Microbiology · Year 2 · from Microbiology
Case 3: Cervical Cancer Screening Abnormality
Presentation
A 28-year-old woman presents to discuss her Pap smear results, which showed HSIL (high-grade squamous intraepithelial lesion). She has no symptoms. She has had three sexual partners and has never received the HPV vaccine. She is a non-smoker. Colposcopy is performed, revealing an acetowhite lesion on the cervix at the 3 o'clock position. Biopsy of this area shows CIN 3 (cervical intraepithelial neoplasia grade 3) with cells demonstrating perinuclear clearing and nuclear atypia consistent with koilocytic changes. HPV testing is positive for HPV type 16.
Clinical Image
Histopathology of cervical biopsy showing koilocytes - squamous cells with characteristic perinuclear clearing (halo) and nuclear atypia, indicating HPV infection.
Image Source: Lecture image - HPV pathology
Questions
- What is the significance of HPV 16 in this case?
- Explain the molecular mechanism by which HPV causes cellular transformation.
- What are the management options for CIN 3?
- How could this condition have been prevented?
Answers
- Significance of HPV 16: HPV 16 is a high-risk HPV type, responsible for approximately 50% of cervical cancers and a significant proportion of oropharyngeal, anal, penile, vaginal, and vulvar cancers. High-risk HPV types (16, 18, 31, 33, 45, 52, 58) have oncogenic potential, unlike low-risk types (6, 11) that cause genital warts. CIN 3 is a precancerous lesion with high risk of progression to invasive cervical cancer if left untreated.
- Molecular mechanism of HPV oncogenesis: HPV oncogenesis is driven by two viral oncoproteins:
- E6 protein: Binds and promotes ubiquitin-mediated degradation of p53, eliminating the cellular response to DNA damage and preventing apoptosis
- E7 protein: Binds and inactivates retinoblastoma protein (Rb), releasing E2F transcription factors and driving uncontrolled cell cycle progression
In productive infection, the viral genome remains episomal and expression is regulated. When HPV DNA integrates into the host chromosome (typically disrupting the E2 regulatory gene), uncontrolled E6/E7 expression drives cellular transformation. The koilocyte (cell with perinuclear clearing) is the cytologic hallmark of HPV infection.
- Management of CIN 3: CIN 3 requires treatment due to significant risk of progression to invasive cancer. Options include:
- Excisional procedures (preferred): LEEP (loop electrosurgical excision procedure) or cold knife conization - provides tissue for histologic assessment
- Ablative procedures: Cryotherapy or laser ablation - destroys tissue without specimen
- After treatment: Close follow-up with repeat cytology and HPV testing
- Hysterectomy is generally not first-line but may be considered in select cases
- Prevention strategies:
- HPV vaccination: The 9-valent vaccine (Gardasil 9) targets HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58. Vaccination is ideally given at ages 11-12 before sexual debut, with catch-up through age 26 (FDA-approved to age 45). The vaccine could have prevented this case.
- Cervical cancer screening: Regular Pap smears and/or HPV testing beginning at age 21 (cytology) or 25 (with HPV testing options)
- Risk reduction: Limiting sexual partners, consistent condom use (partial protection)
- This case emphasizes the importance of vaccination before HPV exposure