Folate deficiency modifies the risk of CIN3+ associated with DNA methylation levels: a nested case-control study from the ASCUS-COL trial.

PURPOSE: To our knowledge, there are very few studies evaluating if the levels of folate modify the risk of cervical intraepithelial neoplasia grade 2 and higher (CIN2+ and CIN3+) associated with the levels of HPV genome methylation, two cofactors related to single carbon metabolism and independently associated with cervical cancer in previous studies. We conducted a case-control study nested in a three-arm randomized clinical pragmatic trial (ASCUS-COL trial) to evaluate the risk of CIN3+ associated with methylation levels according to serum folate concentrations. METHODS: Cases (n = 155) were women with histologically confirmed CIN2+ (113 CIN2, 38 CIN3, and 4 SCC) and controls were age and follow-up time at diagnosis-matched women with histologically confirmed ≤ CIN1 (n = 155), selected from the 1122 hrHPV + women of this trial. The concentrations of serum folate were determined by the radioimmunoassay SimulTRAC-SNB-VitaminB12/Folate-RIAKit and the methylation levels by the S5 classifier. Stepwise logistic regression models were used to estimate the association between folate or methylation levels and CIN2+ or CIN3+. The joint effect of folate levels and methylation on the risk of CIN3+ was estimated using combinations of categorical stratifications. RESULTS: Folate levels were significantly lower in women with CIN3+ than in other diagnostic groups (p = 0.019). The risk of CIN3+ was eight times higher (OR 8.9, 95% CI 3.4-24.9) in women with folate deficiency and high methylation levels than in women with normal folate and high methylation levels (OR 1.4, 95% CI 0.4-4.6). CONCLUSION: High methylation and deficient folate independently increased the risk of CIN3+ while deficient folate combined with high methylation was associated with a substantially elevated risk of CIN3+.

The impact of transformation zone representation on the frequency of abnormal cervical cytological results.

OBJECTIVE: To compare the frequency of abnormal cervical cytological results with and without representation of the transformation zone (TZ) in a medium-sized city in Brazil according to the Bethesda categorization. METHODS: We performed an analytical observational study evaluating cytological results over 15 years from conventional smears collected within the Public Brazilian Health System in Araçatuba, Brazil. Tests were stratified by age and cytological result according to Brazilian guidelines and the Bethesda System. RESULTS: There were 261,881 examinations, 159,251 with and 102,630 without TZ representation. The global frequency of abnormal results was higher in smears with TZ representation (crude odds ratio [OR] 4.03; 95% confidence interval [CI] [3.71-4.38]). Considering only women between 25 and 64 years (the target of the national guidelines), there were higher results for high-grade squamous intraepithelial lesions (OR 11.54; 95% CI 6.74-19.78), low-grade squamous intraepithelial lesions (OR 2.82; 95% CI 2.17-3.67) atypical squamous cell in which high-grade intraepithelial lesion cannot be excluded (OR 6.90; 95% CI 4.91-9.66) and atypical squamous cell of undetermined significance (OR 3.53; 95% CI 3.11-4.01) among cases with TZ representation. CONCLUSION: Samples with TZ representation were associated with higher rates of abnormal results. Health professionals should be regularly trained to understand the weakness of cytological examinations when the TZ is not represented, especially in developing countries.

Relation between naked eye Swede score and the outcomes of atypias of undetermined significance.

INTRODUCTION: Cervical cancer precursor lesions occur due to persistent infection caused by human papillomavirus (HPV). One of the challenges of the Pap test is detecting lesions at a high risk of evolving into cancer. In this context, differentiating patients at low and high risk of developing cervical cancer becomes necessary. The Swede score, a standardized point system assigned based on colposcopy, is the most commonly used method to evaluate suspicious lesions. However, access to colposcopy is limited in low-income countries. It is, therefore, important to assess the applicability of less costly diagnostic methods in these situations to avoid a late diagnosis of cervical cancer. OBJECTIVE: To analyze histological outcomes of cytology tests with atypical squamous cells of undetermined significance (ASC-US and ASC-H) and to compare the performance of the Swede score with and without colposcopy. METHODS: The study was approved by the Ethics Committee via Plataforma Brasil (CAAE no. 41958320.6.0000.5259) and conducted by applying colposcopy score and naked eye score to patients with cytology alterations (ASC-US and ASC-H), with posterior analysis of cytological and histological results and comparison between the scores. RESULTS: A total of 34 women aged ranging from 24 to 65 years, with results of atypia with undetermined significance (ASC-US and ASC-H), were included in the study. The receiver operating characteristic curve was calculated for the naked eye inspection Swede score. The cut-off of 6 was considered to indicate the best sensitivity and specificity (55.56% and 93.75%, respectively). Then, the positive and negative predictive values were 90.91% and 65.22%, respectively. By increasing the cut-off to 7, specificity increased to 100%. For the colposcopic inspection, a cut-off of 6 indicates better specificity and positive predictive value (both 100%), whereas the negative predictive value was 57.14%. CONCLUSION: The correlation between the colposcopic and naked-eye Swede scores was statistically significant (0.82). Further studies with larger samples are important to establish the actual applicability of the naked eye method; however, in the absence of colposcopy, this appears to be an effective and very helpful method to make diagnostic decisions regarding HPV-induced lesions.

