RB1 and viral infectious disease: In humans, it has been hypothesized that p16 overexpression in tumors can be indicative of two main situations: in benign or pre-malignant lesions, p16 may be overexpressed as a consequence of oncogene-induced senescence, whereas in malignant lesions, overexpression appears to be a mechanism to arrest the uncontrolled proliferation caused by failure of the Rb pathway (secondary in this case not to viral infection, but rather to mutational silencing of the Rb gene) [52].