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% 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%) do que as mulheres com sexarca em idade acima da média (12,5%) – Odds Ratio (OR)=1,8 (IC95%=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 ≥ ASC-US (6,7%) do que mulheres com sexarca em idade maior que a média (4,3%) – OR=1,6 (IC95%=1,3-2,0; p<0,001). Conclusões: a infecção por HPV e a presença de alterações citológicas identificadas no rastreio de lesões cervicais em uma população assintomática estiveram significativamente associadas à idade mais precoce no início das relações sexuais. Ademais, identificamos também que as mulheres desta amostra apresentaram diminuição da idade ao início da atividade sexual, nas últimas décadas, sugerindo importante causa para o acréscimo da prevalência de HPV e as lesões decorrentes desta infecção.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% 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%) than the women with the first sexual intercourse at ages above the mean (12.5%) – Odds Ratio (OR) 1.8 (IC95% 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 ≥ ASC-US (6.7%) than the women with the first sexual intercourse at ages above the mean (4.3%) – OR 1.6 (IC95% 1.3-2.;p<0.001). ConclusionS: the high-risk HPV infection and cytological abnormalities identified during the asymptomatic population screening were significantly associated to the women’s age at the first sexual intercourse. Additionally, we have also identified that the women’s age at the first sexual intercourse has decreased during the last decades, suggesting an important contribution to the increase of HPV infection and the subsequent cervical lesions.Comissão Europeia - programa INCO-DEV (International Cooperation Development) Contrato #ICA4-2001-10013

Safety of screening with Human papillomavirus testing for cervical cancer at three-year intervals in a high-risk population: experience from the LAMS study

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 test

Evaluation of visual inspection with acetic acid (VIA), Lugol’s iodine (VILI), cervical cytology and HPV testing as cervical screening tools in Latin America

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.European Union (EU) - INCO-DEV Programme - Contract# ICA4-CT-2001-10013

Human papillomavirus testing as an optional screening tool in low-resource settings of Latin America: experience from the Latin American Screening study

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] ¼ 1.31; 95% CI 1.1–1.6), in women with two or more lifetime sexual partners (OR ¼ 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 ¼ 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 ¼ 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

Copy number alterations associated with clinical features in an underrepresented population with breast cancer

As the most incident tumor among women worldwide, breast cancer is a heterogeneous disease. Tremendous efforts have been made to understand how tumor characteristics as histological type, molecular subtype, and tumor microenvironment collectively influence disease diagnosis to treatment, which impact outcomes. Differences between populations and environmental and cultural factors have impacts on the origin and evolution of the disease, as well as the therapeutic challenges that arise due to these factors. We, then, compared copy number variations (CNVs) in mucinous and nonmucinous luminal breast tumors from a Brazilian cohort to investigate major CNV imbalances in mucinous tumors versus non‐mucinous luminal tumors, taking into account their clinical and pathological features.48 breast tumor samples and 48 matched control blood samples from Brazilian women were assessed for CNVs by chromosome microarray. Logistic regression and random forest models were used in order to assess CNVs in chromosomal regions from tumors.CNVs that were identified in chromosomes 1, 5, 8, 17, 19, and 21 classify tumors according to their histological type, ethnicity, disease stage, and familial history.Copy number alterations described in this study provide a better understanding of the landscape of genomic aberrations in mucinous breast cancers that are associated with clinical features.77FAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo2013/25683-3; 2015/18830-

[comparison Between Reference Oncologic Colpocytology And Severity Of Intraepithelial Cervical Lesions].

The study was designed to compare the Pap smear results, performed on the public health service, with: the results of Pap smear collected on the reference service; the colposcopy and punch biopsy results. The total of 213 women assisted at the women's hospital from January 1989 to April 1991, and followed until July 1998 were selected. Ninety were referred because a Pap smears suggestive of Human Papillomavirus (HPV) induced lesion or cervical intraepithelial neoplasia (CIN) grade 1, and 123, CIN 2 or 3. Among the 90 women referred because of HPV/CIN 1.49% presented CIN 2 or 3 in the Pap smears performed at this service. At the colposcopy, 16/90 women did not present suspicious lesions, and in 10 women, the squamous columnar junction was not observed. At biopsy, 42 (46%) presented CIN 2 or 3. Out of the 123 women referred with Pap smear of CIN 2 or 3.54% presented CIN 2 or 3 at this service. At the colposcopy, 24 women did not present suspicious lesions and the squamous columnar junction was not observed in 12. About biopsy, 61 (49%) presented CIN 2 or 3. The expectant conduct in cases of Pap smear with HPV/CIN 1, should follow a criterion, involving qualified professionals to collect the Pap smear, and should provide people awareness as to control follow-up.34120-

Accuracy Of Intraoperative Frozen Section Diagnosis Of Ovarian Tumors.

