NEW ORLEANS--A diagnostic test under development may be able to detect many head and neck squamous cell carcinomas while they are still in their early stages, David Sidransky, MD, professor in the Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, reported at the 89th annual meeting of the American Association for Cancer Research.
The lining of the mouth and throat renews itself each week, Michael Spafford, MD, one of Dr. Sidransky’s co-authors and a head and neck oncology fellow at Johns Hopkins, said at a press conference. But even though tumor cells are shed with the rest, they usually cannot be detected when saliva is examined under a microscope.
The new test detects tumor cells in saliva by a more sensitive methodology: polymerase chain reaction (PCR), a method for making millions of copies of a specific DNA region. With PCR, Drs. Sidransky and Spafford and their co-workers can target DNA sloughed off by the tumor. They compare certain DNA markers found in the saliva with those in cells in the patient’s blood, looking for genetic changes characteristic of cancer cells. The DNA markers chosen are all microsatellite repeat regions, areas in which a sequence of nucleotides repeats over and over.
In their preliminary pilot feasibility trial, the researchers examined several markers in 21 people with head and neck cancer and 27 people without cancer. They looked at cells in the tumor as well as cells in the saliva. As would be expected, DNA in the healthy control subjects’ saliva matched their other DNA. Normal saliva DNA was seen in both smokers and nonsmokers.
Genetic Alterations Found
In contrast, in 15 (71%) of the people with cancer, the researchers found genetic alterations in cells in the saliva. In some patients, the marker genes had mutated, and in others, the marker genes had disappeared. Still other patients had both types of alterations. These changes matched those in the tumors, supporting the idea that the altered cells in the saliva are indeed cells shed by the tumor.
Head and neck cancer often occurs in places neither patient nor physician can see. As a result, many such cancers are not detected until they are advanced. But therapy for late head and neck cancer can be debilitating, Dr. Spafford said, and the cure rate is less than 50%, compared with nearly 90% when these cancers are caught early. For this reason, a sensitive, specific test for these cancers would be a great help and save many lives.
With a sensitivity of 71%, the new saliva test is not as sensitive as the researchers would like. Their next steps, Dr. Sidransky said, are to increase the number of markers they test for and to automate the test. Testing for more markers should allow them to catch more genetic alterations and so increase the sensitivity while keeping the specificity high. Automation should bring the cost down and make the test far easier to perform in a clinical laboratory.
If their efforts are successful, eventually the test could be used to monitor head and neck cancer patients for recurrence. The test might also be suitable for screening people who are at high risk of developing head and neck cancers, such as smokers.
