Colorectal cancer spatial pattern in the northeast region of São Paulo, Brazil.

Background: This study examined the spatial pattern of the colorectal cancer (CRC) in the 18 municipalities that compose the Regional Health Department of Barretos (RHD-V), which is in the northeast of the state of São Paulo, Brazil. Methods: All incident cases and deaths from CRC between 2002 and 2016 were included. Age-standardized rates (ASR) for incidence and mortality per 100,000 person-years were used to evaluate the spatial distribution for the total and five-year periods. The lethality rates were also assessed. Excess risk maps compared the observed and expected events. Age-standardized net survival was used to evaluate CRC survival. Results: For CRC incidence, the ASR value for the general population over the entire period (2002-2016) was 17.7 (95% CI: 16.7, 18.6), ranging from 16.7 (95% CI: 14.9, 18.4) (2002-2006) to 20.0 (95% CI: 18.3, 21.7) (2012-2016) per 100,000. When males and females were compared, the ASR was 20.1 (95% CI: 18.6, 21.6) and 15.7 (95% CI: 14.5, 17.0) per 100,000, respectively. For CRC mortality (2002-2016), the ASR was 8.2 (95% CI: 7.6, 8.9), ranging from 9.0 (95% CI: 7.8, 10.3) (2002-2006) to 8.2 (95% CI: 7.2, 9.3) (2012-2016) per 100,000. Overall, the excess risk up to 2.0 was more frequent. In terms of survival, municipalities with large port populations had lower survival in comparison with medium port. Conclusions: This study showed a variation in CRC incidence and mortality, with differences considering five-year periods and gender, being the incidence higher in males than females in the entire period, with mortality equivalent to half the incidence. The survival was lower in municipalities with large port populations in comparison with medium port. Knowing spatial patterns of incidence, mortality, lethality, and survival can be necessary to support policymakers to advance or implement effective cancer control programs.

Thyroid Cancer Incidence and Mortality by Socioeconomic Level in the State of São Paulo, Brazil 2001-2017.

OBJECTIVE: Thyroid cancer is rising largely due to greater detection of indolent or slow-growing tumors; we sought to compare the incidence and mortality profiles of thyroid cancer in the State of São Paulo by socioeconomic status (SES). METHODS: Data on thyroid cancer cases diagnosed from 2003 to 2017 in the Barretos Region and from 2001 to 2015 in the municipality of São Paulo were obtained from the respective cancer registries. Corresponding death data were obtained from a Brazilian public government database. Age-standardized rates were calculated and presented as thematic maps. The rates were also calculated by SES and spatial autocorrelation was assessed by global and local indices. RESULTS: There were 419 cases of thyroid cancer and 21 deaths in Barretos, contrasting with the highly populated São Paulo, with 30 489 cases and 673 deaths. The overall incidence rates in São Paulo (15.9) were three times higher than in Barretos (5.7), while incidence rates in women were close to five times higher in Barretos and four times higher in São Paulo than in men. Mortality rates were, in relative terms, very low in both regions. A clear stepwise gradient of increasing thyroid cancer incidence with increasing SES was observed in São Paulo, with rates in very high SES districts four times those of low SES (31.6 vs 8.1). In contrast, the incidence rates in Barretos presented little variation across SES levels. CONCLUSION: Thyroid cancer incidence varied markedly by SES in São Paulo, with incidence rates rising with increasing socioeconomic index. Overdiagnosis is likely to account for a large proportion of the thyroid cancer burden in the capital.

Cancer inequalities in incidence and mortality in the State of São Paulo, Brazil 2001-17.

BACKGROUND: Cancer disparities exist between and within countries; we sought to compare cancer-specific incidence and mortality according to area-level socioeconomic status (SES) in the State of São Paulo, Brazil. METHODS: Cancer cases diagnosed 2003-2017 in the Barretos region and 2001-2015 in the municipality of São Paulo were obtained from the respective cancer registries. Corresponding cancer deaths were obtained from a Brazilian public government database. Age-standardized rates for all cancer combined and the six most common cancers were calculated by SES quartiles. RESULTS: There were 14,628 cancer cases and 7513 cancer deaths in Barretos, and 472,712 corresponding cases and 194,705 deaths in São Paulo. A clear SES-cancer gradient was seen in São Paulo, with rates varying from 188.4 to 333.1 in low to high SES areas, respectively. There was a lesser social gradient for mortality, with rates in low to high SES areas ranging from 86.4 to 98.0 in Barretos, and from 99.2 to 100.1 in São Paulo. The magnitude of the incidence rates rose markedly with increasing SES in São Paulo city for colorectal, lung, female breast, and prostate cancer. Conversely, both cervical cancer incidence and mortality rose with lower levels of SES in both regions. CONCLUSIONS: A clear SES association was seen for cancers of the prostate, female breast, colorectum, and lung for São Paulo. This study offers a better understanding of the cancer incidence and mortality profile according to SES within a highly populated Brazilian state.

