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Tom Carey

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Primary Appointment: Otorhinolaryngology Department
Primary PIBS Dept.: Pharmacology
PubMed Name: carey te
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  We are working to identify the specific characteristics (biomarkers) of head and neck tumors and patient factors that determine response to therapy in organ sparing (i.e. non-surgical) treatment approaches. We have shown that p53 status and expression when combined with Bcl-xL expression can identify low, intermediate and high risk larynx tumors for response to induction chemotherapy and probability of avoiding laryngectomy. Similarly these same markers identify oropharynx tumors that are most likely to respond to organ sparing treatment and those that are least likely to respond and these categories also determine probability of survival among oropharynx cancer patients. High risk human papilloma virus (HPV) content in oropharynx tumors as well as epidermal growth factor receptor expression also play key roles in predicting response to treatment and survival. These factors are modified by smoking and patient gender. Using biomarkers we are now designing laboratory studies to understand how adverse biomarkers can be overcome and we are using biomarker analysis to design new therapeutic studies to assign patients to the most appropriate therapy for their tumor. With this approach we expect to minimize morbidity by reducing treatment intensity for those with highly responsive cancers and to change therapy to maximize effectiveness against those tumors with the worst prognosis. HPV-induced oropharyngeal cancers are now more prevalent than HPV induced uterine cervix cancer in the United States. We are also investigating high risk HPV oral infections and persistence as risk factors for development of head and neck cancers in HIV-infected and HIV non-infected individuals as well as the role of HPV gene expression as markers of viral transformation. Site of HPV integration may alter the biologic behavior of HPV induced oropharyngeal cancers. We are investigating whether intragenic integration foretells a worse prognosis than integration into gene poor regions of the genome. We are also assessing the complexity of genomic alterations as factors in HPV-induced cancers as factors to use in selecting patients for de-intensified therapy as a means of reducing treatment morbidity in patients with HPV-positive low risk disease.