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Title: HPV biology in VIN : viral biomarkers to predict response to treatment
Author: Jones, Sadie
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2016
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Biology in VIN: Viral Biomarkers to Predict Response to Treatment I Summary Vulval intraepithelial neoplasia (VIN) is a condition of vulval skin that is often chronic in nature. The diagnosis is made histologically and can be delayed due to VINs variable clinical presentation. Frequently reported symptoms of pain and itching can be very distressing for patients. If left untreated, VIN has the potential to become malignant. The current standard treatment for VIN is surgical excision. However this approach is not ideal; it can be disfiguring and lead to significant psychosexual morbidity. There are also potentially, significant post operative complications (e.g. infection) and a high rate of recurrence. Alternative treatments are needed. The efficacy of cidofovir and imiquimod treatment was investigated in the RT3 VIN clinical trial, and complete responses were observed in 57% and 61% of patients respectively. The Human Papillomavirus (HPV) plays a major aetiological role in the development of VIN. To further understanding of HPV pathogenesis in VIN, HPV prevalence, HPV integration, HPV methylation and HPV gene expression were investigated in 167 tissue biopsies from patients participating in the RT3 VIN trial. High HPV prevalence of 98.2% was detected. HPV biology was found to be heterogeneous: HPV integration was detected in 71/136 (52.5%) cases; HPV DNA methylation ranged from 0.0% - 94.4%, and there was variable expression of HPV genes. Strong correlations were found between HPV integration, high levels of methylation, low levels of E2 gene expression and deregulated oncogene expression. Variable HPV biology in VIN 3 meant that HPV characteristics had a potential role as predictive biomarkers. HPV E2 region methylation demonstrated greatest potential. E2 methylation > 4% predicted response to cidofovir with 88.2% sensitivity and 84.6% specificity; while E2 methylation < 4% predicted response to imiquimod with 70.6% sensitivity and 62.5% specificity. Further investigation of this biomarker in a large prospective study is justified.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RC0254 Neoplasms. Tumors. Oncology (including Cancer)