June 14, 2010 The presence of human papilloma virus, the virus that causes cervical cancer, in tumors is the most important predictor of survival for people diagnosed with oropharyngeal cancer (cancer of the back of the mouth), according to a new study led by a researcher at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James).
Published online June 7 in the New England Journal of Medicine with a related editorial, this is the first study large enough to show that the presence of human papilloma virus (HPV) in tumors accounts for better response to therapy, rather than other favorable factors that may be present, such as young age and small tumors.
The second leading predictor of survival is lifetime smoking history, followed by cancer stage.
The findings suggest that the HPV status of a patient's tumor and their smoking history may be used in the future, in addition to cancer stage, to determine the aggressiveness of a patient's therapy.
The Phase III clinical trial established by the RTOG examined overall survival and progression-free survival in 323 patients with stage III-IV oropharyngeal cancer treated with a combination of radiation therapy and chemotherapy. Of these patients, 206 had HPV-positive tumors and 117 were HPV-negative. The three-year overall survival rate for patients with HPV-positive tumors was 82.4 percent compared to 57.1 percent with HPV-negative cancer. Progression-free survival rates were 73.7 percent and 43.4 percent, respectively.
When researchers adjusted for other significant determinants of survival, including patient age, race, tumor and nodal stage and tobacco use, patients with HPV-positive cancer had a 58 percent reduction in risk of death relative to patients with HPV-negative tumors. The study noted tobacco use substantially increased risk of death. Results will allow physicians to stratify patients enrolled in clinical trials into low, intermediate or high-risk of death based on HPV status, tobacco use and cancer stage. This information can then be used to better determine which patients are candidates for more intensive investigational therapies.
"Previous studies indicated a relationship exited between the presence or absence of HPV in oropharyngeal tumors and patient survival, but they couldn't determine if other favorable factors present in these patients were responsible for their better outcome," says study leader Dr. Maura Gillison, a medical oncologist and head and neck cancer specialist at the OSUCCC-James.
"These findings close the door on these questions and will allow the field to move forward with clinical trials designed to determine how we should use molecular and behavioral factors to personalize therapy for patients."
Gillison emphasized that there is insufficient data at this time to indicate how a specific patient's cancer therapy should be tailored based on these factors.
The investigators found that at three-years, about 93 percent of patients with HPV-positive tumors who were never or light- smokers were alive, as compared to about 70 percent of patients with HPV-positive tumors who were smokers and about 46 percent of patients with HPV-negative tumors who were smokers. The risk of cancer relapse or death increased by one percent for each additional pack year of tobacco smoking (one pack year is equivalent to smoking one pack a day for a year).
"The two risk factors that place an individual at risk for oropharyngeal cancer are also the most important factors determining patient survival. This is probably because these factors determine the genetic profile of these cancers and how they respond to treatment," Gillison says.
Gillison and her colleagues have since conducted a follow-up study to further investigate the influence of tobacco smoking on oropharyngeal cancer. She reported these findings June 7 at the 2010 annual meeting of American Society of Clinical Oncology.
Oropharyngeal cancer develops in the part of the throat just behind the mouth. The American Cancer Society estimates that 28,500 people in the United States are diagnosed with cancer of the oral cavity and oropharynx each year. While the incidence of head and neck cancer has been declining during the past 30 years, the rate of HPV-positive oropharyngeal cancer is rapidly rising. Today, nearly 70 percent of oropharynx cancer cases are HPV-positive.
Funding from the National Cancer Institute and the National Institute of Dental and Craniofacial Research supported this research.
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- K. Kian Ang, M.D., Ph.D., Jonathan Harris, M.S., Richard Wheeler, M.D., Randal Weber, M.D., David I. Rosenthal, M.D., Phuc Felix Nguyen-Tân, M.D., William H. Westra, M.D., Christine H. Chung, M.D., Richard C. Jordan, D.D.S., Ph.D., Charles Lu, M.D., Harold Kim, M.D., Rita Axelrod, M.D., C. Craig Silverman, M.D., Kevin P. Redmond, M.D., and Maura L. Gillison, M.D., Ph.D. Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer. New England Journal of Medicine, June 7, 2010 DOI: 10.1056/NEJMoa0912217
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