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Introdução: O câncer do colo do útero é um dos principais problemas de saúde pública no Brasil. A infecção persistente por subtipos oncogênicos do papilomavírus humano (HPV), especialmente o HPV-16 e o HPV-18, é responsável por cerca de 70% dos cânceres cervicais. A realização periódica do exame citopatológico é a estratégia mais adotada para o rastreamento do câncer do colo do útero. Diante de resultado sugestivo de lesão intraepitelial de alto grau, existe a necessidade de investigação e tratamento para impedir sua progressão para o câncer. A investigação é realizada em dois passos: colposcopia com biópsia, para posterior exérese da lesão, ou a técnica do “ver e tratar”, na qual a exérese já é realizada na primeira consulta, garantindo menos perdas no seguimento. O tratamento por cirurgia de alta frequência (CAF) consiste em um procedimento ambulatorial, realizado sob visão colposcópica e com anestesia local. Objetivo: Avaliar a concordância dos resultados citológicos prévios das pacientes submetidas a CAF. Materiais e métodos: Foram avaliadas 112 pacientes submetidas a CAF no ambulatório de patologia do trato genital inferior do Centro de Saúde Raul Travassos, em Itaperuna/RJ, atendidas entre julho de 2020 e julho de 2021, retrospectivamente, por revisão de prontuário. Resultados e conclusão: Das 103 pacientes com resultado anatomopatológico de neoplasia intraepitelial cervical (NIC) grau II/II no CAF, as citologias de encaminhamento foram 18 (17,4%) NIC I; nove (8,7%) ASC-US; 54 (52,4%) NIC II/III; 20 (19,2%) ASC-H; duas (1,9%) AGUS; e uma (0,9%) adenocarcinoma. Houve boa concordância (71,6%) entre os resultados citológicos e histológicos. Das pacientes com NIC II/III após o CAF, 26,1% tinham citologia de encaminhamento indicando lesão menor.

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, Supported by the INCO-DEV Program of the European Commission (Project No. ICA4-CT-2001-10013).

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

Objective The recently developed software (CONQUISTADOR), capable of computing all intralaboratory and interlaboratory quality control (QC) indicators, was used to evaluate the diagnostic agreement among 4 cytology laboratories participating in the LAMS Study. Study design The study was an interlaboratory exchange of specially designed 5 slide sets, each comprising 20 (conventional cytology) slides. At the first step, 80 slides (with "clear-cut" cases) were divided into four sets (A, B, C, D) of 20 specimens, each including inadequate and negative cases as well as in different proportions of all diagnostic TBS 2001 categories. In the second round, a fifth set (E) of 20 slides ("difficult cases") was designed, with all diagnostic categories, ASC and AGC included. Common measures of reproducibility (kappa and weighted kappa), accuracy (SE, SP, PPV, NPV) and 3 indices of diagnostic variability were calculated for sets A-D and set E, separately. Results For the 5 slide sets together, the weighted kappa was 0.8 (95% CI 0.76-0.85), which is the lower limit of the "almost perfect" ranking of kappa statistics, indicating an excellent interlaboratory agreement. The interlaboratory reproducibility was lower only for the difficult set (E). Similarly, the sensitivity for set E (70.0%) was lower than that (92.1%) for sets A-D. The diagnostic variability indices were not substantially different between the difficult (set E) and clearcut (sets A-D) cases. Conclusion High interlaboratory reproducibility was obtained for sets A-D ("clear-cut" cases), while more interlaboratory variation was evident in the difficult samples. The new CONQUISTADOR software is a valuable tool in calculating the indicators needed in this intralaboratory and interlaboratory.

Objective: To evaluate the presence of some criteria in cervical smears with atypical glandular cells and their correlation with histological patterns to identify pre-neoplastic and neoplastic lesions. Methods: Seventy-three women referred with an atypical glandular cell smear, who had undergone conization or hysterectomy, were included in this study. Referral Pap smears were reviewed using the set of 27 cyto-morphological criteria that was correlated with the histological diagnosis. Results: Histological results showed intraepithelial or invasive neoplasia in 35 (48%) cases and benign lesions in 38 (52%) cases. After logistic regression and decision tree analysis an increased nuclear/cytoplasmic ratio and the presence of dyskeratotic cells were strongly associated with intraepithelial or invasive neoplasia and the differential cyto-morphological criteria for glandular lesions were decreased cytoplasm, irregular nuclear membranes and the presence of nucleoli. Conclusion: The analysis of individual cyto-morphological criteria can better predict intraepithelial or invasive neoplasia and differentiate glandular from squamous lesions.

