What is the recommended management approach for a patient with a low-grade intraepithelial lesion and Human Papillomavirus (HPV) positive, not types 16 or 18?

Management of Low-Grade Intraepithelial Lesion with HPV Positive (Non-16/18)

For a patient with a low-grade intraepithelial lesion (LSIL) and HPV positive (not types 16 or 18), annual follow-up with repeat HPV testing or cotesting is recommended rather than immediate colposcopy. 1

Management Algorithm

Initial Management:

• If HPV is positive (not types 16 or 18) with LSIL cytology:
  • Return in 1 year for repeat testing is recommended 1
  • HPV testing or cotesting (HPV plus Pap test) is preferred over cytology testing alone 1

Follow-up Testing:

• At 1-year follow-up:
  • If HPV negative: Return to routine screening
  • If HPV positive: Refer for colposcopy
  • If HPV positive for second consecutive time: Colposcopy is always recommended regardless of previous Pap test results 1

Special Considerations:

• If the patient has a history of high-grade lesions (CIN 2, CIN 3, histologic or cytologic HSIL), colposcopy may be warranted instead of annual follow-up 1
• Negative HPV test or cotest results from screening within the last 5 years may reduce risk sufficiently to defer colposcopy 1

Evidence and Rationale

The CDC's 2021 sexually transmitted infections treatment guidelines clearly state that for HPV types other than 16 or 18 with normal cytology, a 1-year return is recommended 1. This approach balances the need for surveillance with avoiding unnecessary procedures.

HPV testing or cotesting is superior to cytology alone for follow-up, as negative HPV testing is less likely to miss disease than normal cytology testing 1. This is why HPV testing or cotesting is preferred for monitoring these patients.

The risk of progression from LSIL to high-grade lesions varies by HPV type. HPV 16 and 18 carry the highest risk for progression to cervical cancer, with HPV 16 being 2-fold and HPV 18 being 1.5-fold more common in squamous cell carcinoma than in HPV-positive LSIL 2. Non-16/18 HPV types generally have lower progression rates, supporting a more conservative management approach.

Long-term Surveillance

If the patient eventually requires treatment for a high-grade precancer:

• Initial post-treatment testing should include HPV test or cotest at 6,18, and 30 months 1, 3
• Long-term surveillance should continue for at least 25 years after treatment, even beyond age 65 1
• Testing should occur at 3-year intervals if using HPV testing or cotesting 1

Important Caveats

• Risk of progression: While most LSILs regress spontaneously, a small proportion can progress to high-grade lesions. The risk is lower with non-16/18 HPV types but not zero 4
• Compliance is crucial: Patient education about the importance of follow-up is essential, as missed follow-up appointments can lead to delayed detection of progression 3
• Smoking increases risk: Daily cigarette smoking is associated with a 1.67-fold increased risk of LSIL progression and should be addressed 5
• Marked cytological atypia: LSILs with marked cytological atypia have a higher rate of progression to HSIL (36% vs 7% for typical LSIL) and may warrant closer monitoring 4

By following this evidence-based approach, the risk of progression to more severe disease can be minimized while avoiding unnecessary procedures for lesions that are likely to regress spontaneously.