Cancer survival in the northwestern of São Paulo State, Brazil: A population-based study.

BACKGROUND: Population-based cancer registry (PBCR) data provide crucial information for evaluating the effectiveness of cancer services and reflect prospects for cure by estimating population-based cancer survival. This study provides long-term trends in survival among patients diagnosed with cancer in the Barretos region (São Paulo State, Brazil). METHODS: In this population-based study, we estimated the one- and five-year age-standardized net survival rates of 13,246 patients diagnosed with 24 different cancer types in Barretos region between 2000 and 2018. The results were presented by sex, time since diagnosis, disease stage, and period of diagnosis. RESULTS: Marked differences in the one- and five-year age-standardized net survival rates were observed across the cancer sites. Pancreatic cancer had the lowest 5-year net survival (5.5 %, 95 %CI: 2.9-9.4) followed by oesophageal cancer (5.6 %, 95 %CI: 3.0-9.4), while prostate cancer ranked the best (92.1 %, 95 %CI: 87.8-94.9), followed by thyroid cancer (87.4 %, 95 %CI: 69.9-95.1) and female breast cancer (78.3 %, 95 %CI: 74.5-81.6). The survival rates differed substantially according to sex and clinical stage. Comparing the first (2000-2005) and last (2012-2018) periods, cancer survival improved, especially for thyroid, leukemia, and pharyngeal cancers, with differences of 34.4 %, 29.0 %, and 28.7 %, respectively. CONCLUSION: To our knowledge, this is the first study to evaluate long-term cancer survival in the Barretos region, showing an overall improvement over the last two decades. Survival varied by site, indicating the need for multiple cancer control actions in the future with a lower burden of cancer.

Cancer Statistics over Time in Northwestern São Paulo State, Brazil: Incidence and Mortality.

BACKGROUND: Population studies can serve as an essential source of information on cancer's etiology, and assessments of cancer trends over time can detect changes. This study aimed to provide statistics over time on cancer incidence and mortality in the Barretos Region, Brazil. METHODS: Cancer incidence data were obtained from the population-based cancer registry of the Barretos Region, and mortality data were obtained from the Official Federal Database from 2002 to 2016. Age-standardized rates for incidence and mortality were calculated. Joinpoint Regression software was used to estimate the average annual percentage changes (AAPC). RESULTS: Age-standardized rates of incidence increased significantly for colon cancer (AAPC: 2.2), rectum and rectosigmoid (AAPC: 2.4), liver (AAPC: 4.7), female breast (AAPC: 2.2), and thyroid cancer (AAPC: 3.8) but decreased for esophageal (AAPC: -3.2), stomach (AAPC: -4.2), lung (AAPC: -2.0), and ovarian cancer (AAPC: -5.6). The mortality increased for liver cancer (AAPC: 2.3) and decreased for pharyngeal cancer (AAPC: -5.8), stomach cancer (AAPC: -6.6), cervical uterine cancer (AAPC: -5.9), prostate cancer (AAPC: -2.4), and ovarian cancer (AAPC: -3.3). CONCLUSIONS: We observed decreases in some cancers related to tobacco smoking and cervical and stomach cancers related to infectious agents, showing strong regional and national prevention programs' successes. But, we also observed rises in many cancer sites linked to lifestyle factors, such as breast or colorectal cancer, without a sign of declining mortality. IMPACT: These results can impact and support cancer control program implementation and improvement at the community level and extrapolate to the state level and/or the whole country.

Cervical lesion assessment using real-time microendoscopy image analysis in Brazil: The CLARA study.

