Not available / text

published_or_final_version / Medicine / Master / Doctor of Medicine

The ability of the HPV-18 E6 gene to impair p53-mediated transcriptional activity induced by DNA damaging agents was investigated. It is demonstrated that E6 can abolish DNA damage induced p53-mediated transcription and that a region from amino acid residue 113 to 117 of HPV-18 E6 protein was necessary for E6 to direct the degradation of p53. The biological importance of the E6/p53 interaction was then directly examined in HPV-16 containing cervical carcinoma derived cells by introducing the monomeric p53 mutant which is resistant to E6 mediated degradation. The two major observations made from this study were: (i) loss of p53 activity plays an important role in maintaining the malignant phenotype of these cells with respect to cell proliferation; (ii) the monomeric p53 mutant without its C-terminal regulatory region was biologically functional with respect to impairing cell proliferation in HPV-16 containing cervical carcinoma derived cells. Finally, it was revealed that the cellular MAP kinase signal transduction pathway was more active in cells expressing the HPV-16 E5 gene than in control cells or cells expressing E6 and E7. These observations help to define the mechanisms by which HPV oncogenes contribute to the development and maintenance of the neoplastic phenotype.

Thesis (MTech (Radiography))--Cape Peninsula University of Technology, 2012 / Introduction: Brachytherapy plays an essential role in the management of patients with cervical cancer. The high cervical cancer burden in Africa presents challenges with regard to provision and sustainability of these services. This study analysed treatment outcomes of two brachytherapy modalities, high dose rate (HDR) and low dose rate (LDR) intracavitary treatment for patients with cervical cancer, and evaluated the problems and challenges of the provision of these services within the African context. Methodology: The study was conducted using a case study approach with mixed methods at two sites in Africa, one in South Africa (Centre I) and the other in Kenya (Centre II). The study explored factors and issues affecting definitive radiotherapy of the patient with cervical cancer at the two sites with a focus on the brachytherapy treatment. The case study provided an opportunity to collect in-depth data consisting of quantitative and qualitative components that generated numeric and textual data. Treatment outcomes of one site treating with HDR and the other LDR intracavitary brachytherapy were retrospectively analysed for a maximum sample size of 193 (91%) patients in the HDR group and 49 (100%) patients in the LDR group. All patients were treated with external beam radiation therapy (EBRT) using parallel opposed beams (POP) for the patients that received LDR brachytherapy, and four field box technique or POP for those that received HDR brachytherapy. The linear quadratic formula was used to calculate the equivalent dose in 2 Gy fractions (EQD2) between the two groups.

Indiana University-Purdue University Indianapolis (IUPUI) / In this study we compared the distribution of HPV types in cervical cancer specimens from women living in either Indiana or Botswana. Paraffin-embedded blocks of formalin-fixed cervical cancer specimens were identified from women living in Indiana (n=51) or Botswana (n=171)

Background: A global cervical cancer health disparity persists despite the demonstrated success of primary and secondary preventive strategies, such as cervical visual inspection (VI). Cervical cancer is the leading cause of cancer incidence and death for women in many low resource areas. The greatest risk is for those who are unable or unwilling to access screening. Barriers include healthcare personnel shortages, cost, transportation, and mistrust of healthcare providers and systems. Using community health workers (CHWs) may overcome these barriers, increase facilitators, and improve participation in screening for women in remote areas with limited access to clinical resources. Aim: To determine whether the accuracy of VI performed by CHWs was comparable to VI by physicians or nurses and to consider the affect components of provider training had on VI accuracy. Methods: A systematic review and quantitative meta-analysis of published literature reporting on VI accuracy, provider type, and training was conducted. Strict inclusion/exclusion criteria, study quality, and publication bias assessments improved rigor and bivariate linear mixed modeling (BLMM) was used to determine the affect of predictors on accuracy. Unconditional and conditional BLMMs, controlling for VI technique, provider type, community, clinical setting, HIV status, and gynecological symptoms were considered. Results: Provider type was a significant predictor of sensitivity (p=.048) in the unconditional VI model. VI performed by CHWs was 15% more sensitive than physicians (p=.014). Provider type was not a significant predictor of accuracy in any other models. Didactic and mentored hours predicted sensitivity in both BLMMs. Quality assurance and use of a training manual predicted specificity in unconditional BLMMs, but was not significant in conditional models. Number of training days, with ≤5 being optimal, predicted sensitivity in both BLMMs and specificity in the unconditional model. Conclusion: Study results suggest that community based cervical cancer screening with VI conducted by CHWs can be as, if not more, accurate than VI performed by licensed providers. Locally based screening programs could increase access to screening for women in remote areas. Collaborative partnerships in “pragmatic solidarity” between healthcare systems, CHWs, and the community could promote participation in screening resulting in decreased cervical cancer incidence and mortality. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2016. / FAU Electronic Theses and Dissertations Collection

