Implementation of quality indicators for vulvar cancer in gynaecological cancer centres certified by the German Cancer Society (DKG).

PURPOSE: In 2018, the first guideline-based quality indicators (QI) for vulvar cancer were implemented in the data-sheets of certified gynaecological cancer centres. The certification process includes guideline-based QIs as a fundamental component. These indicators are specifically designed to evaluate the level of care provided within the centres. This article aims to give an overview of the developing process of guideline based-QIs for women with vulvar cancer and presents the QIs results from the certified gynaecological cancer centres. METHODS: The QIs were derived in a standardized multiple step process during the update of the 2015 S2k guideline "Diagnosis, Therapy, and Follow-Up Care of Vulvar Cancer and its Precursors" (registry-number: no. 015/059) and are based on strong recommendations. RESULTS: In total, there are eight guideline-based QIs for vulvar cancer. Four QIs are part of the certification process. In the treatment year 2021, 2.466 cases of vulvar cancer were treated in 177 centres. The target values in the centres for pathology reports on tumour resection and lymphadenectomy as well as sentinel lymph nodes have increased since the beginning of the certification process and have been above 90% over the past three treatment years (2019-2021). DISCUSSION: QIs based on strong guideline recommendations, play a crucial role in measuring and allowing to quantify essential aspects of patient care. By utilizing QIs, centres are able to identify areas for process optimization and draw informed conclusions. Over the years the quality of treatment of vulvar cancer patients measured by the QIs was improved. The certification system is continuously reviewed to enhance patient care even further by using the outcomes from QIs revaluation.

Treatment of vulvar cancer recurrence with electrochemotherapy: a case-control study.

BACKGROUND: Electrochemotherapy (ECT) is a combined treatment method based on electroporation and simultaneous chemotherapy. In cases where radiotherapy has previously been used, surgery is often the only treatment option for vulvar cancer recurrence with potential resection of clitoris, vagina, urethra or anal sphincter. The unique advantage of ECT is its selectivity for cancer cells while sparing the surrounding healthy tissue. The aim of the study was to compare the ECT treatment of vulvar cancer recurrence for non-palliative purposes with surgical treatment. MATERIALS AND METHODS: Eleven patients with single vulvar cancer recurrence were treated with ECT and followed up for 12 months. As a control group, 15 patients with single vulvar cancer recurrence were treated with wide local excision. The following data were collected, analyzed and compared: Age, body mass index, comorbidities, histological type, location and size of vulvar cancer recurrence, treatment history, details of procedures and hospital stay. RESULTS: The probability curves for local tumor control did not differ between the ECT group and the surgical group (p = 0.694). The mean hospital stay and the mean duration of procedure were statistically significantly shorter in the ECT group (p < 0.001). There were no statistically significant differences between the ECT and surgical groups in terms of mean body mass index, associated diseases, previous treatments, presence of lichen sclerosus, p16 status, gradus, anatomical site of the tumor, and type of anesthesia. CONCLUSION: In this case-control study, treatment of vulvar cancer recurrence with ECT for non-palliative purposes was comparable to surgical treatment in terms of effectiveness. The results need to be confirmed in larger randomized trials.

Antibodies against high-risk human papillomavirus proteins as markers for noncervical HPV-related cancers in a Black South African population, according to HIV status.

