E6-Ap is a ubiquitin ligase. Cellular enzymes load it with activated ubiquitin molecules which are transferred to p53. Ubiquitin loading of p53 targets it for degradation by proteasome mediated proteolysis. The forced entry into S-phase in conjunction with genomic instability, resulting from p53 degradation may lead to malignancy. Location of viral DNA seems to be important in the deregulation of HPV gene expression.
Cancer cells have a higher proportion integrated than premalignant cells.
This controls HPV gene expression. DNA methylation may also play a role. Most herpesviruses are not proven to be responsible for any human cancers, although they may be a cofactor with papilloma for cervical cancer. The virus is present in tumour cells, tracks tightly to and precedes the presence of disease. Latent infection but a switch to the lytic phase may be responsible for the formation of lesions.