The study is informed by inadequate information on factors associated with the prevalence, incidence and mortality of cervical cancer cytological abnormalities in Swaziland. The aim of the study was to explore and describe factors associated with cervical cancer among women of reproductive age between 15 and 49 years in Swaziland. Quantitative descriptive design with a data extraction tool was used to retrospectively generate observational data from 1748 patients’ records in Mbabane Government Hospital from January 2014 through to December 2014. Bivariate logistic regression was used to establish relationship between cervical cancer and each explanatory variable. The overall prevalence of cervical cytology test results was 24.9%. The combination of marital status, HIV status, ART status, age at sexual debut have been identified as factors associated with cervical abnormalities. Most importantly, the results will also serve as evidence for the development of a national cervical cancer screening policy and also strengthening the cancer registry in Swaziland. / Health Studies / M.A. (Public Health)

Thesis (M. Tech.) - Central University of Technology, Free State, 2009

Ho, Ching Sze. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 142-160). / Abstracts in English and Chinese. / DECLARATION --- p.I / ACKNOWLEDGEMENTS --- p.II / ABSTRACT (ENGLISH VERSION) --- p.IV / ABSTRACT (CHINESE VERSION) --- p.VII / TABLE OF CONTENTS --- p.IX / LIST OF FUGURES --- p.XII / LIST OF TABLES --- p.XIII / LIST OF ABBREVIATIONS --- p.XV / Chapter CHAPTER 1: --- INTRODUCTION --- p.1 / Chapter 1.1 --- Biology of human papillomavirus --- p.2 / Chapter 1.1.1 --- History --- p.2 / Chapter 1.1.2 --- Classification --- p.3 / Chapter 1.1.3 --- Genome structure --- p.5 / Chapter 1.1.4 --- Life cycle --- p.9 / Chapter 1.2 --- Epidemiology of cervical cancer --- p.10 / Chapter 1.2.1 --- Cervical intraepithelial neoplasia and cervical cancer --- p.10 / Chapter 1.2.2 --- Spectrum of cervical neoplasia --- p.13 / Chapter 1.2.3 --- Incidence of cervical cancer --- p.15 / Chapter 1.2.4 --- Screening programme --- p.16 / Chapter 1.3 --- Risk factors for cervical cancer --- p.17 / Chapter 1.4 --- Oncogenic HPV infection --- p.20 / Chapter 1.4.1 --- Risk association --- p.21 / Chapter 1.4.2 --- Geographical distribution --- p.23 / Chapter 1.4.3 --- Age distribution --- p.24 / Chapter 1.4.4 --- Oncogenic property of HPV --- p.25 / Chapter 1.4.5 --- Sequence variation --- p.28 / Chapter 1.5 --- Prevention by vaccination --- p.30 / Chapter 1.6 --- Objectives --- p.31 / Chapter CHAPTER 2: --- MATERIALS AND METHODS --- p.33 / Chapter 2.1 --- HPV type and prevalence distribution --- p.34 / Chapter 2.1.1 --- Study population --- p.34 / Chapter 2.1.2 --- Specimen and epidemiological data collection --- p.34 / Chapter 2.1.3 --- DNA extraction --- p.35 / Chapter 2.1.4 --- PCR amplification of DNA --- p.36 / Chapter 2.1.4.1 --- PCR for Beta-globin --- p.36 / Chapter 2.1.4.2 --- PCR for HPV DNA --- p.37 / Chapter 2.1.5 --- HPV typing by reverse line-blot hybridization --- p.39 / Chapter 2.1.6 --- Statistical method --- p.40 / Chapter 2.2 --- HPV 52 SEQUENCE VARIATION --- p.43 / Chapter 2.2.1 --- Study population --- p.43 / Chapter 2.2.2 --- Specimen processing --- p.43 / Chapter 2.2.3 --- DNA extraction --- p.44 / Chapter 2.2.4 --- PCR amplification for sequencing --- p.45 / Chapter 2.2.4.1 --- Optimization of gene-specific PCR --- p.45 / Chapter 2.2.4.2 --- Validation of type-specificity of gene-specific PCR --- p.46 / Chapter 2.2.4.3 --- PCR for HPV52 E6 and E7 --- p.46 / Chapter 2.2.4.4 --- PCR for LI gene --- p.47 / Chapter 2.2.4.5 --- PCR for long control region (LCR) --- p.48 / Chapter 2.2.5 --- Purification of PCR products --- p.49 / Chapter 2.2.6 --- Sequencing --- p.50 / Chapter 2.2.6.1 --- Preparation of template --- p.50 / Chapter 2.2.6.2 --- Purification of template --- p.50 / Chapter 2.2.6.3 --- Sequencer and data analysis --- p.51 / Chapter 2.2.7 --- Statistical methods --- p.51 / Chapter CHAPTER 3: --- RESULTS --- p.54 / Chapter 3.1 --- HPV TYPE AND PREVALENCE DISTRIBUTION --- p.55 / Chapter 3.1.1 --- Study population --- p.55 / Chapter 3.1.2 --- HPV prevalence --- p.59 / Chapter 3.1.2.1 --- Prevalence for HPV infection --- p.59 / Chapter 3.1.2.2 --- HPV age-specific prevalence --- p.68 / Chapter 3.1.3 --- Epidemiological risk profile --- p.73 / Chapter 3.1.3.1 --- Age-adjusted analyses --- p.73 / Chapter 3.1.3.2 --- Multivariate analyses --- p.76 / Chapter 3.2 --- HPV52 SEQUENCE VARIATION --- p.79 / Chapter 3.2.1 --- Study population --- p.79 / Chapter 3.2.2 --- Sequence variability of HPV52 --- p.79 / Chapter 3.2.3 --- HPV52 --- p.82 / Chapter 3.2.3.1 --- Sequence variation of E6 ORF --- p.82 / Chapter 3.2.3.2. --- HPV52 E6 variants and risk for cervical neoplasia --- p.86 / Chapter 3.2.4 --- HPV52 E7 --- p.89 / Chapter 3.2.4.1 --- Sequence variation of E7 ORF --- p.89 / Chapter 3.2.4.2 --- HPV52 E7 variants and risk for cervical neoplasia --- p.93 / Chapter 3.2.5 --- HPV52 LI --- p.95 / Chapter 3.2.5.1 --- Sequence variation of LI ORF --- p.95 / Chapter 3.2.5.2 --- HPV52 LI variants and risk for cervical neoplasia --- p.100 / Chapter 3.2.6 --- HPV52 long control region (LCR) --- p.104 / Chapter 3.2.6.1 --- Sequence variation of LCR --- p.104 / Chapter 3.2.6.2 --- HPV52 LCR variants and risk for cervical neoplasia --- p.110 / Chapter CHAPTER 4: --- DISCUSSION --- p.113 / Chapter 4.1 --- HPV PREVALENCE AND TYPE DISTRIBUTION --- p.114 / Chapter 4.1.1 --- HPV prevalence --- p.114 / Chapter 4.1.2 --- Age-specific prevalence --- p.116 / Chapter 4.1.3 --- Epidemiological risk profile --- p.121 / Chapter 4.1.4 --- Conclusions --- p.126 / Chapter 4.2 --- HPV 52 SEQUENCE VARIATION --- p.127 / Chapter 4.2.1 --- Sequence variability of HPV52 --- p.127 / Chapter 4.2.2 --- Sequence variation of E6 gene --- p.129 / Chapter 4.2.3 --- Sequence variation of E7 gene --- p.132 / Chapter 4.2.4 --- Sequence variation of LI gene --- p.134 / Chapter 4.2.5 --- Sequence variation of LCR --- p.135 / Chapter 4.2.6 --- Conclusions --- p.139 / Chapter 4.3 --- FURTHER STUDIES --- p.140 / REFERENCES --- p.142 / APPENDIXES --- p.A

