Down in the Mouth

Oral cancers kill more often than melanoma and 
Hodgkin's disease, but early diagnosis can give this 
public health menace a kick in the teeth.
by Alicia Di Rado

 

When a Babylonian merchant in 4 B.C. experienced an ulcer on the side of his tongue, he viewed it as a sign of divine displeasure and prayed and uttered incantations for it to go away.

Unfortunately, in 2001 A.D., not much has changed. Many people with persistent oral lesions ignore them, hoping they will vanish, instead of seeking help from a dentist or other health professional. Although some lesions in the mouth are harmless, a dangerous number are not.

Oral cancers, or malignancies of the mouth and throat, are often preventable and detectable. Still, thousands of people lose their lives each year as a result of them.

"At least one person every hour dies of oral cancer," says David Crowe, D.D.S., D.M.Sc., associate professor in the USC Center for Craniofacial Molecular Biology. "Yet it doesn't get nearly the amount of attention that other cancers such as lung, breast or prostate do. I think it's surprising to the general public how big a public health problem it poses."

Harold Slavkin, D.D.S., dean of the USC School of Dentistry, points out that oral cancer kills more often than cervical cancer, melanoma and Hodgkin's disease. And in developing nations around the globe, it is the third most common cancer.

"For 42,000 Americans a year, this is a very real problem," Slavkin says. And even though some prominent figures have been treated for the disease-former Los Angeles Dodger Brett Butler and rock guitarist Eddie Van Halen, just for starters-it remains a mystery to many.

USC oral health experts want to change that.

Seeing Spots

Just a few steps from Slavkin's office at the USC School of Dentistry, rows of patients recline in dental chairs, mouths agape, as young dentists perform examinations.

Such dentists, as well as dental hygienists, often are the first to notice pre-cancerous or cancerous lesions in the mouth, Slavkin explains. Yet the National Institute of Dental and Craniofacial Research (NIDCR), one of the National Institutes of Health, indicates that less than 15 percent of American adults report ever having an exam for early detection of oral cancer.

"Of all patients treated for these cancers, only an average of 50 percent survive for five years," Slavkin says. "One of the reasons the survival rate is poor is that invariably, the diagnosis is made in the late stages of the disease."

Slavkin, the G. Donald and Marian James Montgomery Professor of Dentistry, who served as NIDCR's director before rejoining USC in 1999, has been active nationally in pushing for routine, comprehensive screenings for oral cancer. Such screenings include a visual and digital inspection of the tongue, floor of the mouth and other soft tissue where lesions can develop.

It is not just a dental issue, though. By some accident of history, the human mouth has landed within the health domain of the dentist, but primary care physicians and others need to be knowledgeable about oral health, too, Slavkin says.

Those others include patients themselves.

Just as doctors have encouraged patients to regularly examine their skin for indications of skin cancer, oral cancer experts encourage patients to use a mirror to look for changes in their mouths. After all, many tumors develop in readily visible areas.

So what should patients check for?

Most mouth and tongue cancers cause an ulcer, swelling or raised patch-with coloring or spots that are red, white or both-that is usually painless unless infected, notes Dale Rice, M.D., professor and chair of otolaryngology/head and neck surgery at the Keck School of Medicine of USC. Common sites include the tonsils, tongue, larynx, lips and floor of the mouth.

Other possible symptoms include:

Most oral cancers are squamous cell carcinomas. Squamous cells-flat, scale-like cells-line the oral cavity. Squamous cell carcinomas often begin as dysplastic areas-red or white spots or sores where cells begin to slowly go awry.

"It's important that patients see a doctor or dentist if their sore does not heal within two weeks," says Rice, the David S. Alpert-Leon J. Tiber Chair in Medicine. A dentist usually will refer a patient to an oral surgeon or head and neck physician to take a tiny sample of the

lesion so a pathologist can examine the cells under a

microscope.

Sometimes, though, the first sign a patient notices is a lump in the neck. Many problems, such as tooth or sinus infections, can cause a swollen lymph node. But patients should see a dentist or physician if the lump is one inch across or larger, or if it is growing quickly.

Cut It Out

Next stop: the office of an otolaryngologist, such as Rice, an expert in the anatomically complex head and neck region.

Rice and his fellow doctors first run staging tests to find out if the cancer is localized in one tumor or if it has spread.

These tests include physical exams, in which the doctor feels a patient's neck and jaw to check for swollen nodes (a sign of cancer spread) and uses special fiberoptic instruments to look behind the tongue and inside the throat. If the patient's first symptom was a swollen node, doctors do some detective work to find the original tumor.

They also use imaging, such as computerized tomography (CT) and magnetic resonance imaging (MRI) scans of the head, to see the cancer better. Sometimes doctors ask for a chest X-ray to check the lungs.

Unlike many other cancers, oral cancers seem to spread only through the lymph system, not through blood. That means that these cancers first metastasize to the lymph nodes in the neck.

If a tumor is caught early, is small and has not spread, the best treatment is surgery, Rice says. Once the tumor is removed, such patients have an excellent chance at recovery. Five-year survival rates can be as high as 90 percent-though patients must be vigilant throughout their lives for any sign of new tumors.