Evaluation of 1,030,482 Cervical Smear Results in Brazilian Population.

BACKGROUND: The objective was to determine the prevalence of abnormal cytologic smears in a large population of a Brazilian city. METHODS: Retrospective study of cervical cytology results performed at a private laboratory in São Paulo - Brazil. A total of 1,030,482 cytology tests were performed between January 2010 and December 2015. RESULTS: Among the satisfactory cytologies, we observed abnormal results in 8.9% (91,371). Analyzing the proportion of exams with altered results over the years, there was no change in these rates. We observed that the proportion of abnormal exams decreased with increasing age. Atypical squamous cells of undetermined significance, possibly non-neoplastic (ASC-US) cytology was the most common abnormality found in the general population with 73.19%, followed by low-grade intraepithelial lesion (LSIL) with 20.5%; these 2 cytological abnormalities add up to 93.69 % of all abnormal results. There was an increase in ASC-US with advancing age, a decrease in prevalence of LSIL, especially after the age of 30 and high-grade intraepithelial lesion (HSIL) shows two peaks of elevation, respectively in the age groups of 30-39 years and over 70 years. CONCLUSION: Women under the age of 30 showed a higher prevalence of cytological abnormalities, however most of these changes are low-grade lesions. In older women, cytological abnormalities are largely high-grade lesions, requiring greater care to prevent progression to cancer.

Cervical cytology results among pregnant and non-pregnant women in Brazil.

OBJECTIVE: To compare the prevalence of abnormal cervical smear results among pregnant and non-pregnant women with and without representation of the transformation zone (TZ) in a mid-sized city in Brazil. STUDY DESIGN: This observational analytical and retrospective study analyzed cervical smear results from pregnant and non-pregnant women in a mid-sized city in Brazil. Private data were collected at private clinics over seven years and from public services over 16 years. All results were reported according to Bethesda System. Pregnant women were separated from non-pregnant women, and women were stratified into two age groups (25-29 years and 30-34 years) in general analyses. For TZ representation and cytologic-histologic correlation, there was no age stratification. RESULTS: Among public services cervical smears, the frequency of atypical squamous cells of undetermined significance (ASC-US) was higher for pregnant women in the entire group (odds ratio [OR] 1.91; confidence interval [CI] 1.07-3.39) and among women from 30 to 40 years old (OR 2.79; CI 1.38-5.66). The same occurred for low-grade squamous intraepithelial lesion (LSIL) in the total group (OR 3.50; CI 1.44-8.53) and among women 30 to 40 years old (OR 4.57; CI 1.45-14.42). The frequency of ASC-US was higher in pregnant women with TZ representation exams than those without (OR 4.62; CI 2.17-9.84). The same occurred for those with atypical squamous cells, which cannot exclude high-grade squamous intraepithelial lesion (OR 9.81; CI 1.63-59.15) and LSIL (OR 10.47; CI 3.39-32.36). Among pregnant women with abnormal cervical smear results, 85.74% were followed up through cytology, and an average of 26.12% of patients underwent biopsy, of which almost all were positive for dysplasia. CONCLUSION: Pregnant and non-pregnant women did not differ in cervical smears with actual precursor lesions. Nevertheless, considering the opportunistic nature of Brazilian cervical cancer screening, prenatal visits present an opportunity to perform cervical smears in pregnant women. TZ representation correlated with higher rates of abnormal cervical smears, reinforcing the clinical importance of endocervical/metaplastic cell representation, including among pregnant women.

Is there a higher frequency of anal dysplasia and infection by human papillomavirus in Crohn's disease patients?

The aim of this study was to compare the frequency of dysplasia and human papillomavirus (HPV) infection in the anal canal of patients with Crohn's disease (CD) with a control group and assess whether there is a correlation between use of immunosuppressants and anal manifestation of CD. Patients with CD and control individuals were submitted to anal cytology and material collection for polymerase chain reaction (PCR). The cytology was classified as normal, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or high-grade (HSIL). PCR was considered positive or negative according to virus presence or absence. A total of 117 patients were included (54 in the control group and 63 in the CD group, being 32 without and 31 with immunosuppressants). ASCUS and LSIL were found in 25.9 and 22.2% of control patients and 28.6 and 39.7% of CD patients. HPV was identified in 14.8% of the control group and 27% of the CD group. In CD patients, HPV was found in 37.5 and 16.1% of those without and with immunosuppressants, respectively. Patients with perianal involvement had 15.6% of PCR positivity. There was no statistical difference in dysplasia and infection by HPV between the groups. Use of immunosuppressants did not influence the result, but anal manifestation was inversely proportional to viral detection.

Comparison of cervical cancer screening results among public and private services in Brazil.

