What is the next step for a patient with atypical squamous cells of undetermined significance (ASC-US) and epithelial cell abnormality on a Pap smear with a negative Human Papillomavirus (HPV) test?

Management of ASC-US with Negative HPV Test

For patients with atypical squamous cells of undetermined significance (ASC-US) and epithelial cell abnormality on a Pap smear with a negative HPV test, the recommended management is to repeat cytology at 6 and 12 months or perform HPV testing at 12 months. 1, 2

Initial Management

• Reflex HPV DNA testing is the preferred initial management strategy for ASC-US, with colposcopy recommended only for HPV-positive patients 1, 2
• For HPV-negative ASC-US (as in this case), return to routine screening is generally recommended, but with follow-up due to the epithelial cell abnormality 1, 2
• The risk of underlying high-grade cervical intraepithelial neoplasia (CIN 2,3) in HPV-negative ASC-US is very low, making immediate colposcopy unnecessary 3
• Follow-up options include:
  • Repeat cytology at 6 and 12 months 1, 2
  • HPV testing at 12 months 1, 2

Follow-up Recommendations

• If follow-up cytology shows ASC-US or greater, colposcopy is recommended 1, 2
• If follow-up HPV testing is positive, colposcopy is recommended 1, 2
• If two consecutive repeat cytology tests are negative or if follow-up HPV testing is negative, the patient can return to routine screening 1
• If ASC-US persists for at least 2 years, either continued follow-up or treatment is acceptable 1

Age-Specific Considerations

• For adolescents and young women (≤20 years), follow-up with annual cytological assessment is recommended due to the high rate of spontaneous regression (91% within 36 months) 1
• For women aged 22-27 years, repeat cytology within 6 months is considered safe and equivalent to colposcopy/biopsy in terms of cancer risk 4
• For women aged 28 years and older, more aggressive management may be warranted as the risk of underlying disease increases with age 4, 5

Risk Assessment

• The prevalence of high-risk HPV infection in women with ASC-US decreases with age (74% in women <30 years vs. 19% in women ≥50 years) 5
• Only about 9.7% of women with ASC-US have CIN 2 or more serious abnormality 1, 2
• HPV-negative ASC-US has a very low risk (<3%) of developing CIN2-3 within 3 years 5

Common Pitfalls and Caveats

• Avoid immediate colposcopy for HPV-negative ASC-US as it leads to unnecessary procedures without improving outcomes 1, 2
• Do not dismiss ASC-US completely, even with negative HPV, as there is still a small risk of underlying disease requiring follow-up 2
• Be aware that the reproducibility of ASC-US diagnosis is lower than for other squamous epithelial abnormalities, which may affect management decisions 6
• Remember that persistent ASC-US (appearing on multiple consecutive Pap tests) may warrant colposcopy regardless of HPV status 7