A 35-year-old woman from Mumbai undergoes routine cervical screening and is found to have HPV-16 positive, high-grade squamous intraepithelial lesion (HSIL) on liquid-based cytology. Colposcopy with directed biopsy confirms cervical intraepithelial neoplasia grade 2 (CIN 2). She is otherwise healthy with no immunosuppression. What is the most appropriate next step in management?

Explanation

## Management of CIN 2 with HPV-16 Positivity **Key Point:** CIN 2 (cervical intraepithelial neoplasia grade 2) is a high-grade lesion with significant risk of progression to invasive cancer if untreated. Excisional treatment with margin assessment is the standard of care. ### Why LEEP is the Gold Standard Loop Electrosurgical Excision Procedure (LEEP) is the most appropriate next step because it: 1. **Provides both therapeutic and diagnostic benefit**: Removes the lesion AND allows histopathological examination of margins 2. **Assesses for invasive disease**: Biopsy may have missed invasion; excision specimen allows complete evaluation 3. **Allows margin assessment**: Negative margins predict lower recurrence risk 4. **Is minimally invasive**: Performed in outpatient setting under local anesthesia 5. **Has high cure rates**: ~90% for CIN 2 with negative margins **High-Yield:** CIN 2 has a ~30% risk of progression to invasive cancer if untreated; excisional treatment reduces this to <5% if margins are negative. ### Natural History and Risk Stratification | Feature | CIN 1 | CIN 2 | CIN 3 | |---------|-------|-------|-------| | **Spontaneous regression** | 60–70% | 40% | <5% | | **Progression to invasive** | ~1% | ~5% | ~30% | | **HPV-16/18 prevalence** | 50% | 70% | 80% | | **Recommended management** | Observation or ablation | Excision (LEEP) | Excision (LEEP/cone) | **Clinical Pearl:** HPV-16 positivity in CIN 2 is a strong predictor of persistent/progressive disease; observation is not acceptable. ### Post-LEEP Follow-Up Protocol ```mermaid flowchart TD A[LEEP performed for CIN 2]:::action --> B{Histology margins?}:::decision B -->|Negative margins| C[HPV test at 6 months]:::action B -->|Positive or uncertain margins| D[Repeat LEEP or cold knife cone]:::urgent C --> E{HPV result?}:::decision E -->|HPV negative| F[Return to routine screening]:::action E -->|HPV positive| G[Colposcopy + biopsy]:::urgent D --> H[Reassess margins]:::action ``` **Mnemonic:** **LEEP for CIN 2** — **L**oop excision, **E**xcisional treatment, **E**xamine margins, **P**revent progression. **Warning:** Observation or ablation (without excision) for CIN 2 is inappropriate because: - Margins cannot be assessed - Occult invasion may be missed - Recurrence risk is higher - HPV-16 positive lesions have high progression potential