O carcinoma escamoso do colo uterino é uma das neoplasias de maior incidência em todo o mundo, inclusive no Brasil, sendo responsável pela morte de milhares de mulheres a cada ano, grande parte delas ocorrendo em plena idade produtiva. Ao longo dos últimos cinqüenta anos, diversos pesquisadores têm estudado esta neoplasia. Sabe-se que a fase invasora do carcinoma escamoso do colo uterino é precedida por uma fase intra-epitelial, precursora (neoplasias intra-epiteliais cervicais/ NICs). As lesões precursoras podem ser divididas em dois grandes grupos: as de baixo grau e as de alto grau (Sistema de Bethesda). Se por um lado, o percentual de lesões de alto grau que evoluem para carcinoma escamoso invasor é grande, por outro lado, somente uma pequena parcela de mulheres que têm lesões precursoras de baixo grau vai desenvolver uma lesão invasora. Entretanto, ainda não somos capazes de identificar entre estas mulheres, quais são as que irão progredir para carcinoma escamoso do colo uterino. O presente estudo procurou avaliar a expressão da p16INK4 em pacientes com lesão de baixo grau do colo uterino, correlacionando com a presença de HPV-DNA e sua evolução ao longo do tempo. O estudo acompanhou 118 pacientes por um período máximo de 33 meses, examinando-as com intervalos de 6 meses. A conclusão foi que a p16INK4 se relacionada positivamente com infecção múltipla por HPV e que nestas pacientes a expressão da mesma chega a 100% de células neoplásicas coradas. Algumas pacientes evoluíram para lesão de alto em um período curto de tempo (alguns meses). / Submitted by Marcelo Teixeira (mvteixeira@ucs.br) on 2014-05-30T17:01:47Z No. of bitstreams: 1 Tese Alessandra Eifler Guerra Godoy.pdf: 1370166 bytes, checksum: 0965c1e23a9ee5918d5880f1bd52fb52 (MD5) / Made available in DSpace on 2014-05-30T17:01:47Z (GMT). No. of bitstreams: 1 Tese Alessandra Eifler Guerra Godoy.pdf: 1370166 bytes, checksum: 0965c1e23a9ee5918d5880f1bd52fb52 (MD5) / The squamous carcinoma of the cervix uterine is one of the neoplasias of bigger incidence in the whole world, also in Brazil, being responsible for the death of thousand of women to each year, great part of them occurring in full productive age. Throughout last the fifty years, diverse researchers have studied this neoplasia. We know that the invading phase of the squamous carcinoma of the cervix uterine is preceded by an intra-epithelial phase, precursory (cervical intraepithelial neoplasia - CIN). The precursory injuries can be divided in two great groups: of low degree and of high degree (Bethesda System). If on the other hand, the percentage of injuries of high degree that evolve for invading squamous carcinoma is great, on the other hand, a small parcel of women whom they have precursory injuries of low degree only goes to develop an invading injury. However, not yet we are capable to identify between these women, which are the ones that will go to progress for squamous carcinoma of the cervix uterine. The present study it looked for to evaluate the expression of p16INK4 in patients with injury of low degree of the uterine col, correlating with the presence of HPV-DNA and its evolution throughout the time. The study it folloied 118 patients for a maximum period of 33 months, examining them with intervals of 6 months. The conclusion was that p16INK4 if related positively with multiple infection for HPV and that in these patients the expression of the same one arrives the 100% of neoplastic cells stained. Some patients developed high lesion in a short period of time (several months).