OBJECTIVE: To compare the frequency of cervical smear test results between women seen in private and public health services in a medium-sized city in Brazil. METHODS: This was an observational analytical study analyzing cervical cytologic results over 16 years. Public data were collected from the Brazilian National Health System, and private refers to those collected at private clinics. RESULTS: The overall frequency of unsatisfactory/rejected results was higher in public service examinations (odds ratio [OR] 0.05; 95% confidence interval [CI] 0.04-0.06). The same occurred for atypical squamous cells of undetermined significance (ASC-US) (OR 0.90; 95% CI 0.85-0.95) and atypical squamous cells cannot exclude high grade intraepithelial lesions (ASC-H) (OR 0.55; 95% CI 0.47-0.64) categories. For low-grade squamous intraepithelial lesions, the frequency was higher among women from private services (OR 1.39; 95% CI 1.24-1.55). Among women aged 25-64 years, the frequency of high-grade squamous intraepithelial lesions was higher among women seen in the public service (OR 0.81; 95% CI 0.66-0.99). CONCLUSION: Brazilian public services showed higher frequencies of unsatisfactory/rejected results and higher rates of ASC-US and ASC-H. Focusing on pre-analytical phases and establishing an internal quality control program can help improve these rates even though national protocols guide them.

Alterações em exames citopatológicos realizados em Unidade Básica de Saúde: um estudo analítico transversal / Alterations in cytopathological tests performed in a Basic Health Unit: a cross-cutting analytical study

Objetivo: Com o presente estudo, buscou-se verificar a quantidade de exames de colpocitologia oncótica coletados em Unidade Básica de Saúde (UBS) escolhida, determinar quantas e quais são as alterações encontradas nesses exames e quais foram as condutas e acompanhamentos realizados em pacientes com exames alterados. Métodos: Foram analisados 446 exames de colpocitologia oncótica realizados em uma UBS do centro-oeste do Paraná. As pacientes com exame alterado foram selecionadas e foi feita uma análise desses prontuários a fim de verificar a conduta e o acompanhamento dessas pacientes. Resultados: Foram encontrados 32 exames com alterações, sendo três de uma mesma paciente. Dessas 30 pacientes, a grande maioria correspondia a células escamosas atípicas de significado indeterminado (ASC-US), possivelmente não neoplásicas, e 28 pacientes retornaram para receber uma conduta inicial, sendo principalmente o encaminhamento para a coleta de novo preventivo em seis meses ao serviço de oncologia clínica. Conclusão: O presente estudo concluiu que a hipótese principal foi verdadeira, a qual foi descrita como prevalência significativa de lesões intraepiteliais de alto grau, embora não seja a mais frequente, e descontinuidade por parte das pacientes que obtiveram esse resultado. Além disso, notou-se grande encaminhamento à atenção terciária, o que não é indicado pelo Ministério da Saúde.(AU)

Objective: With the present study, we sought to verify the amount of cytopathological tests collected in the chosen basic health unit, to determine how many and what are the alterations found in these tests and what were the conducts and follow-ups performed in patients with altered exams. Methods: We analyzed 446 preventive tests performed in a basic health unit in the Midwest of Paraná, and patients with altered examination were selected and an analysis of these medical records was made in order to verify the conduct and follow-up of the patients. Results: Thirty-two tests with alterations were performed, 3 of which were the same patient. Of these 30 patients, the vast majority corresponded to atypical cells of squamous meaning ­ possibly non-neoplastic (ASC-US), and 28 patients returned to receive an initial approach, mainly being referred to the collection of preventive new in 6 months and to the clinical oncology service. Conclusion: The present study concluded that the main hypothesis was true, which was described as a significant prevalence of high-grade intraepithelial lesions (HSIL), although not the most frequent, and discontinuity on the part of the patients who obtained this result. In addition, there was a large referral to tertiary care, which is not indicated by the Ministry of Health.(AU)

Perfil dos exames citopatológicos do colo do útero de mulheres residentes no estado de Minas Gerais / Profile of cytopathological examinations of the cerever of women resident in the state of Minas Gerais

Introdução: O diagnóstico precoce e referenciamento ao serviço especializado são essenciais para melhorar as taxas de cura e sobrevida das mulheres acometidas pelo câncer de colo de útero. Assim, a realização deste estudo tornará possível o levantamento de informações que serão essenciais para o desenvolvimento de medidas preventivas, que almejam contribuir com o desenvolvimento de ações de educação em saúde e o diagnóstico precoce para reduzir a morbimortalidade dessa enfermidade. Objetivo: Identificar o perfil dos resultados dos exames citopatológicos do colo do útero de mulheres residentes no estado de Minas Gerais a partir dos dados de exames correspondentes ao ano de 2019, utilizando as variáveis disponibilizadas pelo Sistema de Informação do Câncer. Métodos: Trata-se de um estudo retrospectivo, exploratório, quantitativo realizado por meio de base de dados secundários. Os dados foram submetidos à análise no software SPSS, versão 20.0. Realizou-se estatística descritiva (frequência absoluta, porcentagem, média e desvio padrão). Para verificar associação entre variáveis qualitativas foi utilizado teste qui-quadrado (x²) e exato de Fisher. A força das associações entre as variáveis foi aferida pelo risco relativo (RR) e intervalos de confiança (IC 95%). Resultados: As principais alterações presentes nos exames foram: alterações por células escamosas atípicas de significado indeterminado e lesão intraepitelial de baixo grau. Após análises estatísticas, notou-se que algumas alterações possuem risco maior de se desenvolverem no público fora da faixa etária preconizada, ou seja, entre mulheres com idade <25 anos ou >64 anos. Conclusão: O estudo realizado contribui para identificação do perfil atual vivenciado na área da saúde da mulher e possibilita a criação de condutas e ações que visem intervir frente aos resultados obtidos, impactando positivamente na realidade de Minas Gerais

