Vulvar Squamous Cell Carcinoma Research Articles

Clinical Impact of Pelvic Sentinel Lymph Node Biopsy for Vulvar Squamous Cell Carcinoma.

This study investigated the clinical impact of resection of pelvic sentinel lymph nodes (PSLNs) in squamous cell vulvar cancer (SCVC). Sixty-two groins of 33 patients with SCVC who underwent sentinel lymph node (SLN) resection between 2010 and 2021 at the University Hospital of Cologne, Germany, were analyzed in this retrospective cohort study. The frequency of additionally resectable PSLNs, histological findings, and count rates were analyzed and compared to the findings for inguinal sentinel lymph nodes (ISLNs). In all patients and in 61 (98%) of the 62 radiolabeled groins, at least one SLN could be resected. Five (8%) of the 62 groins had histologically confirmed lymph node metastases (4/33 patients, 12%). Twenty (33%) of the 62 groins underwent additional PSLN resection. Resection of these PSLNs was feasible without causing an additional burden for the patients. None of the PSLNs showed signs of tumor infiltration. Information on the extent of radioactivity for ISLNs and simultaneously for PSLNs, expressed as count rate of intraoperative measurement with the gamma probe, was available for 20 (32%) groins. In three (15%) of these cases, the highest count rate in a SLN was found in a PSLN and not in an ISLN. Resection of PSLNs is feasible and can be performed without short-term complications. In patients with early SCVC, resection of PSLNs is not necessary, even in those with early infiltration of inguinal lymph nodes. The intraoperative count rate of SLN is not relevant for the decision to perform resection.

Prognostic characteristics, recurrence patterns, and survival outcomes of vulval squamous cell carcinoma – A twelve-year retrospective analysis of a tertiary centre

Vulval cancer is a rare gynaecological malignancy. In this study, we present a tertiary centre case analysis to examine the recurrence patterns and survival outcomes of vulval squamous cell carcinoma (SCC). This is a retrospective cohort study of women who received treatment at Oxford University Hospitals between February 2010 and July 2022 for primary vulval SCC. We included 98 cases. The median age at diagnosis was 68 years. Human Papillomavirus (HPV) infection and lichen sclerosis were observed in 21 and 50 cases, respectively. Surgical excision was the primary treatment. Recurrence within 2 years was more common with advanced stage (p = 0.047, RR = 2.26) and extracapsular lymph node spread (p = 0.013, RR = 2.88). Local recurrence was not associated with a specific cut-off value for tumour-free margin. Poor survival outcomes were observed with higher grade (p = 0.01), advanced FIGO stage (p < 0.001), HPV-independent cancer (p = 0.048), lymph node involvement (p < 0.001, HR = 7.14), extracapsular spread (p < 0.001, HR = 7.93), lymphovascular space invasion (p = 0.002, HR = 3.17), tumour diameter wider than 23 mm (p = 0.029, HR = 2.53) and depth of invasion more than 6 mm (p = 0.006, HR = 3.62). Perineural invasion is associated with shorter disease-free survival. Five-year cancer-specific survival rates for stages I, III, and IV were 90.2%, 40.8%, and 14.3%, respectively.

Current Preoperative Management of Vulvar Squamous Cell Carcinoma: An Overview.

