What is the recommended follow-up for a patient with Atypical Squamous Cells of Undetermined Significance (ASCUS) and a negative Human Papillomavirus (HPV) test?

Management of ASCUS with Negative HPV

Women with ASCUS Pap test results and a negative HPV test should return for screening in 3 years, not 5 years, as recommended by the American Cancer Society and the American Society for Colposcopy and Cervical Pathology (ASCCP). 1

Rationale for 3-Year Follow-Up Interval

The 3-year follow-up recommendation is based on several key findings:

• While the absolute risk of CIN3+ after an HPV-negative ASCUS result is low, it is more comparable to the risk after a negative Pap test alone (which requires 3-year follow-up) than to the risk after a negative cotest (which allows 5-year follow-up) 1
• Updated data from Kaiser Permanente Northern California (KPNC) involving over 1.1 million women showed that women with HPV-negative ASCUS have higher risk for CIN3+ and cancer compared to women with negative cotest results 1
• The 5-year CIN3+ risk after HPV-negative/ASCUS (0.48%) is closer to the risk after a negative Pap test (0.31%) than after a negative cotest (0.11%) 2
• The 5-year cancer risk after HPV-negative/ASCUS (0.043%) is also more similar to the risk after a negative Pap test (0.031%) than after a negative cotest (0.014%) 2

Risk Assessment and Management Algorithm

1. Initial Result: ASCUS with negative HPV

   • Manage as low risk but not ultra-low risk
   • Schedule follow-up screening in 3 years 1

2. Special Considerations for Women Ages 60-65

   • Women in this age group with HPV-negative ASCUS have a higher risk of invasive cancer than those with negative cotests 1
   • These women should not exit screening at age 65 based on this result alone 1
   • They should be retested in 3 years and continue surveillance until they have 2 consecutive negative cotests or 3 consecutive negative Pap tests 1

3. Follow-Up Testing at 3 Years

   • Perform HPV test with or without concurrent Pap test 1
   • If follow-up testing is negative → return to routine screening
   • If HPV positive or abnormal cytology → proceed to colposcopy 1

Clinical Implications

The high negative predictive value of HPV testing in ASCUS triage (99.6% for HSIL) provides reassurance that serious lesions are unlikely to be missed with a 3-year follow-up interval 3, 4. However, it's important to note that:

• HPV-negative ASCUS is not equivalent to a negative cotest in terms of risk stratification 1
• The principle of "equal management of equal risks" supports the 3-year interval rather than 5 years 1
• This recommendation affects a large population (over 500,000 women with HPV-negative ASCUS results each year) 1

Documentation and Patient Education

• Clearly document test results, follow-up recommendations, and management decisions in the patient's record 5
• Provide the patient with printed information about cervical cancer screening and a copy of her Pap test result 5
• Explain that while her current risk is low, appropriate follow-up is still necessary to ensure early detection of any potential abnormalities

Common Pitfalls to Avoid

• Don't recommend 5-year follow-up: Despite the negative HPV test, the risk after HPV-negative ASCUS is higher than after a negative cotest 1
• Don't recommend immediate colposcopy: This is unnecessary as the risk of CIN3+ is below the threshold for colposcopy 1
• Don't discharge from screening at age 65: Women aged 60-65 with HPV-negative ASCUS need continued surveillance before exiting screening 1
• Don't assume inadequate sampling: Unlike unsatisfactory Pap tests with negative HPV, ASCUS with negative HPV represents a true finding that requires appropriate follow-up 3