Diversas alterações de expressão proteica decorrentes do desenvolvimento canceroso cervical e dependentes do papilomavírus humano (HPV) vêm sendo apontadas na literatura, dentre elas destacam-se proteínas diretamente influenciadas pela ação de oncoproteínas do HPV, como: transglutaminase 2 (TG2) e p53 e proteínas com expressão modificada relacionada a alterações de controle de ciclo celular, como: p16INK4a, ki-67 e bcl-2. Neste estudo, objetivou-se analisar níveis expressionais de TG2, p16INK4a, p53, Ki-67 e bcl-2 em amostras de lesões escamosas intraepiteliais de baixo (LEIBG) e alto grau (LEIAG), precursoras do carcinoma escamoso de colo uterino e relacionar esta expressão a diferentes tipos virais do HPV. Foram utilizadas amostras histológicas obtidas por biópsia dirigida do colo uterino de pacientes, previamente confirmadas quanto à presença do HPV-DNA por reação em cadeia da polimerase (PCR) e tipagem viral. A quantificação da expressão ocorreu por meio da técnica de imunohistoquímica. Observou-se em LEIBG a elevada expressão de TG2 (p<0.05) e diminuída expressão de p16INK4a (p<0.05) enquanto que em LEIAG, esta proporção inverteu-se (Pearson value = -0.269). A expressão de p53 demonstrou-se variável em relação aos graus de lesão. As expressões de Ki-67 e bcl-2 variaram conforme os níveis teciduais das biópsias coletadas. A proteína p16INK4a apresentou sua expressão associada a HPV considerados de alto risco oncogênico (p<0.001), TG2 teve sua expressão associada ao HPV tipo 11 (p<0.05). Não foram evidenciadas associações significantes entre a expressão de p53, Ki-67 e bcl-2 e os tipos virais. Conclui-se que a expressão dos marcadores estudados foi influenciada pelo processo canceroso no colo uterino e pela infecção do HPV. / Submitted by Ana Guimarães Pereira (agpereir@ucs.br) on 2016-12-01T15:25:28Z No. of bitstreams: 1 Tese Karen Olivia Bazzo.pdf: 1961310 bytes, checksum: 63b5807c5c5cf317075c1e19cf0f168c (MD5) / Made available in DSpace on 2016-12-01T15:25:28Z (GMT). No. of bitstreams: 1 Tese Karen Olivia Bazzo.pdf: 1961310 bytes, checksum: 63b5807c5c5cf317075c1e19cf0f168c (MD5) Previous issue date: 2016-12-01 / Universidade de Caxias do Sul, UCS. / Changes in protein expression resulting from cervical cancer development and dependent on human papillomavirus (HPV) have been indicated in the literature, among them there are proteins directly influenced by HPV oncoproteins, such as transglutaminase 2 (TG2), p53; and proteins with modified expression related to cell cycle control changes, such as p16 INK4a a, ki-67 and bcl-2. This study aimed to analyze expressionais levels of TG2, p16INK4a, p53, ki-67 and bcl-2 in High-grade (HSIL) and low-grade (LSIL) squamous intraepithelial lesion and relate this expression to different viral types of HPV. Tissue samples obtained by biopsy were used directed cervical patients, previously genotyped HPV-DNA. Expression quantification were performed by immunohistochemical technique. It was observed in LSIL the overexpression of TG2 (p<0.05) and decreased expression of p16INK4a (p<0.05) although in HSIL, the proportion was reversed (Pearson value = -0.269). P53 expression was variable in relation to the degree of injury. The expression of ki-67 and bcl-2 levels varied depending beyond the basal layer. p16INK4a presented its expression associated with high-risk types of HPV (p<0.001) and TG2 expression was associated with HPV 11 (p<0.05). No significant associations were found between the viral types and the ki-67, p53 and bcl-2 expression. In conclusion, the expression of the marker is affected by cancerous process and by HPV infection, and expression analysis of these markers may reveal new biomarkers associated with cervical cancer process.

