What does an indeterminate result for high-risk Human Papillomavirus (HPV) on a sample read mean?

Understanding an Indeterminate Result for High-Risk HPV Testing

An indeterminate result for high-risk HPV on a sample read indicates that the test could not conclusively determine whether high-risk HPV types are present, requiring follow-up testing in 2-4 months to establish a definitive result.

What is High-Risk HPV Testing?

High-risk HPV testing is a screening method that detects the presence of oncogenic (cancer-causing) HPV types in cervical cells. According to the National Comprehensive Cancer Network (NCCN):

• The FDA-approved HPV DNA test detects whether any of 13-14 high-risk HPV types are present (types 16,18,31,33,35,39,45,51,52,56,58,59, and 68) 1
• These high-risk types are associated with the development of cervical cancer and precancerous lesions 1
• The test does not specify which particular high-risk type is present in a standard screening 1

Causes of Indeterminate Results

An indeterminate result can occur for several reasons:

• Insufficient sample quantity or quality
• Technical issues during sample processing
• Presence of interfering substances
• Borderline viral load that falls between positive and negative detection thresholds

Management of Indeterminate HPV Results

The management approach for indeterminate high-risk HPV results follows these steps:

1. Repeat testing in 2-4 months - This is the recommended approach for indeterminate results 2
2. Do not assume the result is negative - An indeterminate result should not be interpreted as truly negative, as it may reflect an inadequate sample 2
3. Follow age-appropriate screening guidelines for the repeat test

Risk Assessment and Follow-up

The risk assessment depends on additional factors:

• If cytology (Pap test) is also available and normal: Follow up with repeat co-testing in 2-4 months 3
• If cytology shows abnormalities: Management should follow the appropriate algorithm based on the cytologic finding 1
• If HPV genotyping was performed and HPV 16/18 is positive: Referral for colposcopy is recommended regardless of cytology results 2

Clinical Implications

The clinical significance of an indeterminate result should be understood in context:

• HPV infections are extremely common, with approximately 90% clearing naturally within 1-2 years 3
• Persistent high-risk HPV infection is the primary risk factor for developing cervical precancer and cancer 4
• The risk of high-grade cervical intraepithelial neoplasia (CIN II+) is significantly lower with negative HPV results (0.2-0.4%) compared to positive results (5.7%) 5, 2

Important Considerations

• Do not delay follow-up: While the risk of high-grade lesions is low with indeterminate results followed by negative results, timely follow-up is essential
• Patient counseling: Explain that an indeterminate result is not uncommon and does not necessarily indicate disease
• Documentation: Clearly document the indeterminate result and the follow-up plan in the medical record

Common Pitfalls to Avoid

• Misinterpreting indeterminate as negative: This could lead to delayed diagnosis of significant lesions
• Causing unnecessary anxiety: Avoid alarming language when discussing results with patients
• Immediate colposcopy referral: This is not necessary for indeterminate results alone and would lead to unnecessary procedures 3
• Extended delay in follow-up: Studies show compliance with the recommended 2-4 month follow-up is often low (45.1%), which can lead to missed diagnoses 2

By following these evidence-based guidelines for managing indeterminate high-risk HPV results, clinicians can ensure appropriate follow-up while avoiding unnecessary procedures and patient anxiety.