Human papillomavirus (HPV) proteins may elicit antibody responses in the process toward HPV-related malignancy. However, HPV seroepidemiology in noncervical HPV-related cancers remains poorly understood, particularly in populations with a high prevalence of human immunodeficiency virus (HIV). Using a glutathione S-transferase-based multiplex serology assay, antibodies against E6, E7 and L1 proteins of HPV16 and HPV18 were measured in sera of 535 cases of noncervical HPV-related cancers (anal (n = 104), vulval (n = 211), vaginal (n = 49), penile (n = 37) and oropharyngeal (n = 134)) and 6651 non-infection-related cancer controls, from the Johannesburg Cancer Study that recruited Black South African with newly diagnosed cancer between 1995 and 2016. Logistic and Poisson regression models were used to calculate adjusted odds ratios (aOR) and prevalence ratios (aPR) and 95% confidence intervals (CI) in cases versus controls. HPV16 E6 was more strongly associated with noncervical HPV-related cancers than HPV16 L1 or E7, or HPV18 proteins: anal (females (HPV16 E6 aOR = 11.50;95%CI:6.0-22.2), males (aOR = 10.12;95%CI:4.9-20.8), vulval (aOR = 11.69;95%CI:7.9-17.2), vaginal (aOR = 10.26;95%CI:5.0-21), penile (aOR = 18.95;95%CI:8.9-40), and oropharyngeal (females (aOR = 8.95;95%CI:2.9-27.5), males (aOR = 3.49;95%CI:1.8-7.0)) cancers. HPV16-E6 seropositivity ranged from 24.0% to 35.1% in anal, vulval, vaginal and penile cancer but was significantly lower (11.2%) in oropharyngeal cancer. After adjustment for HIV, prevalence of which increased from 22.2% in 1995-2005 to 54.1% in 2010-2016, HPV16 E6 seropositivity increased by period of diagnosis (aPR for 2010-2016 vs. 1995-2006 = 1.84;95%CI:1.1-3.0). Assuming HPV16 E6 seroprevalence reflects HPV attributable fraction, the proportion of certain noncervical-HPV-related cancers caused by HPV is increasing over time in South Africa. This is expected to be driven by the increasing influence of HIV.

Case report: Primary vulvar adenocarcinoma of mammary gland type-its genetic characteristics by focused next-generation sequencing.

Mammary-like vulvar adenocarcinoma (MLVA) is an exceedingly rare subtype of vulvar adenocarcinoma that shares features with mammary gland tissue. Due to its rarity and lack of consensus, MLVA presents diagnostic challenges to pathologists. We present the case of a 59-year-old female with an ulcerated mass on the right side of the external genitalia, diagnosed as MLVA. Comprehensive immunohistochemistry (IHC) and gene sequencing studies were performed to characterize the tumor. IHC analysis revealed triple expression of hormonal receptors (estrogen receptor, progesterone receptor, and HER2), supporting the mammary gland origin of the tumor. Gene sequencing identified unique genetic mutations associated with the expression of hormonal markers. One fusion gene (ERBB2-NAGLU) has not been reported in any tumors, and other mutations with unique mutation types have not been previously reported in MLVA. Our findings shed light on the molecular characteristics of MLV and may help improve the diagnosis and treatment of this rare type of vulvar adenocarcinoma.

Vulvar leiomyoma in a postmenopausal woman.

Leiomyomas of the uterus are the most common benign tumours of women in the reproductive age group, affecting up to 40%-50% of women older than 35. In postmenopausal women, the incidence is much lower with an estimated incidence of 1%-2% in women in the 60-80 years old age group. Vulvar leiomyomas are much rarer than their uterine counterparts, accounting for only 0.03% of all gynaecological neoplasms and 0.07% of all vulvar tumours. These tumours are well-circumscribed, painless, solitary growths that affect females of all ages. Given the presentation and rarity of vulvar leiomyomas, they are often misdiagnosed as a Bartholin gland cyst, abscess or even cancer preoperatively. We present a case of a woman in her 70s with a 1.5 cm firm mass that was palpated on the left lower vaginal side wall and was initially suspected to be a Bartholin gland cyst or abscess. Initial treatment included antibiotics and an incision and drainage. Two weeks later, the mass had grown to 3 cm in size. Wide excisional biopsy revealed the mass to be a vulvar leiomyoma.

Incidence and Risk Factors for Recurrence and Progression of HPV-Independent Vulvar Intraepithelial Neoplasia.

