Vulvar Cancer Research Articles

Intersecting Pathologies: Vulvar Cancer Complicated by a Fusobacterium necrophorum Infection

Intersecting Pathologies: Vulvar Cancer Complicated by a Fusobacterium necrophorum Infection

Comparison of different histomorphological grading systems in vulvar squamous cell carcinoma.

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. 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. 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. 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.

Ultrasound assessment of lymph nodes for staging of gynecological cancer: consensus opinion on terminology and examination technique.

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.

The relationship between the vaginal and vulvar microbiomes and lichen sclerosus symptoms in post-menopausal women

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.

Systemic hormone therapy after breast and gynecological cancers: an Italian expert group consensus opinion.

The 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.

Precancerous Lesions of HPV-independent Vulvar Squamous Cell Carcinoma: Clinicopathologic Consideration of an Evolving Spectrum.

HPV-independent squamous cell carcinomas of the vulva comprise the majority of vulvar cancers, but their putative precancers represent only a small proportion of the vulvar squamous intraepithelial lesions that are encountered in routine practice. The precancerous lesions of HPV-independent vulvar squamous cell carcinoma encompass a spectrum of lesions that, collectively, may pose significant diagnostic challenges. Included in this spectrum are differentiated vulvar intraepithelial neoplasia [dVIN], the prototypical lesion of the group, which is characterized by a high propensity for progression, a relatively short duration to progression, frequent association with lichen sclerosus, and according to our review of the recent literature, TP53/p53 aberration in 50% to 95% (mean 77.4%) of cases. Regarding the latter, some authors consider TP53/p53 aberration to be a diagnostic requirement for dVIN, although this is controversial, as discussed further herein. Also included in the spectrum of lesions that are considered in this review are possibly related HPV-independent, p53-wild type lesions that have historically been reported as "vulvar acanthosis with altered differentiation" (VAAD), "differentiated exophytic vulvar intraepithelial lesion" (DEVIL), "verruciform lichen simplex chronicus" (vLSC), and which more recently, have collectively been described as "verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN)" or "vulvar aberrant maturation (VAM)." In this review, we perform a comprehensive clinicopathologic review of putative precancerous lesions of HPV-independent squamous cell carcinomas of the vulva, with an emphasis on recent developments in terminology, practical diagnostic issues, biomarkers, and pathogenesis.

Outcomes of groin recurrence in vulvar cancer after primary treatment with a sentinel lymph node procedure

Outcomes of groin recurrence in vulvar cancer after primary treatment with a sentinel lymph node procedure

Role of Vitamin D in Gynecological Cancer: State of the Art

: Vitamin D and Vitamin D Receptors have gained more importance beyond their roles in bone metabolism and calcium homeostasis. Several epidemiological studies have confirmed that vitamin D has a specific function in a wide variety of gynecological cancers, such as ovarian cancer, endometrial cancer, cervical cancer, uterine fibroid, and vulvar cancer. The different anti-cancer mechanisms exerted by vitamin D on tumor cells are cell proliferation, cancer progression, angiogenesis, cell cycle arrest, and inflammation. The role of vitamin D is well emphasized in ovarian cancer and uterine fibroids, with limited studies available on cervical cancer and other types of gynecological cancers. Overall, most epidemiological data support that inadequate or low levels of vitamin D in the circulation are associated with risk and poor prognosis in several types of gynecological cancer. It is evident that vitamin D plays a prominent role as an anticancer agent against numerous types of cancer. This review focuses on the etiology and role of vitamin D and the Vitamin D Receptor in various types of gynecological cancer, as well as the mechanism of Vitamin D and its metabolites in the management of gynecological cancer.

A retrospective analysis of the social determinants of health and impact on overall survival among patients with vulvar cancer

A retrospective analysis of the social determinants of health and impact on overall survival among patients with vulvar cancer

Vulvar squamous cell carcinoma: The role of p53 and p16 immunohistochemistry

Vulvar squamous cell carcinomas (SCC) represent a heterogeneous group of patients with implications for prognosis and response to treatment. Human papillomavirus (HPV)-associated SCC is characterised by p16 positivity, whereas non-HPV SCC often shows aberrant p53 expression. We conducted a retrospective analysis involving 148 patients with vulvar SCC from two Gynecologic Oncology units from Sydney, Australia. Patients’ demographics, tumor characteristics, types of treatment and survival were analyzed and compared to p16 and p53 immunohistochemistry status. The p16-positive group was younger and included a higher prevalence of smokers, while the p53-positive group demonstrated greater comorbidity indices and was associated with tumor features that are independently related to poor prognosis. Compared to p16-positive patients our study has shown significantly higher recurrence rates and lower overall survival in the p53-positive group. Our findings support existing literature, emphasizing the prognostic significance of p16 and p53 in vulvar SCC. Despite the retrospective nature and variations in immunohistochemistry reporting, our study provides valuable insights into patient outcomes, particularly in a demographically diverse population. Future research, like the STRIVE trial, may determine if implementation of p16 and p53 stratified management algorithm will improve outcomes for women with vulvar SCC (McAlpine, 2024).

