What is the next step for a patient with Atypical Squamous Cells of Undetermined Significance (ASCUS) and a positive Human Papillomavirus (HPV) test?

Management of ASCUS with Positive HPV

For a patient with Atypical Squamous Cells of Undetermined Significance (ASCUS) and a positive Human Papillomavirus (HPV) test, immediate colposcopy is the recommended next step. 1

Rationale for Colposcopy

• ASCUS with positive HPV carries a significant risk of underlying high-grade cervical intraepithelial neoplasia (CIN), necessitating colposcopic evaluation 1
• The risk of high-grade histological changes (CIN 2 or higher) is significantly higher when HPV is positive compared to HPV-negative ASCUS 1
• Studies show that HPV-positive ASCUS is associated with CIN2+ in up to 20% of cases, with CIN3+ in approximately 9.7% of non-adolescent women 2, 3
• The National Comprehensive Cancer Network recommends colposcopy as the preferred management for HPV-positive ASCUS, particularly in women over 30 years of age 1

Management Algorithm

1. Confirm HPV status and type if available:

   • If HPV is positive for high-risk types (especially 16/18), immediate colposcopy is indicated 1, 2
   • If HPV is positive but specifically negative for high-risk types, the risk is lower but colposcopy is still recommended 2

2. Proceed with colposcopy:

   • If colposcopy is satisfactory and CIN 2+ is detected, proceed with appropriate treatment (ablative or excision procedure) 1
   • If colposcopy is unsatisfactory, perform endocervical curettage (ECC) and cervical biopsy 1
   • If colposcopy is negative or shows CIN 1, follow-up with repeat co-testing (cytology and HPV) in 12 months 4

3. Age-specific considerations:

   • For women under 21 years: HPV testing is not recommended; repeat cytology at 12 months is preferred 4
   • For women 21-29 years: Colposcopy is recommended for HPV-positive ASCUS 4
   • For women 30 years and older: Immediate colposcopy is strongly recommended due to higher risk of significant disease 1

Evidence Strength and Considerations

• The recommendation for colposcopy in HPV-positive ASCUS is based on strong consensus guidelines with high-quality evidence 1
• HPV testing has higher sensitivity (88-90%) but lower specificity (72-79%) than cytology alone for detecting high-grade lesions 1
• Studies show that adding HPV testing in secondary screening increased the identification of women with CIN2-3 lesions by 33% compared to repeat cytology alone 3
• High viral load (>100 relative light unit/positive control) is associated with more significant disease 5

Important Clinical Considerations

• HPV positivity in older women (≥30 years) is more concerning and less likely to represent transient infection 1
• HPV types 16 and 18 carry the highest risk (17% and 14% respectively for CIN 3+), compared to 3% for other high-risk types 1
• The sensitivity of HPV testing for detecting biopsy-proven HSIL is approximately 87.5%, with specificity of 72.5% 6

Common Pitfalls to Avoid

• Do not delay colposcopy in HPV-positive ASCUS cases in women over 30, as this increases the risk of missed high-grade disease 1
• Do not rely on repeat cytology alone for HPV-positive ASCUS in women over 30, as it has lower sensitivity (76.2%) compared to immediate colposcopy 1
• Do not assume low risk despite ASCUS being a relatively mild cytologic abnormality; the combination with HPV positivity significantly increases risk 1
• Avoid unnecessary colposcopy for ASCUS with negative high-risk HPV, as this can lead to overtreatment 2
• Do not confuse management protocols for ASCUS/HPV-positive (but negative for high-risk types) with those for ASCUS/high-risk HPV-positive 2