What are the next steps for a 41-year-old female with normal Pap (Papanicolaou) cytology but positive Human Papillomavirus (HPV) test for high-risk strains 18/45?

Management of a 41-Year-Old Female with Normal Pap Cytology and HPV 18/45 Positive Test

Colposcopy is recommended for this patient with normal Pap cytology but positive HPV test for high-risk strains 18/45, even with normal cytology, due to the relatively high association of HPV 18 with cervical cancer, particularly adenocarcinoma. 1

Rationale for Colposcopy

• HPV 18 has a relatively high association with cancer, and colposcopy is recommended in all cases, even when cytology is normal 1
• Because of HPV 18's specific association with adenocarcinoma, endocervical sampling is acceptable at the time of colposcopy 1
• The 2021 STI Treatment Guidelines specifically recommend colposcopy for HPV 16 or 18 positive results, regardless of cytology findings 1

Procedure Details

• During colposcopy, the clinician should:
  • Perform a thorough examination of the cervix with acetic acid and Lugol's iodine to identify potential lesions 1
  • Obtain cervical biopsies of any suspicious areas 1
  • Perform endocervical sampling (curettage) due to HPV 18's association with adenocarcinoma 1

Follow-Up Management

The follow-up management will depend on the colposcopy and biopsy results:

• If colposcopy and biopsy are negative:

  • 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 after an abnormal test result 1

• If CIN 2 or higher is detected:

  • Treatment options include ablative or excisional procedures (laser ablation, cryotherapy, LEEP, or cold knife conization) 1
  • After treatment for high-grade precancer, 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

Risk Assessment

• Research shows that women with HPV 18 positive results have approximately 14% risk of CIN 3+ lesions, compared to 17% for HPV 16 and only 3% for other high-risk HPV types 1
• Recent studies demonstrate that delaying colposcopy for 12 months in women with normal cytology but positive high-risk HPV (even non-16/18 types) may pose risks:
  • 6.5% of women with negative cytology but positive non-16/18 HPV were found to have CIN 2+ lesions on immediate colposcopy 2
  • This risk is significantly higher for HPV 16/18, supporting immediate colposcopy in this case 3

Common Pitfalls to Avoid

• Do not rely solely on repeat cytology without HPV testing for follow-up, as negative HPV testing is less likely to miss disease than normal cytology testing alone 1, 4
• Do not delay colposcopy for HPV 18 positive results, even with normal cytology, due to the specific risk of adenocarcinoma 1
• Do not overlook the need for endocervical sampling during colposcopy for HPV 18 positive patients 1
• Avoid extending screening intervals without appropriate follow-up of this high-risk HPV positive result 5

Long-term Considerations

• If initial colposcopy is negative, continued surveillance is essential as women with persistent HPV infection remain at high risk for developing cervical neoplasia 4
• After completing initial post-colposcopy testing, long-term surveillance includes testing at 3-year intervals if using HPV testing or cotesting, or annual testing if using cytology alone 1