A 35-year-old woman has cervical biopsy showing CIN 3 / high-grade squamous intraepithelial lesion (HSIL). HPV genotyping: HPV-16 positive. The oncogenic mechanism of HPV-16 in cervical carcinogenesis primarily involves:
- A Both E6 (p53 degradation) and E7 (pRb inactivation) working together to abrogate both G1 checkpoints ✓
- B HPV E7 protein binding and degrading pRb, releasing E2F and driving cell cycle entry
- C HPV E6 protein binding and ubiquitinating p53 via E6AP ubiquitin ligase, causing p53 degradation
- D HPV L1 capsid protein integrating into the host genome at fragile sites
Explanation
High-risk HPV oncoproteins E6 and E7 cooperate to drive cervical carcinogenesis. E6 binds p53 and recruits E6-AP (E6-associated protein, an E3 ubiquitin ligase), causing ubiquitin-proteasomal degradation of p53, eliminating cell cycle arrest and apoptotic responses to DNA damage. E7 binds and promotes proteasomal degradation of pRb (retinoblastoma protein), freeing E2F transcription factors to drive S-phase entry. Both mechanisms together abrogate the two major G1 checkpoint systems. Integration of viral DNA into the host genome (with loss of E2 — a viral repressor of E6/E7) amplifies oncogene expression.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.