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This study aimed to evaluate the influence of the excised canal length on relapse rates of cervical high-grade squamous intraepithelial lesion (HSIL) treated by loop electrosurgical excision procedure and to find a cut-off point, above which lower recurrence rates could be observed, with low probability of compromising future obstetric outcome, and the relationship with other individual factors related to HSIL recurrence.This was a retrospective cohort study of 2,427 women diagnosed with cervical intraepithelial neoplasia CIN2+ who underwent cervical conization using the high-frequency loop electrosurgical excision procedure surgery technique, to analyze the role of endocervical canal length associated with individual factors in the recurrent disease after CIN2+ treatment and determine a cut-off point for the excised canal length needed to decrease the risk of disease relapse.In 2,427 cases, the relapse rate of HSIL treated was 12%. Compromised margins of conization, HIV+, and endocervical canal length were related directly to relapses ( p.001). The cut-off point, by receiver operating characteristic curve, to calculate the endocervical canal length related to relapses was 1.25 cm of canal excised. Canal length of less than 1.25 cm increased the recurrence rate 2.5 times. Compromised margins and HIV+ increased recurrence rates by more than 5 times.Cervical HSIL recurrence was directly related to the endocervical canal length: excised canal length of 1.25 cm or more decreases recurrence rate; HIV and compromised margins increase the chance of recurrence by more than 5 times.

Objective To evaluate the role of cervical cytology (Pap smear) in the diagnosis of cervical intraepithelial neoplasia 2 or greater (CIN2+), presented exclusively in the endocervical canal, the clinical-epidemiological characteristics of this lesion, the necessary length of canal to be removed to treat, and the rate of invasive lesion hidden in the endocervical canal. Methods Cross-sectional study, by database analysis, of patients with abnormal cytology (high-grade squamous intraepithelial lesion [HSIL]), without visible colposcopy lesion, submitted to loop electrosurgical procedure (LEEP) to evaluate the association of cytology results with the histological product of the conization, to identify the epidemiological characteristics of endocervical lesion and clinical evolution, using a pvalue< 0.05 and 95% CI. Results In 444 cases, the Pap smear sensitivity for CIN2+ diagnosis was 75% (95% CI: 69.8-79.7), specificity was 40% (95% CI: 30.2-49.5), and the prevalence rate of histological lesion was 73% (95% CI: 70.1-78.7). There was a higher prevalence of CIN2+ in women over 42 years old and invasive cancer in those over 56 years old (p

Summary To study the prevalence of anti-nuclear antibodies (ANA) in breast cancer patients and its association with tumour characteristics. Ninety-one patients with breast mass detected by image studies and assigned to conduct diagnostic biopsy and eventual surgical treatment were studied for demographical, tumour data and presence of ANA. Serum of positive ANA patients was screened for the extractable nuclear antigen (ENA) profile. As comparison, 91 healthy individuals matched for age and from the same geographical area were included. In this sample 72 of 91 (79·1%) had malignant lesions (83% ductal infiltrative carcinoma). ANA was positive in 44·4% of patients with malignant tumour and in 15·7% of those with benign lesions (malignant versus benign with P = 0·03). Controls had ANA positivity in 5·4%, and when compared with tumour samples showed P

