Quality Indicators of Cervical Cytopathology Tests in the Public Service in Minas Gerais, Brazil

Abstract Objective The objective of this study is to assess the performance of cytopathology laboratories providing services to the Brazilian Unified Health System (Sistema Único de Saúde – SUS) in the State of Minas Gerais, Brazil. Methods This descriptive study uses data obtained from the Cervical Cancer Information System from January to December 2012. Three quality indicators were analyzed to assess the quality of cervical cytopathology tests: positivity index, percentage of atypical squamous cells (ASCs) in abnormal tests, and percentage of tests compatible with high-grade squamous intraepithelial lesions (HSILs). Laboratories were classified according to their production scale in tests per year ≤ 5,000; from 5,001 to 10,000; from 10,001 to 15,000; and ≥ 15,001. Based on the collection of variables and the classification of laboratories according to production scale, we created and analyzed a database using Microsoft Office Excel 97–2003. Results In the Brazilian state of Minas Gerais, 146 laboratories provided services to the SUS in 2012 by performing a total of 1,277,018 cervical cytopathology tests. Half of these laboratories had production scales ≤ 5,000 tests/year and accounted for 13.1% of all tests performed in the entire state; in turn, 13.7% of these laboratories presented production scales of > 15,001 tests/year and accounted for 49.2% of the total of tests performed in the entire state. The positivity indexes of most laboratories providing services to the SUS in 2012, regardless of production scale, were below or well below recommended limits. Of the 20 laboratories that performed more than 15,001 tests per year, only three presented percentages of tests compatible with HSILs above the lower limit recommended by the Brazilian Ministry of Health. Conclusion The majority of laboratories providing services to the SUS in Minas Gerais presented quality indicators outside the range recommended by the Brazilian Ministry of Health.


Introduction
Several countries have developed and successfully implemented cervical cancer screening programs based on Pap smear testing, as shown by the decrease in cervical cancer incidence and mortality rates. 1,2][5] The internal quality control (IQC) in laboratories are defined as the continuous monitoring of all activities involved in the laboratorial function, which include management of human resources, operating procedures, and quality control.For this reason, the development of methods are needed to ensure that a laboratory meets standard levels of accuracy and reliability in their laboratory report. 6,7In Brazil and other parts of the world, such as the United Kingdom, Europe, Australia, and Mexico, IQC methods are used to reduce false-negative rates in laboratory testing. 8,9n 2012, the Brazilian National Cancer Institute (Instituto Nacional do Câncer -INCA/MS), together with Brazilian Scientific Societies, developed the Quality Management Manual for Cytopathology Laboratories with the objective of improving the reliability of cytopathology testing.10 This manual addresses several IQC methods and provides quality indicators that allow constant monitoring of cytopathology test results.In addition, these indicators allow the assessment of overall and individual performance levels of laboratory personnel who process and analyze cytopathology tests.Some of these indicators are the positivity index (PI), the percentage of atypical squamous cells (ASCs) of undetermined significance in abnormal tests, and the percentage of tests compatible with high-grade squamous intraepithelial lesions (HSILs) in satisfactory tests.10 To emphasize the importance of quality in cytopathology testing, the Brazilian Ministry of Health enacted an ordinance that establishes the National Cytopathology Quality Control Program for Cervical Cancer Prevention (Qualificação Nacional em Citopatologia na Prevenção do Câncer do Colo do Útero). 11Both the Manual and the Ministry Ordinance have defined standards and criteria required to measure the quality of cytopathology testing and to assess the performance of public and private laboratories providing services to the Brazilian Unified Health System (Sistema Único de Saúde -SUS).
Nonetheless, well-defined criteria and recommendations to improve the quality of cytopathology testing in Brazil are

Resumo
Objetivo Avaliar o desempenho dos laboratórios de citopatologia prestadores de serviço para o Sistema Único de Saúde (SUS) no estado de Minas Gerais, Brasil.Métodos estudo descritivo com base nos dados obtidos do Sistema de Informação do Câncer do Colo do Útero no período de janeiro a dezembro de 2012.Para avaliação da qualidade dos exames citopatológicos do colo do útero, foram analisados três indicadores de qualidade: índice de positividade, percentual de ASC (células escamosas atípicas) entre os exames alterados e percentual de exames compatíveis com HSIL (Lesão intraepitelial escamosa de alto grau).Os laboratórios foram classificados conforme escala de produção em: 5.000; entre 5.001 e 10.000; entre 10 not enough to solve one of its main challenges, which is the underperformance of laboratories providing services to the SUS throughout the country whose quality indicators fall outside the limits recommended by the Brazilian Ministry of Health. 12In light of this issue, our study assessed the performance of cytopathology laboratories providing services to the SUS in Minas Gerais.

