What is the next step if an ASCUS (Atypical Squamous Cells of Undetermined Significance) result is obtained on a Pap (Papanicolaou) smear?

Management of ASCUS on Pap Smear

The next step after obtaining an ASCUS result on Pap smear is HPV testing for high-risk types (reflex HPV testing), with colposcopy indicated if HPV-positive, or alternatively repeat cytology in 12 months if HPV testing is unavailable. 1

Age-Stratified Management Algorithm

Women Under 21 Years

• Do not perform HPV testing in this age group, as HPV prevalence is high but progression to cancer is extremely rare 1
• Repeat cytology at 12 months is the recommended approach 1
• If repeat cytology shows negative or persistent ASCUS/LSIL, repeat again at 24 months 1
• Colposcopy is only indicated if cytology shows ASC-H, HSIL, or persistent abnormalities after 3 years 1

Women Ages 21-29 Years

• HPV triage testing is the preferred strategy, with colposcopy for HPV-positive results 2, 3
• If HPV testing is unavailable, repeat cytology in 12 months is acceptable 1
• Current risk for CIN3+ after ASCUS is below the threshold for immediate colposcopy, making HPV triage more efficient than universal colposcopy 1

Women Ages 30-65 Years

• HPV triage is strongly recommended as the primary management strategy 1
• If HPV-positive for high-risk types, proceed directly to colposcopy 2, 3
• HPV-positive ASCUS carries approximately 20% risk of CIN2+ and 9.7% risk of CIN3+ 2
• If HPV-negative, follow-up with co-testing (cytology and HPV) at 3 years, not 5 years as previously recommended 1

Evidence Supporting HPV Triage

The 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 1. HPV testing achieves 88-90% sensitivity for detecting high-grade lesions, compared to 76.2% sensitivity for repeat cytology alone 2, 4.

HPV testing of residual liquid-based cytology specimens provides 89.2% sensitivity for detecting HSIL+, compared to 76.2% for repeat Pap smear 4. This allows identification of high-risk cases from the initial screening specimen without requiring patients to return 4.

Alternative Management Options

If HPV testing is not available, three options exist 1:

1. Repeat cytology at 6 and 12 months: If both tests are negative, resume routine screening every 2 years 1
2. Immediate colposcopy: This is less efficient but ensures no missed high-grade lesions 1
3. Single repeat cytology at 12 months: If negative or shows persistent ASCUS, manage accordingly 1

Important Considerations About HPV Genotyping

Do not perform HPV 16/18 genotyping for ASCUS triage, as it does not alter management 1. While HPV 16 and 18 carry higher risk (17% and 14% respectively for CIN3+), approximately 50% of CIN2+ infections involve other high-risk types (HPV 31,45, etc.) with ~20% risk of CIN2+ 1. Therefore, all women with ASCUS who are positive for any high-risk HPV should proceed to colposcopy 1, 2.

Critical 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 2, 3
• Do not rely on repeat cytology alone for HPV-positive ASCUS, as sensitivity is only 76.2% compared to immediate colposcopy 2, 3
• Avoid unnecessary colposcopy for ASCUS with negative high-risk HPV, as this leads to overtreatment 2
• Do not assume HPV-negative ASCUS at age 65+ allows cessation of screening—these women require retesting at 3 years and continued surveillance until 2 consecutive negative co-tests or 3 consecutive negative Pap tests 1

Follow-up After Colposcopy

If colposcopy is performed and shows 1, 2:

• CIN2+ detected: Proceed with appropriate treatment (ablation or excision)
• CIN1 or negative: Repeat co-testing at 12 months
• Unsatisfactory colposcopy: Perform endocervical curettage and cervical biopsy