Objective To evaluate the performance of the conventional Pap test and liquid-based cytology (LBC) in an ongoing multicenter trial testing optional screening tools (cytolosy, screening colposcopy, visual inspection with acetic acid, visual inspection with Lugol's Iodine, cervicography and Hybrid Capture II [HCII] (Digene Brazil, Sno 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, Sao 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 I.BC 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 cut-off 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. Conclusion 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 CIN 3 with the HSIL cutoff. All 3 tests had lower SE but higher SP as compared to HCII.

OBJETIVO: avaliar a propedêutica em mulheres com atipias de células glandulares no resultado colpocitológico. PACIENTES E MÉTODOS: foram avaliadas prospectivamente 159 mulheres atendidas por resultado citológico de atipias de células glandulares, entre janeiro e dezembro de 2000. Todas foram submetidas a coleta de nova colpocitologia e a colposcopia. Foi realizada biópsia dirigida em 50 casos, curetagem endocervical em 21 e conização em 75. O desempenho dos métodos propedêuticos foi descrito por estimativas de sensibilidade, especificidade, valores preditivos e razão de verossimilhanças, tendo como padrão-ouro o resultado histológico. RESULTADOS: entre as 51 mulheres que apresentaram neoplasia intra-epitelial escamosa, 29 foram de baixo grau e 22 de alto grau. Cinco mulheres apresentaram adenocarcinoma in situ e seis, neoplasias invasoras. Isoladamente, a sensibilidade e a especificidade da colpocitologia foram respectivamente 88,5 e 39%, e da colposcopia, 74 e 42%. A associação da colposcopia com a colpocitologia elevou a sensibilidade para 98,4%, com queda da especificidade para 10%. A curetagem endocervical apresentou sensibilidade muito baixa (25%). CONCLUSÃO: a presença de atipias glandulares na colpocitologia relacionou-se com lesões cervicais pré-neoplásicas e neoplásicas em 62,2% dos casos submetidos a avaliação histológica. A repetição da citologia e a colposcopia permitiram selecionar as mulheres que se beneficiaram com a avaliação histológica. A conização mostrou-se adequada quando os exames mantiveram alterações morfológicas.

OBJETIVO: avaliar a presença do DNA do papilomavírus humano (HPV) de alto risco oncológico antes e quatro meses após excisão da zona de transformação com alça diatérmica em mulheres com neoplasia intra-epitelial cervical (NIC). MÉTODOS: neste estudo clínico prospectivo foram incluídas 78 mulheres submetidas à excisão da zona de transformação tratadas no período de fevereiro a dezembro de 2001. Todas foram submetidas a colposcopia, citologia oncológica e captura híbrida II (CH II) antes da cirurgia e após 4±1,25 meses. Para análise estatística utilizou-se o cálculo do odds ratio (OR) com intervalo de confiança de 95% (IC 95%). RESULTADOS: antes da excisão, 67 (86%) mulheres apresentavam CH II positiva para DNA-HPV de alto risco oncológico e destas, apenas 22 (33%) mantiveram a CH II positiva quatro meses após. A detecção do DNA-HPV após o tratamento não se relacionou com a carga viral prévia, presença de doença nas margens da peça cirúrgica ou idade da mulher. Após quatro meses, a detecção do DNA-HPV associou-se significativamente com a presença de alterações citológicas (OR = 4,8; IC 95% = 1,7-13,7), porém não se relacionou com doença residual ou recidiva histológica (OR = 6,0; IC 95% = 0,8-52,3). CONCLUSÃO: após o tratamento da NIC, a detecção do DNA-HPV diminuiu significativamente porém não se observou relação com a presença de doença residual ou recidiva histológica. PURPOSE: to evaluate the detection of high oncogenic risk human papillomavirus DNA (HPV-DNA) immediately before and 4±1.25 months after large loop excision of the transformation zone (LLETZ) in the treatment of cervical intraepithelial neoplasia (CIN). METHODS: in this clinical prospective study, 78 patients submitted to LLETZ from February to December 2001 were enrolled. All patients were submitted to colposcopic evaluation and had Pap smear and hybrid capture II (HC II) specimens collected immediately before LLETZ and four months after the procedure. Statistical analysis was made through odds ratio (OR) calculations with 95% confidence interval (95% CI). RESULTS: before excision, 67 (86%) women had positive HC II for high oncogenic risk HPV-DNA, while four months afterwards only 22 (33%) maintained positive HC II results. Positive results of HPV-DNA after treatment were not associated with previous viral load, compromised margins in the surgical specimen or age. Four months after the procedure, detection of HPV-DNA was significantly associated with cytological abnormalities (OR = 4.8; CI 95%: 1.7-13.7) but not with histological residual disease or relapse (OR = 6.0; CI 95%: 0.8-52.3). CONCLUSION: HPV-DNA detection was significantly reduced after treatment of CIN, but was not associated with the presence of histologic residual disease or relapse.

