Vulvar cancer is a rare gynecological malignancy with a tremendous disease burden. Vulvar squamous cell carcinoma (VSCC) is the most common histologic type of vulvar cancer and constitutes 80–90%... Show moreVulvar cancer is a rare gynecological malignancy with a tremendous disease burden. Vulvar squamous cell carcinoma (VSCC) is the most common histologic type of vulvar cancer and constitutes 80–90% of all vulvar cancers. The cornerstone of treatment for VSCC consists of surgery with or without radiochemotherapy. In addition, precursors of VSCC often require surgical or medical intervention as well. Treatment of vulvar (pre)malignancies is a challenging balance act, as on the one hand clearance of all lesions is desired, while on the other hand normal vulvar anatomy and function must be preserved as best as possible. Utilizing the current treatment interventions, recurrence occurs in up to 40% of VSCC patients and no major improvements in 5-year survival rates were observed in the last decades. This is partly caused by the difficulty to recognize vulvar (pre)malignant lesionsfor the medical specialist, either macroscopically or pathologically.This highlights the high unmet medical need for preferably non-invasive and accurate diagnostics for vulvar (pre)malignancies. Further, effective therapies are needed with a favorable safety profile that encompass complete reduction of the affected tissue.Therefore, the aim of this thesis has been to search for disease-specific biomarkers to improve the clinical management of vulvar (pre)malignancies. In the present thesis, we have attempted to test several promising innovative instruments in a search for disease-specific biomarkers for vulvar (pre)cancers. A multimodal profiling approach guided this research, based on systems profiling of disease and drug effects in dermatology. The different investigated aspects include imaging, cellular and molecular characteristics and was complemented by patient reported outcomes and physician-based input. Overall we focused on three important cornerstones within this multimodal approach:1 Application of novel non-invasive imaging instruments as dermatoscopy, optical coherence tomography and reflectance confocal microscopy on healthy and diseases vulvar skin to improve diagnostics;2 Establishment of in vitro healthy and VSCC 3D models aimed for future anticancer drug evaluation studies;3 Investigation of promising targets for tumor-specific molecular real time imaging of vulvar (pre)cancers, to assist complete surgical excision. Show less
