What are the next steps for a female patient of reproductive age with a history of regular gynecological check-ups, who has a last Pap (Papanicolau) smear result of Low-grade Squamous Intraepithelial Lesion (LSIL) and is positive for Human Papillomavirus (HPV)?

Management of LSIL with HPV Positivity

For a reproductive-age woman with LSIL cytology and positive HPV testing, perform repeat co-testing (Pap smear and HPV) at 12 months, and proceed to colposcopy only if HPV remains positive or cytology shows ASC-US or greater at that follow-up visit. 1

Age-Specific Considerations

The management approach differs significantly based on age:

Women Aged 21-24 Years

• Do NOT perform HPV testing in this age group, as transient HPV infections are extremely common and lead to unnecessary overtreatment 2, 3
• Repeat cytology alone at 12 months is the recommended approach 2
• Refer to colposcopy only if HSIL or greater appears on repeat cytology at 12 months 2, 3
• At 24-month follow-up, refer to colposcopy if ASC-US or greater is found 3
• Over 90% of LSIL cases in young women regress spontaneously within 24 months, and 91% clear within 36 months 4, 2

Women Aged 25-29 Years

• Either HPV testing at 12 months OR repeat cytology at 6 and 12 months are acceptable options 1, 3
• Proceed to colposcopy if HPV remains positive or if repeat cytology shows ASC-US or greater 1

Women Aged ≥30 Years

• Immediate colposcopy is recommended for this age group, as LSIL is less likely to regress and carries higher risk 2
• The HPV positivity rate in women ≥30 years with LSIL is approximately 57-64%, making HPV triage more useful than in younger women 5
• CIN 2-3 is significantly more likely in HPV-positive women in this age group (13.9% vs 5.7% in HPV-negative women) 5

Follow-Up Algorithm for Reproductive-Age Women (25-29 Years)

At 12-Month Follow-Up:

• Perform repeat co-testing (HPV and cytology) 1
• If HPV remains positive (regardless of cytology): proceed to colposcopy with endocervical sampling 1
• If cytology shows ASC-US or greater (regardless of HPV status): proceed to colposcopy 1
• If both HPV and cytology are negative: return to routine screening 4, 1

If CIN 1 is Diagnosed on Colposcopy:

• Continue surveillance with either HPV testing every 12 months or repeat cytology every 6-12 months 4
• If CIN 1 persists for at least 2 years, either continued follow-up or treatment is acceptable 4
• Treatment (excision or ablation) is only recommended if the colposcopic examination is satisfactory 4

Risk Stratification

The natural history of LSIL supports conservative management:

• Approximately 60% of high-risk HPV infections clear spontaneously within 12 months 1
• More than 90% of LSIL lesions regress within 24 months without treatment 4
• The risk of progression to CIN 2-3 within the first 24 months is low, and many CIN 2-3 lesions found in women with initial CIN 1 represent missed lesions rather than true progression 4

Long-Term Surveillance Requirements

After Resolution:

• Two consecutive negative co-tests are required before extending screening intervals 1
• Use 3-year co-testing intervals (rather than 5-year intervals) for patients with a history of LSIL, due to increased risk of CIN 3+ 1

Critical Pitfalls to Avoid

Do NOT perform immediate excisional procedures without histologic confirmation of CIN 2-3, as this represents overtreatment for LSIL 1

Do NOT ignore reflex HPV testing results if the patient is ≥25 years old—these results should guide management 2, 3

Do NOT test for low-risk HPV types (6,11)—only high-risk oncogenic types should be tested 1

Do NOT rely on cytology alone for treatment decisions—histologic confirmation is required before proceeding with excisional procedures 4

Ensure robust follow-up systems are in place, as loss to follow-up is a major concern in LSIL management 2, 3

Special Circumstances

If Initial Cytology Was HSIL or AGC-NOS (but biopsy showed only CIN 1):

• Either diagnostic excisional procedure OR observation with colposcopy and cytology at 6-month intervals for 1 year is acceptable 4
• This requires satisfactory colposcopy and negative endocervical sampling 4
• Consider reviewing cytology, histology, and colposcopy findings for potential discordance 4