Vulvar Cancer Research Articles

Suppressing Expression of SERPINE1/PAI1 Through Activation of GPER1 Reduces Progression of Vulvar Carcinoma.

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

HPV vaccination in Croatia (2016-2023): Increased vaccine uptake and declining sex disparities

Abstract Background The Human papillomavirus (HPV) is a known cause of cervical cancer, and is associated with the development of vaginal, vulvar, anal, penile, and head and neck cancer. The availability of the HPV vaccine has enabled generations of young people to be protected from HPV-related cancers. In 2016, a national immunization program targeting 14-year-old girls and boys has been initiated in Croatia. To date, systematic data on HPV vaccination coverage (VC) in Croatia is lacking. This study aims to determine HPV VC, examine trends in HPV vaccination in Croatia from 2016 to 2023 in the context of the national vaccination program, and assess differences between sexes. Methods The study is designed as a retrospective analysis covering the data from 2016 to 2023, collected from primary healthcare providers. HPV VC within 2000-2008 birth cohorts (BC) are analyzed for all vaccinated with at least one dose and assessed by sex. The trend in HPV vaccination is shown using joinpoint regression. The chi-square for trend is used to compare the vaccination coverage of females (FVC) and males (MVC). The rate ratio between FVC and MVC is calculated. Results HPV VR increased significantly among observed BCs from 6,44 % in 2000 BC to 44,22 % in 2008 BC (FVC rose from 10,67 % to 52,78 %, and males MVC from 2,47 % to 36,05 %). Joinpoint analysis revealed a statistically significant increase in all birth cohorts, while the steeper increase is seen in 2000-2006 BCs (APC = 35,47, P < 0,05) than in 2006-2008 BCs (APC = 13,93, P < 0,05). FVC is significantly higher than MVC in all birth cohorts (Extended Mantel-Haenszel chi-square for linear trend = 809.23, P < 0,001). The highest FVC/MVC rate ratio was observed in the initial 2000 BC (4,31), and the lowest in the last 2008 BC (1,46). Conclusions In Croatia, HPV VC continuously increases among observed BCs. The positive trend is present in both sexes, and the rate ratio between female and male cohorts is decreasing. Key messages • The study presents a systematical overview of HPV vaccination coverage in Croatia from the beginning of the national immunization program, which is crucial for monitoring progress. • In the following years, if the revealed trends persist or advance, Croatia could be closer to reaching Europe’s Beating Cancer Plan concerning eliminating HPV-related diseases.

The association between body mass index and vulvar and vaginal cancer incidence: findings from a large Norwegian cohort study.

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

Prognostic significance of Standard Uptake Value (SUVmax) and primary tumor size predicting patient survival in vulvar tumors.

Prognostic significance of Standard Uptake Value (SUVmax) and primary tumor size predicting patient survival in vulvar tumors.

The value of a multimodal approach combining radical surgery and intraoperative radiotherapy in the recurrence treatment of gynecological malignancies - analysis of a large patient cohort in a tertiary care center