Orientador : Christiane Pienna Soares / Coorientador: Valeria Valente / Banca: Raquel Alves dos Santos / Banca: Cleverton Roberto de Andrade / Resumo: O câncer de colo de útero é um problema de saúde pública mundial, especialmente nos países em desenvolvimento, configurando a quarta neoplasia feminina mais comum no mundo. A infecção pelo Papilomavírus Humano (HPV) é o principal fator de risco para o desenvolvimento do referido câncer, estando presente em 90% dos casos de câncer de colo uterino na população mundial. Frente a busca por novos agentes quimioterapêuticos, os produtos naturais tem contríbuido intensamente para a identificação dessas substâncias e o desenvolvimento da terapêutica moderna. Maitenina, é um triterpeno quinonametídeo extraído das raízes da plana Maytenus ilicifolia, que possui algumas atividades biológicas já relatadas, como antifúngica, antiprotozoária e principalmente ação antitumoral. No momento não existem relatos na literatura relacionando a atividade da maitenina em células infectadas por HPV-16. O objetivo do presente estudo foi avaliar a citotoxicidade da maitenina em linhagem de carcinoma cervical infectada por HPV-16 (SiHa), não-infectada pelo vírus (C-33 A) e queratinócitos humanos imortalizados (HaCaT), bem como verificar a indução de apoptose e/ou necrose pelo ensaio de Hoechst e Iodeto de Propídeo e indução de apoptose pela atividade de caspase-3 nas três linhagens celulares, além de verificar alterações no ciclo celular das células tratadas com maitenina e o potencial de genotoxicidade e mutagenicidade, além de avaliar a proliferação das três linhagens. O ensaio de citotoxicidade foi realizado pelo método da sulforodamina B, e as três linhagens celulares foram tratadas durante 6, 12 ou 24 horas. Foi possível observar um efeito concentração e tempo resposta nas três linhagens analisadas. O CI50 foi de 3,26, 8,49 e 3,09 μM para as linhagens SiHa, C-33 A e HaCaT respectivamente, no tempo de tratamento de 24 horas. Com o intuito de avaliar o potencial efeito indutor de apoptose foi realizado o ensaio... / Abstract: Cervical cancer is a worldwide public health problem, especially in developing countries, setting the fourth most common female cancer in the world. The infection by human papillomavirus (HPV) is the main risk factor for the development of this cancer, being present in 90% of cases of cervical cancer in the world population. Forward the search for new chemotherapeutic agents, natural products have strongly contributed to the identification of these substances and the development of modern therapeutics. Maytenin is a quinonemethide triterpene extracted from the roots of Maytenus ilicifolia plant, which has some biological activities previously reported as an antifungal, antiprotozoal and especially antitumor action. At the moment there are no reports in the literature relating the activity of maytenin in infected cells by HPV-16. The aim of this study was to evaluate the cytotoxicity of maytenin in cervical carcinoma line infected by HPV-16 (SiHa), non-infected by the virus (C-33 A) and by immortalized human keratinocytes (HaCaT), as well as verifying the induction of apoptosis and / or necrosis by Hoechst test and propidium iodide and the induction of apoptosis by caspase-3 activity in all three cell lines, in addition to check for changes in the cell cycle of treated cells with maytenin and the potential of genotoxicity and mutagenicity, and to evaluate the proliferation of the three cell lines. The cytotoxicity assay was performed by sulforhodamine B method and the three cell lines were treated during 6, 12 or 24 hours. It was possible to observe a concentration effect and response time in three lines analyzed. The IC50 was 3,26, 8,49 and 3,09 μM for SiHa, C-33 A and HaCaT lines respectively, in 24 hours treatment time. In order to evaluate the potential inductive effect of apoptosis it was performed a marking cytomorphological test with Hoechst and propidium iodide in 6 and 12 hours treatment times, and for the three cell lines it was ... / Mestre

Thesis (MTech (Radiography))--Cape Peninsula University of Technology, 2011. / The focus of this study is on the presentation patterns of invasive cancer of the cervix (CaCx) in Zimbabwe. The study was undertaken at a large referral cancer treatment centre in Harare the capital city of Zimbabwe. The main study question addressed was: Are there any changes in the presentation patterns of invasive CaCx in Zimbabwe? This was subdivided into three sub questions: 1) What are the presentation patterns of invasive CaCx among the Zimbabwean women presenting to the major referral centre in terms of histology, stage of the disease, ages of patients, Human immunodeficiency virus (HIV) status and socioeconomic status? 2) What is the trend in the presentation patterns of invasive CaCx in terms of the study variables during the period of study? 3) Are there any correlations that exist among the study variables? This study was conducted because of the sharp contrast that exists in invasive CaCx presentation patterns and incidence between the developed and developing countries. The incidence is now very low in developed countries while it is continuing to rise in developing countries resulting in death among women at a time when they are supposed to be more effective in their families and the nation at large. A retrospective documentary study of patients' files using an observation check list was done from 1998 to 2010. A systematic sample of four years was selected with 1998 as the base year (1998, 2002, 2006 and 2010). To strengthen the sample all the available patients' files for the selected years were considered. On average the majority of the patients (91.75%) presented with squamous cell carcinoma (SCC), 5.5% presented with adenocarcinoma and 2.75% with other types of histology. It was found that (89%) of women presented with late stage disease (stage liB and above). The ages of patients at presentation were between 40 to 60 years. Very few patients had recorded HIV status in 1998 and 2002 but a significant increase in proportion of patients with known HIV status was noted in 2006 (48%) and 2010 (73%). The average percentage for HIV positive patients for 2006 and 2010 was 57% and the average percentage for HIV negative patients was 43%. The majority (58.25%) of the patients were of low socioeconomic status. No significant change in trend was noted for variables except for HIV status where there was a downward trend in the percentage of HIV positive patients and an upward trend in the percentage of HIV negative patients. When correlation analysis was done among the variables no significant association was noted among the variables except that a low degree of association was recorded for the ages of patients and HIV status. The association indicated that young invasive CaCx patients are associated with HIV infection at presentation. The recommendations are that the government should mobilize resources towards prevention and control of invasive cancer of the cervix and awareness campaigns on early presentation should increase. Furthermore the cancer registry should expand its services to cover all health institutions nationwide. It is also recommended that further studies should be done on the presentation patterns of invasive CaCx and of HIV status. Longitudinal studies are recommended in order to monitor changes in presentation patterns.