The role of circulating tumor DNA in the management of vulvar carcinoma with radiation therapy: A preliminary report

The role of circulating tumor DNA in the management of vulvar carcinoma with radiation therapy: A preliminary report

Environmental exposures and the incidence of vulvar carcinoma in the western Pennsylvania catchment area

Environmental exposures and the incidence of vulvar carcinoma in the western Pennsylvania catchment area

Revisiting the benefit of radiosensitizing chemotherapy for older patients with locally advanced vulvar cancer receiving definitive radiotherapy

Revisiting the benefit of radiosensitizing chemotherapy for older patients with locally advanced vulvar cancer receiving definitive radiotherapy

Outcomes of low-volume metastatic disease among patients with early-stage squamous cell carcinoma undergoing sentinel lymph node biopsy: Results from the International Vulvar Cancer Consortium (IVUCCO)

Outcomes of low-volume metastatic disease among patients with early-stage squamous cell carcinoma undergoing sentinel lymph node biopsy: Results from the International Vulvar Cancer Consortium (IVUCCO)

Disparity in vulvar cancer survival between rural, urban, and metropolitan residence: A National Cancer Database analysis, 2012–2019

Disparity in vulvar cancer survival between rural, urban, and metropolitan residence: A National Cancer Database analysis, 2012–2019

Pre-clinical investigation of a novel investigational new drug, SHetA2, for the treatment of vulvar cancer

Pre-clinical investigation of a novel investigational new drug, SHetA2, for the treatment of vulvar cancer

Immune-related adverse events in metastatic/recurrent cervical and vulvar cancer associated with a significant survival advantage

Immune-related adverse events in metastatic/recurrent cervical and vulvar cancer associated with a significant survival advantage

Advances in Vulvar Cancer Biology and Management.

Vulvar squamous cell carcinoma (VSCC), a rare gynecologic malignancy, has been rising in incidence. Molecular classification on the basis of human papilloma virus (HPV) and tumor protein 53 (p53) status has identified three clinically distinct subtypes, but we still treat all VSCCs the same. Here, we review molecular classification of VSCC, outline treatment landscape, and highlight potential for targeted therapies in advanced VSCC. We conducted a comprehensive review of the literature on treatment of advanced VSCC with particular focus on the implications of molecular stratification on the basis of HPV and p53 status on the treatment landscape of advanced VSCC. Incorporation of HPV and p53 status in locoregional treatment decision making has the potential to advise (de)escalation strategies. The role of immunotherapy, alone and in combination, requires further exploration particularly earlier in the course of the disease. In advanced stages, potential for targeted therapies in VSCCs include inhibitors of vascular endothelial growth factor, endothelial growth factor receptor, cell cycle, and DNA damage response, particularly in HPV-negative (HPV-) VSCCs. Targeting the phosphoinositide 3 kinase/mammalian target of rapamycin pathway is attractive in HPV-positive and HPV-/p53 wildtype VSCCs. Trials incorporating antibody-drug conjugates (eg, trophoblast cell-surface antigen 2, human epidermal growth factor receptor 2) should be considered, and basket trials in perineal squamous cell cancers are warranted. Preclinical models are limited and should be expanded to inform trial design. Like other rare cancers, vulvar cancer lags behind in the identification and optimization of precision medicine strategies. Molecular-based preclinical models and rationally designed clinical trials, incorporating high-quality translational studies, are urgently required. These trials will require international collaboration to ensure feasibility and improvement of outcomes for women diagnosed with this disease.

Utilization of miRNAs as Biomarkers for the Diagnosis, Prognosis, and Metastasis in Gynecological Malignancies.

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.

PATHOMORPHOLOGICAL AND PATHOHISTOLOGICAL CHARACTERISTICS OF PRIMARY VULVAR CARCINOMA

The purpose of the study was to determine pathomorphological and pathohistological characteristics of primary vulvar carcinoma. Materials, methods, and study design: A retro- and prospective comprehensive morphological study of 117 patients was conducted at Bondar Regional Cancer Research Center (Donetsk) over the period from 2002 to 2019. Out of 117 we identified 44 patients with primary vulvar cancer without previous inflammatory diseases (cancer de novo). The materials were fixed in formalin and examined using standard methods of histological staining and morphometry. Statistical analysis methods were used to process the data. Results and Discussion: The differentiated VIN type occurred in 61.2% of cases, the undifferentiated type – in 37.8%. VIN1 was characterized by basal cell hyperplasia, VIN2 – by abnormal vertical anisomorphy, VIN3 – by significant abnormal cell stratification and differentiation. Cell proliferative activity increased with VIN severity, with the highest mitotic index and nuclear-cytoplasmic ratio in VIN3. In VIN1, a positive reaction to nuclear proliferation antigen was observed in the lower third of the epithelial layer. In VIN2 and VIN3, the positive reaction covered most of the epithelium. Well-differentiated SCC (G1) was characterized by polymorphic cell complexes with a small number of pathological mitoses and apoptosis. Moderately differentiated SCC (G2) had a pronounced inflammatory reaction and necrosis, with disruption of the basement membrane. Poorly differentiated SCC (G3) demonstrated loss of vertical anisomorphy, high mitotic index and presence of tumor emboli in vessels. Conclusions: The study showed significant differences in the morphological and morphometric characteristics of different types of VIN and invasive vulvar carcinoma. The results will help to improve the diagnosis and treatment of primary vulvar cancer, especially in understanding its pathogenesis and prognostic factors.