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Objective To evaluate the rates of precancerous lesions, colposcopy referral, and positive predictive value (PPV) by age groups of a population-based screening with DNA-HPV testing. Methods The present demonstration study compared 16,384 HPV tests performed in the first 30 months of the program with 19,992 women tested in the cytology screening. The colposcopy referral rate and PPV for CIN2+ and CIN3+ by age group and screening program were compared. The statistical analysis used the chi-squared test and odds ratio (OR) with 95% confidence interval (95%CI). Results The HPV tests were 3.26% positive for HPV16-HPV18 and 9.92% positive for 12 other HPVs with a 3.7 times higher colposcopy referral rate than the cytology program, which had 1.68% abnormalities. Human Papillomavirus testing detected 103 CIN2, 89 CIN3, and one AIS, compared with 24 CIN2 and 54 CIN3 detected by cytology (p Conclusion There was a significant increase in detections of cervix precancerous lesions in a short period of screening with HPV testing. In women

Orientador: Sophie Françoise M. Derchain Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas Resumo: OBJETIVO: avaliar a contribuição da inspeção visual com ácido acético e da captura híbrida II como métodos adjuntos à colpocitologia oncológica na detecção das lesões precursoras ou câncer cervical. SUJEITOS E MÉTODOS: realizou-se inicialmente um estudo descritivo de corte transversal e posteriormente validação de teste diagnóstico. Foram incluídas 809 mulheres (18 a 64 anos) atendidas no Centro de Atenção Integral à Saúde da Mulher da Universidade Estadual de Campinas, de janeiro de 2002 a julho de 2003. Na primeira consulta, as mulheres responderam a um questionário pré-estruturado e todas foram submetidas a exame ginecológico que consistiu em coleta de material para olpocitologia oncológica com espátula de Ayres e escova endocervical; coleta de material para detecção de papilomavírus humano de alto risco oncogênico por captura híbrida II; inspeção visual, com aplicação de ácido acético a 5% e colposcopia com biópsia dirigida das áreas anormais. Para avaliar a associação entre o resultado de cada exame de rastreamento e o resultado da colposcopia foi calculada a razão de prevalência com intervalo de confiança a 95%. Para avaliar o desempenho dos exames de rastreamento na detecção de lesão histológica foram calculadas a sensibilidade e a especificidade, assim como os valores preditivos positivo e negativo de cada método, considerando o padrão-ouro sem doença, a colposcopia normal ou biópsia sem lesão induzida pelo papilomavírus humano e, com doença, biópsia NIC 1 ou mais. Em uma primeira análise avaliou-se o desempenho dos testes para a detecção de qualquer lesão histológica induzida pelo papilomavírus humano e posteriormente este cálculo foi realizado para NIC 2 ou mais. RESULTADOS: das 809 mulheres avaliadas, 12% apresentavam inspeção visual com ácido acético anormal, 19% tinham captura híbrida II positiva e 7% apresentaram alterações na colpocitologia oncológica. Cento e quatorze mulheres (14,7%) foram submetidas à biópsia e, destas, 39 (4,8%) apresentaram lesões associadas com papilomavírus humano, sendo que 12 apresentavam neoplasia intra-epitelial cervical 2 ou mais. Houve uma associação estatisticamente significativa entre os exames de rastreamento e a colposcopia, sendo a melhor associação encontrada com a inspeção visual com ácido acético. Em relação ao desempenho dos exames pode se observar que com sensibilidade maior que 70% para lesão histológica e especificidade de 91%, a inspeção visual com ácido acético apresentou melhor desempenho como método isolado na detecção de neoplasia intra-epitelial 1 ou mais. A sensibilidade da captura híbrida foi maior para a detecção de neoplaisia intra-epitelial 2 ou mais. A especificidade da colpocitologia oncológica foi superior à dos outros dois métodos para lesões de baixo e alto graus, embora sua sensibilidade tenha sido significativamente inferior. Ao avaliar a associação dos diferentes métodos de rastreamento considerando-se sempre pelo menos um positivo, observou-se que a associação da inspeção visual à colpocitologia oncológica aumentou significativamente a detecção de doença histológica sem perda significativa da especificidade. A sensibilidade da associação dos três métodos para o diagnóstico de neoplasia intra-epitelial 1 ou mais foi significativamente melhor do que a da colpocitologia oncológica isoladamente ou associada à inspeção visual com ácido acético. Já para a detecção de lesões de alto grau, a associação da captura híbrida à colpocitologia oncológica foi o método que apresentou melhor sensibilidade sem perda na especificidade. CONCLUSÃO: A inspeção visual com ácido acético contribuiu significativamente na detecção de doença histológica, embora a associação da colpocitologia oncológica e captura híbrida tenha sido o melhor método para detecção de lesões de alto grau Abstract: OBJECTIVE: to assess the contribution of visual inspection with acetic acid and Hybrid Capture II as adjunct methods to Pap test in detecting cervical squamous precursor lesions and cervical cancer and evaluate the performance of these different methods. SUBJECTS AND METHODS: this was a cross-sectional study and validation of diagnostic test. Eight hundred and nine women were included and consecutively attended gynecological consultations at the Campinas State University, Brazil, from January 2002 to July 2003. Pap test, detection of highrisk Human Papillomavirus with visual inspection with acetic acid and hybrid capture II and colposcopy were performed for all patients. Colposcopically abnormal areas were biopsied. To compare the association between visual inspection with acetic acid, hybrid capture II and Pap test with colposcopic result prevalence ratio were used. To evaluate the performance of each test in detecting histologicallyconfirmed lesions sensitivity, specificity and positive and negative predictive values with respective confidence intervals of each test were evaluated. Considering gold standard as normal when colposcopy is normal or biopsy is without disease and abnormal when the biopsy shows intraepithelial neoplasia or more. RESULTS: Among 809 woman tested, visual inspection with acetic acid was considered abnormal in 12%, 8% had abnormal Pap tests and 19% had positive hybrid capture II. One hundred and fourteen (14.7%) women underwent to cervical biopsies, being that of 39 (4.8%) Human Papillomavirus-related lesions, 12 consisted of intraepithelial neoplasia 2 or worse. The association of the screening exams and the colposcopy was statistically significant for all tests but visual inspection with acetic acid had the strongest concordance with a 72% sensibility and 91% specificity. The sensitivity of hybrid capture II was higher in detecting intraepithelial neoplasia 2 or more. The specificity of Pap test was better them the two other tests, although the sensibility was lower. In order to evaluate the association of the different methods considering at least one test positive, the association of visual inspection with acetic acid and Pap test raised the sensibility without low specificity. The sensitivity of the association of the three methods to detect CIN 1 or worst was better than the Pap test alone or associated with VIA. To detect CIN 2 or worst the better association was CH II and Pap test. CONCLUSION: the VIA contributed to detect disease although the association of Pap test and HC II improved the detection of CIN 2 or worst Mestrado Tocoginecologia Mestre em Tocoginecologia

In 2018, WHO called for global action to eliminate cervical cancer. The complexity of the processes involved in terms of prevention is often underestimated. Low- and middle-income countries do not have a robust healthcare framework to ensure high-quality programs. The present article discusses how fragile healthcare systems are barriers to eliminating cervical cancer, and also reports the experience of a Brazilian prevention program. The article considers how cervical cancer can be interpreted as an indicator of inequality: how women's attitudes and access to care determine an early or late diagnosis, and how strategies combining vaccine and DNA-HPV tests are crucial. New vaccine schemes, the critical analysis of local data, strengthening communication, managing sentinel events, and integrating vaccination and screening data for the health information system are some of the key activities to sustainable improvement in both access and quality of care.

