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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]

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]

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]

Objective: Vulvar carcinoma exhibits a robust correlation alongside HPV infection; however, the impact of HPV rank on the prognostic outcomes of radiation therapy within vulvar malignancies stays ambiguous. In the present study, we performed a comprehensive examination as well as meta-analysis to assess the influence of infection with HPV upon the long-term outlook as well as sensitivity of individuals with vulvar cancer undergoing radiation therapy. Methods: A meticulous examination of the existing research was conducted in accordance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A thorough search was conducted in the PubMed, Embase, Web of Science, as well as Cochrane Library databases, covering the entire available literature till April 1, 2023. The studies that met the inclusion criteria contained data about HPV infection and oncological outcomes in patients with vulvar cancer who received radiation therapy. This study was registered in PROSPERO (CRD42023417957). Results: We identified 12 retrospective studies meeting our inclusion criteria, which included a total of 3967 patients. Patients with HPV-associated vulvar cancer achieved a better overall survival rate after radiotherapy (HR=0.71, 95%CI: 0.54-0.93, P=0.01), and showed a significant improvement in disease-free survival (HR=0.75, 95%CI: 0.58-0.97, P=0.09) and progression-free survival (HR=0.31, 95%CI: 0.22-0.45, P,<0.01). Meanwhile, the complete remission rate after radiotherapy was higher for HPV-associated vulvar cancer patients (MH= 4.02, 95% CI: 1.87-8.61, P=0.0003), and the local control rate was better (HR=1.90, 95% CI: 1.15-3.15, P=0.01), exhibiting a reduced incidence of relapse within the field of study (HR=0.21, 95% CI: 0.10-0.42, P<0.001). Conclusion: In comparison to HPV-independent vulvar squamous cell carcinoma, patients with HPV-associated vulvar cancer exhibit higher sensitivity to radiotherapy, with a significant difference in prognosis. Further research should investigate the mechanisms underlying this high sensitivity to radiotherapy caused by HPV, and should be evaluated using high-quality randomized controlled trials. [ABSTRACT FROM AUTHOR]

Introduction: Acquired vulvar lymphangioma (AVL), a rare disease caused by the dilation of superficial lymphatic vessels secondary to deep lymphatic vessel injury, is characterized by a wide range of morphological diversity and massive exudate. This morphological heterogeneity has often led to misdiagnosis or nondiagnosis. The management of AVL presents a therapeutic challenge due to the absence of a standardized treatment protocol. Case presentation: A 53-year-old female patient, previously received surgical treatments for stage IIb cervical squamous cell carcinoma, presented with vulvar enlargement and copious amount of yellow exudate seven years post-treatment. Clinically, the patient exhibited chronic vulvar swelling, with easily-exudated nodules. The vulvar biopsy revealed lymphatic vessel dilation with lymphocyte infiltration, consistent with AVL. Due to the extensive lesions and severe exudate, staged excisions of bilateral vulvar lesions were performed at one-month intervals. Follow-up examinations of this patient for one-year post-surgery showed no evidence of recurrence. Conclusion: In this instance, AVL manifest secondary to cervical cancer surgery, as a result of damage to the deep lymphatic vessels of the vulva, with characteristic symptoms of copious amounts of exudate and vulvar lesions with diverse morphologies, which provides a cautionary note for physicians. Besides, the staged resection strategy in this case may offer insights into surgical treatment protocol for extensive AVL. [ABSTRACT FROM AUTHOR]

Simple Summary: Vulvar cancer is a rare cancer but has a high cure rate if diagnosed early and treated appropriately. In the early 20th century, 5-year survival rates were only 15–20% because of inadequate treatment of both the primary cancer and the groin lymph nodes. By the mid-20th century, 5-year survival rates rose to 60–70% with the introduction of the radical resection of the vulva, together with the radical resection of the groin and usually pelvic lymph nodes. Although cure rates were good, physical and psychological morbidity were high with this extensive surgery. Hence, various modifications have been proposed over the past 50 years to decrease this morbidity without compromising survival, including modifications to the extent of both the vulvectomy and lymph node dissection. This paper looks at the results these modifications have on both survival and morbidity. Vulvar cancer is a rare disease, and cure rates were low until the mid-20th century. The introduction of an en bloc radical vulvectomy and bilateral groin and pelvic lymph node dissection saw them rise from 15–20% to 60–70%. However, this very radical surgery was associated with high physical and psychological morbidity. Wounds were usually left open to granulate, and the average post-operative hospital stay was about 90 days. Many attempts have been made to decrease morbidity without compromising survival. Modifications that have proven to be successful are as follows: (i) the elimination of routine pelvic node dissection, (ii) the use of separate incisions for groin dissection, (iii) the use of unilateral groin dissection for lateral, unifocal lesions, (iv) and radical local excision with 1 cm surgical margins for unifocal lesions. Sentinel node biopsy with ultrasonic groin surveillance for patients with node-negative disease has been the most recent modification and is advocated for patients whose primary cancer is <4 cm in diameter. Controversy currently exists around the need for 1 cm surgical margins around all primary lesions and on the appropriate ultrasonic surveillance for patients with negative sentinel nodes. [ABSTRACT FROM AUTHOR]

Background: Vulvar squamous cell carcinoma (VSCC) arises after an HPV infection or the mutation of p53 or other driver genes and is treated by mutilating surgery and/or (chemo) radiation, with limited success and high morbidity. In-depth information on the immunological make up of VSCC is pivotal to assess whether immunotherapy may form an alternative treatment. Methods: A total of 104 patient samples, comprising healthy vulva (n = 27) and VSCC (n = 77), were analyzed. Multispectral immunofluorescence (15 markers) was used to study both the myeloid and lymphoid immune cell composition, and this was linked to differences in transcriptomics (NanoString nCounter, 1258 genes) and in survival (Kaplan–Meier analyses). Results: Healthy vulva and VSCC are both well infiltrated but with different subpopulations of lymphoid and myeloid cells. In contrast to the lymphoid cell infiltrate, the density and composition of the myeloid cell infiltrate strongly differed per VSCC molecular subtype. A relative strong infiltration with epithelial monocytes (HLADR−CD11c−CD14+CD68−CD163−CD33−) was prognostic for improved survival, independent of T cell infiltration, disease stage or molecular subtype. A strong infiltration with T cells and/or monocytes was associated with drastic superior survival: 5-year survival > 90% when either one is high, versus 40% when both are low (p < 0.001). Conclusion: A hot myeloid and/or lymphoid infiltrate predicts excellent survival in VSCC. Based on the response of similarly high-infiltrated other tumor types, we have started to explore the potential of neoadjuvant checkpoint blockade in VSCC. [ABSTRACT FROM AUTHOR]

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

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]

The aim of the study was to analyze and summarize the available literature data on the modern radiotherapy techniques, indications for radiotherapy (preoperative, radical, postoperative radiation therapy), treatment volumes at different disease stages, and principles of drug and accompanying therapy for patients with vulvar cancer. Material and Methods. The literature review was based on the clinical recommendations of the Ministry of Health of the Russian Federation and National Comprehensive Cancer Network (NCC N), as well as on the search of sources in PubMed and Cochrane Library systems. Literature sources and publications from 2005 to 2023 were included. Results. This contribution outlined the main indications for preoperative, postoperative and radical radiotherapy in patients with vulvar cancer, as well as the basic principles of drug treatment and correction of complications. Potential risk factors for postoperative disease recurrence were identified, the volumes of irradiation at each treatment mode were analyzed, and the feasibility of using brachytherapy in patients with vulvar cancer was discussed. Conclusion. To date, there are recommendations, guidelines for the management of patients with vulvar cancer, as well as clinical trial results. Understanding of the principles of prescribing treatment for vulvar cancer patients can improve local control, overall and recurrence-free survival, and the use of modern radiotherapy techniques will enshure an acceptable quality of life in these patients.

