Impaired sexual health among women treated for vulvar cancer: An integrated review.

BACKGROUND: Although gynaecological cancer's negative effects on sexual function are well known, most studies on the subject have not included vulvar cancer patients or a multidimensional perspective on sexual health. Therefore, this review aimed to address this research gap and explored the impact of vulvar cancer on women's sexual health from a multidimensional perspective. METHODOLOGY: An integrated review was conducted, as described by Whittemore and Knafl. The PubMed, CINAHL, PsycINFO and Embase databases were searched in March 2021 and updated in August 2022 and March 2023. The data were thematically analysed using NVivo, and the PRISMA-ScR and ENTREQ guidelines were followed. FINDINGS: The following themes were identified in the 28 reviewed articles: impact of a changed female body, impact on women's sexual identity, consequences for women's sexual relationships and unmet needs and loneliness caused by taboos about sexual health. DISCUSSION: Women's impaired sexual health after vulvar cancer points to a great need to understand and holistically investigate sexual health. In addition, healthcare professionals have an obligation to care for the sexual health issues of patients with vulvar cancer. However, most questionnaires used in the selected studies revealed a narrow understanding of sexual health and focused on sexuality as a genital activity. CONCLUSION: The sexual health of women with vulvar cancer was tabooed and stigmatised for patients and healthcare professionals. Consequently, women received sparse sexual guidance, felt isolated and had unmet needs. IMPLICATIONS FOR CLINICAL PRACTICE: Healthcare professionals need knowledge and training on how to break taboos and address the sexual needs of vulvar cancer patients. Systematic screenings for sexual health needs should be conducted using a multidimensional perspective. TRIAL AND PROTOCOL REGISTRATION: The protocol was preregistered at the Open Science Framework (www.osf.io), registration DOI: https://doi.org/10.17605/OSF.IO/YDA2Q PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Comparison of cisplatin and mitomycin C/5-FU as radiosensitisers in the treatment of locally advanced vulvar cancer: results of a retrospective, observational, single-institutional cohort study.

PURPOSE: We retrospectively investigated the widely used radiosensitisers cisplatin and mitomycin C/5-fluorouracil (5-FU) in patients with locally advanced vulvar cancer for outcome and toxicity. METHODS: We screened the archive for patients treated with chemoradiation for vulvar cancer diagnosed between 01/2010 and 08/2021 at our institution. The impact of both radiosensitisers on prognosis was compared using Kaplan-Meier method and Cox-regression analysis. RESULTS: One hundred and forty-three patients with vulvar cancer were screened. Twenty-nine patients received chemoradiation (mitomycin C/5-FU n = 14; cisplatin n = 12; others n = 3) as a primary, neoadjuvant or adjuvant treatment. Median follow-up was 15.5 months. Patients in the cisplatin group were older (mean age 54.4 vs. 70.7; p = 0.004). However, the mitomycin C/5-FU group had more advanced tumour stages. The 2-year recurrence-free survival (RFS) was comparable (44.5% vs. 33.3%; p = 0.932). The 2-year overall survival (OS) showed a numerical but not statistically significant difference in favour of the mitomycin C/5-FU group (59.7% vs. 31.7%; p = 0.37). 64.3% (9 out of 14) patients, who received mitomycin C/5-FU achieved clinical complete response (cCR) compared to 41.7% (5 out of 12) who received cisplatin (p = 0.505). Radiodermatitis was the most common adverse event in both groups (81%) and more severe in the mitomycin C/5-FU cohort. Myelotoxicity was frequently observed in both groups. Eighteen patients received an additional radiation boost with 10.0 (9-16) Gy and showed a significantly prolonged RFS (p = 0.027) and OS (p = 0.003). CONCLUSION: Mitomycin C/5-FU may be considered in the treatment of young and healthy patients with locally advanced vulvar cancer.

Guideline-Discordant Care in Early-Stage Vulvar Cancer.