Introduction: Early diagnosis and referral to a specialized service are essential to improve the cure and survival rates of women affected by cervical cancer. Thus, carrying out this study will make it possible to collect information that will be essential for the development of preventive measures, which aim to contribute to the development of health education actions and early diagnosis to reduce the morbidity and mortality of this disease. Objective: Identify the profile of the results of cervical cytopathological examinations of women residing in the State of Minas Gerais from the data of examinations corresponding to the year 2019, using the variables made available by the Cancer Information System.Methods: This is a retrospective, exploratory, quantitative study carried out by means of a secondary database. The data were submitted to analysis using the SPSS software, version 20.0. Descriptive statistics (absolute frequency, percentage, mean and standard deviation) were performed. To verify the association between qualitative variables, the chi-square test (x²) and Fisher's exact test were used. The strength of the associations between the variables was measured by the relative risk (RR) and confidence intervals (95% CI). Results: The main alterations present in the cytopathological exams performed were: changes due to atypical squamous cells of undetermined significance and low- grade intraepithelial lesion. After statistical analysis, it was noted that some changes have a higher risk of developing in the public outside the recommended age range, that is, among women aged <25 years or> 64 years. Conclusion: The study carried out contributes to the identification of the current profile experienced in the area of women's health and enables the creation of conducts and actions that aim to intervene in view of the results obtained, positively impacting the reality of Minas Gerais.

Infecção pelo HPV na região Sul do Brasil: uma revisão integrativa da literatura / HPV infection in southern Brazil: an integrative literature review / Infección por el VPH en el Sur de Brasil: una revisión integradora de la literatura

O papilomavírus humano (HPV) infecta pele e mucosas e causa, na grande maioria dos casos, lesões transitórias que podem evoluir para câncer. O objetivo deste estudo é avaliar, por meio de revisão integrativa, a literatura disponível sobre a frequência da infecção pelo HPV na região Sul do Brasil. Buscou-se nas bases de dados PubMed, Literatura Latino-americana e do Caribe em Ciências da Saúde (Lilacs) e Scientific Electronic Library Online (SciELO) a frequência de HPV na região Sul do Brasil nos últimos dez anos. Foram identificados oito estudos que se enquadraram nos critérios da pesquisa. A prevalência estimada de infecção pelo HPV foi de 46,19%. Os genótipos mais encontrados foram HPV 6, de baixo risco, e os subtipos HPV 16, HPV 18, HPV 31 e HPV 58, de alto risco. Nas amostras classificadas como LSIL/HSIL ou de células escamosas atípicas (ASC), tipos virais de baixo risco HPV 6, HPV 11 e HPV 44 foram os mais prevalentes, enquanto para os de alto risco os subtipos HPV 16, HPV 18 e HPV 58 foram os mais encontrados. Embora tenham sido identificados poucos estudos com essa temática nos últimos anos, a partir dos dados da pesquisa foi possível estimar a prevalência do HPV no Sul do Brasil e seus genótipos mais frequentes. Essa informação é importante para o planejamento das ações de saúde pública e dos serviços de saúde, contribuindo para a elaboração de estratégias de controle e prevenção da infecção.

Human Papillomavirus (HPV) infects skin and mucous membranes, and, in most cases, causes transient lesions that can progress to cancer. Given this scenario, this integrative review sought to evaluate the available literature on the frequency of HPV infection in southern Brazil. Bibliographic search was conducted on the PubMed, Latin American and Caribbean Literature on Health Sciences (Lilacs) and Scientific Electronic Library Online (SciELO) databases for papers on the frequency of HPV in southern Brazil published in the last ten years. Eight studies were identified. Estimate of HPV infection prevalence was 46.19%. Low-risk HPV 6 and high-risk HPV 16 were the most common genotypes, and HPV 18, HPV 31 and HPV 58 the most common subtypes. Risky viral types HPV 6, HPV 11 and HPV 44 were most prevalent in cellular changes classified as LSIL/HSIL or atypical squamous cell (ASC), whereas HPV 16, HPV 18 and HPV 58 prevailed as the high risk subtypes. Despite the small sample size of recent studies, the review was able to identified the prevalence of HPV infection in southern Brazil and its most common genotype, essential information for elaborating public health strategies and preventing infections.