We conducted a prospective evaluation of the diagnostic performance of high-resolution microendoscopy (HRME) to detect cervical intraepithelial neoplasia (CIN) in women with abnormal screening tests. Study participants underwent colposcopy, HRME and cervical biopsy. The prospective diagnostic performance of HRME using an automated morphologic image analysis algorithm was compared to that of colposcopy using histopathologic detection of CIN as the gold standard. To assess the potential to further improve performance of HRME image analysis, we also conducted a retrospective analysis assessing performance of a multi-task convolutional neural network to segment and classify HRME images. One thousand four hundred eighty-six subjects completed the study; 435 (29%) subjects had CIN Grade 2 or more severe (CIN2+) diagnosis. HRME with morphologic image analysis for detection of CIN Grade 3 or more severe diagnoses (CIN3+) was similarly sensitive (95.6% vs 96.2%, P = .81) and specific (56.6% vs 58.7%, P = .18) as colposcopy. HRME with morphologic image analysis for detection of CIN2+ was slightly less sensitive (91.7% vs 95.6%, P < .01) and specific (59.7% vs 63.4%, P = .02) than colposcopy. Images from 870 subjects were used to train a multi-task convolutional neural network-based algorithm and images from the remaining 616 were used to validate its performance. There were no significant differences in the sensitivity and specificity of HRME with neural network analysis vs colposcopy for detection of CIN2+ or CIN3+. Using a neural network-based algorithm, HRME has comparable sensitivity and specificity to colposcopy for detection of CIN2+. HRME could provide a low-cost, point-of-care alternative to colposcopy and biopsy in the prevention of cervical cancer.

Agreement Between Optoelectronic Volumetry and Circumferential Girth Measurements to Diagnose Lymphedema in Patients Submitted to Axillary Radical Lymphadenectomy for Treatment of Cutaneous Melanoma.

Background: To assess the agreement between indirect and optoelectronic volumetries to diagnose lymphedema based on arm volume difference in patients with axillary lymph node dissection (ALND) for cutaneous melanoma. Methods and Results: Patients were assessed by circumferential girth measurements (truncated cone formula) to determine the upper limb volumes (indirect volumetry) and by optoelectronic volumetry (Perometer®) of affected and control limbs. A diagnosis of lymphedema on each measuring method was defined as an absolute volume difference >200 mL or a relative volume >10%. Forty-six patients with ALND were included. There were no significant differences between the volume means or the mean absolute or relative differences measured by each method. Good correlation was observed between the volume of upper limbs for both the left (r = 0.998) and right (r = 0.985) arms. As for the diagnosis of lymphedema, an absolute volume difference >200 mL determined a prevalence of 28% (13/46) of lymphedema by indirect volumetry and 35% (16/46) by optoelectronics volumetry. The crude diagnostic agreement was 93% with a kappa = 85% (agreement adjusted by chance) between methods. If a 10% increase in the relative volume difference between the arms was used as the diagnostic criterion, prevalence was 20% (9/46) and 22% (10/46), respectively. Conclusion: There is good agreement between perometry and circumferential girth measurements when classifying patients as having a difference between arm volumes >200 mL or 10%, the most frequently used cutoffs to diagnose lymphedema.

Detection of HPV E6 oncoprotein from urine via a novel immunochromatographic assay.

Cervical cancer is a significant public health problem, especially in low- and middle-income countries, where women have little access to cervical cancer screening; consequently 80% of cervical cancer related mortality occurs in these regions. The development of screening methods that need less infrastructure thus represents an urgent medical need. The study aims to compare the detection rates of high-risk human papillomavirus 16 and 18 E6 oncoprotein in urine, vaginal self-collected, and cervical scrapes of women using the OncoE6™ Cervical Test and compare the HPV16 and/or HPV18 E6 detection rates with the HPV DNA testing. Paired urine, vaginal self-collected and cervical specimens were collected from 124 women who participated in cervical cancer screening or treatment in this proof-of-concept study and underwent to HPV16/18-E6 testing and high-risk HPV DNA testing prior to treatment of cervical neoplasia or cancer. Concordance between urinary, vaginal and cervical HPV16/18-E6 and HPV-DNA testing was evaluated for patients classified as negative group (

The Quality of Pap Smears from the Brazilian Cervical Cancer Screening Program According to the Human Development Index.

