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Background: There is limited evidence of potential associations between body mass index (BMI) and risk of vulvar and vaginal cancer. We explored these associations in a large cohort of Norwegian women. Methods: The analytical dataset included 889,441 women aged 16–75 years at baseline in 1963–1975. Multivariable Cox regression analyses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between BMI and vulvar and vaginal cancer incidence. Results: During 30.1 million person-years of follow-up, 1748 incident vulvar and 408 incident vaginal cancer cases occurred. The HRs (95% CIs) for vulvar cancer for a BMI of 15- < 18.5, 18.5- < 25, 25- < 30, 30- < 35, ≥ 35 were 0.62 (0.38–1.01), 1.00 (reference), 1.23 (1.10–1.40), 1.43 (1.23–1.66) and 1.72 (1.35–2.20, ptrend < 0.001), and per 5 kg/m2 increment was 1.20 (1.13–1.26). The corresponding HRs (95% CIs) for vaginal cancer were 1.05 (0.52–2.15), 1.00, 0.89 (0.71–1.12), 0.95 (0.68–1.34), and 2.01 (1.29–3.13, ptrend < 0.001), respectively, and per 5 kg/m2 was 1.11 (0.99–1.25). The HR (95% CI) per 5 kg/m2 increase in BMI at ages 16–29 was 1.28 (1.07–1.54, n = 250 cases) for vulvar and 1.53 (1.11–2.11, n = 66 cases) for vaginal cancers. The HR (95% CI) per 5 kg/m2 for early-onset (< 50 years age at diagnosis) vulvar cancer was 0.92 (0.66–1.28, n = 87 cases) and 1.70 (1.05–2.76, n = 21 cases) for vaginal cancer. Conclusion: These results further support the associations between higher BMI and increased risk of vulvar and vaginal cancers, with suggestive stronger associations between BMI in early adulthood for both cancers and for early-onset vaginal cancer. Further studies are needed to elucidate these findings and investigate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Simple Summary: Vulvar tumors are uncommon and have a considerable impact on the functional and aesthetic well-being of those affected. Their treatment necessitates a comprehensive, multidisciplinary approach at various levels, highlighting the importance of having standardized recommendations that are aligned with the latest scientific findings. Are scientific guidelines aligning with the advancements made in this field of oncology, spanning from diagnosis to palliative care at various levels? To address this, we conducted a systematic comparison of the main European and American guidelines for vulvar cancer management to assess their current status of update. From our comparisons, many divergences emerged in management strategies. Among them, lack of reference to the most up-to-date diagnostic classification systems, indication for an integrated gyneco-oncologic and plastic surgical approach to postoperative management with the most modern advanced dressing devices and palliative setting with the use of immuno- and electrochemotherapy. Background: Vulvar carcinoma is an uncommon gynecological tumor primarily affecting older women. Its treatment significantly impacts the quality of life and, not least, aesthetics because of the mutilating surgery it requires. Objectives: The management requires a multidisciplinary team of specialists who know how to care for the patient in her entirety, not neglecting psychological aspects and reconstructive surgery. How do the guidelines address multidisciplinarity, team surgical management, passing through preoperative diagnosis, and follow-up in such a challenging rare tumor to treat? Methods: To answer these questions, we compared the main scientific recommendations to identify similarities and differences in diagnostic and therapeutic management to provide an overview of the gaps that there are currently in European and American international recommendations in providing management guidance in a cancer that is both among the rarest and most difficult to manage. In this way, we aim to encourage an update in practices based on the latest scientific evidence. Results: A review of various international guidelines, some dating back to 2014, shows significant variation in approaches, ranging from initial diagnostic procedures to managing relapses. The most recent guidelines also lacked references to the latest literature, indicating that more robust scientific evidence is needed before new treatments, such as electrochemotherapy for palliation and reconstructive surgery post exenteration, can be widely adopted. Conclusions: From the systematic comparison of the main international guidelines, a strong heterogeneity emerged in the diagnostic and therapeutic recommendations as well as for the multidisciplinary approach that today is essential. Our work certainly stimulated an update of the main guidelines. [ABSTRACT FROM AUTHOR]

Gynecologic cancers (GCs), including cervical cancer (CC), ovarian cancer (OC), endometrial cancer (EC), as well as vulvar and vaginal cancers, represent major health threats to women, with increasing incidence rates observed globally. Conventional treatments, such as surgery, radiation therapy, and chemotherapy, are often hindered by challenges such as drug resistance and recurrence, contributing to high mortality rates. Organoid technology has emerged as a transformative tool in cancer research, offering in vitro models that closely replicate the tumor cell architecture and heterogeneity of primary cancers. Tumor-derived organoids preserve the histological and molecular characteristics of the original tumors, making them invaluable for studying tumor biology, molecular pathways, and the tumor immune microenvironment. Furthermore, organoids play a crucial role in biomarker discovery, drug screening, and the development of personalized therapeutic strategies. In contrast to traditional cell lines and patient-derived xenograft (PDX) models, gynecologic cancer organoids accurately mirror the genetic mutations and specific gene expression profiles of primary tumors. This review provides an overview of recent advancements in the development of gynecologic cancer organoid models, highlighting their contributions to understanding disease mechanisms, facilitating drug discovery, and advancing precision medicine. It also addresses the potential and challenges of organoid technology, with a focus on its role in advancing personalized treatment approaches for GCs. [ABSTRACT FROM AUTHOR]

Vulvar cancer, particularly squamous cell carcinoma (SCC) and melanoma, poses significant diagnostic and therapeutic challenges due to its complex presentation and high rates of postoperative complications. Effective management requires a multidisciplinary approach, integrating the expertise of gynecologic oncologists, dermatologists, plastic surgeons, and other specialists. This review highlights the dermatologist's role in supporting early diagnosis, addressing predisposing conditions such as lichen sclerosus, and managing postoperative wound complications, including surgical site infections and dehiscence. Through two clinical cases, we illustrate how dermatological expertise complements surgical efforts by employing advanced wound care techniques such as negative pressure wound therapy and tailored dressing protocols. By collaborating closely with gynecologists and other team members, dermatologists enhance patient outcomes, ensuring timely recovery and the prevention of long-term sequelae. The article also discusses recent advances in treatment guidelines and targeted therapies, underscoring the importance of integrated care for optimizing patient outcomes in vulvar cancer. [ABSTRACT FROM AUTHOR]

Surgery is the cornerstone of vulvar cancer treatment, but it is associated with a significant risk of complications that may impact prognosis, particularly in older patients with multiple comorbidities. The objective of this study was to evaluate the role of age, comorbidities, and frailty in predicting postoperative complications after vulvar cancer surgery and to develop a predictive nomogram. A retrospective cohort study was conducted, including patients who underwent surgery for vulvar cancer at two Italian institutions from January 2018 to December 2023. A logistic regression model for the rate of Clavien-Dindo 2+ 30-days complications was run, considering the age-adjusted Charlson Comorbidity Index (AACCI), body mass index (BMI), and frailty as exposures. Lesion characteristics and surgical procedures were considered as confounders. Among the 225 included patients, 50 (22.2%) had a grade 2+ complication. The predictive score of the nomogram ranged from 44 to 140. The AACCI (0–64 points) and BMI (0–100 points) were independently associated with a risk of complications. A nomogram including the AACCI and BMI predicts the risk of complications for patients undergoing surgery for vulvar cancer. The preoperative determination of the risk of complications enables surgical planning and allows a tailored peri- and postoperative management plan. [ABSTRACT FROM AUTHOR]

Vulvar cancer is one of the rarest gynecological malignancies. The development of this condition can be associated with either dysplasia linked to human papillomavirus (HPV), primarily affecting younger women, or vulvar dermatoses such as lichen sclerosus, which predominantly affect older women. Over the last decade, the incidence of vulvar cancer has risen by 0.6% annually, while the relative survival rate has declined. Although metastasis to the vulva is uncommon, it can occur, particularly from cancers in nearby organs such as the cervix, bladder, rectum, or anus. More rarely, metastases from breast cancer and renal cell carcinoma have been reported in the vulva. Vaginal metastases from clear cell renal carcinoma are especially rare. In this article, we present the case of a 56-year-old patient diagnosed with clear cell renal carcinoma, who came to our clinic with a lesion on the right labia, which was identified as a metastasis originating from the kidney. Given the rarity of genital metastases in renal cancer, such cases should be examined and discussed to encourage further research and studies. [ABSTRACT FROM AUTHOR]

