DNA shed from head and neck tumors detected in blood and saliva

A proof of principle study successfully identified tumor DNA shed into the blood and saliva of 93 patients with head and neck cancer. A report on the findings was published in Science Translational Medicine (2015; doi:10.1126/scitranslmed.aaa8507).

"We have shown that tumor DNA in the blood or saliva can successfully be measured for these cancers," said Nishant Agrawal, MD, associate professor of otolaryngology and oncology at the Johns Hopkins University School of Medicine in Baltimore, MD.

"In our study, testing saliva seemed to be the best way to detect cancers in the oral cavity, and blood tests appeared to find more cancers in the larynx, hypopharynx, and oropharynx. However, combining blood and saliva tests may offer the best chance of finding cancer in any of those regions."

Dr. Agrawal explained that inborn genetic predispositions for most head and neck cancers are rare, but other mutations that do not generally occur in normal cells have long been considered good targets for screening tests.

In the case of head and neck cancers associated with HPV, which are tumors that are on the rise among Americans, Dr. Agrawal and his colleagues searched patients' blood and saliva samples for certain tumor-promoting, HPV-related DNA. For non-HPV-related cancers, which account for the worldwide majority of head and neck tumors, they looked for mutations in cancer-related genes that included TP53, PIK3CA, CDKN2A, FBXW7, HRAS, and NRAS.

The major risk factors for head and neck cancers are alcohol, tobacco (including chewing tobacco), and HPV infection.

For the study, 93 patients with newly diagnosed and recurrent head and neck cancer gave saliva samples, and 47 of them also donated blood samples before their treatment at The Johns Hopkins Hospital and The University of Texas MD Anderson Cancer Center in Houston, TX. The scientists detected tumor DNA in the saliva of 71 of the 93 patients (76%) and in the blood of 41 of the 47 (87%). In the 47 who gave blood and saliva samples, scientists were able to detect tumor DNA in at least one of the body fluids in 45 of them (96%).

When the scientists analyzed how well their tumor DNA tests found cancers in certain regions of the head and neck, they found that saliva tests fared better than blood tests for oral cavity cancers. All 46 oral cavity cancers were correctly identified through saliva tests, compared with 16 of 34 oropharynx cancers (47%), seven of 10 larynx cancers (70%), and two of three hypopharynx cancers (67%).

"One reason that saliva tests may not have been as effective for cancer sites in the back of the throat is because we didn't ask patients to gargle; we only asked them to rinse their mouths to provide the samples," said Agrawal, a member of Johns Hopkins' Kimmel Cancer Center and Ludwig Center.

Blood tests correctly identified tumor DNA more often in 20 of 22 oropharynx cancers (91%), six of seven larynx cancers (86%), and all three hypopharynx cancers. Taken together, blood and saliva tests correctly identified all oral cavity, larynx, and hypopharynx cancers and 20 of 22 oropharynx cancers (91%).

The scientists caution that further study of their tumor DNA detection method in larger groups of patients and healthy people is needed before clinical effectiveness can be determined, and that refinements also may be needed in methods of collecting saliva and the range of cancer-specific genes in the gene test panel.

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