Table_2_The vulvar microbiome in lichen sclerosus and high-grade intraepithelial lesions.docx

BackgroundThe 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.MethodsWomen with vulvar lichen sclerosus (n = 10), HSIL (n = 5) and healthy controls (n = 10) were included. Swabs were collected from the vulva, vagina and anal region for microbiome characterization by metagenomic shotgun sequencing. Both lesional and non-lesional sites were examined. Biophysical assessments included trans-epidermal water loss for evaluation of the vulvar skin barrier function and vulvar and vaginal pH measurements.ResultsHealthy vulvar skin resembled vaginal, anal and skin-like microbiome composition, including the genera Prevotella, Lactobacillus, Gardnerella, Staphylococcus, Cutibacterium, and Corynebacterium. Significant differences were observed in diversity between vulvar skin of healthy controls and LS patients. Compared to the healthy vulvar skin, vulvar microbiome composition of both LS and vulvar HSIL patients was characterized by significantly higher proportions of, respectively, Papillomaviridae (p = 0.045) and Alphapapillomavirus (p = 0.002). In contrast, the Prevotella genus (p = 0.031) and Bacteroidales orders (p = 0.038) were significantly less abundant in LS, as was the Actinobacteria class (p = 0.040) in vulvar HSIL. While bacteria and viruses were most abundant, fungal and archaeal taxa were scarcely observed. Trans-epidermal water loss was higher in vulvar HSIL compared to healthy vulvar skin (p = 0.043).ConclusionThis study is the first to examine the vulvar microbiome through metagenomic shotgun sequencing in LS and HSIL patients. Diseased vulvar skin presents a distinct signature compared to healthy vulvar skin with respect to bacterial and viral fractions of the microbiome. Key findings include the presence of papillomaviruses in LS as well as in vulvar HSIL, although LS is generally considered an HPV-independent risk factor for vulvar dysplasia. This exploratory study provides clues to the etiology of vulvar premalignancies and may act as a steppingstone for expanding the knowledge on potential drivers of disease progression.</p

Image_2_The vulvar microbiome in lichen sclerosus and high-grade intraepithelial lesions.JPEG

BackgroundThe 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.MethodsWomen with vulvar lichen sclerosus (n = 10), HSIL (n = 5) and healthy controls (n = 10) were included. Swabs were collected from the vulva, vagina and anal region for microbiome characterization by metagenomic shotgun sequencing. Both lesional and non-lesional sites were examined. Biophysical assessments included trans-epidermal water loss for evaluation of the vulvar skin barrier function and vulvar and vaginal pH measurements.ResultsHealthy vulvar skin resembled vaginal, anal and skin-like microbiome composition, including the genera Prevotella, Lactobacillus, Gardnerella, Staphylococcus, Cutibacterium, and Corynebacterium. Significant differences were observed in diversity between vulvar skin of healthy controls and LS patients. Compared to the healthy vulvar skin, vulvar microbiome composition of both LS and vulvar HSIL patients was characterized by significantly higher proportions of, respectively, Papillomaviridae (p = 0.045) and Alphapapillomavirus (p = 0.002). In contrast, the Prevotella genus (p = 0.031) and Bacteroidales orders (p = 0.038) were significantly less abundant in LS, as was the Actinobacteria class (p = 0.040) in vulvar HSIL. While bacteria and viruses were most abundant, fungal and archaeal taxa were scarcely observed. Trans-epidermal water loss was higher in vulvar HSIL compared to healthy vulvar skin (p = 0.043).ConclusionThis study is the first to examine the vulvar microbiome through metagenomic shotgun sequencing in LS and HSIL patients. Diseased vulvar skin presents a distinct signature compared to healthy vulvar skin with respect to bacterial and viral fractions of the microbiome. Key findings include the presence of papillomaviruses in LS as well as in vulvar HSIL, although LS is generally considered an HPV-independent risk factor for vulvar dysplasia. This exploratory study provides clues to the etiology of vulvar premalignancies and may act as a steppingstone for expanding the knowledge on potential drivers of disease progression.</p

