Which statement best describes p16 expression in HPV-driven cervical lesions?

• A. It is not linked to HPV status
• B. It is sometimes overexpressed, but not linked to HPV status
• C. It is overexpressed due to HPV E6/E7
• D. It is only found in endometrial tissue

Answer: (C)

p16 overexpression in HPV-driven cervical lesions occurs because HPV oncoproteins disrupt the RB pathway. p16INK4a normally inhibits CDK4/6 to prevent phosphorylation of RB, keeping the cell from advancing in the cycle. When HPV E7 inactivates RB, the cell’s attempt to restore control leads to increased p16 production, so p16 accumulates. This pattern—strong p16 expression—is a hallmark of HPV-positive CIN and cervical cancer, making p16 a useful surrogate marker for HPV-driven disease. While HPV E6 supports oncogenesis by degrading p53, the link to p16 upregulation is driven primarily by E7’s effect on RB.