RB1 and head and neck cancer: Moreover, HPV status in head/neck cancer appears mutually exclusive with alterations of RB/E2F axis genes, such that HPV-negative cancers often display copy number loss of CDKN2A (encoding p16) and overexpression of CCND1 (encoding Cyclin D1; Cancer Genome Atlas Network, 2015; Gillison et al., 2019; Zapatka et al., 2020), which effectively mimics a subset of the oncogenic effects of E7.