Management of Negative Pap Smear with Positive HPV Test
For a patient with a negative Pap smear (NIL) and positive HPV test, the recommended next step is to repeat both HPV testing and cytology in 12 months. 1
Risk Assessment and Management Algorithm
The finding of a negative Pap smear with positive HPV represents a clinically significant scenario that requires appropriate follow-up. The management approach depends on several factors:
Initial Management
Repeat co-testing at 12 months (HPV test plus Pap smear) is the preferred approach 1
- This allows time to determine if the HPV infection will persist or clear naturally
- Avoids unnecessary colposcopy for transient infections
Alternative approach: HPV genotyping if available
- If positive for HPV types 16 or 18, proceed directly to colposcopy 1
- These high-risk types have stronger association with cervical cancer
Follow-up at 12 months:
- If both HPV and cytology are negative: Return to routine screening 2
- If HPV remains positive OR cytology shows ASC-US or worse: Refer for colposcopy 1, 2
Special Considerations
Age-specific management:
- For women ≥30 years: The above algorithm applies
- For women <30 years: HPV testing is generally not recommended for primary screening, but if performed and positive with negative cytology, follow the same 12-month follow-up protocol 1
Risk factors requiring closer monitoring:
- Previous abnormal results
- Immunosuppression
- History of high-grade lesions
Evidence Quality and Rationale
The recommendation for 12-month follow-up rather than immediate colposcopy is based on the understanding that:
- Most HPV infections are transient and will clear spontaneously within 1-2 years 3
- The risk of high-grade cervical intraepithelial neoplasia (CIN 2+) in women with negative cytology but positive HPV is relatively low (approximately 5.7%) 4
- The negative predictive value of HPV testing is very high (>99%) 4
Common Pitfalls to Avoid
- Overtreatment: Avoid immediate colposcopy or treatment without evidence of cellular abnormalities
- Undertreatment: Don't return to routine screening without appropriate follow-up
- Poor documentation: Ensure all test results and follow-up plans are clearly documented 1
- Loss to follow-up: Develop systems to track patients who need repeat testing
Documentation Requirements
Document the following in the patient's record:
- HPV test result (including genotype if available)
- Pap test result
- Follow-up plan with specific timeframe
- Patient education provided regarding the significance of results
The 2019 American Society for Colposcopy and Cervical Pathology (ASCCP) risk-based management guidelines support this approach, focusing on the patient's risk of developing cervical precancer rather than specific test results alone 1.