To systematically explore vulvar pathology diagnosed prior to vulvar squamous cell carcinoma (VSCC), as well as the association with tumor characteristics, stage and survival outcome, with the aim of improving vulvar cancer prevention strategies. VSCC diagnosed between 2005 and 2019 were identified from a population-based cohort provided by the Dutch Nationwide Pathology Databank. Pathology reports were reviewed to identify vulvar pathology diagnosed before primary VSCC. Data on treatment, tumor stage and survival were collected from the Netherlands Cancer Registry. Prior vulvar pathology was correlated to tumor characteristics and stage. Cox's proportional hazards model was used to assess the impact of clinicopathological variables on survival. A total of 1036 VSCC patients were identified, of whom most (73 %) had no prior biopsy-confirmed vulvar pathology. High-grade squamous intraepithelial lesion (HSIL) and differentiated vulvar intraepithelial neoplasia (dVIN) were diagnosed prior to VSCC in only 8 % and 2 % of cancer patients, respectively, while adjacent HSIL and adjacent dVIN were reported in 35 % and 22 % of surgical VSCC resection specimens, respectively. The remaining 17 % had a benign vulvar pathology diagnosis prior to cancer. Patients showed advanced staged tumors in 15 % and 9 % of patients with prior HSIL and dVIN, respectively, as compared to 32 % in patients without prior vulvar pathology (p < 0.001). There was no independent association between prior vulvar pathology and survival outcomes. The vast majority of VSCC patients were not preceded by a pre-malignant lesion or other benign vulvar pathology, although such lesions were frequently identified adjacent to VSCC in resection specimens. Patients without prior vulvar pathology showed more advanced-stage tumors, which may contribute to less favorable outcomes. • The majority of vulvar cancer patients (73 %) do not have a history of biopsy-confirmed vulvar pathology. • Only 10 % of vulvar cancer patients are diagnosed with a vulvar premalignancy prior to cancer development. • Patients without a history of vulvar pathology develop more advanced staged vulvar cancer and have less favorable outcomes. [ABSTRACT FROM AUTHOR]

Many clinicians recommend that patients diagnosed with HPV‐related gynecologic cancers receive prophylactic HPV vaccination at the time of cancer diagnosis or after cancer treatment. In view of the large use of such practice, we aimed to assess the literature evidence supporting the use of prophylactic HPV vaccines after diagnosis or treatment of HPV‐related gynecologic cancers. Women who develop HPV‐related cervical, vaginal, and vulvar cancers represent a subgroup of patients who may be particularly sensitive to HPV infection and re‐acquire infections. The rationale that the use of prophylactic HPV vaccination at the time or after treatment for cervical, vaginal, and vulvar cancers might reduce the risk of future HPV‐related diseases might be explained by the data coming from the use of HPV vaccination after treatment of pre‐invasive disease; however, the evidence on the use of HPV vaccination in the setting of HPV‐related gynecologic cancers is currently absent. In this context, observational and experimental studies document an important drop in effectiveness of HPV vaccination by age. Physicians should be aware of catch‐up programs in their countries and should be ready to counsel patients about prophylactic HPV vaccine efficacy according to their age. In general, no evidence exists supporting the use of prophylactic HPV vaccine in patients diagnosed with HPV‐related gynecologic cancers; therefore, the European Society of Gynecological Oncology (ESGO) prevention committee opinion is to counsel these patients as any HPV‐related non‐gynecologic cancer (such as anal or oropharyngeal cancer) and non‐cancer patient, suggesting vaccination according to patient's age and prognosis, knowing there is a decrease of efficacy with increasing age. Studies on the use of prophylactic HPV vaccine in patients diagnosed with HPV‐related gynecologic cancers are strongly needed. [ABSTRACT FROM AUTHOR]

Background: Human Papilloma Virus (HPV)-associated Vulvar Squamous Cell Carcinomas (VSCC) present more frequently in young women than HPV-independent tumors. Due to its association with HPV infection, the incidence of vulvar cancer is increasing in young women; however, during pregnancy, it is still extremely rare. Case Report: We present the case of a 36-year-old pregnant woman at 23 weeks of pregnancy, diagnosed with HPV 16-associated VSCC, Federation of Gynecology and Obstetrics (FIGO) stage IB. Information on the coexistence of VSCC with pregnancy is unique, so it seems extremely important to disseminate it to develop the most effective treatment regimen. Additionally, making any decisions regarding therapeutic methods during pregnancy encounters great ethical problems. The size of the tumor was 0.5 cm with a depth of invasion 0.3 cm. The patient underwent therapy and gave birth by cesarean section at 38 weeks of pregnancy because of orthopedic indications. Surgical removal of the vulvar tumor was performed, including a margin of 1.5 cm of healthy tissue. Due to the patient's lack of consent, the sentinel node biopsy was not performed. No recurrence has been observed for 9 years. Conclusions: The poorer prognosis of HPV-associated VSCC is independent of age and stage, with worse outcomes even in early-stage disease. For this reason, it is essential to sensitize clinicians to the possibility of such a diagnosis and to pay attention to the possibility of taking effective treatment during pregnancy, but safe for the fetus. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to evaluate the clinicopathological characteristics and patterns of care among women diagnosed with vulvar malignancy at a tertiary care teaching institute. Additionally, the study aimed to analyse the implications of revised FIGO staging system on stage shift and patient outcomes. Methods: A retrospective observational study was conducted, wherein hospital records of biopsy-proven cases of vulvar cancers managed over a period of 10 years were comprehensively reviewed. The assignment of FIGO staging was performed utilizing both 2009 and 2021 FIGO staging systems for comparative analysis. Statistical analysis was performed using STATA version 17. Survival curves were constructed using the Kaplan-Meier method, with differences assessed using the log-rank test. Additionally, multivariable analysis was conducted using the Cox proportional hazard model. Results: A total of 82 cases meeting the inclusion criteria were enrolled in the study. Management patterns varied widely, with the majority undergoing surgery (73.2%), followed by definitive radiotherapy with or without chemotherapy (10.9%), neoadjuvant radiotherapy and subsequent surgery (4.9%), and palliative care (10.9%). Post-operative radiotherapy was administered in 31.7% of cases. The disease-specific recurrence rate was found to be 32.9%, and the mortality rate was 30.5%. The median Disease-Free Survival (DFS) was 17 months (interquartile range [IQR]: 1–36 months), while the Overall Survival (OS) was 27 months (IQR: 9–52 months). Upon application of the 2021 staging system, a stage shift was observed in 18% of cases of advanced vulvar cancer. The 3-year DFS and OS were reduced for stage IIIA and stage IVA, while showing improvement for stage IIIB. Conclusions: The revised FIGO 2021 staging system offers enhanced simplicity in its application within clinical practice and demonstrates improved correlation with prognosis. Approximately 18% cases experienced restaging under the updated system. Trial registration number: Not applicable. [ABSTRACT FROM AUTHOR]