Brazil is a country with strong socioeconomic disparities, which may explain the different rates of cervical cancer incidence and mortality and influence the quality of cervical cancer screening tests. The aim of this study was to perform a trend analysis of some quality indicators of Pap smears according to the Municipal Human Development Index (MHDI). Information about cytopathological exams (approximately 65,000,000) performed from 2006 to 2014 in women ages 25 to 64 years was obtained from the Cervical Cancer Information System (SISCOLO). The average annual percentage change (AAPC) for each indicator was calculated using the Joinpoint Regression Program, according to MHDI levels. Very low frequencies of unsatisfactory cases (<5%) were observed at different MHDI levels. Although the positivity index in the low- and medium-MHDI groups has increased, the values remained below international recommendations (3%-10%). The HSIL (high-grade squamous intraepithelial lesion) percentage remained stationary at all levels of the MHDI. In the low- and medium-MHDI groups, most quality indicators were below the recommendations by Brazilian National Cancer Institute INCA, with no improvement trend; in the high-MHDI group, the majority of the indicators also presented no improvement, although they show slightly better quality indicators. The MHDI should be considered in the definition of the policies of the screening program for cervical cancer in Brazil, and the current program may require adjustments to achieve improved efficiency.

Identification and performance evaluation of housekeeping genes for microRNA expression normalization by reverse transcription-quantitative PCR using liquid-based cervical cytology samples.

Screening for cervical cancer by cytology has been effective in reducing the worldwide incidence and mortality rates of this disease. However, a number of studies have demonstrated that the sensitivity of conventional cervical cytology may be too low for detection of cervical intraepithelial neoplasias (CIN). Therefore, it is important to incorporate more sensitive molecular diagnostic tests that could substantially improve the detection rates and accuracy for identifying CIN lesions. MicroRNAs (miRNAs) are a class of small non-coding RNAs with the potential to provide robust non-invasive cancer biomarkers for detecting CIN lesions in liquid-based cervical cytology (LBC) samples. At present, there is no consensus on which are the best housekeeping genes for miRNA normalization in LBC. The present study aimed to identify housekeeping genes with consistent and reproducible performance for normalization of reverse transcription-quantitative PCR (RT-qPCR) expression analysis of miRNA using LBC samples. The present study firstly selected six potential candidate housekeeping genes based on a systematic literature evaluation. Subsequently, the expression levels of microRNAs U6, RNU-44, RNU-47, RNU-48, RNU-49 and hsa-miR-16 were measured in 40 LBC samples using RT-qPCR. The stability of each potential housekeeping gene was assessed using the NormFinder algorithm. The results revealed that U6 and RNU-49 were the most stable genes among all candidates requiring fewer amplification cycles and smaller variation across the sample set. However, RNU-44, RNU-47, RNU-48 and hsa-miR-16 stability exceeded the recommended housekeeping value suitable for normalization. The findings revealed that U6 may be a reliable housekeeping gene for normalization of miRNA RT-qPCR expression analysis using LBC samples.

Overall survival and time trends in breast and cervical cancer incidence and mortality in the Regional Health District (RHD) of Barretos, São Paulo, Brazil.

BACKGROUND: Breast and cervical cancers represent a significant cause of morbidity and mortality among women. The purpose of this study was to analyse the survival and time trends in two of the most common female cancers in the Regional Health District (RHD) of Barretos, São Paulo, Brazil. METHODS: From 2000 through 2015, we calculated the breast and cervical cancer incidence and mortality rates per 100,000 women who were age-standardized to the world population. We obtained the time trends using the Joinpoint Regression software. We estimated the overall survival rates using the Kaplan-Meier methods. RESULTS: The age-standardized rates (ASR) for incidence of breast cancer increased annually, with an average annual percentage change (AAPC) of 4.3 (95% Confidence Interval (CI): 2.4 to 6.3) for invasive breast cancer and 10.2 (95% CI: 6.1 to 14.5) for in situ breast cancer. The mortality rates for invasive breast cancer decreased with an AAPC of 0.2 (95% CI: -1.9 to 2.4). The ASR incidence of invasive cervical cancer showed an AAPC of - 1.9 (95% CI: -4.7 to 0.9). For in situ cases, the ASR showed an AAPC of 9.3 (95% CI: 3.3 to 15.7). The ASR mortality for cervical cancer showed an AAPC of - 5.3 (95% CI: -9.5 to - 0.8). The Kaplan-Meier analysis indicated 5-year overall survival rates of 74.3% for breast cancer and 70.7% for cervical cancer. CONCLUSIONS: The incidence of in situ and invasive breast cancer is increasing, while the mortality rates remain stable. We observed an increase in the incidence of in situ cervical cancer and a decrease in invasive incidence rates during the study period, and we noted that the cervical cancer mortality significantly declined during the study period.

