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Promise and Progress - The Profile of a Virulent Cancer

Special Commemorative Issue: The Abeloff Era - Building Upon a Tradition of Excellence

The Profile of a Virulent Cancer

Date: April 1, 2007

In the case of tonsillar cancers, a type of cancer that has been steadily on the rise since 1973, the link to HPV may be a good thing. As Maura Gillison has found, there are many potential opportunities for intervention. In HPV-initiated oral cancers, the virus is very precise at taking out—by itself—two key cancer-related cell pathways, p53 and pRb. It does the damage alone regardless of other oral cancer-causing assaults like smoking and drinking. HPV infection supercedes any other risk factor.

“It doesn’t matter what else you do. The cancer is driven by the virus,” says Gillison.In the case of tonsillar cancers, a type of cancer that has been steadily on the rise since 1973, the link to HPV may be a good thing. There are many potential opportunities for intervention, such as early detection of HPV infection through screening tests as simple as rinsing and spitting in a cup; and potential prevention of infection through developing HPV vaccines. Even those that get the cancer are cured an astonishing 85 percent of the time, according to Gillison’s research, and this is a relevant statistic considering HPV-positive cancers make up about 60 percent of all oropharyngeal cancers in the United States.

In Gillison’s latest research, published in May 2007 in the New England Journal of Medicine, she found the overriding risk factor for the cancer to be multiple oral sex partners. Oral sex is the main way one gets orally infected with HPV, the cumulative term for a group of about 100 sexually transmitted viruses. In this case, the specific virus in question is HPV16.

Gillison collected blood samples and examined a variety of behaviors including, smoking, drinking, family history, poor oral hygiene, multiple oral sex partners, and other sexual behaviors that would expose a person to HPV, in 100 tonsillar cancer patients and healthy controls. She followed participants for five years. People who reported multiple (more than six) oral sex partners through a confidential and anonymous computerized survey had an over 8-fold increased risk of developing cancer. “When you compare that to three-fold for smoking and 2-fold for drinking, this is a very significant odds ratio,” says Gillison.

In Gillison’s earlier research, she identified HPV16 infection as a cause of certain head and neck cancers. Investigators had long known of the presence of HPV in some patients with oral cancers, but Gillison was the first to prove the virus was actually driving the tumors and not just coincidental to them.

Her latest findings are expected to have major prevention and treatment implications. With the favorable outcomes in HPV-positive tonsillar cancer patients, Gillison believes oncologists may be able to begin ratcheting back the very intensive and debilitating therapies given for this type of cancer. “There are few cancers that have the impact on quality of life that these do,” says Gillison.

Most people are familiar with the tonsils in the back of the throat, but there are also tonsils at the base of the tongue. “Targeting the tongue and throat with high doses of anticancer drugs and radiation, affects eating, talking and breathing. I’m talking about walking around with a drool cup because you can’t swallow your own spit,” says Gillison. She believes that less treatment, perhaps by reducing the total dose of radiation therapy, may work just as well in curing HPV-positive oral cancer patients and spare them these nasty side effects.

Gillison is also optimistic about prevention possibilities. HPV vaccines approved just months ago by the FDA to prevent the genital infection that leads to the majority of cervical cancers, could also prevent oral infection, Gillison believes, and she is currently planning clinical trials to test this theory. Gillison also has clinical trials of therapeutic HPV vaccines, designed to stimulate the bodies own immune response to HPV16 in tumors ongoing in the oncology clinic in patients with HPV16-positive head and neck cancers.

Gillison’s findings have attracted the attention of cancer experts worldwide. The Kimmel Cancer Center Marion I. Knott director Martin D. Abeloff is not surprised. “In the case of these cancers, we now know what causes them, the key behavioral risk factor that predisposes someone, potential ways to prevent it, and possible improvements in treatment. I would say that is a good, comprehensive body of work.”