Molecular mechanisms of human papillomavirus-induced carcinogenesis.
Approximately 20% of all cancers are associated with infectious agents. Among them, human papillomaviruses (HPVs) are very common and are now recognized as the etiological agent of cervical cancer, the second most common cancer in women worldwide, and they are increasingly linked with other forms of dysplasia. Carcinogenesis is a complex and multistep process requiring the acquisition of several genetic and/or epigenetic alterations. HPV-induced neoplasia, however, is in part mediated by the intrinsic functions of the viral proteins. In order to replicate its genome, HPV modulates the cell cycle, while deploying mechanisms to escape the host immune response, cellular senescence and apoptosis. As such, HPV infection leads directly and indirectly to genomic instability, further favouring transforming genetic events and progression to malignancy. This review aims to summarize our current understanding of the molecular mechanisms exploited by HPV to induce neoplasia, with an emphasis on the role of the 2 viral oncoproteins E6 and E7. Greater understanding of the role of HPV proteins in these processes will ultimately aid in the development of antiviral therapies, as well as unravel general mechanisms of oncogenesis.
Lehoux
Michaël
M
Laboratory of Molecular Virology, Institut de Recherches Cliniques de Montréal, Montreal, Que., H2W 1R7 Canada.
D'Abramo
Claudia M
CM
Archambault
Jacques
J
D000595:Amino Acid Sequence; D017209:Apoptosis; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D023281:Genomics; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology*
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