Vulvar carcinoma is a rare cancer affecting the genital tract, constituting 4% of gynecological tumors. Vulvar squamous cell carcinoma (VSCC) is the most common type. Diagnosis relies on biopsy during vulvoscopy, plus imaging such as ultrasonography (USG), magnetic resonance imaging (MRI) and positron emission tomography (PET). This review aims to lay out a thorough overview as to the current preoperative management of VSCC, both in case of vulvar and lymph node involvement. The data research was conducted using the following databases: MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library from 2010 to 2024. The selection criteria included only original articles. Seventeen studies were assessed for eligibility. A concordance rate of 62.3% for vHSIL and 65.2% for carcinoma at vulvoscopy, with a sensitivity of 98%, specificity of 40%, PPV (Positive Predictive Value) of 37% and NPV (Negative Predictive Value) of 98% in identifying malignant lesions was found. Regarding the reliability of PET for staging and assessing lymph node involvement, a mean SUV (Standardized Uptake Value) for malignant vulvar lesions of 8.4 (range 2.5-14.7) was reported. In the case of MRI, useful for the evaluation of loco-regional infiltration and lymph node involvement, the ratio of the short-to-long-axis diameter and the reader's diagnostic confidence for the presence of lymph node metastasis yielded accuracy of 84.8% and 86.9%, sensitivity of 86.7% and 87.5%, specificity of 81.3% and 86.2%, PPV of 89.7% and 87.5% and NPV of 76.5% and 86.2%, respectively. A long lymph node axis >10 mm and a short diameter >5.8 mm were found to be predictors of malignancy. At USG, instead, the two main characteristics of potentially malignant lymph nodes are cortical thickness and short axis length; the combination of these ultrasound parameters yielded the highest accuracy in distinguishing between negative and positive lymph nodes. Despite the heterogeneity of the included studies and the lack of randomized clinical trials, this review provides a broad overview of the three imaging tools used for the presurgical management of VSCC. Nowadays, although MRI and PET represent the gold standard, ultrasound evaluation is taking on a growing role, as long as it is carried out by expert sonographer. The management of this rare disease should be always performed by a multidisciplinary team in order to precisely stage the tumor and determine the most suitable treatment approach.

Clinical outcomes with utilization of high-potency topical steroids in patients with lichen sclerosus-associated vulvar cancer

ObjectivesTo evaluate the impact of high-potency topical steroid use on risk of recurrence of lichen sclerosus-associated vulvar cancer. MethodsThis is a retrospective cohort study evaluating patients with lichen sclerosus (LS)- associated vulvar squamous cell cancer (VSCC). Demographic and clinical outcome data were compared between two comparison groups: patients who received steroids, mainly clobetasol, and patients who did not receive steroids following treatment of LS-related vulvar cancer. Categorical variables were compared using Fisher's exact test or chi-square test. Continuous variables were compared using a two-sided student's t-test. Time to recurrence (TTR) and overall survival (OS) were analyzed using Kaplan-Meier survival plot and compared using Mantel-Cox log rank test. Cox proportional hazard regression models were conducted to generate hazard ratios for both TTR and OS. A p value of <0.05 was considered statistically significant. ResultsA total of 49 patients were included, with 36 patients receiving steroid treatment and 13 patients in the expectant management group. The median age of diagnosis was 68. The average BMI was 31.7 +/− 7.0. The median length of follow up was 41 months. The majority of patients were diagnosed with stage I VSCC. There was no difference in demographics or oncologic management of vulvar cancer between the two cohorts. Overall recurrence was decreased among patients who received steroid treatment when compared to patients who did not, 12 patients (33.3%) versus 9 patients (69.2%) respectively (p = 0.048). ConclusionsHigh-potency topical steroid use following treatment of lichen sclerosus-associated vulvar squamous cell carcinoma is associated with decreased risk of recurrence and prolonged median time to recurrence.

Molecular Classification of Vulvar Squamous Cell Carcinoma and Precursor Lesions Using Immunohistochemistry

Abstract Introduction: Vulvar malignancies are very rare. Two pathogenic pathways have been described in the development of vulvar squamous cell carcinoma.One is related to HPV infection and the other is related to TP 53 mutation. HPV infection related squamous cell carcinomas have a good prognosis and squamous cell carcinomas related to TP 53 mutation have the worst prognosis. Recently a third pathway which is neither HPV dependent nor p53 mutant has been identified. This pathway is found to have intermediate prognosis with better clinical outcome. Aims: The aim of this study was to classify vulvar squamous cell carcinoma and its precursor lesions molecularly using two immunohistochemical stains p16 and p53 in a cohort of South Indian population. Subjects and Methods: A retrospective observational study was conducted between January 2011 and December 2020 in the department of histopathology at a tertiary care hospital in Hyderabad, India. A total of 22 cases including all the vulval biopsies with suspected squamous cell carcinoma or precursor lesions and excision specimens operated for squamous cell carcinoma were included in this study. Paraffin blocks of representative cases were stained with hematoxylin and eosin stain, p16 and p53 immunohistochemistry (IHC) stains. Results: Out of 22 cases, two cases (9.0%) were precursor lesions of the vulva and 20 cases (90.9%) were invasive squamous cell carcinoma. Eleven (50%) of these cases were p53 mutant (p53+/p16−), 10 (45.4%) of these cases were HPV positive (p16+/p53−), and one of these cases (4.5%) was neither HPV positive nor p53 mutant (p16−/p53−). Conclusions: Classification of vulvar squamous cell lesions molecularly using simple immunohistochemical stains in routine diagnostic workup will aid in risk stratification of patients and help in their management and prognostication.