Simple Summary: The distinct histopathogenetic pathways of vulvar squamous cell neoplasia have led to a shift from a morphology-based to an etiology/molecular-based histopathologic classification, adopted in the most recent WHO Classification of Female Genital Tumours. There are two main categories: HPV-associated (HPVa) and HPV-independent (HPVi) vulvar squamous neoplasia. Most HPVi VSCCs have an underlying TP53 mutation, but attention has recently focused on the uncommon third molecular subtype: TP53 wild-type HPVi VSCC. We review this shift to the etiology/molecular-based classification of VSCC, emphasizing the diagnostic and treatment implications of this change and highlighting the third molecular subtype. Vulvar carcinoma is a rare disease, meeting the criteria for a "rare cancer", but its incidence is increasing, especially in women <60 years of age. Squamous cell carcinoma (VSCC) accounts for the overwhelming majority of vulvar carcinomas and is the focus of this review. As with many cancers, the increased understanding of molecular events during tumorigenesis has led to the emergence of the molecular subclassification of VSCC, which is subclassified into tumors that arise secondary to high-risk human papillomavirus infection (HPV-associated, or HPVa) and those that arise independently of HPV (HPVi), most commonly in the setting of a chronic inflammatory condition of the vulvar skin. This latter group of HPVi VSCC arises in most cases secondary to mutations in TP53, but recently, attention has focused on the uncommon TP53 wild-type HPVi VSCC. These three molecular subtypes of VSCC (HPVa, HPVi p53 abnormal, and HPVi p53 wild type), as well as their precursor lesions, cannot be diagnosed based on a routine histopathological examination or immunostaining for p53 and p16 as surrogate markers for TP53 mutation and high-risk HPV infection, respectively, are required. The molecular subtyping of VSCC shows high reproducibility and provides important prognostic information. HPVa VSCC has the most favorable prognosis, while HPVi VSCC with TP53 mutations (p53abn) has the worst prognosis, and HPVi VSCC with wild-type TP53 (p53wt) has an intermediate prognosis. In this review, we discuss the evidence supporting this molecular subclassification and its implications for the diagnosis and treatment of VSCC and its precursors. [ABSTRACT FROM AUTHOR]

Assessing the risk of cancer among people living with HIV (PLHIV) in the current era of antiretroviral therapy (ART) is crucial, given their increased susceptibility to many types of cancer and prolonged survival due to ART exposure. Our study aims to compare the association between HIV infection and specific cancer sites in Rwanda. Population‐based cancer registry data were used to identify cancer cases in both PLHIV and HIV‐negative persons. A probabilistic record linkage approach between the HIV and cancer registries was used to supplement HIV status ascertainment in the cancer registry. Associations between HIV infection and different cancer types were evaluated using unconditional logistic regression models. We performed several sensitivity analyses to assess the robustness of our findings and to evaluate the potential impact of different assumptions on our results. From 2007 to 2018, the cancer registry recorded 17,679 cases, of which 7% were diagnosed among PLHIV. We found significant associations between HIV infection and Kaposi's Sarcoma (KS) (adjusted odds ratio [OR]: 29.1, 95% CI: 23.2–36.6), non‐Hodgkin lymphoma (NHL) (1.6, 1.3–2.0), Hodgkin lymphoma (HL) (1.6, 1.1–2.4), cervical (2.3, 2.0–2.7), vulvar (4.0, 2.5–6.5), penile (3.0, 2.0–4.5), and eye cancers (2.2, 1.6–3.0). Men living with HIV had a higher risk of anal cancer (3.1, 1.0–9.5) than men without HIV, but women living with HIV did not have higher risk than women without HIV (1.0, 0.2–4.3). Our study found that in an era of expanded ART coverage in Rwanda, HIV is associated with a broad range of cancers, particularly those linked to viral infections. [ABSTRACT FROM AUTHOR]

Radiation therapy was initially used in dermatology to treat various skin diseases, including acne vulgaris, keloids, plantar warts, tinea capitis and hirsutism. Although it is no longer used in the treatment of many of these diseases, radiation therapy still plays a crucial role in the treatment of keloids, skin cancer and solid organ malignancies. In the past 20 years, the widespread use of intensity-modulated radiation therapy has significantly increased in the management of tumor growth in multiple cancer sites and reduced the incidence of complications in normal organs. However, the occurrence and severity of radiation-induced organ complications still significantly affects the quality of life of patients and remains a research hotspot. Skin tissue is the largest area in the human body, serving as both a barrier and a defender. In patients undergoing radiation therapy, skin is often the first tissue that gets damaged. Especially, when the tumor involves the skin or is close to the skin (i.e., skin cancer, head and neck cancer, breast cancer, vulvar cancer), the treatment targets the superficial tissues, and may have inherent adverse effects on the skin. With the increasing incidence of cancer and the widespread use of radiation therapy in cancer treatment, the radiation-induced skin damage has become a serious problem. In this pursuit, the present study provides a review of the progress in the prevention and treatment of radiation-induced skin damage, thereby providing a reference for the prevention and treatment of radiation-induced skin damage. [ABSTRACT FROM AUTHOR]

• Vulvar Necrotizing Fasciitis (VNF) requires rapid diagnosis and treatment with antibiotics, surgery, and multidisciplinary care. • Analysis of 22 VNF patients found that high heart rate, WBC, CRP, and Clavien-Dindo scores are linked to increased mortality. • Vacuum-Assisted Closure (VAC) therapy significantly lowered CRP levels and treatment costs compared to traditional debridement. • No significant differences were found in hospital stay length or debridement frequency between VAC and traditional methods. Older age, systemic inflammation, and severe postoperative complications are major factors in higher VNF mortality rates. • Older age, systemic inflammation, and severe postoperative complications are major factors in higher VNF mortality rates. Vulvar Necrotizing Fasciitis (VNF) is a critical, severe soft tissue infection characterized by aggressive progression and significant morbidity and mortality. Rapid diagnosis and immediate, comprehensive treatment, including antibiotic therapy, meticulous surgical debridement, and multidisciplinary care, are crucial for improving outcomes. This study aimed to investigate mortality-related factors in VNF and evaluate treatment modalities, focusing on Vacuum-Assisted Closure (VAC) therapy versus traditional debridement. This retrospective study analyzed data from 22 VNF patients. Criteria included adults diagnosed with vulvar necrotizing infections, excluding those transferred or not completing treatment at the center. The study examined mortality-related factors and the efficacy of VAC therapy compared to debridement, considering treatment costs and outcomes. Analysis divided patients into survivors (13) and non-survivors (9). Higher heart rate, elevated WBC and CRP levels, and higher Clavien-Dindo scores were associated with increased mortality. VAC therapy, compared to traditional debridement, resulted in significantly lower CRP levels and reduced treatment costs. However, other parameters such as the length of hospital stay and debridement frequency showed no significant differences. The study highlights that older age, systemic inflammation, and severe postoperative complications are key factors associated with higher mortality in VNF. VAC therapy emerges as a promising modality, effectively reducing systemic inflammation and healthcare costs. Nonetheless, the retrospective nature and the small sample size of the study limit the generalizability of the findings. Future research, particularly larger, multicentric studies, is essential to further explore and validate the effectiveness of VAC therapy in VNF management. [ABSTRACT FROM AUTHOR]

