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Interpretation of p16 and p53 in the Classification of Squamous Cell Carcinoma of the Vulva-An Interobserver Agreement Study

  • 0Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR.
The American Journal of Surgical Pathology +

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December 6, 2024

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December 6, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Interrater agreement for p16 in vulvar squamous cell carcinoma (vSCC) is strong, but p53 and tumor pathway classification show moderate agreement. Academic settings and training improve diagnostic accuracy for vSCC.

Area Of Science

  • Gynecologic Pathology
  • Oncology
  • Diagnostic Biomarkers

Background

  • Vulvar squamous cell carcinoma (vSCC) classification relies on human papillomavirus (HPV) association or independence.
  • Immunohistochemical stains p16 INK4a (p16) and p53 aid in categorizing vSCC into distinct tumor pathways.
  • A recent framework proposed specific p53 expression patterns for vSCC diagnosis.

Purpose Of The Study

  • To evaluate interrater agreement for p16 and p53 interpretation in vSCC.
  • To assess agreement in classifying vSCC into HPV-associated, HPV-independent (TP53 mutant), or HPV-independent (TP53 wild type) pathways.
  • To examine the impact of practice setting and expertise on diagnostic agreement.

Main Methods

  • International, multi-institutional study involving 50 invasive vSCC cases.
  • Evaluation of p16 and p53 immunohistochemical stains by pathologists with varied expertise and practice settings.
  • Assessment of interrater agreement for stain interpretation and tumor pathway classification.

Main Results

  • Strong to near-perfect interrater agreement was observed for p16 interpretation in vSCC.
  • Moderate interrater agreement was found for p53 interpretation and tumor pathway assignment.
  • Higher agreement for p53 and tumor pathway classification was noted in academic practice settings.
  • An educational module significantly improved diagnostic confidence and accuracy for pathologists without gynecologic subspecialty expertise.

Conclusions

  • While p16 interpretation in vSCC is reliable, p53 and tumor pathway classification require further standardization.
  • Practice setting, particularly academic environments, influences diagnostic agreement.
  • Targeted education enhances diagnostic capabilities for vSCC biomarkers, though challenges with specific p53 patterns and HPV testing persist.