BackgroundRecurrent and locally advanced gynecological malignancies have a poor prognosis. In particularly, pelvic local recurrence after previous radiotherapy and/or positive resection margins during surgical treatment for recurrent disease result in low survival rates. Consequently, locoregional control is of utmost importance in this cohort of patients. The aim of this study was to analyze treatment outcomes and determine prognostic factors for patients treated with surgery and intraoperative radiotherapy (IORT) for recurrent and locally advanced gynecological malignancies.Methods40 patients who underwent surgical treatment and IORT between 2010 and 2022 were eligible for inclusion. The median follow-up time was 22 months. The outcomes measured were locoregional control (LRC), overall survival (OS), and survival without distant metastases (DMFS). The Cox proportional hazards model was used for univariate and multivariate analysis to assess the impact of patient variables and treatment factors on the endpoints mentioned. The following variables were analyzed: age at surgical treatment and IORT and initial diagnosis (< 65 vs. ≥65 years, each), disease-free interval (DFI) between initial diagnosis and first recurrence, DFI to surgical treatment and IORT, grading, histology, IORT dose (≤ 13 vs. >13 Gy) and technique (high dose radiotherapy (HDR) vs. IORT using electrons, (IOERT)). Survival curves were generated using the Kaplan-Meier method.ResultsThe mean IORT dose was 13.8 Gy (range 10–18 Gy). Cervical carcinoma was most frequently found in 27.5% of patients followed by endometrial carcinoma and vulvar carcinoma in 25% respectively. The final histopathologic results after surgery with IORT showed no residual tumour in 24 patients (60%), microscopic residual disease in 5 patients (12.5%), resection status could not be evaluated in three patients (7.5%) and the resection status was unknown in eight patients (20%). Subsequently, 27.5% of patients also received adjuvant radiotherapy of the local recurrence bed. However, after IORT, 65% of the women suffered a recurrence. Of these, the recurrences were localized: in-field 32.5%, out-of-field 22.5% and margin-of-field 12.5%. The 3- and 5-year OS was 69% and 55% respectively. The 3- and 5-year LRC was 56% respectively. The 3- and 5-year DMFS was 66% and 49%. Whereas the comparison between groups by IORT dose level (≤ 13 vs. >13 Gy) showed a non-significant trend in favor of the higher dose only for OS (p = 0.094), but not in LRC and DMFS (p > 0.05). OS and DMFS, but not LRC, differed significantly between the HDR-IORT and IOERT groups (p = 0.06 and p = 0.03,) in favor of the HDR-IORT technique. For HDR-IORT technique a trend towards superior OS and LRC was observed in the univariate analysis: HR 3.76, CI 95%: 0.95–14.881, p = 0.059 and HR 2.165 CI 95%: 0.916–5.114, p = 0.078ConclusionsThe survival rate for pelvic recurrence in gynecological malignancies remains poor and comparable with historical data from the last two decades. Particularly HDR-IORT, appears to provide a long-term oncological benefit in carefully selected patients.

Atypical Foot Swelling in Metastatic Endometrial Carcinoma: Role of FDG PET/CT.

An 83-year-old woman with a history of endometrial carcinoma (EMC), treated with surgery and chemotherapy in August 2020, presented with a 1-year history of left foot swelling, tenderness, and heat. Despite multiple consultations, no diagnosis was made, and she developed painful swelling with a limping gait. A biopsy was done on July 14, 2023, confirmed metastatic EMC. FDG PET/CT revealed widespread metastases, including in the lungs, pleura, mediastinal, hilar, inguinal, right external iliac nodes, left labia majora, left iliac bone, left tibia, and left foot. Excision of left inguinal and vulvar tumors also confirmed metastatic EMC.

Squamoid eccrine ductal carcinoma of the vulva: A case report

Abstract Introduction/Objective A 53-year-old female sought medical attention for left vulvar pain and a vulvar lesion. Methods/Case Report Physical examination revealed a 1.0 x 1.0 cm lesion within a background of lichen sclerosus. Biopsy demonstrated a carcinoma with tubular and glandular architecture, areas of squamoid differentiation and widespread perineural invasion. Ancillary immunohistochemistry testing with keratin 7 highlighted foci of ductal differentiation. Tumor cells were also positive for p53, p63, pankeratin, and keratin 5/6. The Ki-67 proliferation index was approximately 15%. Tumor cells were negative for Keratin 20, PAX 8, p16, and CD 34. We diagnosed the lesion as a vulvar sweat gland adenocarcinoma of the squamoid eccrine ductal subtype. Results (if a Case Study enter NA) N/A Conclusion Carcinomas of vulvar sweat gland origin are extremely rare, comprising less than 1% of all vulvar cancers. To the best of our knowledge, this is the first case report of squamoid eccrine ductal carcinoma afflicting the vulva.

