Vulvar Disease Research Articles

Vulvar Paget’s Disease with Inguinal Lymph Node Metastasis: A Case Report

Vulvar Paget's disease is a clinical condition with an invariable course affecting women of advanced age, and is associated with a significant rate of recurrence and dissemination, especially in its invasive form, which has a high metastatic potential. Here we present details of a unique case involving a 77-year-old woman with a history of disease progression over more than a decade. She initially presented with an erythematous lesion in the vulvar region, which was later diagnosed as adenocarcinoma in situ. During follow-up, the affected area extended to the perineal and gluteal regions, indicating an invasive aspect of the tumor. Due to surgical oncology recommendations, tissue resection was not feasible. The pacient experienced a significant worsening of symptoms, including local peeling of the affected region, and a biopsy confirmed Paget's disease in the vulvar region. Subsequently, imaging tests indicated changes in the volume of the inguinal lymph nodes. The patient underwent lymphadenectomy for histological analysis and to prevent systemic dissemination. Indicators of lymph node metastasis, suggestive of a gynecological primary site, were observed. Our case provides valuable insights for pathologists to consider the differential diagnosis of vulvar lesions.

Vulvar Paget's disease: A population-based cancer registry descriptive study

BackgroundAlthough vulvar Paget's Disease (VPD) is a rare skin cancer associated with an excellent prognosis, high recurrence rates are associated with impaired quality of life. ObjectivesOur objective was to investigate the epidemiological and clinical features of VPD diagnosed in a French administrative area (Franche Comté). MethodsThis retrospective study investigated clinical, histologic, therapeutic and follow-up data of patients with VPD diagnosed between 1981 and 2021, including data from the Doubs cancer registry. ResultsAmong the 21 patients included (19 intra-epithelial and 2 invasive VPD), the median time to diagnosis was 24 months [0–110 months], with a median age of 72 years [38–88 years]. An associated cancer was present in 6 patients (29 %). At 5 years of follow-up, the recurrence rate was 26 %, but then increased to 42 % after a median follow-up of 145 months [31–503 months]. Among the 14 patients first surgically treated, incomplete resection (positive margins) was observed in all patients (100 %), associated with a postoperative recurrence rate of 86 % which was much higher than the rate observed in patients first topically treated (20 %). Postoperative adjuvant therapy (surgical revision, laser, imiquimod) significantly increased the recurrence-free survival (p < 0.001). ConclusionsPostoperative recurrence of VPD is frequent, mainly after 5 years, proving the importance of prolonged follow-up. Recurrence-free survival was significantly higher after postoperative adjuvant treatment.

AI-powered visual diagnosis of vulvar lichen sclerosus: A pilot study.

Vulvar lichen sclerosus (VLS) is a chronic inflammatory skin condition associated with significant impairment of quality of life and potential risk of malignant transformation. However, diagnosis of VLS is often delayed due to its variable clinical presentation and shame-related late consultation. Machine learning (ML)-trained image recognition software could potentially facilitate early diagnosis of VLS. To develop a ML-trained image-based model for the detection of VLS. Images of both VLS and non-VLS anogenital skin were collected, anonymized, and selected. In the VLS images, 10 typical skin signs (whitening, hyperkeratosis, purpura/ecchymosis, erosion/ulcers/excoriation, erythema, labial fusion, narrowing of the introitus, labia minora resorption, posterior commissure (fourchette) band formation and atrophic shiny skin) were manually labelled. A deep convolutional neural network was built using the training set as input data and then evaluated using the test set, where the developed algorithm was run three times and the results were then averaged. A total of 684 VLS images and 403 non-VLS images (70% healthy vulva and 30% with other vulvar diseases) were included after the selection process. A deep learning algorithm was developed by training on 775 images (469 VLS and 306 non-VLS) and testing on 312 images (215 VLS and 97 non-VLS). This algorithm performed accurately in discriminating between VLS and non-VLS cases (including healthy individuals and non-VLS dermatoses), with mean values of 0.94, 0.99 and 0.95 for recall, precision and accuracy, respectively. This pilot project demonstrated that our image-based deep learning model can effectivelydiscriminate between VLS and non-VLS skin, representing a promising tool for future use by clinicians and possibly patients. However, prospective studies are needed to validate the applicability and accuracy of our model in a real-world setting.