Image_4_The vulvar microbiome in lichen sclerosus and high-grade intraepithelial lesions.JPEG

BackgroundThe 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.MethodsWomen with vulvar lichen sclerosus (n = 10), HSIL (n = 5) and healthy controls (n = 10) were included. Swabs were collected from the vulva, vagina and anal region for microbiome characterization by metagenomic shotgun sequencing. Both lesional and non-lesional sites were examined. Biophysical assessments included trans-epidermal water loss for evaluation of the vulvar skin barrier function and vulvar and vaginal pH measurements.ResultsHealthy vulvar skin resembled vaginal, anal and skin-like microbiome composition, including the genera Prevotella, Lactobacillus, Gardnerella, Staphylococcus, Cutibacterium, and Corynebacterium. Significant differences were observed in diversity between vulvar skin of healthy controls and LS patients. Compared to the healthy vulvar skin, vulvar microbiome composition of both LS and vulvar HSIL patients was characterized by significantly higher proportions of, respectively, Papillomaviridae (p = 0.045) and Alphapapillomavirus (p = 0.002). In contrast, the Prevotella genus (p = 0.031) and Bacteroidales orders (p = 0.038) were significantly less abundant in LS, as was the Actinobacteria class (p = 0.040) in vulvar HSIL. While bacteria and viruses were most abundant, fungal and archaeal taxa were scarcely observed. Trans-epidermal water loss was higher in vulvar HSIL compared to healthy vulvar skin (p = 0.043).ConclusionThis study is the first to examine the vulvar microbiome through metagenomic shotgun sequencing in LS and HSIL patients. Diseased vulvar skin presents a distinct signature compared to healthy vulvar skin with respect to bacterial and viral fractions of the microbiome. Key findings include the presence of papillomaviruses in LS as well as in vulvar HSIL, although LS is generally considered an HPV-independent risk factor for vulvar dysplasia. This exploratory study provides clues to the etiology of vulvar premalignancies and may act as a steppingstone for expanding the knowledge on potential drivers of disease progression.</p

Image_5_The vulvar microbiome in lichen sclerosus and high-grade intraepithelial lesions.JPEG

BackgroundThe 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.MethodsWomen with vulvar lichen sclerosus (n = 10), HSIL (n = 5) and healthy controls (n = 10) were included. Swabs were collected from the vulva, vagina and anal region for microbiome characterization by metagenomic shotgun sequencing. Both lesional and non-lesional sites were examined. Biophysical assessments included trans-epidermal water loss for evaluation of the vulvar skin barrier function and vulvar and vaginal pH measurements.ResultsHealthy vulvar skin resembled vaginal, anal and skin-like microbiome composition, including the genera Prevotella, Lactobacillus, Gardnerella, Staphylococcus, Cutibacterium, and Corynebacterium. Significant differences were observed in diversity between vulvar skin of healthy controls and LS patients. Compared to the healthy vulvar skin, vulvar microbiome composition of both LS and vulvar HSIL patients was characterized by significantly higher proportions of, respectively, Papillomaviridae (p = 0.045) and Alphapapillomavirus (p = 0.002). In contrast, the Prevotella genus (p = 0.031) and Bacteroidales orders (p = 0.038) were significantly less abundant in LS, as was the Actinobacteria class (p = 0.040) in vulvar HSIL. While bacteria and viruses were most abundant, fungal and archaeal taxa were scarcely observed. Trans-epidermal water loss was higher in vulvar HSIL compared to healthy vulvar skin (p = 0.043).ConclusionThis study is the first to examine the vulvar microbiome through metagenomic shotgun sequencing in LS and HSIL patients. Diseased vulvar skin presents a distinct signature compared to healthy vulvar skin with respect to bacterial and viral fractions of the microbiome. Key findings include the presence of papillomaviruses in LS as well as in vulvar HSIL, although LS is generally considered an HPV-independent risk factor for vulvar dysplasia. This exploratory study provides clues to the etiology of vulvar premalignancies and may act as a steppingstone for expanding the knowledge on potential drivers of disease progression.</p

