What are the next steps for a 41-year-old with a normal Pap (Papanicolau) test result but positive for high-risk Human Papillomavirus (HPV) types 16, 18, and 45?

Management of Normal Pap with Positive HPV 16/18/45

For a 41-year-old woman with normal Pap cytology but positive for high-risk HPV types 16,18, and 45, immediate colposcopy is strongly recommended due to the significantly increased risk of cervical precancerous lesions. 1

Rationale for Immediate Colposcopy

• HPV types 16 and 18 are the most oncogenic HPV types, associated with:

  • 17% risk of CIN III+ for HPV 16 positive patients
  • 14% risk of CIN III+ for HPV 18 positive patients 1
  • HPV 45 is also considered a high-risk type with significant oncogenic potential

• Despite normal cytology, the presence of these specific high-risk HPV types warrants immediate evaluation due to:

  • Higher risk of underlying cervical intraepithelial neoplasia (CIN)
  • Potential for rapid progression to precancerous lesions 2, 1

Management Algorithm

1. Immediate colposcopy (not delayed follow-up) is indicated due to:

   • Presence of HPV 16/18 (CDC recommends colposcopy for any HPV 16 or 18 positive result regardless of cytology) 1
   • Patient's age (>30 years) places her at higher risk category 2
   • Multiple high-risk HPV types detected simultaneously (16,18, and 45)

2. During colposcopy:

   • Complete examination of cervix after application of 3-5% acetic acid solution
   • Multiple biopsies (minimum of two) from the worst abnormal-looking areas 1
   • Endocervical sampling is recommended due to:
     • Patient's age (>35 years)
     • Presence of HPV 18 (associated with adenocarcinoma) 2, 1

3. Follow-up based on colposcopy/biopsy results:

   • If normal or CIN I: HPV testing or co-testing at 12 months 2
   • If CIN II or higher: treatment according to standard guidelines with appropriate excisional or ablative procedures 2

Important Considerations

• Research shows that 45.3% of patients with normal cytology but positive HPV 16 developed CIN II or higher lesions 3
• Even with normal cytology, HPV 16/18 positive patients have a substantial risk of harboring precancerous lesions that may be missed by cytology alone 4
• The false-negative rate of cervical cytology makes waiting for one year potentially risky, particularly with these specific high-risk HPV types 4

Surveillance After Initial Management

• If no lesions are found but HPV 16/18 persists:

  • Repeat co-testing (cytology and HPV) at 12 months 2
  • Continue surveillance for at least 25 years after any treatment for high-grade precancer 2

• Follow-up intervals after normal colposcopy:

  • Using HPV testing/co-testing: every 3 years
  • Using cytology alone: annual testing 1

Pitfalls to Avoid

• Do not delay colposcopy for HPV 16/18 positive patients, even with normal cytology
• Do not rely solely on repeat cytology without HPV testing for follow-up
• Do not underestimate the significance of HPV 45, which also carries substantial risk for progression to precancer
• Avoid inadequate colposcopic examination - ensure multiple biopsies are taken from suspicious areas

The evidence clearly supports immediate colposcopy rather than delayed follow-up for this patient with normal Pap but positive for multiple high-risk HPV types, particularly 16 and 18, which carry the highest oncogenic potential.