Vulval cancer (VC) is an uncommon gynaecological malignancy mostly affecting postmenopausal women. Surgical treatment is associated with high morbidity. Implementation of a "care bundle" of clinical interventions would potentially improve peri-operative outcomes in these patients. The aim of the study is to assess the impact of implementing a care bundle. These data were taken forward as a baseline, after implementation of the care bundle, for comparison as to the impact of the intervention. A literature and guideline review were undertaken to assist with the construction of the care bundle to standardise the care of the VC patient at Belfast City Hospital (BCH). The control group (pre care bundle implementation) included all patients who underwent curative intent surgery for VC from 01 January 2017 until 31 December 2018 at BCH. All patients in this group had pre- and post-operative care according to individual surgical oncologist preference. Study group (post care bundle implementation) included a prospective sample from 01 January 2023 until May 2023 with similar characteristics and comorbidities to the control group. They were followed up for four months. All data were collected electronically and statistical analysis performed including t test 2 samples assuming unequal variable using Excel 2016. Total number of patients in the control group was 40 and in the study group was 14. Complication was less prevalent in the study group (35.7%) compared to 55% in the control group. Moreover, the study group had significantly shorter hospital stay, lower rate of cellulitis in both groin and vulval area and lower rate of hospital re-admission. Major vulval excisions are recognised to be associated with high morbidity. An evidence based team agreed that selection of uniform interventions has been shown to lead to standardisation of care and improvement in the incidence of complications and morbidity. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis protocol aims to evaluate the comparative efficacy of different sentinel lymph node (SLN) detection techniques in the management of vulvar cancer. Vulvar cancer, though rare, predominantly affects older women and requires effective management strategies. The SLN technique has become a standard approach for early-stage cases, offering reduced morbidity compared to complete lymphadenectomy. Currently, various SLN detection methods exist, including the use of Technetium-99m (Tc99m), Indocyanine Green (ICG), and superparamagnetic iron oxide (SPIO), but there is a lack of comprehensive comparison of their efficacy. This review will systematically search relevant databases, including PubMed, Scopus, Cochrane, Web of Science and Embase following PRISMA guidelines, to gather data from clinical trials. The primary outcome will be the detection rates of SLN techniques with secondary outcomes examining patient characteristics and procedural factors. The analysis will utilize random-effects models to compare detection rates across studies. The results of this study aim to provide insights into the optimal SLN detection method with potential implications for clinical practice guidelines in vulvar cancer management. The protocol is registered under the PROSPERO registration number CRD42024590774. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess the survival rates and surgery-related toxicity in patients with locally advanced squamous cell vulvar cancer (LAVC) managed by upfront chemoradiation (CRT) with/without following by surgery. CRT is the primary treatment for patients with unresectable locally advanced squamous cell vulvar carcinoma (LAVC), followed by surgery in case of residual tumor. Patients with AJCC stage II-IV squamous cell vulvar carcinoma referred to Gynecologic Oncology Unit at Fondazione Policlinico Universitario Agostino Gemelli I.R.C.C.S. from January 2016 to February 2023, managed by upfront CRT, were included. 63 patients were included, 21 (33 %) had complete response (cCR) to CRT, 26 (41 %) had partial response (cPR), 1 (2 %) stable disease (cSD), 15 (24 %) had disease progression (cPD). In the whole population, cPR/SD and cPD were associated with reduced PFS (p < 0.001) and overall survival (OS) (p < 0.001), p16 expression was associated with improved PFS (p < 0.001) and OS (p = 0.001). Among patients with clinical residual disease after CRT, 23 patients undergoing surgery experienced improved PFS (p = 0.003) and OS (p = 0.003) compared to those receiving other treatments. Eight (35 %) patients experienced severe (grade ≥ III) postoperative complications; vulvar and groin wound dehiscence/infection were the most common complications; one (4 %) patient died in the postoperative. Patients with pathological residual disease experienced worse PFS (p = 0.013) and OS (p = 0.034). Clinical response to CRT and p16 expression strongly predict survival in LAVC. Surgery for residual disease might be associated with improved survival but is burdened by high rates of complications. Pathologic residual disease correlates with high recurrence rates and poor survival. • Response to chemoradiation and p16 expression predict survival in locally advanced squamous cell vulvar cancer. • Among patients with residual disease, radical surgery is associated with improved survival. • Radical surgery after chemoradiation is associated with high rates of postoperative complications. • Pathologic residual disease is associated with high rates of recurrence and death from disease. [ABSTRACT FROM AUTHOR]

Objectives: To provide an outline of the existing data on penile intraepithelial neoplasia (PeIN), as well as a narrative review on imiquimod (IQ; a toll‐like receptor 7 agonist) treatment and immune microenvironment markers that may predict response to treatment. Methods: A narrative review of the literature from 2000 to the present was conducted on PubMed, and we describe the most relevant data and cross references. Results: The incidence of PeIN is increasing. Local therapy with IQ may offer an easy applicable treatment with complete response rates of up to 63% but can be associated with considerable side‐effects. There is no conclusive data on the optimal treatment schedule for PeIN, but evaluation of treatment results for other human papillomavirus‐related pre‐malignancies suggest three times a week for a duration up to 16 weeks. There are no published studies concerning the PeIN immune microenvironment. However, findings from the few studies on penile cancer and pre‐cancerous vulvar and cervical lesions imply that specific immune cell subpopulations can serve as future predictors for successful immunomodulation treatments such as IQ. Conclusions: Overall, limited data are available on IQ treatment for PeIN and no published data exists on the PeIN immune microenvironment. Further translational studies are warranted to gain more understanding on the pathophysiology of PeIN and potential predictors of progression and of response to topical treatments. [ABSTRACT FROM AUTHOR]

Background: Histopathological biomarkers of carcinomas and their prognostic relevance, such as Broder's grading system (based on the total number of undifferentiated cells) or Bryne's grading system (rating morphological features at the tumor invasive front), have been repeatedly and successfully put to test. Since most studies focus on head and neck cancers or oral carcinomas, for squamous cell carcinoma of the vulva, no standardized and agreed on pathological tumor grading system, yielding prognostic significance, could be determined so far. Material and methods: To determine prognostic associations of different grading systems with regard to groin lymph node metastasis, 73 cases of vulvar carcinomas (VC) were re-examined within our study and Broder's and Bryne's grading system individually performed. To sub-classify between HPV-associated or HPV-independent VC, immunohistochemical p16 stainings were performed. Statistical relationships were evaluated using Spearman correlation and logistic regression analysis, validation was achieved by employment of the likelihood ratio test (LRT) and assessment of ROC curves/AUC values. Results: Within our cohort, Broder's grade I (40≈55%) and Bryne's grade II (48≈66%) were the most frequently assigned histological gradings. We determined a positive correlation of Bryne's grading with the extent of lymph node involvement in HPV-associated tumors and demonstrated the feasibility of Bryne's grading to predict the presence of carcinoma cells within groin lymph nodes (LRT p = 0.0066; AUC value≈0.91) in this cohort. On the other hand, our data suggest that especially HPV-independent tumors may not sufficiently be characterized by current standardly performed grading approaches. Conclusion: Since only Bryne's grading system correlated positively with lymph node involvement in HPV-associated squamous cell carcinoma of the vulva, we propose to include it by name next to the distinct tumor entity on the histopathological report, allowing not only the interpretation of its prognostic relevance but also future research attempts. [ABSTRACT FROM AUTHOR]

The document discusses the role of NRF2/KEAP1 signaling inhibitors in gynecologic cancers, focusing on cervical, ovarian, and endometrial cancers. It highlights how the activation of NRF2/KEAP1 signaling pathway in cancer cells can lead to therapy resistance, impairing the effectiveness of treatments like chemotherapy and radiotherapy. Various natural and synthetic compounds have been identified as inhibitors of NRF2/KEAP1 signaling, showing potential in reducing antioxidant capacity in cancer cells and improving treatment outcomes. The document emphasizes the need for further research and clinical trials to explore the efficacy of these inhibitors in gynecologic cancer treatment. [Extracted from the article]

Purpose: Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with an increased risk of malignancy. The aim of this systematic review was to investigate the prevalence of different malignancies in HS. Methods: This review meets the PRISMA criteria. A data-driven approach was used to conduct the research, which involved a detailed keyword search. The study considered meta-analyses, experimental studies, case-control studies, cross-sectional studies, cohort studies, and recently published cases, published in English or German. Excluded were reviews, summaries, and letters to the editor, as well as studies, which are not based on the human population. Results: Out of the initial 443 publications found, 25 met the inclusion criteria for this systematic review. Patients with HS have a significantly increased risk of cancer, up to 50%. Additionally, the risk of oropharyngeal, central nervous system, colorectal, prostate, vulvar and non-melanocytic skin cancers increase with the severity of HS. The likelihood of comorbid lymphoma in patients with HS is significantly higher compared to healthy controls. In severe cases of HS, malignant degeneration of lesions in the groin, perianal, perineal, and gluteal region can occur in up to 4.6% of cases. This leads to the development of cSCC, which often have a complicated course, are more refractory to treatment and associated with a poorer outcome. The pathogenic mechanisms responsible for the malignant transformation of HS are currently unknown. Conclusions: Patients with HS have a higher risk of cancer compared to the general population. Untreated, long-standing HS lesions can lead to complicated malignant degeneration resulting in cutaneous squamous cell carcinoma. The mechanisms underlying this malignant degeneration are not fully understood. HS patients also have an increased risk of developing other cancers, including prostate, oral, pharyngeal and colorectal cancers of the central nervous system and lymphomas. [ABSTRACT FROM AUTHOR]

