Professor of Viral Pathogenesis & Fellow of Hughes Hall,
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, United Kingdom
Understanding The Cervical Transformation Zone as the Primary Site for Human Papillomavirus-Mediated Carcinogenesis
Host: L. Banks
Abstract
The high risk Human Papillomaviruses cause over 95% cervical cancers, as well as the majority of anal cancers and a significant subset of oropharyngeal cancers. As sexually transmitted viruses, they also cause cancers at other genital sites, but the oropharynx, and the transformation zone (TZ) regions of the anus and the cervix represent hotspots. The normal stratified epithelium, which papillomaviruses require for their productive life cycle is not uniformly present at the cervical TZ, but can emerge during a women’s lifetime, as a result of the normal physiological process of metaplasia. A particular cell type found at the cervical TZ, which resembles the epithelial basal cell in expressing p63 and Keratin 5, appears responsible for the process of metaplasia, and appears linked to the vulnerability of this site to HPV-driven carcinogenesis. These cells, which are known as ‘reserve cells’, are distributed sporadically beneath the mucus covered columnar epithelial layers of the TZ with a characteristic pattern, but appear to support high level HPV gene expression, and can expand in number at the entrances to the cervical crypts following infection. The balance between HPV persistence and regression appears linked to the deregulation of viral gene expression and associated immune evasion functions that can occur at these localized epithelial sites, and the effectiveness of the host immune response, which can clear low grade cervical disease, but which fails to clear crypt entrance infections in women who are at risk of developing cancer. Our emerging understanding of this epithelial site is providing new insight as to how HPV infections might be controlled following therapeutic vaccination, as well as methodologies for more accurately identifying disease location and severity during screening.
International Seminar Programme
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