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. Importance depends on location, skin wart may be unsightly but a wart on the vocal chord may be life threatening. Interferon therapy is useful for genital warts but less useful for oral warts. Virus spread by infectious virions contacting minor epithelial abrasions.