In Silico Studies for Multi-Targeting Justicia Secund Phytochemicals Against Ovarian Cancer

ntroduction/Background of study: Ovarian cancer is the fifth leading cause of cancer deaths among women, accounting for more deaths than any other female gynaecological cancer, which includes cervical, uterine, vaginal and vulvar cancers. Current treatment options include surgery, platinum-based chemotherapy, radiation therapy and the use of targeted therapy such as poly ADP-ribose polymerase (PARP inhibitors), as well as immunotherapy. These therapy options, however, are subject to high rates of resistance and many side effects. AIM/ OBJECTIVES: This research aims to study other viable drug targets for ovarian cancer treatment, as well as new phytocompounds that can serve as new drug options using the in-silico approach. Materials/Methods: The ethanolic leaf extract of Justicia secunda was obtained using conventional methods. Liquid Liquid-liquid fractionation was performed with N-hexane, ethyl acetate and butanol solvents to obtain their fractions alongside the aqueous fraction. Vacuum Liquid Chromatography was performed with the N-hexane fraction and gradient mixtures of N-hexane/ethyl acetate and Dichloromethane/Methanol in various ratios to obtain the subfractions. The compounds were identified using Gas Chromatography-Mass Spectrometry (GC-MS). Full pharmacognostic profiling was performed on the J.secunda leaves. The identified compounds were downloaded from Pubchem and subjected to Molecular docking simulations to obtain their binding affinities with the receptors of interest. Drug-likeness and toxicity assessments were performed on frontrunner compounds. Results: After assessment of the frontrunner compounds, four multitargeting J.secunda phytochemicals were identified: Luteolin, Diosmetin, 5H-Quindoline and 10H-Quindoline.

A dose-response meta-analysis of the relationship between number of pregnancies and risk of gynecological cancers.

Despite several investigations, the association between the number of pregnancies and gynecological cancers remains inconclusive. To address this issue, we conducted a dose-response meta-analysis of observational studies. We searched PubMed, Web of Science, and Scopus databases up to Jun 8, 2023, to identify observational studies that examined the association between the number of pregnancies and gynecologic cancers. To assess the heterogeneity across studies, we used the χ2 test and I2 statistics. We also explored the possibility of publication bias using Begg's and Egger's tests. The overall effect sizes were reported as odds ratios (ORs) with a 95% confidence interval (CI) using a random-effects model. Out of the 87,255 studies initially identified, a total of 101 studies involving 8,230,754 participants were included in the final meta-analysis. Our analysis revealed a positive trend between the number of pregnancies and cervical cancer; however, this association was not found to be statistically significant except for fifth pregnancy. Conversely, our findings showed a significant decreasing trend between the number of pregnancies and the risk of endometrial and ovarian cancers. There was insufficient evidence to establish a relationship between the number of pregnancies and the risk of vaginal, vulvar, and fallopian tube cancers. Our study found a positive trend between the number of pregnancies and cervical cancer and a significant decreasing trend between the number of pregnancies and endometrial and ovarian cancers. These findings may have implications for counseling women about their reproductive health and the potential risks and benefits of pregnancy.

Sudden pruritic eruption in a patient with vulvar cancer.

Sudden pruritic eruption in a patient with vulvar cancer.