Thesis (M. A. (Social Work)) --University of Limpopo, 2018 / Cancer of the cervix is second type of cancer among women in developing countries, and a common problem among women of low socio-economic status in rural communities. The spiral increase of the problem is aggravated by some socio-economic, structural, cultural and political factors. Understanding the risk factors associated with the disease is a step forward towards effective prevention and treatment. Numerous studies have been conducted on knowledge and perceptions of cervical cancer however the information on cervical cancer is still not reaching the majority of women. The study explored the perceptions and attitudes of rural women of Matebeleng village towards cervical cancer, the risk factors, screening tests and the HPV vaccines. A qualitative exploratory case study was conducted. Self-reported data was collected from 22 women. Two focus groups of 7 and 9 and 6 face-face individual interviews were conducted using a semi-structured interview guide. Data was analysed thematically. The research findings revealed that the majority of women in the rural area where the study was conducted never heard of cervical cancer and only few received inadequate information. Few highlighted some of the risk factors but some information was incorrect. Very few participants had only once been screened and the majority have never been tested for cervical cancer. Some became aware of the vaccine through the consent forms from school even though they did not exactly understand the content. The sources of information were the radio, health clinic and random women. The concerns of those who were screened were lack of feedback from the clinic nursing staff after the test, lack of adequate preparation and information before been screened to allay fear and doubt of the unknown and lack of reach out programmes to rural communities. The methods of disseminating information to rural women in their distinct contexts should be examined. Conventional traditional ways of reaching out to rural women could perhaps produce improved results through the integrated approach involving multi-disciplinary teams in educating communities. Key Words: Perceptions, attitudes, rural-based women, cervical cancer, risk factors, screening tests, HPV vaccine