What is the management for a patient with a Pap test showing Human Papillomavirus (HPV) other types positive, but HPV 16 and 18 negative?

Management of HPV-Positive (Other High-Risk Types), HPV 16/18 Negative Pap Test

For a patient with positive high-risk HPV (non-16/18 types) and negative HPV 16/18, the recommended management is repeat co-testing (HPV and cytology) at 12 months, with colposcopy reserved only if HPV remains positive or cytology becomes abnormal at follow-up. 1

Rationale for Conservative Management

The risk stratification for non-16/18 high-risk HPV types differs substantially from HPV 16/18:

• Women with non-16/18 high-risk HPV types have only a 1.5-3% risk of CIN 3+, which falls below the threshold for immediate colposcopy 1
• In contrast, HPV 16 or 18 positive patients carry a 17-21% 10-year cumulative risk of CIN 3+, warranting immediate colposcopy regardless of cytology 1
• Approximately 60% of high-risk HPV infections clear spontaneously within one year, supporting the rationale for observation rather than immediate intervention 1

Management Algorithm

Initial Management (At Time of Positive Result)

• Schedule repeat co-testing (both HPV and cytology) at 12 months from the initial positive HPV result 1
• Do not perform immediate colposcopy for women with negative cytology but positive non-16/18 high-risk HPV 1

At 12-Month Follow-Up

If both HPV and cytology are negative:

• Return to routine age-based screening (typically every 3 years for co-testing) 1

If HPV remains positive (regardless of cytology):

• Proceed to colposcopy with endocervical sampling 1

If cytology shows any abnormality (regardless of HPV status):

• Proceed to colposcopy according to cytology-based management guidelines 1

Important Caveats and Pitfalls

What NOT to Do

• Do not use HPV genotyping for further triage in women already confirmed negative for HPV 16/18 1
• Do not perform treatment based on HPV result alone without histologic confirmation of disease 1
• Do not test for low-risk HPV types (e.g., types 6 and 11) as this is clinically inappropriate 1

Testing Preferences

• HPV testing or co-testing is preferred over cytology alone for follow-up, as negative HPV testing is less likely to miss disease than normal cytology alone 1

Risk Context from Recent Evidence

While the conservative approach is appropriate, clinicians should be aware:

• A 2021 study found that 6.5% of women with non-16/18 high-risk HPV and negative cytology had CIN 2+ lesions on immediate colposcopy-guided biopsy 2
• 2.7% had CIN 3+ lesions, and one patient (0.1%) had invasive cervical cancer 2
• However, this does not change guideline recommendations, as the overall risk remains below the threshold for immediate colposcopy, and the 12-month follow-up strategy balances detection with avoiding overtreatment 1

Post-Colposcopy Management (If Performed)

If CIN 2+ is detected:

• Treatment options include ablative or excisional procedures 1
• Surveillance must continue for at least 25 years post-treatment 1
• Initial post-treatment testing includes HPV test or cotest at 6,18, and 30 months 1
• Long-term surveillance includes testing at 3-year intervals if using HPV testing or cotesting 1

If CIN 1 or less:

• Repeat HPV testing with or without Pap test in 1 year 1