OBJECTIVE: To describe the use of National Comprehensive Cancer Network guideline-concordant inguinofemoral lymph node (LN) evaluation in individuals with early-stage vulvar cancer. METHODS: This retrospective cohort study identified patients with T1b and T2 vulvar squamous cell carcinoma diagnosed between 2012 and 2018 using the National Cancer Database. Factors associated with LN evaluation were examined using logistic regression analyses, adjusting for patient, disease, and facility-level characteristics. Kaplan-Meier survival analysis using log rank test and Cox regression was performed for the entire cohort and a subgroup of older patients , defined as individuals aged 80 years or older. RESULTS: Of the 5,685 patients with vulvar cancer, 3,756 (66.1%) underwent guideline-concordant LN evaluation. In our adjusted model, age 80 years or older (odds ratio [OR], 0.30; 95% CI 0.22-0.42) and Black race (OR 0.72; 95% CI 0.54-0.95) were associated with lower odds of LN evaluation. High-volume hospitals were associated with increased odds of LN evaluation compared with low-volume hospitals (OR 1.62; 95% CI 1.28-2.05). Older individuals who did not undergo LN evaluation had significantly worse overall survival than those with pathologically negative LNs (hazard ratio [HR] 0.45; 95% CI 0.37-0.55) and similar overall survival as those with pathologically positive LNs (HR 1.05; 95% CI 0.77-1.43). CONCLUSION: Guideline-concordant LN evaluation for early-stage vulvar squamous cell carcinoma is low. Lower utilization is associated with older age, Black race, and care at a low-volume hospital.

Multidisciplinary management of patients with pubic osteomyelitis, a rare but serious complication after surgery and radiation therapy for advanced gynaecological cancer.

Pubic osteomyelitis is a rare and often late-onset complication of radiation therapy and surgery for vulvar and vaginal carcinoma. It typically presents with vulvar pain, fever, vaginal discharge and/or gait disorders. Pubic osteomyelitis is often accompanied by fistulas or wound dehiscence in the pelvic area. Its accurate diagnosis and treatment are challenging and require a multidisciplinary team effort. In our patients, multiple combined surgical procedures, long-term antibiotic treatment and days to weeks of hospital admission were necessary to treat pubic osteomyelitis. We emphasise the importance of timely and adequate diagnosis and multidisciplinary approach resulting in a course of treatment that is as effective as possible, limiting the impact on quality of life, which is generally high in this group of patients.

Sinecatechins ointment as a potential novel treatment for usual type vulval intraepithelial neoplasia: a single-centre double-blind randomised control study.

OBJECTIVE: To compare the safety and efficacy of 10% sinecatechins (Veregen® ) ointment against placebo in the treatment of usual type vulvar intraepithelial neoplasia (uVIN). DESIGN: A Phase II double-blind randomised control trial. SETTING: A tertiary gynaecological oncology referral centre. POPULATION: All women diagnosed with primary and recurrent uVIN. METHODS: Eligible patients were randomised 1:1 to receive either sinecatechins or placebo ointment (applied three times daily for 16 weeks) and were followed up at 2, 4, 8, 16, 32 and 52 weeks. MAIN OUTCOME MEASURES: The primary outcome measure, recorded at 16 and 32 weeks, was histological response (HR). Secondary outcome measures included clinical (CR) response, toxicity, quality of life and pain scores. RESULTS: There was no observed difference in HR between the two arms. However, of the 26 patients who were randomised, all 13 patients who received sinecatechins showed either complete (n = 5) or partial (n = 8) CR, when best CR was evaluated. In placebo group, three patients had complete CR, two had partial CR, six had stable disease and two were lost to follow up. Patients in the sinecatechins group showed a statistically significant improvement in best observed CR as compared with the placebo group (P = 0.002). There was no difference in toxicity reported in either group. CONCLUSION: Although we did not observe a difference in HR between the two treatment arms, we found that 10% sinecatechins application is safe and shows promise in inducing clinical resolution of uVIN lesions and symptom improvement, thus warranting further investigation in a larger multicentre study. TWEETABLE ABSTRACT: A randomised control study indicating that sinecatechins ointment may be a novel treatment for uVIN.

[Update on precursors of vulvar carcinoma]. / Lésions vulvaires précancéreuses : mise au point.

Vulvar carcinomas represent 4% of all gynaecological cancers with 838 new cases in France in 2018. The precursor lesions of vulvar carcinomas are differentiated vulvar intraepithelial lesion (dVIN) in a context of lichen sclerosus and vulvar high-grade squamous intraepithelial lesion (HSIL) link to human papillomavirus (HPV) infection. Three typical clinical forms of HSIL are described: the Bowenoid papulosis, the Bowen's disease and the confluent VIN. Histopathology cannot differentiate effectively these two types of lesions. P16 and P53 immunostaining are valuable tools to respectively assess HPV infection and divide different types of dVIN. However, P53 immunostaining is still lacking sensibility to detect dVIN. First line therapies are medical treatment excluding the cases with a doubt of invasion. The gold standard treatment for dVIN and vulvar HSIL are respectively topical corticosteroids and imiquimod. Primary prevention for vulvar HSIL and dVIN are respectively HPV vaccination and early treatment of lichen sclerosus. Destructive therapy can be used in case of medical treatment failure such as CO2 laser, cryotherapy, dynamic phototherapy. Surgical indications should be carefully assessed between the risk of recurrence, the spread of the lesions, the aesthetic and functional aspect. Surgical procedures consist in either superficial vulvectomy or radical vulvectomy with or without flap reconstruction. Recurrence rate after surgery is around 20%.

