What are the next steps for a woman positive for high-risk Human Papillomavirus (HPV) but not types 16 or 18?

Management of Women Positive for High-Risk HPV (Non-16/18)

For women who test positive for high-risk HPV types other than 16 or 18, the next step should be cytology testing (Pap test) followed by annual follow-up if cytology is normal, or immediate colposcopy if cytology shows any abnormality. 1

Initial Management Algorithm

1. Reflex Cytology Testing

   • Ideally performed from the same specimen as the HPV test
   • Should be done automatically by the laboratory to avoid requiring the patient to return 1, 2

2. Based on Cytology Results:

   • If cytology is normal (NILM):

     • Return in 1 year for repeat co-testing (HPV and cytology) 1, 2
     • No immediate colposcopy needed

   • If cytology shows any abnormality (ASC-US or worse):

     • Proceed directly to colposcopy 1, 2

Follow-up Management

If Initial Cytology Was Normal:

• At 12-month follow-up:
  • If HPV-negative and cytology normal: Return to routine screening
  • If HPV-positive (persistent infection): Colposcopy is recommended regardless of cytology results 1
  • If cytology abnormal: Colposcopy is recommended

Important Considerations

• Two consecutive HPV-positive tests: Colposcopy is always recommended, even if cytology remains normal 1
• History of high-grade lesions: May warrant colposcopy even with normal cytology 1
• Risk of progression: While HPV 16/18 carry the highest risk (17-21% for CIN3+), other high-risk HPV types still have approximately 3% risk of CIN3+ 1

Evidence Quality and Clinical Implications

The 2021 CDC guidelines provide the most recent and comprehensive recommendations for managing HPV-positive women 1. These guidelines recognize that while HPV 16/18 carry the highest risk, other high-risk HPV types still pose a significant concern.

Research has shown that approximately 15.6% of women with non-16/18 high-risk HPV can develop high-grade squamous intraepithelial lesions (HSIL) 3, which is lower than for HPV 16/18 but still clinically significant.

Common Pitfalls to Avoid

1. Overlooking persistent infection: Two consecutive positive HPV tests always warrant colposcopy, regardless of cytology results 1

2. Inadequate follow-up duration: After treatment for high-grade precancer, surveillance should continue for at least 25 years 1

3. Using cytology alone for follow-up: HPV testing or co-testing is preferred over cytology alone for follow-up after abnormal results 1, 2

4. Dismissing non-16/18 HPV types: While they carry lower risk than HPV 16/18, they still require systematic follow-up as they can lead to significant disease 3, 4

By following this structured approach to managing women with high-risk HPV (non-16/18), clinicians can ensure appropriate surveillance while avoiding unnecessary procedures, ultimately reducing morbidity and mortality from cervical cancer.