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May 2, 2000

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Hopkins Scientists Link Human Papillomavirus (HPV) To Head and Neck Cancer

Researchers at the Johns Hopkins School of Medicine and School of Hygiene and Public Health have found the sexually transmitted human papillomavirus (HPV) to be a likely cause of certain cancers of the head and neck and also an indicator of improved survival. Their findings are reported in the May 3, 2000, issue of the Journal of the National Cancer Institute.

The investigators studied tumors of 253 patients, ages 17 to 91, with newly diagnosed or recurring squamous cell head and neck cancer. HPV was detected in 62, or 25 percent, of the tumors and, of the HPV-positive tumors, 90 percent contained a high-risk, tumor-promoting form of the virus known as HPV-16. Somewhat unexpectedly, perhaps, those with HPV-positive tumors were 60 percent less likely to die from their head and neck cancer than those with HPV-negative tumors, according to the researchers. The data provide strong evidence that HPVs may be the cause of a defined subset of head and neck cancers, particularly those of the oropharynx (tonsils and throat), and this association with HPV infection also is linked to a markedly improved prognosis. While they currently cannot explain the improved survival, follow-up of participants revealed that the average survival of patients with HPV-positive tumors was 91 months or more but 76 months among patients with HPV-negative tumors. Other factors contributing to poor prognosis included advanced disease, age, and heavy alcohol consumption.

"These data suggest that HPV-positive head and neck cancers may comprise a distinct molecular, clinical, and pathologic disease very different from other types of the disease," says the Oncology Center's Maura L. Gillison, M.D., lead author of the study.

Squamous cell head and neck cancer is a disease largely attributable to environmental exposures--primarily tobacco and alcohol use. Fifteen to 20 percent of these cancers, however, occur in non-smokers and non-drinkers. "In this study, those with HPV-positive tumors in the oropharynx were light- or non-drinkers and non-smokers. We believe that HPV infection of the upper airway may be the cause of tumor development in this group of people," says Gillison. The researchers believe HPV causes the formation of head and neck cancers by producing two HPV-associated oncoproteins or growth-promoting proteins known as E6 and E7, which, in turn, inactivate the p53 and Rb tumor suppressor genes. They are planning a clinical trial of a cancer vaccine used for HPV-associated cervical cancers in these HPV-positive head and neck cancers. The vaccine would be given prior to standard therapy with surgery and/or radiation therapy.

"Although HPV DNA has been detected in head and neck cancers for sometime, its role in cancer development and the means by which HPV is transmitted to the upper airway has remained unclear," says one of the study's senior investigators, David Sidransky, M.D., professor of otolaryngology and oncology.

Although HPV presence in head and neck cancers has not yet been convincingly tied to specific sexual practices, HPV infection in head and neck cancer patients has been linked to the number of sexual partners in other studies, according to the researchers. "All of the evidence points to viral presence preceding disease progression," says Keerti V. Shah, M.D., Dr.P.H., professor of molecular microbiology and immunology.

An estimated 31,000 people in the United States are diagnosed each year with cancer of the oral cavity and pharynx. An additional 8,500 die each year from the disease. HPV is a sexually transmitted virus most recognized for its association with cervical and other genital squamous cell cancers.

In addition to Gillison, Sidransky, and Shah, other participants in this research include Wayne M. Koch, M.D., Randolph B. Capone, M.D., Michael Spafford, M.D., William H.Westra, M.D., Li Wu, Marianna L. Zahurak, M.S., Richard W. Daniel, B.S., Michael Viglione, M.D., and David E. Symer, M.D., Ph.D.

The study was funded by the National Institutes of Health and a Clinical Oncology Research Career Development Program grant.

Related Web site:

The Johns Hopkins Oncology Center: www.hopkins.cancercenter.jhmi.edu

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