What is the next step for a 59-year-old female with a Pap result showing Atypical Squamous Cells of Undetermined Significance (ASC-US) and a negative Human Papillomavirus (HPV) test?

Management of ASC-US with Negative HPV in a 59-Year-Old Woman

For this 59-year-old woman with ASC-US and negative HPV testing, repeat co-testing (Pap and HPV) should be performed in 3 years, and she must not exit screening at age 65 without obtaining at least 2 consecutive negative co-tests or 3 consecutive negative Pap tests. 1, 2

Risk Stratification in Older Women

• Women with HPV-negative ASC-US have a higher risk of cervical cancer than those with completely negative co-testing, and this risk is particularly concerning in women over 60 years of age 2
• Although dysplasia risk may be low after HPV-negative ASC-US in women over 60, cancer risk is disproportionately high 3, 2
• The 5-year risk of CIN3+ after HPV-negative ASC-US (0.48%) is significantly higher than after negative co-testing (0.11%), though lower than after negative Pap alone (0.31%) 4

Follow-Up Algorithm

Immediate Management:

• Do not perform colposcopy, as it is unnecessary for HPV-negative ASC-US and leads to overtreatment 1
• Do not use HPV 16/18 genotyping, as results do not alter management in this context 3, 2

Surveillance Schedule:

• Return for repeat co-testing (Pap and HPV) in 3 years 1, 2
• This 3-year interval is based on expanded data from Kaiser Permanente Northern California including 1.1 million women with extended follow-up 1, 2

At Follow-Up Testing:

• If both tests are negative: continue routine screening 1
• If either test shows abnormalities: manage according to the specific abnormality found 1
• Continue repeat testing at appropriate intervals until two consecutive negative co-tests are obtained if abnormalities persist 1

Critical Considerations for Age 65 Screening Exit

This patient cannot exit screening at age 65 with only this single HPV-negative ASC-US result. 3, 2

• She must obtain either 2 consecutive negative co-tests OR 3 consecutive negative Pap tests before exiting screening 3, 2
• HPV-negative ASC-US results are not sufficiently reassuring to allow women to stop screening at age 65 years 3
• Women who reach age 65 with an HPV-negative ASC-US result should be retested in 3 years and continue surveillance until meeting exit criteria 3

Evidence Quality and Rationale

• The American Cancer Society and American Society for Colposcopy and Cervical Pathology both recommend 3-year follow-up for HPV-negative ASC-US, though this recommendation is graded as "weak" due to limited data in older women 1, 2
• The principle of "equal management of equal risks" guides these recommendations, as women with HPV-negative ASC-US have intermediate risk profiles requiring standardized follow-up 2
• Approximately 0.5% to 1.0% of all women in their 60s will have an HPV-negative ASC-US result 2

Common Pitfalls to Avoid

• Do not allow exit from screening at age 65 with only this recent HPV-negative ASC-US result, as this is insufficient for meeting exit criteria 2
• Do not perform immediate colposcopy for all ASC-US results regardless of HPV status, as this leads to unnecessary procedures 1
• Do not return to screening before 3 years unless new symptoms develop, as earlier testing is unnecessary and may lead to overtreatment 1
• Do not assume this result carries the same ultralow risk as a negative co-test, particularly in this age group where cancer risk is disproportionately elevated 1, 2