Background: While cervical cancer incidence rates (IR) in the United States have dropped in the last 20 years, non‐cervical human papillomavirus (HPV) associated cancers increased. Many people in Texas (TX) live in medically underserved areas and have higher risk of developing HPV‐associated cancers. Since previous studies of these regions focused on cervical cancer, we included other HPV‐associated cancers in our analysis of IR in East TX and the TX‐Mexico Border compared to other TX regions. Methods: Cancer data from 2006 to 2019 were obtained from the TX Cancer Registry. Cases of HPV‐associated cervical, vaginal, vulvar, penile, anal, and oropharyngeal cancers and corresponding patient‐level demographic data were included. We calculated IR per 100,000 and drew heat maps to visualize cancer IR by county. To control potential confounders, we added county‐level risk factors: rates for smoking, excessive drinking, obesity, STIs, primary care provider availability and dentist availability, from the County Health Rankings and Roadmaps program. We reported IRs by region and time and estimated unadjusted and adjusted risk ratio (RR) for association of each type of cancer and region. Lastly, we created adjusted models for each cancer by period to see time trends of regional differences. Results: Risk of anal, cervical, and oropharyngeal cancer was lower at parts of the Border than in the rest of TX in the adjusted model. We also observed increasing anal and oropharyngeal cancer risk and decreasing cervical and vaginal cancer risk over time. Conclusion: Patient sociodemographics, behavioral risk factors, and access to care may contribute to some observed differences in cancer IR across regions. This indicates that targeted prevention efforts towards these regions, especially in low socioeconomic status communities, may benefit future generations. [ABSTRACT FROM AUTHOR]

Vulvar intraepithelial neoplasia, also known as VIN, is a non-invasive squamous lesion and precursor of squamous cell carcinoma (SCC) of the vulva. There is no screening test for vulvar intraepithelial neoplasia. Diagnosis of VIN is made clinically and confirmed with a biopsy. We describe a 66-year-old woman with a condyloma-like tumour located in the skin on the vestibule of the vagina. A biopsy sample was taken from the nodule. The definitive diagnosis is supported by the histological examination (VIN III) and immunohistochemical examination of p16(+), p53(+), and a few cell nuclei. The case provides information on the importance of multidisciplinary cooperation. Lifelong surveillance is essential since the resection of individual lesions does not guarantee the prevention of invasive cancer. [ABSTRACT FROM AUTHOR]

Background Inguinal lymph node dissection plays an important role in the management of melanoma, penile and vulval cancer. Inguinal lymph node dissection is associated with various intraoperative and postoperative complications with significant heterogeneity in classification and reporting. This lack of standardization challenges efforts to study and report inguinal lymph node dissection outcomes. The aim of this study was to devise a system to standardize the classification and reporting of inguinal lymph node dissection perioperative complications by creating a worldwide collaborative, the complications and adverse events in lymphadenectomy of the inguinal area (CALI) group. Methods A modified 3-round Delphi consensus approach surveyed a worldwide group of experts in inguinal lymph node dissection for melanoma, penile and vulval cancer. The group of experts included general surgeons, urologists and oncologists (gynaecological and surgical). The survey assessed expert agreement on inguinal lymph node dissection perioperative complications. Panel interrater agreement and consistency were assessed as the overall percentage agreement and Cronbach's α. Results Forty-seven experienced consultants were enrolled: 26 (55.3%) urologists, 11 (23.4%) surgical oncologists, 6 (12.8%) general surgeons and 4 (8.5%) gynaecology oncologists. Based on their expertise, 31 (66%), 10 (21.3%) and 22 (46.8%) of the participants treat penile cancer, vulval cancer and melanoma using inguinal lymph node dissection respectively; 89.4% (42 of 47) agreed with the definitions and inclusion as part of the inguinal lymph node dissection intraoperative complication group, while 93.6% (44 of 47) agreed that postoperative complications should be subclassified into five macrocategories. Unanimous agreement (100%, 37 of 37) was achieved with the final standardized classification system for reporting inguinal lymph node dissection complications in melanoma, vulval cancer and penile cancer. Conclusion The complications and adverse events in lymphadenectomy of the inguinal area classification system has been developed as a tool to standardize the assessment and reporting of complications during inguinal lymph node dissection for the treatment of melanoma, vulval and penile cancer. [ABSTRACT FROM AUTHOR]

Background/Objectives: Vulvar cancer (VC) comprises a small fraction of female neoplasms with notable high-incidence clusters among German regions. Despite a proposed impact of nationwide lockdowns in response to the COVID-19 pandemic on oncological diseases, the effect on VC staging and tumor characteristics remains yet to be resolved; therefore, analyzing pathological data from patients with squamous cell VC pre-, during, and post-COVID in a high-incidence region may offer insights into potential epidemiological and clinical trends. Methods: We identified a total of 90 patients who were diagnosed at the Institute of Pathology, University Hospital Saarland, between 2018 and 2023, and defined three distinct cohorts: a pre-COVID cohort (2018–2019), a COVID cohort (2020–2021), and a post-COVID cohort (2022–2023). Histomorphological data were collected from the individual patient reports and statistically analyzed using Fisher's exact test or the Kruskal–Wallis test. Results: Although we found no statistically significant differences in age, T-stage, perineural infiltration, blood vessel infiltration, resection status, grading, or resection margin between our three cohorts, surprisingly, we determined a greater extent of lymphovascular infiltration (Fisher's exact test; p = 0.041), as well as deeper tumor infiltration depth (Kruskal–Wallis test; p < 0.001) before the COVID-19 pandemic. Furthermore, we did not identify any soft indications of abnormalities in patient care within our center (unchanged status of the resection margins across all three cohorts). Conclusions: Our results clearly do not support a negative affection of clinical or pathobiological characteristics of VC during or after the pandemic. However, final assessments regarding the pandemic's effect on VC require additional study approaches in various regions, preferably with future extended timeframes of a longer follow-up. [ABSTRACT FROM AUTHOR]