A Mimicker of Differentiated Vulvar Intraepithelial Neoplasia: Reactive Atypia From Noncompliance With Lichen Sclerosus Therapy.

Differentiated vulvar intraepithelial neoplasia (d-VIN) is an HPV-independent precursor to vulvar squamous cell carcinoma. The histology of d-VIN lesions is difficult to differentiate from that of non-neoplastic epithelial disorders, especially lichen sclerosus (LS). The authors present a case of LS, where relying on histopathology alone could have led to misdiagnosis. The patient was a 17-year-old female patient with clinical features of vulvar dermatitis and LS for 2 years. She was counseled to apply clobetasol 0.05% to the affected area daily but reported no improvement after 6 months. A biopsy of the right labia majora revealed histologic findings typical of d-VIN and near-contiguous p53 expression. These features are characteristic of d-VIN. However, d-VIN is exceedingly rare in young patients. The case was reviewed by 6 dermatopathologists and gynecologic pathologists, who observed that the degree of inflammation would be unusual postclobetasol therapy and could be due to noncompliance. A review of the patient's chart revealed that she "does not always remember to apply" clobetasol. The patient's clinician confirmed that there were compliance issues, and the follow-up biopsy was negative for d-VIN. The case was signed out as LS, with a note describing the above, and to rebiopsy if concern persisted. The authors conjecture that inflammatory infiltrates in the biopsied area caused reactive atypia due to lack of adherence to treatment. Although the patient's age helped rule out d-VIN, similar cases in elderly patients may be occurring. Pathologists must be aware that reactive forms of untreated LS can mimic d-VIN, to avoid misdiagnosis.

Evaluation of Multimodality Imaging Based Treatment Volume Determination for Vulvar Squamous Cell Carcinoma (VSCC)

Evaluation of Multimodality Imaging Based Treatment Volume Determination for Vulvar Squamous Cell Carcinoma (VSCC)

Phase II Trial of Cisplatin, Gemcitabine, and Intensity-Modulated Radiation Therapy for Locally Advanced Vulvar Squamous Cell Carcinoma: NRG Oncology/GOG Study 279.

To assess efficacy and toxicity of cisplatin (C) and gemcitabine (G) with intensity-modulated radiation therapy (IMRT) in patients with locally advanced vulvar cancer not amenable to surgery. Patients enrolled in a single-arm phase II study. Pretreatment inguinal-femoral nodal assessment was performed. Sixty-four Gy IMRT was prescribed to the vulva, with 50-64 Gy delivered to the groins/low pelvis. Radiation therapy (RT) plans were quality-reviewed pretreatment. C 40 mg/m2 and G 50 mg/m2 were administered once per week throughout IMRT. Complete pathologic response (CPR) was the primary end point. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and adverse events were assessed with Common Terminology Criteria for Adverse Events v 4.0. Fifty-seven patients enrolled, of which 52 were evaluable. The median age was 58 years (range, 25-58), and 94% were White. Forty (77%) had stage II or III disease, and all had squamous histology. A median of six chemotherapy cycles (range, 1-8) were received. Eighty-five percent of RT plans were quality-reviewed with 100% compliance to protocol. Seven patients came off trial because of toxicity or patient withdrawal. Of 52 patients available for pathologic assessment, 38 (73% [90% CI, 61 to 83]) achieved CPR. No pelvic exenterations were performed. With a median follow-up of 51 months, the 12-month PFS was 74% (90% CI, 62.2 to 82.7) and the 24-month OS was 70% (90% CI, 57 to 79). The most common grade 3 or 4 adverse events were hematologic toxicity and radiation dermatitis. There was one grade 5 event unlikely related to treatment. Weekly C and G concurrent with IMRT sufficiently improved CPR in women with locally advanced vulvar squamous cell carcinoma not amenable to surgical resection.

Biopsy-verified vulvar lichen sclerosus: Incidence trends 1997-2022 and increased risk of vulvar squamous precancer and squamous cell carcinoma.

