ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2021
Molecular characterization of invasive and in situ squamous neoplasia of the vulva and implications for morphologic diagnosis and outcome.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 64 citations in OpenAlex.
- 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
- Synchronous Cervical and Vulvar High-Grade Squamous Intraepithelial Lesions with Unusual p16/p53 Immunophenotype: A Case Report.Reports (MDPI) · 2026Article
- Development of a risk assessment model for the recurrence of high-grade squamous intraepithelial lesions and differentiated vulvar intraepithelial neoplasia in Chinese cohort.Discover oncology · 2026Article
- Review
- The challenges of managing vulval squamous cell cancer in women with Fanconi anaemia: A case report and literature review.Case reports in women's health · 2025Article
- The future of research on vulvar intraepithelial neoplasia: towards precision diagnostics and risk stratification.Journal of the Turkish German Gynecological Association · 2025Article
- HPV-independent vulvar squamous cell carcinoma: a case report and review of the literature.Einstein (Sao Paulo, Brazil) · 2025Review
- Molecular Subtypes of Vulvar Squamous Cell Carcinoma: The Significance of HPV-Independent/p53 Wild Type.Cancers · 2024Review
- Genomic profiles of Japanese patients with vulvar squamous cell carcinoma.Scientific reports · 2024Article
- Article
- Next-generation sequencing in dermatology.Frontiers in medicine · 2023Review
- Human Papillomavirus‒Positive and ‒Negative Vulvar Squamous Cell Carcinoma Are Biologically but Not Clinically Distinct.The Journal of investigative dermatology · 2022Article
- Molecular landscape of vulvovaginal squamous cell carcinoma: new insights into molecular mechanisms of HPV-associated and HPV-independent squamous cell carcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022Article
- Comprehensive Analysis of Co-Mutations Identifies Cooperating Mechanisms of Tumorigenesis.Cancers · 2022Article
- Integration of NRP1, RGS5, and FOXM1 expression, and tumour necrosis, as a postoperative prognostic classifier based on molecular subtypes of clear cell renal cell carcinoma.The journal of pathology. Clinical research · 2021Article
- 2020 WHO Classification of Female Genital Tumors.Geburtshilfe und Frauenheilkunde · 2021Article
- Histological interpretation of differentiated vulvar intraepithelial neoplasia (dVIN) remains challenging-observations from a bi-national ring-study.Virchows Archiv : an international journal of pathology · 2021Article
- Article
- Molecular Landscape of Vulvar Squamous Cell Carcinoma.International journal of molecular sciences · 2021Review
- Assessment of TSPAN Expression Profile and Their Role in the VSCC Prognosis.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC) is an aggressive clinical entity. Current diagnostic guidelines for premalignant lesions are ambiguous, and their molecular profile and progression events are still unclear. We selected 75 samples, from 40 patients, including 33 VSCC, 8 verrucous carcinomas (VC), 13 differentiated-type vulvar intraepithelial neoplasia (dVIN), 11 suspicious for dVIN (?dVIN), 6 differentiated exophytic vulvar intraepithelial lesions (DE-VIL), 2 vulvar acanthosis with altered differentiation (VAAD), and 2 usual-type vulvar intraepithelial neoplasia (uVIN/HSIL). Invasive and precursor lesions were matched in 29 cases. Clinical information, p16 immunohistochemistry, and mutation analysis were performed on all lesions. All dVIN, ?dVIN, DE-VIL, and VAAD were p16 negative, all uVIN/HSIL were p16 positive. In the HPV-independent group, mutations were identified in 6 genes: TP53 (n = 40), PIK3CA (n = 20), HRAS (n = 12), MET (n = 5), PTEN (n = 4), and BRAF (n = 1). TP53 mutations occurred in 73% (22/30) VSCC, 85% (11/13) dVIN, 70% (7/10) ?dVIN and no VC (0/8), DE-VIL (0/6) nor VAAD (0/2). Basal atypia was the only reliable feature of TP53 mutations. ?dVIN lesions that were non-acanthotic and atypical but obscured by inflammation, all harbored TP53 mutations. In lesions without TP53 mutations, PIK3CA (50% VC, 33% DE-VIL, 100% VAAD, 40% VSCC) and HRAS (63% VC, 33% DE-VIL, 0% VAAD, 20% VSCC) mutations were found. Mutational progression from in situ to invasive was seen (7/26, 27%) and usually involved TP53 (4/26, 15%). Cases with TP53 and PIK3CA co-mutations had the worse clinical outcomes (p < 0.001). We recommend testing for p53 in all HPV-independent lesions suspicious for dVIN, even in the presence of marked inflammation or non-acanthotic skin, particularly when close to a margin. VC, VAAD, and DE-VIL, were almost never mutated for TP53, but instead often harbored PIK3CA and HRAS mutations. In VSCC, combined TP53 and PIK3CA mutations may inform prognosis.
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