewed interest in salivary diagnostics by funding seven research groups in a program whose aim is the development and validation of technologies for saliva-based diagnostics and three research groups under a second program pertaining to the salivary proteome, which is designed to create a compilation of all of the proteins present in saliva. This latter program, in addition to creating a catalog of salivary proteins, is likely to identify potential biomarkers of local and systemic diseases. Groups funded under the salivary diagnostic program are listed on a Web site at the University of Washington, Seattle ("http://nidcr.bioeng.washington.edu/index.html"), and the groups funded by NIDCR to catalog the human salivary proteome can be found at their individual Web sites (University of California, Los Angeles, Dr. David Wong; University of California, San Francisco, Dr. Susan Fisher; Scripps Research Institute, Dr. John Yates). The diagnostic devices that are being developed will target periodontal diseases, caries, infectious diseases, cancer, renal diseases, steroid hormones and inflammatory markers for cardiovascular and pulmonary diseases. The technologies being developed also will be effective for tracking new, as-yet unidentified biomarkers discovered in the three proteome projects.
While progress in the development of oral-based diagnostics has been remarkable, many significant challenges remain. The translation of basic research from the bench to the marketplace is expensive and requires clinical studies to validate the tests and compare them with existing blood-based tests. To date, the funding in this area has come largely from NIDCR and has attracted interest from small biotechnology companies. However, large pharmaceutical companies that have the funding necessary to get these products through regulatory approval have remained on the sidelines, presumably waiting for proof-of-concept and preliminary clinical data. In the case of Dr. Wong’s research on oral cancer, these studies are beginning to appear. His finding that expression of four mRNAs present in saliva can predict if that sample came from a control subject or a patient with cancer suggests that an oral POC diagnostic for cancer is indeed feasible. However, there are several issues that still need to be addressed, including the following:
One can make the argument that since the tests are based on saliva, they belong in the domain of the dental community. However, it is not clear that the dental community will embrace these tests, particularly when they are applied to the monitoring of systemic diseases as opposed to oral conditions. While the future is now, how this will play out in the marketplace remains to be determined.
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  M. Glick Sialology, and who owns saliva anyway? J Am Dent Assoc, March 1, 2006; 137(3): 282 - 283. [Full Text] [PDF]
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