OBJECTIVES: Human papillomavirus (HPV)-independent vulvar intraepithelial neoplasia (VIN) is a rare yet aggressive precursor lesion of vulvar cancer. Our objectives were to estimate its long-term incidence, the risk of recurrent disease and progression to vulvar cancer, and risk factors thereof. MATERIALS AND METHODS: Patients with HPV-independent VIN between 1991 and 2019 in a selected region were identified from the Dutch Nationwide Pathology Databank (Palga). Data were collected from the pathology reports. Crude and European age-standardized incidence rates were calculated for 10-year periods. Kaplan-Meier analyses were performed to determine the cumulative recurrence and cancer incidence, followed by Cox regression analyses to identify associated risk factors. RESULTS: A total of 114 patients were diagnosed with solitary HPV-independent VIN without prior or concurrent vulvar cancer. The European age-standardized incidence rate increased from 0.09 to 0.69 per 100,000 women-years between 1991-2010 and 2011-2019. A cumulative recurrence and cancer incidence of 29% and 46% were found after 8 and 13 years of follow-up, respectively. Nonradical surgery was identified as the only independent risk factor for recurrent HPV-independent VIN. Risk factors associated with progression to cancer were increasing age and a mutant p53 immunohistochemical staining pattern. CONCLUSIONS: The incidence of detected HPV-independent VIN has substantially increased the last decade and the subsequent recurrence and vulvar cancer risks are high. Although HPV-independent VIN may present as a wide morphologic spectrum, surgical treatment should aim for negative resection margins followed by close surveillance, especially for p53 mutant lesions.

Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget's disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.

Update on the Sentinel Node Procedure in Vulvar Cancer.

Early-stage vulvar cancer is managed by a local excision of the primary tumor and, if indicated, a sentinel node (SN) biopsy to assess the need for further groin treatment. With the SN procedure, many patients can be treated less radically and will experience less complications and morbidity compared with an inguinofemoral lymphadenectomy (IFL). Still, the SN procedure can be further optimized. Different tracers for detecting the SN are being investigated, aiming to optimize detection rates and decrease the burden of the procedure and short-term complications. Until now, no standardized protocols exist for the pathologic workup of the SN, possibly leading to discrepancies in detection of metastases between institutes using different methods. New techniques, such as one-step nucleic amplification, seem to have potential in accurately detecting metastases in other cancers, but have not yet been investigated in vulvar squamous cell carcinoma (VSCC). Furthermore, several studies have investigated the possibility to broaden the indications for the SN procedure, such as its use in recurrent disease, larger tumors, or multifocal tumors. Although these studies show encouraging results, cohorts are small and further studies are needed. Prospective studies are currently investigating these subgroups. Lastly, several studies investigated optimization of groin treatment of patients with a metastatic SN. Inguinofemoral radiotherapy is a good alternative to IFL in patients with micrometastases in the SN, with comparable efficacy and less treatment-related morbidity. Reduction of the radicality of groin treatment is also possible in other ways, such as omitting contralateral IFL in patients with lateralized tumors and a unilateral metastatic SN. In conclusion, the SN procedure is an established procedure in early-stage VSCC, although optimization of the technique, pathologic workup, indications, and treatment in the setting of metastatic disease are the subject of ongoing research.

Differentiated vulvar intraepithelial neoplasia long-term follow up and prognostic factors: An analysis of a large historical cohort.

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.

Large vulvar fibroepithelial polyp and review of differentials.

Vulval fibroepithelial polyps (FEPs) are a rare type of vulval fibroblastic tumour commonly found in premenopausal women. It is important to obtain an accurate pathological diagnosis because, despite being benign, the condition shares some characteristics with malignant vulva lesions in its differential diagnosis. We present a case of young woman in her 20s with a giant FEP. After surgical excision, the patient did not manifest any signs of recurrence after 1-year follow-up. Our review focuses on the distinguishing characteristics of these rare neoplasms as we explore their differential diagnosis.