Personalizing vulvar cancer workflow in COVID-19 era: a proposal from Vul.Can MDT.

INTRODUCTION: Since the community spread of Coronavirus disease 2019 (COVID-19), the practice of oncologic care at our comprehensive cancer center has changed. Postponing cancer treatment without consideration of its implications could cost more lives than can be saved. In this special situation, we must continue to provide our cancer patients with the highest quality of medical services assuring the safety. This article provides general guidance on supporting curative treatment strategies in vulvar cancer patients. METHODS: At our institution, a vulvar cancer multidisciplinary team (Vul.Can MDT) of specialists is responsible for personalized treatment of this disease. The phase 2 period necessarily requires specific procedures for both outpatient and inpatient pathways and to provide strategies concerning the management of vulvar cancer patients even in case of an eventually concomitant SARS-CoV-2 infection. In brief, an accurate remote and in person triage must be provided routinely and patients submitted to specific diagnostic tests prior to every major treatment or procedure (surgery, RT, and CT) or in case of suspicion for COVID-19 syndrome. The decisional workflow for these women often old and frail, have been rapidly adjusted by our Vul.Can MDT to mitigate the potential risks of COVID-19. RESULTS: The team produced two types of recommendations concerning: (1) safety regulations of care pathways, patients and health care providers, (2) personalized treatment strategies. We present a protocol that can be applied in clinical practice: the flowcharts provided, include the modulation of treatment intensity designed for surgical procedures and radiation, stratified for FIGO stage of disease and intention. CONCLUSION: We suggest that our proposals are applicable in this setting of patients, considering anyway current international recommendations and guidelines.

Antiviral activity of curcumin-nanoemulsion associated with photodynamic therapy in vulvar cell lines transducing different variants of HPV-16.

Vulvar intraepithelial neoplasia (VIN) is associated with human papillomavirus (HPV) infection. Curcumin is a natural bioactive compound with antineoplastic properties. The use of nanoparticles containing curcumin could allow a better performance of this compound in therapies. So, VIN biopsies were collected and HPV DNA detection was performed by PCR, positive samples were genotyped by Restriction Fragment Length Polymorphism (RFLP) and HPV-16 variants were determined by sequencing. HPV-16 positive vulva carcinoma cells (A431) were transduced with E-P and E-350G HPV-16 E6 variants. The viability of the transduced cells treated with nanoemulsions was determined by MTT assay. Besides, apoptosis was evaluated by enzymatic activity of Caspase-3/7. The cell viability assay showed that both the empty nanoemulsion (NE-V) and the nanoemulsion of curcumin (NE-CUR) had little effect on cell viability as compared to control cells. Additionally, we observed that cells irradiated in the presence of NE-CUR presented 90% of cell death. The apoptosis assay further revealed a significant increase in the activity of caspases 3 and 7 in A431 cells expressing both HPV-16 E6 variants after treatment with NE-CUR. Finally, we submitted the HPV transduced A431 cells to organotypic cultures and observed that the combination of treatments affected tissue architecture with evident signals of tissue damage. We concluded that nanoemulsions attain good biocompatibility, since no cytotoxicity was observed and NE-CUR associated with photoactivation showed promising results, leading to death only in cells subjected to irradiation. This drug delivery system associated with photodynamic therapy may become promising in the treatment of vulva lesions.

Vulvar and vaginal neoplasia in women with inflammatory bowel disease.

