A 28-year-old woman has a Pap smear showing koilocytes (perinuclear halos with nuclear atypia) and is diagnosed with CIN I. Which molecular event in HPV-infected keratinocytes is primarily responsible for the characteristic koilocyte morphology?

• A HPV E6 oncoprotein binding and degrading p53, causing nuclear atypia
• B HPV E7 degrading Rb, causing S-phase entry and nuclear atypia
• C HPV late gene L1/L2 capsid proteins assembling in mature superficial keratinocytes, causing cytoplasmic clearing due to viral particle production ✓
• D Inflammatory cytokine-mediated cytoplasmic vacuolation independent of viral proteins

Explanation

Koilocytes are HPV-infected squamous cells with perinuclear cytoplasmic halos and nuclear atypia. The perinuclear clearing (halo) reflects productive viral replication: HPV late proteins L1 (major capsid) and L2 assemble in the upper differentiated layers of the epithelium during productive infection, and the cytoplasmic vacuolation represents viral assembly/transport. E6 degrades p53 and E7 degrades Rb (contributing to nuclear atypia and uncontrolled proliferation), but the cytoplasmic clearing specifically reflects productive viral replication in the superficial layers.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.