Methods
This is a descriptive study performed using data we obtained from the Cervical Cancer Information System (Sistema de Informação do Câncer do Colo do Útero -SISCOLO), from January to December 2012, in Minas Gerais, Brazil.We obtained the data through pre-selected variables using Tabnet, a SISCOLO application, available at the SUS Computer Department (Departamento de Informática do SUS -DATA-SUS).These data are in the public domain with non-restricted access. 13Given that the study is based on test results collected in 2012 that are publicly available via SISCOLO, authorization from the Research Ethics Committee was not required.
In this study, we used IQC indicators recommended by the Brazilian Ministry of Health to assess the quality of cervical cytopathology tests performed by laboratories providing services to the SUS.
The first indicator assessed was the Positivity Index (PI), which expresses the prevalence of cellular alterations and the sensitivity of the screening process for detecting atypias or cervical cancer precursor lesions.Low positivity may indicate that positive samples are not being identified, resulting in false negatives.The Brazilian ministry of health recommends a PI higher than 3%. 10,14he second indicator used was ASC percentage in abnormal tests, which is assessed together with PI.An apparently adequate PI may contain a high percentage of tests compatible with ASCs, which would reflect cytologically ambiguous cases.ASCs should correspond to less than 60% of abnormal tests. 10,11he third and last indicator used was the percentage of tests compatible with HSILs in satisfactory tests.HSILs are considered to be cervical cancer precursor lesions, that is, lesions that may effectively progress to cancer.Thus, detection of HSILs is the main objective of cervical cancer prevention. 10,12This indicator measures the capacity to detect precursor lesions, and recommendations indicate that HSILs should be equal to or greater than 0.4% of satisfactory tests. 10,11o perform a critical assessment of laboratory quality, we classified these three indicators according to the guidelines of the Brazilian Ministry of Health and the National Institute of Cancer (Instituto Nacional de Câncer -INCA), 10 as seen in ►Table 1.
Regarding quality criteria, the Brazilian Ministry of Health Ordinance n. 3,388/2013 11 (QualiCito-Portaria) recommends that Type I Laboratoriesdefined as public or private laboratories that provide services to the SUSprocessing cervical cytopathology tests should have a minimum production of 15,000 tests/year. 11To compare the performance of laboratories according to their production scale, laboratories were classified as 5,000; from 5,001 to 10,000; from 10,001 to 15,000; and > 15,000 tests/year.
Based on the collection of variables and the classification of laboratories according to production scale, we created and analyzed a database using Microsoft Office Excel 97-2003.

Results
In 2012, 146 laboratories provided services to the Brazilian SUS in Minas Gerais and performed 1,277,018 cervical cytopathology tests.Half of these laboratories had production scales lower than or equal to 5,000 tests/year and accounted for 13.1% of all tests performed in Minas Gerais in 2012.A total of 36 laboratories, with production scales between 5,001 and 10,000 tests/year, performed 20.8% of all cervical cytopathology tests in Minas Gerais.Laboratories with production scales of 10,001 to 15,000 tests/ year (17 laboratories in 2012) performed 16.9% of all tests.The remaining 13.7% of laboratories, with production scales greater than 15,000 tests/year, accounted for 49.2% of all tests performed in the entire state during 2012 (►Table 2).►Table 3 describes the classification of quality indicators according to the production scales of the 146 laboratories that provided services to the SUS in Minas Gerais during 2012.Of 73 laboratories performing up to 5,000 tests/year, only 11 showed indicators in the recommended range; the indicators of 47 of these laboratories, corresponding to more than half of the laboratories included in the group, were well below the recommended limits.Regarding laboratories processing from 5,001 to 10,000 tests/year, 26 out of 36 laboratories of this group showed indicators that were much lower than recommended; only two laboratories had indicators in the recommended range.Of the 17 laboratories classified with production scales of 10,001 to 15,000 tests per year, only one laboratory presented quality indicators in the recommended range; 13 of these laboratories were well below the recommended values.
Finally, of the 20 laboratories that performed more than 15,000 tests per year, only three had quality indicators within the recommended range and in 12 of these laboratories, the indicators were well below recommended limits.
Thus, overall, 98 laboratories (67.2%) showed quality indicators well below recommended limits, and only 17 (11.6%) of the 146 laboratories serving the SUS in 2012 presented quality indicators within the range recommended by the Brazilian Ministry of Health.

