published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / Clinical Psychology / Master / Master of Social Sciences

published_or_final_version / Community Medicine / Master / Master of Public Health

Cervical cancer is the ninth leading cause of female cancer deaths in Hong Kong. In 2011, 391 new cases of cervical cancer were diagnosed and the age-standardized incidence rate was 7.2 per 100,000 standard populations. In 2012, 133 women died from this cancer, accounting for 2.5% of female cancer deaths. The age-standardized death rate of cervical cancer was 2.1 per 100,000 standard populations. Human papillomavirus (HPV) infection is an established cause of cervical cancer. HPV vaccines offer more than 70% protection for women against HPV types 16 and 18 infections and their related cervical precancerous lesions and cervical cancer. As there are usually no symptoms in high-risk HPV infection, it is often diagnosed at a late stage. Regular cervical smears can offer early detection of pathological changes and pre-cancerous stage for a timely medical treatment to prevent progression to cervical cancer. The Cervical Screening Programme (CSP) of Department of Health (DH) was launched on 8 March 2004. It is a voluntary program with the objectives to increase the population coverage of cervical screening among women and to reduce the incidence and mortality of cervical cancer in Hong Kong. Women participating in the programme are encouraged to have cervical smears in the medical centres of their own choices and to provide their cervical smear information through their health care providers to the central registry of the CSP - The Cervical Screening Information System (CSIS). As at 31 December 2013, 491,674 women have registered with CSP. When DH implemented CSP in March 2004, a report was published in the same year showing evidence that an organized screening compared with the opportunistic screening could substantially increase benefits and reduce costs. Another local study conducted early this year supported by the Health Services Research Fund also highlighted the importance and urgency in enhancing the current screening protocol. It is of public health interests to study and compare the programme outcomes with countries like Finland, Australia, UK and Japan where different policy was adopted for the prevention of cervical cancer. Information gathered from research papers on epidemiological studies has been collected and analyzed on population benefit (outcome, access, disparities), cost (cost benefit, efficiency, cost containment), equity, feasibility and constituency perspectives in formulation of the policy alternatives. In conclusion, strengthening what is already in place with better allocative efficiency could protect the female population against cervical cancer. From the education perspective, emphasis on the risk of HPV infection in the sex education curriculum would raise the awareness on the precaution of HPV infections amongst young females. Additionally, vaccination at the age of 12 can provide protection against most types of HPV. It is strongly recommended that a cervical screening and HPV co-testing strategy at a triennial interval could provide the best cost and benefit effectiveness. Together they can enhance protection coverage of women at 12 through immunization and from 25 - 64 through active population screening. The ultimate objectives to reduce incidence, mortality and increase coverage could be achieved. / published_or_final_version / Public Health / Master / Master of Public Health

This dissertation explores a diagnostic image analysis framework using multispectral digital colposcopy for real-time in vivo detection of cervical cancer. In the first part of the dissertation, the clinical feasibility of a previously developed multispectral digital colposcope (MDC) is demonstrated using a hamster cheek pouch model of carcinogenesis. Various studies on MDC applications to cervical cancer detection in human subjects are then presented. First, an automated diagnostic image analysis algorithm for cervical cancer using white light reflectance images is presented. The algorithm can identify pre-neoplastic tissue areas from an entire cervix based on intensity changes feature in the reflectance images induced by acetic acid treatment. Then, the information about tissue type is incorporated into the diagnostic image analysis framework. For this purpose, a Markov Random Field (MRF) model is adopted and the results are discussed. One of the practical difficulties of utilizing a MRF model in unpolarized white light reflectance imaging is the specular reflection problem since the effect of specular reflection extends into surrounding tissue areas. Through the use of cross polarized imaging, the effects of specular reflection reduced and the ability to segment images based on tissue types is enhanced, leading to better diagnostic performance. The diagnostic performance of polarized imaging is compared to that of unpolarized imaging. In order to assess the performance of the proposed approach, a gold standard for the entire cervical image is constructed using histopathology results from a whole cervix specimen. The results presented in this dissertation indicate that an automated diagnostic image analysis framework for early detection of cervical cancer has the potential to be clinically applied as a low cost alternative screening technique in developing countries. Advances in imaging technology as well as in image analysis algorithms will continue to reduce the cost of diagnostic imaging systems and improve the imaging and diagnostic capability, leading to an inexpensive, real-time, minimally-invasive alternative to conventional screening techniques for early detection of cervical cancer in developing countries. / text

