UCSF Scientists Aim to Use Saliva to Detect Oral Cancers

Could scrutiny of spit save your life? Cancer researchers may soon know the answer. More than 30,000 new cases of oral cancer are diagnosed each year in the US alone, many when it's too late to prevent death. Dentists and hygienists find oral cancers during exams, but researchers at UCSF now are developing ways to detect cancers earlier - before tumors become visible to the naked eye.To do so they are examining telltale proteins in saliva. Saliva, besides helping your digestion, reflects the state of your body. It contains the same proteins found in your blood, but at much lower levels. Cancers produce proteins abnormally. Cancer researchers have wondered if these abnormalities are reflected in a measurable way in the molecular contents of saliva as well as blood. A few researchers who study oral cancer also have been intrigued by the possibility that relatively high levels of proteins and other molecules from oral cancer cells might end up in saliva. Current methods for oral cancer detection are visual.The dentist and hygienist examine the mouth. Suspicious looking bumps or patches are sampled, so that on the microscopic scale a pathologist can look for cancerous cells. These biopsies are a useful screening tool, but they are time consuming. Furthermore, cutting out tissue can be painful for the patient. Disease screening in saliva might prove to be faster, less invasive, and potentially less expensive than blood tests or biopsies, according to UCSF oral and maxillofacial surgeon Brian Schmidt, DDS, MD, PhD. Schmidt runs a research lab focused in part on molecular sleuthing in saliva. The tricky part, he says, is to reliably detect molecules of interest that may be present only in low amounts. Modified DNA Points to Cancer Risk While Schmidt and others in the lab track telltale proteins, Chi Viet, a second year dental student in Schmidt's lab, examines DNA. She has discovered that it is possible to detect a certain form of DNA in the saliva of oral cancer patients that is not present in healthy patients. Viet is looking at a specific DNA modification called methylation. Cancerous cells often have different patterns of DNA methylation in comparison to normal cells. Viet had the idea to test patterns of DNA methylation in the saliva of oral cancer patients. Viet chose five genes that often become methylated in oral cancers. She measured and compared levels of DNA methylation in these specific genes in saliva and tissue, both in healthy patients and patients with oral cancer. In cases where the genes were truly methylated in the tissue sample, Viet also detected methylation in saliva close to 80 percent of the time. That is not sensitive enough for a diagnostic test. She hopes to add more genes to this testing set to increase the detection rate to 100 percent. While Viet has not yet used this method to try to diagnose patients, these results give her hope that her test could become a useful diagnostic tool in the future. Spitting to Save Lives A successful saliva test could greatly improve oral cancer screening, according to Viet. Screening would be much easier, she says - anyone would rather spit in a cup than have a piece of their mouth cut out for a biopsy. But beyond making patients happier, a saliva test would permit earlier screening that would be especially appropriate for high risk patients - smokers, for instance. If dentists can catch oral cancer before visible tumors or lesions appear, chances are better for long-term survival. A saliva test also would be useful for early detection of oral cancers that grow back despite surgery and treatment. Oral cancer recurs in many cases, and the likelihood of survival falls when it does. Unfortunately, patients who have had tumors removed from their mouths often are more difficult to screen visually. That's because their mouths may have abnormal-looking features from previous tumors and surgeries. A saliva test for a cancer biomarker would greatly improve odds of catching recurrences before they spiral out of control, Schmidt explains. Dentists Do Research Viet's interest in DNA methylation started long before her work on oral cancer. As an undergraduate at UC Davis, she studied the enzymes responsible for DNA methylation. Although she chose to pursue a career in dentistry, her interest in research did not wane. "When I applied to dental school, I still had the mindset of continuing in research," Viet says, "I talked to some people at UCSF about DNA methylation, but to no avail, because nobody in the school was doing anything with that." Viet decided to focus on oral cancer and to come to UCSF early for a summer research project in the Schmidt lab. Once here, however, she had the idea to incorporate her knowledge of DNA methylation into a test for oral cancer. "Brian was extremely supportive of me developing that assay," she says. "We thought it was kind of a stab in the dark," Schmidt says. "But Chi was very enthusiastic about the project and it happened to work out very nicely." Viet's research presentation won first place at UCSF's School of Dentistry Research Day in 2006. She also won the 2008 American Association for Dental Research (AADR) Johnson and Johnson Oral Health Products Hatton Award, junior category, at the AADR's most recent annual meeting in March. Viet plans to continue her research in the Schmidt lab while finishing her dental training. Photo of Chi Viet/Rachel Tompa. Photo of oral cancer/Courtesy of Richard Jordan.

 

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UCSF School of Dentistry

Elevated Salivary Endothelin Levels in Oral Cancer Patients - A Pilot Study

Oral Oncology 43(1):47-41, January 2007 (Previous research by Schmidt and colleagues)