A 30-year-old woman has a 3 cm vulvar lesion with VIN III (high-grade squamous intraepithelial lesion). HPV typing shows HPV-16 positive. Which protein product of HPV-16 is primarily responsible for p16 overexpression seen on IHC of this lesion?
- A E6 oncoprotein — targets p53 for ubiquitin-mediated degradation via E6AP ubiquitin ligase
- B E7 oncoprotein — binds and inactivates Rb protein, releasing E2F transcription factors which activate p16 (CDKN2A) as a compensatory cell cycle brake ✓
- C L1 capsid protein — activates toll-like receptor signaling inducing p16 as part of innate immune response
- D E2 regulatory protein — disrupts p16 promoter methylation causing re-expression
Explanation
In HPV-driven squamous intraepithelial lesions, E7 oncoprotein binds the retinoblastoma protein (pRb) and inactivates it, releasing E2F transcription factors from inhibition. The cell cycle machinery 'senses' the missing Rb-E2F feedback, and CDKN2A (p16) is overexpressed as a compensatory inhibitor of CDK4/6 (which would otherwise phosphorylate Rb). Thus, p16 overexpression by IHC (strong, diffuse, block-positive) is a surrogate marker of high-risk HPV E7 activity. E6 targets p53, not Rb/p16. L1 capsid and E2 have no role in p16 upregulation. p16 IHC is used diagnostically to confirm HPV-driven lesions in cervix, vulva, oropharynx.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.