Immunosuppressive drugs are the cornerstone in the treatment of inflammatory bowel disease (IBD), however they are associated with an increased risk of extra-intestinal cancer. Whether the risk for female genital tract malignancies, including vulvar and vaginal cancer, is increased is less clear. Our aim was to investigate the risk of these malignancies in IBD-patients. Histopathological data of all IBD patients with a vulvar or vaginal (pre-)cancerous lesion were retrieved from the Dutch nationwide network and registry of histopathology and cytopathology from 1991 to 2015. Medical history was retrieved from patient records. Data from the Central Office for Statistics, the Dutch comprehensive cancer organization, and the IBDSL cohort were obtained to calculate the standardized, and age-adjusted incidence rates. Fifty-five patients met the inclusion criteria. A standardized incidence rate of 1.2(95% CI:0.8-1.7) for vulvar and vaginal carcinoma among adult female IBD was calculated, which did not significantly differ from the general population. The use of immunosuppressive therapy did not increase the occurrence of vulvovaginal malignancy, nor did it influence the recurrence rate. However, immunosuppressive drugs ever-users were on average 11 years younger at the time of their gynaecological diagnosis. Overall, our data do not support intensified screening for vulvar or vaginal malignancies in female IBD patients.

Sentinel Lymph Nodes and Precision Surgery in Gynecologic Cancer.

Besides histologic features, the presence of nodal metastasis is the most crucial prognostic factor for recurrence and survival for patients with gynecologic cancer. Conventionally, lymphadenectomy has been performed routinely to assess lymphatic metastasis. However, lymphadenectomy may be unnecessary in early-stage gynecologic cancer, because the percentage of patients with lymph node involvement is very low. The recent use of sentinel lymph node mapping has provided high feasibility, safety, and accuracy in the assessment of nodal metastasis. The National Comprehensive Cancer Network Clinical Practice Guidelines have incorporated the sentinel lymph node for nodal evaluation in vulvar, endometrial, and cervical cancers.

Hyperbaric oxygen therapy as adjuvant for treating wound complications after extensive resection for vulvar malignancy.

INTRODUCTION: Necrosis, wound breakdown, and infection represent major complications associated with radical vulvectomy. We aimed to analyze the feasibility of hyperbaric oxygen (HBO2) therapy as an adjunctive treatment for such complications. METHODS: We performed a retrospective analysis of the medical records, clinical charts, and operative records of vulvar cancer patients who underwent hyperbaric oxygen therapy after extensive surgical resection in our institute between 2012 and 2016, with a comparison of the clinical outcomes of patients with similar surgical procedures andsevere wound complications who did not undergo HBO2. RESULTS: A total of 16 patients were included in the study. In the subgroup treated with HBO2, seven patients were identified. Two patients had primary surgery, while five had recurrent surgery (of these, two had previously undergone radiation therapy). Six patients received reconstructive flaps (five myocutaneous and onefasciocutaneous), while one patient had primary suture. Dehiscence, ischemia and necrosis were estimated to cover 30%-80% of the surgical surface area. Surgical debridement was performed in six patients. Daily 90-minute sessions in the hyperbaric chamber were performed at a pressure of 2.2 atmospheres absolute, with partial oxygen pressure of 1672 mbar. Infection control and satisfactory healing were achieved using 10-61 sessions. All patients in the subgroup who did not receive HBO2 required surgical debridement due to partial or near-total flap necrosis, with two reconstructive interventions required. CONCLUSIONS: Hyperbaric oxygen therapy was an efficient adjuvant for wound healing and infection control in managing wound complications after extensive vulvar resections.

Evidencia empírica de la miel como tratamiento eficaz. En la dehiscecia de sutura tras vulvectomía radical / Empirical evidence of honey as an effective treatment for wound dehiscence after a radical vulvectomy

El cáncer de vulva es uno de los tumores ginecológicos menos frecuentes. La mutilación producida por cirugías radicales, como la vulvectomía, pueden ocasionar importantes secuelas físicas, psíquicas y sexuales en la mujer. El caso clínico que presentamos es el de una mujer de 83 años diagnosticada de cáncer de vulva, a la que se intervino en nuestro centro por recidiva local y que presentó dehiscencia de la cicatriz pocos días después de la cirugía. Nuestro objetivo es mostrar que la cura con miel es una alternativa eficaz, por sus propiedades curativas, en la cura de dehiscencias en las vulvectomías, además de ser una terapia barata, accesible y fácil de aplicar (AU)

Vulvar cancer is one of the less common gynecological tumors. Nevertheless, the mutilation produced by a radical surgery such as the vulvectomy can cause important sequels in women, both physical and psychological. We present a clinical case of an 83-year-old woman diagnosed with vulvar cancer, who underwent a radical vulvectomy after local recurrence at our hospital. She presented a wound dehiscence a few days after the surgery. Our aim is to discuss that honey is an effective alternative cure of wound dehiscence in vulvectomy due to its healing properties; it is also a cheaper treatment, accessible, and easy to apply (AU)

High Incidence of Erysipelas After Surgical Treatment for Vulvar Carcinoma: An Observational Study.

