Management of ASC-US with Negative HPV Testing
Recommended Management
Return to routine screening in 3 years with repeat co-testing (Pap and HPV) or continue routine age-appropriate screening intervals. 1
The American Society for Colposcopy and Cervical Pathology (ASCCP) is clear that women with ASC-US and negative high-risk HPV testing do not require immediate colposcopy, accelerated follow-up, or repeat HPV testing before the next routine screening interval. 1 This recommendation is based on the extremely low risk of high-grade disease in this population—comparable to women with completely normal screening results. 1
Risk Stratification
The 5-year risk of CIN3+ after HPV-negative/ASC-US is only 0.48%, which is similar to the risk after a negative Pap test alone (0.31%) and significantly lower than what would warrant immediate intervention. 2
HPV testing demonstrates 92% sensitivity for detecting CIN2+ lesions when used as a triage tool for ASC-US, and the negative predictive value is 98.5-99.6% for excluding high-grade lesions. 1, 3
The combination of ASC-US cytology with HPV negativity effectively rules out significant disease, as HPV infection is a necessary cause of cervical cancer. 4
Specific Follow-Up Protocol
For women aged 25-29 years: Return in 3 years for repeat Pap testing. 1
For women aged 30-65 years: Return in 3 years for co-testing (Pap + HPV) or continue routine 5-year screening if previously on primary HPV testing. 1, 5
Do not perform repeat HPV testing before the next routine screening interval, as transient cytologic abnormalities without HPV do not merit earlier surveillance. 1
Evidence Basis and Rationale
This recommendation is supported by Level 1 evidence from the ASCUS-LSIL Triage Study (ALTS), which established HPV triage as the gold-standard approach for managing ASC-US. 1
The ASCCP consensus guidelines emphasize that HPV-negative ASC-US carries such low risk that these patients should be managed identically to those with normal screening results. 1
Research comparing 17,191 women with HPV-negative/ASC-US to nearly 1 million women with negative Pap tests found that the 5-year cancer risk was statistically similar (0.043% vs 0.031%, p=0.4), confirming that aggressive follow-up is unnecessary. 2
Common Pitfalls to Avoid
Do not order immediate colposcopy for HPV-negative ASC-US, as this leads to overtreatment and unnecessary procedures in a very low-risk population. 3
Do not repeat HPV testing at 6 or 12 months, as this deviates from evidence-based guidelines and creates unnecessary patient anxiety and healthcare costs. 1
Do not confuse this scenario with HPV-positive ASC-US, which requires immediate colposcopy due to a 9.7-20% risk of CIN2+. 3
Do not apply adolescent management protocols (which avoid HPV testing) to this 27-year-old patient, as HPV triage provides highly informative risk assessment for women aged ≥21 years. 1