Predicting the necessity of adding catheters to intracavitary brachytherapy for women undergoing definitive chemoradiation for locally advanced cervical cancer.

PURPOSE: To identify if baseline patient or magnetic resonance imaging (MRI) features can predict which women are at risk for inadequate tumor coverage with only intracavitary tandem and ovoid (T + O) brachytherapy and to correlate tumor coverage with clinical outcomes. METHODS AND MATERIALS: We performed a retrospective study of 50 women with cervical cancer treated with chemoradiation at a single institution between January 2014 and December 2015. All patients had a 3T-MRI performed at baseline (MRI1) and at the completion of external beam radiation therapy (MRI2). Gross tumor volume initial (GTV-Tinit) was measured on MRI1 and high-risk clinical tissue volume (CTVHR) on MRI2. CTVHR extending beyond point A was classified as too large for adequate coverage with T + O and requiring interstitial needles. Multivariate analysis was performed to determine predictive factors of inadequate coverage. Kaplan-Meier and Cox Regression were performed to correlate inadequate coverage with outcomes. RESULTS: Mean patient age was 49.2 ± 13.2 years, and 84% had Federation of Gynecology and Obstetrics IIB/IIIB disease. Forty-two percent of women were estimated to have inadequate tumor coverage with T + O brachytherapy. The GTV-Tinit volume and dimensions (superior-inferior, left-right, anterior-posterior) on MRI1 were all important predictive factors of inadequate coverage on multivariate analysis. Receiver operating characteristics curves identified optimal thresholds of superior-inferior ≥ 4.5 cm (area under the curve [AUC] = 0.718), left-right ≥ 4.5 cm (AUC = 0.745), anterior-posterior ≥ 5.0 cm (AUC = 0.767), and GTV-Tinit ≥ 85 cm3 (AUC = 0.842). Patients with inadequate coverage had worse clinical outcomes. CONCLUSIONS: Baseline MRI tumor size may predict inadequate CTVHR coverage at the time of brachytherapy (i.e., the need for interstitial needles). This may help identify a subset of women requiring early referral to adequately resourced centers to improve clinical outcomes.

Methylation of the hsa-miR-124, SOX1, TERT, and LMX1A genes as biomarkers for precursor lesions in cervical cancer.

OBJECTIVES: The methylation profile of genes in precursor lesions in cervical cancer was characterized to improve screening techniques for high-grade intraepithelial neoplasia. METHODS: A total of 447 cervical cytology samples obtained from women who underwent colposcopy were examined. The cases were distributed as follows: (1) cervices without cervical intraepithelial neoplasia (CIN; n = 152); (2) cervices with a CIN grade of 1 (CIN 1; n = 147); and (3) cervices with a CIN grade of 2 or 3 (CIN 2/3; n = 148). The methylation pattern for a panel of 15 genes was analysed by quantitative methylation-specific PCR (qMSP) and compared between the groups (≤CIN 1 vs. CIN 2+). RESULTS: In the validation set, seven genes presented significantly different methylation profiles according to diagnosis, namely, DAPK1 (p = 0.001), EPB41L3 (p = 0.001), HIC1 (p = 0.028), hsa-miR-124-2 (p = 0.001), LMX1A (p = 0.001), SOX1 (p = 0.001), and TERT (p = 0.001). Six genes showed a significant increase in the frequency of methylation in the presence of hr-HPV, namely, DAPK1 (p = 0.001), EPB41L3 (p = 0.001), hsa-miR-124-2 (p = 0.001), LMX1A (p = 0.001), SOX1 (p = 0.001), and TERT (p = 0.001). The methylation of the hsa-miR-124 gene showed sensitivity and specificity (86.7% and 61.3%, respectively) similar to that of the HPV test (91.3% and 50.0%, respectively). The independent factors associated with the diagnosis of CIN 2+ and the methylation of the hsa-miR-124-2 (OR = 5.1), SOX1 (OR = 2.8), TERT (OR = 2.2), and LMX1A (OR = 2.0) genes were a positive test for hr-HPV (odds ratio [OR] = 5.5). CONCLUSIONS: Hypermethylation of the hsa-miR-124-2, SOX1, TERT, and LMX1A genes may be a promising biomarker for precursor lesions in cervical cancer regardless of the hr-HPV status.