Utility of special AT-rich sequence-binding protein 2 (SATB2) immunohistochemistry as a marker for secondary perianal paget disease.

A panel-based approach using immunohistochemistry (IHC) is currently used for subtyping perianal Paget disease (PPD) in the absence of a synchronous neoplasm. Special AT-rich Sequence Binding Protein 2 (SATB2) has been established as a sensitive and specific marker for lower gastrointestinal tract carcinomas. We evaluated its performance as a marker of secondary PPD. A panel of IHCs including CK7, CK20, GCDFP-15, CDX2, and SATB2 were performed on fifteen cases of PPD (identified between 1991-2001) and seven cases of primary vulvar Paget disease with perianal involvement. Eight cases (53%) were classified as secondary PPD based on the presence of a synchronous (n = 7) or a metachronous neoplasm (n = 1). There was no differential staining for CK7 (positive in 7/7 primary vs. 7/8 secondary PPD; P = 1.00) and CK20 (positive in 4/7 primary vs. 8/8 secondary PPD; P = .08). GCDFP-15 was positive in 5/7 cases of primary PPD while negative in all cases of secondary PPD (P = .01). CDX2 was positive in all cases of secondary PPD (P = .001) while SATB2 was positive in 7/8 cases of secondary PPD (P = .01). Both CDX2 and SATB2 were positive in 1/7 cases of primary PPD. The addition of an IHC panel in conjunction with clinical/imaging findings can help definitively classify PPD as either primary or secondary in most cases. We show that SATB2 has comparable performance to CDX2 and can be a helpful additional tool.

Single-cell and spatial transcriptomics of vulvar lichen sclerosus reveal multi-compartmental alterations in gene expression and signaling cross-talk.

Vulvar diseases are a critical yet often neglected area of women's health, profoundly affecting patients' quality of life and frequently resulting in long-term physical and psychological challenges. Lichen sclerosus (LS) is a chronic inflammatory skin disorder that predominantly affects the vulva, leading to severe itching, pain, scarring, and an increased risk of malignancy. Despite its profound impact on affected individuals, the molecular pathogenesis of vulvar LS (VLS) is not well understood, hindering the development of FDA-approved therapies. Here, we utilize single-cell and spatial transcriptomics to analyze lesional and non-lesional skin from VLS patients, as well as healthy control vulvar skin. Our findings demonstrate histologic, cellular, and molecular heterogeneities within VLS, yet highlight unifying molecular changes across keratinocytes, fibroblasts, immune cells, and melanocytes in lesional skin. They reveal cellular stress and damage in fibroblasts and keratinocytes, enhanced T cell activation and cytotoxicity, aberrant cell-cell signaling, and increased activation of the IFN, JAK/STAT, and p53 pathways in specific cell types. Using both monolayer and organotypic culture models, we also demonstrate that knockdown of select genes, which are downregulated in VLS lesional keratinocytes, partially recapitulates VLS-like stress-associated changes. Collectively, these data provide novel insights into the pathogenesis of VLS, identifying potential biomarkers and therapeutic targets for future research.

Loss, shame and secrecy in women's experiences of a vulval skin condition: A qualitative study.

