p16 inhibitor of CDK4, p16INK4a, is a 16 kDa tumor suppressor protein. It works as an inhibitor of the CDK4/CDK6-mediated cell cycle regulation of the G1/S phase transition. A decrease in p16 expression can lead to an upregulation of CDK4-mediated activation of retinoblastoma (Rb) protein accelerating cell proliferation. p16 has been shown to be an important factor in cervical cancer, in which upregulation of p16 expression has been reported in cervical lesions such as cervical intra-epithelial neoplasms. In cervical preneoplastic and neoplastic lesions associated with high-risk human papillomavirus (HPV) infection, there is functional inactivation of Rb resulting in an accumulation of p16 protein. Despite the p16 overexpression in association with high-risk HPV, there is no slowing effect on the cell cycle as Rb is inactivated by the HPV E7 oncoprotein. In addition, several studies have shown p16 downregulation in several human cancers. p16 is widely expressed in normal tissues.