Summary Background Cervical cancer is a preventable disease, and the Brazilian screening is opportunistic and has low impact. The current study evaluated an initiative to organize screening using DNA–HPV testing as a replacement for cytology. Methods This demonstration study examined information from 16 384 DNA–HPV tests for screening in women aged 25–64 years from Indaiatuba city between October 2017–March 2020. The comparison was 20 284 women screened using cytology between October 2014–March 2017. The flowchart indicates the repetition of a negative test in five years. HPV16- and/or HPV18-positive tests and the 12 pooled high–risk HPV-positive tests with abnormal liquid–based cytology were referred for colposcopy. If cytology was negative, the HPV test was repeated in 12 months. The analyses evaluated coverage, age–group compliance, and cancer detected. Findings After 30 months, the coverage projection was greater than 80%. The age compliance for the HPV test was 99.25%, compared to 78.0% in the cytology program. The HPV test program showed 86.8% negative tests and 6.3% colposcopy referrals, with 78% colposcopies performed. The HPV testing program detected 21 women with cervical cancer with a mean age of 39.6 years, and 67% of cancers were early–stage compared to 12 cervical cancer cases detected by cytological screening (p=0.0284) with a mean age of 49.3 years (p=0.0158), and one case of early–stage (p=0.0014). Interpretation Organizing cervical cancer screening using DNA–HPV testing demonstrated high coverage and age compliance in a real–life scenario, and it had an immediate impact on cervical cancer detection at an early–stage. Funding University of Campinas, Indaiatuba City, and Roche Diagnostics.

BackgroundA Brazilian guideline on cervical cancer screening was released in 2011. The objective was to verify changes in screening indicators around this period.MethodsAn audit study which sample was all screening tests performed by the public health system of Campinas city from 2010 to 2016. Variables were absolute tests numbers, excess tests, intervals and results, by age. For trend analysis was used Cochran-Armitage × 2 and linear regression.ResultsWere carried out 62,925 tests in 2010 and 43,523 tests in 2016, a tendency at a reduction (P = 0.001). Excess tests were higher than 50% over the years, with a tendency at a reduction (P P P P = 0.04 andP = 0.001, respectively), and a tendency at an increase in HSIL-CIN3 result (P = 0.02).ConclusionThe proportion of cervical cancer screening tests performed out of the recommendation showed a significant reduction in the period. This indicates a tendency to align cervical cancer screening in Campinas with the standards recommended.

Objective This paper searches an ideal cone height for stage definition and safe treatment of cervical microinvasive squamous carcinoma stage IA1 (MIC IA1), avoiding excessive cervix resection, favoring a future pregnancy. Methods A retrospective study was performed involving 562 women with MIC IA1, from 1985 to 2013, evaluating cone margin involvement, depth of stromal invasion, lymph vascular invasion, conization height, and residual uterine disease (RD). High-grade squamous lesions or worse detection was considered recurrence. Univariate and multivariate regression analyses were performed, including age, conization technique (CKC, cold-knife, or ETZ, excision of transformation zone), and pathological results. Conization height to provide negative margins and the risk of residual disease were analyzed. Results Conization was indicated by biopsy CIN2/3 in 293 cases. Definitive treatments were hysterectomy (69.8%), CKC (20.5%), and ETZ (9.7%). Recurrence rate was 5.5%, more frequent in older women (p = 0.030), and less frequent in the hysterectomy group (p = 0.023). Age ≥40 years, ETZ and conization height are independent risk factors for margin involvement. For ages Conclusion Conization 10 mm height for women

A elevada prevalência de sofrimento psíquico presente nos estudantes de medicina, pode acarretar em transtornos mentais, uso de substâncias psicoativas e comportamentos prejudiciais, além de impactar no aprendizado. Estes fatores levaram a Faculdade de Ciências Médicas da Unicamp à criação de um serviço de apoio (GRAPEME) para os seus discentes em 1996. No decorrer dos anos, o GRAPEME sofreu diversas mudanças tanto na sua estrutura física e de recursos humanos, como nas diversas formas de atuação. Atualmente conta com o atendimento individual mas também com iniciativas de intervenções precoces e prevenção, a fim de minimizar o sofrimento e melhorar a qualidade de vida de seus alunos.

Background: Cervical cancer is a preventable disease and the Brazilian screening is opportunistic without impact. This study aims to evaluate an initiative to organize the screening with DNA–HPV testing replacing the cytology. Methods: This demonstration study considered information from 16 384 DNA–HPV tests for screening in women aged 25–64 years, from Indaiatuba city, between OCT2017–MAR2020. The comparison was 20 384 women screened by cytology between OCT2014–MAR2017. The flowchart indicates the repetition in five years of a negative test. If HPV16 and/or HPV18 positive test refers to colposcopy, and if other 12 pooled high–risk HPV positive with abnormal liquid–based cytology refers to colposcopy too. If cytology negative, repeat HPV test in 12 months. The analyses evaluated coverage, age–group compliance, and cancer detected. Findings: After 30 months working, the coverage projection was more than 80%. The age compliance for the HPV test was 99·25% compared to 77·3% in the cytology program. The HPV test program showed 86·8% of negative tests and 6·3% of colposcopy referrals, with 78% of colposcopies done. The HPV testing program detected 21 women with cervical cancer, mean age of 39·6 years, and 76% of cancer at early–stage, compared to 12 cervical cancer cases detected by cytological screening (p=0·0284), mean age of 49·3 years (p=0·0158), and one case at early–stage (p=0·0014). Interpretation: Organizing the cervical cancer screening with DNA–HPV testing demonstrated high coverage and age compliance in a real–life scenario, with immediate impact on cervical cancer detection at an early stage. Funding: University of Campinas, Indaiatuba City, and Roche Diagnostics. Declaration of Interest: None to declare. Ethical Approval: This study was approved by the research ethics committee of the University of Campinas (number 1045580, May 1, 2015).

OBJECTIVE To evaluate the pattern of cervical cancer (CC) diagnosis and outcomes in women under 25. METHODS Thirty-two women younger than 25 years of age treated between 2001 and 2016 were studied and the year, symptom or cytology before diagnosis, time since sexual debut, age group, histology, and stage were considered. Data were compared with older age groups, and survival analysis was performed using a subset of them. RESULTS Thirty-two CC diagnoses (1.5% of all cases) exhibited a positive linear trend (P = 0.075). Driven by cytology, 18 were asymptomatic and 14 were symptomatic (with vaginal bleeding in 11). The mean time since sexual debut was 6.9 years. Advanced stage (44% vs 29%) and adenosquamous histology (12.5% vs 1.7%-5.0%) were higher in younger women. Five-year overall survival rate was 76%, better for squamous cell carcinoma (SCC) (86% vs 43% for other histologies; P = 0.018). There were seven deaths, all within 15 months of diagnosis. Age groups of less than 25 years (53%) and 25-29 years (48.5%) had similar proportions of Stage IA1. CONCLUSION The rate of CC-diagnosed women under 25 years was 1.5% of all cases, exhibiting more advanced stage and non-SCC histology. For asymptomatic women, cytology allowed the diagnosis at an early stage. Being symptomatic and non-SCC was associated with a higher proportion of advanced stages and poor survival.

