Competing-risks regression models in analysis of biomarkers as predictors of high-risk human papillomavirus (HPV) infection outcomes and incident CIN in the LAMS cohort.

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.

Hormonal contraceptives and the length of their use are not independent risk factors for high-risk HPV infections or high-grade CIN.

AIMS: To evaluate the role of hormonal contraceptives as a risk factor of high-risk human papillomavirus (HR-HPV), cervical intraepithelial lesions (CIN) and cervical cancer in our multi-center population-based LAMS (Latin American Screening) study. METHODS: A cohort study with >12,000 women from Brazil and Argentina using logistic regression to analyze the covariates of hormonal contraception (HOC - oral, injections, patches, implants, vaginal ring and progesterone intrauterine system) use followed by multivariate modeling for predictors of HR-HPV and CIN2+. RESULTS: HR-HPV infection was a consistent risk factor of high-grade CIN in all three groups of women. The length of HOC use was not significantly related to high-grade squamous intraepithelial lesions (HSIL)+ Pap (p = 0.069), LSIL+ Pap (p = 0.781) or ASCUS+ (p = 0.231). The same was true with the length of HOC use and histology CIN3+ (p = 0.115) and CIN2+ (p = 0.515). Frequently, HOC users have previously shown more HPV-related lesions, as well as lower HPV prevalence if they were current smokers. But HOC use and time of usage were not independent risk factors of either HR-HPV infection or high-grade CIN using multiple logistic regressions. CONCLUSIONS: No evidence was found for an association between the use of HOC with an increased risk for HR-HPV infection or high-grade CIN in this cohort.

p300 expression is related to high-risk human papillomavirus infections and severity of cervical intraepithelial neoplasia but not to viral or disease outcomes in a longitudinal setting.

To evaluate the role of the expression of the transcription factor p300 as an independent predictor of high-risk human papillomavirus (HR-HPV) infections and outcome of the cervical disease.Cervical biopsy samples taken at enrolment from 225 women of the Latin American Screening study cohort were analyzed for p300 using immunohistochemistry to assess its value as predictor of (a) cervical intraepithelial neoplasia (CIN) grade, and (b) HR-HPV at baseline, as well as (c) outcomes of HR-HPV infections, and (d) development of incident CIN as surrogate endpoints of progressive disease.There was a significant linear trend in increasing upregulation (=pattern shift) of p300 (P=0.0001) in parallel with increasing grade of CIN. When dichotomized (normal/moderately increase vs. strong-intense), upregulated p300 expression predicted CIN3+ with odds ratio=4.16 (95% confidence interval: 1.95-8.86) (P=0.0001) and CIN2+ with odds ratio=3.48 (95% confidence interval: 1.86-6.48) (P=0.0001). p300 was upregulated more often in HR-HPV+ lesions than in those remaining negative. Semiquantitative viral loads were also directly related to upregulation of p300 (P=0.036), but p300 was not a significant predictor of disease progression to either CIN1+ or CIN2+.p300 expression was upregulated in CIN lesions and related to detection and viral load of HR-HPV but not to their outcome or to incident CIN.

Increased risk of oncogenic human papillomavirus infections and incident high-grade cervical intraepithelial neoplasia among smokers: experience from the Latin American screening study.

BACKGROUND: The purpose of this study was to assess the effect of smoking on the prevalence and incidence of high-risk human papillomavirus (hr-HPV) infection and cervical intraepithelial neoplasia (CIN) in a large sample of Latin American women. METHODS: The study examines baseline data on over 12,000 women included in the Latin American Screening Study (Brazil and Argentina), and over 1000 women followed-up for a period of 36 months. Three groups were formed: never smokers, current, and past smokers. The prevalence of hr-HPV infection and CIN were compared between the study groups. In the prospective analysis, women were controlled at 6-month intervals to assess the cumulative risk of incident hr-HPV infection, smear abnormalities, and CIN. RESULTS: A higher prevalence (21.7%) of hr-HPV infection was found among current smokers as compared to never smokers (16.5%) or past smokers (13.5%). Being current smoker was significantly (P <0.01) associated with hr-HPV detection (OR = 1.6; 95% CI = 1.2-2.1). Being a current smoker was a significant predictor of incident hr-HPV during the follow-up [Hazards ratio (HR) = 1.4; 95% CI 1.0-1.9]. For incident CIN2+, being a past smoker (HR = 3.6; 95% CI 1.6-9.8) or current smoker (HR = 3.6; 95% CI 1.5-8.6) were the significant independent predictors. Current and past smokers had a significantly increased risk of incident CIN2+ (P <0.01). CONCLUSIONS: Smoking increases the risk of contracting hr-HPV infection and modifies the effect of a persistent hr-HPV infection by further increasing the risk of developing CIN2+. It seems that this effect modification persists over several years after smoking cessation.

