Introduction: Cervical cancer is the fourth most common malignancy diagnosed in women worldwide. It results from cellular transformation by the high-risk human papillomavirus (HPV) oncogenes E6 and E7, which accounts for more than 99% of diagnosed cases. HPV links its life cycle to epithelial proliferation and differentiation, which requires the cells to remain active in cell cycle. p63 modulates epithelial development as well as proliferation, differentiation and DNA damage response (DDR), which makes it an important target for HPV oncoproteins to allow viral replication and survival in infected cells. Methods: In this study, small interfering RNAs targeting E7 oncoprotein and p63 in the HPV16 positive cervical cancer cell line CaSki were used. Western blotting, proliferation assays, apoptosis assays and cell cycle analysis were applied to examine the effects of E7 and p63 depletion on cell fate. Overexpression of different types of HPV-E7 was performed in the N/Tert-1 keratinocyte cell line to study the effect of E7 overexpression on p63 level. Results: E7 drives the expression of p63 at both transcript and protein levels in cervical cancer cell lines. Downregulation of E7 is accompanied by a remarkable inhibition of cell proliferation and cell cycle arrest in the G0/G1 phase. Depletion of E7 is associated with a significant reduction in p63 expression which is not due to impaired proliferation or induced differentiation. Downregulation of p63 is associated with delayed DDR in cervical cancer cells following treatment with ionising radiation. High-risk HPV E7s are more potent in inducing p63 upregulation and increasing the proliferation rates in keratinocytes. Conclusion: This work for the first time demonstrated that E7 modulates the expression of p63, which regulates DNA damage repair pathways, that promotes efficient and rapid repair of the DNA damage following ionising radiation treatment in cervical cancer cells. Tumour recurrence due to resistance to radiotherapy is common, mostly due to promoted DNA repair ability of cancer cells to reduce radiation-induced toxicity and increase cell survival in response to ionising radiation. These findings might be the key to the development of radioresistance in cervical cancer. The HPV E7-p63 axis may be a novel therapeutic target to enhance radio-sensitivity in HPV-transformed tumours.

Thesis (M.Sc. (Medical Laboratory Sciences)) -- University of the North, 1986 / Refer to the document

Health communication has become a popular way for health promotion. Public service advertisements of disease prevention construct the understanding of disease and actions toward caution and healing. However, the health messages provided by mass media are not neutral and value-free information; instead, they imply with domestic cultural values, moral regulation, and social order by framing people who affect a disease as lack of self-control, self-surveillance, and negligent behavior. A series of cervical cancer preventing advertisements long-term sponsored by P&G is selected for studying samples. The aims of this research are to discover the power, ideology and dominant discourse about women's health in advertisements. Semiotic theory is adopt as analyzing methodology in exploring mainstream discourse about women's health and body regulation in Taiwan, through voice-over, story, and images in advertising. This research finds that information for preventing cervical cancer appeared through media is full of patriarchy ideology. The perception of "healthy" women body is shaped to fit social expectations in female characters, as well-controlled, fragile and protection needed, as well as capability for giving birth of a child. The advertising represents social construction of illness, and defines women's health problems as individual and private responsibility. The importance of national health policy and the force of social control are absent and ignore. Thus, to disclose how patriarchy, dominant ideologies which undermines women's health are implemented in health communication is the main purpose of this paper.

Introduction: Human papillomavirus (HPV) is the sexually transmitted etiologic agent of cervical cancer. While HPV infects both men and women, little is known about HPV infection in men. Specifically, knowledge of the prevalence of type-specific HPV infection and the distribution of these infections by anogenital anatomic site in men is incomplete. Evaluation of factors associated with HPV infection based on complete anogenital sampling and with HPV-16 antibody detection may lead to a better understanding of HPV transmission and prevention.Methods: A total of 493 asymptomatic men ages 18 to 40 years old were recruited in Tucson, Arizona, and Tampa, Florida, from 2003 to 2006. Eligibility requirements included having had sex with a woman within the past year and having no history of genital warts. Testing for HPV from anogenital swabs from six anatomic sites and semen was conducted by PCR and reverse line blot genotyping for 37 HPV types. Serum antibodies for HPV-16 were detected by ELISA. Self-administered demographic, health, and sexual history/behavior questionnaires were collected. HPV prevalence and type distributions by anatomic site were calculated, as was seroprevalence of HPV-16 antibodies. Multivariate logistic regression was used to identify independent risk factors for HPV infection at any anatomic site and for having HPV-16 antibodies.Results: HPV was detected in at least one sample for 303 (65.4%) men, with 29.2% of men having an oncogenic infection and 36.3% having a non-oncogenic infection. Multiple HPV types were detected in 27.2% of men. Factors associated with infection were a greater lifetime number of female sexual partners, currently smoking 10 or more cigarettes per day, lack of condom use, and more sexual partners in the past three months. HPV-16 antibodies were detected in the serum of 63 (12.8%) men, and detection was associated with increasing age and concurrent detection of HPV DNA in perianal or anal canal samples.Discussion: The combination of more complete anogenital sampling and sensitive HPV detection for 37 HPV types resulted in a higher HPV prevalence in asymptomatic men than previously reported. Smoking and condom use were the most important modifiable risk factors for HPV in men. These results have implications for research of HPV transmission.