Background The causal relationship between high-risk (hr) HPV infection and precancerous lesions or cervical cancer has led to the development of strategies to increase screening performance and prevent this cancer. The increased sensitivity of DNA-HPV testing compared to cervical cytology favors DNA-HPV testing as a primary screening test. Cervical cancer screening in Brazil is opportunistic, and this cancer remains a considerable health problem with a high proportion of diagnoses in advanced stages. This paper aims to describe the design and implementation of the Cervical Cancer Screening Program with primary DNA-HPV testing (CCSP-HPV) planned for Indaiatuba City (SP), Brazil; the strategies to achieve higher population coverage; and a study protocol for cost-effectiveness analyses. Methods The CCSP-HPV was designed based on successful guidelines that replaced cervical cytology-based screening by the DNA-HPV test performed at 5-year intervals. The screening will be performed for the female population aged 25-64 years cared for by the public health system and aim to reach 80% coverage after completing the first round. The chosen DNA-HPV test detects 14 hr-HPV types and genotypes HPV-16 and 18. All women with a negative test will be reassessed after five years. Women showing a positive test for HPV-16 and/or 18 will be referred for colposcopy. Those showing the other 12 hr-HPV types will be tested by cytology, and if any abnormality is detected, they will also be referred for colposcopy. The histopathologic evaluation will be reviewed by a pathologist panel and aided by p16 immunohistochemistry. A cost-effectiveness analysis will be performed by a Markov model comparing the cost of the new program and the screening performed by conventional cytology five years prior (2011–2016). Discussion The new screening program is considered a breakthrough for public health regarding cervical cancer, which is the third leading cause of cancer death among Brazilian women. Achieving at least 80% coverage will have the possibility to change this scenario. The proposed program will provide a modern cervical cancer screening method for women, and information about cost-effectiveness will help other similar places support the decision of implementing cervical cancer screening using the DNA-HPV test.

RESUMO A adoção de políticas públicas de inclusão pela Universidade Estadual de Campinas (Unicamp) desde o processo seletivo de 2005, atrelada às modificações nos vestibulares de 2014 e, mais recentemente, no de 2016, possivelmente trouxe grandes mudanças no perfil do estudante de Medicina dessa universidade. Desse modo, o objetivo do presente estudo é avaliar o perfil sociodemográfico desses acadêmicos, bem como suas pretensões na escolha da carreira médica e da futura especialidade. O estudo de corte transversal foi realizado com 290 acadêmicos do primeiro, terceiro e sexto ano da graduação médica da Unicamp por meio de um questionário anônimo aplicado após aprovação do Comitê de Ética em Pesquisa. Houve coleta de dados sociodemográficos, além dos fatores de influência para a escolha da profissão e da especialidade médica. A análise dos dados revelou uma amostra com idade média de 20-24 anos, predominantemente composta por mulheres (63,2%), da etnia branca (77,5%), procedentes do Estado de São Paulo (84,8%) e de regiões interioranas (62,3%). Para o primeiro ano, houve presença de negros (6,6%) e diferença estatística para pardos (22,6%), comparativa com o terceiro e sexto ano, egressos de ensino fundamental (42,5%) e médio (73,6%) públicos, com menor escolaridade materna (ensino médio) e renda familiar inferior (p < 0,001). Por sua vez, o terceiro e sexto ano eram compostos majoritariamente por alunos brancos (76,7% e 90,3%, respectivamente), oriundos de escola privada no ensino fundamental e médio, com maior escolaridade materna (ensino superior ou pós-graduação) e renda familiar mais elevada. Ainda, verificou-se variação das opções de especialidade ao longo do curso (p < 0,001). No primeiro ano, as especialidades mais pretendidas foram Cirurgia/Ortopedia (37,7%), Clínica Médica/Neurologia (23,6%) e Psiquiatria (11,3%). Para o terceiro ano, as especialidades mais desejadas foram Clínica Médica/Neurologia (40%), Cirurgia/Ortopedia (13,4%) e Ginecologia/Obstetrícia (13,3%). Entre os alunos do sexto ano, as especialidades mais escolhidas foram Clínica Médica/Neurologia (24,5%), Ginecologia/Obstetrícia (20,2%) e Cirurgia/Ortopedia (17%). Acadêmicos do primeiro ano também apresentaram diferentes aspirações abrangendo o local de trabalho futuro, com mais desejo de atuar somente no SUS ou em programas internacionais. Nesse contexto, os resultados apontam que a política de bonificação da Unicamp e suas alterações ao longo do tempo, em especial no vestibular de 2016, mostraram-se efetivas em democratizar o acesso à graduação médica, com maior pluralidade demográfica, social, econômica e étnica atreladas a variações na escolha da carreira e da especialidade médica ao longo das turmas analisadas. ABSTRACT Affirmative action policies adopted by University of Campinas (Unicamp) in 2005 entrance exams, added to 2014 modifications, and more recently in 2016, lead to a big profile change of University of Campinas medical students. Therefore, this paper aims to describe academics’ sociodemographic profile, as well as their aspirations in choice of medical career and future specialty. The cross-sectional study included 290 undergraduate years 1, 3 and 6 (Y1, Y3 and Y6) medical students from Unicamp who answered an anonymous questionnaire applied after approval by the Institutional Review Board. Socio demographic data and factors potentially influencing decisions on medical career and specialty choices were analyzed. Data analysis showed a sample composed mostly of white (77.5%), female (63.2%), 20-24 years population, from the State of São Paulo (84.8%) and interior (62.3%). For Y1, there was statistically significant difference for ‘pardo’ (22.6%) – it can be translated as brown – and black (6.6%) – there wasn’t black in Y3 and Y6 – ethnic groups, public school provenience – both elementary school (42.5%) and high school (73.6%) –, lower maternal schooling (high school, p < 0.001) and lower family income (p < 0.001). Years 3 and 6 majority was composed of white academics (76.7% and 90.3%, respectively), coming from private schools (basic education and high school), with further maternal education (higher education/post-graduation) and bigger average income. The influence factors leading to choice for medical specialty modified (p < 0,001) among graduation years. Y1 students opted more frequently for ‘surgery/orthopedics’ (37.7%), ‘medical clinic/neurology’ (23.6%) and ‘psychiatry’ (11.3%). To Y3, the most desired specialties were ‘medical clinic/neurology’ (40%), ‘surgery/orthopedics’ (13.4%) and ‘obstetrician-gynecologist’ (13.3%). Amongst Y6 undergraduates, the most chosen specialties were ‘medical clinic/neurology’ (24.5%), ‘obstetrician-gynecologist’ (20.2%) and ‘surgery/orthopedics’ (17%). Y1 academics also revealed different aspirations regarding intended future workplace, with larger desire to practice only on SUS or on international programs. In this context, results indicate that Unicamp inclusion policy and its modifications over the years, particularly in 2016 entrance exams, have been effective in broadening access to medical education, such as greater socio demographic, economic and ethnic plurality coupled with variations in reasons for choice of medical career and specialty among graduation years analyzed.

Cervical cancer is the third leading cancer in Brazil and national screening program targets women from 25 to 64 years, with the Papanicolaou (Pap) test as the standard method. A few countries or medical associations recommend the start of the screening at age 21, a policy that remains controversial, for the higher risk of unnecessary treatment and morbidities related. Previous studies reported that 1% of the cases diagnosed before the age of 25. The aim of this study is to assess evolution of cases diagnosed among females younger than 25 years old in a regional hospital and their evolution. Cases selected were diagnosed from 2001 to 2015 and medical records were analysed until 2018 in a cohort study, gathering 32 cases (1,6% of 2041 cervical cancer registries, only 2 of them under 20 years old). Data gathered was registered and survival was measured by Kaplan-Meier estimates. There was an increasing trend of cervical cancers (p=0,04), with a higher rate of adenocarcinomas (19%) and stage I cancers (56%). Five-year overall survival rate was 76%, with worse rates among females under 22 years old (66% vs. 82%) and adenocarcinomas (43% vs. 86%). Survival rates between stage I cancer were 100%, in contrast with 46% observed in advanced stages. Therefore, although less frequent, cervical cancer in younger females tend to rise; these findings also suggest a higher rate of adenocarcinoma, with worse survival rates in this histological type and in advanced clinical stages.

