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Title: Human papillomavirus and biomarker analysis to predict high-grade cervical disease in women with persistent low-grade squamous cytological abnormalities
Author: Lippiatt, Jonathan Andrew
ISNI:       0000 0004 2733 5089
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2013
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Persistent HPV infection can cause cervical intraepithelial neoplasia (CIN) and ultimately cervical cancer. Cervical cytology is currently used to screen for CIN with HPV testing recently emerging as an adjunct to cytology. Most women with HPV infection, however, will not go on to develop cancer. Therefore an additional biomarker is required to identify those women most at risk. The BD SurePath Plus™ test (SPP) is a novel immunocytochemistry assay based upon the detection of minichromosomemaintenance protein 2 (MCM2) and MCM7. Studies have shown both MCM2 and MCM7 have the potential for use as a biomarker for CIN2+ and cervical cancer. A two-­‐centre, prospective, observational study was devised to test SPP as triage test in women with persistent low-­‐grade cytology. Two commercial HPV tests were also examined in their role in triage of these women. A further study was conducted to examine viral integration and viral DNA methylation as potential biomarkers of high-­‐grade disease. An assay that determines the status of the HPV E2 gene and the Detection of Integrated Papillomavirus Sequences were used to assess integration. Bisulfite conversion followed by pyrosequencing was used to assess DNA methylation within two regions of the HPV genome (E2 and L1L2). Following the clinical study BD SurePath Plus™ was found to be inferior to HPV testing in the discrimination of high-­‐grade cervical disease. The age of women was found to significantly affect the results of all three tests. Viral integration and viral DNA methylation were both associated with high-­‐grade disease. New sites of viral integration were found in the study and the predilection of common fragile sites and repeat sequences as sites of integration was also reinforced. It was also discovered that integration could affect the accuracy of some HPV and biomarker tests.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RC0254 Neoplasms. Tumors. Oncology (including Cancer) ; RG Gynecology and obstetrics