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HPV Tied to Better Tongue, Tonsil Cancer Outcomes

WEDNESDAY May 14, 2008 -- Tonsil and tongue cancers linked to human papillomavirus (HPV) are most responsive to current chemotherapy and radiation treatments, while those that express high levels of a growth factor called EGFR are the least responsive and most deadly, a new study concludes.

University of Michigan Comprehensive Cancer Center researchers identified a series of markers that identify which patients are most likely to survive these types of cancers. The findings are a promising step toward the development of individualized treatments for tonsil and tongue cancers, according to the authors of two papers published online May 12 in the Journal of Clinical Oncology and expected to be in the July 1 print issue.

"The chemotherapy and radiation therapy we use to treat this type of cancer is very aggressive. If we can identify those patients most likely to respond, we could reduce the intensity of the therapy for those likely to have the best outcomes. At the same time, we hope to identify new treatments that specifically target those tumors that we know are not responding to current therapies," Thomas Carey, co-director of the head and neck oncology program at the U-M Comprehensive Cancer Center, said in a prepared statement. He was the senior author on both papers.

The researchers gave an initial course of chemotherapy to 66 people with advanced oropharyngeal cancer, which includes cancer of the tonsils and the base of the tongue. Patients (54) who responded to this initial treatment then received a full course of simultaneous chemotherapy and radiation. Patients (11) who didn't respond to the initial chemotherapy were referred for surgery.

Of the 54 patients who responded to the initial chemotherapy, 62 percent are alive today without evidence of cancer, and 73 percent fully preserved their organs. Of the 11 patients referred for surgery, only four survived.

"For most patients, the chemoradiation was very effective. But a subset of patients still do not do well. Our next step was to look at the biomarkers to see if we could determine which patients were responding to treatment, based on tumor biology," said Carey, who is also an associate chair and professor of otolaryngology and pharmacology at the U-M Medical School.

The researchers found that 64 percent of the tumors were positive for high-risk strains of HPV. Almost all of the HPV-positive tumors responded to initial chemotherapy, and 78 percent of those patients survived with their organs intact. Of the HPV-negative patients, only four of 15 survived. In addition, patients with the EGFR marker had worse outcomes.

"The combination of markers was an important indicator. Patients whose tumors expressed high levels of EGFR did poorly. But those who had high EGFR and were also HPV-positive had some protection. Patients with high EGFR and low HPV fared the worst," Bhavna Kumar, a research laboratory specialist who was lead author on both papers, said in a prepared statement.

The U-M team also found that patients with low expression of protein called p53 and high expression of a protein called BCLXL also had poor outcomes.

Posted: May 2008


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