Evidence-based clinical guidelines ensure best practice protocols are available in health care. There is a widespread use of human papillomavirus deoxyribonucleic acid (HPV-DNA) tests in Brazil, regardless of the lack of official guidelines. On behalf of the Brazilian Association for the Lower Genital Tract Pathology and Colposcopy (ABPTGIC, in the Portuguese acronym), a team of reviewers searched for published evidence and developed a set of recommendations for the use of HPV-DNA tests in cervical cancer screening in Brazil. The product of this process was debated and consensus was sought by the participants. One concern of the authors was the inclusion of these tests in the assessment of women with cytologic atypia and women treated for cervical intraepithelial neoplasia (CIN). Testing for HPV is recommended in an organized screening scenario to identify women with precursor lesions or asymptomatic cervical cancer older than 30 years of age, and it can be performed every 5 years. It also has value after the cytology showing atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSILs) as a triage test for colposcopy, in the investigation of other cytological alterations when no abnormal findings are observed at colposcopy, seeking to exclude disease, or, further, after treatment of high-grade cervical intraepithelial neoplasia, to rule out residual disease.O uso de diretrizes clínicas baseadas em evidências visa assegurar as melhores práticas na área de cuidado à saúde. O uso de testes de ácido desoxirribonucleico de papilomavírus humano (DNA-HPV) vem crescendo e se disseminando sem que existam recomendações de uso no cenário brasileiro. Em nome da Associação Brasileira de Patologia do Trato Genital Inferior e Colposcopia (ABPTGIC), grupos de revisores pesquisaram evidências e formularam recomendações para o uso dos testes de DNA-HPV no rastreamento do câncer do colo do útero, no seguimento de mulheres com atipias citológicas, e após tratamento de neoplasia intraepitelial cervical (NIC). O produto desse processo foi debatido e foi buscado consenso entre participantes. Os testes de DNA-HPV são recomendados num cenário de rastreamento organizado para identificação de mulheres portadoras de lesões precursoras ou câncer assintomático com mais de 30 anos e podem ser realizados a cada 5 anos. Também têm valor após a citologia mostrando células escamosas atípicas de significado indeterminado (ASC-US) ou lesão intraepitelial escamosa de baixo grau (LSIL) como teste de triagem para colposcopia, na investigação de outras alterações citológicas quando não são observados achados anormais à colposcopia, buscando excluir doença, ou, ainda, no seguimento após tratamento das neoplasias intraepiteliais de alto grau, para exclusão de doença residual.

Objectives To evaluate the prognosis of hysterectomy post-radiotherapy in women with endocervical adenocarcinoma from a university hospital (Unicamp/Brazil), compared to those undergoing exclusive radiotherapy. Methods Were selected 80 cases of women with endocervical adenocarcinomas FIGO IB to IIIB from 1988–2015, 39 treated with radiotherapy followed by hysterectomy and isolated radiotherapy for 41. Disease-free interval (DFI) and overall survival (OS) were analysed using Kaplan-Meier curves and log-rank test. Results There was no difference in OS between the groups (P=0.579) or in the DFI (p=0.963). It was observed that the DFI in patients with residual disease was lower, however without statistical significance (P=0.072). Recurrences were observed in 9/39 patients of the hysterectomy group and 10/41 patients of the isolated radiotherapy group. Residual disease in the hysterectomy group was associated with a higher rate of local and distance recurrence (P=0.028). Conclusions There were no differences in recurrence rates, disease-free interval, and overall survival among the groups, although the detection of residual disease in the hysterectomy was associated with a higher occurrence of recurrences. The findings do not support the routine hysterectomy in women previously irradiated in endocervical adenocarcinoma.

Objectives To evaluate outcomes related to nephrostomy in women before and after cervical cancer treatment for acute obstructive renal failure. Methods Were included 52 cases of women with cervical cancer IIIB+ and acute obstructive renal failure that have undergone nephrostomy at the University Women’s Hospital of Unicamp (Campinas, Brazil), from 2003 to 2017. Two groups were evaluated: before and after radiotherapy treatment (BR and AR). Variables were analyzed by frequencies and survival by Kaplan-Meier curves and log-rank. Results The mean age was 47.8 years old (ST 13.4), and the mean urea and creatinine before the procedure were respectively 134.8 and 13.2 (ST 76.9 and 29.7). Average days of hospitalization were 25 days. After three years of the procedure, 56% of the women in BR and 100% of the women in AR were dead (p=0.047). The six-months overall survival after nephrostomy was 46.4 in BR and 14.8 in AR, while the one-year overall survival was 19.3 in BR and 3.7 in AR (log-rank three-year overall survival P=0.007). Conclusions Nephrostomy for acute renal failure due to cervical cancer is associated with prolonged hospitalization regardless of the stage of the treatment. Overall survival was low in both groups, but higher in women in the BT procedure. Although nephrostomy might be considered useful in treatment-naive patients with obstructive renal failure, the validity of this type of treatment in the group of women that had already undergone treatment is not yet defined.

Objective: To evaluate the indication and performance of systematic lymphadenectomy (SL) in Stage I endometrioid endometrial carcinoma (EEC), at intermediate risk (FIGO IAG2/G3, IBG1/G2) on recurrence, disease-free survival (DFS) and survival. Study design: 194 women underwent hysterectomies by laparotomy, with SL (n = 95) or without SL (n = 99) between 1990 and 2014 was evaluated. Diagnosis period, age, BMI, comorbidities, stage, and adjuvant radiotherapy were analyzed. DFS and cancer-specific survival were analyzed by Kaplan-Meier and log-rank test, and recurrences by Cox regression. Results: SL was performed in 93% (41/44) of women managed before 1998 and decreasing after that (p

Population-based screening programs have reduced significantly cervical cancer burden in high-income countries over the past few decades. Low- and middle-income countries have failed to show a major impact on cervical cancer control, even in settings where cytology- or visual inspection-based screening activities are ongoing. Widespread use of HPV vaccine is the most promising strategy to avoid disease development. Nevertheless, a vaccine population-based approach is still limited to some settings, and the impact of mass vaccination is not expected for some time. In 2016 the American Society of Clinical Oncology issued a stratified guideline addressing global resources disparities. The goal of this chapter is to debate challenges from low- and middle-income countries to implement successful cervical cancer screening programs in order to reduce cancer burden. The feasibility for introduction of new technologies, like the HPV-DNA-based tests, will be analyzed according to the different scenarios. This intends to be a critical review addressing aspects of organization of screening programs in the view of global disparities.

Cervical adenocarcinoma is associated with a poor prognosis, which may be caused by the infiltrative growth pattern and metastasis of tumor cells. There is a lack of consensus on hysterectomy after radiotherapy for the improvement of selected cases. The present study aimed to assess the oncological outcome of post-radiotherapy hysterectomy in females with cervical adenocarcinoma. A total of 39 females with cervical adenocarcinoma at stages IB1 to IIIB, managed primarily with radiotherapy with complete response, and underwent extrafascial hysterectomy as consolidation therapy between 1988 to 2015 were studied. Surgery complications and residual disease were evaluated. A comparison group was constructed, comprising 41 females with cervical adenocarcinoma managed with exclusive radiotherapy or chemoradiotherapy demonstrating complete response, without surgery. Descriptive and survival analysis was performed. The groups were comparable in terms of age, cancer stage, radiotherapy (dose and duration) and follow-up, although 67% of hysterectomies were performed prior to 2002 and 46% of the radiotherapy group received chemoradiation. Late complications were similar. There were nine recurrences (23%) in the case series and 10 recurrences (24%) in the radiotherapy group. Residual disease was detected in 56% (22/39) of uterine specimens, of which 12 were up to 10 mm. Residual disease was associated with recurrence (31% vs. 6%, P=0.028). The overall survival rate was 75% for the case series vs. 88% for the radiotherapy group (P=0.579), and the disease-free survival rate was 79-80% for both. Removal of residual disease by hysterectomy did not improve the overall survival rate (P=0.283) and disease-free survival rate (P=0.072). Post-radiotherapy hysterectomy in cervical adenocarcinoma is a feasible procedure with acceptable complications, however, it did not bring relevant benefits in recurrences, disease-free survival, and overall survival rates.

