British Gynaecological Cancer Society (BGCS) vulval cancer guidelines: Recommendations for practice

Morrison, Jo; Baldwin, Peter; Buckley, Lynn; Cogswell, Lucy; Edey, Katharine; Faruqi, Asma; Ganesan, Raji; Hall, Marcia; Hillaby, K.; Reed, Nick; Rolland, Phil; Fotopoulou, Christina

doi:10.1016/j.ejogrb.2020.05.054

Cited by 48 publications

(50 citation statements)

References 134 publications

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“…Differentiated vulvar intraepithelial neoplasia (dVIN) is the most well-characterized precursor lesion of HPV-independent VSCC [1][2][3][4]. Studies report that dVIN can progress rapidly to VSCC [5,6]; therefore, lesions diagnosed on histology as dVIN are surgically excised [7,8]. However, histological diagnosis of dVIN can be difficult even for experienced pathologists [2], and may suffer from suboptimal reproducibility [9,10].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Immunohistochemical Markers, CK17 and SOX2, as Adjuncts to p53 for the Diagnosis of Differentiated Vulvar Intraepithelial Neoplasia (dVIN)

et al. 2021

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Histological diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN), the precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC), can be challenging, as features of dVIN may mimic those of non-dysplastic dermatoses. To aid the diagnosis, p53-immunohistochemistry (IHC) is commonly used, and mutant expression patterns are used to support a histological diagnosis of dVIN. However, a proportion of dVIN can show wild-type p53-expression, which is characteristic of non-dysplastic dermatoses. Furthermore, recent research has identified a novel precursor of HPV-independent VSCC—the p53-wild-type differentiated exophytic vulvar intraepithelial lesion (de-VIL). Currently, there are no established diagnostic IHC-markers for p53-wild-type dVIN or de-VIL. We evaluated IHC-markers, cytokeratin 17 (CK17), and SRY-box 2 (SOX2), as diagnostic adjuncts for dVIN. For this, IHC-expression of CK17, SOX2, and p53 was studied in dVIN (n = 56), de-VIL (n = 8), and non-dysplastic vulvar tissues (n = 46). For CK17 and SOX2, the percentage of cells showing expression, and the intensity and distribution of expression were recorded. We also performed next generation targeted sequencing (NGTS) on a subset of dVIN (n = 8) and de-VIL (n = 8). With p53-IHC, 74% of dVIN showed mutant patterns and 26% showed wild-type expression. Median percentage of cells expressing CK17 or SOX2 was significantly higher in dVIN (p53-mutant or p53-wild-type) and de-VIL than in non-dysplastic tissues (p < 0.01). Diffuse, moderate-to-strong, full epithelial expression of CK17 or SOX2 was highly specific for dVIN and de-VIL. With NGTS, TP53 mutations were detected in both dVIN and de-VIL. We infer that immunohistochemical markers CK17 and SOX2, when used along with p53, may help support the histological diagnosis of dVIN.

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Section: Introductionmentioning

confidence: 99%

Evaluation of Immunohistochemical Markers, CK17 and SOX2, as Adjuncts to p53 for the Diagnosis of Differentiated Vulvar Intraepithelial Neoplasia (dVIN)

et al. 2021

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Section: Introductionmentioning

confidence: 99%

“…Although our understanding of VSCC carcinogenesis has progressed, treatment options for VSCC patients have not significantly evolved over the years [ 13 , 14 ]. The mainstay of VSCC treatment remains surgery with tumor-free resection margins, confirmed on microscopy [ 13 , 14 , 15 ]. Unfortunately, surgical interventions in the vulva may injure adjacent vital structures such as the urethra or the anus, resulting in post-operative morbidity and a reduced quality of life [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma

