Orientadores: Sophie Françoise Mauricette Derchain, Cecilia Maria Roteli Martins / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-05T07:54:01Z (GMT). No. of bitstreams: 1 Gontijo_RenataClementino_D.pdf: 141945 bytes, checksum: 2c58c2feab74004e7047e409bad433a0 (MD5) Previous issue date: 2005 / Resumo: Introdução: Mulheres com resultado de citologia negativa e sem infecção pelo papilomavírus humano (HPV) têm teoricamente um risco quase nulo de terem uma lesão intra-epitelial escamosa cervical de alto grau ou câncer invasor. Porém, muitas mulheres com citologia negativa e colo uterino morfologicamente normal são infectadas pelo HPV, e o significado clínico desta infecção em relação ao risco de vir a apresentar anormalidades citológicas ou histológicas futuras ainda não está totalmente esclarecido. Objetivo: Investigar a incidência em 24 meses de alterações citológicas e histológicas cervicais segundo a detecção do HPV, em mulheres com citologia inicial normal, incluídas na coorte Latin American Screening study (LAMS). Material e métodos: Um grupo de 365 mulheres com resultado de citologia normal e resultado de Captura Híbrida II (CH II) para HPV de alto risco oncogênico positivo e negativo, foram seguidas por 24 meses em Campinas e São Paulo. Todas as mulheres responderam a um questionário referente aos fatores sociodemográficos e reprodutivos, e foram submetidas à coleta de material para citologia oncológica e CH II. As mulheres com pelo menos um exame positivo e uma amostra aleatória de 10% de mulheres com ambos os testes negativos foram convocadas para colposcopia com biópsia, se necessário, e seguimento semestral com citologia e colposcopia. Foram comparadas as mulheres com infecção pelo HPV com aquelas não infectadas, segundo as características sociodemográficas e reprodutivas, utilizando-se o cálculo do risco relativo (RR) e a análise de regressão logística em stepwise com intervalo de confiança (IC) de 95%. Foram calculados também a taxa de incidência e o RR com IC de 95% de desenvolver anormalidades citológicas ou histológicas durante o seguimento. Tomou-se como padrão-ouro a colposcopia. Quando a colposcopia foi normal ou quando a biópsia apresentou cervicite, as mulheres foram consideradas como diagnóstico negativo. As mulheres cuja biópsia foi compatível com neoplasia intra-epitelial cervical (NIC) grau 1 ou mais foram consideradas como diagnóstico positivo. Resultados: A incidência de lesões de baixo e alto graus na citologia foi maior entre as mulheres com resultado de CH II positivo, tanto aos 12 quanto aos 24 meses de seguimento. Até 12 meses de seguimento, mulheres com CH II de rastreamento positivo apresentaram um RR significativamente maior de lesões de baixo (1,4; IC 95% 1,1-1,7) e alto (1,5; IC 95% 1,4-1,7) graus na citologia. O RR para lesão de alto grau aumentou para 1,7 (IC 95% 1,5-1,9) naquelas acompanhadas por 24 meses. Em relação aos resultados histológicos, a incidência de NIC 1, 2 e 3 também foi maior entre as mulheres com resultado de CH II positivo, tanto aos 12 quanto aos 24 meses de seguimento. As mulheres com CH II positivo apresentaram um RR de 1,5 (IC 95% 1,4-1,6) para NIC 2 e 3 durante o seguimento até 12 meses e este RR aumentou para 1,7 (IC 95% 1,5-1,9) naquelas seguidas até 24 meses. Conclusão: O teste para detecção do HPV associado à citologia pode selecionar entre as mulheres com citologia normal aquelas com maior risco de lesão cervical subseqüente / Abstract: Introduction: Women with normal baseline cytology and non-infected by Human papillomavirus (HPV) have, in theory, no risk to develop a high-grade cervical intraepithelial lesion or cancer. However, many women with normal cytology and with morphologically normal uterine cervix are HPV infected, and, the clinical significance of this infection regarding to the risk of devoloping cytological or histological abnormalities in the future are not totally clear yet. Purpose: To investigate the incidence of cytological and histological cervical lesions in a 24 months follow-up, according to HPV detection among women with baseline normal cytology result, in a subgroup of women included in the Latin American Screening study (LAMS). Study design: A group of 365 women with normal Pap smear whatever the Hybrid Capture (HC) II test result were followed for 24 months at Campinas e São Paulo (Brazil). They answered a questionnaire regarding sociodemographic and reproductive factors and were submitted to a clinical exam, including Pap smear and HC II. Women with at least one positive result and a 10% random sample of women with both tests negative were referred to colposcopy and followed with cytology and colposcopy in a six-month interval. Women with positive and negative HPV test were compared regarding sociodemographic and reproductive factors using relative risk (RR) and stepwise logistic regression analysis calculated with 95% confidence interval (CI). Also the incidence rate and RR of developing any cytological or histological abnormality during the follow-up were calculated within 95% confidence limits. Colposcopy was considered as the gold standard. When colposcopy result was normal or biopsy result was cervicitis it was considered as negative diagnosis. Women with histologic diagnosis of cervical intraepithelial neoplasia (CIN) 1 or higher were considered as positive diagnosis. Results: Incidence of low and high-grade cytological lesion was higher in women with positive HPV testing than in women with negative HPV testing after 12 and 24 months of follow-up. In up to 12 months of follow-up, women with baseline positive HPV test had a significantly higher proportion of low-grade (1.4; 95% CI 1.1-1.7) and high -grade (1.5; 95%CI 1.4-1.7) cytological lesion. The RR for high-grade lesion increased to 1.7 (95%CI 1.5-1.9) for those followed-up in up to 24 months. For histological outcomes, the incidence of CIN 1, 2 or 3 was also higher in women with positive HPV testing than in women with negative HPV testing after 12 and 24 months of follow-up. Women with positive HPV test had a higher RR of CIN 2 and 3 (1.5; 95%CI 1.4-1.6) during the follow-up in up to 12 months and the RR increased to 1.7 (95%CI 1.5-1.9) for those followed-up in up to 24 months. Conclusions: HPV test is useful in addition to cytology to select from women with normal cytology those who are at highest risk for underlying cervical lesion / Doutorado / Tocoginecologia / Doutor em Tocoginecologia