Discussion
The objective of quality control in cytopathology is to improve the test's performance to eliminate false-negative results. 14,15rom a practical standpoint, false-negatives are of greater concern in routine testing than false-positive results, given that non-diagnosed women may not seek follow-up and will live with the risk of developing precursor lesions. 16In turn, false-positive results also have negative effects because they lead to unnecessary surgeries and clinical procedures that can negatively affect women's reproductive and sexual life, not to mention the clear psychological impacts of these procedures. 3he PI is an indicator that expresses the prevalence of cellular alterations in cytopathology tests and the screening program's sensitivity for detecting lesions in the examined population.Brazil has a low PI associated with a high number of ASC alterations, indicating that cervical cancer precursor lesions are not being diagnosed. 12he results of this study showed that most laboratories providing services to SUS in 2012, regardless of production scale, showed PI values well below the Ministry of Health's recommended range, which is a PI greater than 3%. 10Even when laboratories showed intermediate quality indicators, with PIs greater than 3%, the detection levels of HSILs were low.
The distribution of cervical cytopathology tests among a large number of laboratories with small production scales may have a negative effect on the professional expertise of the personnel who analyze cytological slides, thus leading to false-negative results.Moreover, a production of less than 5,000 tests/year is also a possible cause of higher error rates during slide reading. 17The Brazilian Ministry of Health, as stated in ordinance n. 3,388 of December 2013, encourages laboratories to perform more than 15,000 tests/year. 11However, this study showed a greater proportion of laboratories with quality A working group composed of cytologists and cytotechnologists was created to analyze data and to debate quality and good practices in gynecological cytopathology laboratories.This working group discussed the issue of laboratories with cytopathology test volumes below 5,000 tests/year.According to the results presented, it is unclear how these laboratories should be monitored because the literature has been based on various assumptions, which means that further research on this subject is needed. 18he low PI values found in this studycompared with the values observed in countries with successful cervical cancer prevention programs, such as the United States (PI 6.8%) and the United Kingdom (PI 6.4%) -indicate the presence of falsenegative results and support the need to reevaluate and/or implement IQC in such laboratories. 10,19ssessing the diagnostic frequency of ASCs may contribute in elaborating laboratory quality control measures, establishing national standards, and reaching acceptable percentages for ASC diagnosis.In addition, the constant monitoring of this diagnostic category enables the evaluation of its behavior over time and, if there are changes, it allows the opportunity to assess and explain them.High numbers of false-negatives and false-positives and an excess of ASC diagnoses in cervical cytopathology reports have raised global concerns.Thus, the adoption of IQC measures in laboratories that perform this type of test is crucial to minimize these problems. 20SILs are considered to be the actual precursor lesions to cervical cancer, as these lesions can progress to cancer.This makes HSIL detection the main objective of cervical cytopathology tests.For this reason, the percentage of tests compatible with HSIL is an indicator of the capacity to detect precursor lesions and should be greater than 0.4%, a value based on results obtained in countries with successful screening programs able to reduce the incidence and mortality of cervical cancer, such as the United States (HSIL 0.5%). 21 concern raised by our study is that almost 80% of laboratories serving the SUS in 2012 have shown values for the indicator HSIL/Sat (high squamous intraepithelial lesion / satisfaction) below or well below the recommended levels, regardless of the production scale.Of 20 laboratories performing more than 15,000 tests/yearwhich are responsible for more than 50% of all tests performed in Minas Geraisonly three showed HSILs in the recommended range; 14 of these high-volume laboratories showed HSIL values below or well below the recommended, indicating that cervical cancer precursor lesions are not being detected.The performance of IQC in cytopathology laboratories aims to reduce misdiagnoses of high-grade lesions by retesting cytological slides, because a slide previously classified as negative might be identified as a false-negative. 22 group of researchers assessed quality indicators in laboratories that performed External Quality Control (EQC) and found that all quality indicatorsparticularly highgrade lesion detectionimproved in these laboratories after continuous education.This result demonstrates the importance of EQC in improving the capacity of detecting cervical cancer precursor lesions in professionals that perform cytopathology tests. 23The correct identification, diagnostic confirmation, treatment, and follow-up of these cellular alterations, which represent true cervical cancer precursor lesions, might prevent their progression to invasive cancer. 12,24n Minas Gerais, cervical cancer is the cancer with the second highest incidence among women, 25 and our results show that several laboratories either do not detect or detect a low number of cervical cancer precursor lesions.Therefore, there is a need to invest not only in internal and external quality control of laboratories performing cervical cancer diagnosis, but also in strict inspections of such laboratories by competent authorities, as stated in the Brazilian Ministry of Health Ordinance n. 3,388, 11 issued December 30, 2013, so that statistics regarding cervical cancer may improve in the near future.

Table 1
Classification of quality indicators according to Brazilian Ministry of Health recommendations Abbreviations: ASC/Abnormal, Percentage of atypical squamous cells (ASCs) in abnormal tests; HSIL, Percentage of high-grade squamous intraepithelial lesions (HSILs) in satisfactory tests.Data source: Brazil (2012). 10RBGO Gynecology and Obstetrics Vol.38 No. 2/2016 Quality Indicators of Cervical Cytopathology Tests in the Public Service in Brazil Tobias et al. 67

Table 3
Classification of quality indicators of laboratories serving the SUS in Minas Gerais according to production scale

Table 2
Distribution of cytopathology laboratories serving the SUS in Minas Gerais according to production scale and processed tests in 2012 Quality Indicators of Cervical Cytopathology Tests in the Public Service in Brazil Tobias et al. indicators within the recommended range for the 'production scale 5,000 tests/year' category.