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Incidence trends for invasive and non-invasive disease are explored. A nested case control study of those women who progress from non-invasive disease to carcinoma is performed. The incidence of vulval carcinoma in Grampian remains stable. Incidence rates of all non-invasive chronic vulval skin disorders, regardless of underlying aetiology are rising dramatically. Age specific incidence rates suggest that there may be significant ascertainment bias in rising incidence rates for each of these skin disorders. No distinction could be found between the relative risks for women with vulval litchen sclerosus or vulval intraepithelial neoplasia developing subsequent carcinoma. Vulval squamous hyperplasia appears to be of low malignant potential. The malignant risk of vulval lichen sclerosus or vulval intraepithelial neoplasia within Grampian is currently in the order of 9% over ten years of follow-up. The presence of HPV 16 DNA does not appear to confer an increased risk of subsequent malignant transformation in women with biopsy-proven chronic vulval skin disorders. Although p-53 overexpression is not associated with an increased risk of subsequent malignant transformation, there are patterns of altered expression that may identify a high risk group of women. Those women that have been identified as suffering from a chronic vulval skin disorder before they develop invasive disease appear to have more favourable prognostic factors at presentation. The primary role of viral carcinogenesis in vulval carcinoma has been overestimated in the current literature. p53 aberrations may be a unifying factors in the biology of vulval carcinoma, with HPV acting as a co-factor in some cases. Aggressive surgical management for vulval intraepithelial neoplasia solely for the purposes of anticipating a rise in invasive disease rates should be resisted. An increase in resource allocation for the purpose of close surveillance of women with vulval lichen sclerosis or vulval intraepithelial neoplasia now seems justified.

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No description available.

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This thesis considers aspects of modelling solid tumours. We begin by considering the common assumption that nutrient or drug concentrations in avascular tumour spheroids are radially symmetric. We derive a simple Poisson equation for biomolecular diffusion into an avascular tumour, but with highly oscillatory boundary conditions due to the surrounding capillary network. We find that the assumption of radial symmetry is legitimate for biomolecules that are taken up in sufficient quantities by proliferating cancer cells; however radially symmetric profiles need not be observed otherwise. We then investigate how the gap between an avascular tumour and the neighbouring vasculature varies as the tumour grows. This is explored by (i) using scaling arguments based on ordinary differential equations, (ii) coupling the rate of oxygen flux from the vasculature to oxygen evolution within the tumour, and (iii) deriving a system of six coupled non-linear partial differential equations modelling the tumour evolution. It is found that as the tumour grows any initial gap between the tumour and neighbouring vasculature closes since there is no mechanism which would sufficiently up-regulate non-cancerous cell proliferation. This is in contrast to the intra-cornea implantation observations, upon which several mathematical models are based. Finally, we study the growth and treatment of a vascular tumour subjected to chemotherapies, particularly when the therapies can exhibit an anti-angiogenic effect and resistance to the therapy is incorporated. A multi-compartment model is derived for the evolution of a tumour undergoing treatment and parameters are estimated, with extensions to incorporate numerous different therapy protocols in the literature. We find that anti-angiogens can be effective, though the appropriate scheduling is counter-intuative and contradicts many standard therapy rules. We conclude that chemotherapy protocol design is very sensitive to the mode of action of the drug and simple general strategies will, in many cases, not be the most effective.