Background: Pott's Puffy tumor (PPT) is a complicated frontal sinusitis that is also described as frontal bone osteomyelitis and a localized sub periosteal abscess. Early diagnosis and immediate active treatment are necessary to prevent severe neurologic sequelae. Case Presentation: Here, we report on a case of Pott's puffy tumor in a previously healthy 13-year-old girl with a worsening headache and swelling of the frontal bone accompanied by vomiting and fever. Magnetic resonance imaging revealed osteomyelitis of the frontal bone. A foreign body was discovered and removed via endoscopy which was then followed by 6 weeks of parenteral and enteral antibiotic therapy, resulting in resolution of all symptoms. Conclusion: A complete history in terms of trauma and insect bite or foreign body in the nose is paramount for a correct diagnosis, and performing a full examination of ear, nose and throat (ENT) to rule out a foreign body is advised. [ABSTRACT FROM AUTHOR]

The vagina hosts a community of microorganisms known as the vaginal microbiota. This community is relatively stable and straightforward, with Lactobacillus species being the most dominant members. The vaginal microbiota has various functions that are essential for maintaining human health and balance. For example, it can metabolise dietary nutrients, produce growth factors, communicate with other bacteria, modulate the immune system, and prevent the invasion of harmful pathogens. When the vaginal microbiota is disrupted, it can lead to diseases and infections. The observed disturbance is distinguished by a reduction in the prevalence of Lactobacillus and a concurrent rise in the number of other bacterial species that exhibit a higher tolerance to low oxygen levels. Gynecologic cancers are a group of cancers that affect the female reproductive organs and tissues, such as the ovaries, uterus, cervix, vagina, vulva, and endometrium. These cancers are a major global health problem for women. Understanding the complex interactions between the host and the vaginal microorganisms may provide new insights into the prevention and treatment of gynecologic cancers. This could improve the quality of life and health outcomes for women. [ABSTRACT FROM AUTHOR]

Background: Vulvar stenosis is a debilitating condition that compromises sexual function, urination, and the ability to undergo gynecological examinations. The purpose of this study is to describe the technique of capillary perforator perineal flaps (CPPF) for the correction of vulvar stenosis. Methods: We retrospectively examined patients with vulvar stenosis treated through surgical separation and reconstruction with CPPF. The procedure involved vulvar separation with the creation of a subsequent defect, repaired using a flap, harvested laterally to the labia majora including a capillary perforator and transferred through a subcutaneous tunnel to repair the vulvar defect. The functional outcome was evaluated with the Bradford scale, comparing the preoperative and postoperative scores using the Student's t-test. Results: thirteen patients were included, three with stenosis following treatment for vulvar cancer and ten due to lichen sclerosus. In total, we analyzed 29 flaps, with an average size of 15.6 cm2. We always included just one perforator in the flap and no postoperative complications. Stenosis was resolved in all patients, with no recurrences one year after the surgery. The preoperative average severity of the stenosis was 2.3 + 0.6, reducing to 0.3 + 0.4 post-intervention, indicating a significant improvement (p < 0.01). Conclusions: CPPF has proven to be a quick and safe method for the reconstruction of vulvar stenosis. [ABSTRACT FROM AUTHOR]

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

Indocyanine green (ICG), a well-known molecule employed in medicine for over five decades, has emerged as a versatile dye widely embraced across various surgical disciplines. In gynecologic oncology, its prevalent use revolves around the detection of sentinel lymph nodes. However, the true potential of ICG extends beyond this singular application, owing to its pragmatic utility, costeffectiveness, and safety profile. Furthermore, ICG has been introduced in the theranostic landscape, marking a significant juncture in the evolution of its clinical utility. This narrative review aims to describe the expanding horizons of ICG fluorescence in gynecologic oncology, beyond the sentinel lymph node biopsy. The manifold applications reported within this manuscript include: 1) lymphography; 2) angiography; 3) nerve visualization; 4) ICG-driven resections; and 5) theranostic. The extensive exploration across these numerous applications, some of which are still in the preclinical phase, serves as a hypothesis generator, aiming to stimulate the development of clinical studies capable of expanding the use of this drug in our field, enhancing the care of gynecological cancer patients. [ABSTRACT FROM AUTHOR]

There is limited data regarding the use of immunotherapy for patients with vulvar squamous cell carcinoma and coexisting autoimmune disease. Cemiplimab is a PD-1 inhibitor approved for use in patients with locally advanced and metastatic cutaneous squamous cell carcinoma. However, little is known about its efficacy in the setting of vulvar cancer. We present a case of advanced vulvar squamous cell carcinoma treated with induction chemotherapy and immunotherapy with cemiplimab followed by definitive chemoradiation in the setting of multiple autoimmune diseases. She achieved a complete clinical response and experienced no worsening of her autoimmune conditions despite cessation of her immunosuppressants and initiating an immune checkpoint inhibitor. We review existing data on neoadjuvant treatment of vulvar cancer and the use of cemiplimab in genital and inguinal squamous cell carcinomas. Ongoing exploration of cemiplimab’s efficacy in vulvar cancer and safety in immunosuppressed patients is critical.

The study analysed the case of a 74-year-old woman with a diagnosis of FIGO IVA vulvar carcinoma. The patient was also suffering from other diseases such as type 2 diabetes, hypertension, obesity, and permanent atrial fibrillation. Among the patient’s most significant nursing problems, self-care deficit, impaired mobility, impaired ability to perform hygiene and self-toileting, and lack of knowledge about disease were singled out. The aim of the work is to present knowledge and explain the subject of the therapeutic process and nursing problems of a patient with advanced vulvar cancer based on an individual case study. ICNP® reference terminology was used to develop care plans. The midwife’s care of a patient with advanced vulvar cancer requires special consideration of education, health promotion, and self-management activities, assisting with hygiene activities, and providing psychological support. The overarching goal in the patient’s care is to strive for the highest possible degree of self-care.

Abstract Human papillomavirus (HPV) is a common sexually transmitted virus that can cause cervical cancer and other diseases. Dynamic transmission models (DTMs) have been developed to evaluate the health and economic impacts of HPV vaccination. These models typically include many parameters, such as natural history of the disease, transmission, demographic, behavioral, and screening. To ensure the accuracy of DTM projections, it is important to parameterize them with the best available evidence. This study aimed to identify and synthesize data needed to parametrize DTMs on the natural history of HPV infection and related diseases. Parameters describing data of interest were grouped by their anatomical location (genital warts, recurrent respiratory papillomatosis, and cervical, anal, vaginal, vulvar, head and neck, and penile cancers), and natural history (progression, regression, death, cure, recurrence, detection), and were identified through a systematic literature review (SLR) and complementary targeted literature reviews (TLRs). The extracted data were then synthesized by pooling parameter values across publications, and summarized using the range of values across studies reporting each parameter and the median value from the most relevant study. Data were extracted and synthesized from 223 studies identified in the SLR and TLRs. Parameters frequently reported pertained to cervical cancer outcomes, while data for other anatomical locations were less available. The synthesis of the data provides a large volume of parameter values to inform HPV DTMs, such as annual progression rates from cervical intraepithelial neoplasia (CIN) 1 to CIN 2+ (median of highest quality estimate 0.0836), CIN 2 to CIN 3+ (0.0418), carcinoma in situ (CIS) 2 to local cancer+ (0.0396), and regional to distant cancer (0.0474). Our findings suggest that while there is a large body of evidence on cervical cancer, parameter values featured substantial heterogeneity across studies, and further studies are needed to better parametrize the non-cervical components of HPV DTMs.