Objetivo: determinar os fatores associados ao achado de carcinoma microinvasor no cone de mulheres com biópsia colpodirigida prévia compatível com neoplasia intra-epitelial cervical (NIC) 3 e avaliar a proporção de margens comprometidas. Pacientes e Métodos: foram revisados os prontuários de 385 mulheres (média de idade: 39 anos) submetidas à conização a frio ou por cirurgia de alta freqüência (CAF) com alça no período de janeiro de 1993 a julho de 2000. Estes procedimentos foram indicados por biópsia compatível com NIC 3. Resultados: o diagnóstico do cone foi compatível com NIC 3 em 243 mulheres (63%) e com NIC 2 em 13 (3%). Apenas 10 apresentaram HPV/NIC 1 (3%) e oito não tinham doença residual no cone. Entretanto, 101 mulheres apresentaram carcinoma microinvasor no cone (26%) e 10 (3%) carcinoma invasor franco. A idade, o estado menstrual e o número de partos não estiveram relacionados com a gravidade da lesão no cone. Mulheres com alterações da colpocitologia oncológica sugestivas de invasão apresentaram um risco significativamente maior de apresentar carcinoma microinvasor ou invasor no histológico final (p

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).

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., European Commission, INCO-DEV Programme (contract# ICA4-CT-2001-10013). The generous contribution of DIGENE Corporation (USA) donating the HCII tests at our disposal is gratefully acknowledged.

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., This study is a part of the ongoing LAMS (Latin American Screening) study, entitled: Improving Health Systems Towards Equality-Based Control of Cervical Cancer in Latin America, and is supported by the INCO-DEV Program of the European Commission (Project No. ICA4-CT-2001-10013). The generous contribution of Digene Corporation (USA) who donated the HCII tests at our disposal is gratefully acknowledged.

The sensitivity (Se) and the specificity (Sp) are the two most common measures of the performance of a diagnostic test, where Se is the probability of a diseased individual to be correctly identified by the test while Sp is the probability of a healthy individual to be correctly identified by the same test. A problem appears when all individuals cannot be verified by a gold standard. This occurs when there is not a definitive test for detection of the disease or the verification by a gold standard is an impracticable procedure according to its cost, accessibility or risks. In this paper we develop a Bayesian analysis to estimate the disease prevalence, the sensitivity and specificity of screening tests in the presence of a covariate and in the absence of a gold standard. We use the Metropolis–Hastings algorithm to obtain the posterior summaries of interest. We have as motivation for the investigation the LAMS (Latin American Screening) Study, an extensive project designed for comparing screening tools for cervical cancer in Brazil and Argentina. When applied to the analysis of data from LAMS Study, the proposed Bayesian method shows to be a useful alternative to estimate measures of performance of screening tests in the presence of covariates and when a gold standard is not available. An advantage of the method is the fact that the number of parameters to be estimated is not limited by the number of observations, as it happens with several frequentist approaches. However, it is important to point out that the Bayesian analysis requires informative priors in order for the parameters to be identifiable. The method can be easily extended for the analysis of other medical data sets.

