How should a 61-year-old woman with low-grade squamous intraepithelial lesion (LSIL) on Pap cytology and a negative high-risk human papillomavirus (HPV) test be managed?

Management of 61-Year-Old Woman with LSIL and Negative HPV

This patient requires continued surveillance with repeat cotesting (Pap + HPV) in 1 year, and she cannot discontinue cervical cancer screening at age 65 based on this result alone. 1

Why This Result Prevents Routine Screening Discontinuation

The combination of LSIL cytology with negative HPV testing creates a discordant result that carries significantly elevated risk compared to normal screening:

• The 5-year risk of CIN 3+ after HPV-negative LSIL is approximately 0.54-1.1%, which is roughly 4 times higher than the risk after a completely negative cotest (0.27%). 1
• This elevated risk exceeds the threshold that would allow routine 5-year screening intervals or age-based discontinuation. 1
• Women over age 65 with a history of abnormal cytology (including LSIL) must continue screening even when HPV is negative, and may only discontinue after establishing adequate negative screening history. 2, 1

Recommended Management Algorithm

Immediate Next Steps:

• Do NOT proceed to colposcopy at this time unless there are visible cervical lesions on examination. 2
• Repeat cotesting (Pap + HPV) in 1 year rather than returning to routine 5-year intervals. 1

Subsequent Management Based on Follow-Up Results:

If repeat cotest shows:

• Any cytologic abnormality (ASC-US or higher) OR positive HPV → Refer immediately to colposcopy. 1
• Negative cytology AND negative HPV → Continue enhanced surveillance with cotesting every 3 years (not 5 years) until adequate negative screening history is established. 1

Requirements for Screening Discontinuation:

This patient cannot stop screening at age 65 until she achieves either:

• Two consecutive negative cotests (both Pap and HPV negative), OR
• Three consecutive negative Pap tests alone 1
• The most recent test must be performed within the prior 5 years. 2

Clinical Rationale and Evidence Nuances

Why HPV-Negative LSIL Occurs:

• While 71-86% of LSIL cases are typically HPV-positive 3, 4, this discordant result (LSIL with negative HPV) can occur due to:
  • Sampling error
  • Low viral load below detection threshold
  • Non-HPV-related cellular changes mimicking LSIL
  • Recent clearance of HPV infection with persistent cytologic changes

Age-Specific Considerations:

• In women ≥40 years, only 56-73% of LSIL cases are HPV-positive, making this discordant result more common in older women. 4, 5
• The negative predictive value of HPV testing for CIN3+ in LSIL approaches 100% in women ≥40 years when HPV is truly negative. 4

Why Colposcopy Is Not Immediately Indicated:

• Colposcopy has limited sensitivity for detecting all cervical lesions, so even a negative colposcopy would not eliminate the need for continued surveillance. 1
• The absolute risk, while elevated compared to normal screening, does not reach the threshold that mandates immediate colposcopic evaluation (unlike HSIL or ASC-H). 2
• Conservative management with enhanced surveillance is appropriate given the patient's age and the relatively low absolute risk. 2

Common Pitfalls to Avoid

• Do not assume this patient can discontinue screening at age 65 simply because she is approaching that age—the abnormal cytology history requires continued surveillance. 1
• Do not return to routine 5-year screening intervals after a single negative follow-up test—she needs 3-year cotesting until adequate negative history is documented. 1
• Do not perform immediate colposcopy unless subsequent testing shows persistent abnormalities or HPV positivity. 2, 1
• Do not ignore this result as "low-risk" because HPV is negative—the discordance itself signals elevated risk requiring enhanced surveillance. 1

Documentation and Patient Counseling

• Clearly document that this patient has not met criteria for screening discontinuation and requires ongoing surveillance. 2
• Counsel the patient that she will need to continue screening beyond age 65 until adequate negative results are established. 1
• Ensure robust follow-up systems are in place, as loss to follow-up in this population can result in missed high-grade lesions. 6