Table_5_The vulvar microbiome in lichen sclerosus and high-grade intraepithelial lesions.docx

BackgroundThe 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.MethodsWomen with vulvar lichen sclerosus (n = 10), HSIL (n = 5) and healthy controls (n = 10) were included. Swabs were collected from the vulva, vagina and anal region for microbiome characterization by metagenomic shotgun sequencing. Both lesional and non-lesional sites were examined. Biophysical assessments included trans-epidermal water loss for evaluation of the vulvar skin barrier function and vulvar and vaginal pH measurements.ResultsHealthy vulvar skin resembled vaginal, anal and skin-like microbiome composition, including the genera Prevotella, Lactobacillus, Gardnerella, Staphylococcus, Cutibacterium, and Corynebacterium. Significant differences were observed in diversity between vulvar skin of healthy controls and LS patients. Compared to the healthy vulvar skin, vulvar microbiome composition of both LS and vulvar HSIL patients was characterized by significantly higher proportions of, respectively, Papillomaviridae (p = 0.045) and Alphapapillomavirus (p = 0.002). In contrast, the Prevotella genus (p = 0.031) and Bacteroidales orders (p = 0.038) were significantly less abundant in LS, as was the Actinobacteria class (p = 0.040) in vulvar HSIL. While bacteria and viruses were most abundant, fungal and archaeal taxa were scarcely observed. Trans-epidermal water loss was higher in vulvar HSIL compared to healthy vulvar skin (p = 0.043).ConclusionThis study is the first to examine the vulvar microbiome through metagenomic shotgun sequencing in LS and HSIL patients. Diseased vulvar skin presents a distinct signature compared to healthy vulvar skin with respect to bacterial and viral fractions of the microbiome. Key findings include the presence of papillomaviruses in LS as well as in vulvar HSIL, although LS is generally considered an HPV-independent risk factor for vulvar dysplasia. This exploratory study provides clues to the etiology of vulvar premalignancies and may act as a steppingstone for expanding the knowledge on potential drivers of disease progression.</p

Table_3_The vulvar microbiome in lichen sclerosus and high-grade intraepithelial lesions.docx

BackgroundThe 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.MethodsWomen with vulvar lichen sclerosus (n = 10), HSIL (n = 5) and healthy controls (n = 10) were included. Swabs were collected from the vulva, vagina and anal region for microbiome characterization by metagenomic shotgun sequencing. Both lesional and non-lesional sites were examined. Biophysical assessments included trans-epidermal water loss for evaluation of the vulvar skin barrier function and vulvar and vaginal pH measurements.ResultsHealthy vulvar skin resembled vaginal, anal and skin-like microbiome composition, including the genera Prevotella, Lactobacillus, Gardnerella, Staphylococcus, Cutibacterium, and Corynebacterium. Significant differences were observed in diversity between vulvar skin of healthy controls and LS patients. Compared to the healthy vulvar skin, vulvar microbiome composition of both LS and vulvar HSIL patients was characterized by significantly higher proportions of, respectively, Papillomaviridae (p = 0.045) and Alphapapillomavirus (p = 0.002). In contrast, the Prevotella genus (p = 0.031) and Bacteroidales orders (p = 0.038) were significantly less abundant in LS, as was the Actinobacteria class (p = 0.040) in vulvar HSIL. While bacteria and viruses were most abundant, fungal and archaeal taxa were scarcely observed. Trans-epidermal water loss was higher in vulvar HSIL compared to healthy vulvar skin (p = 0.043).ConclusionThis study is the first to examine the vulvar microbiome through metagenomic shotgun sequencing in LS and HSIL patients. Diseased vulvar skin presents a distinct signature compared to healthy vulvar skin with respect to bacterial and viral fractions of the microbiome. Key findings include the presence of papillomaviruses in LS as well as in vulvar HSIL, although LS is generally considered an HPV-independent risk factor for vulvar dysplasia. This exploratory study provides clues to the etiology of vulvar premalignancies and may act as a steppingstone for expanding the knowledge on potential drivers of disease progression.</p

