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Pathways to Discovery: Summer 2013

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Research Reveals Five Subgroups of Head and Neck Cancer

Researchers at the University of Chicago Medicine Comprehensive Cancer Center (UCCCC) have classified head and neck cancers into five subgroups, each with unique characteristics that may help personalize treatment decisions for patients.

Head and neck cancer comprises cancers of the mouth, tonsils, nose, sinuses, throat, and upper esophagus. It is the 6th most common cancer worldwide. Risk factors include human papilloma virus (HPV) infection, similar to cervical cancer, as well as tobacco and alcohol use.

“We are in the middle of an epidemic of HPV-associated tumors,” said Tanguy Seiwert, MD, assistant professor of medicine. “Usually those cancers have a better prognosis, but there is a subgroup of patients who do very poorly and, unfortunately, we have no reliable means of identifying them.”

Dr. Seiwert and colleagues set out to understand why some head and neck cancers responded favorably to treatment and why others fared worse. They used advanced genomic and bioinformatics analysis tools to determine the genetic profiles of 134 head and neck tumors. These tumors had all been previously treated with standard therapy so that now the researchers could compare “genetic fingerprints” with the outcomes.

Based on their study, they were able to classify head and neck cancer into 5 different subgroups. Three types––hypoxic, basal, and classical––were not associated with HPV, had a poor prognosis, and showed unique features that may be useful to guide therapy in the future. For example, Dr. Seiwert said that some features, such as lack of oxygen supply (hypoxia), strongly correlated with subtypes and may explain why some patients respond favorably to radiation or epidermal growth factor receptor (EGFR) inhibitors.

Out of the other two types, which were both HPV-associated, the researchers found that type A was associated with a better outcome than type B.

“It was really striking that the HPV-positive tumors, which were previously believed to be one entity, were actually two different subtypes,” Dr. Seiwert said. “Our study brings us one step closer to predicting which patients will need more intensive treatment, and which patients may safely undergo a better tolerated treatment with fewer side effects.”

He said that because these tumors often occur in young patients, it would be particularly helpful to know which patients can be safely and effectively treated with less intense therapy to avoid long-term side effects.

Dr. Seiwert’s group submitted their findings for publication. In addition, Dr. Seiwert delivered a presentation about the genetic make-up of these tumors at the recent annual meeting of the American Society of Clinical Oncology in Chicago. “The mutational spectrum of every tumor is different, but certain patterns are emerging that classify tumors and may guide our understanding of individual tumors,” he said.

Interestingly, these patterns may cross tumor types; in other words, certain head and neck tumors show features similar to aggressive breast cancers or bladder cancers, potentially enabling treatments that are based on shared biology in multiple cancers. The clear goal is to develop new or intelligently re-use existing therapies to target the specific mutations. “It’s a process that will take years to complete, but promises a more rational and personalized approach to cancer care,” said Dr. Seiwert.

The UCCCC head and neck cancer team, led by Everett Vokes, John E. Ultmann Professor of Medicine and Radiation Oncology, is leading the field with outstanding treatment outcomes. “Not only do we want to be known as a center of excellence for treatment, but also as leaders in precision medicine for head and neck cancer,” Dr. Vokes said. “It seems that this classification system could potentially be a valuable tool to personalize the treatment for our patients.”