To make sure no cancerous cells have migrated, surgeons may also remove several lymph nodes in the neck for pathologists to analyze, or they may recommend radiation to eradicate any lingering cancer cells.

Once a cancer has spread, though, a team that may include surgeons, oncologists, radiologists and plastic surgeons meets to determine the best treatment plan. Patients are usually treated with surgery, radiation or both, though in later stages, chemotherapy may be used, too.

If patients need reconstruction on delicate areas, plastic surgeons and prosthodontists (dentists specially trained in prosthetics) often team with head and neck surgeons to rebuild the jaw, teeth or other facial features after the tumor is removed. Speech pathologists and physical therapists may help patients recover function after treatment.

Unfortunately, surgery for late-stage cancers can mean disfiguring scarring and defects, requiring skin grafts and muscle flaps. Besides the tremendous emotional impact of such procedures, accompanying radiation treatment may lead to loss of salivary glands and reduced sense of taste. Chemotherapy carries its own collection of side effects. In addition, the longer the cancer progresses, the more aggressive, resistant and unpredictable its spreading cells become-all the more reason to detect such a cancer early, and adopt healthy habits to help prevent it.

Smoke and Mirrors

To understand the cancer's potential causes is to deter it. Oral cancer's prime culprit: tobacco smoking or chewing.

"Tobacco is the leading cause of head and neck cancers," Rice says. "Up to 90 percent of these cases are smoking-related."

Drinking alcohol increases risk, as well.

"If you smoke more than a pack a day or consume more than five alcoholic beverages a day, you're an A-list candidate for these types of cancers," Rice says.

Researchers believe alcohol and tobacco interact in some way in the mouth to create an even more carcinogenic cocktail. And, adds Slavkin, drinking alcohol may not be the only problem.

"Alcohol can come in mouthwash, too," Slavkin says. "If you're a smoker and use mouthwash to mask your smoker's breath, you could get hit by a double whammy."

Sun exposure, as well, increases the risk of cancer on the lips. In a 1996 study published in Cancer Causes and Control, Susan Preston-Martin, Ph.D., professor of preventive medicine, and her colleague Janice Pogoda showed that plain old lipstick, used regularly, guards against lip cancer. Lip cancer rates for men, who do not regularly protect their lips, are seven times higher than rates for women. The implication for cancer control efforts, says Preston-Martin, means that people, especially men, should use lip protection of some sort, even if it is just Chapstick.

Researchers are also studying the role of diet and genetic defects in oral cancer, as well as the influence of microbes such as herpes and the human papilloma virus, which has already been implicated in cervical cancer.

Still, some people who seemingly have no risk factors still end up with the disease, so everyone should be aware of symptoms and keep an eye on the mirror for early detection. But for now, when it comes to prevention, one item is key, emphasizes Rice: "Stop smoking. It's the single most important thing you can do for your health."

Strange Cells

Deep within Crowe's lab at USC, thousands of oral cancer cells bathe in petri dishes filled with pinkish goo. These cells hold a secret: how oral cancer works on a genetic level.

In some ways, oral cancer is a strange creature. Several of the genes so important in other cancers do not appear to play a role in this one, Crowe says. That means researchers must track down new genetic suspects to understand how the cancer starts, develops and spreads.

Some aspects of the disease, though, are consistent with its cancerous colleagues. Like other cancers associated with smoking, oral cancers show DNA damage on the gene p53, whose failure has already been associated with about 60 percent of human cancers.

But people do not get cancer from one genetic error, Crowe explains. It takes a number of steps, involving numerous genetic mutations, before cancer gets rolling, and researchers are trying to trace those steps. "We need to find out how you get from a p53 defect to oral cancer," he says.

When scientists understand how the cells become cancerous, they can proceed clinically on several fronts. Once the first markers of oral cancer are found, for example, doctors might be able to easily detect disease early using an oral rinse on patients to test for the presence of telltale molecules. And if they understand what makes the cells go awry, they may be able to design medicines that reverse aberrant growth.

That area-reversing or preventing cellular abnormalities-is Crowe's focus.

Crowe works with retinoids, compounds related to vitamin A. Scientists already know that one such compound, isotretinoin, can reverse premalignant oral patches, but as Crowe points out, "the problem, as with many chemopreventive drugs, is that it has side effects." So, he and fellow researchers are looking for synthetic derivatives that may help without harm.

Around the country, researchers are diving into promising areas of investigation surrounding the cancer. Some "tweak" viruses to use in gene therapy to target and kill oral cancer cells; others are creating antibodies that attach themselves to oral cancer cells, forming a roadblock against chemicals-called growth factors-that cancer cells need to grow.

Maybe we have progressed a long way in oral health since the Babylonian Empire, after all.

Says Crowe: "We've made big strides against oral cancer. I'm much more optimistic about this cancer in 2001 than I was in 1991." 

For more information about the prevention, detection and treatment of oral cancer, or to learn more about The Doctors of USC, call 1-800-USC-CARE (1-800-872-2273).

Back
Next
Index