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The quantification of human papillomavirus (HPV) oncogene transcripts, E6 and E7, may be predictive of viral oncogenesis and cancer progression. The main objectives of this study were to determine the HPV genotype prevalence and distribution in Edmonton, Alberta, and characterize a quantifiable association of HPV E6/E7 mRNA expression with the presence of cervical disease. Successful clinical trial design and patient enrolment lead to the first controlled characterization of HPV genotype epidemiology in Alberta. HPV-16 was identified as the most prevalent genotype, followed by several non-vaccine genotypes (HPV-31, -52). Despite rigorous experimentation and a significant correlation between high-risk HPV infection and cervical lesions (p<0.05), absolute quantification of viral oncogenesis was unsuccessful. The ability to quantify oncogene transcriptional activity may, in time, revolutionize cervical cancer screening programmes, akin to the Pap smear several decades ago. However, as experienced in this study and in others, great challenges and even greater questions remain unanswered.

Made available in DSpace on 2014-06-11T19:26:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2004Bitstream added on 2014-06-13T18:54:33Z : No. of bitstreams: 1 silva_lb_dr_botfm.pdf: 605089 bytes, checksum: bec6d983893cad255fb1520e318c457b (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Investigar a viabilidade da detecção do linfonodo sentinela (LNS) utilizando o mapeamento linfático radioisotópico com 99m-Técnécio–fitato em pacientes submetidas a histerectomia radical e linfadenectomia pélvica para tratamento de câncer de colo uterino. Entre julho de 2001 e fevereiro de 2003, 56 pacientes com câncer de colo uterino estádios (FIGO) I (n=52) e II (n=4) foram submetidas à detecção do linfonodo sentinela por meio da linfocintilografia pré-operatória (99mTc-fitato injetado no colo uterino às 3, 6, 9 e 12h , na dose de 55-74MBq e volume de 0,8ml) e do mapeamento linfático intra-operatório com gamma probe. A histerectomia radical foi abortada em três casos devido à infiltração parametrial constatada durante a cirurgia, sendo realizada somente a ressecção dos linfonodos sentinelas. As demais 53 pacientes foram submetidas à histerectomia radical com linfadenectomia pélvica. Os linfonodos sentinelas foram identificados utilizando-se o gamma probe e foram enviados para avaliação histopatológica durante o procedimento cirúrgico. Das 56 pacientes selecionadas, o linfonodo sentinela foi detectado em 52 (92,8%), num total de 120 detectados pela linfocintilografia (média de 2,2 por paciente) e no per-operatório pelo gamma probe. Na cadeia ilíaca externa foram identificados 44% deles, 39% na fossa obturatória, 8,3% na bifurcação das ilíacas e 6,7% na cadeia ilíaca comum. Em 31 pacientes (59%), ele foi identificado unilateralmente e em 21 (41%) bilateralmente. Metástase linfonodal foi confirmada em 17 (32%) casos. Em 10 (59%), somente o linfonodo sentinela apresentava metástase. Os 98 que se apresentaram negativos à hematoxilina-eosina foram encaminhados para avaliação imunohistoquímica para citoqueratina. Cinco (5,1%) micrometástases foram identificadas por essa técnica. A sensibilidade do linfonodo sentinela foi de 82,3%... / Investigate the feasibility of sentinel lymph node identification using radioisotopic lymphatic mapping with technetium-99m-labeled phytate in patients undergoing radical hysterectomy with pelvic lymphadenectomy for treatment of cervical cancer. Between July 2001 and February 2003, 56 patients with cervical cancer FIGO stages I (n = 52) and II (n = 4) underwent sentinel lymph node detection with preoperative lymphoscintigraphy (99mTc-labeled phytate injected into the uterine cervix, at 3, 6, 9 and 12 o`clock, at a dose of 55-74 MBq in a volume of 0.8 ml) and intraoperative lymphatic mapping with a handheld gamma probe. Radical hysterectomy was aborted in three cases because parametrial invasion was found intraoperatively, and we performed only sentinel node resection.The remaining 53 patients underwent a radical hysterectomy with complete pelvic lymphadenectomy. Sentinel nodes were detected using a handheld gama-probe and removed for pathological assessment during the abdominal radical hysterectomy and pelvic lymphadenectomy. In 56 eligible patients, the sentinel node was detected in 52 patients (92,8%). A total of 120 sentinel lymph nodes were detected by lymphoscintigraphy (mean 2.27 nodes per patient) and intraoperatively, by gamma probe. Forty-four percent of sentinel nodes were found in the external iliac area, 39% in the obturator region, 8,3% in interiliac region and 6,7% in the common iliac area. In thirty-one patients (59%), unilateral sentinel nodes were found. The remaining 21 patients (41%) had bilateral sentinel nodes. Microscopic nodal metastases were confirmed in 17(32%) of cases. In 10(59%) of these patients, only sentinel nodes had metastases. The 98 sentinel nodes that were negative on hematoxylin and eosin were submitted to cytokeratin immunohistochemical analysis. Five (5,1%) micrometastases... (Complete abstract click electronic access below)