El virus del papiloma humano (VPH) infecta la piel y las mucosas y, en la mayoría de los casos, provoca lesiones transitorias que pueden progresar a cáncer. El objetivo de este estudio es evaluar, a través de una revisión integradora, la literatura disponible sobre la frecuencia de infección por VPH en la región Sur de Brasil. Se realizaron búsquedas en las bases de datos PubMed, Literatura Latinoamericana y del Caribe en Ciencias de la Salud (Lilacs) y Scientific Electronic Library Online (SciELO) para determinar la frecuencia del VPH en la región Sur de Brasil en los últimos diez años. Se identificaron ocho estudios que cumplieron con los criterios de búsqueda. La prevalencia estimada de infección por VPH fue del 46,19%. Los genotipos más comunes fueron el VPH 6 de bajo riesgo y los subtipos VPH 16, VPH 18, VPH 31 y VPH 58 de alto riesgo. En muestras clasificadas como LSIL/HSIL o células escamosas atípicas (ASC), los tipos virales de bajo riesgo VPH 6, VPH 11 y VPH 44 fueron los más prevalentes, mientras que para los subtipos de alto riesgo VPH 16, VPH 18 y VPH 58 fueron los más frecuentes. Aunque se identificaron pocos estudios sobre este tema en los últimos años, con base en los datos de la encuesta, fue posible estimar la prevalencia del VPH en el Sur de Brasil y sus genotipos más frecuentes. Esta información es importante para planificar acciones de salud pública y servicios de salud, contribuyendo al desarrollo de estrategias de control y prevención de infecciones.

Effective methylation triage of HPV positive women with abnormal cytology in a middle-income country.

The S5-methylation test, an alternative to cytology and HPV16/18 genotyping to triage high-risk HPV-positive (hrHPV+) women, has not been widely validated in low-middle-income countries (LMICs). We compared S5 to HPV16/18 and cytology to detect cervical intraepithelial neoplasia Grade 2 or worse (CIN2+) and CIN3+ in hrHPV+ women selected from a randomized pragmatic trial of 2661 Colombian women with an earlier-borderline abnormal cytology. We included all hrHPV+ CIN2 and CIN3+ cases (n = 183) age matched to 183

High-risk Human Papillomavirus Testing for Triage of Women with Previous Cytological Abnormalities from the Vale do Ribeira Region.

OBJECTIVE: To evaluate the performance of the hybrid capture 2 (HC2) high-risk papillomavirus (hrHPV) assay and cytological test in women with previous abnormalities, to detect cervical intraepithelial neoplasia grade 2 or worse (≥ CIN 2). METHODS: A cytological test and HC2 (Qiagen, Gaithersburg, Maryland, EUA) for hrHPV were conducted in 359 liquid-based (Sure Path, Becton Dickinson, TriPath Imaging, Burlington, NC, USA) samples collected from women from the Vale do Ribeira Region, during July 2013 and September 2015 with previous cytology classified as atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions (ASC-H), and atypical glandular cells (AGC). The histopathological examination was conducted in 179 women. The performance evaluations were calculated using the "exact" Clopper-Pearson 95% confidence interval (CI) test by MEDCALC (Medcalc Software Ltd, Ostend, Belgium). RESULTS: The ≥ CIN 2 frequency was 11.7% (21/179). The HC2 for hrHPV and repeat cytology to detect ≥ CIN 2 obtained, respectively, a sensitivity of 90.5% (95%CI = 69.6-98.8) and 90.5%, (95%CI = 69.6-98.8), a specificity of 65.8% (95% CI = 57.9-73.2) and 43.7% (95%CI = 35.8-51.8), a positive predictive value of 26.0% (95% CI = 21.4-31.3) and 17.6%, (95%CI = 14.9-20.6), and a negative predictive value of 98.1% (95%CI = 93.3-99.5) and 97.2% (95% CI = 90.1-99.2). CONCLUSION: Hybrid capture 2 for hrHPV improves the performance of the detection of ≥ CIN 2, without compromising sensitivity, and provides a greater safety margin to return to the triennial screening of women undergoing follow-up due to previous abnormalities, without underlying ≥ CIN 2.

OBJETIVO: Avaliar o desempenho da captura híbrida 2 (CH2) para papilomavírus humano de alto risco (HPVar) e repetição do exame citopatológico em mulheres com anormalidades em citologia anterior, para detectar neoplasia intraepitelial cervical grau 2 ou pior (≥ NIC 2). MéTODOS: Foi realizado exame citopatológico e CH2 para HPVar (Qiagen, Gaithersburg, Maryland, EUA) em 359 amostras em meio líquido (Sure Path, Becton Dickinson, TriPath Imaging, Burlington, NC, USA) coletadas de mulheres da região do Vale do Ribeira, durante julho de 2013 e setembro de 2015 com citologia anterior classificada como células escamosas atípicas de significado indeterminado (ASC-US), lesão intraepitelial de baixo grau (LSIL), células escamosas atípicas, não podendo excluir lesão de alto grau (ASC-H) e células glandulares atípicas (AGC). O exame histopatológico foi realizado em 179 mulheres. As avaliações de desempenho foram calculadas usando o teste de intervalo de confiança (IC) "exato" de Clopper-Pearson de 95% pelo software MEDCALC (Medcalc Software Ltd, Ostend, Bélgica). RESULTADOS: A frequência de ≥ NIC 2 foi 11,7% (21/179). A CH2 para o HPVar e a citologia de repetição para a detecção ≥ NIC 2 obteve, respectivamente, sensibilidade de 90.5% (IC 95% = 69,6­98,8) e 90,5% (IC 95% = 69,6­98,8), especificidade de 65,8% (IC 95% = 57,9­73,2) e 43,7%, (IC 95% = 35,8­51,8), valor preditivo positivo de 26,0% (IC 95% = 21,4­31,3) e 17,6%, (IC95% = 14,9­20,6), e valor preditivo negativo de 98,1% (IC 95% = 93,3­99,5) e 97,2%, (IC 95% = 90,1­99,2). CONCLUSãO: No geral, a CH2 para HPVar aprimora o desempenho para detecção de ≥ NIC 2, sem comprometer a sensibilidade e proporciona maior margem de segurança do retorno ao rastreio trienal de mulheres com anormalidades citológicas prévias, sem ≥ NIC 2 subjacente.