Presentation_1_Oral prednisolone suppresses skin inflammation in a healthy volunteer imiquimod challenge model.pptx

Imiquimod (IMQ) is a topical agent that induces local inflammation via the Toll-like receptor 7 pathway. Recently, an IMQ-driven skin inflammation model was developed in healthy volunteers for proof-of-pharmacology trials. The aim of this study was to profile the cellular, biochemical, and clinical effects of the marketed anti-inflammatory compound prednisolone in an IMQ model. This randomized, double-blind, placebo-controlled study was conducted in 24 healthy volunteers. Oral prednisolone (0.25 mg/kg/dose) or placebo (1:1) was administered twice daily for 6 consecutive days. Two days after treatment initiation with prednisolone or placebo, 5 mg imiquimod (IMQ) once daily for two following days was applied under occlusion on the tape-stripped skin of the back for 48 h in healthy volunteers. Non-invasive (imaging and biophysical) and invasive (skin punch biopsies and blister induction) assessments were performed, as well as IMQ ex vivo stimulation of whole blood. Prednisolone reduced blood perfusion and skin erythema following 48 h of IMQ application (95% CI [−26.4%, −4.3%], p = 0.0111 and 95% CI [−7.96, −2.13], p = 0.0016). Oral prednisolone suppressed the IMQ-elevated total cell count (95% CI [−79.7%, −16.3%], p = 0.0165), NK and dendritic cells (95% CI [−68.7%, −5.2%], p = 0.0333, 95% CI [−76.9%, −13.9%], p = 0.0184), and classical monocytes (95% CI [−76.7%, −26.6%], p = 0.0043) in blister fluid. Notably, TNF, IL-6, IL-8, and Mx-A responses in blister exudate were also reduced by prednisolone compared to placebo. Oral prednisolone suppresses IMQ-induced skin inflammation, which underlines the value of this cutaneous challenge model in clinical pharmacology studies of novel anti-inflammatory compounds. In these studies, prednisolone can be used as a benchmark.</p

Table_4_The vulvar microbiome in lichen sclerosus and high-grade intraepithelial lesions.docx

BackgroundThe 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.MethodsWomen with vulvar lichen sclerosus (n = 10), HSIL (n = 5) and healthy controls (n = 10) were included. Swabs were collected from the vulva, vagina and anal region for microbiome characterization by metagenomic shotgun sequencing. Both lesional and non-lesional sites were examined. Biophysical assessments included trans-epidermal water loss for evaluation of the vulvar skin barrier function and vulvar and vaginal pH measurements.ResultsHealthy vulvar skin resembled vaginal, anal and skin-like microbiome composition, including the genera Prevotella, Lactobacillus, Gardnerella, Staphylococcus, Cutibacterium, and Corynebacterium. Significant differences were observed in diversity between vulvar skin of healthy controls and LS patients. Compared to the healthy vulvar skin, vulvar microbiome composition of both LS and vulvar HSIL patients was characterized by significantly higher proportions of, respectively, Papillomaviridae (p = 0.045) and Alphapapillomavirus (p = 0.002). In contrast, the Prevotella genus (p = 0.031) and Bacteroidales orders (p = 0.038) were significantly less abundant in LS, as was the Actinobacteria class (p = 0.040) in vulvar HSIL. While bacteria and viruses were most abundant, fungal and archaeal taxa were scarcely observed. Trans-epidermal water loss was higher in vulvar HSIL compared to healthy vulvar skin (p = 0.043).ConclusionThis study is the first to examine the vulvar microbiome through metagenomic shotgun sequencing in LS and HSIL patients. Diseased vulvar skin presents a distinct signature compared to healthy vulvar skin with respect to bacterial and viral fractions of the microbiome. Key findings include the presence of papillomaviruses in LS as well as in vulvar HSIL, although LS is generally considered an HPV-independent risk factor for vulvar dysplasia. This exploratory study provides clues to the etiology of vulvar premalignancies and may act as a steppingstone for expanding the knowledge on potential drivers of disease progression.</p

