What is the management for atypical squamous cells of unknown significance (ASC-US)?

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Last updated: June 10, 2025View editorial policy

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From the Guidelines

Management of atypical squamous cells of unknown significance (ASC-US) typically involves HPV DNA testing as the preferred initial approach. For women with ASC-US who test positive for high-risk HPV, colposcopy is recommended 1. If HPV testing is unavailable, repeat cytology at 12 months is an alternative. For women under 25 years old, repeat cytology in 12 months is preferred over HPV testing due to the high prevalence of transient HPV infections in this age group 1. During colposcopy, if significant lesions are identified, biopsies should be taken for histological confirmation. Women with ASC-US who test negative for high-risk HPV can return to routine screening (typically every 3-5 years depending on age). For pregnant women with ASC-US, management follows the same guidelines as non-pregnant women, though colposcopy can be deferred until after delivery unless high-grade disease is suspected.

Some key points to consider in the management of ASC-US include:

  • The use of HPV DNA testing for triage of ASC-US results, which can help identify women who require colposcopy and those who can return to routine screening 1
  • The importance of follow-up and surveillance for women with ASC-US, including repeat cytology and colposcopy as needed 1
  • The need to balance the risk of missing significant cervical abnormalities with the risk of unnecessary procedures and potential harm to patients 1

In terms of specific management options, the following are recommended:

  • HPV DNA testing for women with ASC-US, with colposcopy recommended for those who test positive for high-risk HPV 1
  • Repeat cytology at 12 months for women who test negative for high-risk HPV or who are under 25 years old 1
  • Colposcopy and biopsy for women with significant lesions identified during colposcopy 1

From the Research

Management for Atypical Squamous Cells of Unknown Significance (ASC-US)

The management for ASC-US is a multi-step process that involves several tests and procedures to determine the presence of cervical precancer or cancer.

  • The first step is to perform a human papillomavirus (HPV) test to determine if the patient is infected with one of the 13 carcinogenic HPV genotypes 2.
  • If the HPV test is positive, a combination of HPV genotyping and cervical cytology (Papanicolaou testing) can identify the risk of precancer 2.
  • For patients with current precancer risks of less than 4%, repeat HPV testing is recommended in 1,3, or 5 years depending on 5-year precancer risk 2.
  • For patients with current precancer risks of 4% through 24%, such as those with low-grade cytology test results (atypical squamous cells of undetermined significance [ASC-US] or low-grade squamous intraepithelial lesion [LSIL]) and a positive HPV test of unknown duration, colposcopy is recommended 2.
  • HPV DNA testing of residual specimens collected for routine cervical cytology can help identify those who have underlying high-grade squamous intraepithelial lesions (HSIL) 3.
  • The sensitivity of HPV DNA testing for HSIL was equivalent to, if not greater than, that of the repeat Pap test 3.
  • For women with ASC-US Pap tests, HPV DNA testing of residual specimens collected for routine cervical cytology can help identify those who have underlying HSIL 3.
  • The risk of progression to dysplasia varied by age and was lowest among women between the ages of 41-50 4.
  • Among women with high-risk HPV (HRHPV+) and ASC-US, 25-30% progressed to dysplasia 4.
  • Cervical abnormalities were found in a significant proportion of cases with ASC-US and high-risk HPV testing 5.
  • Five-year risks of CIN 3+ and cervical cancer among women with HPV testing of ASC-US Pap results were similar to those among women testing Pap-negative alone, although statistically distinguishable 6.
  • Women with HPV-negative/ASC-US had a similar risk as women testing Pap-negative alone but had a higher risk than women testing HPV-negative/Pap-negative 6.
  • Women with HPV-positive/ASC-US had a slightly higher risk of CIN 3+ and cancer than those with low-grade squamous intraepithelial lesion (LSIL) 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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