Population-based data on the epidemiology of vulvar lichen sclerosus (LS) are sparse and only few prospective studies have investigated the malignant potential of the disease. We used the nationwide Danish Pathology Registry to first assess the incidence of biopsy-verified vulvar LS in the period 1997-2022 and second to examine the incidence of vulvar high-grade squamous precancer and squamous cell carcinoma (SCC) in women with biopsy-verified vulvar LS (1978-2019) compared with that expected in the general female population. For the latter aim, we computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). During our study period, the age-standardized incidence rate of vulvar LS increased from 5.0 (1997-1998) to 35.7 (2021-2022) per 100,000 person-years. Compared with the general female population, women with biopsy-verified vulvar LS had significantly increased rates of vulvar high-grade squamous precancer (SIR = 8.5; 95% CI: 7.2-10.0) and SCC (SIR = 16.2; 95% CI: 14.2-18.4). The SIRs of vulvar high-grade squamous precancer and SCC did not vary substantially according to length of follow-up. This nationwide and population-based study shows a 7-fold increase in the incidence of biopsy-verified vulvar LS since 1997. Data also show that women with biopsy-verified vulvar LS have 8.5 and 16 times higher than expected incidence of vulvar high-grade squamous precancer and SCC, respectively. The substantially increased incidence of vulvar high-grade squamous precancer and SCC following LS is important in relation to the clinical management and follow-up of LS patients.

Abstract 6454: Genomic characterization of vulvar squamous cell carcinoma

Abstract Introduction: Understanding the molecular underpinnings of vulvar squamous cell carcinoma (vSCC) has strong potential for clinical impact, given the unmet need for this rare cancer. vSCCs have two main etiologies, including human papillomavirus (HPV) infection or skin conditions such as lichen sclerosis. Clinically, few treatment options with limited efficacy are available for recurrent vSCCs and large whole transcriptome disease subtyping studies are limited due to the rarity of this cancer type. Here, we present a whole transcriptome subtyping study of 244 vSCC clinical samples with DNA genomic profiling. Furthermore, we compared vSCCs to other SCC disease subtypes (pan-SCC), including lung, esophageal, skin, urothelial, anal, and head and neck (HN). Our goal was to gain novel insights into the molecular landscape of vSCCs to inform new routes of therapy. Methods: Deidentified records of SCC patients were selected from the Tempus clinico-genomic database. The vSCC cohort was predominantly composed of, but not exclusively, naive or pre-treatment primary tissue. The pan-SCC cohort was limited to randomly sampled primary pre-treatment female samples with paired RNA and DNA sequencing. To perform vSCC subtyping, we used bulk RNA-seq and clustered the samples using FastPG-CC, an internally developed consensus-clustering extension of FastPG, a graph-based parallelized clustering tool. We next performed differential expression, pathway analysis, and cell type abundance estimation. Results: Unbiased gene expression clustering analysis identified three vSCCs clusters; an HPV+ cluster (HPV+, 32% of vSCC samples), HPV- cluster (HPV-, 33%), and an intermediate cluster which contained both HPV+ and HPV- samples (Mix, 35%). The HPV- cluster was enriched for TP53 and TERT promoter mutations, EMT and tumor microenvironment gene expression-derived pathways, and was most similar to HPV- oral HN tumors. The HPV+ cluster was enriched with PIK3CA mutations, cell cycle gene expression and was most similar to other HPV+ SCC samples, including cervical, anal, and HN. The Mix cluster was enriched for neutrophils, fatty acid metabolism and was most similar to skin SCC. Conclusions: We performed a multi-modal molecular subtyping analysis on a large cohort of vSCCs and identified three molecular subtypes, which enabled us to identify heterogeneity within vSCC, and observe that a subset of vSCCs share features with SCC tumor types for which there are emerging therapy options. Thus, this approach identifies a subset vSCCs that may be responsive to existing SCC therapeutics. Citation Format: Sara R. Selitsky, Tasha Thong, Kimberley Roche, Justin Guinney, Praveen Sethupathy, Catherine Igartua. Genomic characterization of vulvar squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6454.

Update on the Sentinel Node Procedure in Vulvar Cancer.

