Management of ASC-US with Negative HPV Testing
For a patient with ASC-US cytology and negative HPV testing, repeat cervical cytology in 12 months is recommended, followed by return to routine screening if normal. 1
Risk Stratification
ASC-US with negative HPV represents a low-risk scenario, with a 5-year risk of CIN3+ of only 0.48% and cancer risk of 0.043%. 2
This risk profile is closer to a negative Pap test alone (0.31% CIN3+ risk) than to a completely negative cotest (0.11% CIN3+ risk), meaning the HPV-negative result provides substantial but not complete reassurance. 2
The negative predictive value of HPV testing for excluding high-grade lesions is 98.5-99.6%, making this a reassuring but not zero-risk scenario. 3
Management Algorithm
Initial Follow-Up
Repeat Pap testing at 12 months is the recommended approach for HPV-negative ASC-US. 1
This represents an updated recommendation from older guidelines that suggested 5-year intervals, now shortened to account for the slightly elevated risk compared to completely negative cotesting. 1
Subsequent Management Based on 12-Month Results
If the repeat Pap test is normal: Return the patient to routine screening intervals (every 3 years for cytology alone, or every 5 years for cotesting if age ≥30 years). 1
If the repeat Pap shows ASC-US or more serious abnormality: Manage according to the specific abnormality found, following standard guidelines for that result. 1
Continue repeat testing at 6- and 12-month intervals until two consecutive negative results are obtained if abnormalities persist. 1
Age-Specific Considerations
For women aged 30-65 years, cotesting (HPV plus cytology) remains the preferred screening approach with 5-year intervals when both tests are negative. 1
When ASC-US is found with negative HPV in this age group, the follow-up interval is specifically shortened to 12 months rather than the standard 5-year cotest interval. 1
Critical Pitfalls to Avoid
Do not return to routine 5-year screening immediately after HPV-negative ASC-US, as the risk is higher than after a completely negative cotest and warrants closer surveillance. 1
Do not screen too soon (before 12 months), as this is unnecessary and may lead to overtreatment of transient abnormalities. 1
Do not perform immediate colposcopy for ASC-US with negative HPV, as this leads to unnecessary procedures in a low-risk population. 4
Do not assume HPV-negative ASC-US is sufficiently reassuring to allow women to stop screening at age 65, as the risk remains elevated compared to truly negative results. 1
Evidence Supporting This Approach
The recommendation is based on expanded data analysis from over 1.1 million women with extended follow-up, demonstrating that the 3-year interval (with initial 12-month follow-up) is more appropriate than the 5-year interval for HPV-negative ASC-US. 1
The principle of "similar management of similar risks" supports this approach, as HPV-negative ASC-US carries intermediate risk between a negative Pap alone and a completely negative cotest. 1
High-grade histological changes after colposcopic evaluation for ASC-US are typically detected in less than 12% of cases overall, and significantly lower when HPV is negative. 1, 4