Is Proflavine Exposure Associated with Disease Progression in Women with Cervical Dysplasia? A Brief Report.

Proflavine is an acridine dye used with high-resolution microendoscopy for in vivo diagnostic evaluation of cervical epithelial cells. However, there are concerns that even short-term exposure of cervical tissue to dilute proflavine may increase cervical cancer risk. We performed a retrospective analysis of women referred for colposcopy to Barretos Cancer Hospital comparing the risk of cervical disease progression in those whose cervical tissue was (n = 232) or was not exposed (n = 160) to proflavine. Patients in both groups underwent treatment and follow-up based on histopathologic results and per the local standards of care. Progression of disease was evaluated by comparing histopathology from the initial visit to the worst subsequent histopathology result from all follow-up visits. Mean duration of follow-up was 18.7 and 20.1 months for the proflavine-exposed and controls groups, respectively. There were no significant differences in disease progression from normal/CIN1 to CIN2/3 or from any initial diagnosis to invasive cancer between the proflavine exposed and control groups overall. Risks of cervical dysplasia progression observed in this study are in agreement with those of the natural history of cervical cancer. Our results suggest that cervical exposure to dilute proflavine does not increase the risk of cervical precancer and cancer.

Diagnosing Cervical Neoplasia in Rural Brazil Using a Mobile Van Equipped with In Vivo Microscopy: A Cluster-Randomized Community Trial.

Cervical cancer is a leading cause of death in underserved areas of Brazil. This prospective randomized trial involved 200 women in southern/central Brazil with abnormal Papanicolaou tests. Participants were randomized by geographic cluster and referred for diagnostic evaluation either at a mobile van upon its scheduled visit to their local community, or at a central hospital. Participants in both arms underwent colposcopy, in vivo microscopy, and cervical biopsies. We compared rates of diagnostic follow-up completion between study arms, and also evaluated the diagnostic performance of in vivo microscopy compared with colposcopy. There was a 23% absolute and 37% relative increase in diagnostic follow-up completion rates for patients referred to the mobile van (102/117, 87%) compared with the central hospital (53/83, 64%; P = 0.0001; risk ratio = 1.37, 95% CI, 1.14-1.63). In 229 cervical sites in 144 patients, colposcopic examination identified sites diagnosed as cervical intraepithelial neoplasia grade 2 or more severe (CIN2+; 85 sites) with a sensitivity of 94% (95% CI, 87%-98%) and specificity of 50% (95% CI, 42%-58%). In vivo microscopy with real-time automated image analysis identified CIN2+ with a sensitivity of 92% (95% CI, 84%-97%) and specificity of 48% (95% CI, 40%-56%). Women referred to the mobile van were more likely to complete their diagnostic follow-up compared with those referred to a central hospital, without compromise in clinical care. In vivo microscopy in a mobile van provides automated diagnostic imaging with sensitivity and specificity similar to colposcopy. Cancer Prev Res; 11(6); 359-70. ©2018 AACR.

Trend analysis of the quality indicators for the Brazilian cervical cancer screening programme by region and state from 2006 to 2013.

BACKGROUND: Quality indicators for the Brazilian cervical cancer screening programme can provide a perspective on its effectiveness in Brazilian macro-regions and states. The aim of this study was to perform a trend analysis of the cervical cancer screening program's quality indicators, according to Brazilian regions and states, from 2006 to 2013. METHODS: Using information from approximately 62,000,000 exams obtained from the Information System of Cervical Cancer Screening (SISCOLO), joinpoint analysis was used to calculate the Annual Percentage Change (APC). RESULTS: The estimated number of women in the target age group (25-64 years) who underwent Pap testing over a three-year interval was lower than that recommended by international guidelines in the North, Northeast and Midwest regions, and the trends for this indicator remained stationary over the years in all regions of Brazil. Overall, the index of positivity in Brazilian regions and states is below that preconized by the Brazilian National Cancer Institute (INCA). Additionally, the frequencies of unsatisfactory cases are in line with international guidelines but above those preconized by INCA guidelines. All positive cytological diagnoses were lower than those preconized by INCA. CONCLUSIONS: The results show that the cervical cancer screening programme is still far from efficient because most of the quality indicators in Brazilian regions and states are outside of the parameters preconized by national and international organizations.