Introduction. Surgical treatment of vulvar cancer (VC) entails mental and somatic disturbances due to pain, body image changes, and sexual dysfunction, which are closely associated with impaired social functioning and reduced overall quality of life. However, the results evaluating the impact of rehabilitation programmes on various components of quality of life in these patients remain limited. Aim. to evaluate the effectiveness of rehabilitation programs in relation to the psycho-emotional sphere during 36 months following surgical treatment of early-stage VC. Materials and methods. The randomized controlled study included female patients with VC, divided into two parallel groups of those who received a personalized program of comprehensive rehabilitation (VC-1) and rehabilitation according to the general principles regulated in the national clinical guidelines (VC-2). 36 patients each were randomly assigned to VC-1 and VC-2 groups. The control group included 80 women without female cancer. The VC-2 group was recommended physical activity, psychological support, and anti-edema therapy for lymphostasis. The personalized rehabilitation program in the VC-1 group additionally included lifestyle modification, cognitive-behavioral therapy, intimate hygiene training, magnesium, vitamin B6 and folic acid supplementation, correction of sexual disorders, phytotherapy and physiotherapy from the 3rd month, and climatotherapy and landscape therapy from the 6th month. The “Well-being, Activity, Mood” (WAM) questionnaire was administered at the preoperative visit, 1 week, 1, 3, 6, 12, 24 and 36 months after surgery. Scores were presented as Me [Q25; Q75], differences were considered significant at p 0.05. Results. In the control group, scores on all WAM domains were within normal values throughout the study. In the 1st week after the surgery, well-being and activity decreased to unfavorable values in both VC-1 and VC-2 groups. Mood, however, showed significant positive dynamics compared to baseline. Subsequently, the improvement in the WAM domains was significantly faster and more pronounced in the VC-1 group than in the VC-2 group, reaching the range of favorable values by the 12th month, but not reaching the control group. Conclusion. The personalized comprehensive rehabilitation program showed efficacy on well-being, activity and mood on the WAM questionnaire compared to basic rehabilitation. However, rehabilitation measures should be continued one year after surgery.

Introduction: Basosquamous carcinoma (BSC) of the vulva is an uncommon tumor that primarily consists of basal cell carcinoma with squamous differentiation. Also known as metatypical basal cell carcinoma, BSC is typically classified as a skin cancer and represents only 2% of non-melanoma skin malignancies. This type of carcinoma has a poorer prognosis than basal cell carcinoma due to its increased local aggressiveness and metastatic potential. Case Presentation: We present the case of a 59-year-old woman with a 3-year history of a slow-growing and painful vulvar lesion. Clinical examination revealed a 35-mm nodular, ulcerating, and non-pigmented lesion located on the labia majora. A biopsy confirmed the diagnosis of BSC, and staging assessments indicated no evidence of metastasis. The patient underwent partial radical vulvectomy and sentinel lymph node biopsy, with histological analysis revealing distinct features characteristic of BSC, including basaloid cell islands and areas of significant squamous differentiation. The excision margins were tumor-free, and all six lymph nodes examined were negative for metastases. Regular surveillance for 6 months was conducted without signs of recurrence. Conclusion: After reviewing the literature, this case represents the sixth documented instance of vulvar BSC. Compared to basal cell carcinoma, BSC has a poorer prognosis, with a higher potential for recurrences and metastases. While basal cell carcinoma is much more prevalent among vulvar and skin malignancies, recognizing the squamous differentiation component is crucial for ensuring wider margins during surgical excision.

Mammary-like adenocarcinoma of the vulva is a malignancy with a low incidence rate compared with the squamous cell carcinoma occurring at the same site. We present a rare case of mammary-like adenocarcinoma of the vulva with multiple-organ involvement using 18F-FDG PET/CT. This study indicates that 18F-FDG PET/CT can not only detect the primary lesion but also distinguish the stage of the mammary-like adenocarcinoma of the vulva. [ABSTRACT FROM AUTHOR]

ABSTRACT Background/Objectives Methods Results Conclusion Pediatric vulvar psoriasis in girls is under‐recognized and under‐treated due to its nonspecific clinical appearance. This paper aims to describe the signs and symptoms of pediatric vulvar psoriasis and treatment strategies used by our group.A retrospective cohort study was undertaken at a private pediatric dermatology referral practice from January 2016 to December 2022. Clinical data were prospectively collected and recorded in an online patient database. Treatment regimens were individualized and titrated to clinical response.In 100 girls with vulvar psoriasis, the most common presentation was an erythematous vulvar eruption (97%) which was well‐demarcated in 52% of children and appeared as a plaque in one‐fourth. The perianal skin was involved in 48% of cases. Extragenital psoriasis was present in 69% of patients. Most children responded to initial induction treatment with moderate‐potency topical corticosteroid ointment followed by maintenance with topical tar solution. Systemic treatment was not required for purely vulvar psoriasis compared with 3% of children with extragenital psoriasis.Vulvar psoriasis in girls presents as a chronic erythematous vulvitis, with perianal involvement in half the cases, but without vaginitis. It is a remitting and relapsing skin condition that requires long‐term topical management. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2021 and the Annual Treatment Report for 2016, on the outcomes of patients who started treatment in 2016.The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2021 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2016 was analyzed by using the Kaplan–Meier, log‐rank, and Wilcoxson tests.Treatment was initiated in 2021 for 8006 patients with cervical cancer, 13 912 with endometrial cancer, 8337 with ovarian, tubal, and peritoneal cancer, 2375 with ovarian borderline tumors, and with the others (226 vulvar cancer, 161 vaginal cancer, 437 uterine sarcoma, 47 uterine adenosarcoma, 160 trophoblastic diseases). This clinicopathological information was summarized as the Patient Annual Report. The 5‐year survival rates of the patients with cervical cancer were 92.3%, 77.0%, 56.1%, and 30.3% for stages I, II, III, and IV, respectively. The 5‐year survival rates for the patients with endometrial cancer were 94.1%, 88.8%, 71.2%, and 24.5% for stages I, II, III, and IV, respectively. The 5‐year survival rates for the patients with ovarian cancer (surface epithelial‐stromal tumors) were 91.3%, 78.8%, 54.3%, and 36.8% for stages I, II, III, and IV, respectively.The annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan. [ABSTRACT FROM AUTHOR]

Vulvar lichen sclerosus (VLS) is a chronic inflammatory mucocutaneous disease known to be associated with human papillomavirus‐independent vulvar squamous cell carcinoma. Evidence on the association with other types of cancer, however, is sparce. We conducted a large nationwide cohort study examining the incidence of non‐vulvar cancers among women with biopsy‐verified VLS compared with the general female population. By using the nationwide Pathology Registry, we identified all women in Denmark with a biopsy‐verified VLS diagnosis during 1978–2019 (n = 16,921). The cohort was followed up in the Danish Cancer Registry until 2022 for a subsequent non‐vulvar cancer diagnosis. Standardized incidence ratios (SIRs) were computed with 95% confidence intervals (CIs) as relative risk estimates of all specific non‐vulvar cancer sites. Compared with general female population rates, women with biopsy‐verified VLS had decreased rates of several non‐vulvar cancers, including HPV‐related cancers (combined estimate: SIR = 0.5; 95% CI: 0.3–0.7), and lung (SIR = 0.6; 95% CI: 0.5–0.7), liver (SIR = 0.5; 95% CI: 0.2–0.9), and thyroid cancer (SIR = 0.5; 95% CI: 0.3–0.9). The decreased SIRs tended to sustain throughout the follow‐up period following the VLS diagnosis. This large nationwide cohort study shows that women with biopsy‐verified VLS may have a long‐term reduced risk of developing HPV‐related (cervical, vaginal, oropharyngeal, and anal) and smoking‐associated cancers (lung, liver, and cervical) as well as thyroid cancer. Future studies focusing on the mechanisms behind the decreased cancer risk are needed. What's new? Vulvar lichen sclerosus (VLS) may progress to vulvar cancer risk, whereas the association with other cancer types is unknown. Here, the authors investigated the incidence of non‐vulvar cancers among women in Denmark who were diagnosed with biopsy‐verified VLS between 1978 and 2019. Relative to the general population, cancer risk was decreased among VLS patients. This was especially the case for cancers associated with human papillomavirus infection and for smoking‐related cancers. The findings suggest that VLS patients practice cancer‐avoiding behaviors or there may exist a yet unknown mechanism linking VLS with reduced risk of certain cancer types. [ABSTRACT FROM AUTHOR]

