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A study published yesterday found that a combination of biomarkers, rather than DNA alone, is a more effective way of determining the involvement of human papillomavirus in causing head and neck cancers. Brown researchers - working with colleagues at Dartmouth, Boston University and other institutions - found that patients with head and neck cancers caused by HPV fared better than patients with head and neck cancers caused by other factors, such as smoking. The study, published in the journal Cancer Research, determined that a combined biomarker approach that examines both DNA and biomarkers provides the best prediction of patient outcomes.

"It is important to assess which tumors are driven by a virus and which ones aren't," said Karl Kelsey, professor of community health, pathology and laboratory medicine and contributing author of the study.

HPV, commonly known as a cause of cervical cancer, is also a known cause of head and neck squamous cell carcinoma. The study in particular focused on HPV16, a strain specifically associated with increased risk of throat cancer. When HPV infects a host and integrates into its genome, two viral proteins, called E6 and E7, are constructed and activated. The E6 and E7 proteins then inhibit the function of tumor suppressor proteins, notably retinoblastoma protein ­- the inactivation of which can lead to the development of cancer. 

Kelsey defined biomarkers as indicators of particular conditions that allow clinicians to make decisions about a patient's care. In this study, researchers examined blood serum levels of antibodies to E6 and E7 viral proteins. They also stained the tumors for p16, a protein that signals the inactivation of tumor suppression. They found that HPV E6 and E7 antibodies, in the absence of p16 overexpression, were associated with improved patient survival - and this combination of biomarkers proved superior to other biomarkers in predicting patient outcome. Through identification of antibodies to the E6 and E7 biomarkers, researchers can glean a more accurate measure of HPV DNA in tumors.

The study also shows that amplification and identification of HPV16 DNA from head and neck tumors alone is not an accurate method for predicting patient mortality.

Patients who were HPV16 DNA positive but lacked antibodies to E6 or E7 did not demonstrate reduced mortality, while patients with the antibodies showed a significant reduction in overall mortality, regardless of HPV16 DNA detection.

In addition, "Individually, p16 overexpression is not informative to predict overall survival," said primary author Caihua Liang GS, a doctoral student in community health.

Pierre Saintigny, assistant professor at MD Anderson Cancer Center, said the study could have a "major impact in defining patients having poor prognosis." Saintigny praised the use of a large population sample and the study's methodology. 

Since the treatment for head and neck cancer is aggressive, identification of the cause of head and neck tumors could allow physicians to use less harmful treatment options with tumors caused by HPV. "These tests might be useful in the future for early detection," Saintigny added.

Though less aggressive treatment for HPV-related cancers may be possible, "the most important part (of the study) is the correct diagnosis of virus-associated tumors," Kesley said.


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