OBJETIVO: Analisar a história de rastreamento citológico anterior em mulheres que apresentaram alterações citológicas e confi rmação histológica para câncer cervical. MÉTODOS: Estudo transversal com 5.485 mulheres (15-65 anos) que se submeteram a rastreamento para o câncer cervical entre fevereiro de 2002 a março de 2003, em São Paulo e Campinas, SP. Aplicou-se questionário comportamental e foi feita a coleta da citologia oncológica convencional ou em base líquida. Para as participantes com alterações citológicas indicou-se colposcopia e, nos casos anormais, procedeu-se à biópsia cervical. Para investigar a associação entre as variáveis qualitativas e o resultado da citologia, utilizou-se o teste de qui-quadrado de Pearson com nível de signifi cância de 5%. RESULTADOS: Dentre os resultados citológicos, 354 (6,4%) foram anormais, detectando-se 41 lesões intra-epitelial escamosa de alto grau e três carcinomas; em 92,6% revelaram-se normais. De 289 colposcopias realizadas, 145 (50,2%) apresentaram alterações. Dentre as biópsias cervicais foram encontrados 14 casos de neoplasia intra-epitelial cervical grau 3 e quatro carcinomas. Referiram ter realizado exame citológico prévio: 100% das mulheres com citologia compatível com carcinoma, 97,6% das que apresentaram lesões intra-epiteliais de alto grau, 100% daquelas com confi rmação histológica de carcinoma cervical, e 92,9% das mulheres com neoplasia intra-epitelial cervical grau 3. A realização de citologia anterior em período inferior a três anos foi referida, respectivamente, por 86,5% e 92,8% dessas participantes com alterações citológicas e histológicas. CONCLUSÕES: Entre as mulheres que apresentaram confi rmação histológica de neoplasia intra-epitelial cervical grau 3 ou carcinoma e aquelas que não apresentaram alterações histológicas não houve diferença estatisticamente signifi cante do número de exames citológicos realizados, bem como o tempo do último exame citológico anterior., OBJECTIVE: To examine previous Pap smear history in women screened for cervical cancer with cytological or histological abnormalities. METHODS: Cross-sectional study in a sample of 5,485 women (15–65 years old) who self-referred to cervical cancer screening in Sao Paulo and Campinas, Southeastern Brazil, between February 2002 and March 2003. A behavioral questionnaire was applied and cervical specimens were obtained for testing by Pap smears or liquid-based cytology. Women who had abnormal cytology were referred for colposcopic examination and, if abnormal, for cervical punch biopsy. To explore factors associated to cervical abnormalities Pearson’s chiwas conduted square test at a 5% signifi cance level. RESULTS: Cytological abnormalities were found in 354 women (6.4%) and included 41 high-grade squamous intra-epithelial lesions and 3 carcinomas; 92.7% were normal results. Colposcopy was performed in 289 women, and 145 (50.2%) showed abnormal results. Punch biopsies showed 14 cervical intraepithelial neoplasias grade 3 and 4 carcinomas. Previous Pap smears were reported in all women who had cytology suspected of carcinoma, 97.6% of those with high-grade squamous intra-epithelial lesions, all women with histological diagnosis of carcinoma and 92.9% of those who had cervical intraepithelial neoplasias grade 3 histologically. Previous Pap smear in the last tree years was reported by 86.5% and 92.8% of women with abnormal cytology and biopsy, respectively. CONCLUSIONS: There was no statistically signifi cant difference regarding the number of Pap tests and time since their last test between women with histologically diagnosed carcinoma and cervical intraepithelial neoplasia grade 3 compared with those with normal cytology., European Commission - Projeto Latin América Study (LAMS – DEV Contract #ICA4-CT-2001-10013)

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

To assess the prevalence of high-risk genital human papillomavirus (HPV) infection by age group and risk factors associated.Cross-sectional study in a sample of 2,300 women (15-65 years old) who self-referred to cervical cancer screening in Sao Paulo and Campinas, Southeastern Brazil, between February 2002 and March 2003. An epidemiological questionnaire was applied and cervical specimens were obtained for cytology and hybrid capture II test (HCII) for HPV detection. Statistical analysis included Pearson Chi-square and unconditional multiple logistic regression model (forward likelihood ratio).High-risk genital HPV infection prevalence in this sample was 17.8% and age distribution was as follows: 27.1% (25 years), 21.3% (25-34 years), 12.1% (35-44 years), 12.0% (45-54 years) and 13.9% (55-65 years). Subjects with the highest number of lifetime sexual partners had the highest rates of genital HPV infection. To be living with a partner, aged 35 to 44 years, and former smokers were protective factors. High-risk genital HPV infection was 14.3% in normal cytology, 77.8% in high grade squamous intraepithelial lesions and in the two cases (100%) of cervical cancer.High-risk HPV prevalence was high in the sample studied. The highest prevalence of HPV infection was seen in women under 25 years old and then a new increase was seen over the age of 55 and the highest rates were found among those with many sexual partners during their lifetime.