Vulval lichen sclerosus (LS) is a chronic dermatological condition affecting the anogenital area, causing intense itching, pain and bleeding. It can change the terrain of the vulva, causing loss of vulval anatomy and altered texture and appearance of the skin. There has been little research into how women experience the materialities of a dermatological vulval disease. We aimed to understand experiences of living with LS, using a feminist lens to examine the influence of societal attitudes towards women's bodies and the vulva. We conducted qualitative interviews with 20 women with vulval LS, taking a critical feminist grounded theory approach. While we found that women's experiences of vulval LS symptoms was normalised as a part of womanhood, there was a silencing of speech about the vulva generally, and vulval symptoms more specifically. This caused profound shame and loneliness, and was a barrier to disclosing and seeking help for vulval symptoms, leading to delayed diagnosis and disease progression. Loss of vulval architecture resulted in a loss of (feminine) self and the sense of a body which was whole.

Vulvar Inspection During Cervical Cancer Screening Procedures: The Ugly Reality.

Vulvar examination during procedures for cervical carcinoma screening (CCS) can be a valid chance for early diagnosis of vulvar diseases and precancerous lesions. With this aim an online questionnaire was sent to the members of the Italian Cervical Carcinoma Screening Group (GISCi) from either first level group (FLG, Pap/human papillomavirus test sampling) or second level group (SLG, colposcopy and treatments) to assess if and how vulvar examination was performed. 86% of FLG and 90.2% of SLG report performing vulvar examination prior to CCS procedures. 15% of SLG cannot manage basic vulvar diseases and they refer patients to specialized center. 54.3% underline lack of standardized protocol in case of vulvar disease detection. Despite most health care professionals report examining the vulva during CCS procedures, vulvar cancer early diagnosis is still challenging.

Complex anti-relapse therapy of various variants of the course of the vulvar lichen sclerosus: A randomized prospective study

Aim. To develop and evaluate the effectiveness of complex therapy of vulvar lichen sclerosus (VLS), considering the clinical and immunological variant (CIV) of the disease. Materials and methods. A randomized prospective study included 292 patients 20-70 years old with different CIVs of the VLS course: atrophic (n=101), sclerosing (n=154), scleroatrophic (n=37), as well as 35 females with VLS in the comparison group of the same age category. Based on the clinical, immunological, and morphological features of the VLS course, a complex anti-relapse therapy was developed, the effectiveness of which was evaluated after a year of follow-up in comparison with the standard of care (SoC) of patients (from the comparison group) based on the number of disease relapses and the results of the Vulvar Quality of Life Index Questionnaire (VQLI) survey of women with vulvar diseases. Results. In patients with the sclerosing variant of VLS, short courses of topical glucocorticoids during exacerbations are justified; in patients with the scleroatrophic variant – topical calcineurin inhibitors, in the atrophic variant – a protein-peptide complex from porcine blood leukocytes (vaginal suppositories and cream-balsam with lanolin) containing interleukin-1, 6, tumor necrosis factor α, transforming growth factor, macrophage migration inhibitory factor. Patients with any variant of VLS are instructed to follow household and hygienic recommendations, use emollients daily, take prophylactic doses of vitamins A, E, and D to correct its deficiency or insufficiency, as well as use local enzyme therapy, as indicated, aimed at preventing or treatment of cicatricial changes. Local estrogens were prescribed only to women with genitourinary menopausal syndrome in the peri- and postmenopausal period. The developed complex anti-relapse therapy of VLS showed greater clinical efficacy compared to SoC: 3.7-fold decrease in episodes of disease exacerbation, as well as a significant (p=0.001) 1.3-fold decrease in the negative effect of VLS on the QoL of patients in the main clinical group (15.4 points according to the VQLI assessment – a mild effect on QoL) compared to SoC with the average score of 27.6, which corresponded to a strong negative effect of the disease on QoL. Conclusion. The results of the study support the distinction of VLS CIVs and the need to consider their features when choosing an effective therapy for the disease. Properly selected complex, supportive therapy of VLS can significantly increase the QoL of patients, minimize the number of relapses, and prevent the development of complications, including, probably, the risk of malignant transformation.

Vulvar skin disease in the pediatric population.