Objective To investigate the therapeutic efficacy of combining fractional CO2 laser with triamcinolone acetonide and econazole nitrate cream for the treatment of vulvar lichen sclerosus (VLS). Methods The clinical data of 113 patients with vulvar lichen sclerosus (VLS ) were retrospectively analyzed. The patients were divided into an observation group and a control group based on different treatments received. Clinical symptoms (vulvar itching, painful intercourse) and signs (vulvar skin color, vulvar skin elasticity, range of vulvar lesions) were scored using the Cattaneo scoring criteria. The Cattaneo scores before and after treatment were recorded for each patient, and comparisons were made between groups in terms of Cattaneo scores and occurrence of adverse reactions. The therapeutic efficacy of fractional CO2 laser combined with triamcinolone acetonide and econazole nitrate cream was evaluated. Results After three treatments, both groups exhibited a significant decrease in Cattaneo scores, with a statistically significant difference (P < 0.05 ). The study group demonstrated a significantly greater reduction in Cattaneo scores compared to the control group (P < 0.05). Furthermore, the cure rate of VSL was higher in the study group than in the control group (25.86% vs. 10.91%, P < 0.05). Regarding adverse effects, there was no statistically significant difference between the two groups (P > 0.05). Conclusions Compared to the single application of fractional CO2 laser, the combination of fractional CO2 laser with triamcinolone acetonide and econazole nitrate cream demonstrates enhanced efficacy in alleviating signs and symptoms among patients with vulvar sclerosing tundra, while minimizing adverse reactions. This approach holds significant potential for clinical implementation. [ABSTRACT FROM AUTHOR]

ABSTRACT The lymphatic pathway is an important route of metastasis in gynecological malignancy. Therefore, the examination of lymph nodes is an essential part of the ultrasound evaluation in patients with known or suspected gynecological malignancy. The lymph nodes most frequently involved in gynecological malignancy (apart from vulvar cancer) are parietal (retroperitoneal) and visceral abdominopelvic lymph nodes. In advanced disease, more distant lymph‐node regions, such as the inguinal, axillary and supraclavicular lymph nodes, can also be involved. The standardized description of lymph nodes has been published previously by the Vulvar International Tumor Analysis (VITA) collaborative group. Herein, a collaborative group of gynecologists and gynecological oncologists with extensive ultrasound experience presents a systematic methodology for ultrasonographic lymph‐node assessment performed as part of the locoregional and distant work‐up to assess the extent of gynecological malignancy. The aim of this consensus opinion is also to describe the anatomical classification and drainage pathways of the lymphatic system as relevant to the gynecological organs. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Lichen sclerosus is a chronic inflammatory condition of unknown etiology that affects the genital and extragenital skin, which can lead to sexual dysfunction and has been associated with vulvar cancer. The vaginal microbiome has a critical role in gynecologic health, but little is known about the microbiome in lichen sclerosus. This study investigated the vaginal and vulvar microbiomes of 27 post-menopausal women with lichen sclerosus. The most abundant genera detected in the vaginal microbiome were Lactobacillus, Gardnerella, and Anaerococcus, while Lactobacillus, Anaerococcus, and Staphylococcus were the most abundant in the vulvar microbiome. The vaginal samples clustered into two main groups, Lactobacillus dominant (n = 6, > 50% microbiome Lactobacillus) and polymicrobial (n = 21) with no dominant genus. The vulvar samples were mainly polymicrobial (n = 25). Actinomyces, Anaerococcus, and Ezakiella in the vaginal microbiome and Actinomyces and Ezakiella in the vulvar microbiome were significantly associated with lichen sclerosus symptoms (adjusted p < 0.05). In this population of post-menopausal women with lichen sclerosus the majority have diverse, non-Lactobacillus dominant microbiomes, which is considered less optimal for gynecologic health based on studies of pre-menopausal women. Actinomyces, Ezakiella, and Anaerococcus were associated with lichen sclerosus symptoms. Understanding the role of these bacteria in lichen sclerosus pathogenesis will be an essential future investigation. [ABSTRACT FROM AUTHOR]

AbstractThe specific Italian Group of Study of the Menopause formulated a consensus opinion on the use of estrogen therapy (ET) or combined estro-progestin hormone therapy (HT) after breast and gynecological cancers. This consensus is based on the risk of recurrence of the specific cancer during ET/HT, the presence of steroid receptors in cancer cells, the use of adjuvant hormone therapies and data on the use of ET/HT after cancer. The following positions were reached. ET/HT can be used after vulvar cancers and melanoma, but with great caution after the rare adenocarcinomas. ET/HT can be used after cervical cancer, but ET should be used with caution after adenocarcinomas. ET/HT can be used after International Federation of Obstetrics and Gynecology (FIGO) stage I–II estrogen-dependent endometrial cancers, except in Black women, and can probably be used after estrogen-independent endometrial cancers. ET/HT cannot be administered or should be used with great caution after most uterine sarcomas. ET/HT can probably be used after ovarian neoplasms except for granulosa cell tumors, and with great caution after low-grade serous ovarian carcinoma and serous borderline ovarian tumors. ET/HT can be used with great caution in women after estrogen receptor (ER)/progesterone receptor (PR)-positive breast cancer and is probably allowed after ER/PR-negative breast cancer. [ABSTRACT FROM AUTHOR]

Adjuvant radiotherapy to the vulva in vulvar squamous cell carcinoma (VSCC) is frequently performed albeit strong evidence is lacking. This systematic review aims to summarize the current literature on this topic. 19 retrospective studies were included and analyzed, focusing on the primary outcome of local recurrence. The publications present conflicting results. While the benefit of adjuvant radiotherapy to the groins in case of node-positive VSCC is well established, the indication criteria and effectiveness of adjuvant radiotherapy to the vulva remain unclear. Based on the studies included in this review, the current evidence suggests that adjuvant radiotherapy to the vulva might not significantly reduce the risk of recurrence or only in certain subgroups. Most of the studies do not consider individual risk factors such as HPV status, resection margin, lymph node stage, grading and others. As a result, the comparability and reliability of these findings are limited. This review aims to highlight the need of further research addressing the risk stratification, considering both oncologic risk factors and adverse events. • Indication criteria are controversial as potential prognostic factors are not consistently considered across studies. • Lymph node status is the most important prognostic factor and should trigger discussion about adjuvant local treatment. • Future studies should aim to differentiate subgroups and stratify patients according to risk factors such as HPV. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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. Results: 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Gynecological cancer is a term referring to malignancies that typically involve ovarian, cervical, uterine, vaginal, and vulvar cancer. Combined, these cancers represent major causes of morbidity and mortality in women with a heavy socioeconomic impact. MiRNAs are small non-coding RNAs that are intensively studied in the field of cancer and changes in them have been linked to a variety of processes involved in cancer that range from tumorigenesis to prognosis and metastatic potential. This review aims to summarize the existing literature that has linked miRNAs with each of the female malignancies as potential biomarkers in diagnosis (circulating miRNAs), in tumor histology and prognosis (as tissue biomarkers), and for local (lymph node) and distant metastatic disease. [ABSTRACT FROM AUTHOR]