The objective of this study was to assess whether human papillomavirus (HPV) detection with hybrid capture II (HC II) can help predict the presence and the nature, glandular or squamous, of histologic cervical lesions in women referred due to atypical glandular cells (AGC) or high-grade squamous intraepithelial lesion (HSIL). A total of 247 women were included. Referral Pap smears comprised AGC (51 cases), AGC plus HSIL (28 cases), adenocarcinoma in situ (10 cases), and HSIL (158 cases). All patients were tested for high-risk HPV with HC II and had a histologic assessment of their cervix. Histologic analysis showed 38 women with (15.3%) cervicitis, 194 with (75.5%) squamous lesions, and 15 with (9.2%) glandular neoplasia. The overall rate of high-risk HPV detection was 77%. Almost 70% of AGC-HPV–negative patients did not have a pathologically proven cervical neoplasia, whereas 76% of women with AGC-HPV–positive result were diagnosed with a squamous or glandular neoplasia. Most (95%) of the lesions in patients with AGC-HSIL were of squamous nature, and HPV detection did not contribute to their differentiation from glandular lesions. We conclude that in women with AGC, HPV positivity strongly correlated with the presence of glandular or squamous cervical lesion but did not help distinguishing women with squamous from those with glandular neoplasia.

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.

The objective of this study was to evaluate alterations in Pap smear, hybrid capture II (HCII), and visual inspection with acetic acid (VIA) in 684 women treated at a primary health care unit. The performance and agreement of the exams were evaluated. The study also described social, demographic, and reproductive factors and their association with uterine cervical lesions. Women had specimens taken for Pap smear, HCII, and VIA. When at least one of the tests was positive, colposcopy was performed and targeted biopsies were taken from any suspicious lesions. Performance of tests was evaluated. Women's distribution in relation to social, demographic, and reproductive factors and histological diagnosis was evaluated using the odds ratio. Among 198 women with at least one positive screening test, only 21 showed histological disease. Sensitivities of the tests were similar. VIA and Pap smear presented higher specificity than HCII. Only absence of a previous Pap smear was associated with the presence of histological disease. Pap smear performed better than VIA and HC II. Absence of previous cytology was associated with histological disease.

Avaliar as alterações na citologia oncológica, na captura híbrida II e na inspeção visual com ácido acético (IVA) a 5% em 684 mulheres atendidas em uma unidade de saúde, e avaliar o desempenho e a concordância entre os exames. Procurar descrever as características sócio-demográficas e reprodutivas (SDR) destas mulheres e sua associação com a presença de doença. As mulheres foram submetidas à coleta de citologia, captura e IVA, e as com exame positivo foram submetidas à colposcopia com biopsia, se necessário. Foi calculado o desempenho dos testes e a associação dos fatores SDR com o diagnóstico histológico foi avaliada por intermédio do cálculo do odds ratio. Embora 198 mulheres apresentassem pelo menos um teste alterado, apenas 21 apresentaram lesão histológica. A sensibilidade dos testes foi semelhante enquanto as especificidades da IVA e da citologia foram maiores que a da captura híbrida II. Apenas a ausência de citologia esteve associada à presença de doença. O desempenho da citologia foi maior que o da IVA, que foi maior que o da captura. A ausência de citologia foi associada com doença histológica. The objective of this study was to evaluate alterations in Pap smear, hybrid capture II (HCII), and visual inspection with acetic acid (VIA) in 684 women treated at a primary health care unit. The performance and agreement of the exams were evaluated. The study also described social, demographic, and reproductive factors and their association with uterine cervical lesions. Women had specimens taken for Pap smear, HCII, and VIA. When at least one of the tests was positive, colposcopy was performed and targeted biopsies were taken from any suspicious lesions. Performance of tests was evaluated. Women's distribution in relation to social, demographic, and reproductive factors and histological diagnosis was evaluated using the odds ratio. Among 198 women with at least one positive screening test, only 21 showed histological disease. Sensitivities of the tests were similar. VIA and Pap smear presented higher specificity than HCII. Only absence of a previous Pap smear was associated with the presence of histological disease. Pap smear performed better than VIA and HC II. Absence of previous cytology was associated with histological disease.