ObjectivesTo evaluate pathologic features with implications on surgical radicality in women treated with radical hysterectomy and pelvic lymphadenectomy for cervical cancer stage IA1 with lymph vascular space invasion (LVSI) and stage IA2 by correlating findings in conization and hysterectomy specimens.MethodsWomen with cervical cancer stage IA1 with LVSI and stage IA2 diagnosed by loop electrosurgical excisional procedure or cold knife conization were treated with radical hysterectomy and pelvic lymphadenectomy from January 1999 to December 2011 in 2 institutions.ResultsFifty patients were enrolled: 40 with stage IA2 and 10 with stage IA1 with LVSI. Median age was 43 (30–67) years. All patients underwent cervical conization for diagnosis (45 loop electrosurgical excisional procedure, 5 cold knife). Lymph vascular space invasion was detected in 15 patients (30%). Two patients had positive pelvic nodes. No parametrial involvement was detected in the entire cohort. Positive margins were present in 35 patients, and residual disease was detected in 22 patients (44%). Positive margins predicted residual disease at radical hysterectomy (P = 0.02). Medium follow-up time was 51 months. One patient developed a pelvic recurrence, and there were no disease-related deaths.ConclusionsPatients with positive margins in cone biopsy specimens have an increased risk of residual disease at radical hysterectomy and require careful evaluation before conservative surgery. Pelvic lymph node evaluation is essential because lymph node metastasis may occur even in early stages. The lack of parametrial invasion in this study reinforces the knowledge that the select group of patients with microinvasive cervical carcinoma stages IA1 LVSI and stage IA2 have a very low risk of parametrial infiltration. Less radical surgery can be carefully considered for these patients.

To assess the value of vaginal screening cytology after hysterectomy for benign disease.This cross-sectional study used cytology audit data from 2,512,039 screening tests in the metropolitan region of Campinas from 2000 to 2012; the object was to compare the prevalence of abnormal tests in women who had undergone a hysterectomy for benign diseases (n=53,891) to that of women who had had no hysterectomy. Prevalence ratios (95% confidence intervals, 95% CI) were determined, and chi-square analysis, modified by the Cochrane-Armitage test for trend, was used to investigate the effects of age.The prevalence of atypical squamous cells (ASC), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion or squamous-cell carcinoma (HSIL/SCC) was 0.13%, 0.04% and 0.03%, respectively, in women who had undergone hysterectomy, and 0.93%, 0.51% and 0.26% in women who had not undergone hysterectomy. The prevalence ratios for ASC, LSIL and HSIL/SCC were 0.14 (0.11-0.17), 0.08 (0.06-0.13) and 0.13 (0.08-0.20), respectively, in women with a hysterectomy versus those without. For HSIL/SCC, the prevalence ratios were 0.09 and 0.29, respectively, for women50 or ≥50 years. The prevalence rates in women with a previous hysterectomy showed no significant variation with age.The prevalence rates of ASC, LSIL and HSIL/SCC were significantly lower in women with a previous hysterectomy for benign disease compared with those observed in women with an intact uterine cervix. This study reinforces the view that there is no evidence that cytological screening is beneficial for women who have had a hysterectomy for benign disease.

Drug abuse (addiction) has been listed among the risk factors for human papillomavirus (HPV) infections, but no case-control studies exist to rule out sexual behaviour and other potential confounders. The aim of this study is to evaluate the role of drug addiction as an independent predictor of HR-HPV infections and (cervical intraepithelial neoplasia) CIN2+ in an age-matched case-control (1:4) study nested within the prospective Latin American Screening (LAMS) study cohort. All 109 women in the LAMS cohort (n=12,114) reporting drug abuse/addiction were matched with four controls (n = 436) of non-abusers strictly by age. Conditional logistic regression analysis was used to estimate the co-variates of drug abuse, and the whole series (n=545) was analysed for predictors of HR-HPV and CIN2+ using univariate and multivariate regression models. Oncogenic HPV infections were significantly (P=0.019) more prevalent among abusers (37.7%) than in controls (21.9%), but there was no difference in high-grade squamous intraepithelial lesions (P=0.180) or CIN2+ lesions (P=0.201). In multivariate conditional logistic regression, number of lifetime sexual partners (P=0.0001), ever smokers (P=0.0001), non-use of OCs (P=0.013), ever having sexually transmitted diseases (STD) (P=0.041) and no previous Pap smear (P=0.027) were independent co-variates of drug addiction. Drug abuse was not an independent risk factor of high-risk (HR)-HPV infection, which was significantly predicted by (1) age below 30 years (P=0.045), (2) more than five lifetime sexual partners (P=0.046) and (3) being current smoker (P=0.0001). In multivariate model, only HR-HPV infection was an independent risk factor of CIN2+ (P=0.031), with adjusted OR=11.33 (95% CI 1.25-102.50). These data indicate that drug addiction is not an independent risk factor of either HR-HPV infections or CIN2+, but the increased prevalence of HR-HPV infections is explained by the high-risk sexual behaviour and smoking habits of these women., European Commission (LAMS denotes Latin American Screening study funded by European Commission), INCO-DEV Programme (Contract No. ICA4-CT-2001-10013). The generous contribution of DIGENE Inc. (USA) donating the HCII tests at our disposal is gratefully acknowledged

The objective of the study was to investigate the expression of p53 and p16INK4ain cervical intraepithelial neoplasia (CIN) and their relation with disease severity and high-risk human papillomavirus (HR-HPV) status. A series of 125 women with previous positive Pap smear were selected for this cross-sectional study. All patients underwent gynecological examination, including colposcopy. Specimens for Pap smears, Hybrid Capture 2 (HC2) test, and pathologic analysis were obtained. After evaluation of CIN grade, immunohistochemical detection of proteins p53 and p16INK4awas performed on paraffin-embedded sections. The extent of immunoexpression of both proteins was analyzed in relation to CIN grade and HR-HPV status. CIN was graded as 1 in 21, 2 in 17, and 3 in 87 specimens. p16INK4apositivity (at least 5% of epithelial cells stained) was found in 99 of 125 cases (79.2%) and was significantly higher in high-grade lesions as compared to low-grade CIN (P< 0.001). The expression of p53 did not differ across histologic strata. Protein expression neither of p16INK4anor of p53 correlated with HR-HPV status. Expression of p16INK4awas not related with that of p53. Our study gives further support to previous findings of strong association of p16INK4aimmunostaining with severity of epithelial atypia, but this protein may not be considered a predictor of HR-HPV status determined with HC2. By contrast, immunoexpression of p53 was related neither to CIN grade nor to HR-HPV status.

