What is the recommended management for a 29‑year‑old woman with a low‑grade squamous intraepithelial lesion (LSIL) on Pap test and a negative high‑risk human papillomavirus (HPV) test?

Management of LSIL with Negative HPV in a 29-Year-Old Woman

Primary Recommendation

Repeat co-testing (Pap + HPV) in 1 year is the recommended management for a 29-year-old woman with LSIL cytology and negative high-risk HPV testing. 1

Rationale and Risk Assessment

• The combination of LSIL with negative HPV testing represents a significantly lower risk profile than HPV-positive LSIL, with only approximately 12% risk of underlying CIN2+ compared to 20% when HPV is positive. 2, 3

• The negative predictive value of HPV testing for CIN3+ in women with LSIL is exceptionally high (98.9-100%), meaning that the absence of high-risk HPV makes significant disease highly unlikely. 3, 4

• Immediate colposcopy is NOT indicated for this patient because the guidelines reserve colposcopy for HPV-positive LSIL cases, where the risk of underlying high-grade disease justifies immediate evaluation. 1

Management Algorithm

Immediate Management

• Do not perform colposcopy at this time, as the patient's risk profile does not warrant it. 1
• Schedule repeat co-testing (Pap + HPV) in 12 months rather than returning to routine 3-year screening intervals. 1, 5

Follow-Up at 12 Months

• If repeat co-test is negative (negative cytology AND negative HPV): Return to routine age-appropriate screening intervals. 1
• If any abnormality persists (ASCUS or higher cytology) OR HPV becomes positive: Refer to colposcopy immediately. 1, 5

Evidence Quality and Guideline Basis

• This recommendation is based on strong consensus from the American Society for Colposcopy and Cervical Pathology (ASCCP), which established that HPV-negative abnormal cytology does not require the same aggressive management as HPV-positive results. 1

• The ASCUS-LSIL Triage Study (ALTS) demonstrated that HPV testing has 92% sensitivity for detecting CIN2+ lesions, validating its use as a reliable risk stratification tool. 1

Age-Specific Considerations

• At age 29, this patient is in the age group where transient HPV infections and low-grade cytologic abnormalities are most common, but the negative HPV test significantly reduces concern for progressive disease. 4

• Women under 30 with LSIL have higher rates of HPV positivity (91.1%) compared to women ≥30 years (73%), so a negative HPV test in this age group is particularly reassuring. 4

Common Pitfalls to Avoid

• Do not proceed to immediate colposcopy based solely on the LSIL cytology result when HPV is negative—this would result in unnecessary procedures with low diagnostic yield. 1, 3

• Do not return the patient to routine 3-year screening intervals after a single HPV-negative LSIL result, as the 5-year risk of CIN3+ (1.1%) remains elevated compared to completely negative screening (0.27%). 5

• Do not perform HPV genotyping at this stage, as it does not change management when HPV testing is already negative. 1

• Ensure the patient understands the importance of returning for 12-month follow-up, as compliance with recommended follow-up intervals is often suboptimal (only 45-54% in some studies). 6, 2

What Makes This Case Different from HPV-Positive LSIL

• HPV-positive LSIL requires immediate colposcopy because the combination carries approximately 20-26% risk of CIN2+ and warrants direct visualization. 1, 2

• HPV-negative LSIL has only 12% risk of CIN2+, which is low enough to justify surveillance rather than immediate intervention. 2, 3

• Only 1.7% (2/539) of HPV-negative LSIL cases progress to HSIL, compared to 5.7% (3/53) of HPV-positive cases. 6