• 4/11/2004
  • San Francisco
  • E. J. Mundell
  • Health Day News

New biopsy test could change how doctors treat tumors of tongue, mouth

Oral cancer specialists have found a way to determine which patients are most likely to benefit from surgery and which are not.

Oncologists typically recommend that all patients with pre-cancerous white patches on the tongue or mouth have surgery to remove the suspicious area. But a new biopsy technique may change all that, Norwegian researchers say. The new findings are “actually challenging things that we are currently doing,” says oral cancer expert Dr. Deborah Greenspan, of the University of California, San Francisco.

A study summarizing the findings appears in the April 1 issue of the New England Journal of Medicine. Oral cancers are strongly linked to smoking and to the use of snuff, chew and other forms of smokeless tobacco. The disease is much more prevalent in men than women, with more than 20,000 cases of oral cancer reported in U.S. males each year. The disease typically begins as a small, innocuous leukoplakia (literally, “white patch”) on the surface of the tongue or cheek “which to the patient may actually be completely asymptomatic and can only be picked up for the most part by a dentist or dental hygienist during a good oral exam,” Greenspan says. The large majority of oral leukoplakias will not turn malignant but do warrant a biopsy, especially in tobacco users. If pre-cancerous cell changes called dysplasia are spotted during a biopsy, most doctors will “recommend that the whole area of the change — where it is white — be excised,” Greenspan says.

Surgical removal of oral leukoplakia does not always prevent oral cancer from developing later on down the road, however. Scientists have long sought a biopsy “marker” that might help determine who would benefit from surgery and who would not.

For the new study, researchers led by Dr. Jon Sudbo, of the Norwegian Radium Hospital in Oslo, examined data on the treatment and long-term survival of 150 patients diagnosed with pre-cancerous oral leukoplakia. Doctors biopsied tissue samples from each patient, examining them under the microscope for cellular abnormalities. All of the patients underwent surgery involving removal of the “white patch” area plus enough surrounding tissue to create what the doctors hoped would be a cancer-free margin. Sudbo’s team then tracked the patients’ rates of cancer recurrence and long-term survival for six years.

About a third (47) of the patients went on to develop oral cancer, the researchers report. Of that group, 21 eventually died from the disease, despite early surgical removal of the oral leukoplakia.
However, looking over the patients’ biopsy results, the researchers discerned a clear pattern: All patients who died had tested positive on their original biopsy for a particular cellular aberration called “aneuploidy,” in which cells look disordered, with an overabundance of DNA.

Based on their findings, the Norwegian researchers now believe surgical removal of leukoplakia characterized by aneuploidy “does not reduce the high risk of carcinoma and death from oral cancer.” Right now, tests for aneuploidy are only performed in research labs, says Greenspan, whose commentary on the study also appears in the April 1 issue of the New England Journal of Medicine. “But I think this paper is suggesting that we need to develop methods to actually look for aneuploidy in cells during biopsy — it’s not routinely done. This is something we have to start taking very seriously.”

“We also have to determine why removing the lesion does not influence this particular type of cancer,” Greenspan says. “The finding is intriguing, since it runs counter to almost everything we know about the treatment of cancers found elsewhere in the body.”

The finding may also shift the focus of treatment for individuals with aneuploid leukoplakias away from surgery and toward new drug therapies. Cox-2 inhibitor medications — which include painkillers such as aspirin, ibuprofen and Celebrex — have shown some promise in preventing oral cancer, Greenspan notes.

In the meantime, prevention remains key. “My advice to the public is, first of all, don’t smoke and don’t use smokeless tobacco,” Greenspan says. “Secondly, people should get good, regular oral exams. I think that’s extremely important, because one of the things that we do know is that when oral cancer is caught early and treated when the lesion is very small, the prognosis is much better.” And saying ‘Ah!’ in front of your bathroom mirror isn’t enough. A proper oral exam is best left to dentists, dental hygienists and other professionals, Greenspan adds. “You can’t rely on your own inspection. It doesn’t take very long, but you need somebody with a good light and a mouth mirror. They examine very carefully inside of the cheek, the floor of the mouth and the tongue,” she says.

SOURCES: Deborah Greenspan, B.D.S., D.Sc., professor, clinical oral medicine, University of California, San Francisco; April 1, 2004, The New England Journal of Medicine