Putting saliva to the test to ward off disease


Within two years, you may be able to go for a regular dental visit, spit into a cup and before your appointment is over, find out from an analysis of your saliva whether you're at risk for oral cancer.

Currently, dentists have to do a thorough mouth exam to probe for oral cancer, which will strike more than 28,000 Americans a year and kill more than 7,000.

Within a few more years, a fancier spit test may determine whether you're at risk for a number of other diseases as well, including breast cancer, Type 2 diabetes, ovarian cancer, Alzheimer's disease and rheumatoid arthritis.

If you're among the avant garde, you might even have a tiny chip implanted in your cheek to monitor proteins in saliva such as CRP, a protein that is often linked to an increased risk of heart disease. With constant monitoring, the chip could sound an alarm -- maybe a beep, maybe an electronic message to your doctor -- whenever levels of a particular protein are too high or too low.

Until a few years ago, the technology to analyze minute quantities of genetic material and proteins in saliva was simply not good enough for many of the tests doctors want to do or tests consumers could do in the privacy of their own homes, said Dr. David Wong, associate dean of research at the UCLA School of Dentistry and co-director of head and neck cancer research program at the Jonsson Cancer Center at UCLA.

In the brave new world of genomics and proteomics -- the study of genes and the proteins they make -- the best body fluid to analyze disease risk may soon be saliva, not blood. Saliva, the slippery fluid that helps moisten and digest food, is a medical gold mine because it is almost identical to the clear part of blood, but with everything, including infectious organisms, present in weaker concentrations.

Saliva testing is less invasive, less painful, less likely to cause infection and potentially cheaper than blood testing because there's no need for a phlebotomist to draw blood. And because it's so easy to test saliva repeatedly during the day, doctors believe they will be able to use saliva-based tests to keep track of real-time physiological changes such as how an infection is responding to antibiotics.

The idea of using saliva for detection is not new. Among ancient peoples, legend has it that saliva was used as a primitive lie-detector test. A person accused of wrongdoing would be given a handful of rice and told to swallow it; if he couldn't, it meant he was dry-mouthed, nervous and guilty.

Medically, researchers have long been fascinated by what can be studied in saliva: There are already saliva-based tests on the market to detect the AIDS virus, alcohol, illicit drugs, the influenza virus, hormones that signal premature labor or ovulation, as well as levels of testosterone, estrogen or the stress hormone, cortisol. Some tests and saliva-collection kits are approved for home use, though many others are not.

"As a screening test, the beauty of saliva is the ease with which the sample can be obtained," said Dr. Stephen Sonis, chief of oral medicine at the Dana-Farber Cancer Institute and senior surgeon at Brigham and Women's Hospital in Boston.

To encourage development of salivary tests, the National Center for Dental and Craniofacial Research has earmarked $64 million, said Larry Tabak, the center's director.

The institute is putting an additional $15 million into a totally new idea: compiling a complete catalog of all the proteins in saliva, called the Salivary Proteome Program. By knowing normal levels, doctors -- and consumers -- will be able to tell if protein levels become abnormal, said Wong of UCLA, who heads a major portion of the cataloguing effort.

In a small study reported late last year, Wong's team discovered that, out of about 3,000 distinct bits of genetic material called RNA in saliva, the presence of four particular types suggests cancer of the mouth, tongue, larynx or pharynx -- before symptoms are apparent.

When these four RNA molecules are all present in saliva, there's a 91 percent chance that the person has oral cancer, said Wong, though it's not clear yet whether these bits of RNA are detectable because their corresponding genes are activated or whether they are simply a sign of the body's inflammatory response to the cancer.

In April, Dr. Joseph Califano, associate professor of head and neck surgery at the Johns Hopkins Medical Institutions, reported on a study looking at saliva samples from 94 people with oral cancer and 656 healthy volunteers. Increases in another type of genetic material, mitochondrial DNA, are a reliable marker for head and neck cancer, he said. An increase in mitochondrial DNA in saliva is also associated with smoking, he said, even if the person stopped smoking 20 years earlier.

A routine screening test for oral cancer using saliva "is the future," Califano said, once the kinks are worked out. But "even if you caught only 60 percent of the people with cancer, that would help because this cancer has a 50 percent mortality rate."

Other researchers have already shown that proteins such as her-2-neu and ca-125 -- linked, respectively, to breast and ovarian cancer -- can be detected in saliva, suggesting that a screening test for these cancers could also be developed.

Even a person's risk for depression and substance abuse and his or her chance of responding to antidepressant medications may be amenable to saliva testing, said Dr. Charles Glatt, a psychiatrist, geneticist and neuroscientist at UCLA.

Currently, researchers are trying to determine whether saliva DNA testing can accurately assess how well a person's brain controls levels of serotonin, an important neurotransmitter linked to depression.

Not all diseases are yielding easily to saliva detection, though. It would be a huge boon if diabetics, for instance, could monitor their saliva instead of their blood for sugar levels. But so far, saliva-based sugar tests have not worked, said Wong, who remains hopeful that other markers in saliva may yet be used to diagnose Type 2 diabetes.

At the very least, these and other new studies constitute a "proof of principle" that, with ever-improving detection technology, saliva may become the diagnostic fluid of the future.

Judy Foreman's column appears every other week. Past columns are available on www.myhealthsense.com.

Copyright © 2019, The Baltimore Sun, a Baltimore Sun Media Group publication | Place an Ad