When HPV infects host cells, several HPV DNA-coded proteins initiate cellular changes. Two such areas in the genome are the open reading frames E1 to E7 and the late open reading frames L1 and L2. The proteins encoded by E1 to E7 regions of the genome are responsible for HPV-gene regulation and cell transformation. Proteins resulting from L1 and L2 form the viral shell.
E6 and E7 encoded proteins are the most important HPV proteins in malignancy transformations. These viral proteins work together to convert normal host cells to malignant cells. E6 proteins interact with intracellular protein p53 and E7 proteins interact with intracellular retinoblastoma (Rb) protein. Intracellular proteins p53 and Rb regulate cellular growth. Both p53 and Rb are tumor suppressor proteins.
When chromosomal damage occurs in normal cellular growth, p53 halts cellular growth and allows DNA repair enzymes to repair damage. Rb also halts cellular growth in DNA damage by inducing apoptosis (cellular death). When HPV E6 proteins bind to p53 and HPV E7 to Rb, mutations accumulate, unchecked cellular growth occurs, and a state of chromosomal instability results. This instability and unregulated cellular growth increases the chance of forming malignant cells.
Viral E1, E2, and E5 encoded proteins may also damage cellular processes when HPV infects cells and can lead to malignant transformations.