What are the next steps for a patient with an Atypical Squamous Cells of Undetermined Significance (ASCUS) result on a Pap smear?

Management of ASCUS Pap Smear Results

Primary Management Strategy

Perform reflex HPV testing for high-risk types immediately, and refer to colposcopy if HPV-positive; if HPV-negative, repeat co-testing in 3 years. 1, 2

The algorithm is straightforward and age-dependent:

For Women Ages 21-65 Years

• HPV triage testing is the preferred first-line strategy for all women with ASCUS results, as it achieves 88-90% sensitivity for detecting high-grade lesions compared to only 76.2% sensitivity for repeat cytology alone. 1, 3

• If HPV-positive for high-risk types: Proceed immediately to colposcopy with directed biopsy, as HPV-positive ASCUS carries approximately 20% risk of CIN2+ and 9.7% risk of CIN3+. 1, 4

• If HPV-negative: Return for repeat co-testing (Pap plus HPV) at 3 years, not 5 years—this shorter interval is based on analysis of over 1.1 million women showing HPV-negative ASCUS carries slightly higher risk than completely negative co-testing. 1

For Women Under Age 21

• Do not perform HPV testing, as HPV prevalence is extremely high in this age group but progression to cancer is exceedingly rare. 1

• Instead, repeat cytology at 12 months. 1

If HPV Testing Is Unavailable

• Acceptable alternatives include repeat cytology at 6 and 12 months until three consecutive negative results, or single repeat cytology at 12 months. 1, 2

• If a second ASCUS result occurs during follow-up, proceed to colposcopy. 2

Critical Evidence Supporting This Approach

The landmark ASCUS-LSIL Triage Study (ALTS) demonstrated that HPV triage is at least as sensitive as immediate colposcopy for detecting CIN III while referring approximately half as many women to colposcopy—a major advantage in avoiding overtreatment. 1, 3

Research confirms that HPV DNA testing identifies 89.2% of women with histologic HSIL or cancer, with specificity of 64.1%, making it superior to repeat Pap testing alone (76.2% sensitivity). 3

Special Clinical Scenarios

ASCUS with Concurrent Infections

• If severe inflammation from bacterial vaginosis or yeast infection is present: Treat the infection first, then repeat the Pap smear in 2-3 months, as these infections cause reactive cellular changes that can mimic dysplasia. 2

• However, treatment of infection does not eliminate the need for HPV testing or appropriate follow-up—if the repeat Pap shows persistent ASCUS, proceed with HPV triage as outlined above. 2

• Consider immediate colposcopy if the patient has poor reliability for follow-up, history of previous abnormal Pap tests, high-risk sexual behaviors, or immunocompromised status, as the small delay from treating infections may not outweigh the risk of loss to follow-up. 2

Women Ages 60-65 with HPV-Negative ASCUS

• Do not exit screening with this result, as these women have disproportionately higher cancer risk despite low precancer risk. 1

• They must be retested at 3 years and continue surveillance until achieving 2 consecutive negative co-tests or 3 consecutive negative Pap tests. 1

Management After Colposcopy

• If CIN2+ is detected: Proceed with appropriate treatment (ablation or excision). 1, 4

• If CIN1 or negative: Repeat co-testing at 12 months. 1, 4

• If colposcopy is unsatisfactory: Perform endocervical curettage and cervical biopsy. 1, 4

Common Pitfalls to Avoid

• Never delay colposcopy in HPV-positive ASCUS cases in women over 30 years, as this increases risk of missed high-grade disease—remember that one-third of high-grade squamous intraepithelial lesions in screening populations are initially identified from ASCUS Pap results. 1, 2

• Do not perform HPV 16/18 genotyping for ASCUS triage, as it does not alter management—all women with ASCUS who are positive for any high-risk HPV should proceed to colposcopy. 1, 2

• Avoid unnecessary colposcopy for ASCUS with negative high-risk HPV, as the current risk for CIN3+ is below the threshold for colposcopy and this leads to overtreatment in this low-risk population. 1

• Do not rely on repeat cytology alone for HPV-positive ASCUS, as sensitivity is only 76.2% compared to immediate colposcopy. 1

• Never assume ASCUS is benign—high-grade histological changes (CIN 2 or higher) are detected in up to 12% of ASCUS cases overall, and significantly higher when HPV-positive. 2, 4

• Surgery has no role in the initial management of ASCUS. 2