Orientador: Paulo Traiman / Coorientador: Agnaldo Lopes da Silva Filho / Resumo: Investigar a viabilidade da detecção do linfonodo sentinela (LNS) utilizando o mapeamento linfático radioisotópico com 99m-Técnécio-fitato em pacientes submetidas a histerectomia radical e linfadenectomia pélvica para tratamento de câncer de colo uterino. Entre julho de 2001 e fevereiro de 2003, 56 pacientes com câncer de colo uterino estádios (FIGO) I (n=52) e II (n=4) foram submetidas à detecção do linfonodo sentinela por meio da linfocintilografia pré-operatória (99mTc-fitato injetado no colo uterino às 3, 6, 9 e 12h , na dose de 55-74MBq e volume de 0,8ml) e do mapeamento linfático intra-operatório com gamma probe. A histerectomia radical foi abortada em três casos devido à infiltração parametrial constatada durante a cirurgia, sendo realizada somente a ressecção dos linfonodos sentinelas. As demais 53 pacientes foram submetidas à histerectomia radical com linfadenectomia pélvica. Os linfonodos sentinelas foram identificados utilizando-se o gamma probe e foram enviados para avaliação histopatológica durante o procedimento cirúrgico. Das 56 pacientes selecionadas, o linfonodo sentinela foi detectado em 52 (92,8%), num total de 120 detectados pela linfocintilografia (média de 2,2 por paciente) e no per-operatório pelo gamma probe. Na cadeia ilíaca externa foram identificados 44% deles, 39% na fossa obturatória, 8,3% na bifurcação das ilíacas e 6,7% na cadeia ilíaca comum. Em 31 pacientes (59%), ele foi identificado unilateralmente e em 21 (41%) bilateralmente. Metástase linfonodal foi confirmada em 17 (32%) casos. Em 10 (59%), somente o linfonodo sentinela apresentava metástase. Os 98 que se apresentaram negativos à hematoxilina-eosina foram encaminhados para avaliação imunohistoquímica para citoqueratina. Cinco (5,1%) micrometástases foram identificadas por essa técnica. A sensibilidade do linfonodo sentinela foi de 82,3%... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Investigate the feasibility of sentinel lymph node identification using radioisotopic lymphatic mapping with technetium-99m-labeled phytate in patients undergoing radical hysterectomy with pelvic lymphadenectomy for treatment of cervical cancer. Between July 2001 and February 2003, 56 patients with cervical cancer FIGO stages I (n = 52) and II (n = 4) underwent sentinel lymph node detection with preoperative lymphoscintigraphy (99mTc-labeled phytate injected into the uterine cervix, at 3, 6, 9 and 12 o'clock, at a dose of 55-74 MBq in a volume of 0.8 ml) and intraoperative lymphatic mapping with a handheld gamma probe. Radical hysterectomy was aborted in three cases because parametrial invasion was found intraoperatively, and we performed only sentinel node resection.The remaining 53 patients underwent a radical hysterectomy with complete pelvic lymphadenectomy. Sentinel nodes were detected using a handheld gama-probe and removed for pathological assessment during the abdominal radical hysterectomy and pelvic lymphadenectomy. In 56 eligible patients, the sentinel node was detected in 52 patients (92,8%). A total of 120 sentinel lymph nodes were detected by lymphoscintigraphy (mean 2.27 nodes per patient) and intraoperatively, by gamma probe. Forty-four percent of sentinel nodes were found in the external iliac area, 39% in the obturator region, 8,3% in interiliac region and 6,7% in the common iliac area. In thirty-one patients (59%), unilateral sentinel nodes were found. The remaining 21 patients (41%) had bilateral sentinel nodes. Microscopic nodal metastases were confirmed in 17(32%) of cases. In 10(59%) of these patients, only sentinel nodes had metastases. The 98 sentinel nodes that were negative on hematoxylin and eosin were submitted to cytokeratin immunohistochemical analysis. Five (5,1%) micrometastases... (Complete abstract click electronic access below) / Mestre