Efficacy, safety, and acceptability of thermocoagulation for treatment of cervical intraepithelial neoplasia in a hospital setting in Brazil.

OBJECTIVE: To analyze the acceptability, safety, and effectiveness of thermocoagulation for the treatment of histologically proven cervical intraepithelial neoplasia grade 2-3 (CIN2-3) lesions. METHODS: In a retrospective study, data were obtained for women treated for CIN2-3 lesions by thermocoagulation at the Hospital de Clínicas de Porto Alegre, Brazil, between March 6, 2012, and October 29, 2013, and followed up after 1 year. The proportions of women with no evidence of disease, adverse effects, or complications were determined. RESULTS: Among 52 women included, 44 (85%) had no evidence of disease 1year after thermocoagulation. The rate of no disease at follow-up was similar for women treated for CIN2 (17/20 [85%]) and CIN3 (27/32 [84%]). No serious adverse effects or complications requiring hospitalization were observed during the follow-up period. CONCLUSION: Thermocoagulation is useful in the management of ectocervical CIN and should be integrated into public health services for management of cervical cancer.

Conventional Pap smear and liquid-based cytology as screening tools in low-resource settings in Latin America: experience of the Latin American screening study.

OBJECTIVE: To evaluate the performance of the conventional Pap test and liquid-based cytology (LBC) in an ongoing multicenter trial testing optional screening tools (cytology, screening colposcopy, visual inspection with acetic acid, visual inspection with Lugol's Iodine, cervicography and Hybrid Capture II [HCII] (Digene Brazil, São Paulo, Brazil) conventional and self-sampling), for cervical cancer in Brazil and Argentina. STUDY DESIGN: A cohort of 12,107 women attending four clinics (Campinas, São Paulo, Porto Alegre, Buenos Aires) were randomized into the 8 diagnostic arms. Women testing positive with any of the tests were referred for colposcopy, and cervical biopsies were used as the gold standard to assess performance characteristics of the diagnostic tests. Conventional Pap smears were sampled by all clinics (n = 10,240), and LBC (Autocyte PREP, [TriPath Imaging, Burlington, North Carolina, U.S.A.], n=320, and DNA-Citoliq [Digene Brazil], n =1,346) was performed by 1 of the clinics. RESULTS: Conventional Pap smears showed no squamous intraepithelial lesions (normal) in 8,946 (87.4%) and LBC in 1,373 (82.4%). Using high grade squamous intraepithelial lesions (HSIL) as the cutoff, Pap smears predicted high grade (cervical intraepithelial neoplasia [CIN] 3) with OR 63.0 (95% CI, 36.90-107.70), standard error (SE) 59%, SP 97.8%, positive predictive value (PPV) 68.1% and negative predictive value (NPV) 96.7%. The same figures for Autocyte PREP were: OR 9.0 (95% CI, 2.43-33.24), sensitivity (SE) 33.3%, specificity (SP) 100%, PPV 100% and negative PV (NPV) 88.8%. DNA-Citoliq detected CIN 3 as follows: OR 11.8 (95% CI 2.60-53.26), SE 40.0%, SP 94.6%, PPV 40.0% and NPV 94.6%. Lowering the cutoff to low grade squamous intraepithelial lesions increased SE and NPV but compromised SP and PPV. The detection rates for high grade lesions after an atypical squamous cells of undetermined significance diagnosis were similar with the 3 techniques. In our settings, the 3 methods of cervical cytology were slightly different in performance. The conventional Pap smear had the highest SE, while Autocyte PREP had 100% SP and PPV in detecting CIN3 with the HSIL cutoff. All 3 tests had lower SE but higher SP as compared to HCII.

Performance characteristics of Pap test, VIA, VILI, HR-HPV testing, cervicography, and colposcopy in diagnosis of significant cervical pathology.