Genotipos de VPH y cambios citológicos cervico-uterino en pacientes de una consulta ginecológica privada del Estado Carabobo, Venezuela. Marzo-octubre de 2017 / HPV genotypes and cervical cytological changes in patients who attended a private gynecology appointment in the state of Carabobo, March-October 2017

Resumen Introducción: La infección genital por el Virus de Papiloma Humano (VPH) se ha asociado con el cáncer cérvicouterino (CCE) al provocar la aparición de lesiones precursoras de cáncer en la zona de transformación de la unión escamo-columnar del cuello uterino. Existen más de 100 tipos de VPH, clasificados en bajo riesgo oncogénico (VPH-BR) y alto riesgo oncogénico (VPH-AR). Estudios reportan la infección por genotipos de alto riesgo en el 100% de los CCE. En Venezuela, el 67,7% de los CCE, se relacionan con el genotipo de VPH-AR 16. Objetivo: Detectar la presencia de VPH en pacientes con cambios citológicos cervicouterino. Metodología: Se incluyeron 49 pacientes que presentaban cambios citológicos, se tomaron las muestras de la región endocervical y exocervical para la detección y genotipificación del virus mediante la técnica de Multiple PCR. Resultados: Las alteraciones citológicas presentes fueron Células Escamosas Atípicas (69,4%), Células Glandulares Atípicas (4,1%), Lesión Escamosa Intraepitelial de Bajo Grado (16,3%), y Lesión Escamosa Intraepitelial de Alto Grado (10,2%). La detección molecular demostró que 16,3% presentaba VPH, 62,5% correspondían a VPH-AR, 25% a VPH-BR, 12,5% al genotipo 16 y no se detectó el genotipo 18. Se reportó un solo caso de coinfección. Conclusiones: A diferencia de otros estudios, no se encontró una relación estadísticamente significativa entre la presencia del virus y la aparición de cambios citológicos cervicouterino en esta población. No obstante, se detectaron genotipos de alto riesgo oncogénico, lo que puede traducirse en una mayor incidencia de cáncer cervicouterino a futuro.

Abstract Introduction: Genital infection by the Human Papilloma Virus (HPV) has been associated with cervical cancer (CC) since it causes the appearance of precursor cancer lesions in the transformation area of ​​the squamous-columnar junction of the cervix. There are more than 100 types of HPV that are classified as low oncogenic risk (LR-HPV) and high oncogenic risk (HR-HPV). Studies report that the infection by high-risk genotypes is present in 100% of CC. In Venezuela, 67.7% of CC is related to the HPV-16 genotype. Objective: This study seeks to detect the presence of HPV in patients with cervical cytological cell changes. Methodology : Forty-nine patients with cytological changes were studied. The endocervical and ectocervical areas were sampled to detect and genotype the virus by using the Multiplex PCR technique. Results: The cytological alterations presented were: Atypical Squamous Cells (69.4%), Atypical Glandular Cells (4.1%), Low-grade Squamous Intraepithelial Lesion (16.3%) and High-grade Squamous Intraepithelial Lesion (10.2%). Besides, the general molecular detection showed that 16.3% had HPV, 62.5% of it corresponded to HR-HPV, 25% to LR-HPV, and 12.5% ​​to genotype 16. The genotype 18 was not detected, and only one co-infection case was reported. Conclusions: Unlike other studies, a statistically significant relationship was not found between the virus presence and the appearance of cervical cytological cell changes in this population. However, genotypes with high oncogenic risk were detected, which may lead to a higher incidence of cervical cancer in the future.

High-risk human papillomavirus testing for triage of women with previous cytological abnormalities from the Vale do Ribeira region / Teste de papilomavírus humano para triagem de mulheres com alterações em citologia anterior provenientes da região do Vale do Ribeira

