What does an ASCUS (Atypical Squamous Cells of Undetermined Significance) result mean?

What Does ASCUS Mean?

ASCUS (Atypical Squamous Cells of Undetermined Significance) represents cervical cells that show changes more pronounced than normal inflammation but are insufficient to be classified as precancerous lesions—it is a category of morphologic uncertainty that requires risk stratification through HPV testing to determine appropriate management. 1, 2

Understanding the Diagnosis

ASCUS is the most common abnormal Pap test result, accounting for approximately 4-7.4% of all cervical cytology smears. 2, 3 The interpretation means that some, but not all, features of a low-grade squamous intraepithelial lesion (LSIL) are present, creating diagnostic uncertainty. 4 This is not a specific diagnosis but rather indicates cells that are atypical enough to warrant further evaluation but not clearly abnormal. 4

Clinical Significance and Risk

The underlying risk of high-grade cervical disease (CIN 2 or worse) in women with ASCUS is approximately 9.7%. 1, 2 However, this risk varies dramatically based on HPV status:

• HPV-positive ASCUS: 5-year risk of high-grade lesions and cancer is 18% 2
• HPV-negative ASCUS: 5-year risk drops to only 1.1% 2

Research shows that among women with ASCUS who undergo colposcopy, approximately 49% have low-grade cervical intraepithelial neoplasia (either condyloma or CIN I), and 9% have high-grade disease (CIN II or CIN III). 5

What Happens Next: Management Algorithm

The preferred management strategy is reflex HPV DNA testing, which serves as the critical risk stratifier. 1, 2

If HPV Testing is Positive:

• Proceed directly to colposcopy for visual examination and potential biopsy of the cervix 1, 2
• This is the most important next step because HPV-positive status significantly elevates cancer risk 2

If HPV Testing is Negative:

• Return to routine screening with repeat co-testing (Pap + HPV) in 1 year 2
• If both tests remain negative at 1-year follow-up, return to age-appropriate routine screening intervals 2
• If HPV becomes positive or cytology shows ASCUS or worse at follow-up, proceed to colposcopy 2

If HPV Testing is Unavailable:

• Repeat cytology at 6 and 12 months until three consecutive negative results are obtained 1
• If a second ASCUS result occurs during the 2-year follow-up period, colposcopic evaluation should be performed 4, 1

Special Circumstances Requiring Different Management

ASCUS with Qualifier Statements:

If the pathology report indicates "ASCUS with suspicion for neoplastic process":

• Manage as if LSIL is present, which typically requires colposcopy regardless of HPV status 4, 1

If ASCUS is associated with severe inflammation:

• Evaluate for infectious processes (bacterial vaginosis, Candida, sexually transmitted infections) 4, 1
• Treat any identified infections appropriately 4
• Re-evaluate with repeat Pap test after 2-3 months following treatment 4, 1

High-Risk Patients:

Immediate colposcopy should be considered for patients with: 4, 1

• Previous abnormal Pap tests
• Poor adherence to follow-up
• Immunocompromised status (especially HIV infection)

Special Population: HIV-Infected Women

HIV-infected women with ASCUS face substantially higher risks. Research demonstrates that 60% of HIV-infected women with ASCUS develop squamous intraepithelial lesions, compared to only 25% of HIV-uninfected women. 6 HIV-infected women with ASCUS require more aggressive follow-up and should be considered for colposcopy, particularly those with CD4+ counts <200 cells/μL. 6

Important Caveats and Common Pitfalls

Do Not Assume ASCUS is Benign:

While many ASCUS cases represent reactive changes, studies show progression to LSIL occurs in approximately 17.5% of cases and to HSIL in 2.5% during 18-24 month follow-up. 7 Failure to follow up on ASCUS results is a common cause of delayed diagnosis of cervical cancer. 2

HPV Status is Critical:

Approximately 64% of women with ASCUS are HPV positive. 8 The inter- and intra-observer reproducibility of ASCUS interpretation is poor, making objective HPV testing essential for proper risk stratification. 4

Vaccination Does Not Change Management:

If you have ASCUS, HPV vaccination can still be beneficial to prevent new infections with vaccine-targeted types not already acquired, but it does not treat existing infections or lesions. 8 Continued cervical cancer screening remains necessary even after vaccination. 8

Avoid Delays:

Delays in follow-up beyond 180 days are associated with increased risk of progression to more serious disease. 2 Timely adherence to the recommended management algorithm is essential for preventing cervical cancer.