p16

p16, also known as p16(INK4a) or cyclin-dependent kinase inhibitor 2A (CDKN2A), is a tumor suppressor protein encoded by the CDKN2A gene on chromosome 9p21. It plays a critical role in regulating the cell cycle and reducing stem cell proliferation with age to protect against cancer. In the context of dysplasia, p16 overexpression reflects the body’s attempt to prevent neoplastic progression. 

p16 IHC is a surrogate marker of high-risk, transcriptionally active HPV in many anogenital and oropharyngeal lesions, typically showing diffuse ‘block-positive’ nuclear and cytoplasmic immunohistochemical reaction in HPV infected cells. HPV induces expression ofE7, which inactivates and promotes degradation of pRb, releasing E2F and driving p16 upregulation. Accordingly, block-positive p16 supports an HPV-driven process across a range of precancerous lesions and carcinomas.

• Identification of HPV-related neoplastic lesions in anogenital and oropharyngeal tissues.
• Distinguishing HPV-related cervical dysplasia and cancer from atrophic or reactive changes using combined immunohistochemical demonstration of p16 and Ki-67. Co-expression of p16 and Ki67 is indicative of high-risk HPV infection and not seen in reactive conditions.
• Differentiation of cervical adenocarcinomas (typically p16-positive) from endometrial adenocarcinomas (p16-negative or patchy staining).

Tonsil is a recommended choice for both positive and negative tissue control. Scattered reticulated crypt epithelial cells are expected to show moderate to strong nuclear and cytoplasmic staining reaction. Dispersed germinal center macrophages and dendritic cells should exhibit a weak but distinct nuclear and cytoplasmic staining reaction. Conversely, no staining reaction should be observed in most lymphocytes or in normal superficial squamous epithelial cells.