We sought to evaluate the performance of diagnostic tools to establish an affordable setting for early detection of cervical cancer in developing countries. We compared the performance of different screening tests and their feasibility in a cohort of over 12,000 women: conventional Pap smear, liquid-based cytology, visual inspection with acetic acid (VIA), visual inspection with Iodine solution (VILI), cervicography, screening colposcopy, and high-risk human papillomavirus (HPV) testing (HR-HPV) collected by physician and by self-sampling. HR-HPV assay collected by the physician has the highest sensitivity (80 %), but high unnecessary referrals to colposcopy (15.1 %). HR-HPV test in self-sampling had a markedly lower (57.1 %) sensitivity. VIA, VILI, and cervicography had a poor sensitivity (47.4, 55, and 28.6 %, respectively). Colposcopy presented with sensitivity of 100 % in detecting CIN2+, but the lowest specificity (66.9 %). Co-testing with VIA and VILI Pap test increased the sensitivity of stand-alone Pap test from 71.6 to 87.1 % and 71.6 to 95 %, respectively, but with high number of unnecessary colposcopies. Co-testing with HR-HPV importantly increased the sensitivity of Pap test (to 86 %), but with high number of unnecessary colposcopies (17.5 %). Molecular tests adjunct to Pap test seems a realistic option to improve the detection of high-grade lesions in population-based screening programs.

Value of the International Federation for Cervical Pathology and Colposcopy (IFCPC) Terminology in predicting cervical disease.

OBJECTIVE: To evaluate the colposcopic accuracy according to the International Federation for Cervical Pathology and Colposcopy (IFCPC) 2002 terminology. MATERIALS AND METHODS: A series of 3,040 women derived from a general population were screened by means of Pap smear, unaided visual inspection, and high-risk human papillomavirus testing. All colposcopic examination results with abnormal findings and with biopsy confirmation (n = 468) were recorded, reviewed by 2 blinded colposcopists according to the IFCPC nomenclature, and included in this analysis. RESULTS: The IFCPC terminology was easily reproduced by the 2 observers with excellent interobserver agreement (kappa =.843). Colposcopy had a sensitivity of 86% and a specificity of 30.3% in distinguishing healthy cervix from that with cervical intraepithelial neoplasia (CIN)/carcinoma. In distinguishing healthy cervix/low-grade lesions (CIN 1) from that with high-grade lesions (CIN 2/3)/carcinoma, colposcopy had a sensitivity of 61.1% and a specificity of 94.4%. Colposcopic findings graded as major changes had the highest positive predictive value for detecting high-grade lesion/carcinoma. The colposcopic abnormalities within the transformation zone and large lesions were more closely related to high-grade lesion/carcinoma, whereas a sharp outer border, multiple colposcopic abnormalities, and iodine negativity were not statistically related to severe lesions. CONCLUSIONS: Colposcopy using the new IFCPC classification is a potentially effective screening method; when used for diagnosis, a histological sampling is necessary. The categorization of major changes and minor changes is appropriate. It is important to describe the lesion localization in relation to the transformation zone and the lesion size because these characteristics are related to high-grade lesions.

Associação entre idade ao início da atividade sexual e subseqüente infecção por papilomavírus humano: resultados de um programa de rastreamento brasileiro / Association between age at first sexual intercourse and subsequent human papillomavirus infection: results of a Brazilian screening program

OBJETIVO: descrever a idade de início da atividade sexual (sexarca) e a sua associação com a idade das mulheres com a infecção por papilomavírus humano (HPV) e com as alterações citológicas no exame de papanicolaou. MÉTODOS: mulheres da população geral foram recrutadas para participar de um estudo de rastreamento de câncer cervical e lesões pré-malignas. Após a aplicação de questionário comportamental, foram submetidas ao rastreamento com gia cervical e teste para DNA de HPV de alto risco, por meio de Captura Híbrida 2. Este projeto faz parte do Latin American Screening Study, que envolve mulheres do Brasil e da Argentina, e os dados aqui apresentados referem-se aos centros brasileiros nas cidades de Porto Alegre, São Paulo e Campinas. RESULTADOS: de 8.649 mulheres entrevistadas, 8.641 relataram atividade sexual prévia e foram incluídas na análise. A média de idade no momento da entrevista foi de 38,1±11,04 anos, com início da atividade sexual em média aos 18,5±4,0 anos. Identificamos que a idade do início da atividade sexual aumenta de acordo com o aumento da faixa etária no momento da entrevista, isto é, mulheres mais novas relataram sexarca mais precoce que mulheres mais velhas (p<0,001). Em relação à infecção por HPV de alto risco, do total de mulheres que haviam iniciado as relações sexuais, 3.463 foram testadas, com 17,3 por cento de positividade para HPV. Notadamente, em todos os centros, as mulheres com idade ao início da atividade sexual abaixo da média da população entrevistada apresentaram positividade maior para HPV (20,2 por cento) do que as mulheres com sexarca em idade acima da média (12,5 por cento) - Odds Ratio (OR)=1,8 (IC95 por cento=1,5-2,2; p<0,001). Em relação à citologia, mulheres com sexarca abaixo da média de idade apresentaram também maior percentual de citologia alterada > ou = ASC-US (6,7 por cento) do que mulheres com sexarca em idade maior que a média...