Diversas alterações de expressão proteica decorrentes do desenvolvimento canceroso cervical e dependentes do papilomavírus humano (HPV) vêm sendo apontadas na literatura, dentre elas destacam-se proteínas diretamente influenciadas pela ação de oncoproteínas do HPV, como: transglutaminase 2 (TG2) e p53 e proteínas com expressão modificada relacionada a alterações de controle de ciclo celular, como: p16INK4a, ki-67 e bcl-2. Neste estudo, objetivou-se analisar níveis expressionais de TG2, p16INK4a, p53, Ki-67 e bcl-2 em amostras de lesões escamosas intraepiteliais de baixo (LEIBG) e alto grau (LEIAG), precursoras do carcinoma escamoso de colo uterino e relacionar esta expressão a diferentes tipos virais do HPV. Foram utilizadas amostras histológicas obtidas por biópsia dirigida do colo uterino de pacientes, previamente confirmadas quanto à presença do HPV-DNA por reação em cadeia da polimerase (PCR) e tipagem viral. A quantificação da expressão ocorreu por meio da técnica de imunohistoquímica. Observou-se em LEIBG a elevada expressão de TG2 (p<0.05) e diminuída expressão de p16INK4a (p<0.05) enquanto que em LEIAG, esta proporção inverteu-se (Pearson value = -0.269). A expressão de p53 demonstrou-se variável em relação aos graus de lesão. As expressões de Ki-67 e bcl-2 variaram conforme os níveis teciduais das biópsias coletadas. A proteína p16INK4a apresentou sua expressão associada a HPV considerados de alto risco oncogênico (p<0.001), TG2 teve sua expressão associada ao HPV tipo 11 (p<0.05). Não foram evidenciadas associações significantes entre a expressão de p53, Ki-67 e bcl-2 e os tipos virais. Conclui-se que a expressão dos marcadores estudados foi influenciada pelo processo canceroso no colo uterino e pela infecção do HPV. / Universidade de Caxias do Sul, UCS. / Changes in protein expression resulting from cervical cancer development and dependent on human papillomavirus (HPV) have been indicated in the literature, among them there are proteins directly influenced by HPV oncoproteins, such as transglutaminase 2 (TG2), p53; and proteins with modified expression related to cell cycle control changes, such as p16 INK4a a, ki-67 and bcl-2. This study aimed to analyze expressionais levels of TG2, p16INK4a, p53, ki-67 and bcl-2 in High-grade (HSIL) and low-grade (LSIL) squamous intraepithelial lesion and relate this expression to different viral types of HPV. Tissue samples obtained by biopsy were used directed cervical patients, previously genotyped HPV-DNA. Expression quantification were performed by immunohistochemical technique. It was observed in LSIL the overexpression of TG2 (p<0.05) and decreased expression of p16INK4a (p<0.05) although in HSIL, the proportion was reversed (Pearson value = -0.269). P53 expression was variable in relation to the degree of injury. The expression of ki-67 and bcl-2 levels varied depending beyond the basal layer. p16INK4a presented its expression associated with high-risk types of HPV (p<0.001) and TG2 expression was associated with HPV 11 (p<0.05). No significant associations were found between the viral types and the ki-67, p53 and bcl-2 expression. In conclusion, the expression of the marker is affected by cancerous process and by HPV infection, and expression analysis of these markers may reveal new biomarkers associated with cervical cancer process.

