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Boston---Scientists at the Forsyth Institute have found that three bacterial species are associated with the most common form of oral cancer—a discovery the researchers hope will lead to a simple diagnostic test for the often-fatal disease.

The findings also open the question of whether bacteria might, in some way, play a causal role.

The current discovery, reported in the July 7 Journal of Translational Medicine, suggests that elevated levels of three particular bacteria in saliva indicate the presence of oral squamous cell carcinoma (OSCC)—one of the deadliest of cancers because it often goes undetected in its early stages.

"Finding bacteria associated with OSCC encourages us to hope that we have discovered an early diagnostic marker for the disease," said Donna Mager, DDS, PhD., Assistant Member of the Staff in the Department of Periodontology and Molecular Genetics and the principal investigator. "If future studies bear this out, it may be possible to save lives by conducting large-scale screenings using saliva samples."

The Forsyth scientists posit that oral cancer may change the oral ecology, thus allowing certain bacteria to colonize more rapidly than others.

However, according to J. Max Goodson, DDS, PhD., Director of Clinical Research at Forsyth and a co-author of the study, "We cannot rule out the possibly that the bacteria themselves may be causally involved in the development of the disease." (Other bacteria, such as H. pylori, for example, have been implicated in augmenting the development of certain cancers).

The Forsyth approach, which focuses on testing saliva for particular bacteria, differs from --and could complement-- another recently reported approach in which saliva would be monitored for evidence of altered genetic activity in oral tissues.

The current paper, "The Salivary Microbiota as a Diagnostic Indicator of Oral Cancer," reports on a study, begun in 2000, in which the scientists compared bacterial samples from the saliva of 229 healthy subjects with samples from 45 patients who had been diagnosed with oral cancer. The team found elevated levels of three bacterial species (C. gingivalis, P. melaninogenica and S. mitis) in oral cancer patients. The scientists obtained similar findings when they controlled for gender, age, and smoking history.

According to Mager, "Those results led us to hypothesize that the three species could serve as diagnostic indicators for OSCC. And, in fact, we found that elevated salivary counts of the three bacteria correctly identified 80% of individuals with oral cancer and 83% of controls."

If their findings are replicated in future studies, the Forsyth team envisions a simple saliva test that could be administered by dental technicians in large screenings, mailed to a diagnostic center, and returned to doctors or dentists within several days.

The need for screening
Government statistics show that, every year, some 30 thousand US residents are diagnosed with oral cancer. Of those diagnosed, more than 90 per cent are found to have OSCC. If discovered and treated early, OSCC has a five-year survival rate of 80-to-90 percent. But 60 percent of OSCC cases are not diagnosed until the later stages and fewer than 54 per cent of individuals diagnosed in those stages live for five years—placing OSCC among the deadliest of cancers.

"Far too many people are not diagnosed until their oral cancer is in its advanced stages," Mager said. In part, that is because, in its early stages, oral cancer may be asymptomatic or mimic benign conditions, so those who have it do not seek dental or medical care. "A saliva test would be an easy, non-invasive way to diagnose or monitor patients."

Until such a test exists, Mager added, "I cannot overemphasize how important it is for every adult to be examined by a dental or medical health professional for signs of oral cancer at least once a year." Although oral cancer is primarily a disease of adults over the age of 40, younger adults are also at risk--especially if they chew spit tobacco or smoke and also consume alcohol. Individuals with no known risk factors may also develop oral cancer. "Therefore, all adults should be examined every year," Mager said.

Forsyth/Oral Cancer

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Future research
The scientists plan future research to reproduce their results and to evaluate how well saliva tests predict the progression of pre-cancerous conditions toward oral cancer. The team also seeks to study the relationship of oral bacteria to a variety of cancers and diseases.

According to Goodson, "This research is important for the questions it raises. Do oral bacteria contribute to oral cancer? Can oral bacteria be used as indicators of disease? As we address these questions, we will begin to understand the nature of interactions between man and the bacteria we live with."

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