Vulvar skin disease is an underrecognized pediatric condition encompassing a wide range of conditions, from isolated vulvar disease to vulvar manifestations of systemic illnesses. This review highlights the most current research discussing clinical features, risk factors, and treatments. Recent studies confirm that labial adhesions resolve more quickly with estrogen treatment. Topical corticosteroids remain first-line for treatment of vulvar lichen sclerosus, and some procedural interventions are showing promising results. Latest evidence shows efficacy of biologic agents in hidradenitis suppurativa and vulvar Crohn's. Vaginal voiding remains an underrecognized cause of irritant vulvovaginitis. Lately vulvar aphthae have been associated with coronavirus disease 2019. Distinguishing between infantile perianal pyramidal protrusion, molluscum, and condyloma can be aided by differences in morphologic features. Vulvar dermatoses have a high impact on children's health and wellbeing. Clinician familiarity with recognition and latest advancements in vulvar dermatoses can aid in prompt diagnosis, management, and appropriate referrals. Vulvar biopsy and vaginal cultures should be used prudently. Treatments include topicals, behavioral modification, systemic medications, and procedures.

Barriers to identifying, diagnosing, and treating vulval lichen sclerosus in primary care: a mixed methods survey study.

Vulval lichen sclerosus (VLS) is a skin condition which causes pain, itching, anatomical changes, and increases vulval cancer risk by up to 22 times. VLS is treatable, with use of topical steroids allowing symptom resolution and complication prevention. Diagnostic delay and misdiagnosis of VLS is common. Previous studies found that women attribute this to poor interactions with and knowledge of clinicians. Most VLS is diagnosed in primary care. To investigate primary care clinicians' views on confidence in identifying and managing vulval skin disease and VLS, barriers to diagnosis, education on vulval skin disease, and diagnostic criteria for VLS. A mixed methods survey was distributed via professional events and networks. Qualitative data was analysed in NVivo using inductive thematic analysis. Spearman's rank correlation was used to correlate participant characteristics and confidence. There were 122 responses, the majority from GP trainees (48%) and GPs (43%). Confidence in diagnosing, identifying, and treating VLS positively correlated with female gender, time in role, and examination frequency. Themes identified include patients not knowing normal, male clinicians: deskilling and reluctance, lack of clinician knowledge, and uncertainty around diagnosis and treatment. 38% of participants never participated in teaching or learning on vulval skin disease. Almost all (98%) participants feel diagnostic criteria would be helpful. This study illuminates the multiple barriers to diagnosis and treatment of VLS. The results confirm that clinicians share patient concerns that knowledge is poor, highlight the importance of developing clear diagnostic criteria, and will allow us to target training to those lacking in confidence.

Predicting the development of vulvar lichen sclerosus

Relevance. The issue of timely diagnosis and treatment of vulvar lichen sclerosus has become especially acute in recent years due to the “rejuvenation” of the disease and the risk of its malignancy. In this regard, it is urgent to search for effective methods for predicting and early detection of the disease. The aim of the study - to develop amodel for predicting vulvar lichen sclerosus based on established clinical and anamnestic risk factors. Materials and Methods. The prospective case-control study included 404 women aged 20 to 70 years, of which 344 were patients with vulvar lichen sclerosus and 60 were women without vulvar diseases. At the first stage, acomparative statistical correlation analysis of the clinical and anamnestic data of the subjects was carried out using the Spearman correlation coefficient (R0.15), Chi-square tests, Phi and Cramer statistics, the Mann-­Whitney U test and the Student t test (p 0.05). The data obtained were used to develop aneural network model for predicting vulvar lichen sclerosus in the second stage of the study. Results and Discussion. Based on established reliably significant (p0.05) obstetric-­gynecological, somatic, infectious, hygienic and household factors influencing the risk of developing vulvar lichen sclerosus (Rindicator - from 0.16 to 0.38 confirms the statistical significance of correlations), aneural network model for predicting vulvar lichen sclerosus was developed (the percentage of correct classification on the test sample is the maximum possible value - 100%) and acomputer program was written that automates the procedure for predicting the disease. Conclusion. The neural network model for predicting the disease, developed on the basis of reliably (p0.05) significant risk factors for vulvar lichen sclerosus, has high prognostic properties, and acomputer program written on its basis allows the doctor in amatter of minutes to identify the patient at risk for the development of vulvar lichen sclerosus and give she needs preventive recommendations aimed at preventing or early detection of the disease.