Bartholin gland carcinoma is one of the less common histology accounting for 0.1 – 5 % of all vulvar malignancies and is mostly seen in postmenopausal women. It accounts for 0.001 % of all female malignancies. Clinical presentation is delayed to its deep-seated position in vulva. It has a propensity for frequent recurrences and distant metastases. Owing to the disease rarity, there are no well-defined management guidelines. We describe here the challenges in diagnosis and management of a case of adeno-squamous carcinoma of bartholin gland in a postmenopausal woman. Unlike the usual presentation, our case presented in an early stage with symptom of itching per vaginum. Radical surgery was the primary treatment modality with no requirement for adjuvant treatment and the patient is disease free at two years post treatment. However, adeno-squamous carcinoma of vulva has a propensity for perineural invasion and early nodal metastases and a dismal five-year survival.

Background: Lymph node metastasis in vulvar cancer is a critical prognostic factor associated with higher recurrence and decreased survival. A survival benefit is reported with adjuvant radiotherapy but with potential significant morbidity. We aim to clarify whether there is high-quality evidence to support the use of adjuvant radiotherapy in this setting. Objectives: The aim of the study was to assess the effectiveness and safety of adjuvant radiotherapy to locoregional metastatic nodal areas. Search Methods: We conducted a comprehensive and systematic literature search of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Google Scholar, ClinicalTrials.gov, and the National Cancer Institute. We considered only randomized controlled trials (RCTs). Main Results: We identified 1,760 records and finally retrieved only one eligible RCT (114 participants with positive inguinofemoral lymph nodes). All women had undergone radical vulvectomy and bilateral inguinal lymphadenectomy and had been randomized to adjuvant radiotherapy or to intraoperative ipsilateral pelvic lymphadenectomy without adjuvant radiotherapy. At 6 years, the overall survival (OS) was 51% versus 41% in favor of radiotherapy (HR 0.61; 95% CI 0.30--1.3) without significance and with very low certainty of evidence. At 6 year, the cumulative incidence of cancer-related deaths was 29% versus 51% in favor of adjuvant radiotherapy (HR 0.49; 95% CI 0.28--0.87). Recurrence-free survival at 6 years was 59% after adjuvant radiotherapy versus 48% after pelvic lymphadenectomy (HR 0.39; 95% CI 0.17--0.88). Three (5.3%) versus 13 (24.1%) groin recurrences were noted, respectively, in the adjuvant radiotherapy and pelvic lymphadenectomy groups. There was no significant difference in acute toxicities for pelvic lymphadenectomy compared to radiotherapy. In women with positive pelvic lymph nodes (20%), the OS at 6 year was 36% compared with 13% in favor of adjuvant radiotherapy. Late cutaneous toxicity rate appeared to be greater after radiotherapy (19% vs. 15%) but with less chronic lymphedema (16% vs. 22%). Conclusion: There is only very low-quality evidence on administering adjuvant radiotherapy for inguinal lymph node metastases. Although the identified study was a multicenter RCT, there was a reasonable imprecision and inconsistency because of small study numbers, wide confidence intervals in the data, and early trial closure, resulting in downgrading of the evidence. [ABSTRACT FROM AUTHOR]

Background: Data on the incidence and comorbidity of Lichen sclerosus (LS), based on validated nationwide population-based registries, remains scarce. Objective: To explore the incidence and association of comorbidities with LS in Sweden, emphasizing its potential links to malignancies and autoimmune disorders. Methods: A population-based retrospective open cohort study was conducted using the National Patient Register to identify all individuals diagnosed with LS (ICD-10 code L90.0) from 1 January 2001 to 1 January 2021. The study included 154,424 LS patients and a sex and age matched control group of 463,273 individuals to assess the incidence and odds ratios for various cancers and premalignant conditions. Results: The incidence of LS in Sweden was 80.9 per 100,000 person per year, with higher incidence in females (114.4) than in males (47.2). LS patients showed an increased odds ratio for vulvar cancer (OR = 8.3; 95% CI = 7.5–9.0), penile cancer (OR = 8.9; 95% CI = 7.3–11.0), prostate cancer (OR = 1.2; 95% CI = 1.1–1.2), testicular cancer (OR = 1.4; 95% CI = 1.1–1.7), bladder cancer (OR = 1.1; 95% CI = 1.1–1.2), breast cancer (OR = 1.4; 95% CI = 1.3–1.4), leukoplakia of the vulva (OR = 253.5; 95% CI = 221.9–289.6), and leukoplakia of the penis (OR = 5.1; 95% CI = 4.9–5.4). Conclusions: This study underscores the significantly increased association of various cancers and premalignant conditions in LS patients, highlighting the critical need for efficacious treatment and diligent follow-up. The association between LS and autoimmune diseases further necessitates comprehensive investigation to understand the underlying mechanisms and clinical management implications. Future research is essential to confirm these findings and elucidate the role of LS in cancer development. [ABSTRACT FROM AUTHOR]

Gender-affirming vaginoplasty (GAV) comprises the construction of a vulva and a neovaginal canal. Although technical nuances of vulvar construction vary between surgeons, vulvar construction is always performed using the homologous penile and scrotal tissues to construct the corresponding vulvar structures. Therefore, the main differentiating factor across gender-affirming vaginoplasty techniques is the tissue that is utilized to construct the neovaginal canal. These tissue types vary markedly in their availability, histology, and ease of harvest and have different advantages and disadvantages to their use as neovaginal lining. In this narrative review, the authors provide a comprehensive overview of the tissue types and associated operative approaches used for construction of the neovagina in GAV. Tissue choice is guided by several factors, such as histological similarity to natal vaginal mucosa, tissue availability, lubrication potential, additional donor site morbidity, and the specific goals of each patient. Skin is used to construct the neovagina in most cases with a combination of pedicled penile skin flaps and scrotal and extra-genital skin grafts. However, skin alternatives such as peritoneum and intestine are increasing in use. Peritoneum and intestine are emerging as options for primary vaginoplasty in cases of limited genital skin or revision vaginoplasty procedures. The increasing number of gender-affirming vaginoplasty procedures performed and the changing patient demographics from factors such as pubertal suppression have resulted in rapidly evolving indications for the use of these differing vaginoplasty techniques. This review sheds light on the use of less frequently utilized tissue types described for construction of the neovaginal canal, including mucosal tissues such as urethral and buccal mucosa, the tunica vaginalis, and dermal matrix allografts and xenografts. Although the body of evidence for each vaginoplasty technique is growing, there is a need for large prospective comparison studies of outcomes between these techniques and the tissue types used to line the neovaginal canal to better define indications and limitations. [ABSTRACT FROM AUTHOR]

