Abstract
Human papillomavirus (HPV) infections of the high-risk types are strongly linked to the development of cervical carcinoma. The HPV oncoproteins E6 and E7 are thought to play a crucial role in this process through their interactions with the p53 protein and the retinoblastoma susceptibility gene product pRb, respectively. E6 binds to p53 protein promoting its degradation. This is considered to contribute to the oncogenesis of HPV-associated anogenital cancer. On the other hand, in HPV-negative cervical carcinoma, p53 mutations are thought to have a role in the transformation process. A total of 122 HPV-positive cervical carcinoma tissue samples were evaluated for the presence of mutations in exons 5-8 of the p53 gene by single-stranded conformation polymorphism analysis and DNA sequencing. Only four missense point mutations were detected. These findings suggest that other mechanisms independent of p53 inactivation may play a role in the genesis of cervical carcinomas.
Highlights
Carcinoma of the uterine cervix is the third most frequent of the female genital malignancies
Four missense point mutations were detected. These findings suggest that other mechanisms independent of p53 inactivation may play a role in the genesis of cervical carcinomas
Almost all of human cervical carcinomas harbor human papillomavirus (HPV) DNA sequences, and the viral E6 and E7 oncoproteins are generally expressed within these tumors [21]
Summary
Carcinoma of the uterine cervix is the third most frequent of the female genital malignancies. Among more than 70 HPV types reported to date, types HPV 16 and 18 are the most prevalent and are found in more than 90% of primary cervical carcinomas in different geographic regions of the world [3,4]. These high-risk HPVs encode two transforming gene products, E6 and E7, whose proteins bind to p53 and pRb, respectively [5,6,7]. The level of p53 in HPV-containing cervical carcinoma cell lines and HPV-immortalized keratinocytes is generally lower than the level seen in primary cells and the half-life is decreased [6]
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