Rolfe, Kerstin Jane; (2003) The molecular pathology of neoplastic and non-neoplastic vulval disease. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

It has been proposed that there are two types of squamous cell carcinoma of the vulva, one being associated with 'high-risk' human papillomavirus (HPV) with a recognisable pre-malignant lesion (vulval intraepithelial neoplasia; VIN). A second, which appears not to be associated with HPV and about which there, has been controversy relating to the pre-malignant stage. Clinical and histological association has linked non-neoplastic epithelial disorders (e.g. lichen sclerosus; LS) with this form of vulval cancer; however, epidemiological evidence has shown that few patients will progress to develop cancer. Little research has been undertaken to assess the pre-malignant potential of these lesions. The aim of this study was to assess the malignant potential of such lesions as well as the molecular pathology of vulval cancer itself and to elucidate if the pathways to vulval cancer from VIN and LS are different. Using archival tissue and frozen tissue from invasive carcinoma, epidermis adjacent to the cancer (LS, squamous hyperplasia (SH) and VIN) and normal vulval skin, different techniques were used to assess molecular changes both in vulval malignancy and non-neoplastic changes. Such markers were also used in a clinicopathological analysis of survival for vulval cancer. Furthermore, since the treatment of non-neoplastic epithelial disorders may affect such molecular processes these were also analysed. Furthermore blood analysis and clinical features were assessed along with molecular changes to distinguish the similarities or different features between the vulval cancers associated with HPV and the adjacent lesions and vulval cancers associated with non-neoplastic epithelial disorders of the vulva. Neoplastic and non-neoplastic cell cycle and apoptotic proteins were found to demonstrate abnormal expression, particularly in relation to corticosteroid treatment in LS and in neoplastic changes or adjacent to neoplasia. HPV-16 appeared to play a role in the development of both VIN and vulval cancer associated with VIN. Pathways leading to vulval cancer all appear to involve the G1/S pathway though through different means.

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