Background: Evidence from observational studies suggested a connection between immune cells and gynecologic malignancies. To investigate potential causative associations between immunophenotype traits and gynecologic malignancies, we used a two-sample Mendelian randomization analysis. Methods: The genetic instrumental variables of 731 immunophenotypes of peripheral blood were obtained by the GWAS database; the GWAS data of common gynecologic cancers were obtained from FinnGen study. The main statistic method was the inverse-variance weighted method. We also used the weighted mode, weighted median, and MR Egger for evaluations. The MR Steiger directionality test was further used to ascertain the reverse causal relationship between immune cells and gynecologic cancers. Results: We identified 50 highly probable immunophenotypes and 65 possible ones associated with gynecologic malignancies. The majority of the B cell panel was protective factors in cervical cancer. However, there was a correlation found in the B cells panel with a probable factor associated with an elevated risk of endometrial cancer. Immunophenotypes in the monocyte panel were linked to a lower probability of ovarian cancer and vulvar cancer. All of the gynecologic cancers in our study had no statistically significant impact on immune cells, according to reverse MR analysis. Conclusion: Our study firstly emphasized the genetically predicted causality between immune cells and gynecologic malignancies. This knowledge will be critical to formulating the measures to prevent malignancies in female at risk in future clinical practice. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPVs) are responsible for approximately 5% of all cancers, with high-risk types causing nearly all cervical cancer cases. While cervical cancer is the most recognized outcome of HPV infection, the virus also contributes to vulvar, vaginal, penile, anal, and head and neck cancers. HPV types 16 and 18 are the primary culprits in these malignancies. HPVs exhibit strict host specificity and encompass over 100 types, some linked to benign conditions like genital warts. The viral oncoproteins E6 and E7 play a crucial role in cancer development by inhibiting tumor suppressor genes. HPV-related diseases manifest in various ways, from common conditions like anogenital and plantar warts to rare presentations such as recurrent respiratory papillomatosis, conjunctival papillomas, and middle ear carcinomas. The clinicians must recognize this diversity to ensure the accurate diagnosis and management. Preventive measures, particularly large-scale vaccination, are essential to reduce the incidence and complications of HPV-related diseases. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is a common sexually transmitted virus that can cause cervical cancer and other diseases. Dynamic transmission models (DTMs) have been developed to evaluate the health and economic impacts of HPV vaccination. These models typically include many parameters, such as natural history of the disease, transmission, demographic, behavioral, and screening. To ensure the accuracy of DTM projections, it is important to parameterize them with the best available evidence. This study aimed to identify and synthesize data needed to parametrize DTMs on the natural history of HPV infection and related diseases. Parameters describing data of interest were grouped by their anatomical location (genital warts, recurrent respiratory papillomatosis, and cervical, anal, vaginal, vulvar, head and neck, and penile cancers), and natural history (progression, regression, death, cure, recurrence, detection), and were identified through a systematic literature review (SLR) and complementary targeted literature reviews (TLRs). The extracted data were then synthesized by pooling parameter values across publications, and summarized using the range of values across studies reporting each parameter and the median value from the most relevant study. Data were extracted and synthesized from 223 studies identified in the SLR and TLRs. Parameters frequently reported pertained to cervical cancer outcomes, while data for other anatomical locations were less available. The synthesis of the data provides a large volume of parameter values to inform HPV DTMs, such as annual progression rates from cervical intraepithelial neoplasia (CIN) 1 to CIN 2+ (median of highest quality estimate 0.0836), CIN 2 to CIN 3+ (0.0418), carcinoma in situ (CIS) 2 to local cancer+ (0.0396), and regional to distant cancer (0.0474). Our findings suggest that while there is a large body of evidence on cervical cancer, parameter values featured substantial heterogeneity across studies, and further studies are needed to better parametrize the non-cervical components of HPV DTMs. [ABSTRACT FROM AUTHOR]

Gynecological cancer diagnosed during pregnancy requires accurate diagnosis and staging to determine optimal treatment based on gestational age. Cervical and ovarian cancers are the most common and multidisciplinary team collaboration is pivotal. Magnetic resonance imaging and ultrasound can be used without causing fetal harm. In cervical cancer, early‐stage treatments can often be delayed until fetal lung maturation and cesarean section is recommended if disease prevails, in combination with a simple/radical hysterectomy and lymphadenectomy. Chemoradiotherapy, the recommended treatment for advanced stages, is not compatible with pregnancy preservation. Most gestational ovarian cancers are diagnosed at an early stage and consist of nonepithelial cancers or borderline tumors. Removal of the affected adnexa during pregnancy is often necessary for diagnosis, though staging can be performed after delivery. In selected cases of advanced cervical and ovarian cancers, neoadjuvant chemotherapy may be an option to allow gestational advancement but only after thorough multidisciplinary discussions and counseling. [ABSTRACT FROM AUTHOR]

Introduction: Laparoendoscopic single-site inguinal lymphadenectomy (LESS-IL), a minimally invasive technique, has been reported in patients with vulvar or vaginal cancer regarding its safety and feasibility. However, the long-term outcomes, especially oncologic outcomes, are still lacking. We aimed to evaluate the long-term outcomes of LESS-IL to confirm its safety further. Patients and Methods: Data were prospectively collected from patients with vulvar or vaginal cancer who underwent LESS-IL at our institution between July 2018 and June 2021. The patients were followed up for at least 12 months. All procedures were performed according to treatment standards. Short- and long-term complications and oncologic outcomes were analysed. Results: A total of 16 patients undergoing 28 LESS-IL procedures were identified, amongst whom 4 underwent unilateral LESS-IL. The median numbers of excised groin lymph nodes were 9.0 (6.5-11.8) and 10.5 (8.3-12.0) in each left and right groin, respectively. Short-term complications occurred in 4 (25%) patients, including 18.7% lymphocele and 6.3% wound infection. Long-term complications regarding lower-limb lymphoedema appeared in 6 (37.5%) patients. Most short- and long-term complications were Clavien-Dindo 1 or 2, accounting for 90% of all post-operative issues. After a median follow-up of 27 (21.3-35.8) months, only 1 (6.3%) patient had isolated inguinal recurrence at 13 months postoperatively. No local or distant recurrence occurred. Conclusion: Our results suggest that LESS-IL is associated with little incidence of complications and promising oncologic outcomes, further demonstrating the safety and feasibility of the LESS-IL technique in patients requiring IL. [ABSTRACT FROM AUTHOR]