Dasgupta

Ewing‐Graham

Swagemakers

et al. 2021

Cancers

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DNA methylation is the most widely studied mechanism of epigenetic modification, which can influence gene expression without alterations in DNA sequences. Aberrations in DNA methylation are known to play a role in carcinogenesis, and methylation profiling has enabled the identification of biomarkers of potential clinical interest for several cancers. For vulvar squamous cell carcinoma (VSCC), however, methylation profiling remains an under-studied area. We sought to identify differentially methylated genes (DMGs) in VSCC, by performing Infinium MethylationEPIC BeadChip (Illumina) array sequencing, on a set of primary VSCC (n = 18), and normal vulvar tissue from women with no history of vulvar (pre)malignancies (n = 6). Using a false-discovery rate of 0.05, beta-difference (Δβ) of ± 0.5, and CpG-island probes as cut-offs, 199 DMGs (195 hyper-methylated, 4 hypo-methylated) were identified for VSCC. Most of the hyper-methylated genes were found to be involved in transcription regulator activity, indicating that disruption of this process plays a vital role in VSCC development. The majority of VSCCs harbored amplifications of chromosomes 3, 8, and 9. We identified a set of DMGs in this exploratory, hypothesis-generating study, which we hope will facilitate epigenetic profiling of VSCCs. Prognostic relevance of these DMGs deserves further exploration in larger cohorts of VSCC and its precursor lesions.

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“…The width of the surgical margin (1 cm vs. 2 cm) was relatively narrow in the M-MTIT group; however, this did not result in an increased incidence of microscopic positive margins (3.5% vs. 3.6%, P=0.980). Based on our findings and available evidence, we believe that a macroscopic tumor-free margin should be at least 1 cm [1][2][3][22][23][24].…”

Section: Discussionmentioning

confidence: 99%

“…Locally advanced vulvar cancer is associated with a significant risk of local recurrence, and the tumor margin status has been validated as a significant prognostic factor 1 , 2 , 21 . To decrease the risk of local recurrence, most guidelines recommend a histological tumor-free margin of at least 8 mm 1 , 3 , 22 - 24 , which corresponds to a surgical margin of 1-2 cm 25 . There is evidence showing 0% recurrence rates for > 8 mm margins and 47% when the margins are ≤ 8 mm 3 , 25 , 26 .…”

Section: Discussionmentioning

confidence: 99%

Comparison of two types of the triple incision technique in the treatment of patients with locally advanced vulvar cancer

Liang

Liu

et al. 2020

Int. J. Med. Sci.

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Objective: In 2012, we proposed and described a modified triple incision technique (MTIT) for vulvar cancer patients with locally advanced disease. The MTIT has undergone a series of modifications, and a modified MTIT (M-MTIT) has been developed. The purpose of this study was to introduce the M-MTIT and compare it with the MTIT. Study design: This was a retrospective cohort study. Fifty-seven vulvar cancer patients with clinical stage T2 (≥ 4 cm) or T3 disease were included. Of these patients, 28 underwent the MTIT and 29 underwent the M-MTIT. Data on surgery-related complications and survival outcomes were compared. Results: Patients who were treated with the M-MTIT developed significantly less surgery-related morbidities than patients treated with the MTIT (24.1% vs. 60.7%, P = 0.005). Wound breakdown was the most common complication in our cohort, which occurred less frequently in the M-MTIT group than in the MTIT group (10.3% vs. 35.7%, P = 0.022). Multivariate logistic regression analysis identified the M-MTIT as an independent predictor of a reduced risk of wound breakdown. The incidence of other complications, including lymphedema, wound infection and cellulitis, was lower in the M-MTIT group than in the MTIT group; however, the differences did not reach statistical significance. The median follow-up time of this study was 33 months. Kaplan-Meier survival graphs did not show significant differences in recurrence-free survival or overall survival between the two groups. Conclusions: The M-MTIT correlates with lower morbidity rates than the MTIT and does not compromise oncological safety. The M-MTIT can be considered a safe and feasible option for vulvar cancer patients with locally advanced disease.

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British Gynaecological Cancer Society (BGCS) vulval cancer guidelines: Recommendations for practice

Cited by 48 publications

References 134 publications

Evaluation of Immunohistochemical Markers, CK17 and SOX2, as Adjuncts to p53 for the Diagnosis of Differentiated Vulvar Intraepithelial Neoplasia (dVIN)

Evaluation of Immunohistochemical Markers, CK17 and SOX2, as Adjuncts to p53 for the Diagnosis of Differentiated Vulvar Intraepithelial Neoplasia (dVIN)

Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma

Comparison of two types of the triple incision technique in the treatment of patients with locally advanced vulvar cancer

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