Abstract Objective To evaluate the performance of the hybrid capture 2 (HC2) high-risk papillomavirus (hrHPV) assay and cytological test in women with previous abnormalities, to detect cervical intraepithelial neoplasia grade 2 or worse (≥ CIN 2). Methods A cytological test and HC2 (Qiagen, Gaithersburg, Maryland, EUA) for hrHPV were conducted in 359 liquid-based (Sure Path, Becton Dickinson, TriPath Imaging, Burlington, NC, USA) samples collected from women from the Vale do Ribeira Region, during July 2013 and September 2015 with previous cytology classified as atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions (ASC-H), and atypical glandular cells (AGC). The histopathological examination was conducted in 179 women. The performance evaluations were calculated using the "exact" Clopper-Pearson 95% confidence interval (CI) test by MEDCALC (Medcalc Software Ltd, Ostend, Belgium). Results The ≥ CIN 2 frequency was 11.7% (21/179). The HC2 for hrHPV and repeat cytology to detect ≥ CIN 2 obtained, respectively, a sensitivity of 90.5% (95% CI = 69.6-98.8) and 90.5%, (95%CI = 69.6-98.8), a specificity of 65.8% (95% CI = 57.9-73.2) and 43.7% (95%CI = 35.8-51.8), a positive predictive value of 26.0% (95% CI = 21.4-31.3) and 17.6%, (95%CI = 14.9-20.6), and a negative predictive value of 98.1% (95%CI = 93.3-99.5) and 97.2% (95% CI = 90.1-99.2). Conclusion Hybrid capture 2 for hrHPV improves the performance of the detection of ≥ CIN 2, without compromising sensitivity, and provides a greater safety margin to return to the triennial screening of women undergoing follow-up due to previous abnormalities, without underlying ≥ CIN 2.

Resumo Objetivo Avaliar o desempenho da captura híbrida 2 (CH2) para papilomavírus humano de alto risco (HPVar) e repetição do exame citopatológico em mulheres com anormalidades em citologia anterior, para detectar neoplasia intraepitelial cervical grau 2 ou pior (≥ NIC 2). Métodos Foi realizado exame citopatológico e CH2 para HPVar (Qiagen, Gaithersburg, Maryland, EUA) em 359 amostras em meio líquido (Sure Path, Becton Dickinson, TriPath Imaging, Burlington, NC, USA) coletadas de mulheres da região do Vale do Ribeira, durante julho de 2013 e setembro de 2015 com citologia anterior classificada como células escamosas atípicas de significado indeterminado (ASC-US), lesão intraepitelial de baixo grau (LSIL), células escamosas atípicas, não podendo excluir lesão de alto grau (ASC-H) e células glandulares atípicas (AGC). O exame histopatológico foi realizado em 179 mulheres. As avaliações de desempenho foram calculadas usando o teste de intervalo de confiança (IC) "exato" de Clopper-Pearson de 95% pelo software MEDCALC (Medcalc Software Ltd, Ostend, Bélgica). Resultados A frequência de≥ NIC 2 foi 11,7% (21/179). A CH2 para o HPVar e a citologia de repetição para a detecção ≥ NIC 2 obteve, respectivamente, sensibilidade de 90.5% (IC 95% = 69,6-98,8) e 90,5% (IC 95% = 69,6-98,8), especificidade de 65,8% (IC 95% = 57,9-73,2) e 43,7%, (IC 95% = 35,8-51,8), valor preditivo positivo de 26,0% (IC 95% = 21,4-31,3) e 17,6%, (IC95% = 14,9-20,6), e valor preditivo negativo de 98,1% (IC 95% = 93,3-99,5) e 97,2%, (IC 95% = 90,1-99,2). Conclusão No geral, a CH2 para HPVar aprimora o desempenho para detecção de ≥ NIC 2, sem comprometer a sensibilidade e proporciona maior margem de segurança do retorno ao rastreio trienal de mulheres com anormalidades citológicas prévias, sem≥ NIC 2 subjacente.

Evaluation of uterine cervical cancer in pregnancy: A cross-sectional study.

OBJECTIVE: Evaluate the prevalence and the regression rate of cytological alteration in pregnant patients below the recommended age by the Brazilian Guidelines for the Screening of Uterine Cervical Cancer Guideline in the prenatal service of Maternidade Escola da Universidade Federal do Rio de Janeiro. STUDY DESIGN: We included the cytopathological exams of all pregnant patients that attended on the outpatient from January 2010 to May 2016. For the identification of the pregnant women, the Management and Integrated System and the Uterine Cervical Cancer Information System of the institution were used. We performed X2 test. The level of significance was 0.05. RESULTS: The study totaled 5825 cytopathological exams, of which 1822 were from pregnant patients ≤ 24 years of age. Only 4.06 % (74/1822) of altered results were found (p < 0.05). The most frequent change was low-grade squamous intraepithelial lesion with a prevalence of 1.92 % (35/1822) whereas high-grade squamous intraepithelial lesion had 0.16 % (3/1822). The regression rate in pregnant patients ≤24 years of age was 34,32 %. CONCLUSION: There was a low prevalence of cytological abnormalities in pregnant patients ≤ 24 years, low frequency of high-grade squamous intraepithelial lesion among the altered cytologies and a high spontaneous regression rate, therefore screening is not recommended before the age determined by the Brazilian Guideline.

Psychosocial impact of inclusion of HPV test on the management of women with atypical squamous cells of undetermined significance: a study within a randomised pragmatic trial in a middle-income country.