Human papillomavirus (HPV) is a double-stranded DNA virus, typically infecting mucosal or cutaneous epithelial keratinocytes. Today, more than 118 different HPV types have been formally described. Sexual transmission of mucosal HPVs is very common and generally asymptomatic, but HPV infection can be associated with benign lesions such as condylomata acuminata or, in rare cases, with malignant lesions such as cervical cancer. Two prophylactic vaccines are currently available in Europe, protecting against HPV-16 and HPV-18 (Cervarix&63720;) or against HPV-6, HPV-11, HPV-16 and HPV-18 (Gardasil&63720;). In order to assess the impact of the vaccination program, it is mandatory to obtain geographically widespread date on the baseline HPV prevalence and type distribution in cervical samples from women, presenting or not, normal or abnormal cytologic or histologic results. We undertook an epidemiological study in the Capital Region of Brussels to determine the HPV prevalence and type-distribution in 1526 cervical samples of women presenting a cytology within normal limits (WINL), atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intra-epithelial lesions (LSIL), high-grade squamous intra-epithelial lesions (HSIL) or invasive cervical cancer (ICC). The HPV prevalence was 10.8% (95%CI: 8.8-12.8) for NILM, 34.5% (95%CI: 28.3-40.8) for ASC-US, 54.0% (95%CI: 47.4-60.6) for LSIL and 100% for HSIL and ICC. With an HPV-16 and HPV-18 prevalence of 63.3% (95%CI: 44.1-67.7) and 73.5% (95%CI: 63.0-84.0) in mono-infected HSIL and ICC, respectively, HPV 16/18 L1 VLP vaccines would be expected to significantly reduce the management and treatment of women suffering from HSIL and ICC in the Capital Region of Brussels. We also detected HPV-30, HPV-53, HPV-66 and HPV-68 in mono-infected HSIL and ICC samples, possibly providing arguments for the reconsideration of the carcinogenicity of these types. <p>Vertical transmission of HPV was also previously reported, but in most cases one could not exclude a placental contamination by HPV positive cells from an infected birth canal. In order to confirm that the placenta can be infected with HPV, we analysed residual cells from 35 transabdominally obtained placental samples from pregnant women undergoing chorionic villous sampling for screening of suspected foetal abnormalities and found that two samples were positive for HPV-16 and HPV-62, respectively. The clinical importance of these results remains to be elucidated, but the previously observed association between placental HPV infection and pregnancy loss might gain further in importance. HPV gene regulation in placental trophoblastic cells has not been studied so far. We studied the HPV-16 early gene expression regulation in transiently transfected monolayer cultured trophoblastic cells with an HPV-16 long control region (LCR) driven reporter plasmid. We observed important differences in constitutive HPV-16 LCR activities between trophoblastic cell lines and could identify progesterone as an important inducer of HPV-16 early gene expression. Steroid hormones are induced during pregnancy and could therefore lead to an enhanced expression of the E5, E6 and E7 proteins upon placental HPV infection. Since these proteins were previously shown to affect trophoblast adhesion, survival, migration and invasion, their enhanced expression might eventually contribute to pregnancy loss. We furthermore found that the transcription of episomally maintained HPV-16 is not regulated by E2 or E1, but by E5, E6 and/or E7. <p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