O carcinoma escamoso do colo uterino é uma das neoplasias de maior incidência em todo o mundo, inclusive no Brasil, sendo responsável pela morte de milhares de mulheres a cada ano, grande parte delas ocorrendo em plena idade produtiva. Ao longo dos últimos cinqüenta anos, diversos pesquisadores têm estudado esta neoplasia. Sabe-se que a fase invasora do carcinoma escamoso do colo uterino é precedida por uma fase intra-epitelial, precursora (neoplasias intra-epiteliais cervicais/ NICs). As lesões precursoras podem ser divididas em dois grandes grupos: as de baixo grau e as de alto grau (Sistema de Bethesda). Se por um lado, o percentual de lesões de alto grau que evoluem para carcinoma escamoso invasor é grande, por outro lado, somente uma pequena parcela de mulheres que têm lesões precursoras de baixo grau vai desenvolver uma lesão invasora. Entretanto, ainda não somos capazes de identificar entre estas mulheres, quais são as que irão progredir para carcinoma escamoso do colo uterino. O presente estudo procurou avaliar a expressão da p16INK4 em pacientes com lesão de baixo grau do colo uterino, correlacionando com a presença de HPV-DNA e sua evolução ao longo do tempo. O estudo acompanhou 118 pacientes por um período máximo de 33 meses, examinando-as com intervalos de 6 meses. A conclusão foi que a p16INK4 se relacionada positivamente com infecção múltipla por HPV e que nestas pacientes a expressão da mesma chega a 100% de células neoplásicas coradas. Algumas pacientes evoluíram para lesão de alto em um período curto de tempo (alguns meses). / The squamous carcinoma of the cervix uterine is one of the neoplasias of bigger incidence in the whole world, also in Brazil, being responsible for the death of thousand of women to each year, great part of them occurring in full productive age. Throughout last the fifty years, diverse researchers have studied this neoplasia. We know that the invading phase of the squamous carcinoma of the cervix uterine is preceded by an intra-epithelial phase, precursory (cervical intraepithelial neoplasia - CIN). The precursory injuries can be divided in two great groups: of low degree and of high degree (Bethesda System). If on the other hand, the percentage of injuries of high degree that evolve for invading squamous carcinoma is great, on the other hand, a small parcel of women whom they have precursory injuries of low degree only goes to develop an invading injury. However, not yet we are capable to identify between these women, which are the ones that will go to progress for squamous carcinoma of the cervix uterine. The present study it looked for to evaluate the expression of p16INK4 in patients with injury of low degree of the uterine col, correlating with the presence of HPV-DNA and its evolution throughout the time. The study it folloied 118 patients for a maximum period of 33 months, examining them with intervals of 6 months. The conclusion was that p16INK4 if related positively with multiple infection for HPV and that in these patients the expression of the same one arrives the 100% of neoplastic cells stained. Some patients developed high lesion in a short period of time (several months).

