What are the next steps for a 34-year-old patient with a normal Pap (Papanicolau) smear but positive for Human Papillomavirus (HPV) 18/45?

Management of Normal Pap with Positive HPV 18/45

For a 34-year-old patient with normal Pap smear but positive HPV 18/45, colposcopy is recommended due to the high association of HPV 18 with cervical cancer, particularly adenocarcinoma. 1

Rationale for Colposcopy

• HPV 18 has a relatively high association with cervical cancer, and colposcopy is recommended in all cases, even if the cytology test is normal 1
• Because of the specific association of HPV 18 with adenocarcinoma, endocervical sampling is acceptable at the time of colposcopy 1
• The 2021 CDC STI Treatment Guidelines specifically recommend colposcopy for HPV 18-positive results regardless of cytology findings 1

Procedural Considerations

• During colposcopy, the clinician should:
  • Perform a thorough examination of the transformation zone 1
  • Consider endocervical sampling due to HPV 18's association with adenocarcinoma 1
  • Take directed biopsies of any suspicious areas 2

Follow-up After Colposcopy

The follow-up plan depends on colposcopy findings:

• If colposcopy is negative (no lesions):

  • HPV testing or cotesting (HPV plus Pap) at 12 months is recommended 1
  • HPV testing or cotesting is preferred over cytology alone for follow-up 1

• If colposcopy reveals CIN 1 or less:

  • Repeat HPV testing with or without concurrent Pap test in 1 year 1
  • If positive again, refer for colposcopy 1

• If colposcopy reveals CIN 2+ (moderate or severe dysplasia):

  • Treatment options include ablative or excisional procedures 1
  • After treatment, surveillance should continue for at least 25 years 1
  • Initial post-treatment testing includes HPV test or cotest at 6,18, and 30 months 1

Clinical Considerations

• HPV 18 is the second most oncogenic HPV type after HPV 16, with particularly strong association with adenocarcinoma 3
• Studies show that approximately 14% of women with HPV 18 infection develop CIN 3 or higher lesions 1
• Research indicates that 96% of adenocarcinoma in situ cases are linked to HPV types 16,18, or 45 3

Common Pitfalls to Avoid

• Do not delay colposcopy: Unlike other high-risk HPV types with normal cytology where waiting 1 year is acceptable, HPV 18 warrants immediate colposcopy due to its high association with adenocarcinoma 1
• Do not overlook endocervical sampling: Due to HPV 18's association with adenocarcinoma, which may develop higher in the endocervical canal, endocervical sampling is particularly important 1
• Do not discontinue surveillance too early: Even after negative colposcopy, continued surveillance is essential as HPV 18 persistence carries significant risk 4

Algorithm for Management

1. Immediate colposcopy with endocervical sampling 1
2. Based on colposcopy/biopsy results:
   • Normal/CIN 1: HPV testing or cotesting in 12 months 1
   • CIN 2+: Treatment followed by surveillance for at least 25 years 1
3. If HPV testing remains positive at follow-up, refer for repeat colposcopy 1