Management of ASCUS with Negative HPV Testing
For a patient with ASCUS cytology and negative HPV testing, repeat Pap testing should be performed in 3 years, not the previously recommended 12 months. 1
Updated Screening Interval
The American Cancer Society updated their recommendation in 2025 from a 12-month to a 3-year interval for repeat Pap testing after HPV-negative ASCUS results, based on expanded data analysis from over 1.1 million women with extended follow-up. 1
This recommendation applies the principle of "similar management of similar risks"—the 5-year risk of CIN3+ after HPV-negative ASCUS is 0.48%, which is closer to the risk after a negative Pap test alone (0.31%) than after a completely negative cotest (0.11%). 1, 2
The risk profile, while higher than a completely negative cotest, remains relatively low and does not warrant the more intensive 12-month surveillance previously recommended. 1
Management Algorithm
Initial Management:
- Repeat Pap testing at 3 years after the HPV-negative ASCUS result 1
At Follow-up:
- If the repeat Pap test is normal: return to routine age-appropriate screening intervals 1
- If the repeat Pap shows ASCUS or more serious abnormality: manage according to the specific abnormality found (which would typically involve colposcopy if HPV-positive) 1
Critical Distinctions to Understand
HPV-negative ASCUS is NOT the same as a negative cotest—the risk is approximately 4-fold higher than after both tests are negative, which is why the interval is 3 years rather than 5 years. 1
High-grade histological changes (CIN2+) are detected in less than 12% of ASCUS cases overall, and this risk is substantially lower when HPV is negative. 1
The negative predictive value of HPV testing in ASCUS cases is extremely high at 99% for excluding HSIL. 3
Common Pitfalls to Avoid
Do not return to screening too soon (before 3 years)—this leads to unnecessary procedures and overtreatment. 1
Do not wait 5 years between screenings after HPV-negative ASCUS—the risk is higher than after a completely negative cotest and requires the shortened 3-year interval. 1
Do not perform immediate colposcopy for all ASCUS results regardless of HPV status—this leads to unnecessary procedures when HPV is negative. 1
Do not assume this result is sufficiently reassuring to allow early exit from screening at age 65—HPV-negative ASCUS does not meet criteria for stopping screening. 1
Age-Specific Context
For women aged 30-65 years, cotesting (HPV plus cytology) remains the preferred screening approach, with 5-year intervals when both tests are completely negative. 1
When ASCUS is found with negative HPV in this age group, the interval is specifically shortened to 3 years based on the intermediate risk profile. 1