Obstetric, somatic and infectious risk factors for vulva sclerotic lichen

Relevance. Until now, disputes among scientists about its etiology, pathogenesis, nomenclature and risk factors for the development of vulvar lichen sclerosis have not subsided, which actualizes the need for scientific research aimed at solving these problems. The aim of the study - to establish statistically significant clinical and anamnestic risk factors for vulvar lichen sclerosis. Materials and Methods. An electronic database was formed with data from 344 patients with lichen sclerosus of the vulva and 60 women without vulvar diseases aged 20-70 years on hereditary, obstetric-­gynecological, somatic and infectious history. Astatistical comparative correlation analysis of the obtained data was carried out using the Spearman correlation coefficient (R0.15), nonparametric Mann - Whitney U test and Student t test (p0.05), Chi-square tests, Phi and Cramer statistics. Results and Discussion. Statistically significant (p0.05) risk factors for the development of vulvar lichen sclerosus (R, in descending order) were established: the presence of fibrocystic mastopathy (-0.29); late menarche (15 years and older) (-0.28); onset of menopause (-0.25); recurrent vulvo-­vaginal infections (-0.18); recurrent bacterial vaginosis (-0.18); autoimmune thyroiditis(-0.16) and stage II obesity (-0.16). Also, the average number of abortions and births (1.23 and 1.49, respectively) in the group of patients with lichen sclerosis of the vulva is statistically significantly greater (p0.05) than the average value (0.27 and 1.13, respectively) in control group. Conclusion. The data obtained on the impact of obesity and autoimmune thyroiditis on the risk of developing vulvar sclerotic lichen are consistent with the results of global studies and confirm the association of the disease with autoimmune and metabolic disorders. Recurrent vulvo-­vaginal infections and dysbiotic processes in the vagina can be both acause and aconsequence of vulvar lichen. The relationship between fibrocystic mastopathy and vulvar lichen sclerosus remains debatable and requires further research. Late menarche, the onset of menopause, alarge number of abortions and childbirth can also be considered triggers for vulvar lichen sclerosus in patients with agenetic predisposition to the disease.

Adverse healthcare experiences are correlated with increased time to diagnosis in women with vulvar inflammatory dermatoses: a retrospective cohort survey.

This retrospective cohort survey of over 300 women examined diagnostic delay in vulvar dermatoses compared with nonvulvar control conditions (e.g. psoriasis or atopic dermatitis). Adverse healthcare experiences (e.g. uncertainty of which provider to consult, embarrassment in talking to providers) occurred more often for participants with vulvar disease and were significantly correlated with increased time to diagnosis in this group, which was not the case in control conditions. The findings suggest opportunities to improve care for people with vulvar disease.

O04 Vulval Psoriasis in Children: A Clinical Audit and Review of Literature

Abstract Objective Vulval psoriasis is frequently under-recognised, under-­diagnosed and under-treated in children due to its nonspecific presentation. This retrospective chart review is aimed to describe the symptoms, signs, and management of vulval psoriasis in children in a private vulval disease referral practice. Materials and methods A retrospective, single-centre cohort study of children was undertaken at a large, combined dermatology and gynaecology practice from January 2016 to January 2023. Clinical photographs and treatment data were systematically collected and recorded in an online patient database. Treatment regimens were individualised and titrated to clinical response. Results This seven-year retrospective cohort study included a total of 100 children with vulval psoriasis. The most common presentation was nonspecific erythema (85%) that is well-demarcated in one-third of children and appears as a raised plaque in one-fifth of children. In 78% of the patients, evidence of psoriasis was found on other parts of the skin. Initial induction treatment with potent topical corticosteroid followed by maintenance treatment with less potent topical steroids and topical tar creams. 5% of children required systemic treatment. Conclusions and Relevance Vulval psoriasis often presents as a nonspecific chronic erythematous vulvitis without vaginitis. It is a chronic relapsing skin condition that requires long-term management. Systematic treatment is required in a small proportion of children.