Early-stage vulvar cancer is managed by a local excision of the primary tumor and, if indicated, a sentinel node (SN) biopsy to assess the need for further groin treatment. With the SN procedure, many patients can be treated less radically and will experience less complications and morbidity compared with an inguinofemoral lymphadenectomy (IFL). Still, the SN procedure can be further optimized. Different tracers for detecting the SN are being investigated, aiming to optimize detection rates and decrease the burden of the procedure and short-term complications. Until now, no standardized protocols exist for the pathologic workup of the SN, possibly leading to discrepancies in detection of metastases between institutes using different methods. New techniques, such as one-step nucleic amplification, seem to have potential in accurately detecting metastases in other cancers, but have not yet been investigated in vulvar squamous cell carcinoma (VSCC). Furthermore, several studies have investigated the possibility to broaden the indications for the SN procedure, such as its use in recurrent disease, larger tumors, or multifocal tumors. Although these studies show encouraging results, cohorts are small and further studies are needed. Prospective studies are currently investigating these subgroups. Lastly, several studies investigated optimization of groin treatment of patients with a metastatic SN. Inguinofemoral radiotherapy is a good alternative to IFL in patients with micrometastases in the SN, with comparable efficacy and less treatment-related morbidity. Reduction of the radicality of groin treatment is also possible in other ways, such as omitting contralateral IFL in patients with lateralized tumors and a unilateral metastatic SN. In conclusion, the SN procedure is an established procedure in early-stage VSCC, although optimization of the technique, pathologic workup, indications, and treatment in the setting of metastatic disease are the subject of ongoing research.

The risk of vaginal, vulvar and anal precancer and cancer according to high-risk HPV status in cervical cytology samples.

High-risk human papillomavirus (hrHPV) is the cause of virtually all cervical cancers, most vaginal and anal cancers, and some vulvar cancer cases. With HPV testing becoming the primary screening method for cervical cancer, understanding the link between cervical hrHPV infection and the risk of other anogenital cancers is crucial. We assessed the risk of vulvar, vaginal and anal cancer and precancer (VIN2+, VaIN2+ and AIN2+) in a prospective cohort study including 455,349 women who underwent cervical hrHPV testing in Denmark from 2005 to 2020. We employed Cox proportional hazard models, adjusting for age, calendar year and HPV vaccination status, and estimated hazard ratios (HRs) and 95% confidence intervals (CI). We used the Aalen Johansen estimator to calculate the absolute risks of VIN2+, VaIN2+ and AIN2+. In total, 15% of the women were hrHPV positive at baseline. A positive cervical hrHPV test was associated with increased incidence of vulvar, vaginal and anal squamous cell carcinoma (SCC). Five-year risk estimates of VIN2+, VaIN2+ and AIN2+ among hrHPV-positive women (0.45%, 0.14% and 0.12%) were higher than among hrHPV-negative women (0.14%, 0.01% and 0.05%). Particularly high risk was observed among the hrHPV-positive women of the oldest age, with a history of anogenital precancer and those not HPV vaccinated. In conclusion, our study confirms the association between cervical hrHPV infection and non-cervical anogenital precancers and cancers. Currently, no established risk threshold or guidelines for follow-up. As HPV testing becomes the primary method for cervical cancer screening, future data will help define high-risk groups and acceptable risk thresholds.

Vulvar squamous cell carcinoma with a fatal outcome

Vulvar cancer is one of the least common forms of gynecologic malignancies. At least 75 percent of vulvar cancer are squamous cell carcinoma, being mainly associated with human papillomavirus infection.

Differentiated vulvar intraepithelial neoplasia long-term follow up and prognostic factors: An analysis of a large historical cohort.

