Monocyte infiltration is an independent positive prognostic biomarker in vulvar squamous cell carcinoma.

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.

The vulvar microbiome in lichen sclerosus and high-grade intraepithelial lesions.

Background: The role of the vulvar microbiome in the development of (pre)malignant vulvar disease is scarcely investigated. The aim of this exploratory study was to analyze vulvar microbiome composition in lichen sclerosus (LS) and vulvar high-grade squamous intraepithelial lesions (HSIL) compared to healthy controls.

Methods: Women with vulvar lichen sclerosus ( = 10), HSIL ( = 5) and healthy controls ( = 10) were included.

The development of in vitro organotypic 3D vulvar models to study tumor-stroma interaction and drug efficacy.

Background: Vulvar squamous cell carcinoma (VSCC) is a rare disease with a poor prognosis. To date, there's no proper in vitro modeling system for VSCC to study its pathogenesis or for drug evaluation.

Methods: We established healthy vulvar (HV)- and VSCC-like 3D full thickness models (FTMs) to observe the tumor-stroma interaction and their applicability for chemotherapeutic efficacy examination.

Sentinel lymph node procedure in early-stage vulvar cancer: Correlation of lymphoscintigraphy with surgical outcome and groin recurrence.

Introduction: In early-stage vulvar squamous cell carcinoma (VSCC) a sentinel lymph node (SLN) procedure is regarded successful if at least one SLN is removed with minimal residual radioactivity. An inguinofemoral lymphadenectomy is considered if not all SLNs visualized on lymphoscintigraphy can be found, with subsequent increased morbidity. We correlated lymphoscintigraphy findings with surgical outcome and groin recurrence with focus on number of SLNs found.

Incidence of inguinofemoral lymph node metastases at the first local recurrence of vulvar cancer: a Dutch nationwide study.

Background: Up to 40% of vulvar cancer patients present with local recurrence within 10 years of follow-up. An inguinofemoral lymphadenectomy (IFL) is indicated if not performed at primary treatment. The incidence and risk factors for lymph node metastases (LNM) at first local recurrence, however, are unclear.

Reflectance confocal microscopy as a non-invasive imaging tool in vulvar high-grade squamous intraepithelial lesions and lichen sclerosus: A descriptive morphological study in patients and healthy volunteers.

Incorrect and delayed diagnosis of vulvar high-grade squamous intraepithelial neoplasia (vHSIL) and lichen sclerosus (LS) increases malignant progression risks and negatively impacts prognosis and quality of life. There is a need to improve diagnosis and monitoring. Reflectance confocal microscopy is a non-invasive imaging tool that visualizes skin structures at cellular resolution.

Immune Monitoring of Mycophenolate Mofetil Activity in Healthy Volunteers Using T Cell Function Assays.

Mycophenolate mofetil (MMF) is part of the standard immunosuppressive treatment after transplantation and usually given as "one-dose-fits-all" together with a calcineurin inhibitor (CNI). Although drug concentrations are frequently monitored, there is still a group of patients who experience side effects related to excessive or insufficient immune suppression. We therefore aimed to identify biomarkers that reflect the overall immune status of the patient and might support individualized dosing.

Dermatoscopy and Optical Coherence Tomography in Vulvar High-Grade Squamous Intraepithelial Lesions and Lichen Sclerosus: A Prospective Observational Trial.

Objective: This study aimed to examine potential discriminatory characteristics of dermatoscopy and dynamic optical coherence tomography (D-OCT) on vulvar high-grade squamous intraepithelial lesions (vHSIL) and lichen sclerosus (LS) compared with healthy vulvar skin.

Methods: A prospective observational clinical trial was performed in 10 healthy volunteers, 5 vHSIL and 10 LS patients. Noninvasive imaging measurements using dermatoscopy and D-OCT were obtained at several time points, including lesional and nonlesional vulvar skin.

Frailty and treatment decisions in older patients with vulvar cancer: A single-center cohort study.

Introduction: Vulvar cancer is a disease that mainly affects older women. Frailty is an important predictor of outcomes and geriatric assessment can help tailor treatment decisions and improve outcomes. This study aims to assess the prevalence of frailty in older women with vulvar cancer, and how it relates to integrated geriatric care and treatment according to the oncological guidelines.

Intradermal vaccination of HPV-16 E6 synthetic peptides conjugated to an optimized Toll-like receptor 2 ligand shows safety and potent T cell immunogenicity in patients with HPV-16 positive (pre-)malignant lesions.

Background: Amplivant is a molecularly optimized Toll-like receptor 2 ligand that can be covalently conjugated to tumor peptide antigens. In preclinical models, amplivant-adjuvanted synthetic long peptides (SLPs) strongly enhanced antigen presentation by dendritic cells, T cell priming and induction of effective antitumor responses. The current study is a first-in-human trial to investigate safety and immunogenicity of amplivant conjugated to human papillomavirus (HPV) 16-SLP.

Monitoring of Ex Vivo Cyclosporin a Activity in Healthy Volunteers Using T Cell Function Assays in Relation to Whole Blood and Cellular Pharmacokinetics.

Therapeutic drug monitoring (TDM) of calcineurin inhibitors (i.e., tacrolimus and cyclosporin A) is standard of care after solid organ transplantation.

The Paget Trial: topical 5% imiquimod cream for noninvasive vulvar Paget disease.

Background: Vulvar Paget disease is an extremely rare skin disorder, which is most common in postmenopausal women. Most vulvar Paget disease cases are noninvasive; however, it may be invasive or associated with an underlying vulvar or distant adenocarcinoma. The current treatment of choice for noninvasive vulvar Paget disease is wide local excision, which is challenging because of extensive intraepithelial spread and may cause severe morbidity.

