Spit Test

By Dan Gordon

Published Oct 1, 2006 12:00 AM

Spit gets a bad rap. We can't live without it — the liter of saliva we produce each day enables us to talk and eat, yet spit remains underappreciated. Discharging one's saliva in public is considered rude, aiming the juice at another person the ultimate insult.

But what if you could find out if you have certain types of cancer or other diseases — early enough to cure them, and within a day, maybe even less — just by spitting into a cup? Would we feel differently about spit? Could it even become... cool?

Probably. And researchers at the UCLA School of Dentistry are working to make that happen. This month, their breakthrough research into diagnosing oral cancer through a simple spit test will be presented at the American Dental Association's annual convention in Las Vegas. In fact, dentists in attendance there will be able to take their own spit test.

Most oral cancers aren't diagnosed until a patient, or their dentist, actually sees something wrong. But the School of Dentistry's advance is a simple saliva test that detects oral cancer at its earliest stage, before symptoms develop. In pilot studies, the test has been given to 100 oral cancer patients and 100 healthy people, correctly identifying oral cancer 82 percent of the time. (By comparison, the blood test currently used widely for the diagnosis of prostate cancer is approximately 70 percent accurate.) The saliva test will be studied in a larger, multicenter clinical trial beginning later this year; if successful, it could soon become a routine part of dental practices. Saliva is easy to collect and poses none of the risks, fears or invasiveness of blood tests, allowing patients to avoid a needle prick.

Oral cancer will be diagnosed this year in approximately 30,000 Americans, only half of whom will survive more than five years. But if the cancer is detected early, there is an 80–90 percent chance of survival.

"Oral cancer is a debilitating disease that, when not deadly, can result in profound facial disfigurement, speech impairment, and an inability to eat normally," says David T. Wong, the dental school's associate dean of research and a member of UCLA's Jonsson Cancer Center, who is leading the effort. "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 to aid in avoiding such outcomes."

But there's more at stake here. The dental school's diagnostics breakthrough is a telling demonstration of how dental practitioners are increasingly working more closely with patients and their M.D.s. The initial foray into salivary diagnostics carries the promise of a new era in which a wide range of diseases — such as breast cancer and type 2 diabetes — might be found simply, cheaply and more quickly, saving lives. "Being able to detect disease before clinical symptoms is seen as the Holy Grail in many areas of medicine," Wong says. "The ability to do so using noninvasive means is still a quest."

Scientists have long recognized that saliva contains the full complement of proteins, hormones, antibodies and other molecular substances frequently measured in standard blood tests to monitor health and disease, but they lacked the tools to analyze the fluid. But the advent of nanotechnology — ultra-tiny machines that read the simplest cell structure — is ushering in new ways to identify, collect, preserve and amplify genetic material and proteins, removing a big barrier to the undertaking.

In 2002, the National Institute of Dental and Craniofacial Research, part of the federal National Institutes of Health, invested $85 million in studies aimed at turning saliva diagnostic tests into a clinical reality. UCLA, one of seven institutions to receive funding, engaged in identifying the genetic changes that can be found in saliva at the outset of the disease process and developing the technology that will quickly and accurately analyze human saliva to determine whether these disease markers are present. The initiative included researchers from UCLA's Henry Samueli School of Engineering and Applied Science.

Studying saliva samples taken from oral cancer patients, Wong and colleagues identified messenger RNA biomarkers — molecules carrying genetic information in cells — that, when elevated, are predictive of the disease. They concluded that high levels of four cancer-associated messenger RNA molecules out of the 3,000 found in saliva create a signature that sets apart people with early cancers of the mouth, tongue, larynx and pharynx from healthy people.

In the test, a patient's saliva sample is measured for the four RNA biomarkers, and the result is a score that indicates within 24 hours whether the patient is at risk for oral cancer. If a larger study soon to be conducted across the country confirms the UCLA results, the oral cancer spit test will move a giant step closer to reality.

Wong and colleagues also plan to explore the potential for finding salivary biomarkers that might result in spit tests for breast and pancreatic cancers, type 2 diabetes and Alzheimer's disease. "Now that we have proved the concept that saliva can contain important clinical information for oral cancer, the next question is to see whether diseases outside the mouth can be revealed in the saliva," he says. Wong suspects that they can, citing studies that have shown that certain biomarkers move from the blood to the saliva.

Wong sees a future in which all dentists are equipped with spit detectors to diagnose diseases. "It may seem like science fiction now," he says, "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 makeup as expressed in her spittle."

The Facts About Oral Cancer

Approximately 30,000 people will be diagnosed this year with cancer of the mouth and/or part of the throat. Most oral cancers can be traced to tobacco and alcohol use.

Only half of those diagnosed with oral cancer survive five years. Because the disease spreads quickly, the key is early detection.

Early symptoms include persistent changes in the mouth or throat, such as sores, swelling or numbness, and difficulty eating or swallowing. The disease is often detected by dentists during regular visits.

Strategies to lower the risk of oral cancer include avoidance of tobacco products, drinking alcohol in moderation if at all, using lip balm that contains sunscreen, and eating the five daily servings of fruits and vegetables recommended by the National Cancer Institute.

For more information on oral cancer, visit the National Institute of Dental and Craniofacial Research's Web site at www.nidcr.nih.gov. To get inside information on healthy mouths, check out the School of Dentistry's Web site at http://uclasod.dent.ucla.edu.