Elucidating the HPV E6/E7 Oncogenic Functions at Different Anatomical Sites
Vjekoslav Tomaić, dr.sc.
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Human Papillomaviruses (HPVs) cause over 600,000 cancers annually. These occur at diverse anatomical sites, and include anogenital and head and neck (HN) cancers. Of these the most important is cervical cancer, which is the leading cause of cancer-related death in women in many parts of the world. HPVs encode two oncoproteins, E6 and E7 that are directly responsible for the development of HPV-induced malignancies. They do this cooperatively by targeting diverse cellular pathways involved in the regulation of cell cycle control and apoptosis. Most importantly, there is a continued requirement for E6 and E7 expression throughout tumorigenesis, with loss of either protein resulting in a cessation of transformed cell growth. Therefore, these viral proteins represent excellent targets for therapeutic intervention and understanding the molecular mechanisms underlying their respective functions is critical for developing such antiviral therapies. In recent years there has been dramatic increase in the number of HPV-associated cancers at other anatomical sites, especially in the HN region. Cancers found in this area largely contain HPV-16 sequences and the time frame between initial infections and cancer progression is much shorter in comparison with the anogenital cancers, indicating potentially major differences in how these viruses induce cancer development at different anatomical sites. Determining if this is a reflection of different modes of virus-host interactions in these sites will be the main focus of this project.