• 5/31/2005
  • Boston, MA
  • Judy Foreman
  • Boston Globe

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 this disease, which will strike more than 28,000 Americans this year and kill more than 7,000.

Within a few more years, you may be able — with a fancier spit test — to find out if you’re at risk for a number of other diseases, 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 C-reactive protein, which has been linked to an increased risk of heart disease. The chip could sound an alarm — maybe a beep, maybe an electronic message to your doctor — whenever levels of a particular protein drift too high or too low.

Until a few years ago, the technology to analyze minute quantities of genetic material and proteins in saliva was not good enough for many of the tests doctors want to do or tests consumers could do in their homes, said Dr. David Wong, associate dean of research at the UCLA School of Dentistry.

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 goldmine 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.

Researchers have long been fascinated by what can be studied in saliva, and there are already saliva-based tests on the market to detect the presence of 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.

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, tests can be developed to tell whether protein levels become abnormal, said Wong, who heads a major portion of the cataloging 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 ones suggests cancer of the mouth, tongue, larynx or pharynx — before symptoms are apparent. When these four RNA molecules are all present, 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 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 have been 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.