It is estimated that 6742 South African women are diagnosed with cervical cancer and 3681 women die from the disease every year. In 1993, The Centers for Disease Control declared cervical cancer an Acquired Immunodeficiency Syndrome defining illness. Apart from persistent human papillomavirus infection, HIV infection is the most common co-factor contributing to cervical cancer in South Africa. Studies have noted that in HIV positive women, there has been an occurrence of faster progression to more advanced stages of cervical cancer with high cases of treatment failure and recurrence. There is limited literature available regarding the prognosis of HIV positive women who suffer from cervical cancer. Women who are HIV positive and have cervical cancer have not been evaluated in detail regarding their response and adherence to cervical cancer treatment. Standard treatment protocols for this set of patients have not been defined. The aim of this study was to assess how HIV positive women who have been diagnosed with cervical cancer responded and adhered to cervical cancer therapy which includes: curative radiotherapy; curative chemotherapy; concurrent chemoradiation or palliative radiotherapy. The study also evaluated the effects of the concurrent use of antiretrovirals and cervical cancer treatment. This was done to determine whether invasive cervical cancer in women who were HIV positive could be managed using the same treatment protocols as patients who were HIV negative. A historical cohort design was employed for the study. The study was conducted at the Oncology Department of a tertiary level hospital located in the Eastern Cape Province, South Africa. The total sample consisted of 196 medical records of women diagnosed with cervical cancer between 2005 and 2008. One hundred women were HIV negative, 83 were HIV positive and the HIV status of 13 women could not be determined. The records were audited over a period of two years from the date of diagnosis. The term „complete response‟ referred to patients who had no recurrence of cervical cancer and no evidence of metastases after undergoing treatment. At one month following treatment there was a significant difference in the incidence of complete response between the HIV positive patients and the HIV negative patients (Chi2 = 16.4, d.f. = 1, p = 0.00005, Cramer‟s V = 0.31). The significant difference in response to treatment between the HIV positive patients and the HIV negative patients was maintained at six months after treatment (Chi2 = 15, d.f. = 1, p = 0.00011, Cramer‟s V = 0.34), 12 months after treatment (Chi2 = 20.5, d.f. = 1, p = 0.00001, Cramer‟s V = 0.37), 18 months after treatment (Chi2 = 9.8, d.f. = 1, p = 0.00173, Cramer‟s V = 0.28) and 24 months after treatment (Chi2 = 5.0, d.f. = 1, p = 0.02571, Cramer‟s V = 0.26). At each of these intervals, cases of treatment failure and metastases were significantly higher in the HIV positive women than in the HIV negative women. Although there was no significant difference in the incidence of adherence between the HIV negative women, the HIV positive women who were on HAART and the HIV positive women who were not on HAART, there was a significant difference in the incidence of the various reasons for non adherence between the various groups. These reasons included: missed scheduled appointments (Chi2 = 2.9, d.f. = 2, p = 0.02385, Cramer‟s V = 0.31); low blood count (Chi2 = 4.0, d.f. = 2, p = 0.01327, Cramer‟s V = 0.15); radiotherapy induced skin breakdown (Chi2 = 0.6, d.f. = 2, p = 0.04581, Cramer‟s V = 0.16) and radiotherapy induced diarrhoea (Chi2 = 6.9, d.f. = 2, p = 0.03118, Cramer‟s V = 0.19). According to the 2004 National Antiretroviral Treatment Guidelines, cervical cancer patients would fall into the WHO stage IV category of HIV disease thus all patients with confirmed diagnosis of invasive cervical cancer should be commenced on antiretrovirals as soon as the cancer diagnosis is made regardless of their CD4 count. However, in the current study, 13 percent (n= 83) of the HIV positive women were not on antiretrovirals. The study concluded that HIV positive women had a higher incidence of both treatment failure and metastases to cervical cancer treatment. Standard radiotherapy and concurrent chemoradiation cervical cancer treatment protocols should be still be used in both HIV negative patients and HIV positive patients so as not to compromise tumour control. Furthermore, in accordance with the antiretroviral treatment guidelines, all HIV positive patients with cervical cancer should receive antiretrovirals irrespective of their CD4 count.