Recurrent ectopic primary breast adenocarcinoma of the vulva with a 19-year follow-up period.

We present a case of an ectopic breast adenocarcinoma of the vulva with metastatic local recurrence and a total follow-up period of 19 years, the longest documented in the literature to our knowledge. Following surgical excision, radiation therapy and hormonal treatment after the recurrence, the patient has remained disease free. This case demonstrates the potential for malignant transformation in accessory breast tissue and highlights the importance of close surveillance and regular physical examinations in patients with a history of ectopic breast malignancy.

A pilot study of p53 immunohistochemistry in atypical squamous lesions, using a vulvar scoring system.

BACKGROUND: Histopathologic overlap between cutaneous squamous cell carcinoma (cSCC) and its indolent mimics likely leads to the overdiagnosis of cSCC. OBJECTIVE: To perform a pilot study of the p53 immunohistochemical scoring system developed on vulvar squamous lesions in cSCC. METHODS: The consistency and reliability of p53 immunostaining using a scoring system developed on vulvar cases, as compared with TP53 genomic sequencing, was studied in an initial cohort of 28 cutaneous cases. p53 labeling was further assessed in an additional 63 cases of atypical squamous lesions, including 20 atypical squamous lesions classified by the authors as benign, 22 cases diagnosed as cSCC without high-risk features, and 21 cases of high-risk cSCC (cSCC-HR). RESULTS: The concordance of p53 labeling and TP53 sequencing was 82.1%. Four positive patterns of p53 mutation were identified: basal, parabasal/diffuse, null, and cytoplasmic. p53 positivity in atypical, benign squamous lesions (10%) was significantly lower than that of low-risk cSCC (63.6%, p = 0.0004) or cSCC-HR (90.5%, p < 0.0001). p53 positivity in low-risk cSCC versus cSCC-HR was not statistically significant (p = 0.07). CONCLUSION: p53 Labeling may be a helpful biomarker to support the diagnosis of cSCC and distinguish cSCC from atypical but benign mimics.

The risk of vaginal, vulvar and anal precancer and cancer according to high-risk HPV status in cervical cytology samples.

High-risk human papillomavirus (hrHPV) is the cause of virtually all cervical cancers, most vaginal and anal cancers, and some vulvar cancer cases. With HPV testing becoming the primary screening method for cervical cancer, understanding the link between cervical hrHPV infection and the risk of other anogenital cancers is crucial. We assessed the risk of vulvar, vaginal and anal cancer and precancer (VIN2+, VaIN2+ and AIN2+) in a prospective cohort study including 455,349 women who underwent cervical hrHPV testing in Denmark from 2005 to 2020. We employed Cox proportional hazard models, adjusting for age, calendar year and HPV vaccination status, and estimated hazard ratios (HRs) and 95% confidence intervals (CI). We used the Aalen Johansen estimator to calculate the absolute risks of VIN2+, VaIN2+ and AIN2+. In total, 15% of the women were hrHPV positive at baseline. A positive cervical hrHPV test was associated with increased incidence of vulvar, vaginal and anal squamous cell carcinoma (SCC). Five-year risk estimates of VIN2+, VaIN2+ and AIN2+ among hrHPV-positive women (0.45%, 0.14% and 0.12%) were higher than among hrHPV-negative women (0.14%, 0.01% and 0.05%). Particularly high risk was observed among the hrHPV-positive women of the oldest age, with a history of anogenital precancer and those not HPV vaccinated. In conclusion, our study confirms the association between cervical hrHPV infection and non-cervical anogenital precancers and cancers. Currently, no established risk threshold or guidelines for follow-up. As HPV testing becomes the primary method for cervical cancer screening, future data will help define high-risk groups and acceptable risk thresholds.

Evaluation of the impact of a protocol for immediate vulvar reconstruction after vulvectomy.

