What is the recommended management for a 36‑year‑old woman with a Pap smear showing high‑grade squamous intraepithelial lesion and a positive high‑risk human papillomavirus test?

Management of HSIL with Positive High-Risk HPV

Immediate Colposcopy is Mandatory

A 36-year-old woman with HSIL cytology and positive high-risk HPV must undergo immediate colposcopy with directed biopsy, as this combination carries a very high risk of underlying high-grade cervical intraepithelial neoplasia (CIN 2/3) or invasive disease. 1

Primary Management Algorithm

Step 1: Immediate Colposcopic Evaluation

• Colposcopy should be performed without delay for all women with HSIL cytology, regardless of HPV status, due to the substantial risk of underlying CIN 2/3 or invasive cancer. 1
• During colposcopy, the cervix should be examined with 10x-16x magnification after application of 3-5% acetic acid solution to identify abnormal areas requiring biopsy. 2
• Colposcopically directed biopsies must be performed on all suspicious areas to rule out invasive disease and determine the extent of preinvasive disease. 2
• If the entire squamocolumnar junction is not visualized (unsatisfactory colposcopy), endocervical curettage should be performed. 1, 2

Step 2: Expedited Treatment Option

• For non-pregnant patients aged ≥25 years with HSIL and positive HPV 16, expedited treatment (see-and-treat) may be considered as an alternative to colposcopy with biopsy, based on the extremely high risk of underlying high-grade disease. 3, 4
• This approach allows for immediate excisional treatment at the time of initial colposcopy without waiting for biopsy confirmation, reducing the number of procedures and potential loss to follow-up. 3

Step 3: Management Based on Biopsy Results

If CIN 2/3 is confirmed:

• Treatment with excisional procedure (LEEP or cold-knife conization) is recommended. 2
• For CIN 2 in younger women desiring fertility preservation, observation may be considered, though this is less applicable at age 36. 2
• For CIN 3, treatment with excisional procedure is mandatory. 2

If biopsy shows only CIN 1 or is negative despite HSIL cytology:

• This represents a significant discordance that requires careful evaluation. 1
• Endocervical curettage should be performed if not already done. 1, 2
• Repeat colposcopy or diagnostic excisional procedure (LEEP) may be warranted given the high-grade cytology. 1

Evidence Strength and Clinical Context

• The positive predictive value of HSIL cytology for underlying CIN 2/3+ is approximately 90.5% when hrHPV is positive, making immediate intervention essential. 5
• In women with HSIL cytology, 89.3% test positive for high-risk HPV, and the combination significantly elevates risk. 5
• HPV 16 is present in 61% of invasive cervical carcinomas and 68% of severe dysplasias, making HPV 16-positive HSIL particularly concerning. 6

Critical Pitfalls to Avoid

• Never delay colposcopy for repeat cytology or HPV testing when HSIL is diagnosed—this is the most serious cytologic abnormality short of invasive cancer. 1
• Do not rely on negative hrHPV testing to downgrade management if HSIL cytology is present; approximately 8.3% of morphologically diagnostic HSIL cases may be hrHPV negative by standard testing but still harbor high-grade disease. 7
• Do not perform HPV genotyping before colposcopy—colposcopy is indicated regardless of specific HPV type when HSIL is present. 4
• Endocervical curettage is contraindicated in pregnancy, though colposcopy should still be performed. 4, 2

Post-Treatment Surveillance

• After treatment for high-grade precancer, surveillance must continue for at least 25 years with HPV testing or co-testing at 6,18, and 30 months post-treatment. 2
• More frequent screening is recommended for immunocompromised women, including those with HIV. 2