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Overview 

This month, several news reports have featured promising research in salivary diagnostics that could hold potential for future point-of-care applications for detecting cancer and other systemic diseases. First, researchers from Johns Hopkins University (JHU) reported preliminary success using a salivary rinse to collect cellular samples and measure alterations in a panel of 21 hypermethylated genes associated with head and neck squamous cell carcinoma. The exploratory study, published in the journal Clinical Cancer Research,1 received press coverage from MedPageToday,2 Reuters Health,3 and the Baltimore Sun.4

The JHU scientists gathered saliva samples from over 200 individuals with head and neck cancer (plus 527 healthy controls) and analyzed the samples for hypermethylated genes, or chemical changes to DNA. After gentle exfoliative brushing of oral soft tissues, study participants were asked to rinse and gargle with saline solution to provide samples of epithelial cells, which the JHU researchers evaluated in tandem with samples of serum and tissue from head and neck tumors.

Overall, the authors identified a panel of eight genes as having the best predictive potential in distinguishing salivary rinses from head and neck cancer patients and healthy controls. They also found that combinations of three or four genes were more accurate in detecting (or excluding) the presence of head and neck cancer than individual genetic markers. On the other hand, the authors reported a range of false-positive readings among non-cancer (control) patients, and that some combination panels showed high specificity but low sensitivity, making them less suitable for population-based screening programs. The JHU research team is pursuing further study to develop refined biomarker panels for head and neck cancer screening, especially for individuals at higher risk (e.g., smokers) and previous head and neck cancer patients, who are at increased risk for tumor recurrence or development of other cancers.

Another widely promoted study, from the University of Texas-Houston, identified 49 salivary proteins that were found to be differentially expressed in breast cancer patients. The study appeared in the January 2008 issue of Cancer Investigation,5 and received coverage from MedicalNewsToday6 and other news groups.

The UT-Houston researchers evaluated whole saliva specimens from three groups of patients: healthy women, women diagnosed with benign breast tumors, and women with ductal carcinoma in situ. After analyzing the pooled saliva specimens, the authors found 49 salivary proteins that differentiated women with breast cancer from healthy patients and women with benign breast tumors. While encouraged by their findings, the UT-Houston researchers evaluated small patient cohorts (10 subjects in each pool), and concluded that “further study is required to determine the sensitivity and specificity of these proteins with respect to their diagnostic utility.” Their research, however, does add to a growing body of evidence that salivary protein by-products could serve as useful biomarkers for detecting disease in remote areas of the body.

Finally, the New York Times,7 Time Magazine,8 and WebMD9 covered a study published in the New England Journal of Medicine,10 which found that gene variants in five chromosomal regions can help predict levels of prostate cancer risk, especially for men with a family history of the disease. In the study, scientists from Wake Forest University, Johns Hopkins, and the Karolinska Institute in Stockholm evaluated 16 single-nucleotide polymorphisms (SNPs) in DNA samples from nearly 2,900 Swedish men with prostate cancer. After comparing samples from cancer cases and healthy controls, they found that men with 5 of the SNPs, plus family history of the disease, accounted for almost half of the prostate cancer cases in the study population. In all, men who had all 5 SNPs and a family history of prostate cancer were 9.5 times more likely to have the disease. The authors called their study a “first step toward defining a genetic association with prostate cancer,” and said the findings require independent validation in other study populations.

It should be noted that the NEJM study only used DNA derived from blood, not from saliva, as reported by several news agencies. Nevertheless, DNA and numerous protein components can appear in human saliva, although in lower amounts than in blood or serum. “Science in the News” will closely monitor ongoing research on prostate cancer screening tests, particularly applications that use saliva as a diagnostic fluid.

The new studies underscore the importance of ongoing research in salivary diagnostics and the need for enhanced early detection tests as an essential step toward saving cancer patients’ lives. With expanded research and validation of candidate salivary biomarkers for disease detection, there will be greater potential to develop faster, oral-fluid-based diagnostic tools for use in clinical practice. For additional information in this promising area of research, visit the following “Science in the News” features at ADA.org: 

Footnotes 

1. Carvalho AL et al. Evaluation of promoter hypermethylation detection in body fluids as a screening/diagnosis tool for head and neck squamous cell carcinoma. Clinical Cancer Research 14, 97-107, January 1, 2008. Abstract available at: http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=18172258. Accessed January 22, 2008.

2. Smith M. Gargling could help detect cancer. MedicalNewsToday, January 2, 2008. Available at: http://www.medpagetoday.com/HematologyOncology/ OtherCancers/tb1/7810. Accessed January 23, 2008.

3. Dunham W. Mouth rinse can detect for head and neck cancers. Reuters Health, January 2, 2008. Available at: http://www.nlm.nih.gov/medlineplus/news/fullstory_59572.html. Accessed January 23, 2008.

4. O’Brien D. Salivary salvation. Baltimore Sun, January 17, 2008. Available at: www.baltimoresun.com/news/health/bal-to.hs.saliva17jan17,0,7824228.story. Accessed January 23, 2008.

5. Streckfus CF, Mayorga-Wark O, Arreola D, Edwards C, Bigler L, Dubinsky WP. Breast cancer related proteins are present in saliva and are modulated secondary to ductal carcinoma in situ of the breast. Cancer Investigation 10 January 2008. Epub ahead of print. Abstract available at:  http://www.informaworld.com/smpp/ content~content=a789439485~db=all~order=pubdate.
Accessed January 22, 2008.

6. Abnormal proteins in saliva identify breast cancer, benign tumor cells, study finds. MedicalNewsToday, January 15, 2008. Available at: http://www.medicalnewstoday.com/articles/93956.php. Accessed January 22, 2008.

7. Kolata G. $300 to learn risk of prostate cancer. The New York Times, January 17, 2008. Available at:
http://www.nytimes.com/2008/01/17/health/17cancer.html?_r=1&scp=1&sq=prostate&st=nyt&oref=slogin”?. Accessed January 25, 2008.

8. Mahr K. Genes increase prostate cancer risk. Time Magazine, January 16, 2008. Available at: http://www.time.com/time/health/article/0,8599,1704160,00.html?imw=Y. Accessed January 25, 2008.

9. Hitti M. Prostate cancer gene test coming soon. WebMD, January 16, 2008. Available at: http://www.webmd.com/prostate-cancer/news/20080116/prostate-cancer-gene-test-coming-soon. Accessed January 25, 2008.

10. Zheng SL et al. Cumulative association of five genetic variants with prostate cancer. N Engl J Med. 2008 Jan 16; [Epub ahead of print]. Available at: http://content.nejm.org/cgi/content/abstract/NEJMoa075819?resourcetype=HWCIT. Accessed January 23, 2008. 

Additional Resources 

Science in the News is a service by the American Dental Association (ADA) to present current information about science topics in the news. The ADA is a professional association of dentists committed to the public's oral health, ethics, science and professional advancement; leading a unified profession through initiatives in advocacy, education, research and the development of standards. As a science-based organization, the ADA's evaluation of the scientific evidence may change as more information becomes available. Your thoughts would be greatly appreciated.

Document Posted January 2008