Vulvar cancers are usually diagnosed at an advanced stage and require wide surgical resections in the form of vulvectomy. Immediate vulvar reconstruction can potentially reduce the reoperation rate and postoperative complications. With this objective, we introduced a protocol for immediate vulvar reconstruction. This study, five years after its introduction, assesses the impact of this intervention on the postoperative evolution of vulvectomy patients. In January 2017 we introduced a protocol for immediate vulvar reconstruction that considered four criteria of high risk for postoperative dehiscence. Patients who meet the criteria were reconstructed at the time of the vulvectomy. To assess the impact of the protocol, we prospectively registered all included patients over a 5 years period (2017-2022). As a control group, we reviewed the vulvectomised patients at our centre from January 2012 to January 2017 (5 years) who would have met the protocol. No statistically significant differences were found in the epidemiological data (age, diabetes mellitus diagnosis, and obesity diagnosis) or in the tumour characteristics (tumour size). We obtained a statistically significant difference in the incidence of complications and need for reintervention, in favour of the reconstruction group. Our study shows the medical and economic benefits for vulvar cancer patients of immediate vulvar reconstruction.

Primary vulvar adenocarcinoma of intestinal type: Report of two cases showing molecular similarity with colorectal adenocarcinoma.

Primary vulvar adenocarcinoma is a particularly rare tumor with poorly understood histogenesis and unclear clinical characteristics and prognosis. Vulvar adenocarcinoma of intestinal type (VAIt) is a very uncommon subtype of primary vulvar adenocarcinoma and only 27 cases have been described in the literature in the past. Of these cases, two have been described as human papillomavirus (HPV)-associated VAIt. The current report presents two additional cases of primary VAIt showing variants in the KRAS, TP53, and DPYD genes and no evidence of HPV DNA by real-time polymerase chain reaction (RT-PCR). Next-generation sequencing (NGS) revealed TP53 pathogenic variants in both cases, but only one case had aberrant p53 protein immunohistochemical characteristics. KRAS and DPYD mutations were identified separately in the two cases. Due to their capacity to imitate the spread of more prevalent gastrointestinal carcinomas, these tumors may present diagnostic issues. Additional cases can contribute to a better understanding of the pathophysiology and prognosis of VAIt.

Diagnosis of verruciform acanthotic vulvar intra-epithelial neoplasia (vaVIN) using CK17, SOX2 and GATA3 immunohistochemistry.

AIMS: Verruciform acanthotic vulvar intra-epithelial neoplasia (vaVIN) is an HPV-independent, p53 wild-type lesion with distinct morphology and documented risk of recurrence and cancer progression. vaVIN is rare, and prospective distinction from non-neoplastic hyperplastic lesions can be difficult. CK17, SOX2 and GATA3 immunohistochemistry has emerging value in the diagnosis of HPV-independent lesions, particularly differentiated VIN. We aimed to test the combined value of these markers in the diagnosis of vaVIN versus its non-neoplastic differentials in the vulva. METHODS AND RESULTS: CK17, SOX2 and GATA3 immunohistochemistry was evaluated on 16 vaVINs and 34 mimickers (verruciform xanthoma, lichen simplex chronicus, lichen sclerosus, psoriasis, pseudo-epitheliomatous hyperplasia). CK17 was scored as 3+ = full-thickness, 2+ = partial-thickness, 1+ = patchy, 0 = absent; SOX2 as 3+ = strong staining ≥ 10% cells, 2+ = moderate, 1 + =weak, 0 = staining in < 10% cells; and GATA3 as pattern 0 = loss in < 25% basal cells, 1 = loss in 25-75% basal cells, 2 = loss in > 75% basal cells. For analysis, results were recorded as positive (CK17 = 3+, SOX2 = 3+, GATA3 = patterns 1/2) or negative (CK17 = 2+/1+/0, SOX2 = 2+/1+/0, GATA3 = pattern 0). CK17, SOX2 and GATA3 positivity was documented in 81, 75 and 58% vaVINs, respectively, versus 32, 17 and 22% of non-neoplastic mimickers, respectively; ≥ 2 marker positivity conferred 83 sensitivity, 88 specificity and 86% accuracy in vaVIN diagnosis. Compared to vaVIN, SOX2 and GATA3 were differentially expressed in lichen sclerosus, lichen simplex chronicus and pseudo-epitheliomatous hyperplasia, whereas CK17 was differentially expressed in verruciform xanthoma and adjacent normal mucosa. CONCLUSIONS: CK17, SOX2 and GATA3 can be useful in the diagnosis of vaVIN and its distinction from hyperplastic non-neoplastic vulvar lesions. Although CK17 has higher sensitivity, SOX2 and GATA3 are more specific, and the combination of all markers shows optimal diagnostic accuracy.

