P16

P16 is a cell cycle negative regulatory protein that can competitively bind and inhibit cyclin dependent kinase 4 (CDK4), which will obstruct the production of phosphorylated retinoblastoma protein (pRb), thereby preventing cells from entering the S phase. Some research found that human papilloma virus (HPV) can reduce pRb activity to eliminate negative feedback inhibition, which will induce high expression of P16 and cause cell cycle disorder, thereby initiating cellular carcinogenesis. Therefore, P16 is mainly used as a diagnostic indicator for high-risk cervical HPV infection. For example, P16 is diffusely strongly expressed in HSIL but locally weakly expressed in LSIL, which makes it become one of the differential markers. Meanwhile, the combination of P16 and Ki-67 has important guiding significance for the diagnosis, treatment, and prognosis of cervical cancer. In addition, the loss of P16 is related to poor prognosis of various tumors such as gastric cancer, colorectal cancer, and thyroid cancer.