Background: Due to the lack of a large series of benign and malignant vulvar lesions, the features of dermoscopy are not well established. Objective: The aim of our study was to describe the epidemiological profile and the clinical and dermoscopic characteristics that may indicate malignancy or benignity in vulvar hyperpigmentation. Materials and Methods: From June 2020 to June 2023, we conducted a retrospective, prospective study involving 42 patients with 59 pigmented lesions. Results: The parallel, homogeneous, and globular patterns were observed in benign lesions (nevi, lentigo, melanosis). The cerebriform pattern was observed in seborrheic keratosis and Bowen's disease (BD). In cases of BD, we also observed white, structureless areas, glomerular vessels, a homogeneous brownishgray area, and brown dots. Conclusion: Good clinico-dermoscopic correlation should guide the diagnosis and management of pigmented vulvar lesions. Dermoscopy may be helpful in distinguishing between a benign lesion and a malignant lesion, yet in cases of doubt, a biopsy may be necessary. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) remains a global health concern because it contributes to the initiation of various HPV-associated cancers such as anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancer. In HPV-associated cancers, oncogenesis begins with an HPV infection, which is linked to the activation of the Janus protein tyrosine kinase (JAK)/STAT signaling pathway. Various STAT signaling pathways, such as STAT3 activation, have been well documented for their tumorigenic role, yet the role of STAT1 in tumor formation remains unclear. In the current study, STAT1−/− mice were used to investigate the role of STAT1 in the tumorigenesis of a spontaneous HPV E6/E7-expressing oral tumor model. Subsequently, our candidate HPV DNA vaccine CRT/E7 was administered to determine whether the STAT1−/− host preserves a therapeutic-responsive tumor microenvironment. The results indicated that STAT1−/− induces robust tumorigenesis, yet a controlled tumor response was attained upon CRT/E7 vaccination. Characterizing this treatment effect, immunological analysis found a higher percentage of circulating CD4+ and CD8+ T cells and tumor-specific cytotoxic T cells. In addition, a reduction in exhaustive lymphocyte activity was observed. Further analysis of a whole-cell tumor challenge affirmed these findings, as spontaneous tumor growth was more rapid in STAT1−/− mice. In conclusion, STAT1 deletion accelerates tumorigenesis, but STAT1−/− mice maintains immunocompetency in CRT/E7 treatments. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems. Patients with SLE are prone to a variety of malignancies, especially neoplasms of the female reproductive tract. Synchronous tumors, considered to involve multiple sites, are rare in the female reproductive tract. There are hardly any reports of SLE with synchronous reproductive tract tumors. Case presentation: We report the occurrence of two to three reproductive tract tumors in two women with SLE. A 52-year-old woman was diagnosed with vulvar cancer and cervical cancer. Another woman, aged 67, was diagnosed with concurrent vulvar cancer, vaginal cancer, and cervical cancer and also presented with a suspected lung cancer. Conclusion: The presence of synchronous tumors of the reproductive tract in patients with SLE is uncommon and can be easily disregarded. It is crucial to highlight that SLE patients with multiple primary malignancies exhibit notable late-stage presentation at the time of diagnosis, inadequate disease-free survival, poor overall survival, rapid progression rates, and mortality. Consequently, greater awareness must be raised regarding synchronous reproductive tract tumors in patients with SLE. Regular comprehensive cancer screening and management should be implemented for individuals diagnosed with SLE. [ABSTRACT FROM AUTHOR]

Background: Vulvar migration is a rare complication of filler injection for breast augmentation, generally presenting as repeated pain and fever. We will report a case of woman with polyacrylamide hydrogel breast injection develops vulvar abscess. Case presentation: A woman with a history of polyacrylamide hydrogel breast injection was noted to have vulvar abscess due to migration of filler materials. Filler removal surgery and vacuum sealing drainage was performed for this patient. The patient was discharged from the hospital with no further complications. After a review of pertinent literature, only four previous case reports are found. Local inflammatory response, infection, large volume injections, inframammary fold destruction, hematogenous or lymphatic migrate, trauma, gravity and external pressure could play essential parts in the migration of injected filler. Conclusion: Polyacrylamide hydrogel migration poses a worldwide challenge, necessitating personalized solutions. Our case study underscores the importance of comprehensive examinations for individuals with a history of filler breast injection when suspecting vulvar filler migration. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgery is the cornerstone in the treatment of most gynecological cancers and is associated with significant risks. Gynecological cancer patients are generally elderly, overweight, and have a sedentary lifestyle, which are all factors associated with surgical complications. Prehabilitation entails the optimizing of a patient's condition prior to surgery, and has been introduced with the goal of improving postoperative outcomes and recovery. A prehabilitation program has been implemented at an academic hospital in The Netherlands and comprises a physical exercise intervention, nutritional intervention, psychological intervention, and an intoxication cessation program. In this study, we assessed the feasibility of this program in terms of recruitment, adherence, and safety of implementation into the standard care of gynecological oncology patients. The principal finding was that the implementation of a prehabilitation program for gynecological oncology patients is feasible, with high recruitment and adherence rates. In addition, we did not encounter any major adverse events, suggesting its safety. Prehabilitation is an upcoming strategy to optimize patient's functional capacity, nutritional status, and psychosocial well-being in order to reduce surgical complications and enhance recovery. This study aims to assess the feasibility of implementing a multimodal prehabilitation program into the standard care of gynecological oncology patients at an academic hospital in terms of recruitment, adherence, and safety, which were assessed by the number of patients eligible, recruitment rate, participation rate, and adherence to individual modalities. Data were derived from the F4S PREHAB trial, a single-center stepped-wedge trial implementing a multimodal prehabilitation program among various surgical specialties. All patients undergoing elective surgery as part of treatment for ovarian, uterine, and vulvar cancer at the Radboudumc, an academic hospital in The Netherlands, between May 2022 and September 2023 were considered eligible for the F4S PREHAB trial and, consequently, were included in this cohort study. The multimodal prehabilitation program comprised a physical exercise intervention, nutritional intervention, psychological intervention, and an intoxication cessation program. A total of 152 patients were eligible and approached for participation of which 111 consented to participate, resulting in a recruitment rate of 73%. Participants attended an average of six exercise sessions and adhered to 85% of possible training sessions. Respectively, 93% and 98% of participants adhered to the prescribed daily protein and vitamin suppletion. Ten participants were referred to a psychologist and completed consultations. Out of nine active smokers, two managed to quit smoking. A total of 59% adhered to alcohol cessation advice. No adverse events were reported. This study demonstrates that introducing a multimodal prehabilitation program into the standard care of gynecological oncology patients is feasible in terms of recruitment and adherence, with no serious adverse events. [ABSTRACT FROM AUTHOR]

Introduction: Vulvar cancer is a rare gynecological cancer affecting mostly older women. The aim of this population‐based study was to investigate the incidence and net survival of vulvar cancer in Swedish women from 1960 to 2019. Material and methods: Data were retrieved from the mandatory Swedish Cancer Registry consisting of all women diagnosed with vulvar cancer between 1960 and 2019. Only women with a morphologically verified diagnosis of vulvar cancer were included. The individuals were then further matched with the Swedish Death Registry up until May 31, 2020. Results: In total, 8499 women were included with the following morphologies: squamous cell carcinoma 7250 (85.8%), malignant melanoma 539 (6.4%), adenocarcinoma 401 (4.8%) and other: 259 (3.1%). More than 50% of vulvar cancer cases occurred in women aged between 65 and 84 years of age. The 5‐year age‐standardized net survival increased from 53.0% (95% confidence interval [CI] 48.9–57.5) in 1960 to 72.1% (95% CI 68.8–75.5) in 2019. The proportion of adenocarcinoma among all cases increased from 2.0% to 8.7% between the 1960s and 2010s and an increase in age‐standardized 5‐year net survival was found for adenocarcinoma. Conclusions: The age‐standardized incidence of vulvar cancer cases in Sweden was stable between 1960 and 2019. During the study period, an increase in adenocarcinoma and a decrease in malignant melanoma cases was found. Five‐year net survival increased by 20 percent units during the study period. For squamous cell carcinoma, an increased age‐specific 5‐year net survival was observed for all age groups, apart for women aged ≥85. [ABSTRACT FROM AUTHOR]

