150 Carcinogenesis of HPV

Human papillomavirus are oncogenic DNA virus able to transform cutaneous and mucosal epithelial cells. The most relevant transforming mechanisms is the down-regulation of 2 oncosuppressor genes: p53 and pRb. For their frequency of detection in invasive lesions some genotypes have been defined “high risk” and their carcinogenicity has been referred to (1) their capacity to induce persistent infections, for the efficacy to escape the host immune system, (2) the binding affinity of their E6/E7 oncoprotein to the respective oncosuppressors, and (3) their efficacy to induce genomic instability. In vivo risk of cancer progression, in particular transition from pre-invasive to invasive cancer lesions, and the subsequent frequency of developing metastatic lesions as well as responsivity to anticancer treatment, is due to specific virus-host interactions and genomic damages. As paradigm the better prognosis and higher responsivity to treatment of HPV-positive oropharyngeal cancers in comparison to HPV-negative cancers. Mutations in genes of the apoptotic pathway, particularly the TP53 gene, have been analyzed in cervical cancers. A significant higher mutation frequency of TP53 gene in the CAC adenocarcinoma (32 of 241; 13.3%) compared to SCC squamous cell carcinoma (39 of 657; 5.9%; P = 0.0003, χ(2) test) has been identified. Three codons (175, 248 and 273) were the most commonly mutated in both, codon 249 mainly in SCC, codon 282 only in CAC. The G to A and C to T transitions were the prevalent type of mutations in both SCC and CAC (48.7% and 53.5% of all mutations, respectively). The frequency of C to A transversion was relatively high only in CAC (25%), while the mirror mutation G to T was comparatively frequent in SCC (14.6%).