A 40-year-old woman has a cervical biopsy showing CIN 3 with p16 block positivity and high-risk HPV (type 16) on genotyping. The molecular mechanism by which HPV E7 oncoprotein causes S-phase entry in infected cells is:

• A E7 binds and degrades p53 via ubiquitin-proteasome
• B E7 activates telomerase to immortalize infected cells
• C E7 binds pRb, releasing E2F transcription factors to activate S-phase gene expression ✓
• D E7 inhibits cyclin-dependent kinase inhibitor p27 by phosphorylation

Explanation

HPV E7 is the primary driver of cell cycle dysregulation in HPV-infected squamous cells. E7 protein directly binds the retinoblastoma protein (pRb) through an LXCXE motif, disrupting the pRb-E2F complex. Normally, hypophosphorylated pRb sequesters E2F transcription factors; E7 binding mimics hyperphosphorylation, releasing E2F to activate transcription of S-phase genes (cyclin E, DHFR, thymidylate kinase). This explains the utility of p16 immunohistochemistry as a surrogate marker — E7-mediated Rb inactivation removes feedback inhibition of p16, causing p16 overexpression in high-grade HPV-associated lesions. E6 (not E7) degrades p53.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.