Human papillomavirus HPV

HPV are small, double-standard DNA viruses that specifically infect squamous epithelial cells. HPV represents a heterogeneous group of viruses with over 70 different HPV genotypes identified. Only keratinocytes can be infected, and the virus has evolved a unique model of replication with absolute dependence upon the microenvironment of differentiating squamous epithelium for infection, replication, viral capsid synthesis, and particle assembly. HPV virus and tumours

Convincing epidemiological studies have implicated an infectious agent in the aetiology of cervical cancer. Longitudinal studies have established high-grade cervical intra-epithelial neoplasia (CIN) as a pre-malignant precursor lesion to invasive cancer. Genital warts show an identical epidemiological pattern to cervical cancer and, in addition, HPV induces cellular changes previously interpreted as cervical dysplasia in cervical smears and tissue. Molecular confirmation of this association using PCR has demonstrated 'high-risk' HPV types in high-grade CIN lesions and other squamous intra-epithelial lesions such as PIN: penile intraepithelial neoplasia, AIN: anal intraepithelial neoplasia, and VIN: vulva intraepithelial neoplasia.

Studies of HPV-positive cervical cancer have shown integration of viral DNA; the E6 and E7 genes are regularly overexpressed. Proteins encoded by E6 and E7 in high-risk HPV types are oncoproteins, p53 being targeted for degradation by E6 protein, whilst E7 protein inactivates retinoblastoma (Rb) protein. Conversely, the E6 and E7 proteins encoded by 'low-risk' HPV types 6/11, show dramatically lower activity in these functions when compared to those encoded by 'high-risk' HPV types.

The role of HPV types in other tumour types such as oesophageal, laryngeal, and oropharyngeal cancer needs to be further defined. Epidemiological evidence suggests that HIV-infected patients have a higher incidence of HPV-associated anogenital tumours, namely cervical cancer in women and anal cancer in men.

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