Objective The aim of this study was to assess the time trends and pattern of cervical cancer diagnosed in the period from 2001 to 2012 by means of an opportunistic screening program from two developed regions in Brazil. Methods An observational study analyzing 3,364 cancer records (n = 1,646 from Campinas and n = 1,718 from Curitiba region) available in hospital-based cancer registries was done. An additional 1,836 records of CIN3/AIS from the region of Campinas was analyzed. The statistical analysis assessed the pooled data and the data by region considering the year of diagnosis, age-group, cancer stage, and histologic type. The Cochran-Armitage trend test was applied and p-values < 0.05 were considered significant. Results The total annual cervical cancer registered from2001 to 2012 showed a slight drop (273-244), with an age average of 49.5 y, 13 years over the average for CIN3/AIS (36.8 y). A total of 20.6% of the diagnoses (1.6% under 25 y) were done out of the official screening age-range. The biennial rate of diagnoses by age group for the region of Campinas showed an increase trend for the age groups under 25 y (p = 0.007) and 25 to 44 y (p = 0.003). Stage III was the most recorded for both regions, with an annual average of 43%, without any trend modification. There was an increasing trend for stage I diagnoses in the region of Campinas (p = 0.033). The proportion of glandular histologic types registered had an increased trend over time (p = 0.002), higher for the region of Campinas (21.1% versus 12.5% for the region of Curitiba). Conclusion The number, pattern and trends of cervical cancer cases registered had mild and slow modifications and reflect the limited effectivity of the opportunistic screening program, even in developed places. Resumo Objetivo Avaliar as tendências temporais e padrão de diagnóstico de câncer de colo de útero (CCU) através de programa de rastreamento oportunístico em duas regiões brasileiras desenvolvidas, no período de 2001 a 2012. Métodos Estudo observacional com 3.364 registros de câncer (n = 1.646 da região de Campinas e n = 1.718 da região de Curitiba) obtidos de sistemas de registro hospitalar de câncer. Para a região de Campinas foram analisados 1.836 registros adicionais de CIN3/AIS. A análise estatística avaliou os dados agrupados e por região considerando o ano de diagnóstico, grupo etário, estágio de câncer e tipo histológico, e utilizou o teste de tendência Cochran-Armitage com valor p < 0,05. Resultados O total anual de CCU registrado no período de 2001 a 2012 apresentou uma ligeira queda (273 para 244), comidade média de 49,5 anos, 13 amais que a idade média (36,8 anos) para CIN3/AIS. O total de diagnósticos realizados fora da faixa etária oficial de rastreamento foi 20,6% (1,6% abaixo de 25 anos). Houve uma tendência de aumento de casos nas faixas etárias inferior a 25 anos (p = 0,007) e de 25 a 44 anos (p = 0,003) para a região de Campinas. Ambas as regiões apresentaram maior proporção diagnósticos de câncer em estágio III (43% em média), sem modificação de tendência. Houve tendência crescente para diagnóstico em estágio I na região de Campinas (p = 0,033) e da proporção de tipos histológicos glandulares em ambas regiões (p = 0,002), 21,1% para a região de Campinas e 12,5% para Curitiba. Conclusão O número, o padrão e as tendências dos casos registrados de câncer de colo de útero apresentaram modificações pequenas e lentas ao longo do tempo, reflexo da efetividade limitada do programa de rastreio oportunista, mesmo em locais desenvolvidos.

Objective: To evaluate serum concentrations of mannose-binding lectin (MBL) in women presenting with different human papillomavirus (HPV)-associated cervical lesions. Subjects and Methods: A total of 364 women, who underwent screening for cervical cancer or treatment at the Erasto Gaertner Cancer Hospital (HEG), Curitiba, Brazil, were enrolled in the study. Based on the latest cervical colposcopy-guided biopsy results, the women were divided into 4 groups: cervical intraepithelial neoplasia CIN-I (n = 54), CIN-II (n = 72), CIN-III (n = 145), and invasive cancer (n = 93). A time-resolved immunofluorometric assay was used to measure the MBL concentrations in serum. The statistical analysis was done using GraphPad Prism 6.0. Comparisons were performed by Kruskal-Wallis and Mann-Whitney tests and analyzed by χ2 test; continuous variables are presented as medians and categorical variables as frequencies. Results: The median MBL concentrations in decreasing order were as follows: invasive cancer: 1,452 ng/mL, CIN-I: 1,324 ng/mL, CIN-II: 1,104 ng/mL, and CIN-III 1,098 ng/mL. However, no statistical significance was found among the 4 groups with HPV-associated lesions (p = 0.11). Equally, the MBL levels did not show a significant association between the age of the patients and the severity of the cervical lesions (p = 0.68). No statistical significance was found in the median values of MBL or in the status of MBL deficient (1,000 ng/mL) among the women in each group (p = 0.77). Conclusion: In this study, there was no statistically significant difference in MBL serum levels among the groups with CIN. Hence MBL serum concentration appeared not to have influenced the progression of HPV-related preinvasive cervical lesions into invasive cancer.

