What is the next step for a 56-year-old female with a negative PAP (Papanicolaou) smear and a positive HPV (Human Papillomavirus) Aptima test?

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Management of 56-Year-Old Female with Negative PAP and Positive HPV

Repeat HPV testing with or without concurrent PAP test in 1 year is the recommended next step for this patient. 1

Rationale for 1-Year Follow-Up

This management approach is based on the 2019 ASCCP risk-based guidelines, which recognize that a negative PAP (NILM - negative for intraepithelial lesion or malignancy) with positive HPV represents a relatively low-risk scenario. 1 The key determining factor is whether this patient had negative screening results within the previous 5 years:

  • If she had negative HPV testing or co-testing within the past 5 years: The guidelines specifically allow deferral of colposcopy in favor of repeat testing at 1 year. 1
  • If she had a previous HPV-positive result: Immediate colposcopy is indicated, as two consecutive HPV-positive tests warrant direct referral regardless of cytology. 1

Critical Decision Point: HPV Genotyping

If HPV genotyping is available and shows HPV 16 or 18, proceed directly to colposcopy regardless of negative cytology. 1 This is because:

  • HPV 16 carries the highest risk for progression to high-grade disease 1
  • HPV 18 has relatively high association with adenocarcinoma, and endocervical sampling should be performed at colposcopy 1
  • For non-16/18 high-risk HPV types with negative cytology, the 1-year follow-up strategy remains appropriate 2

Follow-Up Protocol at 1 Year

At the 1-year visit, perform repeat HPV testing (with or without PAP): 1

  • If HPV negative or both tests negative: Return to routine age-appropriate screening 2
  • If HPV remains positive: Refer to colposcopy 1, 2
  • If cytology shows ASC-US or worse: Refer to colposcopy 1, 2

Important Caveats

Do not extend the initial follow-up interval beyond 12 months. 2 While some data suggest safety in longer intervals for postmenopausal women, the first surveillance visit should occur at 1 year to ensure appropriate risk stratification. 3

HPV testing alone or repeat cytology alone is preferred over cytology-only follow-up because negative HPV testing has higher negative predictive value for excluding high-grade disease compared to cytology alone. 1

Avoid common pitfalls:

  • Do not perform immediate colposcopy unless HPV 16/18 positive or there is a history of consecutive HPV-positive results 1
  • Do not recommend excisional procedures or hysterectomy based solely on a single positive HPV test with negative cytology 2
  • Ensure the patient understands this is active surveillance, not dismissal of the finding 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Management of Non-High-Risk HPV Positive Status

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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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