What is the next step for a patient with an Atypical Squamous Cells of Undetermined Significance (ASCUS) Pap smear result and a negative Human Papillomavirus (HPV) test?

Management of ASCUS Pap Smear with Negative HPV Test

For a patient with Atypical Squamous Cells of Undetermined Significance (ASCUS) on Pap smear and negative HPV test, the recommended next step is follow-up with cotesting (Pap and HPV) at 3 years rather than 5 years. 1

Rationale for 3-Year Follow-up

The management of ASCUS with negative HPV has evolved based on risk assessment data:

• Initially, 5-year follow-up was recommended based on early Kaiser Permanente Northern California (KPNC) cohort data suggesting the risk was similar to negative cotesting
• However, updated KPNC data with larger sample sizes demonstrated that risk after HPV-negative ASCUS is actually higher than after negative cotesting 1
• This led to the current recommendation of 3-year follow-up rather than 5 years

Risk Assessment and Management Algorithm

1. Initial ASCUS with negative HPV:

   • Risk for CIN3+ is below the threshold for immediate colposcopy
   • HPV-negative status significantly reduces risk compared to HPV-positive ASCUS

2. Follow-up recommendations:

   • Cotest (Pap and HPV) at 3 years 1
   • Do not return to routine 5-year screening until normal cotest results are obtained

3. Special considerations for different age groups:

   • For women aged 30-65: Follow the 3-year cotest interval
   • For women ≥65 years: Cannot exit screening with HPV-negative ASCUS result alone
     • Must have 2 consecutive negative cotests or 3 consecutive negative Pap tests 1

Important Clinical Considerations

• HPV 16/18 genotyping is not recommended for further assessment of women with ASCUS Pap test results, as it does not alter management 1
• The negative predictive value of HPV testing with ASCUS is extremely high (99% in some studies), providing reassurance that significant disease is unlikely 2
• Avoid overtreatment in patients with ASCUS and negative HPV, as the risk of high-grade lesions is very low

Common Pitfalls to Avoid

1. Returning to 5-year screening intervals too soon

   • Despite negative HPV, ASCUS still warrants closer follow-up than routine screening

2. Recommending immediate colposcopy

   • Not necessary for ASCUS with negative HPV as risk is below colposcopy threshold

3. Repeating Pap/HPV testing too soon

   • Studies show that repeating tests before 3 years does not improve outcomes and may lead to unnecessary procedures

4. Assuming HPV-negative ASCUS in older women allows for screening exit

   • Women ≥65 years with HPV-negative ASCUS have disproportionately high cancer risk and require additional negative tests before discontinuing screening 1

By following these evidence-based guidelines, clinicians can appropriately manage patients with ASCUS Pap smears and negative HPV tests, balancing the need for surveillance with avoiding unnecessary procedures.