Background: Palliative radiotherapy plays a crucial role in managing symptomatic gynecological cancers (GCs). This article aims to systematically review literature studies on palliative pelvic radiotherapy in cervical, endometrial, ovarian, vaginal, and vulvar cancers. The primary focus is centered around evaluating symptom relief, quality of life (QOL), and toxicity in order to ascertain optimal radiotherapy regimens. Methodology: For this thorough review, we mainly relied on Medline to gather papers published until November 2023. Selected studies specifically detailed symptomatology and QOL responses in palliative pelvic radiotherapy used for GCs. Results: Thirty-one studies, mostly retrospective studies and those lacking standardized outcome measures, showed varied responses. Encouraging outcomes were noted in managing hemorrhage (55%) and pain control (70%). However, comprehensively assessing overall symptom response rates and toxicity remained challenging. Investigations into 10 Gy fractionation revealed benefits in addressing tumor-related bleeding and pain in female genital tract cancers. Conclusions: Palliative pelvic radiotherapy effectively manages symptomatic GCs. Nonetheless, unresolved dosing and fractionation considerations warrant further investigation. Embracing modern therapies alongside radiotherapy offers improved symptom control, emphasizing the importance of selecting suitable patients for successful GC palliation interventions. [ABSTRACT FROM AUTHOR]

Introduction: Vulvar cancer carries a favourable prognosis in early stages. However, therapeutic options for advanced or recurrent cases are limited despite a variety of therapeutic modalities, such as extensive surgical resection, chemotherapy, and radiotherapy. The most important emerging treatment modalities are immune checkpoint inhibitors. This systematic review and meta-analysis aims to assess the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, in women with advanced vulvar cancer. Materials and methods: Following a comprehensive search, review, and appraisal, two relevant single-arm studies were included. Meta-analysis was conducted using R4.3.0 software and RStudio 2023.03.0, presenting the overall effect size with a 95% confidence interval. Heterogeneity was assessed using I² and the Cochrane Q Χ² statistics. Results: Out of 154 studies screened for eligibility, two single-arm studies involving 119 patients receiving pembrolizumab for advanced vulvar cancer were included. The pooled objective response rate (ORR) was overall 10% (95% CI: 0.00-0.84) and 9% (95% CI: 0.00-0.89) in the PD-L1 positive subgroup. In the intention-to-treat (ITT) population, 31% (95% CI: 0.04-0.85) exhibited any clinical benefit (complete response, partial response, or stable disease). In the ITT population at six months, progression-free survival (PFS) was 19% (95% CI: 0.01-0.82), and overall survival (OS) was 48% (95% CI: 0.08-0.90). At 12 months, PFS decreased to 9% (95% CI: 0.00-0.85), and OS was 33% (95% CI: 0.04-0.85). No statistically significant heterogeneity was observed in PFS and OS analyses. Discussion and conclusion: This study suggests that one-third of women with advanced or recurrent vulvar cancer may, without the influence of PD-L1 status, benefit from pembrolizumab treatment despite a decline in both PFS and OS at 12 months. These findings provide support for considering pembrolizumab in the treatment paradigm for this specific subset of cancer patients. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) encompasses a diverse array of viruses, comprising approximately 200 serotypes that affect humans. While the majority of HPV strains are associated with benign skin or mucous membrane growths, a subset is implicated in severe health conditions, such as cervical, anal, vulvar, and vaginal cancers. Despite the established effectiveness of HPV vaccines in preventing cervical and anal carcinomas in particular, their therapeutic potential in addressing cutaneous diseases linked to diverse HPV strains remains an intriguing area of investigation. This narrative review critically examines the existing literature to assess the viability of HPV immunization as a therapeutic intervention for prevalent cutaneous conditions. These include genital and extragenital cutaneous warts, epidermodysplasia verruciformis, and keratinocyte carcinomas. The findings suggest a promising dual role for HPV vaccines in preventing and treating dermatologic conditions while emphasizing future research directions, including the immunization perspective against β-HPVs. Moreover, the presence of conflicting study outcomes underscores the imperative for larger-scale, randomized trials with well-matched control groups to validate the efficacy of HPV immunization in the dermatologic context. This review contributes valuable insights into the evolving landscape of HPV-vaccine applications in the field of dermatology. [ABSTRACT FROM AUTHOR]

Abstract Objective To report the prevalence of malignant transformation of vulvar lichen sclerosus (VLS) and possible risk factors. Methods This is a cohort study with data analysis from medical records of 138 patients with histological diagnosis of VLS registered at the Vulvar Pathology Outpatient Clinic of the University Hospital, between 2007 and 2017. Predominance of risk factors was performed using logistic regression analysis. The variables studied were the length of follow-up, age, regular or irregular follow up; presence of symptoms (dyspareunia, pruritus and/or vulvar burning); histology characteristics, the presence of epithelial hyperplasia; and the presence of autoimmune diseases. Results There were 138 patients included in the study, and among them five progressed to malignant transformation. The patients had a median age of 59 years and 83% were symptomatic. The most frequent symptom was itching with 72%. Autoimmune diseases were present in 11.6%, the most prevalent being thyroid disease. All five case of malignant transformation (0.6%) had an irregular follow up. The logistic regression analysis was used among the studied variables, and no statistical significance was found among them (p ≥ 0.05). The relationship between hyperplasia and the clinical outcome of malignant transformation, in which non-significant but acceptable p value close to 0.05 was observed. Conclusion The prevalence of malignant transformation in patients with VLS was 0.6%, and common factors were the lack of adherence to medical treatments and the loss of follow-up.

The WHO’s initiative to eliminate cervical cancer by 2030 does not address the increasing incidence of vulvar, anal, and oropharyngeal cancers linked to high-risk HPV. Currently, the prevention of these three cancers faces various obstacles, such as a lack of specialized screening programs, well-defined management guidelines, and widespread public awareness. Without any interventions, the incidence of these three cancers will likely rise in the upcoming years, increasingly affecting younger individuals. We recommend expanding the WHO’s initiative to include vulvar, anal, and oropharyngeal cancers. This involves developing screening and management protocols similar to those for cervical cancer, implementing gender-neutral HPV vaccination programs, establishing clear referral pathways to specialized centers, promoting public awareness, and providing education to healthcare providers and high-risk individuals.