Thesis (M.S.)--Georgia State University, 2007. / Title from file title page. Yu-sheng Hsu, committee chair; Mark Faupel, Xu Zhang, committee members. Electronic text (93 p. : col. ill.) : digital, PDF file. Description based on contents viewed Sept. 17, 2008. Includes bibliographical references (p. 49-51).

Thesis (M. Sc. (Biochemistry)) -- University of Limpopo, 2019 / Cervical cancer is the fourth most common cancer in females, and the seventh of all cancer types in both genders, with an estimated 500,000 new cases each year. As with liver cancer, a large majority (around 85%) of the global burden occurs in the less developed regions, where it accounts for almost 12% of all female cancers. About 90% of cervical cases are associated with human papillomavirus (HPV) as a causative agent and this virus is frequently transmitted through sexual contact involving exchange of fluids (Walboomers et al., 1997). Due to the ineffectiveness, undesirable side effects and costly treatment for the disease the current study was aimed at determining the anti-proliferative effects of extracts of selected medicinal plants for their anticancer activity on HeLa cell line invitro. In order to accomplish the outcome of this research study, medicinal plants (Toona cilliata, Seriphium plumosum and Schkuhria pinnata) from Limpopo Province (South Africa) with history of traditional use on cervical cancer-associated patients were selected. The Toona cilliata plant leaves were collected from Tzaneen, area while Seriphium plumosum and Schkuhria pinnata leaves were collected from Mankweng area. The dried leaves were grounded into powder and extracted using acetone. Thereafter, extracted leaf materials of selected plants were subjected to fingerprint profiling using TLC silicon coated plates immersed in tanks with different mobile phases (TEA, CEF and EMW) of various increasing polarities since. The plates were sprayed with vanillin/H2SO4, dried and visualised under UV light. Scavenging ability of the plant extracts was determined through investigating the presence of antioxidant activities using 0.2% of the 2,2- diphenyl-1- picrylhydrazyl (DPPH) indicator. The quantitative presence of total phenolic and flavonoids contents was also determined using garlic and quercetin as standards, respectively. Quantitative antioxidant scavenging activities were also determined and ascorbic acid was used as a positive control. This was followed by quantitative determination of ferric reducing power and thereafter the EC50 values of the extracts were determined by linear regression. Cell proliferation or viability was determined using the 3[4, 5 dimethylthiazol-2-yl]-2-5 diphenyltetrazolium (MTT) assay with actinomycin as a xv positive control and untreated cells as the negative control. Apoptotic effects of the extracts were determined using the Annexin V Fluos staining kit. This was followed by determining whether apoptosis was calcium dependent or independent using a calorimetric assay. In comparing the acetone extract yield per 10 g leaves of plants, Toona cilliata leaves exhibited the highest yield followed by Seriphium plumosum and with the least yield from Schkuhria pinnata. The finger print profile showed the prominent separation and was achieved from all the plants when using the non-polar TEA solvent. All plants were shown to contain extracts with varying levels of antioxidant activity especially when using CEF and EMW mobile phases. When evaluating the total phenolic and flavonoids contents all plant extracts exhibited presence of phenolic compounds with high presence observed in Seriphium plumosum and Toona cilliata. Extracts from Seriphium plumosum and Toona cilliata showed to have higher concentrations of phytochemicals that may be of a benefit in antioxidant activities as compared to Schkuhria pinnata in relation to the positive control and a similar trend were observed in the ferric reducing power assay. Extracts from Seriphium plumosum were shown to have the best IC50 scavenging values followed by Toona cilliata and Schkuhria pinnata respectively. All the plants exhibited free radical scavenging abilities with Seriphium plumosum shown to possess higher activities in comparison with the positive control. All the plants exhibited a dose-dependent cytotoxicity activity against the HeLa cervical cell line. Evidence of induced apoptotic activity was observed in HeLa cells when using extracts from Seriphium plumosum and Toona cilliata. Induction of apoptosis by plant extracts was shown to be calcium dependent as there was a decrease in calcium concentration with a decrease in the number of viable cells. In conclusion, the leaf extracts from Toona cilliata, Seriphium plumosum and Schkuhria pinnata contain compounds of various polarities with freeradical, antioxidant and anti-cancerous activities that may be beneficial if further studies are conducted to identify chemical compounds that may inhibit anticervical cancer activities.