Quality of Life Among Women with Vulvovaginal Candidiasis in a Tertiary Care Centre in India

ABSTRACT: Vulvovaginal candidiasis (VVC) is a frequent, irritating, and recurrent infection. These infections create a danger to the well-being of the women and have a detrimental impact on their quality of life (QoL). The aim of this study is to assess the quality of life (QoL), among women with VVC.The study design: prospective study design ;Study site:Paalana hospital of medical sciences , Study duration :7month.The sample size n=130. Severity of VVC is determined by using VSQ questionnaire (Vulvovaginal symptom questionnaire) and Vulvar disease quality of life index (VDQoL questionnaire) used to assess the quality of life. Statistical analysis was carried out by using Graphpad prism software, un-paired student t-test to determine P-value between pre-treatment and post-treatment. In this study, 130 cases were collected; among the collected data; VVC was more common in women in the reproductive age range. Quality of life (QoL) is determined by VDQoL with subdomains like (Nil effect,Mild,Moderate and Severe,Very severe effect) . After the course of treatment, their QoL is determined by administering the same questionnaire to the patients. By comparing the Pre-test and Post-test, patients with Nil effect (p-value 0.66), Mild effect (p&lt;0.0001), &amp; Moderate effect (p&lt;0.0001). Based on the findings of the study, it can be concluded that vulvovaginal candidiasis have a negative impact on the patient's quality of life. The majority of women having a mild effect of VVC on their QoL .

Application of a diagnosis flow draft based on appearance impression for detection of vulvar disease.

The aims of this retrospective study were to evaluate the clinical applicability of the latest International Society for the Study of Vulvovaginal Disease (ISSVD) and International Federation for Cervical Pathology and Colposcopy (IFCPC) terminology for vulvar diseases, and to explore a new evaluation flow to optimize decision-making on diagnosis. A total of 1,068 patients with 5,340 qualified vulvar images were evaluated by observers using 2011 ISSVD and 2011 IFCPC terminology systems. The sensitivity, specificity, positive predictive value, negative predictive value, Youden Index and Overall Diagnostic Value (ODV) were calculated for each finding in the two systems. Then the disease diagnosis order and a diagnosis flow draft (DFD) were obtained. A total of 15 kinds of vulvar diseases were diagnosed. The proportion of patients accompanied with cervical or vaginal intraepithelial neoplasia was highest (83.3 %) in vulvar Paget's disease group (p<0.001). Total area of lesions was larger in vulvar Paget's disease, lichen simplex chronicus and lichen sclerosus group (p<0.001). Among the top five findings of ODV, some findings inferred several (≥6) kinds of diseases, while some findings only exist in a certain disease. When the DFD was used, the agreement between the initial impression and histopathology diagnosis was 68.8 %, higher than those when ISSVD an IFCPC terminology systems used (p=0.028), and it didn't change with the experience of the observer (p=0.178). Based on the findings in ISSVD and IFCPC terminology systems, we explored a DFD for observers with different experience on the detection of vulvar disease.