Purpose: Human papillomavirus (HPV) is the most common sexually transmitted infection, responsible for multiple HPV-related diseases, including almost all cervical cancers. The highly effective HPV vaccination has been recommended under the German HPV national immunization program (NIP) since 2007 and is reimbursed by health insurances. Vaccination uptake rates, however, remain suboptimal and data on the real-world impact of HPV vaccination in Germany are lacking. This study aims to demonstrate the population-level impact of Germany's NIP on HPV-related anogenital diseases among young women. Methods: Retrospective claims data analysis using a classic impact study design comparing disease prevalence among 28- to 33-year-old women before and after introduction of the HPV-immunization program in Germany. Claims data representing approximately two thirds of German health insurances were used. HPV-related disease outcomes included cervical cancer and high grade precancers (cervical intraepithelial neoplasia (CIN) 2+), anogenital warts, as well as vulvar, vaginal, and anal precancer/cancer. Results: Significant declines were seen for CIN2+, anogenital warts, and vaginal precancer/cancer. Prevalence of CIN2+ declined 51.1% from 0.92% (95% CI = 0.78%, 1.08%) to 0.45% (95% CI = 0.38%, 0.53%). There was a 38.6% decline in anogenital warts prevalence from 0.44% (95% CI = 0.36%, 0.54%) to 0.27% (95% CI = 0.22%, 0.32%) and 75.0% decline in vaginal precancer/cancer prevalence from 0.04% (95% CI = 0.02%, 0.07%) to 0.01% (95% CI = 0.00%, 0.02%). Conclusion: The German HPV-immunization program has led to significant declines in female anogenital disease among young women in Germany, highlighting the importance of the vaccination. Moreover, the data suggest that increasing vaccination coverage in Germany could further strengthen the public-health impact of its HPV-immunization program. [ABSTRACT FROM AUTHOR]

Objectives: To explore the dermoscopic features of lichen sclerosus in different parts of the external genitalia in children. Methods: A retrospective analysis of the dermoscopic features of 42 female children with vulvar lichen sclerosus treated in the Department of Dermatology of Shanxi Children's Hospital from January 2020 to May 2023. Results: Among the 42 female children, aged 3–14 years (mean: 7.24 ± 2.43 years), the duration of vulvar lichen sclerosus ranged from 3 months to 2 years (mean: 9.83 ± 4.93 months). Clinical lesions occurred in the labia minora in 18 cases (42.9%), labia majora in 38 cases (90.5%), posterior fourchette in 36 cases (85.7%), perianal area in 13 cases (31.0%), anterior fourchette in 17 cases (40.5%), clitoris in seven cases (16.7%), and interlabial sulcus in 11 cases (26.2%). Dermoscopic findings common in the labia majora included follicular keratotic plugs, cloverleaf‐like structures, comedo‐like openings, and linear vessels (p <.05); however, purple–red globules and patches and white linear streaks were more common in the posterior fourchette (p <.05), whereas dotted vessels were more common in the labia minora (p <.05). Conclusions: Common dermoscopic findings in pediatric vulvar lichen sclerosus were yellow‐white structureless areas, white linear streaks, follicular keratotic plugs, and cloverleaf‐like structures; yellow‐white structureless areas and white linear streaks showed the highest specificity. The dermoscopic findings varied among different affected areas, which provides a basis for further understanding of the characteristics of different sites of vulvar lichen sclerosus in the pediatric population. [ABSTRACT FROM AUTHOR]

Background/Aim: The serine proteinase inhibitor 1 (SERPINE1) gene codes for the plasminogen activator inhibitor 1 (PAI1) protein and is thought to play a tumor supportive role in various cancers. In this work we aimed to uncover the role PAI1 plays in the proliferation, migration, and invasion of vulvar cancer (VC), and define the protein’s function as an oncogene or tumor suppressor. Materials and Methods: Through treatment with an agonist (G1) and antagonist (G36) of G-coupled estrogen receptor 1 (GPER1), an upstream regulator of SERPINE1 expression, and a forward transfection knockdown protocol, the expression of SERPINE1/PAI1 in VC cells was altered. The effects these altered SERPINE1/PAI1 levels had on tumor cell functions were then examined. Proliferation was analyzed using the resazurin assay, while migration was studied via the gap closure assay. Through colony- and tumor sphere- formation assays clonogenicity was tested, and western blots showed protein expression. Results: In A431 VC cells, when the levels of PAI1 were reduced via knockdown or treatment with G1, migration, proliferation, and colony growth was reduced. Treatment with G36 increased expression of PAI1 and increased migration and colony size in CAL39 cells. Conclusion: Based on the findings in this study, suppressing PAI1 expression in VC cells appears to reduce their progression and tumorigenic potential. Therefore, PAI1 could possibly function as an oncogene in VC. GPER1 appears to be a suitable target for suppressing PAI1 in VC. [ABSTRACT FROM AUTHOR]

Lipschütz ulcer (LU) is a condition known for painful vulvar ulcers, typically affecting young women and often linked to infectious agents. Recent reports have indicated a potential connection between LU and COVID‐19 vaccination, particularly after the second or booster doses. This study presents a case of LU following the first dose of tozinameran in a young woman who had a previous SARS‐CoV‐2 infection and investigates similar cases globally. An 18‐year‐old woman experienced vulvar pain and ulcers 2‐days after her initial COVID‐19 vaccine dose. After ruling out infections through serological tests, a diagnosis of LU was made, and her symptoms resolved after 10 days. A literature search and VigiBase® analysis revealed 11 cases of LU following COVID‐19 vaccination, and 519 vulvovaginal ulcer cases associated with these vaccines were identified in Vigibase®, with a median onset of 2 days. Most LU cases occurred after the second dose or booster shots. The primary hypothesis for this association is a type 3 hypersensitivity reaction mediated by immune complexes, possibly triggered by prior exposure, as many cases occurred after the second dose. Interestingly, the presented case suggests that prior COVID‐19 infection could serve as sensitization. In conclusion, this study highlights the potential occurrence of LU after the initial COVID‐19 vaccine dose in young patients with prior COVID‐19 infection. While the risk of recurrence after subsequent vaccinations or infections remains uncertain, the benefits of vaccination outweigh the risks. Clinicians and patients should be aware of this potential issue to make informed decisions regarding vaccination. [ABSTRACT FROM AUTHOR]