Background Antinuclear antibodies (ANA) have been found in several types of cancer although the meaning of its presence is not completely known. Aim To study the prevalence of ANA in patients with cervical intraepithelial lesion and invasive cervical cancer. Methods A total of 205 women who underwent screening for cervical cancer or treatment at the Erasto Gaertner Cancer Hospital in Curitiba - Brazil, were enrolled in the study. Based on their latest cervical colposcopy-guided biopsy results, they were divided into four groups: CIN-I: 19.4%; CIN-II: 24.0%; CIN-III: 24.0%; and invasive cancer: 32.4%. As control were studied 68 healthy controls. ANA was searched by immunofluorescence in Hep-2 cells evaluating the pattern and titer. Results Controls had 4/68 (5.8%) of ANA positivity and patients with CIN and invasive cancer had 15.1% (p = 0.001). Patients with CIN-I and CIN-II had the same prevalence of ANA as controls (p = 1.0 and p = 0.11 respectively), but not those with CIN-III (p = 0.03) and invasive cancer (p = 0.05). The most common ANA immunofluorescence pattern was fine speckled pattern (38.7%) and fine dense speckled pattern (38.7%); the mean titer was 1:160. Conclusion ANA is more common in invasive cervical lesions than in controls or non invasive lesions. To understand the meaning of this finding more studies are needed.

BACKGROUND: Brazilian opportunistic screening programs for cervical cancer have limited impact. In the regions of two cities (Campinas and Curitiba) with high human development indices, consistent information from 96-97% of all cervical cancer cases managed within the public healthcare system is available. OBJECTIVE: To estimate the incidence rate (IR) and temporal trends in these regions, covering 2001-2012. DESIGN AND SETTING: A population-based cohort study was conducted under the assumption that all cervical cancer cases were managed in cancer referral center hospitals. METHODS: 3,364 records (1,646 from Campinas; 1,718 from Curitiba) were analyzed to provide estimates of IR, age-standardized IR (ASR) and cervical cancer trends (shown per 100,000 women/year). Longitudinal patterns were analyzed using linear regression and shown as annual percentage change (APC); P < 0.05 for significance. RESULTS: Annual IR and ASR estimates for cervical cancer ranged from 3.8 to 8.0 over 2001-2012, decreasing over more recent years, and were similar for the two regions. The age-specific IR was about 50% lower among women aged 45 years or older (IR-2001/IR-2012: Campinas = 14.8/8.0; Curitiba = 18.7/8.3; P < 0.001). There was an increasing APC trend in Campinas among women aged 15-24 years, and a decreasing IR trend for squamous-cell histology in both regions (P < 0.05). CONCLUSION: Cervical cancer incidence estimates showed slowly decreasing trends in both regions, most evidently for women aged 45 years or older and for squamous-cell histology. These findings reflect the opportunistic nature of the population screening program, despite the comparatively high economic development level in the two regions.

The present study aimed to evaluate the association between altered methylation and histologically confirmed high grade cervical intraepithelial neoplasia (hgCIN).Methylation levels in selected host (CADM1, MAL, DAPK1) and HPV (L1_I, L1_II, L2) genes were measured by pyrosequencing in DNA samples obtained from 543 women recruited in Curitiba (Brazil), 249 with hgCIN and 294 without cervical lesions. Association of methylation status with hgCIN was estimated by Odds Ratio (OR) with 95% confidence interval (CI).The mean methylation level increased with severity of the lesion in the host and viral genes (p-trend 0.05), with the exception of L1_II region (p-trend = 0.075). Positive association was found between methylation levels for host genes and CIN2 and CIN3 lesions respectively [CADM1: OR 4.17 (95%CI 2.03-8.56) and OR 9.54 (95%CI 4.80-18.97); MAL: OR 5.98 (95%CI 2.26-15.78) and OR 22.66 (95%CI 9.21-55.76); DAPK1: OR 3.37 (95%CI 0.93-12.13) and OR 6.74 (95%CI 1.92-23.64)]. Stronger risk estimates were found for viral genes [L1_I: OR 10.74 (95%CI 2.66-43.31) and OR 15.00 (95%CI 3.00-74.98); L1_II: OR 73.18 (95%CI 4.07-1315.94) and OR 32.50 (95%CI 3.86-273.65); L2: OR 4.73 (95%CI 1.55-14.44) and OR 10.62 (95%CI 2.60-43.39)]. The cumulative effect of the increasing number of host and viral methylated genes was associated with the risk of CIN2 and CIN3 lesions (p-trend 0.001).Our results, empowered by a wide cervical sample series with a large number of hgCIN, supported the role of methylation as marker of aggressiveness.