Myoepithelioma-like tumor of vulva: a clinicopathological analysis of 5 cases

Myoepithelioma-like tumor of vulva: a clinicopathological analysis of 5 cases

9185 Pembrolizumab-Induced New-Onset Type 1 Diabetes Mellitus: A Case Report

Abstract Disclosure: D. Teng: None. T.L. Connelly: None. M. Ahmad: None. R. Saeed: None. Introduction: Immune checkpoint inhibitors are becoming essential in the treatment of various cancers. Pembrolizumab is a monoclonal antibody that binds PD-1 receptors, thereby enabling an anti-tumor response by preventing T-cell suppression. Common side effects associated with pembrolizumab include thyroid disorders, hepatitis, pneumonitis, and acute kidney injury, among others. We describe an interesting case of a woman presenting with diabetic ketoacidosis (DKA) in the setting of pembrolizumab-associated new-onset type 1 diabetes mellitus, which was reported at 0.1% during initial clinical trials but is now being increasingly recognized as a complication of immune checkpoint therapy. Case Description: The patient is a 70-year-old female with past medical history notable for stage IIIA vulvar squamous cell carcinoma initially diagnosed and treated in 2017, with recurrence in 2022 and in 2023, at which point pembrolizumab therapy was initiated. Approximately one month after her first dose, the patient presented to the emergency department with palpitations, nausea, non-bloody vomiting, polydipsia, and non-bloody diarrhea. On arrival, the patient’s vital signs were as follows: 97.2 °F, BP 128/74 mmHg, heart rate 80 bpm, respiratory rate 18 per minute, and SpO2 100% on room air. No acute findings were noted on physical exam. Initial blood work was notable for: pH 7.146, lactate 2.4 mmol/L, bicarbonate 8 mmol/L, anion gap 37 mmol/L, creatinine 1.59 mg/dL, glucose 563 mg/dL, C-peptide 0.16 ng/mL, HbA1c 6.9%, and WBC 18.8 B/L with neutrophilic predominance. Urinalysis was notable for 4+ glucose and 4+ ketones. The patient was admitted to the progressive care unit and DKA protocol was initiated including the administration of IV fluids, insulin infusion, and electrolyte replacement. Additional blood work was unrevealing, including insulin autoantibodies &amp;lt;0.4 U/mL, negative islet cell IgG cytoplasmic autoantibodies, and negative anti-GAD65 antibodies. The patient was eventually discharged with outpatient Endocrinology follow-up. Discussion: Immunotherapy is quickly redefining the standard of care in the treatment of several types of malignancies through the leveraging of the body’s immune defense apparatus. Pembrolizumab prevents the deactivation of T-cells via the PD-1/PD-L1 pathway. Unfortunately, this also predisposes non-cancerous cells to autoimmune destruction by these T-cells. It is proposed that such is the mechanism by which pancreatic beta islet cells are destroyed in the setting of pembrolizumab use, thereby resulting in a rapid reduction in insulin production capability. New-onset type 1 diabetes complicated by DKA is potentially life-threatening, and so we believe this case highlights the need for both pre-treatment counseling as well as follow-up screening following initiation of pembrolizumab therapy. Presentation: 6/2/2024

The impact of concurrent HIV-infection on women with vulvar cancer: Comparison of clinical characteristics and outcome.

HPV-related vulvar cancer is increasing in prevalence, especially in women living with HIV. Treatment of vulva cancer is based on evidence from HPV-independent cancers, which affect older women. The impact of HIV on vulvar cancer characteristics and treatment outcomes needs to be elucidated. A retrospective observational study compared the clinical characteristics, treatment, and outcomes of 92 HIV-positive and 131 HIV-negative women with vulvar cancer at our institution. Using descriptive statistics, HIV-positive and negative patients were compared and Cox regression models were tested for differences in mortality and recurrence. HIV-positive patients were 20 years younger than HIV-negative patients (p < 0.001). More than 50% of patients presented with advanced stage cancer, however this was independent of HIV-status. Although HIV infection was associated with poorer survival (p = 0.022); rates of cure (p = 0.933) and recurrence rates (p = 0.8) were similar in HIV-positive and negative women. Vulvar cancer occurs at a much younger age in women living with HIV. Awareness among HIV-positive women and health care providers would lead to diagnosis of vulvar cancer at an earlier stage. Treatment protocols for HPV-related vulvar cancer should not be altered due to HIV status and should take into consideration the young age of the patients.

The prognostic values of lymph node ratio for gynecological cancer: a systematic review and meta-analysis.

The aim of this study was to determine the relationship between the lymph node ratio (LNR) and the prognostic values of gynecological cancer. 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), progression-free 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 I 2 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. A total of 34 studies with 23,202 cases were included in this meta-analysis. A meta-analysis found that higher LNR was associated with worse OS (HR = 2.42, 95% CI: 2.07-2.83; I 2 = 77.4%, p < 0.05), PFS (HR = 1.97, 95% CI: 1.66-2.32; I 2 = 0.00%, p > 0.05), and DFS (HR = 3.18, 95% CI: 2.12-4.76; I 2 = 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; I 2 = 72.6%, p < 0.05), ovarian cancer (OC) (HR = 2.05, 95% CI: 1.66-2.54; I 2 = 76.7%, p < 0.05), endometrial cancer (EC) (HR = 2.16, 95% CI: 1.48-3.16; I 2 = 53.6%, p < 0.05), and vulvar cancer (VC) (HR = 8.13, 95% CI: 3.41-19.43; I 2 = 57.2%, p < 0.05). 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. https://www.crd.york.ac.uk/PROSPERO/#recordDetails, CRD42024541187.

