How is insensitivity to growth inhibitory signals by tumor suppressor genes?

RB gene (governs cell cycle), key in regulation of cell cycle, keep cell in G1 anti-proliferative gene (regulates G1/S checkpoint), central for malignant transformation, one of four regulators is mutated in most human cancer (p16, cyclin D, CDK4, RB), may occur by viral proteins targetting RB like HPV deletes RB function. TP53 most common mutated gene in human cancer, p53 is suppressed and its function by CDKN1A transcription increase is G0 activation, induce permenant cell cycle arrest, and trigger apoptosis. stressed by DNA damage assist in repair and induce repair genes. More than 70% of cancers are by mutation in p53, 30% of malignant have defective genes upstream./downstream of p53. So RB external changes, p53 internal (DNA damage) also could be by HPV