Thesis (M.Med. (Radiation Oncology)) -- University of Limpopo, 2020 / Introduction Invasive cervical cancer (ICC) constitutes almost 50% of all cancer conditions diagnosed and treated at the Polokwane/Mankweng Hospital Complex (PMHC). HIV infection is also a very common condition. There is no consensus on the relationship between the two clinical conditions among patients treated at PMHC. There is a need to describe the simultaneous occurrence of the two clinical conditions among these patients to define a rational approach to these conditions’ clinical management. Methodology This was a retrospective review of medical records of patients diagnosed with ICC who were treated at PMHC in Limpopo Province, South Africa in 2013. Results Three hundred and twenty-nine medical records were reviewed in this study; 64% of the patients were HIV-negative, and only 35% were HIV-positive. Thirty-five percent of the patients were younger than 50 years of age, followed by those aged 50–59 years (23%). Among women in the age group 30–59 years, the most common ICC stages were IIB and IIIB. In women older than 60 years, stages IIB, IIIA, IIIB and IVA were the most common. In the HIV-positive women, 18% had a CD4 cell count of less than 200/μL, compared to 2% in the HIV-negative women (p <0.05). Among the HIV-negative women, stages IIIB (49.8%) and IIB (24.6%) were the most common, where as among those who were HIV-positive, stages IIIB (55.6%) and IIB (22.6%) dominated. Conclusion This retrospective study did not find any relationship between HIV infection and ICC in patients treated at PMHC. However, it indicated that a significant proportion of HIV-positive women with ICC had lower CD4 cell counts compared to those of HIV-negative women. KEY CONCEPTS: Invasive cervical cancer, Human immunodeficiency virus, Stage, Prevalence, CD4 cell count, Age, Polokwane/Makweng Hospital Complex

Cervical cancer is the second most commonly diagnosed cancer and the third leading cause of cancer death among women in less developed countries. Screening for cervical cancer is the most accepted and successful strategy for cervical cancer control. The purpose of the study was to investigate factors that determine cervical cancer screening practice among women in Addis Ababa, Ethiopia and develop guidelines to improve the utilisation of cervical cancer screening services. The researcher used the health belief model (HMB) as the theoretical foundation of the study and a convergent parallel mixed methods design. Quantitative data was obtained from screened and not screened women attending maternal health services at selected public health centres. Statistical Package for Social Sciences (SPSS) Version 23 was used for entry and analysis of data Qualitative data was obtained in key informant interviews from health service professionals on their perceptions of women‟s cervical cancer screening uptake at the health centres. The study found that higher age >35 years category (X2 =33.618 and p-value <0.001), contraceptive use (X2 value=20.7 and p-value <0.001), having two or more children, and knowledge of cervical cancer and screening (chi-value X2 =51.649, p-value=0.001) were strongly associated with screening practice. In addition, women‟s perception of susceptibility (t-test=3.42 and 3.432, p-value=0.001) was a predictor of screening. Lack of awareness was a serious barrier to cervical cancer screening and health service providers‟ information was a strong promoter of screening. The study recommends promoting and facilitating health education on cervical cancer at all health facilities; organising awareness campaigns, education programmes, and community mobilisation to raise awareness of cervical cancer screening; integrating cervical cancer screening with other reproductive health services, and capacitating the health professionals in order to increase utilisation of cervical cancer screening services. Consequently, the researcher used the findings of the study to develop guidelines to improve the uptake and quality of cervical cancer screening services. / Health Studies / D. Litt. et Phil. (Public Health)

Indiana University Purdue University Indianapolis / Human papillomaviruses (HPV) are the etiologic agents of most cervical dysplasia and all cervical carcinoma. Integration of high risk HPV into the human genome is thought to be a critical event in the progression from cervical dysplasia to invasive cervical carcinoma. The ability to use molecular assays in the detection and evaluation of HPV integration is essential in informing clinical models for early intervention and therapies. We therefore sought to determine the feasibility of real time-PCR (RT-PCR) as a molecular tool in detecting the physical state, episomal versus integration of HPV 16 and 18 DNA in cervical cancers. Tyramide amplified fluorescent DNA in situ hybridization (FISH) was used to look for evidence of HPV 16/18 integration using formalin-fixed, paraffin-embedded sections of cervical carcinomas. RT-PCR used the ratio of the E2 and E6 genes as a surrogate for determining the physical state of HPV 16 and 18 in 35 infected tissues. Results of RT-PCR showed that 16 cervical specimens (45.7%) contained episomal HPV, 17 cervical samples (48.6%) harbored the integrated form of HPV DNA, and 2 samples (5.7 %) contained both integrated and episomal forms of HPV. Results of the two assays were compared in 25 cervical carcinomas. For 13 of the 25 cervical samples there was an agreement in determining the physical state of HPV. RT-PCR, using the E2/E6 ratio as an assay for HPV integration appears to be promising and may prove to be an essential clinical method in the future.