Our objective was to evaluate the association of adjuvant radiation therapy (RT) to subsequent second primary malignancies (SPMs) in endometrial cancer survivors. Patients with endometrial cancer as their first malignancy were identified from 8 registries of the Surveillance, Epidemiology, and End Results (SEER) database. SPMs were defined as any type of primary malignancy that occurred more than 12 months after the diagnosis of endometrial cancer. Fine-Gray competing risk regression and Poisson regression were used to evaluate the radiotherapy-associated risk (RR) for SPMs. The Kaplan-Meier method was applied to assess the survival outcomes of endometrial cancer patients. Of 62,108 endometrial cancer patients,16,846 patients (27.12%) were in the RT group, and 45,262 patients (72.88%) were in the no-RT group. During the 30-year follow-up period, the cumulative incidence of SPMs was 20.9% and 19.7% in each group, respectively. In both multivariable competing risk regression analysis and Poisson regression analysis, adjuvant RT was found to be associated with a higher risk of developing colon and rectum cancer (adjusted hazard ratio (HR), 1.29; 95% confidence interval (CI), 1.12–1.50; P < 0.001; adjusted RR, 1.29; 95% CI, 1.11–1.49; P < 0.001), lung and bronchus cancer (adjusted HR, 1.27; 95% CI, 1.08–1.50; P = 0.004; adjusted RR, 1.26; 95% CI, 1.07–1.49; P = 0.005), vulva cancer (adjusted HR, 1.72; 95% CI, 1.04–2.85; P = 0.036; adjusted RR, 1.74; 95% CI, 1.03–2.88; P = 0.035), urinary bladder cancer (adjusted HR, 1.86; 95% CI, 1.41–2.46; P < 0.001; adjusted RR, 1.85; 95% CI, 1.40–2.44; P < 0.001), and non-Hodgkin lymphoma (adjusted HR, 1.37; 95% CI, 1.06–1.77; P = 0.016; adjusted RR, 1.37; 95% CI, 1.05–1.76; P = 0.017). However, a slightly decreased risk of breast cancer was observed in patients who underwent adjuvant RT (adjusted HR, 0.89; 95% CI, 0.80–0.98; P = 0.021; adjusted RR, 0.88; 95% CI, 0.80–0.98; P = 0.020). The RR for colon and rectum cancer decreased with age and elevated with increasing latency since endometrial cancer diagnosis, and the RR for urinary bladder cancer showed a similar tendency with latency. SPMs can significantly impair the survival outcomes of primary endometrial cancer survivors. Our findings suggest that adjuvant RT for endometrial cancer patients increases the risk of non-Hodgkin lymphoma and several types of solid cancer. Long-term surveillance of these patients should be recommended for detecting SPMs. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the relationship between the lymph node ratio (LNR) and the prognostic values of gynecological cancer. Materials and Methods: PubMed, Web of Science, Embase, and the Central Cochrane Library were used to search for studies on LNR and gynecological cancer published before 18 April 2024. The effect measure for meta-analysis of primary outcomes was the hazard ratio (HR) for overall survival (OS), progressionfree survival (PFS), and disease-free survival (DFS). Pooled HRs and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Sensitivity analysis was applied to evaluate the robustness of the results. The I2 statistic was used to measure heterogeneity. Subgroup analysis and meta-regression were chosen to illustrate the potential heterogeneity of the risk factors for outcomes. Publication bias was assessed using Egger's test and Begg's funnel plots. Results: A total of 34 studies with 23,202 cases were included in this metaanalysis. A meta-analysis found that higher LNR was associated with worse OS (HR = 2.42, 95% CI: 2.07-2.83; I2 = 77.4%, p < 0.05), PFS (HR = 1.97, 95% CI: 1.66-2.32; I2 = 0.00%, p > 0.05), and DFS (HR = 3.18, 95% CI: 2.12-4.76; I2 = 64.3%, p < 0.05). Moreover, meta-analysis revealed significant differences in the association between LNR and OS of cervical cancer (CC) (HR = 2.53, 95% CI: 1.94-3.31; I2 = 72.6%, p < 0.05), ovarian cancer (OC) (HR = 2.05, 95% CI: 1.66-2.54; I2 = 76.7%, p < 0.05), endometrial cancer (EC) (HR = 2.16, 95% CI: 1.48-3.16; I2 = 53.6%, p < 0.05), and vulvar cancer (VC) (HR = 8.13, 95% CI: 3.41-19.43; I2 = 57.2%, p < 0.05). Conclusion: We observed a clear association between higher LNR and poorer prognosis in our study of patients with gynecological cancer. Further prospective studies are warranted to determine the optimal LNR and whether LNR can guide adjuvant therapy use in gynecological cancer. It is essential to conduct further prospective studies to establish the optimal LNR threshold, determine the minimum threshold of lymph node removal, and investigate whether LNR can serve as a reliable marker for guiding adjuvant therapy choices in gynecological cancer. [ABSTRACT FROM AUTHOR]

Gynecological cancer, the most common form of cancers in women worldwide, initiates in the reproductive organs of females. More often, the common treatment measures, i.e. surgery, radiation, and medical oncology are found to be unsuccessful in the treatment of gynecological tumors. Emerging evidence indicates that extracellular vesicles (EVs) play a significant role in the pathogenesis of gynecological cancers by distinct mechanisms. The present review highlights how EVs contribute to the progression of different types of gynecological cancers such as cervical cancer, endometrial cancer, ovarian cancer, vaginal cancer, uterine sarcoma, gestational trophoblastic disease (GTD), and vulvar cancer. The primary focus is to understand how EVs’ cargo alters the phenotypic response of the recipient cells, thereby contributing to the progression of the disease, thus can be considered as a prognostic and diagnostic biomarker. A brief discussion on the role of EVs in the diagnosis and prognosis of different gynecological cancer types is also highlighted. Targeting the biogenesis of the EVs, their inside cargo, and EVs uptake by the recipient cells could be a potential therapeutic approach in the treatment of gynecological cancer beside conventional therapeutic means. [ABSTRACT FROM AUTHOR]

Vulvar cancer is rare with incidence of 45,240 new cases globally which account for 4% of all genitourinary tract neoplasma. It is considered as a postmenopausal disease, however incidence age has decreased over the years because of high prevalence of persistent high-risk human papillomavirus (hrHPV) infection. Vulvar cancer diagnosis in young women is challenging. Prompt and adequate diagnosis, and treatment can ensure the life quality. A 23 years old patient was admitted to Department of Operative Gynecology for treating malignant vulvar neoplasma. She was reffered to our clinic for electrocauterization after being diagnosed of condylomata accuminata. Physical examination revealed vulva atrophy with smooth discolored skin patches on both sides. A 2 cm exophytic lesion was noted ~10 mm from clitoris on right labia majora. Multifocal biopsy was performed for suspect finding which proved invasive vulvar squamous keratinizing cancer. Positron emission tomography-computed tomography (PET/CT) scan showed individual lymph nodes on right inguinofemoral region which were moderately metabolically active. Wide excision of cancer was performed with unilateral inguinofemoral lymphadenectomy. Macroscopic evaluation of entire specimen depicted 2.4 x 2.2 x 0.5 cm HPV associated invasive vulvar squamous keratinizing cancer, vulvar high grade squamous intraepithelial lesion (vHSIL) or usual type vulvar intraepithelial neoplasia (uVIN3) and lichen sclerosus. Healthcare professionals in primary care centers should be adequately trained, aware of and familiar with vulvar malignancies in younger women despite their rarity. Early diagnosis can improve outcomes in vulvar cancer via reducing morbidity and mortality. The individualized surgical treatment is the preferred strategy for patients at present. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Klippel–Trénaunay syndrome can present with atypical manifestations such as a bleeding vulvar hemangioma. This case report, the first documented in Uganda, highlights the need for awareness of such presentations and underscores the importance of continuous follow‐up in female patients to manage potential complications throughout adolescence and pregnancy. Klippel–Trénaunay syndrome (KTS) is a rare congenital disorder marked by bone and soft tissue hypertrophy, port‐wine stains, and varicosities. Cases involving genital hemangiomas are rare. This report highlights a 5‐year‐old girl in Uganda with typical KTS features, including hypertrophy and port‐wine stains, along with a bleeding vulvar hemangioma, emphasizing its uncommon presentation and potential complications. Treatment involved compression bandaging and timolol 0.2% solution. This case underscores the importance of awareness of atypical manifestations of hemangiomas with KTS and continuous follow‐up for female patients, especially through adolescence and pregnancy, due to potential complications such as prepubertal per vaginal bleeding, menorrhagia, and post‐partum bleeding. [ABSTRACT FROM AUTHOR]

To determine if nutritional status effects response to immunotherapy in women with gynecologic malignancies. A retrospective chart review was conducted on gynecologic cancer patients who received immunotherapy at a single institution between 2015 and 2022. Immunotherapy included checkpoint inhibitors and tumor vaccines. The prognostic nutritional index (PNI) was calculated from serum albumin levels and total lymphocyte count. PNI values were determined at the beginning of treatment for each patient and assessed for their association with immunotherapy response. Disease control response (DCR) as an outcome of immunotherapy was defined as complete response, partial response, or stable disease. One hundred and ninety-eight patients received immunotherapy (IT) between 2015 and 2022. The gynecological cancers treated were uterine (38%), cervix (32%), ovarian (25%), and vulvar or vaginal (4%) cancers. The mean PNI for responders was higher than the non-responder group (p < 0.05). The AUC value for PNI as a predictor of response was 49. A PNI value of 49 was 43% sensitive and 85% specific for predicting a DCR. In Cox proportional hazards analysis, after adjusting for ECOG score and the number of prior chemotherapy lines, severe malnutrition was associated with progression-free survival (PFS) (HR = 1.85, p = 0.08) and overall survival (OS) (HR = 3.82, p < 0.001). Patients with PNI < 49 were at a higher risk of IT failure (HR = 2.24, p = 0.0001) and subsequent death (HR = 2.84, p = 9 × 10−5). PNI can be a prognostic marker to predict response rates of patients with gynecologic cancers treated with immunotherapy. Additional studies needed to understand the mechanistic role of malnutrition in immunotherapy response. [ABSTRACT FROM AUTHOR]

Background: 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. Objectives: To investigate the value of the LNR and the count of LN on overall survival (OS) and recurrence-free survival (RFS). Design: This study is a retrospective, longitudinal, institution-based study. Methods: 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. Results: 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]