Immortalization of human cells and their malignant conversion by high riskhuman papillomavirus genotypes

Papillomaviruses cause certain common human cancers, most notably carcinoma of the cervix. The viral oncoproteins E6 and E7 are essential components i n malignant conversion, although, in spite of being necessary, they are not sufficient for the development of the malignant phenotype. High risk HPV o ncogenes fulfill dual functions in genome-harboring cells: their derived on coproteins stimulate cell growth by pleiotropic effects. At the same time t hey act as progression factors by inducing mutations in host cell DNA and a neuploidy. The mechanism underlying the process towards malignant conversio n, usually covering a long latency period between primary infection and can cer emergence, is presently not fully understood. It emerges, however, that cancer development depends on the interruption of at least two signalling cascades (labeled as CIF I and CIF II) that interfere with the function of viral oncoproteins (CIF I) and with the transcription of viral oncogenes (C IF II). Further modifications of host cell genes most likely mediate the es cape from immune surveillance mechanisms of the host and the development of metastases.