What is the recommended management for a high‑grade squamous intra‑epithelial lesion (HSIL) corresponding to cervical intraepithelial neoplasia grade 2‑3 (CIN 2‑3) in a woman aged 25 years or older?

Management of High-Grade Squamous Intraepithelial Lesion (HSIL) / CIN 2-3 in Women ≥25 Years

For women aged 25 years and older with histologically confirmed CIN 2-3, treatment with excisional or ablative procedures is the standard recommendation, though active surveillance has emerged as an acceptable alternative in carefully selected cases who meet strict criteria and can comply with intensive monitoring. 1, 2

Primary Management Options

Treatment (Standard Approach)

Excisional or ablative treatment is strongly recommended for most women ≥25 years with CIN 2-3 due to the significant progression risk. 2 The rationale is compelling:

• CIN 2 carries a 22% risk of progression to carcinoma in situ or invasive cancer if untreated, with 35% persisting and only 43% regressing spontaneously 2
• CIN 3 has a 14% progression risk to invasive cancer, with 56% persisting and 32% regressing 2
• Approximately 2% of women with HSIL cytology harbor invasive cancer at diagnosis 1

Treatment Modalities

When colposcopy is satisfactory (squamocolumnar junction and upper lesion limit visible):

• Loop electrosurgical excision procedure (LEEP) is preferred as the most cost-effective excisional method with high cure rates 1
• Ablative methods (cryotherapy, laser ablation) are acceptable alternatives for smaller lesions when colposcopy is satisfactory 1, 2

When colposcopy is unsatisfactory:

• LEEP or cold-knife conization is mandatory; ablation is unacceptable because you cannot exclude invasive disease 1
• Cold-knife conization is preferred when microinvasion is suspected 1

Treatment Outcomes

• Overall failure rates range 5-15% across different modalities, with no significant difference between excisional and ablative approaches 3, 2
• Women remain at increased risk for invasive cervical cancer (56 per 100,000) for at least 20 years post-treatment, necessitating long-term surveillance 2

Active Surveillance (Acceptable Alternative)

Active surveillance is an acceptable management option for women ≥25 years who meet strict selection criteria, based on the 2025 British Society of Colposcopy and Cervical Pathology/European Society of Gynaecologic Oncology consensus. 3 This represents a significant evolution in management philosophy.

Mandatory Selection Criteria for Active Surveillance

Active surveillance should only be offered when ALL of the following are met:

• The squamocolumnar junction and upper limit of all lesions must be fully visible 3
• Patient is willing and likely to comply with intensive monitoring visits 3
• No immunosuppression (immunosuppressed women should be treated, not observed) 3
• No previous cervical treatment (previously treated women should not be offered surveillance) 3
• Multidisciplinary review with expert pathology confirmation of the CIN 2 diagnosis 3

Risk Factors Suggesting Treatment Over Surveillance

The following factors increase progression risk and should weigh heavily toward treatment rather than surveillance:

• HPV-16 or HPV-18 genotypes (if available) 3, 4
• Large lesion size or involvement of >2 quadrants 3
• High-grade index cytology 3
• Major colposcopic changes (versus minor changes) 4
• Age >30 years (though no absolute upper age limit exists, the long-term invasion risk should be discussed) 3

Research supports these risk stratifications: HPV-16 infection predicts lower regression rates (OR 5.4 for regression with non-HPV-16 types), as do major colposcopic findings (OR 2.8 for regression with minor changes) and low-grade cytology (OR 4.1 for regression with ASC-US/LSIL versus HSIL). 4

Active Surveillance Protocol

If surveillance is chosen:

• Histological confirmation required at baseline and at least annually until HPV-negative or treatment decision made 3
• Additional histological confirmation required for worsening or persistent lesions 3
• Natural history data show 55.4% cumulative regression by 12 months and 62.9% by 24 months, with 29.3% progression to CIN 3+ by 12 months 3

Post-Treatment Follow-Up

HPV DNA testing at 6-12 months is the preferred follow-up strategy, with approximately 90% sensitivity compared to 70% for cytology alone. 1, 2 After 2 consecutive "negative for intraepithelial lesion or malignancy" results, return to routine screening is recommended. 1

Special Populations

Pregnant Women

Treatment is deferred unless invasive cancer is suspected or confirmed—this is the only indication for therapy during pregnancy. 3, 5

• Colposcopy with biopsy of lesions suspicious for CIN 2-3 or cancer is recommended 5
• Endocervical curettage is absolutely contraindicated 5
• CIN 2-3 has minimal progression risk during pregnancy with high postpartum regression rates (up to 69%) 2
• Re-evaluation with cytology and colposcopy no sooner than 6 weeks postpartum 5

Immunosuppressed Women (Including HIV)

Immunosuppressed women should not be offered active surveillance and should be treated. 3

• HIV-infected women have significantly increased recurrence risk after treatment and require careful long-term follow-up with frequent cytologic screening and colposcopy 1, 2

Critical Pitfalls to Avoid

• Do not use HPV testing or repeat cytology for triage of HSIL cytology—the disease risk is too high (53-66% have CIN 2+ on colposcopy, 84-97% on LEEP) 1
• Do not perform ablation when colposcopy is unsatisfactory—you cannot exclude invasive disease 1
• Do not assume cytological HSIL equals histological CIN 2-3—they are not equivalent 3, 2
• Colposcopy can miss significant CIN 2-3 lesions, emphasizing the importance of careful evaluation and appropriate follow-up 1
• Do not offer active surveillance to immunosuppressed or previously treated women 3