PURPOSE: to investigate women’s age at their first sexual intercourse and its correlation with their present age, human papillomavirus (HPV) infection and cytological abnormalities at Pap smear. METHODS: women from the general population were invited to be screened for cervical cancer and pre-malignant lesions. After answering a behavior questionnaire, they were submitted to screening with cervical cytology and high-risk HPV testing with Hybrid Capture 2 (HC2). This report is part of the Latin American Screening (LAMS) study, that comprises centers from Brazil and Argentina, and the data presented herein refer to the Brazilian women evaluated at the cities of Porto Alegre, São Paulo and Campinas. RESULTS: from 8,649 women that answered the questionnaire, 8,641 reported previous sexual activity and were included in this analysis. The mean age at the interview was 38.1±11.0 years and the mean age at the first sexual intercourse was 18.5±4.0 years. The age at the first sexual intercourse increased along with the age at the interview, i.e., younger women reported they had begun their sexual life earlier than older women (p<0.001). From the total of women who had already begun having sexual intercourse, 3,643 patients were tested for high-risk HPV infection and 17.3 percent of them had positive results. In all the centers, it became clear that the women with the first sexual intercourse at ages below the mean age of all the population interviewed presented higher rates of HPV infection (20.2 percent) than the women with the first sexual intercourse at ages above the mean (12.5 percent) - Odds Ratio (OR) 1.8 (IC95 percent 1.5-2.2;p<0,001). According to the cytology, the women with first sexual intercourse at ages under the mean, presented higher percentage of abnormal cytology > or = ASC-US (6.7 percent) than the women with the first sexual intercourse at ages above the mean...

Fasceíte necrotizante em pacientes obstétricas / Necrotizing fasciitis in obstetric patients

Objetivos: relatar a experiência com casos de fasceíte necronizante (FN) ocorridos no Serviço de Ginecologia e Obstetrícia do Hospital de Clínicas de Porto Alegre e analisar sua associação com alguns fatores de risco citados na literatura. Métodos: foram analisados retrospectivamente pacientes do Hospital de Clínicas de Porto Alegre que tiveram diagnóstico de FN, no período de janeiro de 1990 a dezembro de 1997. Resultados: Foram encontrados 2 casos de FN pós-cesariana e 1 caso pós-cirúrgico por gestação ectópica. Nenhuma das pacientes apresentava complicações clínicas ou fator de risco para FN e a cirurgia foi realizada em caráter emergencial em todos os casos. A freqüência de FN no estudo foi de 2,6/ 10000 cesarianas e a mortalidade zero. Conclusão: a FN é uma síndrome clínica de ocorrência não muito comum, mas com grande morbimortalidade. Na afecção há envolvimento da ferida operatória e dos planos fasciais. O rápido manejo e a instituição do tratamento precoce e intensivo levam a bons resultados e à diminuição da mortalidade.

