What would you do if a smear showed possible Low-grade Squamous Intraepithelial Lesions (LSIL)?

Management of Low-Grade Squamous Intraepithelial Lesion (LSIL) on Cervical Cytology

For adult women (≥21 years) with LSIL on Pap smear, proceed directly to colposcopy with directed biopsy—this is the standard of care because no effective triage strategy exists and approximately 12% will have CIN 2,3 or worse within two years. 1

Age-Based Management Algorithm

Adults (Age ≥21 years)

Immediate colposcopy is recommended because the ASCUS-LSIL Triage Study (ALTS) demonstrated that no useful triage strategy was identified for LSIL in adults, making colposcopy the most efficient initial approach 1. HPV DNA testing is not recommended as a triage tool because 82-86% of women with LSIL are HPV positive, rendering it clinically useless for decision-making 1, 2.

After Satisfactory Colposcopy:

If biopsy shows CIN 1 or negative findings:

• Follow with repeat cytology at 6-month intervals OR HPV DNA testing at 12 months 1, 2
• If two consecutive cytology results are negative at 6 and 12 months, return to routine screening 1, 2
• If repeat cytology shows ASC-US or greater, refer back to colposcopy 1
• If HPV testing at 12 months is positive, perform colposcopy; if negative, return to routine screening 1, 2
• Do not treat CIN 1 immediately—over 90% of LSIL lesions regress within 24 months, and treatment represents overtreatment with risks including cervical stenosis and preterm birth in future pregnancies 2, 3

If biopsy shows CIN 2 or CIN 3:

• Proceed with treatment using LEEP, cryotherapy, cold knife conization, or laser ablation 1

After Unsatisfactory Colposcopy:

• Perform endocervical curettage (ECC) in addition to directed cervical biopsy 1
• If ECC is negative or shows CIN 1, follow the same protocol as satisfactory colposcopy with negative/CIN 1 findings 1

Adolescents and Young Women (Age <21 years)

Do NOT perform immediate colposcopy—instead, repeat cytology at 12 months 1. This conservative approach is justified because HPV infections clear rapidly in this age group, LSIL regression rates exceed 50%, and progression to cancer is extremely rare 1, 2.

Follow-up protocol:

• At 12 months: If cytology is negative, ASC-US, or LSIL, repeat again at 24 months 1
• At 24 months: If negative after this 3-year period, resume routine screening 1, 2
• Refer to colposcopy only if: repeat cytology at 12 months shows ASC-H or HSIL, OR cytology at 24 months shows ASC-US or greater 1
• HPV testing is unacceptable in this age group 1

Critical Clinical Pitfalls to Avoid

Loss to follow-up is the greatest risk: In high-risk populations, up to 42% of patients with LSIL are lost to follow-up when colposcopy is delayed 4. If you have concerns about patient compliance or access to care, immediate colposcopy is strongly preferred over repeat cytology strategies 1, 4.

Do not confuse cytologic LSIL with histologic CIN 1: Cytologic LSIL has poor correlation with histology—studies show overdiagnosis rates of 11.7% and underdiagnosis rates of 31% 3. This is why colposcopy with biopsy is essential for accurate diagnosis 3.

Recognize high-risk LSIL features: If the cytology report describes LSIL with marked cytological atypia (≥5 cells with nuclear enlargement ≥5 times normal or multinucleation with ≥5 nuclei), the risk of subsequent HSIL increases to 36% versus 7% for standard LSIL, and excisional cone biopsy should be strongly considered 5.

HPV genotyping provides additional risk stratification: While not part of standard algorithms, HPV 16/18 positivity increases HSIL risk to 32%, and multiple HPV subtypes increase risk to 46%, compared to 16% for non-16/18 high-risk types and 12% for HPV-negative cases 6. This information can guide intensity of follow-up when available 6.

Prior screening abnormalities matter: For HPV-negative LSIL cases, those with prior screening abnormalities have a 23% HSIL rate versus only 4% without prior abnormalities 6.

Special Populations

Immunocompromised or HIV-infected women: These patients have higher risk of persistence and progression of LSIL and require more intensive follow-up, though specific modified algorithms are not well-defined in the guidelines 2, 7.

If CIN 1 persists for ≥2 years: Either continued follow-up or treatment becomes acceptable 1. If treatment is selected and colposcopy is satisfactory, either excision or ablation is acceptable 1.