Differentiated vulvar intraepithelial neoplasia (dVIN) is a high-risk preinvasive vulvar lesion and precursor of human papillomavirus-independent vulvar squamous cell carcinoma (VSCC). Due to its rarity, literature data on its malignant potential are scant. The aim of the study is to assess the risk of developing VSCC in patients surgically treated for dVIN not associated with VSCC (solitary dVIN) and the risk of VSCC recurrence in patients treated for dVIN associated with VSCC (dVIN-VSCC) at first diagnosis. A historical cohort study was performed in a northern Italy referral center for vulvar neoplasms. All consecutive women surgically treated for histologically confirmed dVIN from 1994 to 2021 were collected. Primary outcome was cancer risk or recurrent cancer risk, secondary outcomes were risk factors associated with VSCC development or recurrence. Kaplan-Meier method and log-rank test were used to estimate cancer risk or recurrent cancer risk differences and uni- and multivariate Cox regression analyses to identify risk factors associated with VSCC development in solitary dVIN and recurrence of dVIN-VSCC. Seventy-six patients with dVIN at preoperative biopsy were included: at excisional specimens 44 were solitary dVIN and 32 were dVIN-VSCC. The absolute risk of VSCC development after solitary dVIN treatment was 43.2% with median time to to VSCC diagnosis of 25.4 months (range 3.5-128.0 months). VSCC recurrence absolute risk in treated dVIN-VSCC patients was 31.3% with median time to VSCC recurrence of 52.9 months (range 6.5-94.8 months). At uni- and multivariate regression analyses, only compliant topical ultrapotent corticosteroid treatment after solitary dVIN excision showed an ability to prevent VSCC development. No protective effect by corticosteroid treatment was shown for VSCC recurrence in dVIN-VSCC patients. Smoking was associated with higher cancer recurrence risk in dVIN-VSCC patients on both uni- and multivariate regression analyses. Patients with dVIN have a high risk of developing both primary and recurring VSCC. Early recognition, long-term follow up, and compliant ultrapotent topical corticosteroid treatment are recommended.

High concordance of molecular subtyping between pre-surgical biopsy and surgical resection specimen (matched-pair analysis) in patients with vulvar squamous cell carcinoma using p16- and p53-immunostaining

ObjectiveVulvar squamous cell carcinoma (VSCC) can be stratified into three molecular subtypes based on the immunoexpression of p16 and p53: HPV-independent p53-abnormal (p53abn) (most common, biologically aggressive), HPV-associated, with p16-overexpression (second most common, prognostically more favourable) and more recently recognised HPV-independent p53-wildtype (p53wt) (rarest subtype, prognostically intermediate). Our aim was to determine whether molecular subtypes can be reliably identified in pre-operative biopsies and whether these correspond to the subsequent vulvectomy specimen. MethodsMatched-paired pre-surgical biopsies and subsequent resection specimen of 57 patients with VSCC were analysed for the immunohistochemical expression of p16 and p53 by performing a three-tiered molecular subtyping to test the accuracy rate. ResultsMost cases 36/57 (63.2%) belonged to the HPV-independent (p53-abn) molecular subtype, followed by HPV-associated 17/57 (29.8%) and HPV-independent (p53wt) 4/57 (7.0%). The overall accuracy rate on biopsy was 91.2% (52/57): 97.3% for p53-abnormal, 94.1% for p16-overexpression and 50% for p16-neg/p53-wt VSCC.Incorrect interpretation of immunohistochemical p53 staining pattern was the reason for discordant results in molecular subtyping in all five cases. In one case there was an underestimation of p53 pattern (wildtype instead of abnormal/aberrant) and in one case an overestimation of the p53 staining pattern (abnormal/aberrant instead of wildtype). In 3/5 there was a “double positive” staining result (p16 overexpression and abnormal/aberrant p53 staining pattern). In that cases additional molecular workup is required for correct molecular subtyping, resulting in an overall need for molecular examination of 3/57 (3.5%). ConclusionsCompared to the final resections specimen, the three-tiered molecular classification of VSCC can be determined on pre-surgical biopsies with a high accuracy rate. This enables more precise surgical planning, prediction of the response to (chemo) radiation, selection of targeted therapies and planning of the optimal follow-up strategy for patients in the age of personalised medicine.

PD-L1 Expression in HPV-associated Versus HPV-independent Invasive Vulvar Squamous Cell Carcinoma.