A large sample-based case-control study of related risk factors of two types of lichenoid vulvar disease (LVD)

PurposeThe purpose of this study is to identify the associated factors of two types of lichenoid vulvar disease (LVD) and to compare the differences in related factors between the different pathological types of lichenoid vulvar disease (LVD). MethodsThe study conducted at the West China second Hospital of Sichuan University included a total of 1770 patients with biopsy-confirmed vulvar lichen simplex chronicus (VLSC)and vulvar lichen sclerosus(VLS), along with 1209 patients with normal vulvovagina as control. Further pathological subtype analysis was carried out on 163 cases of vulvar lichen simplex chronicus and 51 cases of vulvar lichen sclerosus. In addition, Univariate chi-square test and multivariate logistic regression were used to analyze the lichenoid vulvar disease group and vulvovaginal normal control group. ResultsUnivariate analysis revealed that there were statistically significant differences (P < 0.05) in factors between the LVD group and the control group, except for living type, sleep habit, history of drinking, and allergic diseases. There was no significant difference in late sleep, spicy diet, and coffee intake in the factors of life and eating habits and the concomitant disease factors. Furthermore, univariate analysis showed that except for eating seafood, humid living environment, residence, caffeinated drinks, hypertension, and vaginitis, there were statistical differences in the related factors of LVSC. ConclusionThe incidence about lichenoid vulvar disease is influenced by various factors such as dietary habits, living environment, mental stress, concomitant diseases, hormone levels and so on, and there were no significant differences in these factors between VLS and VLSC except for income, work stress, systemic immune diseases, and menopause.

Insights from a joint pediatric dermatology-gynecology vulvar clinic: A retrospective study.

Pediatric vulvar disease has not been widely explored in the medical literature. Few studies focus on vulvar disease in skin of color. The vulvar disease can be distressing for young patients given the sensitive location, and providers may lack experience in diagnosing and managing vulvar dermatoses. We sought to characterize the conditions seen, diagnostic challenges encountered, and the racial and ethnic factors associated with vulvar diseases in our multidisciplinary pediatric dermatology-gynecology vulvar clinic at Children's National. Medical records of 220 patients who presented to our multidisciplinary pediatric dermatology-gynecology clinic were reviewed retrospectively. Lichen sclerosus (LS) (36%, n = 80), inflammatory vulvitis (11%, n = 23), and vitiligo (9%, n = 19) were the three most frequent conditions observed. These conditions were often misdiagnosed as one another. There was a mean delay in diagnosis after symptom onset in LS patients of 16.43 months. LS, inflammatory vulvitis, and vitiligo are common vulvar diseases among pediatric patients. Accurate diagnosis is important because LS must be treated aggressively to prevent sequelae. Further studies are warranted to help differentiate LS and vitiligo with consideration of skin tone.

The vulvar microbiome in lichen sclerosus and high-grade intraepithelial lesions.

The role of the vulvar microbiome in the development of (pre)malignant vulvar disease is scarcely investigated. The aim of this exploratory study was to analyze vulvar microbiome composition in lichen sclerosus (LS) and vulvar high-grade squamous intraepithelial lesions (HSIL) compared to healthy controls. Women with vulvar lichen sclerosus (n = 10), HSIL (n = 5) and healthy controls (n = 10) were included. Swabs were collected from the vulva, vagina and anal region for microbiome characterization by metagenomic shotgun sequencing. Both lesional and non-lesional sites were examined. Biophysical assessments included trans-epidermal water loss for evaluation of the vulvar skin barrier function and vulvar and vaginal pH measurements. Healthy vulvar skin resembled vaginal, anal and skin-like microbiome composition, including the genera Prevotella, Lactobacillus, Gardnerella, Staphylococcus, Cutibacterium, and Corynebacterium. Significant differences were observed in diversity between vulvar skin of healthy controls and LS patients. Compared to the healthy vulvar skin, vulvar microbiome composition of both LS and vulvar HSIL patients was characterized by significantly higher proportions of, respectively, Papillomaviridae (p = 0.045) and Alphapapillomavirus (p = 0.002). In contrast, the Prevotella genus (p = 0.031) and Bacteroidales orders (p = 0.038) were significantly less abundant in LS, as was the Actinobacteria class (p = 0.040) in vulvar HSIL. While bacteria and viruses were most abundant, fungal and archaeal taxa were scarcely observed. Trans-epidermal water loss was higher in vulvar HSIL compared to healthy vulvar skin (p = 0.043). This study is the first to examine the vulvar microbiome through metagenomic shotgun sequencing in LS and HSIL patients. Diseased vulvar skin presents a distinct signature compared to healthy vulvar skin with respect to bacterial and viral fractions of the microbiome. Key findings include the presence of papillomaviruses in LS as well as in vulvar HSIL, although LS is generally considered an HPV-independent risk factor for vulvar dysplasia. This exploratory study provides clues to the etiology of vulvar premalignancies and may act as a steppingstone for expanding the knowledge on potential drivers of disease progression.