CD161 expression and regulation defines rapidly responding effector CD4+ T cells associated with improved survival in HPV16-associated tumors.

Background: Expression of killer cell lectin-like receptor B1 (), the gene encoding the cell surface molecule CD161, is associated with favorable prognosis in many cancers. CD161 is expressed by several lymphocyte populations, but its role and regulation on tumor-specific CD4+ T cells is unknown.

Methods: We examined the clinical impact of CD4+CD161+ T cells in human papillomavirus (HPV)16+ oropharyngeal squamous cell carcinoma (OPSCC), analyzed their contribution in a cohort of therapeutically vaccinated patients and used HPV16-specific CD4+CD161+ tumor-infiltrating lymphocytes and T cell clones for in-depth mechanistic studies.

The Human Vulvar Microbiome: A Systematic Review.

The link between cancer and the microbiome is a fast-moving field in research. There is little knowledge on the microbiome in ((pre)malignant) conditions of the vulvar skin. This systematic review aims to provide an overview of the literature regarding the microbiome composition of the healthy vulvar skin and in (pre)malignant vulvar disease.

Integrin αvβ6 as a Target for Tumor-Specific Imaging of Vulvar Squamous Cell Carcinoma and Adjacent Premalignant Lesions.

Surgical removal of vulvar squamous cell carcinoma (VSCC) is associated with significant morbidity and high recurrence rates. This is at least partially related to the limited visual ability to distinguish (pre)malignant from normal vulvar tissue. Illumination of neoplastic tissue based on fluorescent tracers, known as fluorescence-guided surgery (FGS), could help resect involved tissue and decrease ancillary mutilation.

Primary vulvar squamous cell carcinomas with high T cell infiltration and active immune signaling are potential candidates for neoadjuvant PD-1/PD-L1 immunotherapy.

Background: A profound insight into the immune landscape of vulvar squamous cell carcinoma (VSCC) is lacking. Here, an in-depth interrogation of T cell infiltration, local immune contexture, signaling pathways and checkpoint molecule expression was performed in early-stage and late-stage VSCC.

Methods: The type, location, and infiltration pattern of T cells were studied in 109 patients with primary VSCC FIGO stage I-III.

PROTECT: Prospective Phase-II-Trial Evaluating Adaptive Proton Therapy for Cervical Cancer to Reduce the Impact on Morbidity and the Immune System.

External beam radiation therapy (EBRT) with concurrent chemotherapy followed by brachytherapy is a very effective treatment for locally advanced cervical cancer (LACC). However, treatment-related toxicity is common and reduces the patient's quality of life (QoL) and ability to complete treatment or undergo adjuvant therapies. Intensity modulated proton therapy (IMPT) enables a significant dose reduction in organs at risk (OAR), when compared to that of standard intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT).

Evaluation of treatment, prognostic factors, and survival in 198 vulvar melanoma patients: Implications for clinical practice.

Objective: To identify clinicopathological characteristics, treatment patterns, clinical outcomes and prognostic factors in patients with vulvar melanoma (VM).

Materials & Methods: This retrospective multicentre cohort study included 198 women with VM treated in eight cancer centres in the Netherlands and UK between 1990 and 2017. Clinicopathological features, treatment, recurrence, and survival data were collected.

Near-infrared fluorescence imaging compared to standard sentinel lymph node detection with blue dye in patients with vulvar cancer - a randomized controlled trial.

Objective: The aim of this study was to assess the superiority of ICG-Tc-nanocolloid for the intraoperative visual detection of sentinel lymph nodes (SLNs) in vulvar squamous cell carcinoma (VSCC) patients compared to standard SLN detection using Tc-nanocolloid with blue dye.

Methods: In this multicenter, randomized controlled trial, VSCC patients underwent either the standard SLN procedure or with the hybrid tracer ICG-Tc-nanocolloid. The primary endpoint was the percentage of fluorescent SLNs compared to blue SLNs.

Vulvar cancer subclassification by HPV and p53 status results in three clinically distinct subtypes.

Objective: There is great need for better risk stratification in vulvar squamous cell carcinoma (VSCC). Our aim was to define the prognostic significance of stratifying VSCC based on p16 and p53 immunohistochemistry (IHC) as surrogate markers for HPV and TP53 mutations.

Methods: A large retrospective cohort of surgically treated women with primary VSCC was used.

Survival outcomes of patients with advanced mucosal melanoma diagnosed from 2013 to 2017 in the Netherlands - A nationwide population-based study.

Background: Mucosal melanoma (MM) is rare and has a poor prognosis. Since 2011, new effective treatments are available for advanced melanoma. It is unclear whether patients with mucosal melanoma equally benefit from these new treatments compared with patients with cutaneous melanoma (CM).

CD39 Identifies the CD4 Tumor-Specific T-cell Population in Human Cancer.

The accumulation of tumor-specific CD4 and CD8 effector T cells is key to an effective antitumor response. Locally, CD4 T cells promote the recruitment and effector function of tumor-specific CD8 T cells and activate innate killer cells in the tumor. Here, we show that tumor-specific CD4 T cells were predominantly present in the CD39 subset of tumor-infiltrating lymphocytes (TIL).

A pre-existing coordinated inflammatory microenvironment is associated with complete response of vulvar high-grade squamous intraepithelial lesions to different forms of immunotherapy.

Immunotherapy of vulvar high-grade squamous intraepithelial lesion (vHSIL) is investigated as an alternative for surgery, because of high comorbidity and risk of recurrence. Limited evidence exists on the role and composition of the immune microenvironment in current immunotherapeutic approaches for vHSIL. The vHSIL of 29 patients biopsied before treatment with imiquimod were analyzed by two multiplex seven-color immunofluorescence panels to investigate the pre-existing T-cell and myeloid cell composition in relation to treatment response.