Papillomas of the upper respiratory tract are caused by human papillomaviruses (HPVs). These histologically benign tumors cause a high degree of morbidity and significant mortality. The objective of this Clinical Research Center application is to focus a multidisciplinary approach to this disease. The program consists of an interactive working group of basic scientists and clinicians, sharing their expertise to study aspects of the papillomas ranging from the viral molecule to the infected individual. Through the interactions of this group, insights are provided into mechanisms of pathogenesis and therapeutic response that would not exist if either basic science or clinical studies alone were done. Persistence and expression of the HPV DNA and subsequent host response are recurrent sub-themes of this project. From these studies, we will develop a base of knowledge that will lead to better ways to cure or control respiratory papillomas. The projects within this program are: 1. Study the regulation of the early HPV promoters, and determine whether epidermal growth factor, a key regulator of the papilloma phenotype, alters transcription. 2. Determine the efficacy of a new photosensitizer for photodynamic therapy, and determine why only some patients respond to this therapy. 3. Study interactions between the HPV regulatory region and tissue factors in the control of viral expression and replication. 4. Study the effects of antisense oligonucleotides on HPV DNA persistence, and establish the background data for possible future therapy.
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