OBJETIVO: Avaliar o uso da laparoscopia como método diagnóstico e terapêutico na abordagem inicial de tumores anexiais em população de risco para malignidade, bem como fatores clínicos associados à falha do método e conversão para laparotomia, e comparar taxas de complicação com pacientes cuja abordagem inicial se deu por laparotomia. MÉTODOS: Estudo prospectivo com 210 mulheres com exames de imagem prévios constando tumor anexial, das quais 133 foram incluídas. Destas, 45 foram submetidas à laparoscopia e 88, à laparotomia. Catorze das 45 cirurgias iniciadas por laparoscopia foram convertidas a laparotomia no intraoperatório. Foi avaliado se idade, índice de massa corporal (IMC), número de cirurgias abdominais prévias, CA-125, índice de risco de malignidade (IRM), diâmetro do tumor, duração da cirurgia e número de complicações cirúrgicas diferiram entre os grupos laparoscopia, laparoscopia com conversão à laparotomia e laparotomia. Foi também avaliado o motivo reportado pelos cirurgiões como falha da laparoscopia e a razão da conversão para laparotomia. RESULTADOS: A taxa de tumores malignos neste estudo foi de 30%. Houve diferença nos valores de CA-125, IRM e diâmetro do tumor entre os grupos laparoscopia e laparotomia. A duração da cirurgia foi maior no grupo de laparoscopias convertidas à laparotomia, porém as taxas de complicação cirúrgica foram semelhantes entre os grupos e, quando isolados os tumores benignos, as taxas de complicação cirúrgica da laparoscopia se mostraram inferiores à laparotomia. Dentre os fatores em estudo, apenas o tamanho do tumor esteve relacionado à conversão para laparotomia. CONCLUSÃO: Este estudo sugere que a abordagem inicial de pacientes com tumores anexiais de risco para malignidade é segura e não aumenta as taxas de complicação, mesmo em pacientes que necessitem de conversão para laparotomia; entretanto, nos casos de dúvida, é preciso avaliar a necessidade de consultar ginecologistas com experiência em laparoscopia avançada e no tratamento de câncer. O tamanho do tumor esteve relacionado à conversão para laparotomia. PURPOSE: To assess clinical factors, histopathologic diagnoses, operative time and differences in complication rates between women undergoing laparoscopy or laparotomy to diagnose and treat an adnexal mass and their association with laparoscopy failure. METHODS: In this prospective study, 210 women were invited to participate and 133 of them were included. Eighty-eight women underwent laparotomy and 45 underwent laparoscopy. Fourteen of the 45 laparoscopies were converted to laparotomy intraoperatively. We assessed whether age, body mass index (BMI), previous abdominal surgeries, CA-125, Index of Risk of Malignancy (IRM), tumor diameter, histological diagnosis, operative time and surgical complication rates differed between the laparoscopy group and the group converted to laparotomy and whether those factors were associated with conversion of laparoscopy to laparotomy. We also assessed surgical logs to evaluate the reasons, as stated by the surgeons, to convert a laparoscopy to laparotomy. RESULTS: In this research, 30% of the women had malignant tumors. CA-125, IRM, tumor diameter and operative times were higher for the laparotomy group than the laparoscopy group. Complication rates were similar for both groups and also for the successful laparoscopy and unsuccessful laparoscopy groups. The surgical complication rate in women with benign tumors was lower for the laparoscopy group than for the laparotomy group. The factors associated with conversion to laparotomy were tumor diameter and malignancy. During laparoscopy, adhesions a large tumor diameter were the principal causes of conversion. CONCLUSION: This study suggests that laparoscopy for the diagnosis and treatment of adnexal masses is safe and does not increase complication rates even in patients who need conversion to laparotomy. However, when doubt about the safety of the procedure and about the presence of malignancy persists, consultation with an expert gynecology-oncologist with experience in advanced laparoscopy is recommended. A large tumor diameter was associated with the necessity of conversion to laparotomy.

ObjectiveThe objective of this study was to evaluate the impact of cervical cytology screening on the prevalence of cervical cytological results in women, as a function of age and test interval.MethodsThis is a cross-sectional study of cytology screening data of 2,002,472 tests obtained from previously screened women and 217,826 tests from unscreened women. The central cytopathology laboratory database was analyzed. The tests were collected for screening purposes from Campinas metropolitan region, Brazil. A prevalence ratio (PR) with a 95% confidence interval was calculated for the screened women, in relation to the unscreened women, and for different tests intervals. Protection afforded by screening (1-PR) was calculated.ResultsFor high-grade squamous intraepithelial lesion, the PR was 0.97 (0.83–1.13) for women aged 20 years or younger and 0.99 (0.86–1.14) for women aged 20 to 24 years, decreasing significantly in women aged 25 to 29 years (PR, 0.63 [0.52–0.76]). The PR for squamous cell carcinoma, adenocarcinoma in situ (AIS), and invasive adenocarcinoma showed a significant reduction in all age groups older than 30 years. For the age group ranging from 30 to 59 years, protection for squamous cell carcinoma, AIS, and invasive adenocarcinoma was 83% or higher for screening intervals from 1 to 5 years. Protective effect was not demonstrated for screening intervals longer than 5 years for AIS and invasive adenocarcinoma.ConclusionsCytology screening is effective at preventing cytological high-grade squamous intraepithelial lesion, squamous cell carcinoma, AIS, and invasive adenocarcinoma. On the basis of cytological results, protection against AIS and invasive adenocarcinoma was observed with screening intervals shorter than 5 years. Cytological screening in women 25 years or younger should be critically evaluated.

This study was conducted to evaluate 3 different methods, used alone or in combination, of screening for cervical intraepithelial neoplasia (CIN), and to compare the outcomes with colposcopic findings. Eight hundred nine patients were recruited to undergo cervical screening with visual inspection of the cervix using acetic acid (VIA), human papillomavirus (HPV) testing using hybrid capture II (HCII), and conventional Pap smear. Social and demographic information and clinical history were obtained at the enrollment visit by interview and questionnaire before pelvic examination. After collection of Pap and HCII samples, VIA was conducted 1 minute after application of 5% acetic acid to the cervix. Cervical abnormalities were recorded according to the Atlas of Visual Inspection. The presence of areas suggestive of condyloma, CIN 1, CIN 2, CIN 3, or cancer was recorded as positive VIA results. All patients underwent colposcopy after pelvic examination, and suspicious areas were biopsied. There were 99 (12%) patients with positive VIA results, of which 28% were suspected condyloma, 57% were thought to be CIN 1, 13% were suspicious for CIN 2/3, and one was a potential case of invasive cancer. In all, there were 57 (7%) positive Pap smear results, including 22 atypical squamous cells of undetermined significance (ASCUS) (38% of abnormalities), 20 low-grade squamous intraepithelial lesions (LSIL) (35%), 14 high-grade intraepithelial lesions (HSIL) (25%), and one diagnosis of atypical glandular cells (AGC) (2%). One smear was inadequate for evaluation. HPV testing identified 151 (19%) patients positive for high-risk HPV. In the final histologic diagnoses, 40 (5%) women had cervical neoplasia, including 29 CIN 1, 7 CIN 2, 3 CIN 3, and one invasive cancer. The sensitivity and specificity for each test alone or in combination are shown in Tables 1 and 2. For identifying CIN 2 or worse, HCII had the highest sensitivity (73%) and Pap smear was the most specific (93%). Together, Pap and HCII had the highest sensitivity (82%) for detection of CIN 2 or worse. The highest specificity was seen in the combination of VIA and Pap smear (83%).

To assess the prediction potential of a 5-biomarker panel for detecting high-risk human papillomavirus (HR-HPV) infections and/or cervical intraepithelial neoplasia (CIN) progression. Five biomarkers, lipocalin, plasminogen activator inhibitor-2, p300, interleukin-10, and stratifin, were assessed in cervical biopsies from 225 women of the Latin American Screening Study. Competing-risks regression models were constructed to assess their predictive power for (i) HR-HPV outcomes (negative, transient, or persistent infection) and (ii) CIN outcomes (no progression, incident CIN1, CIN2, or CIN3). p300, LCN2, stratifin were significantly associated with prevalent HR-HPV but lost their significance in multivariate analysis. In the multivariate model, only p300 was an independent predictor of CIN3 (odds ratio=2.63; 95% confidence interval, 1.05-6.61; P=0.039). In univariate competing-risks regression, lipocalin predicted permanent HR-HPV-negative status, but in the multivariate model, IL-10 emerged as a independent predictor of HPV-negative status (subhazard ratio=4.04; 95% confidence interval, 1.81-9.01; P=0.001). The clinical value of the panel in predicting longitudinal outcomes of HR-HPV infection and/or incident CIN is limited., Supported by the European Commission, INCO-DEV Programme (Contract# ICA4-CT-2001-10013).