The goal of this work was to evaluate retrospectively, as quality control, the accuracy of frozen section diagnosis in ovarian tumors. We compared 243 frozen section results with the final diagnosis in paraffin sections, from cases studied from January 1994 to April 1999. Results with the two methods were analyzed on two parameters: (a) malignant potential and (b) histological type. As for malignant potential, frozen section diagnosis agreed with the paraffin diagnosis in 94% of all cases (98.5% for malignant tumors, 94% for benign tumors, and 78.6% for borderline tumors). There was one false-positive and 13 false-negative cases. Sensitivity and specificity values for malignant tumors were 93 and 99%; for borderline tumors, 61 and 99%; and for benign tumors, 98 and 93%. With respect to histological type, in 203 cases (84%) the pathologists had no doubt in the diagnosis; in 40 cases (16%) diagnosis was given as compatible with. In 35 of these (87.5%) the initial diagnosis was confirmed by paraffin. Frozen section diagnosis seems to be a reliable method for ovarian tumors, with high sensitivity for malignant neoplasms and a low false-positive rate which allow the best choice of treatment. The most frequent problems arise with borderline and granulosa cell tumors.81230-

Vascular endothelial growth factor (VEGF) polymorphisms and outcome of epithelial ovarian cancer patients

sem informação27641st Annual Congress of the European-Society-for-Medical-Oncology (ESMO)2016-10-07Copenhagen, Dinamarcasem informaçã

Aided Visual Inspection With Acetic Acid (via) And Hpv Detection As Optional Screening Tools For Cervical Cancer And Its Precursor Lesions.

To assess the contribution of visual inspection with acetic acid (VIA) and Hybrid Capture II (HCII) as adjunct methods to the Pap test in detecting cervical neoplasia. This was a cross-sectional study with 809 women who consecutively attended gynecological consultations at Campinas University, Brazil, from January 2002 to July 2003. Pap test, HCII, VIA, and colposcopy were offered to all patients. Performance of tests (alone or in combination) in detecting histologically confirmed lesions was evaluated. Of the 40 patients with CIN, 69% had CIN1, 26% CIN2 or CIN3 and one patient had invasive carcinoma. VIA had the best performance in detecting CIN, yielding 72% sensitivity and 91% specificity. Considering only CIN2 or worse as significant lesions, HCII had the best sensitivity (73%), while the Pap test was the most specific (93%). Combining the three exams, 92% of the CIN1 or worse were detected. When CIN1 was excluded from the analysis, Pap smear plus HCII delivered 82% sensitivity and 79% specificity. However, this combination yielded a very low (5%) PPV. VIA and HCII contributed to the screening of cervical neoplasia in a group of Brazilian women, but the cost-effectiveness of conjoint screening modalities is still debatable.32225-

High Risk Hpv And P53 Protein Expression In Cervical Intraepithelial Neoplasia.

Cervical intraepithelial lesions due to HPV infection are common in Brazil. An understanding of the mechanisms of the interaction between HPV and host factors is still incomplete. In spite of the high incidence of cervical cancer in Brazil, such studies with Brazilian patients are scarce. The purpose of this study was to correlate the presence of high-risk types of HPV and expression of p53 protein, grade of cervical lesion, age, high-risk sexual behaviors and smoking. It was also intended to establish whether p53 expression might be useful as a marker for CIN progression. HPV detection was performed on paraffin sections using biotin-labeled probes by in situ hybridization. p53 protein expression was evaluated by immunohistochemistry. Seventy-eight patients with cervical dysplasia were included in the study. CIN 1 was diagnosed in 38 cases, and CIN 2+3 in 40 cases. High-risk HPV was detected in 42 patients. No correlation was found between the grade of cervical lesion or the presence of HPV and smoking, and high-risk sexual behavior. Expression of p53 was significantly higher in CIN 1, as compared with CIN 2+3, but did not correlate with HPV status. Higher expression of p53 protein in early lesions supports the hypothesis of a partially protective role of the wild-type p53 in early stages of cervical lesions.7145-