Master of Science / Department of Journalism and Mass Communications / Nancy W. Muturi / Background: Cervical cancer is one of the leading lethal diseases diagnosed in women globally. By early diagnosis and vaccine, cervical cancer can be prevented. Young adults are mainly at risk of cancer-causing HPV. But they are not motivated to take HPV vaccine and screening test. It is crucial to communicate young adults by education and information about cancer. Electronic health (e-Health) communication strategy has the potential to raise awareness about cancer prevention and control. This study examined the key motivational determinants that are associated with college student’s cervical cancer and HPV prevention behavior in relation to their online health information seeking behavior. Method: An online survey among college students (n= 405), age range 18- 35 years was conducted. All measures were from validated instruments and modified to examine the current study’s objectives structured with key variables derived from the Protection-Motivation theory (PMT). Data from the survey were analyzed statistically using Statistical Package for the Social Sciences (SPSS) software. The reliability of the scales used was assessed through the calculation of coefficient alpha and the dimensionality of the scale was tested through confirmatory factor analysis using the principal components method of extraction. Descriptive of the study variables, Pearson correlation coefficient, One-way ANOVA, and multiple linear regression analysis were done to test the research questions and hypothesis. Results: Result showed that, perceived vulnerability to HPV (β= .17, t= 4.53, p= .000), self-efficacy (β= .13, t= 2.91, p< .01), and response costs (β= .46, t= 10.44, p= .000) were the key motivational variables that are associated with college student’s HPV vaccine and Pap test. In testing predictors for online health information seeking behavior, perceived response-efficacy (β= .20, t= 3.41, p= .001) and response costs (β= .19, t= 3.21, p= .001) gained significance in the model. Also, a Pearson correlation coefficient showed a positive association between college student’s online health information seeking behavior and motivation for preventive measures (r = .10, p = .05). Result demonstrated that, college student’s knowledge about HPV and cervical cancer influenced their motivation for HPV vaccine and Pap test (p< .001) but knowledge did not influence their online health information seeking behavior (p= .43). Conclusion: E-Health strategy can be an effective tool for targeting young adults and should be explored further in cancer communication and vaccine promotion. It is important for cancer communication interventions to promote e-Health strategy and enhance the usage of online health information seeking behavior. The contents of online health education and information need to be upgraded to provide the maximum benefits to the public.

Background: Based primarily on studies concerning early-stage tumours (treated surgically), and locally advanced disease (treated with chemoradiation), the prognosis for women with adenocarcinoma (AC) or adenosquamous (AS) carcinoma has been reported to be poorer than those with squamous cell carcinoma (SCCA) of the cervix. It is unclear whether differences in prognosis also persist in the setting of recurrent or metastatic disease treated using chemotherapy doublets with or without bevacizumab. Methods: Cases were pooled from three Gynaecologic Oncology Group randomised phase III trials of chemotherapy doublets. Pearson's test was used to evaluate response rate (RR) of AC/AS vs SCCA, Kaplan-Meier method to estimate progression-free survival (PFS) and overall survival (OS), and Cox proportional hazards model to estimate the impact of histology on PFS and OS. Results: Of 781 evaluable patients, 77% (N = 599) had SCCA and 23% (N = 182) AC/AS. There were no significant differences in RRs between histologic subgroups. The adjusted hazard ratio (HR) for death for SCCA vs AC/AS was 1.13 (95% CI 0.93, 1.38 P = 0.23). When comparing SC/AS (N = 661, 85%) to AC alone (N = 120, 15%), the adjusted HR for death was 1.23 (95% CI 0.97, 1.57, P = 0.09). Conclusions: AC/AS and SCCA have similar survival in recurrent or metastatic cervical carcinoma when treated with chemotherapy doublets.