Salivary diagnostics and the role of the dental hygienist.Introduction
In 1993, Irwin Mandel, DDS, authored two manuscripts concerning salivary diagnostics. (1,2) In the two articles, he describes salivary diagnostics as a "late-bloomer" in the field of diagnostics with most of the technical advances occurring in the late 20th century. He also coined the phrase, "saliva as a mirror of the body." Considering the recent advances in salivary research, his statement appears to be prophetic.
There have been significant recent advancements in the field of proteomics, an aspect of genomics that uses large-scale protein separation and identification to study protein structure and behavior within a species, and in the field of nanotechnology, a branch of engineering that deals with the use of nano-scale machines within the molecular environment. These advancements are paving the way for diagnostic tests that will be capable of rapid multi-analyte detection in both laboratory and non-laboratory settings. Technological advancements have also benefited biomarker research to the point where saliva is now recognized as an excellent diagnostic medium that can be collected simply and noninvasively. (3) These recent developments may expand the role of dental hygienists.
In a recent review of the use of saliva as research material, Schipper, et al, discussed how over the past 50 years, the pace of salivary research has accelerated with the advent of new techniques that illuminated the biochemical and physicochemical properties of saliva. The field of salivary research is rapidly advancing due to the use of novel approaches that include metabolics, genomics, proteomics and bioinformatics. (4) There are many aspects of salivary diagnostics, which cover both oral and systemic diseases in the literature. (3,4) Due to the broad scope of salivary diagnostics, this section will focus on the non-oral diagnostic use of saliva--breast cancer detection.
The real impetus for salivary diagnostics began with the "ground-breaking" work performed by Joyce Jenzano, RDH, MS, who conducted research in the Dental Research Center at the University of North Carolina, Chapel Hill. During the mid 1980s, Jenzano employed the use of saliva to detect tumors that were remote from the oral cavity. (5) This study used salivary kallikrein, an enzyme, as its marker and attempted to determine if there were significant differences between healthy individuals, individuals with benign lesions, and subjects diagnosed with breast and gastrointestinal malignancies. The results of the study demonstrated that higher levels of salivary kallikrein were observed among patients diagnosed with malignant tumors as compared with those individuals diagnosed with benign tumors and a cohort of healthy controls. Subsequent investigations determined the presence of kallikrein in both the parotid and submandibular secretions. (5-8)
With respect to cancer antigens in saliva, Di-Xia found that saliva contained CA 125, a glycoprotein complex that is a tumor marker for epithelial ovarian cancer. (9) In comparing salivary CA 125 concentrations among healthy controls, women with benign lesions and those with ovarian cancer, Di-Xia found a significantly elevated CA 125 concentration among the ovarian cancer group as compared to the nonmalignant controls. The results of the study by Di-Xia using saliva as a diagnostic fluid for ovarian cancer suggested that the salivary CA 125 assay may have a better diagnostic value than the serum assay. (9)
Epidermal growth factor levels have been reported to be present in saliva. (10) A study by Navarro reported higher epidermal growth factor concentrations in the saliva of women with primary breast cancer or recurrence of breast cancer when compared to women without disease present. (10) The highest concentrations of epidermal growth factor were found in the local recurrence subgroup, presenting an opportunity for this marker to be used in postoperative follow-up. (10)
The use of mass-spectrometry (analysis of a substance's chemical composition by sorting its gaseous ions according to their mass and charge) has come to the forefront in salivary protein analysis. (11) Recent studies have yielded salivary protein profiles in both health and disease. The alteration of the normal salivary protein profile in disease states such as breast cancer have produced biomarkers for early disease detection, which could lead to point of care breast cancer screening devices. (12) These screening devices could be even used in the dental hygiene environment.
How Do Salivary Diagnostics Relate to the Dental Hygiene Practitioner?
Using a salivary breast cancer-screening device approved by the U.S. Food and Drug Administration as an example, it becomes evident how salivary diagnostics will impact the dental hygiene profession. Dental hygienists are at the apex of the health delivery system! Thousands of individuals utilize dental hygiene services at private practices and dental clinics per year--especially women with families. Moreover, these individuals visit their attending hygienist twice a year on a routine basis. No other profession has access to the population like the dental profession! It would take billions of dollars to duplicate this existing health care infrastructure. The screening paradigm is not new, as both dentists and hygienists screen for hypertension using the sphygmomanometer. This practice has saved many lives. Collectively, it becomes apparent that if saliva develops further as a useful diagnostic tool and the hygienist can detect serious, life-threatening illnesses such as cancer earlier than the medical community, then Mandel's vision will have come true and saliva will be "More Than a Lick and a Promise."
(1.) Mandel ID: Salivary diagnosis: promises, promises. Ann NY Acad Sci. 1993a; 694: 1-10.
(2.) Mandel ID: Salivary diagnosis: more than a lick and a promise. J Am Dent Assoc. 1993; 124: 85-7.
(3.) Nunn PJ: Saliva: you might be surprised what it can do. Access 2005; 2(19): 16-22.
(4.) Schipper R, Loof A, De Groot J, et al. SELDI-TOF-MS of saliva: methodology and pre-treatment effects. J Chromatogr B. 2007; 847: 46-53.
(5.) Jenzano JW, Courts NF, Timko DA, Lundblad RL (1986a). Levels of glandular kallikrein in whole saliva obtained from patients with solid tumors remote from the oral cavity. J Dent Res. 1986a; 65(1): 67-70.
(6.) Jenzano JW, Daniel PA, Kent RT et al. Evaluation of kallikrein in human parotid and submandibular saliva. Arch Oral Biol. 1986b; 31(9): 627-628.
(7.) Jenzano JW, Coffey JC, Heizer WD, et al. The assay of glandular kallikrein and prekallikrein human mixed saliva. Arch Oral Biol. 1988; 33(9): 641-644.
(8.) Jenzano JW, Brown CK, Mauriello SM. Temporal variations of glandular kallikrein, protein and amylase in mixed human saliva. Arch Oral Biol. 1987;32(10): 757-59.
(9.) Chien DX, Schwartz PE. CA 125 assays for detecting malignant ovarian tumors. Obstet Gynecol. 1990; 75: 701-704.
(10.) Navarro MA, Mesia R, Diez-Gibert O, et al. Epidermal growth factor in plasma and saliva of patients with active breast cancer and breast cancer patients in follow-up compared with healthy women. Breast Can Res Treat. 1997; 42: 83-6.
(11.) Streckfus CF, Dubinsky W. Proteomic analysis of saliva for cancer diagnosis. Expert Rev. Proteomics. 2007, 4(3): 329-32.
(12.) Streckfus CF, Mayorga-Wark O, Daniel Arreola D, et al. Breast cancer related proteins are present in saliva and are modulated secondary to ductal carcinoma in situ of the breast. Can Invest. 2008; 26(2): 159-67.
(13.) Lingen MW: Point of care salivary diagnostics for systemic disease screening: if someone builds it, will dentistry come? Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009; 1-2.
Charles F. Streckfus, DDS, MA, FAAOM, FAGD, is currently a professor in the Department of Diagnostic Sciences, a Fellow of the Academy of Oral Medicine and a Fellow of the American Academy of Dentistry. He has published numerous peer-reviewed journal articles and has been invited to speak at many national and international conferences. He has received many honors and awards, including the National Institutes for Dental Research: Merit Award and the prestigious President's Award for Scientific Excellence, Presented by the International Society for Preventive Oncology, 6th International Symposium Predictive Oncology Intervention Strategies, Pasteur Institute, Paris France, February 12, 2002.