Biomarker Reliability Investigated for Salivary Oral Cancer Tests

Richard Gawel


Many researchers are investigating the use of salivary diagnostic tests to identify oral squamous cell carcinoma (OSCC), with promising results so far and screening kits already reaching commercial markets. But these tests are complicated because many potential biomarkers for OSCC also are involved in chronic inflammation.

The Texas A&M University College of Dentistry and other institutions are collaborating on a pilot study measuring the levels of 7 previously reported potential OSCC salivary mRNA biomarkers in patients with chronic periodontitis and comparing them to levels found in patients with OSCC and healthy controls.

They found that salivary S100P mRNA could be a reliable biomarker for OSCC detection regardless of the presence of chronic periodontitis. However, chronic periodontitis could significantly affect the levels of the other 6 mRNAs, negatively influencing their reliability as biomarkers for oral cancer detection.

Yi-Shing Lisa Cheng, DDS, MS, PhD, associate professor of diagnostic sciences at the Texas A&M University College of Dentistry, discussed her team’s latest research and what will come next in identifying potential biomarkers that could be used to diagnose OSCC and save lives.

Q: Why would a salivary test for OSCC be beneficial?

A: The 5-year survival rate for OSCC (63%) is still too low, especially when compared to breast cancer (89%) and prostate cancers (99%), and delayed diagnosis is believed to be the major reason for this low survival rate. Salivary biomarker tests are noninvasive, and sample collection is easy. It can and may already be an excellent approach for screening or as a diagnostic adjunct for early detection of OSCC. 

Q: The study looked at chronic periodontitis. Could other oral health issues like plaque and caries produce biomarkers that overlap with OSCC? 

A: It is known that certain pathways are involved in both inflammation and cancer. (The NF-kappa B pathway is one of the examples.) Therefore, it is not surprising to see that several so-called oral cancer salivary biomarkers are inflammatory cytokines or molecules associated with oxidative stress, and these salivary biomarkers also have changed their levels when there is oral inflammation without cancer presence. Some of them have even been used as biomarkers for monitoring inflammatory diseases. I think the real question may be if the changes of those overlapping salivary biomarkers could interfere with the detection of oral cancer or cause false positive cancer reports when the patient has only the inflammatory disease but no cancer.

Answering this question requires testing the potential oral cancer salivary biomarkers in patients who have only oral inflammatory disease but no cancer and comparing the levels of those salivary biomarkers to the levels found in oral cancer patients. This is a process called validation. To make OSCC biomarkers usable and valuable for clinical application, validation is just as important as discovering new biomarkers, and that’s what our research group has been doing.

We are not familiar with the research on salivary biomarkers for caries. For plaque-associated gum inflammation, such as gingivitis and periodontitis, we have found that at least advanced periodontitis can affect the levels of several salivary biomarkers, which can interfere with accurate detection of oral cancer if we use those biomarkers as indicators for cancer development.

Q: What is the next step of research? 

A: There have been more than 100 potential salivary biomarkers reported in the literature, and almost all of them were identified by comparing the levels found in oral cancer to those found in healthy controls who did not have any oral inflammatory disease. Therefore, they all need to be validated, especially since chronic inflammation is so common in the oral cavity. We have tested more than 20 of them, and we will continue this validating process if funding permits.

The study, “Chronic Periodontitis Can Affect the Levels of Potential Oral Cancer Salivary mRNA Biomarkers,” was published by the Journal of Periodontal Research.

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