Objective To evaluate the performance of mesothelin, CA125, HE4 and ROMA index in the detection of malignant ovarian tumors. Study Design This is a cross-sectional study including 199 women with adnexal masses (67 with malignant tumors and 132 with benign tumors) and 150 healthy women (controls). We used a recursive multivariate partitioning algorithm to assess the contribution of each of the serum markers and the ROMA index to the discrimination of women with malignant tumors. Also, the areas under the ROC curves (AUC) for each of the serum markers and for the ROMA index were compared using the Venkatraman's projection-permutation test. Results In the recursive model, CA125 had the best performance in discriminating women with malignant tumors. In women with normal-range CA125 levels, none of the other markers contributed to the discrimination of women with malignant tumors. In women with elevated CA125 levels, elevated HE4 levels were associated with an increased risk of harboring a malignant tumor. The AUC for mesothelin was smaller than that for all the other curves, and both the ROMA index and CA125 had better AUC than HE4. Conclusion In women with normal CA125 levels, neither mesothelin nor HE4 contributed to discriminate women with malignant ovarian tumors; however, for women with elevated CA125 levels HE4 may help discriminating those who have a malignant ovarian tumor.

To examine the effect of smoking on the incidence of low- and high-grade cervical intraepithelial neoplasia (CIN) in women with a baseline Pap smear of atypical squamous cells (ASC) or a low-grade squamous intraepithelial lesion (LSIL). Objective. To examine the effect of smoking on the incidence of low‐ and high‐grade cervical intraepithelial neoplasia (CIN) in women with a baseline Pap smear of atypical squamous cells (ASC) or a low‐grade squamous intraepithelial lesion (LSIL). Design. Prospective study in which a cohort of women with normal colposcopy and ASC/LSIL at baseline were followed at 6‐month intervals of up to 36 months. Women were grouped in post‐hoc analysis according to their smoking behavior: never (or past) smokers and current smokers. Setting. This report was based on data from the Latin American Screening Study, conducted in São Paulo, Campinas, Porto Alegre (Brazil) and Buenos Aires (Argentina). Population. A subset of 150 women derived from a cohort of 1,011 women. Methods. Multivariate Cox analysis and Kaplan–Meier curves were used. Main outcome measures. Low‐ and high‐grade CIN during follow‐up. Results. The only factor related to an increased risk of developing CIN was the positive high‐risk (hr) HPV status (hazard ratio (HR) = 3.42; 95% CI: 1.11–9.43). A total of 21 cases of incident CIN were detected during follow‐up. Of these, 11 appeared in the group of 67 smokers and 10 among the 83 non‐smoker women (log‐rank, p = 0.33). Smoking status was not associated with the risk of developing CIN (HR = 0.73; 95% CI: 0.40–1.33). However, when restricting the analysis to high‐grade CIN only (11 cases), the probability of developing the disease was significantly higher among smokers (p = 0.04). Conclusions. Smoking contributes additional risk for developing high‐grade CIN in women with ASC or LSIL cytology but normal colposcopy., LAMS (Latin American Screening) study, entitled: Improving health systems towards equality‐based control of cervical cancer in Latin America, and supported by the Inco‐Dev Program of the European Commission (Project No. ICA4‐CT‐2001‐10013). The contribution of Digene Inc. (USA)

To assess whether human papillomavirus (HPV) testing is a safe enough approach to warrant extension of the screening intervals of baseline Papanicolaou (Pap)-/HPV- women in low-income settings., European Commission, INCO-DEV Programme (Contract # ICA4-CT-2001-10013). The generous contribution from DIGENE Inc. (USA) donating the HC 2 tests

Orientadores: Sophie Françoise Mauricette Derchain, Luis Otavio Zanatta Sarian Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas Resumo: Objetivo: Avaliar a relação da expressão do p53 e do p16INK4a em diferentes graus de neoplasia intra-epitelial cervical (NIC) e suas possíveis relações com a recidiva/persistência da NIC após conização diatérmica e a infecção persistente de papilomavírus humano (HPV) de alto risco oncogênico. Sujeitos e métodos: Este foi um estudo de corte, com análise intermediária em corte transversal, para o qual foram selecionadas mulheres submetidas à conização diatérmica no período de fevereiro de 2001 a abril de 2004. Os resultados deste estudo são apresentados em dois artigos: o primeiro consiste em corte transversal incluindo 125 espécimes cirúrgicos de mulheres submetidas a conização diatérmica. Foram avaliadas a expressão do p53 e do p16INK4a em diferentes graus de NIC e sua relação com a infecção pelo HPV de alto risco oncogênico realizado através da Captura de Híbridos 2 (CH2). No segundo artigo, com análise longitudinal foram incluídas 104 mulheres com NIC 2 ou 3, seguidas por até 24 meses após conização diatérmica. Foram avaliadas a expressão de p16INK4a e p53 como fatores préditivos de persistência/recidiva de NIC e a sua relação com a infecção persistente por HPV de alto risco oncogênico após o conização cervical diatérmica. Resultados: No primeiro artigo foram incluídos 21 casos cervicites/NIC1, 17 NIC2 e 87 NIC3. Noventa e nove (79,2%) casos foram positivos para p16INK4a (> 5% do epitélio corado), significativamente maior em lesões de alto grau (p< 0.001). A expressão do p53 não variou de acordo com o grau histológico. Não houve correlação entre a expressão da p16INK4a e a detecção do HPV de alto risco oncogênico. A expressão do p16INK4a não teve relação com a do p53. No segundo artigo, 104 mulheres com NIC 2 ou 3 foram acompanhadas por 24 meses, e detectou-se 12 casos de recidiva/persistência de NIC, sendo 8 nos primeiros 6 meses. Entre as mulheres com recidiva/persistência de NIC, 9 (75%) apresentaram presistência do HPV de alto risco oncogênico. A expressão da p16INK4a foi moderada/forte em 96 casos (92%) e mais de 50% dos núcleos estavam corados para p53 em 80 (78%). A análise prospectiva não detectou diferença significativa na recidiva/persistência da NIC durante o follow up com segundo a expressão do p16INK4a ou do p53. Nenhum dos parametros estudados teve relação com a infecção persistente pelo HPV. Conclusões: este estudo está em concordância com o conhecimento atual e mostra uma associação da positividade para p16INK4a com a severidade da lesão cervical, embora esta proteína não esteja associada com a detecção de HPV de alto risco oncogênico pela CH2. Não houve correlação entre a expressão de p53 e a positividade para HPV nem houve associação da expressão do p53 com a do p16INK4a. A análise prospectiva não mostrou correlação entre a expressão do p 16 INK4a e do p53 e a recorrência/persistência da NIC ou persistência do HPV de alto risco oncogênico no seguimento de mulheres com NIC 2 ou 3 tratadas com conização diatérmica Abstract: Objective: to concurrently investigate the immunoexpression of p53 and p16INK4a4 in different grades of cervical intra-epithelial neoplasia (CIN) and their relation with the persistence/ recurrence of CIN and persistent infection by high-risk Human Papillomavirus (hr-HPV) after electrosurgical cervical conization. Subject and methods: a series of 125 women subjected to electrosurgical conization was selected for this cross-sectional and cohort study. Enrollment was carried out between February 2001 and April 2004. The results of this study are presented in two articles: the first one consists of a cross-sectional analisys, including 125 surgical specimens of women who underwent diathermic conization. Expression of p53 and p16INK4a were evaluated in different grades of CIN and their relation with hr-HPV infection was evaluated with HC2. The second article is a longitudinal analysis on 104 women with CIN 2 and 3, followed up for 24 months after electrosurgical cervical conization. Expression of p16INK4a and p53 were tested as predictive markers of persistent/recurrent CIN and persistent infection by hr-HPV during follow up after electrosurgical cervical conization. Results: in the first series, 21 cases of CIN1, 17 CIN2 and 87 CIN3 were included. Ninety-nine (79.2%) cases stained moderate/strongly to p16INK4a, significantly higher in high-grade CIN (p< 0.001). p53 expression did not relate with the grade of CIN and there was no relation between p16INK4a expression and hr-HPV detection. Expression p16INK4a and p53 were not correlated. In the second article, 104 women with CIN 2 or 3 were followed up for 24 months, and 12 (11%) persistent/recurrent CIN were observed, eight of them during the first 6 months follow-up. Among women with persistent/recurrent CIN, 9 (75%) presented persistent hr-HPV detection. p16INK4a expression was moderate/strong in 96 cases (92%) and p53 stained in more than 50% of the nuclei in 80 (77%). The expression of p16INK4a or p53 was not associated with persistent/recurrent CIN during follow-up. None of the studied parameters correlated with persistent hr-HPV detection. Conclusion: these results showed a strong association between p16INK4a expression and grade of CIN, although this protein was not associated with hr-HPV detection by HC2. There was no relation between p53 and hr-HPV detection or p16INK4a expression. Prospective analysis showed that p16INK4a and p53 expression was not related with persistent/recurrent CIN or persistent hr- HPV detection during follow-up of women conservatively treated for CIN 2 or 3 Doutorado Tocoginecologia Doutor em Tocoginecologia

