What is the recommended follow-up for a female of reproductive age with a normal Pap (Papanicolau) test result and a positive Human Papillomavirus (HPV) test result, but negative for high-risk types 16, 18, and 45?

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Recommended Follow-Up for Normal Pap with HPV-Positive (Non-16/18/45) Result

Repeat Pap and HPV cotesting in 1 year is the recommended management for a woman of reproductive age with normal cytology and positive high-risk HPV that is negative for types 16,18, and 45. 1

Management Algorithm

The 1-year follow-up interval is specifically indicated for this clinical scenario:

  • Women with normal Pap smears but positive high-risk HPV (excluding types 16,18, and 45) should undergo repeat testing in 1 year with HPV testing with or without concurrent Pap 1
  • This recommendation is based on the 2021 CDC STI Treatment Guidelines and 2019 ASCCP Risk-Based Management Consensus Guidelines 1
  • The presence of non-16/18 high-risk HPV types with normal cytology carries lower immediate risk for CIN3+ compared to HPV 16/18 positivity 2, 1

What Happens at the 1-Year Follow-Up Visit

Testing options and subsequent management:

  • The preferred approach is HPV testing with or without concurrent Pap, rather than cytology alone, as HPV testing provides superior disease detection 1
  • If both tests are negative at 1 year, return to routine 3-year screening intervals 1
  • If HPV remains positive or cytology becomes abnormal, refer for colposcopy 1

Why Not Immediate Colposcopy

Colposcopy is not indicated in this scenario because:

  • HPV types 16 and 18 are the only genotypes that warrant immediate colposcopy despite normal cytology, as they carry the highest risk for CIN3+ 1
  • Your patient tested negative for HPV 16,18, and 45, placing her in a lower-risk category 1
  • Many HPV infections clear spontaneously within 12-24 months, particularly in younger women of reproductive age 1

Why Not 3-Year or 5-Year Intervals

Longer intervals are inappropriate for this result:

  • Five-year intervals are only appropriate for women aged 30 years and older with completely negative cotesting (both Pap and HPV negative) 3, 4
  • Three-year intervals apply to women with resolved HPV infections (previously positive, now negative) or those with negative cotesting who are under age 30 3
  • A single HPV-positive result with normal cytology requires closer surveillance than completely negative results 1

Risk Stratification Context

Understanding the risk level:

  • Persistent HPV positivity at 1 year significantly elevates risk and warrants colposcopy 1
  • Type-specific persistent infections carry a 10-year cumulative CIN3+ risk of 20.4%, while new infections carry only 3.4% risk 5
  • About three-quarters of women with HPV infection and normal cytology clear their infections within approximately 3 years 5

Common Pitfalls to Avoid

Key management errors to prevent:

  • Do not extend the screening interval beyond 1 year for HPV-positive women with normal cytology, even though immediate risk is relatively low 1
  • Do not perform HPV 16/18 genotyping for women who already have normal cytology with non-16/18 HPV, as it does not alter management 2
  • Do not confuse this scenario with HPV-negative/ASC-US results, which require 3-year follow-up 4

References

Guideline

Repeat Testing Interval for Normal PAP with Positive HPV

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Cervical Cancer Screening Guidelines for Young Women

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Retesting Interval for Negative HPV and Negative Pap

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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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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