Accuracy of p16 IHC in Classifying HPV-Driven OPSCC in Different Populations

Area of Science:

• Oncology
• Virology
• Pathology

Background:

• High-risk human papillomavirus (HPV) infection is a key factor in oropharyngeal squamous cell carcinoma (OPSCC) development and prognosis.
• P16 immunohistochemistry (IHC) is a common marker for HPV-driven OPSCC, but its accuracy varies.
• The reliability of p16 IHC as a standalone diagnostic tool is questioned due to potential false positive results.

Purpose of the Study:

• To evaluate the reliability of p16 IHC as a standalone marker for HPV-driven OPSCC across different populations.
• To propose a method for calculating p16 IHC false positive rates based on HPV prevalence.
• To assess the implications of p16 IHC false positives on treatment decisions.

Main Methods:

• Literature review on p16 IHC and HPV prevalence in OPSCC.
• Analysis of the correlation between p16 IHC false positive rates and HPV prevalence.
• Development of a formula to estimate false positive rates.
• Review of prognostic data for p16-positive/HPV-negative OPSCC cases.

Main Results:

• False positive rates for p16 IHC are inversely related to the prevalence of HPV-driven OPSCC in a population.
• A formula is proposed to calculate p16 IHC false positive rates using population-specific HPV prevalence data.
• P16-positive/HPV-negative OPSCC cases share a similar prognosis to p16-negative OPSCC, indicating they are false positives.

Conclusions:

• While p16 IHC is valuable for OPSCC prognosis, it is not a definitive standalone marker for HPV-driven disease.
• Relying solely on p16 IHC positivity for treatment de-intensification can be risky due to false positives.
• HPV nucleic acid testing should be used for confirmation, particularly in regions with low HPV-related OPSCC prevalence.