What is the appropriate management for a patient with a positive high‑risk human papillomavirus (HPV) test, normal Papanicolaou (Pap) smear, and a history of low‑grade squamous intraepithelial lesion (LSIL) more than five years ago?

Management of HPV-Positive, Normal Cytology with Remote LSIL History

A patient with high-risk HPV positivity and normal cytology should undergo colposcopy, regardless of the remote LSIL history from over 5 years ago. 1

Primary Management Recommendation

Immediate colposcopy is the preferred next step for any adult woman with a positive high-risk HPV test and normal cytology (also termed HPV-positive NILM or "HPV-positive, cytology-negative"). 1 This recommendation applies even though the cytology is currently normal, because:

• HPV positivity with any cytology result—including normal cytology—carries significant risk of underlying high-grade CIN, with studies showing that HPV-positive women harbor CIN 2+ in approximately 10-12% of cases even when cytology appears normal. 1
• The American Society for Colposcopy and Cervical Pathology (ASCCP) and National Comprehensive Cancer Network (NCCN) both recommend colposcopy as the preferred management for HPV-positive results in women ≥30 years, with higher risk of underlying significant disease in this age group. 1

Why the Remote LSIL History Matters

The history of LSIL >5 years ago further elevates this patient's risk profile and reinforces the need for enhanced surveillance:

• Women with a history of LSIL or ASC-US require 3-year cotesting intervals (rather than 5-year intervals) even after achieving negative HPV results, because their 5-year risk of CIN3+ remains elevated at approximately 1.1% compared to 0.27% after negative cotesting in women without such history. 2
• A patient cannot discontinue screening at age 65 based on prior abnormal cytology alone; she must establish either 2 consecutive negative cotests or 3 consecutive negative Pap tests before discontinuing screening. 2
• The ASCCP consensus conference data demonstrate that prior cytologic abnormalities confer approximately four times higher risk of future CIN3+ compared to women with consistently normal screening. 2

Colposcopy Protocol and Follow-Up

If colposcopy is satisfactory:

• CIN 2+ detected: Proceed with appropriate treatment (ablative or excision procedure such as LEEP, cryotherapy, or laser ablation). 1
• CIN 1 or negative findings: Repeat HPV testing or cotesting at 12 months (not earlier). 1, 3
• If 12-month HPV remains positive or cytology shows ASC-US or higher: Refer back to colposcopy. 1
• If 12-month testing is negative: Return to 3-year cotesting intervals (not 5-year intervals) given the prior LSIL history. 2

If colposcopy is unsatisfactory:

• Perform endocervical curettage (ECC) and cervical biopsy, then manage according to histologic findings. 1

Common Pitfalls to Avoid

• Do not delay colposcopy based on the assumption that normal cytology provides reassurance; HPV positivity overrides the cytology result in risk stratification. 1
• Do not rely on repeat cytology alone for HPV-positive cases in women ≥30 years, as cytology has lower sensitivity (76.2%) compared to immediate colposcopy for detecting high-grade disease. 1
• Do not order HPV genotyping (HPV 16/18) before colposcopy; colposcopy is indicated for all high-risk HPV types in this context, and genotyping does not change the immediate management. 1
• Do not assume low risk despite "normal" cytology; the combination of HPV positivity with any cytology result—even normal—significantly increases risk compared to HPV-negative women. 1
• Do not return to 5-year screening intervals after negative follow-up testing; this patient requires 3-year cotesting indefinitely due to her prior LSIL history. 2

Evidence Strength

This recommendation is based on strong consensus guidelines from ASCCP (2019), NCCN, and ACOG, with Level 1 evidence from large cohort studies (Kaiser Permanente Northern California data) demonstrating that HPV-positive women—regardless of cytology—have substantially elevated risk of CIN 2+ that warrants colposcopic evaluation. 1, 2 The ALTS trial further established that HPV testing has 88-90% sensitivity for detecting high-grade lesions, making HPV positivity a critical trigger for colposcopy even when cytology is reassuring. 1