ArticleHistopathology2025
Six-pattern p53 interpretation in 1293 vulvar squamous cell carcinomas: inter-pathologist variation and pattern distribution according to p16 status.
Article in Histopathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Vulvar Squamous Cell Carcinoma: Scientific Progress and Impacts to Pathology Practice.International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists · 2026Review
- Squamous Cancers and Precancers of the Vulva: Emerging Diagnostic, Prognostic and Predictive Biomarkers in Pathology.Cancers · 2026Review
- Synchronous Cervical and Vulvar High-Grade Squamous Intraepithelial Lesions with Unusual p16/p53 Immunophenotype: A Case Report.Reports (MDPI) · 2026Article
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13 authors.
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Abstract
aimsVulvar squamous cell carcinoma (VSCC) is classified into human papillomavirus (HPV)-associated and HPV-independent types, primarily using p16 immunohistochemistry, with p53 staining playing a complementary role since a subset of HPV-independent VSCC is driven by TP53 mutations. We aimed to assess the robustness of the six-pattern p53 classification by evaluating interobserver agreement and mapping pattern distribution in relation to p16 status.
methodsWe performed p53 immunohistochemistry on 1293 VSCC cases, comprising 832 p16-negative and 461 p16-positive cases. Eight pathologists independently evaluated p53, with each case assessed by two pathologists. Expression was classified as wild-type (scattered or mid-epithelial) or mutated (basal overexpression, parabasal/diffuse overexpression, absent or cytoplasmic). Interobserver agreement was measured using kappa statistics.
resultsOverall concordance across the six p53 patterns was 66.7%, increasing to 86.9% when dichotomized as wild-type versus mutated. In the p16-negative cases, concordance was 68.8% across all six patterns and 82.6% when dichotomized. Corresponding rates in the p16-positive cases were 62.9% and 94.6%. Kappa values for pairwise assessments ranged from 0.44 to 0.73 (six-pattern) and from 0.60 to 0.88 (dichotomized). After resolving discordant cases, 79.9% of p16-negative cases showed a mutated pattern, and 20.1% were wild type (scattered). Among the p16-positive cases, 93.1% exhibited a wild-type pattern.
conclusionsFindings support the clinical robustness of the six-pattern p53 framework, as interobserver agreement was high and most discrepancies were unlikely to impact tumour classification. While p16 proved helpful in p53 interpretation, certain cases remained challenging due to p53 heterogeneity or ambiguous p16/p53 combinations indicating a need for additional molecular testing in such instances.
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