OBJECTIVES: Vulvar carcinoma is mainly treated surgically and has an overall good prognosis. Despite the development of minimally invasive surgical procedures in recent years, morbidity remains significant. The aim of the study was to determine the incidence and risk factors of erysipelas after surgical treatment for vulvar carcinoma. METHODS: This retrospective observational study was performed within the Comprehensive Cancer Centre South. The study included patients (N = 116) who underwent surgery for primary vulvar carcinoma between 2005 and 2012. Patients with International Federation of Gynecology and Obstetrics stage IA and IV were excluded. Clinical and histopathological data were analyzed using logistic regression, χ(2) tests, Fisher exact tests, independent t tests, and nonparametric tests. Primary outcome was the incidence of postoperative erysipelas and determination of risk factors for erysipelas. Secondary outcome included other comorbidities. RESULTS: A total of 23 patients (20%) with vulvar carcinoma had 1 or more episodes of erysipelas. The risk of developing erysipelas was significantly higher in patients who underwent lymph node dissection than in those who underwent sentinel node biopsy (36% [n = 12] and 14% [n = 11], respectively, P = 0.008) and in patients with lymphedema than in those without (30% [n = 7] and 12% [n = 11], respectively, P = 0.048). Patients with diabetes tended to have a higher incidence of erysipelas than those without (28% vs 18%, P = 0.27). CONCLUSIONS: Erysipelas occurs frequently in patients who undergo surgical treatment for vulvar carcinoma. The risk of erysipelas is 3 times higher in patients who undergo lymph node dissection and in those with lymphedema than in those without, and it tends to be high in patients with diabetes.

Angiokeratoma of Fordyce response to long pulsed Nd:YAG laser treatment.

Angiokeratoma of Fordyce can be easily diagnosed by their typical erythra and cured by varied therapeutic methods including surgery, electrocoagulation, cryotherapy, or various laser systems. Which are the optimal therapeutic methods? There are no consentaneous opinions in the reported articles. We present our characteristic treatment with the application of long pulsed neodymium-dopedyttrium-aluminum-garne (lpNd:YAG) laser in the treatment of angiokeratoma of Fordyce. A 1064 nm lpNd:YAG laser (spot size: 5 mm/7 mm, energy:90-130 J/cm(2) , and pulse duration: 10-20 ms.) was used to treat the patient's lesions. The desirable clinical endpoint of the treatment was lesions shrunk and turned pallor immediately after the irradiation. The treatment interval was at least 8 weeks. Of the 11 patients, 9 of them were cured and 2 of them were improved. The mean treatment sessions were 2.2 times. None of them had a scar formation and any other side effects. All of them were satisfied with the treatment results. We conclude that angiokeratoma of Fordyce responded well to lpNd:YAG laser treatment. It provided a simple, rapid, and no bleeding treatment in treating Angiokeratoma of Fordyce.

[Chemoradioresistance of the female reproductive system cancer--can local laser hyperthermia contribute to its overcoming?].

There is presented the method of local laser hyperthermia on the domestic nanotechnological optic-fiber device LAZON-FT integrated into the program of brachytherapy for tumors of the female reproductive system. This is a universal radiosensibilizator that demonstrates the acceleration of tumor regression also during local and systemic chemotherapy--tumor regression at 50-705 in such conditions permits recommend it in locally advanced cervical and endometrial cancer as well as cancer of the vulva and vagina in the frames of combined use with brachytherapy and chemotherapy.

Radioprotectant and Cytotoxic Effects of Spirulina in Relapsed Verrucous Vulvar Cancer: A Case Report.