Image_3_The vulvar microbiome in lichen sclerosus and high-grade intraepithelial lesions.JPEG

BackgroundThe 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.MethodsWomen with vulvar lichen sclerosus (n = 10), HSIL (n = 5) and healthy controls (n = 10) were included. Swabs were collected from the vulva, vagina and anal region for microbiome characterization by metagenomic shotgun sequencing. Both lesional and non-lesional sites were examined. Biophysical assessments included trans-epidermal water loss for evaluation of the vulvar skin barrier function and vulvar and vaginal pH measurements.ResultsHealthy vulvar skin resembled vaginal, anal and skin-like microbiome composition, including the genera Prevotella, Lactobacillus, Gardnerella, Staphylococcus, Cutibacterium, and Corynebacterium. Significant differences were observed in diversity between vulvar skin of healthy controls and LS patients. Compared to the healthy vulvar skin, vulvar microbiome composition of both LS and vulvar HSIL patients was characterized by significantly higher proportions of, respectively, Papillomaviridae (p = 0.045) and Alphapapillomavirus (p = 0.002). In contrast, the Prevotella genus (p = 0.031) and Bacteroidales orders (p = 0.038) were significantly less abundant in LS, as was the Actinobacteria class (p = 0.040) in vulvar HSIL. While bacteria and viruses were most abundant, fungal and archaeal taxa were scarcely observed. Trans-epidermal water loss was higher in vulvar HSIL compared to healthy vulvar skin (p = 0.043).ConclusionThis study is the first to examine the vulvar microbiome through metagenomic shotgun sequencing in LS and HSIL patients. Diseased vulvar skin presents a distinct signature compared to healthy vulvar skin with respect to bacterial and viral fractions of the microbiome. Key findings include the presence of papillomaviruses in LS as well as in vulvar HSIL, although LS is generally considered an HPV-independent risk factor for vulvar dysplasia. This exploratory study provides clues to the etiology of vulvar premalignancies and may act as a steppingstone for expanding the knowledge on potential drivers of disease progression.</p

Table_1_The vulvar microbiome in lichen sclerosus and high-grade intraepithelial lesions.docx

BackgroundThe 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.MethodsWomen with vulvar lichen sclerosus (n = 10), HSIL (n = 5) and healthy controls (n = 10) were included. Swabs were collected from the vulva, vagina and anal region for microbiome characterization by metagenomic shotgun sequencing. Both lesional and non-lesional sites were examined. Biophysical assessments included trans-epidermal water loss for evaluation of the vulvar skin barrier function and vulvar and vaginal pH measurements.ResultsHealthy vulvar skin resembled vaginal, anal and skin-like microbiome composition, including the genera Prevotella, Lactobacillus, Gardnerella, Staphylococcus, Cutibacterium, and Corynebacterium. Significant differences were observed in diversity between vulvar skin of healthy controls and LS patients. Compared to the healthy vulvar skin, vulvar microbiome composition of both LS and vulvar HSIL patients was characterized by significantly higher proportions of, respectively, Papillomaviridae (p = 0.045) and Alphapapillomavirus (p = 0.002). In contrast, the Prevotella genus (p = 0.031) and Bacteroidales orders (p = 0.038) were significantly less abundant in LS, as was the Actinobacteria class (p = 0.040) in vulvar HSIL. While bacteria and viruses were most abundant, fungal and archaeal taxa were scarcely observed. Trans-epidermal water loss was higher in vulvar HSIL compared to healthy vulvar skin (p = 0.043).ConclusionThis study is the first to examine the vulvar microbiome through metagenomic shotgun sequencing in LS and HSIL patients. Diseased vulvar skin presents a distinct signature compared to healthy vulvar skin with respect to bacterial and viral fractions of the microbiome. Key findings include the presence of papillomaviruses in LS as well as in vulvar HSIL, although LS is generally considered an HPV-independent risk factor for vulvar dysplasia. This exploratory study provides clues to the etiology of vulvar premalignancies and may act as a steppingstone for expanding the knowledge on potential drivers of disease progression.</p