Orientador: Paulo Cesar Giraldo / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-08T21:42:54Z (GMT). No. of bitstreams: 1 EleuterioJunior_Jose_D.pdf: 17867889 bytes, checksum: 0d9e1c3f2399c5be86d6fbf719dc98c4 (MD5) Previous issue date: 2007 / Resumo: Objetivos: Estudar a importância de determinados marcadores de diagnóstico e prognóstico de lesões escamosas genitais, com ênfase nos estudos de p16INK4a e HPV de alto risco. Material e Métodos: Marcadores tumorais foram revisados em 21 estudos publicados entre 1994 e 2005, no sentido de identificar aqueles que teriam melhor valor diagnóstico e/ou prognóstico das lesões intra-epiteliais escamosas. Revisão mais apurada avaliou os marcadores p16INK4a e HPV de alto risco em lesões do colo uterino (36 publicações entre 1994 e 2006). Estudou-se a associação do p16INK4a e HPV de alto risco em 96 amostras de colo utenno (13 casos de lesão intra-epitelial escamosa de alto grau (HSIL), 26 casos de lesão intra-epitelial escamosa de baixo grau (LSIL) e 57 biópsias normais. O p16INK4a foi identificado por imuno-histoquímica, usando-se o p16INK4a kit (E6H4 clone, DakoCytomation, Carpinteria, CA) e o DNA-HPV foi classificado por captura híbrida (Digene®). Associações foram avaliadas pelo índice KAPPA. No artigo foram envolvidos 54 homens, parceiros sexuais assintomáticos de mulheres com lesão intra-epitelial escamosa de baixo grau associada com HPV de alto risco, com a finalidade de verificar se a presença do HPV de alto risco poderia ajudar a identificar os casos com maior risco de ter lesões intra-epiteliais penianas, devendo submeter-se à biópsia. O DNA-HPV foi testado por captura híbrida (Digene®) em raspados do pênis. Peniscopia identificou lesões suspeitas que resultaram em biópsias. Resultados: As revisões demonstraram uma clara potencialidade clínica no uso da associação do p16INK4a e do HPV de alto risco no diagnóstico das SIL do colo uterino, e um possível uso como fator prognóstico. O p16INK4a foi detectado em 92,3% das HSIL, em 15,4% das LSIL e em nenhum caso de histologia normal. Encontrou-se respectivamente sensibilidade, especificadade, valor preditivo positivo e valor preditivo negativo de 92,3%, 100%, 100% e 98,3%, de p16INK4a para HSIL e 100%, 70,42%, 43,3% e 100% do HPV de alto risco para HSIL. No segundo estudo o HPV de alto risco estava presente em 25,9% dos parceiros. A peniscopia levou a 13 biópsias (24,07%) com os seguintes diagnósticos: condiloma (2 casos), PIN I (2 casos), PIN II (1 caso) e histologia normal (8 casos). O teste de HPV de alto risco revelou 80% de sensibilidade, 100% de especificidade, 100% de valor preditivo positivo e 88,9% de valor preditivo negativo para identificação de lesões penianas, mostrando que homens com HPV de alto risco positivo têm maior chancer de ter lesões escamosas penianas em biópsias guiadas pela peniscopia que aqueles com lesões aceto-brancas com teste de HPV negativo, (p = 0.007); OR = 51 (Cl 1.7-1527.1). Conclusões: Marcadores como o HPV de alto risco têm um potencial muito grande para aumentar o poder diagnóstico das HSIL e, principalmente, supor o prognóstico da evolução destas lesões, principalmente quando associado ao p16INK4a / Abstract: Objectives: To study the importance of the diagnostic and prognostic markers of genital squamous lesions, meanly p16INK4a and high risk HPV. Material And Methods: Squamous intra-epithelial lesion tumoral markers were revised in 21 publications between 1994 and 2005 to identify those with diagnostic and prognostic value. More accurate revision assessed the markers p16INK4a and high risk HPV (36 publications between 1994 and 2006). The p16INK4a and high-risk Human papillomavirus were investigated in 96 samples of the cervix (13 cases of high grade squamous intraepithelial lesions, 26 cases of low grade intraepithelial lesions and 57 normal tissues). The p16INK4a was identified by immunohistochemistry using the p16INK4a kit (E6H4 clone, DakoCytomation, Carpinteria, CA). and Human papillomavirus DNA was classified by hybrid capture (Digene®). Associations were evaluated by the KAPPA index. In the other report fifty four asymptomatic male sexual partners of women with low grade squamous intraepithelial lesions (LSIL) associated to high risk HPV were examined, between April 2003 and June 2005, to verify if the high risk HPV could help to identify those with more risk to have a squamous penile lesion. The DNA-HPV was tested by second generation Hybrid Capture (Digene ®) in penile scraped samples. Peniscopy identified suspicious lesions leading to biopsy. Results: The revisions showed the clinical potentiality of the concomitant use of high risk HPV and p16INK4a in diagnosis of cervical SIL and a possible utility in prognosis of genital squamous intra-epithelial. In 96 cervical biopsies, p16INK4a was detected in 92.3% of the high-grade squamous intraepithelial lesions, in 15.4% of the low-grade and in none of the normal tissues. The sensitivity, specificity, positive predictive value and negative predictive value for high-grade lesion