CONTEXT: There is no adequate preoperative method for differentiating between benign and malignant pelvic masses. Evaluations of CA 125 serum levels, ultrasonography findings and menstrual state have been tested in isolation as diagnostic methods. The evaluation of these three methods in association with each other could improve diagnostic performance. OBJECTIVE: To evaluate the risk-of-malignancy index by combining serum CA 125 levels, ultrasound score and menopausal status in preoperative diagnoses for women with pelvic masses clinically restricted to the ovaries and without clear evidence of malignancy. DESIGN: Cross-sectional study. SETTING: Centro de Atenção Integral à Saúde da Mulher, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil. PARTICIPANTS: 158 women admitted between January 1996 and March 1998 for surgical exploration of pelvic masses. PROCEDURES: The risk-of-malignancy index was calculated as US x M x CA 125, performed preoperatively. Ultrasound findings were classified according to the shape, size, multiplicity, presence of wall expansion involvement or ascites, using a score system (US). Menopausal status was considered as 1 for premenopausal and 3 for postmenopausal (M), and CA 125 serum levels were considered in absolute values. STATISTICAL ANALYSIS: Most relevant variables were included in a logistic multiple regression model, fitted using the ultrasound score, the serum CA 125 level and the menopausal status. The model was used for evaluating the performance of each individual predictor in determining the malignancy of these tumors and identifying the risk-of-malignancy index. RESULTS: The best individual performance was found in CA 125 levels (sensitivity of 78%, specificity of 75%), followed by ultrasound score (sensitivity of 75%, specificity of 73%) and menopausal status (sensitivity of 73%, specificity of 69%). The performance obtained for the risk-of-malignancy index at the cut-off point of 150 was a sensitivity and specificity of 79%. The area under the ROC curve for the risk-of-malignancy index was 0.90, which was greater than the area for CA 125 levels (0.83) or ultrasound score (0.79). CONCLUSION: The risk-of-malignancy index using ultrasound morphological score, serum CA 125 levels and menopausal status might be of value in the preoperative assessment of ovarian carcinomas. CONTEXTO: Não existem métodos pré-operatórios adequados para diferenciar massas pélvicas benignas de malignas. A avaliação do CA 125, dos achados ultra-sonográficos e do estado menstrual têm sido testados como métodos diagnósticos isolados. O uso destes três métodos em associação poderia levar a um aumento do seu desempenho. OBJETIVOS: Avaliar o índice de risco de malignidade incorporando a dosagem de CA 125 sérico, escore ultra-sonográfico e estado menopausal, no diagnóstico pré-operatório de mulheres com massas pélvicas clinicamente restritas ao ovário e sem evidências claras de malignidade. TIPO DE ESTUDO: Estudo de corte transversal. LOCAL: Centro de Atenção Integral à Saúde da Mulher, Universidade Estadual de Campinas. PARTICIPANTES: 158 mulheres admitidas entre janeiro de 1996 à março de 1998 para exploração cirúrgica de massa pélvica ovariana. PROCEDIMENTOS: O índice de risco de malignidade foi calculado como US x M x CA 125, avaliados pré-operatoriamente. Achados ultra-sonográficos foram classificados de acordo com a forma, tamanho, multiplicidade, presença de envolvimento de parede ou ascite em um sistema de escore (US). Para o estado menopausal foi considerada a pontuação de 1 para pré-menopausal e 3 para pós-menopausal (M), e a dosagem dos níveis séricos de CA 125 sérico foi considerada em seu valor absoluto. ANÁLISE ESTATÍSTICA: As variáveis mais relevantes foram incluídas em um modelo de regressão logística múltipla, usando o escore ultra-sonográfico, o nível de CA 125 e o estado menopausal. Foi usada para avaliar o desempenho de cada preditor individual em determinar a malignidade destes tumores e identificar o índice de risco de malignidade. RESULTADOS: O melhor desempenho individual foi encontrado na dosagem de CA 125 (sensibilidade de 78%, especificidade de 75%), seguido pelo escore ultra-sonográfico (sensibilidade de 75%, especificidade de 73%) e estado menopausal (sensibilidade de 73%, especificidade de 69%). O desempenho obtido pelo índice de risco de malignidade no ponto de corte de 150 foi sensibilidade e especificidade de 79%. A área sob a curva ROC para o índice de risco de malignidade foi 0,90, maior que a área para o CA 125 (0,83) ou escore ultra-sonográfico (0,79). CONCLUSÃO: O índice de risco de malignidade usando escore morfológico ultra-sonográfico, dosagem de CA 125 sérico e estado menopausal pode ser de valor no acesso pré-operatório do carcinoma ovariano.