História da colposcopia: do invento de Hinselmann aos ensaios clínicos atuais / Colposcopy history: from Hinselmann's invention to current clinical trials

A colposcopia, apresentada pelo médico alemão Hans Hinselmann, em 1925, permaneceu por vários anos estagnada, em vista das restrições alemães no pós-guerra. Na década de 60, a colposcopia retoma sua difusão principalmente pela necessidade de um exame complementar ao rastreamento citológico. Inúmeras nomenclaturas passaram a ser utilizadas, dificultando o estudo da técnica. Índices colposcópicos procuravam prever o resultado histológico através da pontuação dos achados colposcópicos, mas não tiveram reconhecimento e aplicação difundida. Numa tentativa de unificar a descrição colposcópica, a Federação Internacional de Patologia Cervical e Colposcopia apresentou, em 1975, 1990 e 2002 novas classificações colposcópicas internacionais. A colposcopia assumiu na atualidade um papel intermediário entre citologia e histologia. Entretanto, autores têm mostrado sensibilidade elevada da colposcopia, sugerindo que esta seja empregada como método de rastreio de patologia cervical, mas sua especificidade tem sido questionada. A nova nomenclatura de 2002 procura apresentar mais detalhadamente quais achados colposcópicos estão associados à normalidade, lesões de baixo grau, alto grau ou carcinoma, procurando melhorar a descrição colposcópica. Mas como será o desempenho da colposcopia com esta classificação? Até o momento, nenhum estudo científico abordou a nova Classificação Internacional, analisando-a em termos de sensibilidade, especificidade e valores preditivos dos achados colposcópicos.

Avaliaçäo dos programas de "screening" para o câncer do colo uterino no estado do Rio Grande do Sul / Evaluation of cervical cancer screening programs in the state of Rio Grande do Sul, Brazil

Com o objetivo de comparar duas modalidades de screening de câncer de colo uterino por exame citopatológico (CP) desenvolvidas no Rio Grande do Sul: uma, sazonal e isolada, promovida pelo Ministério da Saúde em 1998 e outra, regular, promovida pela Secretaria de Saúde do Estado do Rio Grande do Sul, no período de 1991 a 1996, foram avaliados e comparados os resultados obtidos, concluindo-se que a campanha sazonal do Ministério da Saúde apresentou desempenho desfavorável, quando comparado ao programa regular da Secretaria da Saúde estadual, sugerindo que rastreamentos isolados são menos eficazes que rastreamentos planejados e contínuos...

Estudo da eficácia e tolerabilidade do fenticonazol no tratamento da vaginose bacteriana - Estudo duplo-cego, randomizado, prospectivo, controlado e comparado com grupo placebo / Eficacy and tolerability of fenticonazol for bacterial vaginosis treatment - double-blind study, randomized, prospective, compared to placecbo

Objetivo: Avaliar a eficácia e segurança do uso do fenticonazol no tratamento da vaginose bacteriana por Gardnerella vaginalis em um estudo placebo controlado. Métodos: Participaram do estudo 47 mulheres, randomizadas para receber fentico- nazol ou placebo. Utilizou-se dose de 5g ao dia de fenticonazol creme vaginal 2(por cento) por sete dias. As avaliações foram feitas em 3 visitas (dias 1, 9 e 28 após início do tratamento) e incluíram exame ginecológico, avaliação da secreção vaginal, teste das aminas, pesquisa de clue cells e medida de pH da secreção vaginal. Resultados: A proporção de cura no grupo tratado com fentíconazoi 85(por cento), foi sígnificatívamente maior do que a do grupo placebo, 35(por cento ) (P=0.003). A proporção de recorrência de infecção no grupo tratado com fenticonazol foi de 11,8 (por cento), significativamente menor que no grupo placebo, 50(por cento) (P=0,089). Apenas uma paciente apresentou efeito adverso definitivamente relacionado ao tratamento caracterizado por ardência vaginal de intensidade moderada.Conclusão: O fenticonazol se apresentou como uma alternativa eficaz no tratamento da vaginose bacteriana, com proporção de cura e índice de recorrência estatisticamente significativos quando comparados com o grupo placebo.

Embolia por líquido amniótico: relato de caso / Amniotic fluid embolism: a case report

Os autores relatam um caso de parada cardiorrespiratória em uma paciente previamente hígida submetida à cesariana e atendida no Centro Obstétrico do HCPA. A parada cardiorrespiratória ocorreu após a retirada do feto, evoluindo para quadro de edema pulmonar e coagulopatia intravascular disseminada (CIVD). O quadro clínico e laboratorial foi sugestivo de embolia por líquido amniótico e a paciente teve evolução favorável. Neste relato são discutidos aspectos da etiopatogenia, diagnóstico e terapia da embolia por líquido amniótico, uma complicação rara, com taxas de mortalidade em torno de 90 por cento dos casos