Objectives: Due to low incidence of vulvar cancer (VC), incidence and predictors for development of venous thromboembolism (VTE) are poorly understood. We examined incidence and risk factors associated with VTE in patients undergoing surgery for VC. Methods: We included patients who underwent surgery for VC from the National Surgical Quality Improvement Program database. VTE within the 30-day postoperative period was captured with Current Procedural Terminology codes. Baseline demographics and clinical characteristics were compared between patients with and without VTE. Univariable and multivariable-adjusted exact logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between risk factors and VTE. Results: We identified 1414 patients undergoing procedures for VC from the NSQIP database. Overall, 11 (0.8 %) patients developed VTE. Univariable predictors of VTE included surgery type [compared with simple vulvectomy: radical vulvectomy only (OR = 7.97, 95 % CI = 1.44, infinity) and radical vulvectomy plus unilateral IFN (OR = 15.98, 95 % CI = 2.70, infinity)], unplanned readmission (OR = 11.56, 95 % CI = 2.74, 46.38), deep surgical site infection (OR = 16.05, 95 % CI = 1.59–85.50), and preoperative thrombocytosis (OR = 6.53, 95 % CI = 0.00, 34.86). In a multivariable-adjusted model, longer operative time (≥72 min OR = 11.33, 95 % CI = 1.58–499.03) and preoperative functional status [compared with complete independence: total dependence (OR = 53.88, 95 % CI = 0.85, infinity) and partial dependence (OR = 53.88, 95 % CI = 0.85, infinity)] were associated with VTE. Conclusion: In this cohort of patients with VC undergoing radical vulvectomy, VTE incidence was low. Surgery type, longer operative time, dependent functional status, and wound disruption were identified as risk factors. Our findings highlight opportunities for prophylactic intervention in certain patients.

ObjectiveTo assess whether radiation completion within a planned timeframe in locally advanced squamous cell vulvar cancer impacts overall survival (OS).MethodsThe National Cancer Database from 2004 to 2017 was used to identify women ≥18 years old with stage II-IVA squamous cell vulvar cancer. We included women who received radiation alone (RT) or concurrent chemoradiation (CRT) for initial vulvar cancer treatment. Primary outcome was overall survival associated with time of delay in radiation completion.ResultsThere were 2378 women identified (n = 856 RT and n = 1522 CRT). Median age was 67 (IQR 56-78), majority (88.35%) were white with advanced stage III or IVA (72.29%) disease. Median radiation dose was 5720 c-Gray (IQR 5040-6300). Radiation completion with delay ≥7 days resulted in reduction in survival compared to delay of

Steatocystoma multiplex is a benign disorder involving the pilosebaceous unit, characterised by the presence of numerous cutaneous cystic lesions in the dermis. While cases with random occurrence are commonly observed, the condition can also be transmitted genetically in an autosomal dominant fashion. The lesions are frequently seen in body parts with a high number of pilosebaceous units including the axillae, scalp, trunk, thighs, arms, and less frequently occurring on the genitals and breasts. Hereby, the authors present a case report of a 48-year-old female who presented to the Outpatient Department of Dermatology with multiple asymptomatic swellings on her vulva since nine years. On physical examination, the swellings were noted to be calcified nodules. These nodules were excised and sent for histopathological analysis that revealed the diagnosis of steatocystoma multiplex. Steatocystoma multiplex can occur as sporadic, familial, or as a part of a syndrome. Although the lesions themselves are symptomless, their presence in the genital region makes walking difficult, thereby hampering routine work and adversely affecting the quality of life of the patient. There is also a need to educate patients regarding its benign nature and possible treatment options. Hence, the present case report aimes to emphasise the importance of its early identification, diagnosis, and to raise awareness among general practitioners. [ABSTRACT FROM AUTHOR]

Purpose of the study. Studying the relative copy number of 12 genes: MYC, PTEN, CCND1, PIK3CA, TP53, CDKN2A, MDM2, MCL1, NFKBIA, MTAP, BIRC2, KMT2C, to search for potential prognostic cancer markers in vulvar cancer (VR).Patients and methods. The study included 50 patients aged 29–80 years with the diagnosis of squamous cell carcinoma of the vulva without metastases – group 1 (n = 25) and with metastases to the lymph nodes – group 2 (n = 25). Total DNA from paraffin blocks of tumor and conditionally healthy vulvar tissue served as the material for the study. The relative copy number of genes (RCQ) was assessed using the RT-qPCR method: MYC, PTEN, CCND1, PIK3CA, TP53, CDKN2A, MDM2, MCL1, NFKBIA, MTAP, BIRC2, KMT2C and reference genes: GAPDH and B2M. Raw RT-qPCR data were analyzed using Bio-Rad CFX Manager software (ver. 2.1). RCQ of the genetic locus was calculated using the formula 2-ΔCt. Analysis of the significance of differences included determination of the OR (CI 95 %), Chi-square, Mann-Whitney U-test. Differences were considered statistically significant at p < 0.05.Results. Amplification was observed for 9 genes: MYC (48 % of cases), MCL1 (39 %), NFKBIA (46 %), CCND1 (52 %), PIK3CA (48 %), TP53 (62 %), MDM2 (40 %), BIRC2 (54 %), KMT2C (42 %); losses were recorded for 3 genes PTEN (44 % of cases), MTAP (32 %), CDKN2A (36 %). In the 2nd group of patients, a statistically significant 1.7-fold increase in RCQ of the CCND1 gene (p < 0.05) and a 1.9-fold decrease in RCQ of the PTEN gene (p < 0.05) were found.Conclusion. In the study, CCND1 amplification events and/or PTEN loss were associated with lymph node metastasis in RV patients. Thus, the copy numbers of these genes may serve as prognostic markers of the disease.

Introduction: The etiology and clinical presentation of vulvar carcinomas, especially vulvar lesions, are not fully understood. Because the vulva and cervix are anatomically connected, human papillomavirus (HPV) is the main cause of cervical lesions. Thus, this study explored the potential characteristics and effects of specific HPV infection types across vulvar lesions and concurrent cervical lesions. Methods: This retrospective, cross-sectional study analyzed patients with cervical HPV or cytological results and concurrent vulvar biopsy who were seen in our hospital colposcopy clinic in Shanxi Province, China, between 2013 and 2023. Data on age, menopause status, vulvar manifestations, and cytology and HPV infection testing results were collected. Attributable fractions and multinominal logistic models were used to evaluate HPV genotyping and clinical characteristics across vulvar lesions. Results: Among the 1,027 participants, 83 (8.1%) had vulvar intraepithelial neoplasia (VIN) of high grade or worse (VIN2+), and 127 (12.4%) had nonneoplastic epithelial disorders of the vulva (NNEDV). A total of 175 patients had either VIN2+ or cervical intraepithelial neoplasia (CIN) lesions of grade 2 or worse (CIN2+). The most common HPV genotypes for VIN2+ or concurrent VIN2+/CIN2+ were HPV16, HPV52, and HPV58, although attributable fractions differed among lesions. Patients with normal cytological or histopathological result were more likely to have NNEDV detected, while abnormal cervical diagnosis was associated with higher detection of VIN2+. Multinominal logistic modeling showed that age and HPV16 infection were risk factors for VIN2+ or concurrent VIN2+/CIN2+; however, only vulvar presentation with depigmentation was a risk factor for NNEDV. Among patients with low-grade CIN1/VIN1, compared with those who were HPV16 negative, those who were HPV16 positive were at 6.63-fold higher risk of VIN2+/CIN2+ [95% confidence interval (CI): 3.32, 13.21]. Vulvar depigmentation was also associated with increased risk of NNEDV (odds ratio: 9.98; 95% CI: 3.02, 33.04). Conclusions: Chinese women may be at specific, high risk for HPV infection types associated with VIN or CIN. The use of cervical cell HPV detection along with vulvar presentation during cervical cancer screening may also contribute to vulvar lesion detection. [ABSTRACT FROM AUTHOR]