Objective: Io evaluate the expression of p16INK4a and p53 biomarkers in conization specimens from patients with high grade cervical intraepithelial neoplasia (HG-CIN), correlating them with the ability to predict the recurrence. Methods : we conducted a retrospective study of patients with HG-CIN in cervical biopsy treated with conization between January 1999 and January 2006 who had a minimum follow-up of 18 months. The expression of the p16 and p53 was assessed by tissue microarrays and correlated with disease recurrence. For analysis, we used the test of proportions (chi-square), considering value p0.05). p53 had a positive predictive value (PPV) of 42% and negative predictive value (NPV) of 73%, sensitivity 70%, specificity of 47% and accuracy of 59%. The p16, PPV 42%, NPV 72%, sensitivity 66%, specificity of 49% and accuracy of 56%. Conclusion : immunohistochemistry expression of p53 and p16 showed low sensitivity and low specificity as predictors of HG-CIN recurrence after conization treatment. Objetivo : avaliar a expressão dos biomarcadores p16INK4a e p53, nas peças de conização de pacientes com neoplasia intraepitelial cervical de alto grau (NIC-AG), correlacionando com a capacidade de predizer o risco de recorrência. Métodos : estudo retrospectivo de pacientes com NIC-AG em biópsia de colo uterino, tratadas por conização, entre janeiro de 1999 e janeiro de 2006 e seguimento mínimo de 18 meses. A expressão dos biomarcadores p16 e p53 foi avaliada através de técnica de microarranjos teciduais e correlacionada com a recorrência da doença. Para análise utilizou-se o teste das proporções (qui-quadrado), considerando valor p0,05). O p53 apresentou valor preditivo positivo (VPP) de 42% e valor preditivo negativo (VPN) de 73%, sensibilidade de 70%, especificidade de 47% e acurácia de 59%. O p16, VPP de 42% e VPN de 72%, sensibilidade de 66%, especificidade de 49% e acurácia de 56%. Conclusão : a expressão imunoistoquiímica do p53 e do p16 apresentaram baixa sensibilidade e baixa especificidade como marcadores capazes de predizer a recorrência da NIC-AG tratada por conização.

The symptoms of ovarian tumor are not specific and a rare presentation of the tumor is as the content of an inguinal hernia. We reported a case of an 82-year-old woman, diagnosed with breast cancer and with a concomitant hypoecoic adnexal mass at the ecographic exam. The patient was treated with conservative breast surgery and laparotomy. A cystic-solid ovarian lesion was found inside the right inguinal canal. Frozen-section examination was negative for malignancy, and the anatomopathological analysis revealed a borderline ovarian tumor.

Purpose This study proposes to assess MBL serum concentrations in HPV positive women that developed high risk preinvasive lesions, CIN III. Materials and methods A total of 90 consecutive women (mean age 32.2 years, range 18–45 years) with CIN III lesions confirmed by cone biopsy were enrolled as cases at the gynecology cancer department of the Erasto Gaertner Hospital, a center of reference for cancer treatment in Southern Brazil. All the patients were HPV positive. In addition, 81 healthy women, voluntary blood donors, were enrolled as healthy control subjects (mean age 33.3 years, range 14–71 years) with no evidence of HPV infection, tested by hybrid capture, or CIN lesions, from the same geographic area. Results The median concentration of MBL in the cases was 912 ng/ml (IQR: 100–5820 ng/ml) and in the controls was 1207.3 ng/ml (IQR 100–4320.6 ng/ml). No statistically significant difference was observed between cases and controls. Conclusion This study reports data on MBL serum concentrations in HPV infected women for the first time. The analysis of our findings did not show a statistically significant difference between MBL serum concentrations in HPV women that developed CIN III lesions and healthy controls.

The symptoms of ovarian tumor are not specific and a rare presentation of the tumor is as the content of an inguinal hernia. We reported a case of an 82-year-old woman, diagnosed with breast cancer and with a concomitant hypoecoic adnexal mass at the ecographic exam. The patient was treated with conservative breast surgery and laparotomy. A cystic-solid ovarian lesion was found inside the right inguinal canal. Frozen-section examination was negative for malignancy, and the anatomopathological analysis revealed a borderline ovarian tumor.

