Vulvar cancer is a rare gynaecological malignancy, associated with either human papillomavirus (HPV) infections or genetic mutation(s) in the tumour suppressor gene TP53. This thesis consists... Show moreVulvar cancer is a rare gynaecological malignancy, associated with either human papillomavirus (HPV) infections or genetic mutation(s) in the tumour suppressor gene TP53. This thesis consists of two parts. In the first section we intended to investigate several important clinical issues in the treatment of vulvar cancer. We investigated the value of a tumour-free margin of minimal 8 mm for prevention of local recurrences and found that this margin can potentially be smaller than currently advised. Besides that, we researched the surgical treatment of the groins and found that patients with metastases in the groins can be safely treated by surgical removal of the enlarged lymph nodes followed by radiotherapy instead of extensive surgery of the groins. This can reduce treatment related morbidity in patients that need surgical treatment of their groins. The second part of this thesis focusses on the pathogenesis of vulvar cancer with an emphasis on HPV-independent vulvar cancers. Our research suggests a possible third subtype of vulvar cancer, the HPV-independent and TP53 wild type vulvar cancers. This further distinction possibly influences treatment and follow-up regimen for vulvar cancer patients. Show less