DNA and Light Detect Cancer in the Brain, Head and Neck

Two advances in detection technologies coming out of Johns Hopkins Medicine could soon up the odds of surviving cancers of the brain, head and neck.

In one breakthrough, researchers have employed an imaging technique that uses safe near-infrared light to differentiate between healthy brain tissue and that which has become cancerous. They hope to advance their work so that neurosurgeons can see 3-D color-coded maps of patient brains while they are performing surgery to more accurately remove tumors.

In another, scientists were able to detect tumor DNA in the saliva and blood of people suffering from head and neck cancers. In diagnostic tests using both body fluids, they were able to successfully identify cancers in 96 percent of patients.



In the first research announcement, biomedical engineers and neuroscientists say they have used an imaging technique called optical coherence tomography to peer into brain tissue and see the difference between cancerous cells and normal. OCT has been used for years to identify disease in the retina, gastric tract, heart and breast.

The technique shines near-infrared light on the tissue and records differences in how different elements scatter the light waves. Johns Hopkins researchers refined the method so it can be used for brain surgery. They did it by relying on two characteristics of brain cancer cells: they form tumors that tend to be denser than healthy tissue and they don’t have the normal myelin sheaths that coat healthy cells. These facts mean that tumors scatter light differently than surrounding unaffected tissue, a property that can be detected by OCT.

The team developed algorithms that convert the signal differences picked up by the OCT sensor into a 3-D map of tissue color-coded red for cancerous tissue and green for healthy.

“We envision that the OCT would be aimed at the area being operated on, and the surgeon could look at a screen to get a continuously updated picture of where the cancer is – and isn’t,” said biomedical engineer Xingde Li, the coauthor of the study that appeared last week in the journal Science Translational Medicine.



They expect to begin clinical trials on the device this summer. They’ve already seen success in a proof of concept using human brain tissue removed during normal surgeries and performing their own surgeries on mice with brain tumors.

“As a neurosurgeon, I’m in agony when I’m taking out a tumor,” said Dr. Alfredo Quinones-Hinojosa, a professor of neurosurgery, neuroscience and oncology who coauthored the paper. “If I take out too little, the cancer could come back; too much, and the patient can be permanently disabled. We think optical coherence tomography has strong potential for helping surgeons know exactly where to cut.”



(An illustration of a new technique using optical coherence tomography that could help surgeons differentiate a human brain tumor, red, from surrounding noncancerous tissue, green. Graphic courtesy of Kut et al./Johns Hopkins Medicine.)

The second advance focuses on head and neck cancers, which are distinct from brain cancer because they typically start in the linings of the mouth, nose and throat. These areas have specialized cells, called squamous cells, that line the mucous membranes and sometimes succumb to their own cancers.



The DNA-identifying work successfully found head and neck cancers triggered by the human papillomavirus, a sexually transmitted disease, by searching for virus DNA fragments in the blood and saliva. HPV-caused tumors are on the rise in the U.S., and the CDC says 72 percent of all cancers of the back of the throat are linked to the virus. To zero in on maladies arising from a patient’s own DNA, the team looked for mutations in genes that are known to cause head and neck cancers. They took saliva samples from 93 patients newly diagnosed with disease and blood samples from more than half of them. Using just the saliva samples, the researchers detected tumor DNA fragments in 76 percent of patients. Blood analysis found tumor DNA in 87 percent of samples. For those who gave blood and saliva samples, tumor DNA was found in at least one of the two body fluids in 96 percent of patients.

“We have shown that tumor DNA in the blood or saliva can successfully be measured for these cancers,” said Dr. Nishant Agrawal, an associate professor of otolaryngology and oncology, and the coauthor of the study published today in Science Translational Medicine. “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.”



There is still more work to be done before this advance can become a diagnostic tool used by doctors. It needs to be tried on a larger group of subjects to see if it works as they believe, and healthy people need to be included in the test to get data on them. Also, the researchers need to understand whether their method produces false positives identified by the method.

If it works as hoped, the test, which appears capable of detecting early-stage cancers, could help the 50,000 people in this country alone who are diagnosed with head and neck cancer every year. Current practice takes biopsies of lesions, which only appear in later stages of disease.

“Our ultimate goal is to develop better screening tests to find head and neck cancers among the general population and improve how we monitor patients with cancer for recurrence of their disease,” said oncologist Dr. Bert Vogelstein, a coauthor of the study.



(Schematic showing the shedding of tumor DNA from head and neck cancers into the saliva or plasma. Tumors from various anatomic locations shed DNA fragments containing tumor-specific mutations and human papillomavirus DNA into the saliva or the circulation. The detectability of tumor DNA in the saliva varied with anatomic location of the tumor, with the highest sensitivity for oral cavity cancers. The detectability in plasma varied much less in regard to the tumor’s anatomic location. Graphic courtesy Wang et al./Science Translational Medicine.)



Top gif: Created from video that shows the color-coded, 3-D optical property map obtained from a brain cancer patient. Courtesy of Kut et al./Science Translational Medicine.