Cervical cancer is reported to be the first among the five leading cancers affecting women in South Africa and the leading cancer among Black females. There is a high incidence and mortality rate among underserved and under-screened women presenting with cervical cancer as they are often unable to access screening facilities. Very little has been done to establish the factors in private health care provision that influence the implementation of cervical screening programmes. The study investigates factors influencing cervical cancer screening programme implementation among private medical practitioners in Soshanguve to establish whether private practitioners assume their roles in cervical screening. The intention is to provide guidelines for a screening programme that could be implemented in private health facilities. The study is qualitative, explorative, descriptive and contextual, using interviews and observation as the main data-collection methods. Lack of awareness and interest, failure to inform patients about cervical screening, age and gender of medical practitioners were among the factors identified. The study concluded that awareness programmes about cervical screening and materials containing information on cervical cancer and predisposing factors should be designed. The utilization of cheaper laboratory service providers could increase participation by making the test affordable and accessible to cash patients. The establishment of a private Pap clinic within medical practices or even as an independent entity is also recommended. / Health Studies / M.A. (Public Health)

Cervical cancer is reported to be the first among the five leading cancers affecting women in South Africa and the leading cancer among Black females. There is a high incidence and mortality rate among underserved and under-screened women presenting with cervical cancer as they are often unable to access screening facilities. Very little has been done to establish the factors in private health care provision that influence the implementation of cervical screening programmes. The study investigates factors influencing cervical cancer screening programme implementation among private medical practitioners in Soshanguve to establish whether private practitioners assume their roles in cervical screening. The intention is to provide guidelines for a screening programme that could be implemented in private health facilities. The study is qualitative, explorative, descriptive and contextual, using interviews and observation as the main data-collection methods. Lack of awareness and interest, failure to inform patients about cervical screening, age and gender of medical practitioners were among the factors identified. The study concluded that awareness programmes about cervical screening and materials containing information on cervical cancer and predisposing factors should be designed. The utilization of cheaper laboratory service providers could increase participation by making the test affordable and accessible to cash patients. The establishment of a private Pap clinic within medical practices or even as an independent entity is also recommended. / Health Studies / M.A. (Public Health)

Text in English / Cervical cancer remains the leading cause of cancer mortality among women worldwide, a burden in the developing countries and commonly detected through symptoms at later invasive stages. The study aimed at establishing knowledge and awareness of the importance of cervical cancer screening in the Makhuduthamaga Sub-district by exploring the perceptions of women and professional nurses and through the review of the National Cervical Cancer Screening Policy (2013). Recommendations to address the gap in knowledge and to inform the National Cervical Cancer Screening Policy were developed based on the study findings. A mixed-method approach was used in this study through a sequential explanatory design, which is quantitatively driven was used. Quantitative data were obtained by using a researcher developed checklist. The checklist was developed from variables stated in the National Cervical Cancer Screening Policy and was used to review its implementation. Qualitative data was obtained through in-depth interviews with individual women and focus group discussions with professional nurses. The study was conducted in ten randomly selected clinics of Makhuduthamaga Sub-district. Purposive sampling was done to obtain qualitative data. An average score of 9.7 was obtained for all ten clinics that participated in the study with regard to the evaluation of the implementation of the National Cervical Cancer Screening Policy. Only 6 (60%) clinics implemented the policy whereas 4 (40%) clinics did not implement the policy. Women and professional nurses perceived cervical cancer screening as important. Lack of knowledge among women regarding cervical cancer screening contributed to the majority of women not screening for cervical cancer. Lack of resources, the 10 year interval of normal cervical cancer screening, the use of disposable vaginal speculums and brushes, lack of standardized cervical cancer screening training, centralization of cytology laboratories came out as factors that negatively influence the uptake of cervical cancer screening. Cervical cancer screening awareness campaigns, availability of resources and standardized in-service trainings on cervical cancer screening were recommended to enhance the cervical cancer screening uptake. Key concepts: / Health Studies / D. Litt. et Phil. (Health Studies)

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences