What does ASC-US (Atypical Squamous Cells of Undetermined Significance) mean?

ASC-US: Atypical Squamous Cells of Undetermined Significance

ASC-US (Atypical Squamous Cells of Undetermined Significance) is a cervical cytology finding that indicates cellular changes that are abnormal but not definitively precancerous, requiring follow-up to rule out more serious cervical disease. 1

Definition and Clinical Significance

• ASC-US represents approximately 4% of all cervical cytology smears and indicates cellular changes that are more pronounced than inflammatory or reactive processes but insufficient to be classified as cervical intraepithelial lesions (CIN) 1, 2
• The risk of underlying high-grade cervical disease (CIN 2 or worse) in non-adolescent women with ASC-US is approximately 9.7% 1
• ASC-US is the most common abnormal Pap test result and serves as an important triage point in cervical cancer screening 1

Management Recommendations

For Non-Adolescent Women (Age 21 and Older):

• The preferred management of ASC-US in adult women is reflex HPV DNA testing 1

• For HPV-positive ASC-US:

  • Colposcopy is recommended for immediate evaluation 1
  • If previous screening results were negative within the past 5 years, repeat HPV testing with or without concurrent Pap test in 1 year is an acceptable alternative 1

• For HPV-negative ASC-US:

  • Repeat HPV test with or without concurrent Pap test in 3 years 1
  • The negative predictive value of HPV testing is high, allowing safe extension of follow-up intervals 1

• Alternative acceptable approaches if HPV testing is unavailable:

  • Repeat cytology at 6 and 12 months 1
  • Immediate colposcopy 1

For Special Populations:

• For women aged 21-24 years: Management may differ due to high rates of HPV infection and spontaneous regression in this age group 1
• For pregnant women: Colposcopic biopsy of lesions suspicious for cancer or CIN 2/3 is preferred, but biopsy of other lesions is acceptable; endocervical curettage is unacceptable 1
• For HIV-infected women: More aggressive follow-up is warranted as they have higher rates of progression to SIL (60% vs 25% in HIV-negative women) 1, 3

Risk Stratification

• HPV status is the most important risk stratifier for women with ASC-US 1
• The 5-year risk of histologic HSIL and cancer for HPV-positive ASC-US is 18%, compared to only 1.1% for HPV-negative ASC-US 1
• Other risk factors include:
  • Immunosuppression, particularly HIV infection with low CD4+ counts 3
  • Previous abnormal cervical screening results 1
  • Persistent HPV infection, especially with high-risk types 2

Follow-up After Initial Management

• If colposcopy is negative, follow-up includes:

  • Repeat cytology at 6 and 12 months, or
  • HPV testing at 12 months, with colposcopic reevaluation if HPV testing is positive or cytology is ASC-US or greater 1

• For persistent ASC-US results:

  • HPV testing is recommended to identify women at higher risk for progression 2
  • Higher rates of HPV positivity (51%) are found in women with persistent ASC-US 2

Common Pitfalls and Caveats

• ASC-US is often overdiagnosed, leading to unnecessary follow-up procedures and patient anxiety 4
• Laboratory reporting rates for ASC-US vary widely, with some labs reporting rates >9% (median rate is 2.8%) 5
• ASC-US should not be confused with ASC-H (atypical squamous cells cannot exclude HSIL), which carries a much higher risk (up to 50%) of underlying CIN 2/3 and requires immediate colposcopy 1
• Failure to follow up on ASC-US results is a common cause of delayed diagnosis of cervical cancer 1
• Timely follow-up is essential - delays beyond 180 days are associated with increased risk of progression 1

Subclassification

• Some systems subclassify ASC-US into categories such as:

  • Probably neoplastic (PN)
  • Probably reactive (PR) 6
  • Due to processing defects
  • With "mature" cytoplasm
  • In post-menopausal women
  • Atypical metaplasia
  • With keratinized cytoplasm 4

• This subclassification can help guide clinical management, as ASCUS-PN has a higher association with underlying CIN than ASCUS-PR 6