Prevalence of high risk HPV DNA in esophagus is high in Brazil but not related to esophageal squamous cell carcinoma.

BACKGROUNDS: The first publication that associated Human Papillomavirus (HPV) infection and esophageal cancer was published in 1982. However, data are still contradictory and require further investigation. The aim of this study was to identify high risk HPV DNA in esophageal tissue of patients with and without esophageal squamous cell carcinoma (ESCC) and correlate HPV presence with classical risk factors. METHODS: Invited patients signed the informed consent form, and interviews were conducted in order to obtain information about sociodemographic and lifestyle behavior. During endoscopy, esophageal biopsies were collected from case and controls. Multiplex polymerase chain reaction genotyping was conducted on endoscopic biopsies to identify HPV types and HPV-16 was further evaluated by specific PCR real time. RESULTS: Among 87 cases, 12 (13.8%) had tumors harboring high risk HPV DNA and among 87 controls, 12 (13.8%) had high risk HPV DNA (OR:1.025 [CI:0.405:2.592]). Variables regarding consumption of alcohol and use of tobacco continued to characterize risk factors even after adjustments by presence or absence of high risk HPV. CONCLUSION: HPV was demonstrated to be frequently and similarly associated to normal and malignant esophageal tissues, but not as an independent risk factor to esophageal cancer. IMPACT: To contribute to the Brazilian population data on this subject, which is still contradictory.

Organized Cervical Cancer Screening Program in Barretos, Brazil: Experience in 18 Municipalities of São Paulo State.

OBJECTIVES: The aim of this report is to demonstrate the Barretos Cancer Hospital initiative of organizational, laboratorial, and human resources training in the implementation of an organized cervical screening program in low-resource settings. METHODS: We developed a computational program to report all epidemiological, clinical, and laboratorial findings, and to trace all necessary information to recruit women for regular screening or for referral for complementary exams after liquid-based Pap test analyses. RESULTS: All Pap tests were collected in liquid medium and in 2014 more than 160,000 tests were analyzed and 2,900 colposcopy examinations were performed. From 2012 to 2015, the percentage of exams collected increased from 54.6% in 2012 to 62.4% in 2013, 68.4% in 2014, and 71% in 2015. Per 1,000 Pap tests, 0.4 cases of invasive cancer were diagnosed; for in situ carcinoma, 1.9 cases were identified. More importantly, between 2011 and 2015, 89.4% of all carcinomas were detected at clinical stage 0 or I (in situ carcinoma), and only 5% at stages III and IV. CONCLUSIONS: Since the organized system was implemented, 98% of women have attended their recall for colposcopy. So far, we have not reached the target of 70% of women for this proposal, as recommended by the international standards.

HPV infection and p53 and p16 expression in esophageal cancer: are they prognostic factors?

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly lethal malignant tumor. Currently, Human papillomavirus (HPV) is suggested as a potential risk factor for esophageal cancer (EC) in addition to the classic risk factors, alcohol and tobacco, but this hypothesis still remains contradictory. We sought to investigate wether HPV and well-known biomarkers (p16 and p53) and patient-related factors that may have impact on survival of ESCC. METHODS: We conducted a prospective cohort study. By using multiplex PCR, we determined the prevalence of high risk HPV in ESCC, and evaluated the immunohistochemical expression of p16 and p53, molecular markers related to esophageal carcinogenesis in order to verify the potential influence of these variables in patients's survival. Survival rates were estimated using Kaplan-Meier methods. A multivariate confirmatory model was performed using Cox proportional hazards regression. RESULTS: Twelve (13.8%) of 87 patients were HPV-DNA positive. Positive reactions of p16 and p53 were 10.7% and 68.6%, respectively. Kaplan-Meier analysis indicated that men (p = 0.025) had poor specific-cancer survival and a shorter progression-free survival (p = 0.050) as compared to women; III or IV clinical stage (p < 0.019) had poor specific-cancer survival and a shorter progression-free survival (p < 0.001) compared to I and II clinical stage; not submitted to surgery (<0.001) and not submitted to chemoradiotherapy (p = 0.039) had a poor specific-cancer survival, as well. The multivariate analysis showed that HPV, p16 and p53 status are not predictive parameters of progression-free and specific-cancer survival. CONCLUSION: HPV infection and p53 and p16 expression are not prognostic factors in ESCC.