UCLA School of Dentistry Researchers Have Standardized a Saliva-based Test for Oral Cancer, Ushering in an Era of New Possibilities for Cancer Detection

Posted on: Thursday, 03/09/2006

Researchers from the UCLA School of Dentistry are reporting for the first time that they have developed the first standardized saliva RNA test for oral cancer. Now ready for further clinical testing, this new tool for detecting cancer will provide enormous clinical value in reducing the mortality and morbidity of oral cancer patients and improving their quality of life.

Dr. Jianghua Wang, a researcher in the dentistry school, will announce the test's readiness today in Orlando, Fla., at the annual meeting of the American Association for Dental Research.

In addition, the Journal of the American Dental Association has published a feature article on UCLA's salivary diagnostics research in its March issue.

According to the National Institute of Dental and Craniofacial Research, oral cancer will be diagnosed in an estimated 30,000 Americans this year and will cause more than 8,000 deaths, killing approximately one person every hour. Oral cancer is the sixth most common cancer in men and the 14th most common cancer in women. On average, only half of those diagnosed with the disease will survive more than five years. In particular, a study published by the JointCenter for Political and Economic Studies notes that black men suffer the highest rates of oral cancer, and the lowest survival rates, of any group in the United States.

However, if the cancer is detected early, there is an 80 percent to 90 percent chance for survival, and the promise held out by salivary diagnostics is that it will become easier to diagnose oral cancer in its early stages.

"Oral cancer is a debilitating disease that, when not deadly, can result in profound facial disfigurement, speech impairment, and an inability to eat normally," said Dr. David Wong, the associate dean of research and a professor in the division of oral biology and medicine at the UCLA School of Dentistry, director of the UCLA Dental Research Institute, and a member of UCLA's Jonsson Cancer Center. "Our motivation in investigating the saliva signature for oral cancer was to create a simple yet highly accurate way to detect this disease early enough in its progression to aid in avoiding such outcomes."

Traditionally, cancer researchers have used blood serum and urine to detect cancer signatures. Saliva contains the same biomarkers as those found in blood, but until recently scientists lacked the tools that would allow them to analyze the fluid. The advent of nanotechnology enabled scientists to uncover the components of saliva, including the distinct messenger ribonucleic acids (RNAs) that serve as oral cancer signatures, on an atomic or molecular scale.

To create the saliva-based test for oral cancer, UCLA School of Dentistry scientists first identified seven RNAs — molecules that carry information in cells — that when found in saliva are very useful for oral cancer detection. Analyzing saliva for the presence of four statistically significant oral cancer biomarkers, the saliva RNA test for oral cancer has been tested in 100 oral cancer patients and 100 healthy people and has proved highly successful in detecting oral cancer with an overall accuracy rate of 82 percent. As a basis for comparison, the prostate specific antigen blood test currently in wide use for the diagnosis of prostrate cancer is about 70 percent accurate.

The standardized saliva-based test for oral cancer detection developed at the school now can be used anywhere in the world to reliably generate comparable data across clinical sites. As the test is still in its research phase, it should be administered by health care providers such as physicians and dentists in clinical offices, hospitals or reference labs. In the coming months, researchers hope to engage in a national multi-center study of the test in association with the National Cancer Institute.

Dr. No-Hee Park, dean of the UCLA School of Dentistry, acknowledged the wide implications of the test.

"The test developed by Dr. Wong and his colleagues breaks new ground in the area of cancer diagnostics and is a strong example of the type of highly relevant translational science that emanates from the field of dentistry today," Park said.

Key advantages of the saliva-based test for oral cancer are that it does not require the use of needles and is simple to perform. A patient gives a sample of saliva — about 0.5 ml of which is required for testing — which is stabilized with a preservative. Using polymerase chain reaction technology, a scientist measures the levels of four messenger RNA biomarkers and then analyzes the quantitative outcome according to an algorithm designed to yield a score which indicates whether the patient is at risk for oral cancer. The test takes 24 hours to perform.

"The saliva-based test for oral cancer meets the pressing need for a quick, inexpensive, non-invasive and convenient diagnostic tool," Wong said.

The development of the saliva-based test for oral cancer marks the first step toward perfecting salivary diagnostics for a wide range of diseases including breast cancer and type II diabetes. The results of Dr. Wong's research also indicate areas for further scientific inquiry including the question of whether saliva may also serve as a prognostic tool to guide treatment plans.

"It may seem like science fiction now," Wong said, "But one day we may be able to use saliva to tell us not only that an individual has cancer, but the best way to treat that person according to her genetic make-up as expressed in her spittle. Our research is still in its infancy and I suspect there is a world of clues hidden in saliva waiting to be discovered."

In partnership with a German company, Qiagen GmbH, researchers have identified the ideal preservative and stabilizer for RNA in saliva.  Called "RNA Saliva Protect," the product is used in the saliva-based test. As yet, there is not a commercial partner producing the test itself.

The research leading to the development of the saliva-based RNA test for oral cancer was funded by the National Institute of Dental and Craniofacial Research and UCLA's JonssonCancer Center.

The UCLA School of Dentistry is dedicated to improving the oral health of the people ofCalifornia, the nation and the world, and has established an international reputation for its teaching, research and public service initiatives. The school provides education and training programs that develop leaders in dental education, research, the profession and the community; conducts research programs that generate new knowledge, promote oral health, and investigate the cause, prevention, diagnosis and treatment of oral disease; and delivers patient-centered oral health care to the community and state. Created in 1964, the school graduated its first class in 1968.