Objective: To assess the psychosocial impact of human papillomavirus (HPV) testing, colposcopy, and Pap-smear, as triage strategies after a Pap-smear with atypical squamous cells of undetermined significance (ASCUS). We also sought to evaluate the psychosocial impact based on the results of the strategies. Methods: Nested within a randomised pragmatic trial, which compared an immediate colposcopy, repeat Pap-smear, and high risk HPV test, we enrolled 675 women between 2012 and 2014. Participants completed surveys at enrollment, two weeks after triage test results, and 1 year thereafter to assess cervical cancer and HPV knowledge, self-esteem, anxiety and HPV impact (HIP). Results: Knowledge, self-esteem, anxiety and HIP improved with no differences among arms. At the baseline, 31.4% and 32.7% of the participants had state anxiety and trait anxiety, respectively, which decreased to 10.7% and 13.3% in the last survey. Compared to HPV-negative women, HPV-positive women in the second survey had worse HIP scores (HPV-: M 22.9 [SD: 15.20]; HPV+: M 35.9 [SD: 19.91]; p < 0.001), trait anxiety (HPV-: M 15.4 [SD 12.73]; HPV+: M 22.9 [SD 13.29]; p = 0.001), and state anxiety (HPV-: M 10.7 [SD 11.25]; HPV+: M 21.4 [SD 14.81]; p < 0.001). Conclusions: HPV testing as a triage strategy for women with ASCUS does not differ from colposcopies or Pap-smears in terms of psychosocial outcomes.

Adenocarcinoma cervical: diagnóstico na atenção primária e secundária à saúde / Cervical adenocarcinoma: diagnosis in primary and secondary health care

O adenocarcinoma cervical é uma patologia grave cuja incidência tem aumentado, principalmente em pacientes jovens. Um diagnóstico oportuno, na assistência primária e secundária à saúde, com métodos convencionais, melhora sobremaneira o prognóstico da paciente, a um custo tolerável para países em desenvolvimento.(AU)

The cervical adenocarcinoma is a serious pathology whose incident has increased mainly in young patients. One opportunistic diagnosis, in primary and secondary health care, with conventional methods, greatly improves the prognosis of the patients, at a cost tolerable to developing countries.(AU)

Detection of Zika Virus and Human Papilloma Virus in Cervical Cytology Samples using Two Real Time PCR Based Techniques in Ecuadorian Women diagnosed with ASCUS.

OBJECTIVE: Atypical Squamous Cells of Undetermined Significance(ASCUS) is the most reported result on pap smears. It is most commonly related to Human Papillomavirus (HPV) infections. However, other pathogens (EBV, Chlamydia) have been reported on cervical samples with abnormal results. Zika virus(ZIKV) has been found to induce cellular abnormalities on different tissues and its presence has been identified on genital secretions. METHODS: Two real-time PCR has been made on cervical samples from the gynecological service of a third level hospital on Guayaquil-Ecuador. This work was part of a bigger study of ZIKV presence on different body fluids. RESULTS: From 89 samples obtained, 19 received an ASCUS result. From these 5 were positive for ZIKV and 5 were positive for HPV, there were no co infections. CONCLUSION: Given the presence of ZIKV RNA and the absence of HPV DNA on cervical samples diagnosed as ASCUS, it might be plausible that ZIKV could be a triggering factor for the induction of cellular changes observed on these cells.

Células escamosas atípicas de significado indeterminado (ASC-US): seguimento de exames analisados no Instituto Adolfo Lutz / Atypical squamous cells of indeterminate significance (ASC-US): follow-up of assay in Instituto Adolfo Lutz

Células escamosas atípicas de significado indeterminado (ASC-US) é uma categoria bastante subjetiva, que abrange alterações morfológicas, as quais, qualitativamente ou quantitativamente, são insuficientes para definir uma lesão intraepitelial escamosa. Dados da literatura afirmam que aproximadamente 75% retornam à normalidade após repetição da citologia, porém, parte delas, na histologia, são lesões com alto potencial neo¬plásico. Objetivos: Avaliar o seguimento de mulheres com ASC-US e a adesão às condutas preconizadas. Métodos: Foi realizada busca dos exames posteriores das mulheres com resultado de ASC-US em 2015, atendidas no Núcleo de Anatomia Patológica do Instituto Adolfo Lutz. Foram avaliados o tempo médio de repetição, idade e exame posterior. Resultados: Das 675 mulheres participantes do estudo, 71,7% repetiram a citologia com intervalo médio de 9 meses e média de idade de 37 anos. Na citologia de repetição, 77,7% foram NILM. Dos exames de repetição alterados, 1,7% (8/484) foi HSIL na citologia, 13,3% (4/30) foram NIC e 3,3% (2/3) foram CAI na histologia. Considerando as diretrizes brasileiras, 17,5% das mulheres abaixo dos 25 anos, 39,9% entre 25 e 64 anos e 34,4% acima dos 65 repetiram o exame no intervalo recomendado. Conclusão: A maioria dos resultados posteriores foi negativa, porém, uma parte considerável das mulheres apresentou alteração no exame de repetição. Dos exames histopatológicos realizados, a maioria apresentou resultado de cervicite, porém, foram detectadas lesões mais graves subjacentes em 16,6% destas mulheres, evidenciando a importância do acompanhamento e investigação apropriada.