In this paper we develop a Bayesian analysis to estimate the disease prevalence, the sensitivity and specificity of three cervical cancer screening tests (cervical cytology, visual inspection with acetic acid and Hybrid Capture II) in the presence of a covariate and in the absence of a gold standard. We use Metropolis-Hastings algorithm to obtain the posterior summaries of interest. The estimated prevalence of cervical lesions was 6.4% (a 95% credible interval [95% CI] was 3.9, 9.3). The sensitivity of cervical cytology (with a result of ≥ ASC-US) was 53.6% (95% CI: 42.1, 65.0) compared with 52.9% (95% CI: 43.5, 62.5) for visual inspection with acetic acid and 90.3% (95% CI: 76.2, 98.7) for Hybrid Capture II (with result of >1 relative light units). The specificity of cervical cytology was 97.0% (95% CI: 95.5, 98.4) and the specificities for visual inspection with acetic acid and Hybrid Capture II were 93.0% (95% CI: 91.0, 94.7) and 88.7% (95% CI: 85.9, 91.4), respectively. The Bayesian model with covariates suggests that the sensitivity and the specificity of the visual inspection with acetic acid tend to increase as the age of the women increases. The Bayesian method proposed here is an useful alternative to estimate measures of performance of diagnostic tests in the presence of covariates and when a gold standard is not available. An advantage of the method is the fact that the number of parameters to be estimated is not limited by the number of observations, as it happens with several frequentist approaches. However, it is important to point out that the Bayesian analysis requires informative priors in order for the parameters to be identifiable. The method can be easily extended for the analysis of other medical data sets.

OBJETIVO: avaliar o desempenho da citologia oncológica (CO), de captura híbrida II (CH II) e da inspeção visual com ácido acético na detecção de lesões pré-neoplásicas e neoplásicas cervicais. MÉTODOS: 2281 mulheres foram submetidas a exame clínico além da coleta de material para citologia, para CH II para detecção de DNA-HPV. Foi feita a inspeção visual do colo após aplicação do ácido acético a 5% (IVA). As mulheres com pelo menos um exame positivo eram convocadas para colposcopia, que também foi realizada em 420 mulheres com todos os exames normais. O desempenho dos testes foi calculado utilizando como padrão ouro a colposcopia com ou sem biopsia. RESULTADOS: a CO foi anormal em 209 mulheres (9,2%); a CH II foi positiva em 399 (17,5%) e em 249 (10,9%) foram encontradas alterações na IVA. Entre as 2281 mulheres avaliadas, 671 (29,4%) apresentaram pelo menos um resultado de exame positivo, embora apenas 82 (3,6%) apresentassem doença confirmada histologicamente (50 NIC1, 20 NIC2, sete NIC3 e cinco carcinomas invasores). As sensibilidades da IVA e da CH II foram semelhantes e significativamente maiores que a da CO. A especificidade da CO foi maior que a da IVA e da CH II. Nos casos com resultado de CO negativo, a IVA apresentou melhor desempenho comparada à CH II. CONCLUSÃO: o desempenho da CO associada à IVA foi melhor que o da CO associada à CH II e do que o da CO isolada. OBJECTIVE: to evaluate the performance of Pap smear, hybrid capture II (HC II), and visual inspection with acetic acid in the detection of pre-invasive and invasive cervical lesions. METHODS: a total of 2281 women were submitted to a clinical exam, including Pap smear, HC II for HPV DNA detection and visual inspection with 5% acetic acid (VIA). When at least one of the tests was positive, colposcopy was performed and targeted biopsies were taken from suspicious lesions. Colposcopy was also performed in 420 women with negative results. Test performance was evaluated, using colposcopy as the gold standard, with or without biopsy. RESULTS: Pap smear, VIA and HC II were positive in 9.2, 10.9 and 17.5% of all women screened, respectively. Although at least one positive test was found in 671 women (29.4%), only 82 (3.6%) presented histologically confirmed disease (50 NIC1, 20 NIC2, 7 NIC3, and 5 invasive carcinoma). VIA and HC II sensitivities were similar and significantly higher than Pap smear. Pap smear showed better specificity than VIA and than HC II. In women with a negative Pap smear result, VIA showed better performance than HC II. CONCLUSION: Pap smear combined with VIA performed better than Pap smear combined with HC II or than Pap smear alone.