Two etiological pathways have been implicated in the pathogenesis of vulvar squamous cell carcinoma (VSCC): a high-risk human papillomavirus (HPV)-associated route and an HPV-independent pathway characterized by TP53 mutations. Programmed cell death ligand 1 (PD-L1) has become increasingly useful in predicting the response to checkpoint inhibitor therapy in squamous cell carcinomas at various anatomical sites. This study aimed to assess the association between PD-L1 expression and the VSCC subtype to evaluate the utility of PD-L1 in prognostication and therapeutic selection based on HPV status. PD-L1 status was assessed using 3 separate metrics for the extent of PD-L1 staining in various cell types: immune cell score, tumor proportion score (TPS), and combined positive score. The study group consisted of 25 HPV-associated and 28 HPV-independent VSCCs. PD-L1 expression was positive in the majority of VSCCs according to all 3 scoring metrics (84.9% by immune cell score, 77.3% by TPS, and 90.6% by combined positive score). PD-L1 expression was observed in the majority of cases in both groups (60%-96.4%). PD-L1 expression using the TPS method was greater in HPV-independent tumors than in HPV-associated tumors ( P = 0.004), and high PD-L1 expression was also more common in the HPV-independent subtype ( P = 0.016 using the TPS method and P = 0.013 using the combined positive score method). Our findings contribute to the growing evidence that PD-L1 is expressed in the majority of invasive VSCCs, and thus may serve as an attractive therapeutic target. PD-L1 expression is higher in HPV-independent tumors, suggesting that this subtype may be more responsive to PD-L1 inhibitor therapy.

Survival nomograms for vulvar squamous cell carcinoma based on the SEER database and a Chinese external validation cohort.

The aim of study was to construct a nomogram to effectively predict the overall survival (OS) and cancer-specific survival (CSS) for patients with vulvar squamous cell carcinoma (VSCC). The training cohort consisted of 5405 patients with VSCC, extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Eighty-four patients with VSCC were selected from the disease database of the Shengjing Hospital of China Medical University from 2014 to 2020, and enrolled as the external validation cohort. Significant independent prognostic factors were identified using Cox regression analysis and used to develop nomograms to predict 1-, 3-, and 5-year OS and CSS in patients with VSCC. The nomogram predicting OS was developed based on tumor size, histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, regional lymph node involvement, distant metastases, surgery, chemotherapy, age, and race. The nomogram for CSS was constructed using the similar factors, excluding race but including marital status. The nomogram for 1-, 3-, and 5-year OS demonstrated robust performance with receiver operating characteristic curves (AUCs) exceeding 80% (0.86, 0.84, and 0.82), outperforming the FIGO staging alone (0.77, 0.75, and 0.72). Similarly, for CSS, our nomograms achieved larger AUCs of 0.89, 0.88, and 0.86 compared with FIGO staging alone (0.81, 0.79, and 0.78). The nomograms more accurately predict prognosis than simple FIGO staging. Moreover, the nomograms developed in this study provide a convenient, operable, and reliable tool for individual assessment and clinical decision-making for patients with VSCC.

Lymph node ratio as an indicator of nodal status in the assessment of survival and recurrence in vulvar cancer: A cohort study.

Inguinal lymph node (LN) metastasis and particularly the number of metastatic lymph nodes (NMLN) represent a determinant prognostic factor in vulvar squamous cell carcinoma (VSCC). However, the NMLN may be related to the number of removed LNs. Therefore, the lymph node ratio (LNR) reflects not only the burden of LN involvement but also the quality and extent of lymphadenectomy. To investigate the value of the LNR and the count of LN on overall survival (OS) and recurrence-free survival (RFS). This study is a retrospective, longitudinal, institution-based study. This study included 192 patients treated for VSCC at the Salah Azaiez Institute between 1994 and 2022. Clinical, pathological, and evolutionary data were reported. Survival curves were generated by the Kaplan-Meier method, and predictive factors of outcome were analyzed using Cox proportional hazards models. Surgery consisted of a radical vulvectomy, hemivulvectomy, and pelvic exenteration in, respectively, 96.4%, 2.1%, and 1.6% of cases followed by adjuvant radiotherapy in 38.5% of cases. LN dissection was bilateral in 88.5% of cases. LNR = 0, LNR = 0-0.2, and LNR ⩾0.2 were recorded in, respectively, 64.7%, 22.1%, and 13.2% of cases. With a mean follow-up time of 35 ± 42.06 months, the 5-year OS was 52.5% and the 5-year RFS was 55.8%. On multivariate analysis, the independent prognostic factors of OS were the LNR (hazard ratio (HR) = 5.702; 95% confidence interval (CI) = 2.282-14.245; p < 0.0001), Federation of Gynecology and Obstetrics (FIGO) stage (HR = 2.089; 95% CI = 1.028-4.277; p = 0.042), and free margins (HR = 2.247; 95% CI = 1.215-4.155; p = 0.01). Recurrences were recorded in 37.5% of cases. Independent prognostic factors of RFS were the LNR (HR = 2.911; 95% CI = 1.468-5.779; p = 0.002), FIGO stage (HR = 1.835; 95% CI = 1.071-3.141; p = 0.027), and free margins (HR = 2.091; 95% CI = 1.286-3.999; p = 0.003). Surgical margin, FIGO stage, and LNR represent the independent prognostic factors of survival and LNR showed superior prognostic predictive accuracy compared with the revised 2021 FIGO staging system for predicting OS and RFS in VSCC.