to evaluate the results of treatment to which patients with high grade intraepithelial cervical neoplasia (HSIL) are submitted, as well as their follow-up during pregnancy.retrospective study based on the review of the medical report of 30 patients with diagnosis of high-grade squamous intraepithelial lesions (HSIL) during pregnancy and attended to at a tertiary hospital in southern Brazil from 1990 to 2002. Diagnosis was performed by colposcopy and biopsy, with repetition of the colposcopy during the pregnancy and after delivery. The diagnoses of regression and progression of lesions were evaluated.from 30 patients, 3 were excluded of the sample because the diagnosis of high-grade squamous intraepithelial lesions (HSIL) was not confirmed by the colposcopy with biopsia. Four patients were submitted to treatment during pregnancy, and one of them presented preterm delivery at the 32nd week. Twenty-three patients were submitted to expectant treatment, underwent a new colposcopy and biopsy, and then were submitted to conisation surgery at about the 11(th) week after the end of pregnancy. In 7.4% of the cases, there was lesion regression in the surgical specimen.all patients with diagnosis should be submitted to colposcopy and biopsy to exclude the possibility of invasive lesion. The expectant procedure for intraepithelial lesions is the most widely chosen and safe due to the possibility of regression in the postpartum period.

Our objective was to investigate the relationship between IFNG (+874 T/A) polymorphism and cervical intraepithelial neoplasia (CIN) in a population of Brazilian women. Ninety-six women, CIN II (48) and CIN III (48) and 50 normal controls, were enrolled in this study. DNA was extracted from blood samples by the salting out method and polymerase chain reaction (PCR) amplified. IFNG genotyping was performed by the PCR-Sequence Specific Primer method, using the Cytokine Genotyping Tray. There were no differences in genotypic frequencies between CIN patients and controls. However, after sample stratification into CIN II and III, a higher frequency of the AA genotype in CIN II versus control group (P = 0.05) was observed. When the comparison was performed between CIN groups, a higher frequency of the AA genotype in CIN II versus CIN III (P = 0.05) was observed. This study suggests that IFNG +874 T/A polymorphism responsible for the genetic differences in interferon (IFN)-gamma production may influence the human papillomavirus (HPV) clearance and cervical malignant progression. Further understanding of the role of this cytokine may contribute to the development of a biomarker of HPV infection and resulting in the improvement of squamous intraepithelial lesions treatment.

Background The causal association between persistent human papillomavirus (HPV) infection and cervical cancer has been established, but the mechanisms that favor HPV persistence in cervical cells are still unknown. The diminished capability of the immune system to control and resolve HPV infection is one of several hypotheses. The tolerogenic protein HLA-G has shown aberrant expression in a variety of cancers, which has been suggested as a mechanism for tumor escape from immunosurveillance. In the present study we evaluate the role of epigenetic modification (promoter de-methylation) of the HLA-G gene on susceptibility to HPV infection and development of high-grade cervical lesions. Methods A case–control study was carried out in Curitiba, Brazil, between February and June 2010. A total of 789 women aged 15–47 years were recruited: 510 controls with normal cervical cytology, and 279 cases with histologically confirmed cervical intraepithelial neoplasia grade 2 (CIN2, N = 150) or grade 3 (CIN3, N = 129). All women were administered a questionnaire by interview, which collected information on demographic and lifestyle factors, and a cervical sample was collected. HPV DNA detection was performed by GP5+/GP6+ primer-mediated PCR. HPV-positive samples were genotyped by multiplex PCR. A pilot analysis of HLA-G promoter methylation was carried out in a subset of the study population (96 cases and 76 controls) by pyrosequencing. HLA-G methylation and HPV infection status of cases and controls were compared, and confounding factors were computed by t Student and non-parametric Wilcoxon tests. Comparison of HLA-G methylation between cases and controls was assessed by the Bonferroni correction. The association of HLA-G methylation with CIN2/3 was evaluated by logistic regression. Results HPV prevalence was 19.6% in controls and 94.3% in CIN2/3 cases. HPV16, 31, 33, 35 and 18 were the most prevalent types. Methylation analysis of seven CpGs in the HLA-G promoter did not reveal any spontaneous de-methylation events in CIN2/3 cases (mean proportion of methylation: 75.8%) with respect to controls (mean 73.7%; odds ratio 1.01, 95% confidence interval 0.96, 1.07). Conclusions This study did not support the hypothesis that spontaneous de-methylation events in the HLA-G promoter play a primary role in promoting escape from immunosurveillance in the development of precancerous cervical lesions.