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Title: Development of screening and therapeutic intervention strategies for cervical cancer in rural regions of sub-Saharan Africa
Author: Chituku, Tsitsi Grace
ISNI:       0000 0004 7963 5999
Awarding Body: University of Huddersfield
Current Institution: University of Huddersfield
Date of Award: 2019
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Cervical cancer is the most common and lethal form of cancer in women in sub-Saharan African countries. Whilst screening for cervical cancer is available in the more affluent cities, it is currently not widely available in poor, rural areas and women typically present with advanced disease. The need for 'screen and treat' strategies in these regions is as obvious as it is imperative. The purpose of this study is twofold; (i) to conduct a pharmacoeconomic analysis of the benefits of early detection in Zimbabwe and (ii) to develop the preclinical rationale for the use of the enzyme activated prodrug EO9 as a locoregional therapy for cervical cancer. We were able to show that it is feasible to provide cervical screening with VIA to a population of women in rural Zimbabwe by conducting two screening programmes where 469 women were screened for cervical cancer. The prevalence rate of VIA positive women was 1.5%. It would cost approximately US$1.85 to screen each woman. Without screening, women would present with late stage disease and this is much more expensive to treat. EO9 is a prodrug that is activated by oxidoreductases such as NAD(P)H:Quinone oxidoreductase 1 (NQO1) to DNA damaging species. A panel of cell lines were characterised with respect to NQO1 genotype and phenotype and chemosensitivity studies were conducted using the MTT assay. The results of this study demonstrate that a good correlation between NQO1 activity and response to EO9 exists and the role of NQO1 in the activation process was confirmed using the NQO1 inhibitor dicoumarol. Together with evidence of elevated NQO1 in CIN and SCC compared to normal cervix tissue, these results strongly support the use of EO9 as a locoregional therapy for pre-invasive cervical cancer. In conclusion, this study has demonstrated that the simple use of VIAC screening in rural areas of Zimbabwe is feasible and popular amongst women. Early detection together with vaccination would significantly reduce the burden and suffering caused by this disease and the pharmacoeconomic benefits would be attractive to health care providers. Provided novel formulations for EO9 could be developed, there is a strong case for establishing clinical trials to test the safety and efficacy of EO9 as a locoregional therapy for cervical cancer.
Supervisor: Phillips, Roger Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Q Science (General) ; RA0421 Public health. Hygiene. Preventive Medicine