An Updated Review Summarizing the Pharmaceutical Efficacy of Genistein and its Nanoformulations in Ovarian Carcinoma.

Implementing lifestyle interventions as a primary prevention strategy is a cost-effective approach to reducing the occurrence of cancer, which is a significant contributor to illness and death globally. Recent advanced studies have uncovered the crucial role of nutrients in safeguarding women's health and preventing disorders. Genistein is an abundant isoflavonoid found in soybeans. Genistein functions as a chemotherapeutic drug against various forms of cancer, primarily by modifying apoptosis, the cell cycle, and angiogenesis and suppressing metastasis. Furthermore, Genistein has demonstrated diverse outcomes in women, contingent upon their physiological characteristics, such as being in the early or postmenopausal stages. The primary categories of gynecologic cancers are cervical, ovarian, uterine, vaginal, and vulvar cancers. Understanding the precise mechanism by which Genistein acts on ovarian cancer could contribute to the advancement of anti-breast cancer treatments, particularly in situations where no specific targeted therapies are currently known or accessible. Additional investigation into the molecular action of Genistein has the potential to facilitate the development of a plant-derived cancer medication that has fewer harmful effects. This research could also help overcome drug resistance and prevent the occurrence of ovarian cancers.

Cost-Effectiveness of 9-Valent HPV Vaccination for Patients Treated for High-Grade Cervical Intraepithelial Neoplasia in the UK

Patients who have been treated for high-grade cervical intraepithelial neoplasia (CIN grade ≥2) are at a high risk for subsequent CIN and other cancers and diseases related to human papillomavirus (HPV). HPV vaccination can reduce the risk of subsequent disease in patients surgically treated for grade 2 or greater CIN; however, there is no formal recommendation for prophylactic HPV vaccination in this high-risk population, and the cost-effectiveness is unknown. To assess the incremental lifetime outcomes, costs, and cost-effectiveness of integrating peritreatment 9-valent HPV (9vHPV) vaccination in combination with posttreatment surveillance for the prevention of cervical cancer and other HPV-attributable diseases in patients surgically treated for grade 2 or greater CIN vs posttreatment surveillance alone from a UK payer perspective. This economic evaluation used 3 independent Markov model structures. Model inputs for vaccine efficacy, utilities, and costs were obtained from published sources, and cervical cancer screening data were obtained from the National Health Service Cervical Screening Program. Costs were adjusted to 2022 to 2023 reference years. Data were analyzed from October 2022 to September 2023. Peritreatment vaccination with 9vHPV in combination with posttreatment surveillance compared with posttreatment surveillance alone. Clinical outcomes included grade 1, 2, or 3 CIN; cervical cancer; vaginal cancer; vulvar cancer; anal cancer; head and neck cancer; genital warts; and recurrent respiratory papillomatosis. Incremental cost-effectiveness ratios (ICERs) using a willingness-to-pay threshold (WTP) of £20 000 (US $26 200) per quality-adjusted life-year (QALY) were estimated. Deterministic sensitivity analysis and probabilistic sensitivity analysis were performed. Vaccination with 9vHPV in conjunction with posttreatment surveillance was cost-effective, with a favorable ICER of £13 789.07 (US $18 064.68) per QALY gained (ie, below the WTP of £20 000 per QALY) vs posttreatment surveillance alone. The resulting ICER was £52 358.01 (US $68 588.99) per HPV-related cancer averted and £64 090 (US $83 958.18) per HPV-related cancer death averted. The ICER was most sensitive to discount rate, incidence of HPV infection, vaccine price, and age at initial treatment for grade 2 or greater CIN. Results of the probabilistic sensitivity analysis showed peritreatment 9vHPV vaccination was cost-effective at the WTP recommended by the UK's Joint Committee on Vaccination and Immunisation (90% of iterations <£30 000 [US $39 300] per QALY) in 100% of iterations. These findings suggest that peritreatment prophylactic 9vHPV vaccination is a cost-effective option for preventing subsequent HPV-attributable diseases in patients surgically treated for grade 2 or greater CIN.