Hybrid capture II (HC II) test for oncogenic human papillomaviruses (HPV) was carried out in a cohort of 4284 women at their first clinical visit. Overall prevalence of HPV was 17.1%, decreasing with age from 33.9% among women below 20 years to only 11.0% among those older than 41 years. HPV prevalence was significantly higher among current smokers (odds ratio [OR] = 1.31; 95% CI 1.1–1.6), in women with two or more lifetime sexual partners (OR = 1.9; 95% CI 1.6–2.4), and those women with two or more sexual partners during the past 12 months prior to examination (OR = 1.6; 95% CI 1.2–2.2). HPV detection increased in parallel with increasing cytologic abnormality, being highest in women with high-grade squamous intraepithelial lesion (P = 0.001). Specificity of the HPV test in detecting histologically confirmed cervical disease was 85% (95% CI 83.9–86.1). Sensitivity of the HPV test in detecting histologic abnormalities increased in parallel with disease severity, ranging from 51.5% for cervical intraepithelial neoplasia (CIN) 1 to 96.5% for CIN 3 and 100.0% for cancer, with respective decline of positive predictive value. These data suggest that HPV testing with HC II assay might be a viable screening tool among this population with relatively high prevalence of cervical disease.

Objective To assess the role of HPV as determinant of the incident cytological abnormalities (SIL) and cervical lesions (CIN) during a 24-month follow-up of baseline PAP smear-negative subgroup of women included in the Latin American Screening study (LAMS). Study design A group of 365 women with normal Pap smear and negative or positive high-risk Hybrid Capture II test were prospectively followed-up for 24 months at Campinas and São Paulo (Brazil). The incidence rate (IR) and risk ratio (RR and 95% CI) of developing cytological or histological abnormality during the follow-up was calculated for HPV-negative and HPV-positive women. Results During the 12-month follow-up, women HPV-positive at baseline had developed a significantly higher rate of incident LSIL (IR = 3.5%, RR = 1.4; 95% CI 1.1–1.7) and HSIL (IR = 0.7%, RR = 1.5; 95% CI 1.4–1.7) abnormality. For HSIL, the IR increased to 2.1% and the RR increased to 1.7 (95% CI 1.5–1.9) among those followed for 24 months. Similarly, women with positive HPV tests were at a higher risk of developing CIN 2–3 (IR = 2.6%, RR = 1.5; 95% CI 1.4–1.6) during the first 12 months of follow-up, and for those followed for 24 months, this RR increased further to 1.7 (95% CI 1.5–1.9) although the IR was 0.7%. Conclusions Oncogenic HPV infections comprise a significant risk factor for incident cervical abnormalities, and HPV test is a useful adjunct to cytology in detecting the high-risk patients among baseline PAP smear-negative women., This study was funded by European Commission, INCO DEV Contract #ICA4-CT-2001-10013.

Objectives: To assess the performance indicators of visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI) in four Latin American centres participating in the ongoing Latin AMerican Screening (LAMS) study, in settings with moderate incidence of cervical disease and with poorly to moderately well-organized cervical cancer screening. Setting: Three Brazilian centres (São Paulo, Campinas and Porto Alegre) and one Argentine centre (Buenos Aires) recruited a total of 11,834 healthy women to undergo VIA, VILI, conventional Pap smear and Hybrid Capture II (HCII). Methods: Women who had a positive result from any of these tests were subjected to colposcopy and biopsies (if necessary), and women with high-grade cervical intraepithelial neoplasia (CIN) were properly treated. To control for verification bias, 5% of women with normal tests were referred for colposcopy, as were 20% of HCII-negative women. Results: Data on VIA ( n=11,834), VILI ( n=2994), conventional Pap smear ( n=10,138) and HCII ( n=4195) were available for test comparisons, calculating sensitivity, specificity, and positive and negative predictive values. Overall test positivity was 11.6% for VIA, 23.0% for VILI, 2.2% for Pap smear (LSIL threshold), 1.1% for Pap smear (HSIL threshold) and 17.1% for HCII. VIA was positive in 61.8% of the women with CIN 1, 57.0% of those with CIN 2, 35.0% of women with CIN 3 and in 21 of 28 (75%) of women with cancer. Approximately 10% of women with no detectable disease had an abnormal VIA. Regarding VILI, 83.3% of women diagnosed with CIN 1 and 62.5% of those with CIN 3 had an abnormal test. VILI failed to detect one of three cases of cancer. Both the sensitivity, specificity and positive predictive value of VIA and VILI in detecting CIN 2 or CIN 3 could be significantly improved depending on the combination with Pap smear or HCII (sensitivity up to 100.0% and specificity up to 99.8%). Conclusions: The LAMS study failed to reproduce the performance figures obtained with VIA and VILI (as stand-alone tests) in some other settings, where the prevalence of cervical disease was higher. However, a combined use of VIA or VILI with the Pap test or HCII allowed specific detection of cervical abnormalities.

Objectives: We compared the indication of laparoscopy for treatment of adnexal masses based on the risk scores and tumor diameters with the indication based on gynecology-oncologists' experience. Methods: This was a prospective study of 174 women who underwent surgery for adnexal tumors (116 laparotomies, 58 laparoscopies). The surgeries begun and completed by laparoscopy, with benign pathologic diagnosis, were considered successful. Laparoscopic surgeries that required conversion to laparotomy, led to a malignant diagnosis, or facilitated cyst rupture were considered failures. Two groups were defined for laparoscopy indication: (1) absence of American College of Obstetrics and Gynecology (ACOG) guideline for referral of high-risk adnexal masses criteria (ACOG negative) associated with 3 different tumor sizes (10, 12, and 14 cm); and (2) Index of Risk of Malignancy (IRM) with cutoffs at 100, 200, and 300, associated with the same 3 tumor sizes. Both groups were compared with the indication based on the surgeon's experience to verify whether the selection based on strict rules would improve the rate of successful laparoscopy. Results: ACOG-negative and tumors ≤10 cm and IRM with a cutoff at 300 points and tumors ≤10cm resulted in the same best performance (78% success = 38/49 laparoscopies). However, compared with the results of the gynecology-oncologists' experience, those were not statistically significant. Discussion: The selection of patients with adnexal mass to laparoscopy by the use of the ACOG guideline or IRM associated with tumor diameter had similar performance as the experience of gynecology-oncologists. Both methods are reproducible and easy to apply to all women with adnexal masses and could be used by general gynecologists to select women for laparoscopic surgery; however, referral to a gynecology-oncologist is advisable when there is any doubt.