were 92.3%, 100%, 100%, and 98.3%, respectively when considering p16INK4a expression, and 100%, 70.2%, 43.3% and 100%, respectively when considering high-risk HPV. In the male partner study high risk HPV was present in 25.9% (14/54) of the cases. Peniscopy led to 13 biopsies (24.07%). Condyloma (2 cases), PIN I (2 cases), PIN II (1 case) and normal tissue (8 cases) were found. The high risk HPV test presented 80% sensitivity, 100% specificity, 100% positive predictive value and 88.9% negative predictive value for the identification of penile lesions. So, there was a greater chance in finding HPV lesions in the biopsy in the positive cases for high risk HPV with abnormal peniscopy than in the negative cases for high risk HPV with anormal peniscopy (p = 0.007); OR = 51 (CI 1.7-1527.1). Conclusions: Markers as high risk HPV have a potential to increase the diagnostic of HPV induced lesions and maybe indicate the evolution, meanly associated with p16INK4a / Doutorado / Tocoginecologia / Doutor em Tocoginecologia

M.Tech. / The aim of this study was to determine the effects of the application of therapeutic reflexology as a complementary medicine, in women with cervical cancer who were receiving radiation therapy with curative intent. Therapeutic reflexology is a therapy that involves stimulating specific reflexes in the hands, feet, body and ears by applying pressure to these reflexes with the thumbs and fingers, using specific techniques. All the body’s organs, glands and other parts of the body are reflected in the feet, body, hands and ears can be stimulated by working over the skin surface with the thumbs and fingers for a specific effect. These specific reflexes have been mapped in miniature on the feet, hands, body and ears (Graham, 1998: 5). Therapeutic reflexology promotes homeostasis within the body, by stimulating reflexes pertaining to organs and glands, and achieving normalisation of organs and glands in the receiver of the treatment. The therapy is non - invasive and non - pharmacological, and has no contra-indications (Graham, 1998: 8). Therapeutic reflexology is often used as a complementary or alternative medicine, yet very little information is available on its effects, which requires further research (Milligan, 2002: 489-96). The number of cancer patients using reflexology as a complementary therapy to allopathic medicine is rapidly rising (Apostolides, 1998: 71-95) It is because of this rise in the number of patients seeking complementary therapy that it is of vital importance that more accurate, results-orientated information is made available to both the patient and the medical practitioner. These findings will allow the patient and medical practitioner to make an informed decision regarding the choices available to complement allopathic medicine, to enhance wellbeing, and achieve better results for the allopathic protocol. A sample group of forty-four women were chosen by simple random selection. Twenty three were treated with therapeutic reflexology, and twenty one were given the placebo treatment for six weeks, while undergoing radiation therapy. The patients chosen for the sample group had stage IIIb as well as stage IIb cervical cancer, and were receiving radiation treatment. The result of the study has been determined by evaluating a questionnaire answered by each patient, after each treatment. The control group who received placebo treatment answered the same questionnaire, formulated in accordance with the Likert Scale, for means of comparison.

The effect of the inclusion of sexual behaviour, particularly three sexual orientation classes, on the transmission dynamics of HPV and cervical cancer incidence was investigated. A comprehensive literature review of mathematical models of HPV transmission and the natural history of cervical cancer was concluded. A mathematical model using ordinary differential equations was developed, which incorporated the three sexual orientation classes, and a sexual mixing algorithm for modelling the transmission dynamics. Reproduction numbers, determined through a simplified version of the developed model, indicated that the bisexual population could form a bridge between the heterosexual and homosexual population. The level of interaction is determined by the selection preferences of a bisexual individual to form a partnership with an individual of the same or opposite sex. The model was simulated, with parameters based on a South African population and HPV type 16/18, to investigate the effects of HIV status, sexual orientation and various vaccination strategies on HPV transmission and cervical cancer incidence. The results indicated that HIV status is a significant factor when determining cervical cancer incidence. The results regarding vaccination strategies agreed with results from the literature review with a two sex before sexual debut and catch up program the most effective, noting that with increased vaccination coverage of females the marginal impact on cervical cancer incidence of this approach diminished.