Favorable Toxicity and Local Control with Ultrahypofractionated Radiation Therapy (UH-RT) for Melanoma of the Lower Genital Tract (LGT)

To report our experience using UH-RT +/- immunotherapy (IO) in women with melanoma of the LGT. We retrospectively identified 23 patients who received UH-RT to primary tumor for vulvovaginal melanoma from 2012 to 2022. Median age was 69 years (IQR: 62-76). Stage included localized, node positive, or metastatic. 18 (78%) had tumors involving the vagina/cervix and 5 (22%) had vulvar tumors. 6 patients had c-KIT mutations; 13 patients were wild-type; 4 patients were unknown. 12 (52%) were treated at initial presentation (cohort A) and 11 (48%) at local progression/recurrence following prior therapy (cohort B). In cohort A, most (n = 11) received concurrent IO. In cohort B, 3 recurred after surgery alone, 4 after systemic therapy alone and 4 after surgery and systemic therapy. RT consisted of 6 Gy x 6 (n = 11), 6 Gy x 5 (n = 10) and 5 Gy x 5-6 (n = 2) delivered to the primary tumor + 0.5 cm margin. Patients initiated IO either ≥3 months preRT (n = 8), concurrent with RT (n = 12) or ≥3 months following RT (n = 2). 1 patient in cohort B did not receive IO. Toxicity was graded using CTCAE v 5. Overall survival (OS) was measured from end of RT. Cumulative incidence of local progression was measured from end of RT. Kaplan-Meier method and Cox regression were used for survival analyses. Landmark method was used for timing of IO. Median follow-up as determined by reverse Kaplan-Meier method was 60 months (95% CI: 37-N/A). Overall incidence of acute/late grade 2+ toxicity for the entire cohort was 34%. Grade 2 acute toxicity included: dermatitis (n = 3), urinary (n = 2), vaginitis (n = 2) and diarrhea (n = 1). 3 patients experienced grade 3 acute dermatitis. 1 patient experienced late grade 2 vaginitis. No grade 3 or 4 toxicity was noted. No significant differences in toxicity were noted between RT regimens. Local disease control was achieved in 61% of patients. Local only, local and distant, and distant-only progression were seen in 17%, 22%, and 30% of patients respectively. 2-year cumulative incidence of local progression was 33% for the whole cohort, 28% for cohort A, and 36% for cohort B (p = 0.4). On UVA, factors associated with local progression were vulvar disease (p = 0.02) and c-KIT mutation (p = 0.011). No significant difference in local control was noted based on biologic effective dose (BED10 < = 48Gy vs >48Gy) (p = 0.06). Median OS for entire cohort, cohort A, and cohort B were 46, 72, and 30 months, respectively. 2-year survival (95% CI) was 67% (50%-91%), 73% (51%-100%), and 64% (41%-99%) respectively. On UVA, non-local disease at time of RT (p = 0.016) and receipt of IO ≥3 months prior to RT (p = 0.030) had worse OS. UH-RT+/- IO for melanoma of the LGT is well-tolerated with local disease control achieved in 61% of patients. Vulvar primary and c-Kit mutations were associated with worse local control. Additional follow-up may be necessary to determine the value of dose escalation.