The purpose of this program project grant is to study the biology of the human papillomaviruses (HPVs) that cause recurrent papillomas of the upper respiratory tract, and to optimize photodynamic therapy for this disease. From these studies we hope to develop a base of knowledge that will lead to better ways to cure or control laryngeal papillomas. The studies to be done can be grouped into two broad categories. The first group of projects is focused on the basic biology of the HPVs. Project 1 will study activation of latent HPV to determine whether the virus can be activated by exogenous agents. Project 4 will study the role of the 5'end of the HPV regulatory region in the control of viral expression and replication. Project 5 will investigate the reasons why we cannot establish a stable latent infection in vitro, to better understand viral persistence in latent infection. The second group of projects is focused on therapy for papillomavirus induced disease. Project 2 is the continuation of a clinical trial of photodynamic therapy (PDT) for laryngeal papillomas, using dihematoporphyrin ether as the activating drug. In this study, the dose of drug will be optimized, to determine both clinical efficacy and the ability to cure the patient of latent infection. Project 3 uses an animal model to test a new photoactivating drug, methyl-pheophorbide-A-hexyl-ether (MPAHE). Rabbit papillomas induced with the cottontail rabbit papillomavirus will be treated with MPAHE-PDT, to determine whether the drug is more effective than DHE, and whether it is less likely to cause severe and prolonged photosensitivity. This project will also attempt to develop a rabbit model for latent infection, to facilitate all studies of latency in the future.