MO52-6 Results of treatment for FIGO stage I-II vulvar squamous cell carcinoma at Viet Nam National Cancer Hospital

MO52-6 Results of treatment for FIGO stage I-II vulvar squamous cell carcinoma at Viet Nam National Cancer Hospital

Effect of HPV Oncoprotein on Carbohydrate and Lipid Metabolism in Tumor Cells.

High-risk HPV infection accounts for 99.7% of cervical cancer, over 90% of anal cancer, 50% of head and neck cancers, 40% of vulvar cancer, and some cases of vaginal and penile cancer, contributing to approximately 5% of cancers worldwide. The development of cancer is a complex, multi-step process characterized by dysregulation of signaling pathways and alterations in metabolic pathways. Extensive research has demonstrated that metabolic reprogramming plays a key role in the progression of various cancers, such as cervical, head and neck, bladder, and prostate cancers, providing the material and energy foundation for rapid proliferation and migration of cancer cells. Metabolic reprogramming of tumor cells allows for the rapid generation of ATP, aiding in meeting the high energy demands of HPV-related cancer cell proliferation. The interaction between Human Papillomavirus (HPV) and its associated cancers has become a recent focus of investigation. The impact of HPV on cellular metabolism has emerged as an emerging research topic. A significant body of research has shown that HPV influences relevant metabolic signaling pathways, leading to cellular metabolic alterations. Exploring the underlying mechanisms may facilitate the discovery of biomarkers for diagnosis and treatment of HPV-associated diseases. In this review, we introduced the molecular structure of HPV and its replication process, discussed the diseases associated with HPV infection, described the energy metabolism of normal cells, highlighted the metabolic features of tumor cells, and provided an overview of recent advances in potential therapeutic targets that act on cellular metabolism. We discussed the potential mechanisms underlying these changes. This article aims to elucidate the role of Human Papillomavirus (HPV) in reshaping cellular metabolism and the application of metabolic changes in the research of related diseases. Targeting cancer metabolism may serve as an effective strategy to support traditional cancer treatments, as metabolic reprogramming is crucial for malignant transformation in cancer.

Reconstruction methods in vulvar cancer: a narrative review

Background : Vulvar cancer is a rare type of cancer that accounts for 1% of all cancers in women and about 3-8% of all gynecological cancers in the world. Although resection of the lesion is the first choice for treatment, reconstructive methods of the vulva have been increasingly used recently. Flaps are most commonly used for this purpose. However, it is important to remember that the reconstruction must be adjusted to the patient's needs, taking into account the geometry of the wound, as well as potential secondary complications.Aim of the study: The aim of this study is to present the different methods of plastic surgery for vulvar cancer, which included V-Y, VRAM, ALT, DIEP and lotus flaps. The following article focuses on describing the above methods, presenting their advantages and disadvantages, in which cases they can be used, and potential complications.Material and methods: The literature review was conducted in the PubMed database. The inclusion criteria used in the review included compliance with topic, publication date after 2015 and English language. Articles of low credibility, duplicated, not in English language and with abstracts unrelated to the topic were excluded. Results: Of the articles found, 32 studies were eventually to be reviewed. The research shows that the choice of reconstruction method can be difficult, while there is no single correct approach in vulvar cancer cases.Conclusions: In summary, the interdisciplinary collaboration between the gynecologist oncologist, the surgeon and the radiotherapist, plays a key role in the treatment process.

Typing of Vulvar Squamous Cell Carcinoma: Why it is Important?

The classification of vulvar squamous cell carcinoma (VSCC), as in endometrial cancer, has shifted from the histology-based descriptors toward molecular-based identifiers. Recently, it has been reported that there are 3 genetically distinct and clinically significant subtypes of VSCC: HPV-associated VSCC, HPV-independent/p53 wild-type VSCC, and HPV-independent/p53-mutated VSCC. Each group has different prognostic implications as well as response to treatment, thus reinforcing the need for this 3-tier molecular classification. This molecular subtyping can easily be done on vulvar biopsies using p16 and p53 immunohistochemistry stains to further improve risk prediction and individualized treatment decisions, leading to better patient outcomes.