A dissertation submitted in fulfilment of the requirements for the degree of Masters in Science in the School of Molecular and Cell Biology, University of the Witwatersrand Johannesburg, 2013 / Cervical cancer is a gynaecological malignant disorder and is a common cause of death in women of the sub-Saharan Africa, striking nearly half a million of females each year worldwide. Cervical cancer is due to the persistence infection of human papillomavirus (HPV), a formidable virus that targets the cervix and is present in most cancers of the cervix. In South Africa, plants used to treat cancer are rare and there is a need for screening further plant extracts in order to identify potentially new anti-cancer drug discovery leads. The purpose of this study was to screen Tulbaghia violacea (TV) and Agave palmeri (AG) for anti-cancer therapy in the cervical cancer cell lines HeLa and ME-180 and in the fibroblast cell line KMST-6. Staurosporine (ST) was used as a positive control. AG and TV crude plant extracts were screened for apoptosis induction, followed by elucidation of the role of Bax, Bcl-2, p53, Rb, RBBP and Mdm2 genes in cervical cancer. Plant extracts of TV and AG were time (24 hours) and dose (50, 100, 150 μg/ml) dependently screened against cervical cancer cell lines HeLa, ME-180 and in KMST-6 for anti-cancer activity using the thiazolyl blue test (MTT) assay. With an IC50 ~ 150 μg/ml, T. violacea extract exhibited significant cytotoxicity on both HeLa and ME-180 cancer cell lines, whilst A. palmeri was cytotoxic to ME-180 cells and 25nM ST as a positive control had a cytoxicity effect on all cell lines including the KMST-6, yet TV and AG had no cytotoxic effect on KMST-6. The annexin-V/FITC detection assay was performed to evaluate the occurrence of apoptosis. Crude extracts of TV and AG together with ST induced significant apoptosis of HeLa, ME-180 and KMST-6 cells. The crude extracts were further analysed for DNA fragmentation, protein expression and gene expression by Western Blot and RT-PCR respectively, to investigate whether these extracts have an effect on the on the expression of Bax, Bcl-2, p53, Rb, RBBP6, Mdm2 and the relationship between p53 and RBBP6. Morphological and biochemical changes were seen in this study. A further mixed response by several genes was observed following treatment with the two plant extracts, where RBBP6 was seen to be spliced in cancer cells while Bax was induced and Bcl-2 was inhibited, but the levels of p53 remained the same. Preliminary, the extracts of TV and AG induce cell death by down-regulating Bcl-2 and Mdm2. Quantitative RT-PCR showed that when p53 was silenced RBBP6 was up-regulated and vice versa. From these results it was deduced that RBBP6 gene interacts with p53 during cervical cancer development. The anti-proliferative activity together with the characterization of p53, RBBP6 and Mdm2 and concentrations of these plant extract could be manipulated as diagnostic markers and potential therapeutic targets for cancer treatment; however, further studies on these plant extracts need to be performed to validate results obtained in this study.

published_or_final_version / Pathology / Master / Master of Medical Sciences

published_or_final_version / Obstetrics and Gynaecology / Doctoral / Doctor of Philosophy