The prognostic significance of primary tumor site in vulvar cancer: a population-based cohort study.

To investigate the association of primary tumor site with prognosis in vulvar cancer, stratified by vulvar squamous cell carcinoma (SCC) and non-SCC histological types. This population-based retrospective study enrolled patients with vulvar cancer from the Surveillance, Epidemiology, and End Results database between January 2000 and December 2018. The primary outcome was cancer-specific survival (CSS). The prognostic difference between labium majus, labium minus and clitoris groups was investigated using Kaplan-Meier analyses and Cox proportional hazards regression analyses. A total of 3,465 eligible patients with vulvar cancer were included with a mean age of 54.5 years. Among the 1,076 (31.1%) patients with non-SCC, the multivariate Cox regression analyses showed that labium minus-sited disease (hazard ratio [HR]=1.85; 95% confidence interval [CI]=1.27-2.71; p=0.001) and clitoris-sited disease (HR=2.37; 95% CI=1.47-3.85; p<0.001) were significantly associated with worse CSS, compared with labium majus-sited disease. However, among the 2,389 (68.9%) patients with SCC, no significant association of primary tumor site with CSS was found (p>0.05). Kaplan-Meier analyses also showed that the primary tumor site had a significant prognostic effect in vulvar non-SCC (p<0.001) but not in vulvar SCC (p=0.330). Among vulvar non-SCC, patients with labium minus-sited disease had a significantly worse prognosis than those with labium majus-sited disease, and a significantly better prognosis than those with clitoris-sited disease. Gynecologic oncologists should consider the prognostic effect of primary tumor site in vulvar non-SCC, and make optimal, personalized treatment and surveillance strategies based on different primary tumor sites.

Prevalence of prescribing topical corticosteroids to patients with lichen sclerosus following surgery for vulvar cancer: a survey among gynaecologic oncologists in The Netherlands

Background Vulvar lichen sclerosus (LS) is a chronic inflammatory dermatosis which can progress to precursor lesion differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar squamous cell carcinoma (VSCC). The risk of developing recurrent vulvar cancer following LS-associated VSCC is high. Evidence suggests that treatment of LS with topical corticosteroids (TCS) can prevent progression to dVIN, VSCC and recurrences. However, current guidelines do not give any recommendation on the management of LS following surgery for VSCC. The aim of this study was to conduct a survey among all registered gynaecologic oncologists (GOs) in the Netherlands to evaluate the current management of LS patients without a history of VSCC (LSnoVSCC) and patients with LS following surgery for VSCC (LSVSCC). Methods An online survey was distributed to all registered GOs in the Netherlands. Primary outcome measures were the frequency, type and duration of TCS treatment prescribed for LSnoVSCC and LSVSCC patients, separately. As a secondary outcome measure, reasons for treating or not treating patients with LSnoVSCC and LSVSCC with TCS were analysed. Results Forty-four GOs completed the survey, resulting in a response rate of 75%. TCS were prescribed more often to patients with LSnoVSCC as compared to patients with LSVSCC (86% versus 52%, respectively, p < 0.001). If treatment was initiated, ultra-potent (class IV) TCS were most commonly prescribed for an indefinite period of time for both patient groups. The most reported reason for treating patients in both groups with TCS was symptoms, followed by clinical aspects of the lesion and prevention of progression to dVIN and VSCC. Conclusion The majority of GOs who participated in our study endorse the utilisation of long-term ultra-potent TCS therapy in both patients with LSnoVSCC and LSVSCC. Nevertheless, Dutch GOs are currently prescribing TCS more frequently to patients with LSnoVSCC than to patients with LSVSCC.