Immune Profiling of Vulvar Squamous Cell Cancer Discovers a Macrophage-rich Subtype Associated with Poor Prognosis.

The incidence rates of vulvar squamous cell cancer (VSCC) have increased over the past decades, requiring personalized oncologic approaches. Currently, lymph node involvement is a key factor in determining prognosis and treatment options. However, there is a need for additional immune-related biomarkers to provide more precise treatment and prognostic information. Here, we used IHC and expression data to characterize immune cells and their spatial distribution in VSCC. Hierarchical clustering analysis identified distinct immune subtypes, of which the macrophage-rich subtype was associated with adverse outcome. This is consistent with our findings of increased lymphogenesis, lymphatic invasion, and lymph node involvement associated with high macrophage infiltration. Further in vitro studies showed that VSCC-associated macrophages expressed VEGF-A and subsequently induced VEGF-A in the VSCC cell line A-431, providing experimental support for a pro-lymphangiogenic role of macrophages in VSCC. Taken together, immune profiling in VSCC revealed tumor processes, identified a subset of patients with adverse outcome, and provided a valuable biomarker for risk stratification and therapeutic decision making for anti-VEGF treatment, ultimately contributing to the advancement of precision medicine in VSCC. SIGNIFICANCE: Immunoprofiling in VSCC reveals subtypes with distinct clinical and biological behavior. Of these, the macrophage-rich VSCC subtype is characterized by poor clinical outcome and increased VEGF-A expression, providing a biomarker for risk stratification and therapeutic sensitivity.

Vulvar Carcinoma: Standard of Care and Perspectives.

PURPOSE: Treatment of vulvar carcinoma (VC) is challenging. The objectives of this review were to describe for clinicians the epidemiologic and clinical aspects of VC, the standard of care in terms of primary local treatment and systemic therapies, and the recent innovations and perspectives emerging from translational research in immuno-oncology. DESIGN: We conducted a comprehensive review outlying the clinical aspects and biologic background of vulvar cancer, highlighting modern treatment strategies on the basis of a personalized approach. RESULTS: Epidemiologic data showed a recent rise in incidence of VC, attributed to human papillomavirus. Surgery is the mainstay of primary treatment, but multimodal approaches are frequently required in the presence of adverse prognosis histopathologic factors. Chemoradiation is indicated when organ-sparing surgery is not feasible. However, inability to achieve high locoregional control rates in advanced cases and the morbidity associated with local treatments are still key issues. Recent clinical data showed the benefit of individualized strategies combining organ-sparing surgical strategies, less invasive lymph node staging procedures, and refinement in radiotherapy modalities. Among the most important research area, there is a sound rationale for testing modern systemic approaches such as immune checkpoint inhibitors in selected patients with recurrent and/or metastatic tumors. Although no specific data exist for VC, the role of supportive care and post-treatment rehabilitation strategies is also crucial. CONCLUSION: There are still insufficient studies dedicated to patients with VC. Public health programs for prevention, screening, and early diagnosis are required, and clinical research should be strengthened to provide high-quality clinical evidence and improve patients' oncologic and functional outcomes.