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HPV and p16 Testing in Oropharyngeal Squamous Cell Carcinoma

Methodology, Interpretation, and Significance



HPV in OPSCC Oncogenesis — Genome

Slide 11

March 2012

The HPV circular genome is usually around 8,000 base pairs in length and contains approximately 80 genes, which are categorized as early-designated as “E” or late – designated as “L”. The designations of early and late refer to the temporal sequence of gene expression. Upon entrance into the cell nucleus, HPV early genes, E1, E2, E6, and E7, are pivotal in establishing approximately 20-100 intranuclear viral DNA episomes. As the basal cell undergoes division, viral episomal replication will simultaneously occur. Whereas infected cells will continue to undergo division even as they make their way into the suprabasal layers, uninfected cells will not divide and exhibit maturation that we observe in the strata of benign squamous epithelium. As infected cells migrate towards the surface, there is upregulation of early and late genes; ultimately, fully formed virions including capsid proteins are ready for release.

It turns out that E6 and E7 oncoproteins are expressed in low- and high-risk genotypes; however, these proteins bind tumor suppressor proteins with greater affinity when expressed by high-risk genotypes. In fact, it appears that E6 and E7 must be derived from high-risk genotypes to actually induce and transform cells in vitro.

Late genes, L1 and L2, are capsid proteins that appear to require initiation by the promoter p670.

HPV in OPSCC Oncogenesis — Genome

 


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