Pathogenesis of human papillomavirus-associated mucosal disease
The Journal of Pathology
MetadataShow full item record
Groves, I., & Coleman, N. (2014). Pathogenesis of human papillomavirus-associated mucosal disease. The Journal of Pathology, 235 527-538. https://doi.org/10.1002/path.4496
Human papillomaviruses (HPVs) are a necessary cause of carcinoma of the cervix and other mucosal epithelia. Key events in high-risk HPV (HRHPV)-associated neoplastic progression include persistent infection, deregulated expression of virus early genes in basal epithelial cells and genomic instability causing secondary host genomic imbalances. There are multiple mechanisms by which deregulated virus early gene expression may be achieved. Integration of virus DNA into host chromosomes is observed in the majority of cervical squamous cell carcinomas (SCCs), although in ∼15% of cases the virus remains extrachromosomal (episomal). Interestingly, not all integration events provide a growth advantage to basal cervical epithelial cells or lead to increased levels of the virus oncogenes E6 and E7, when compared with episome-containing basal cells. The factors that provide a competitive advantage to some integrants, but not others, are complex and include virus and host contributions. Gene expression from integrated and episomal HRHPV is regulated through host epigenetic mechanisms affecting the virus long control region (LCR), which appear to be of functional importance. New approaches to treating HRHPV-associated mucosal neoplasia include knockout of integrated HRHPV DNA, depletion of virus transcripts and inhibition of virus early gene transcription through targeting or use of epigenetic modifiers.
human papillomavirus, mucosa, oncogene, E6/E7, epigenetics, integration, squamous cell carcinoma
We thank Cancer Research UK and the Medical Research Council for funding our research, some of which is described in this review.
External DOI: https://doi.org/10.1002/path.4496
This record's URL: https://www.repository.cam.ac.uk/handle/1810/246806