What does an ASCUS (Atypical Squamous Cells of Undetermined Significance) result on a Pap (Papanicolaou) smear mean?

Understanding ASCUS on Pap Smear Results

ASCUS (Atypical Squamous Cells of Undetermined Significance) on a Pap smear represents equivocal cytological findings that may or may not be associated with HPV infection, requiring follow-up to rule out significant cervical disease. 1

What ASCUS Means

• ASCUS indicates cellular changes that are more pronounced than normal inflammatory or reactive changes but insufficient to be classified as a definitive cervical intraepithelial lesion (CIN) 1, 2
• Approximately 64% of women with ASCUS are HPV positive, with high-risk HPV types being of particular concern 3
• Only 5-10% of women with ASCUS harbor serious cervical disease, but more than one-third of high-grade squamous intraepithelial lesions (HSILs) in screening populations are initially identified from ASCUS Pap results 4
• Studies show approximately 6.7% of women with ASCUS have histologic HSIL or cancer when further evaluated 4

Management Options for ASCUS

Preferred Approach

• Reflex HPV DNA testing is the preferred initial management strategy for patients with ASCUS 1
• If HPV positive (approximately 39% of cases), proceed to colposcopy 1, 4
• If HPV negative, return to routine screening as the risk of underlying high-grade disease is very low 1

Alternative Approaches

• If HPV testing is unavailable, repeat cytology at 6 and 12 months until three consecutive negative results is an acceptable alternative 1, 5
• If a second ASCUS result occurs during the 2-year follow-up period, colposcopic evaluation should be performed 1, 5
• Immediate colposcopy is an acceptable but not preferred alternative approach 1

Special Considerations

• For ASCUS with suspicion for neoplastic process, manage as if low-grade squamous intraepithelial lesion (LSIL) is present, which typically requires colposcopy 1, 5
• For ASCUS with severe inflammation, evaluate for infectious processes and re-evaluate after appropriate treatment, preferably after 2-3 months 1, 5
• High-risk patients (previous abnormal Pap tests or poor adherence to follow-up) should be considered for immediate colposcopy 1, 5

Follow-up After Initial Management

• After negative colposcopy, repeat cytology at 6 and 12 months or HPV testing at 12 months 1
• If follow-up shows HPV positive or cytology ASCUS or greater, return for colposcopy 1
• Studies show that combining HPV testing with repeat Pap testing provides the highest sensitivity (96.9%) for detecting high-grade cervical lesions 4

Clinical Significance and Outcomes

• Without proper follow-up, ASCUS can progress to more serious conditions in approximately 18% of cases 2
• Persistence of ASCUS occurs in about 74% of cases, while regression happens in approximately 8% 2
• HPV-positive women with ASCUS are at significantly higher risk for having or developing cervical precancer or cancer 1, 4
• Colposcopic evaluation after repeated ASCUS findings has shown that approximately 30% of patients will have LSIL or HSIL, justifying this additional investigation 6

Common Pitfalls to Avoid

• Dismissing ASCUS as clinically insignificant - despite being an equivocal finding, it requires appropriate follow-up 1, 6
• Failing to recognize that ASCUS in HPV-positive women carries a higher risk of underlying disease 1, 4
• Using an overly restrictive threshold (such as LSIL or more severe) for repeat Pap smear triage, which has been shown to be ineffective for detecting high-grade cervical precancerous lesions 7
• Neglecting to consider special populations (e.g., HIV-infected women) who require more frequent screening and follow-up 5