CONTEXT: The treatment of relapsed verrucous vulvar cancer (VVC) is difficult. When vulvar cancer relapses, the treatment response is low for second-line treatments. Conversely, toxicity is high. Therefore, scientists need to identify different treatment methods. OBJECTIVES: The case study was intended to examine the benefits of combining treatment with microalgae and metronidazole with radiotherapy to increase the response to treatment. SETTING: The study took place in the Department of Radiation Oncology at Bezmialem Vakif University, in Istanbul, Turkey. PARTICIPANT: The case study involved an 81-y-old female patient whose vulvar tumor was excised and who came to the research team's radiation oncology service for postoperative radiation. She had 2 comorbid disorders: Alzheimer's disease and cardiovascular disease. INTERVENTION: A relapse had occurred in the 15-d postoperative period. Because of the patient's age and comorbid disorders, the research team decided to treat the new tumor only with concurrent radiochemotherapy and a weekly dose of cisplatin that contained chemoradiotherapy, for a total of 25 mg. At the 52.2 Gy dose level, grade 3 radiation skin toxicity occurred in the radiated area, although the research team had obtained an 80% response to the radiochemotherapy. The treatment was interrupted because of toxicity but also due to a deterioration in the patient's general health. Progression of the tumor continued, and the tumor's diameter increased to 7 cm after a 4-mo period. The research team then initiated radiotherapy again, combining it with spirulina in a 750 mg/dose at 2 doses/d and metronidazole in a 500 mg/dose at 3 doses/d, to decrease radiation toxicity and increase radiosensitivity. Radiotherapy was applied at 200 cGy per fraction with a total dose of 2400 cGy, with only 1 anterior local-tumor field. RESULTS: The patient showed a complete response to radiotherapy, and the tumor disappeared at the 2400 cGy radiation dose. No toxicity occurred related to the skin or the woman's general health. Her Karnofsky performance score increased to 90% from 50%, which was the initial score of the second treatment.

Cryotherapy for massive vulvar lymphatic leakage complicated with lymphangiomas following gynecological cancer treatment.

Vulvar lymphatic leakage is a severe complication associated with gynecological cancer treatments. However, standard treatment strategies have not yet been determined. We encountered a rare case of a 76-year-old multiparous woman suffering from massive lymphatic fluid leakage from the entire vulva, and papules developed and were identified as lymphangiomas. A large amount of straw-colored discharge continued from all vulvar papules, which extended over the mons pubis. Nine years ago, the patient had undergone a radical hysterectomy with concurrent chemoradiation for uterine cervical cancer treatment. Her serum albumin level was 1.9 mg/dl, which was attributed to the loss of a large amount of lymph fluid due to leakage from the vulva. Her quality of life gradually decreased because of general fatigue and the need for frequent diaper exchanges every 2 h. The patient received a less-invasive treatment with cryotherapy using liquid nitrogen. She also received a multimodality treatment consisting of the intravenous administration of albumin, massage of the lower limbs and intensive rehabilitation. Cryotherapy was administered once a week for 3 months. Her discharge almost stopped and vulvar lymphangiomas decreased without any major complications. To the best of our knowledge, this is the first case report of massive lymphatic leakage complicated with vulvar lymphangiomas. Additionally, this case may represent the first successful treatment of vulva lymph leakage by cryotherapy without recurrence. Cryotherapy may have the potential to improve the quality of life as a less-invasive treatment for gynecological cancer survivors without serious complications.

Comprehensive evaluation of caspase-14 in vulvar neoplasia: an opportunity for treatment with black raspberry extract.

OBJECTIVE: The aim of this study is to determine the expression of caspase-14, a key protein in maturation of squamous epithelia, in archival malignant and premalignant vulvar squamous lesions and examine in-vitro effects of a black raspberry extract (BRB-E) on a vulvar squamous cell carcinoma (VSCC) cell line. METHODS: VSCC cell cultures were exposed to different BRB-E concentrations and used to create cell blocks. Immunohistochemistry for caspase-14 was performed on cell block sections, whole tissue sections, and a tissue microarray consisting of normal vulvar skin, lichen sclerosus (LS), classic and differentiated vulvar intraepithelial neoplasia (cVIN and dVIN respectively), and VSCC. RESULTS: LS demonstrated abnormal full thickness (5/11) or absent (1/11) caspase-14 staining. dVIN often showed markedly reduced expression (4/7), and cVIN occasionally demonstrated either absent or reduced caspase-14 (6/22). VSCC predominantly had absent or markedly reduced caspase-14 (26/28). VSCC cell cultures demonstrated a significant increase in caspase-14 (p=0.013) after BRB-E treatment: 7.3% (±2.0%) of untreated cells showed caspase-14 positivity, while 21.3% (±8.9%), 21.7% (±4.8%), and 22.6% (±5.3%) of cells were positive for caspase-14 after treatment with 200, 400, and 800 µg/mL BRB-E, respectively. Pair-wise comparisons between the treatment groups and the control demonstrated significant differences between no treatment with BRB-E and each of these treatment concentrations (Dunnett's adjusted p-values: 0.024, 0.021, and 0.014, respectively). CONCLUSIONS: Caspase-14 is frequently decreased in premalignant and malignant vulvar squamous lesions, and is upregulated in VSCC cell culture by BRB-E. BRB-E should be further explored and may ultimately be incorporated in topical preparations.