The purpose of this study is to investigate specific contributing factors affecting quality assurance in the diagnosis of conventional cervical smears. More than half of South- African women fail to have one cervical smear in their lifetime and +/- 50 percent of those who do have cervical smears taken, are lost to follow-up. Since cervical cancer is the most common malignancy amongst women in developing countries, the medical profession will have to endeavor to screen a higher rate of women and ensure a 100 percent quality assurance with every patient treated in order to reduce the unacceptable high incidence of cervical carcinoma. At this stage it seems like an impossible task to screen all women in South Africa, due to far-off rural areas, shortage of medical professionals and the lack of knowledge of some women of the necessity of cervical smears. Many newly qualified South-African doctors leave the country to go and work elsewhere. South Africa then in turn has to recruit doctors from other countries to staff the State hospitals and clinics. Some areas have one doctor to thousands of patients, insufficient nursing personnel and inadequate equipment. Doctors in some areas cannot cope with the volume of work and the long hours. One has to accept that the quality of the management of some patients is affected negatively. There are a number of medico-legal issues (world wide) in relation to aspects of cervical cancer prevention practices which are controversial and are of particular concern to all of those involved in cervical cancer prevention. Various countries have therefore formed different national organizations to address the medico-legal issues in screening for the prevention of cancer. These organizations monitors procedures, internal quality control as well as external quality control. In South Africa, medico-legal cases are not so prevalent, but may become so shortly. The South-African medical professionals therefore have to ensure that their quality of work conforms to accepted good practice in all circumstances. State hospitals serve thousands of patients per month and it is an every day occurrence to see long queues of patients sitting waiting for doctors and who often have to come back the following day. The situation appears to be much improved in private practice and since patients have medical cover and accessible medical facilities. Since cervical cancer is the most common malignancy amongst women in developing countries, the medical profession will have to endeavor to screen a higher rate of women and ensure a 100 percent quality assurance with every patient treated in order to reduce the unacceptable high incidence of cervical carcinoma. At this stage it seems like an impossible task to screen 100 percent of women in South Africa, due to far-off rural areas, the shortage of medical professionals and ignorance of patients. Quality assurance is therefore of paramount importance to every medical professional for every patient treated. Laboratories all worldwide have been, or are in the process of being accredited by their specific accreditation authorities. The main reason for this is improvement of quality control and therefore quality assurance. The South African National Accreditation Society (SANAS) now accredits various laboratories in South Africa with the view of accreditting all laboratories within a certain time limit. The Ampath laboratory Port Elizabeth was successfully accredited during 2001. Accredited laboratories have to uphold a very high degree of quality to remain accredited. A team of professionals inspects the laboratory every 2 years and other quality assurance staff inspects the laboratories every few months. All aspects of the laboratory are checked, e.g. the qualification of staff, their registration with the Health Professions Council of South Africa (HPCSA), their curriculum vitaes, equipment, safety of the laboratory etc. Since the laboratory chosen for this study, is accredited, the author evaluated every cervical smear that was received in the laboratory since the year 2000, with the following objectives in mind: · Whether the presence or absence of an endocervical component has an effect on the adequacy of cervical smears · To determine the effect of using smaller coverslips on quality assurance in the cytology laboratory · Evaluate the effect that manual re-screening of smears has on quality assurance in the cytology laboratory. As there is a shortage of cytotechnologists and pathologists worldwide, several countries make use of automated screening devices as primary screening or secondary screening for quality assurance. These devices were tested in some laboratories in South Africa but were found to be very expensive and sensitivity and specificity were not up to standard. Sensitivity is a measure of the ability of a test to detect the abnormal - Sensitivity is the ratio of true positives to true positives + false negatives. Specificity is a measure of the ability of a test to correctly identify the negative - Specificity is the ratio of true negative to true negatives + false positives. The automated screening machines failed to identify abnormal cells amongst inflammatory cells, as well as in very blood stained smears. Several other problems also occurred and an increasing number of smears had to be manually rescreened, thus making this exercise costly and not helpful as a quality assurance instrument. The slides used for this thesis, have been retrieved from the archives of the Ampath laboratory in Port Elizabeth. Fourteen specific contributing factors affecting quality assurance in the diagnosis of cervical smears are also discussed and conclusions and recommendations given.