The aim of this thesis was to study novel tools and biomarkers for improved detection of vulvar premalignant disease and aid the investigation of potential new drug targets for the indication of... Show moreThe aim of this thesis was to study novel tools and biomarkers for improved detection of vulvar premalignant disease and aid the investigation of potential new drug targets for the indication of vulvar and HPV-driven diseases.Firstly, this thesis focuses on the recognition and validation of imaging-based biomarkers for recognition of diseases of the skin and external genitalia. Clinical studies were performed using 3D photography, dermatoscopy optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) on vulvar HSIL, lichen sclerosus, cutaneous warts and anogenital warts. These techniques were subsequently implemented in a clinical trial in which a novel small molecule was tested for safety and exploratory efficacy for the treatment of cutaneous warts.Furthermore, this thesis explores sequencing-based biomarkers for vulvar disease, facilitating insight into the aetiology of vulvar diseases and identifying potential new therapeutic targets. The currently available literature on the vulvar microbiome composition was investigated and expanded in an observational study characterising the vulvar microbiome composition of healthy volunteers, vulvar HSIL patients and lichen sclerosus patients. Lastly, a perspective on recent developments in the field of premalignant vulvar disease is provided, with recommendations for future applications of the biomarkers studied in this thesis. Show less