MMP-9/RECK imbalance: a mechanism associated with high-grade cervical lesions and genital infection by Human Papillomavirus (HPV) and Chlamydia trachomatis

"Manuscript"

The role of macroH2A1 in prostate carcinogenesis

Dissertação de mestrado em Genética Molecular

Critical analyses of the introduction of liquid-based cytology in a public health service of the state of São Paulo, Brazil

OBJECTIVE The aim of this study was to compare the performance of the current conventional Pap smear with liquid-based cytology (LBC) preparations. STUDY DESIGN Women routinely undergoing their cytopathological and histopathological examinations at Fundação Oncocentro de São Paulo (FOSP) were recruited for LBC. Conventional smears were analyzed from women from other areas of the State of São Paulo with similar sociodemographic characteristics. RESULTS A total of 218,594 cases were analyzed, consisting of 206,999 conventional smears and 11,595 LBC. Among the conventional smears, 3.0% were of unsatisfactory preparation; conversely, unsatisfactory LBC preparations accounted for 0.3%. The ASC-H (atypical squamous cells - cannot exclude high-grade squamous intraepithelial lesion) frequency did not demonstrate any differences between the two methods. In contrast, the incidence of ASC-US (atypical squamous cells of undetermined significance) was almost twice as frequent between LBC and conventional smears, at 2.9 versus 1.6%, respectively. An equal percentage of high-grade squamous intraepithelial lesions were observed for the two methods, but not for low-grade squamous intraepithelial lesions, which were more significantly observed in LBC preparations than in conventional smears (2.2 vs. 0.7%). The index of positivity was importantly enhanced from 3.0% (conventional smears) to 5.7% (LBC). CONCLUSIONS LBC performed better than conventional smears, and we are truly confident that LBC can improve public health strategies aimed at reducing cervical lesions through prevention programs.

Historical analysis of the Brazilian cervical cancer screening program from 2006 to 2013: a time for reflection

BACKGROUND: The Cervical Cancer Database of the Brazilian National Health Service (SISCOLO) contains information regarding all cervical cytological tests and, if properly explored, can be used as a tool for monitoring and managing the cervical cancer screening program. The aim of this study was to perform a historical analysis of the cervical cancer screening program in Brazil from 2006 to 2013. MATERIAL AND METHODS: The data necessary to calculate quality indicators were obtained from the SISCOLO, a Brazilian health system tool. Joinpoint analysis was used to calculate the annual percentage change. RESULTS: We observed important trends showing decreased rates of low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and an increased rate of rejected exams from 2009 to 2013. The index of positivity was maintained at levels below those indicated by international standards; very low frequencies of unsatisfactory cases were observed over the study period, which partially contradicts the low rate of positive cases. The number of positive cytological diagnoses was below that expected, considering that developed countries with low frequencies of cervical cancer detect more lesions annually. CONCLUSIONS: The evolution of indicators from 2006 to 2013 suggests that actions must be taken to improve the effectiveness of cervical cancer control in Brazil.

Clinical characteristics of women diagnosed with carcinoma who tested positive for cervical and anal high-risk human papillomavirus DNA and E6 RNA

High-risk human papillomavirus (hrHPV) is an essential cause of cervical carcinoma and is also strongly related to anal cancer development. The hrHPV E6 oncoprotein plays a major role in carcinogenesis. We aimed to evaluate the frequency of hrHPV DNA and E6 oncoprotein in the anuses of women with cervical carcinoma. We analyzed 117 women with cervical cancer and 103 controls for hrHPV and the E6 oncogene. Positive test results for a cervical carcinoma included 66.7 % with hrHPV-16 and 7.7 % with hrHPV-18. One case tested positive for both HPV variants (0.9 %). The samples from the anal canal were positive for HPV-16 in 59.8 % of the cases. Simultaneous presence of HPV in the cervix and anal canal was found in 53.8 % of the cases. Regarding expression of E6 RNA, positivity for HPV-16 in the anal canal was found in 21.2 % of the cases, positivity for HPV-16 in the cervix was found in 75.0 %, and positivity for HPV-18 in the cervix was found in 1.9 %. E6 expression in both the cervix and anal canal was found in 19.2 % of the cases. In the controls, 1 % tested positive for HPV-16 and 0 % for HPV-18. Anal samples from the controls showed a hrHPV frequency of 4.9 % (only HPV16). The presence of hrHPV in the anal canal of women with cervical cancer was detected at a high frequency. We also detected E6 RNA expression in the anal canal of women with cervical cancer, suggesting that these women are at risk for anal hrHPV infection.

High-aspect-ratio tridimensional electrode arrays for neural applications

Tese de Doutoramento em Engenharia Biomédica.