Neovaginoplasty With Nile Tilapia Skin: Cytological and Microbiota Evaluation.

OBJECTIVES: To study the clinical, cytological, and vaginal microbiota findings in patients with Mayer-Rokitansky-Küster-Hauser syndrome who underwent neovaginoplasty using Nile tilapia fish skin. METHODS: This is a cross-sectional study with 7 cisgender women with Mayer-Rokitansky-Küster-Hauser syndrome who had previously undergone neovagina reconstruction using Nile tilapia fish skin at a university hospital. Local institutional review board approval and written permission from the patient were obtained. Between August 2019 and November 2021, within 12 to 24 months after surgery, vaginal specimens were obtained for conventional oncotic and hormonal cytology, and for Gram staining. The Nugent scores were calculated. Colposcopy was also performed. RESULTS: Squamous cells without atypia were found in all patients. Five patients had intermediate vaginal microbiota (Nugent score of 4), which was determined by the presence of few lactobacilli on Gram staining. In hormonal cytology, 4 patients presented with findings compatible with menacme. No colposcopic change was observed. When postsurgical dilation was performed correctly, a mean vaginal length of 8.3 cm was maintained after 1 year of follow-up. CONCLUSIONS: Squamous cells without atypia were present in neovaginas with Nile tilapia fish skin. Most vaginal contents revealed intermediate microbiota and hormonal results compatible with menacme. Studies with a greater number of patients are necessary for a more comprehensive understanding of the microbiome in neovaginas with this new technique, thereby providing support for the treatment and prevention of associated pathologies.

Anal High-risk HPV and Liquid-based Cytology of Immunocompetent Brazilian Women with Genital High-risk HPV / HPV de alto risco e citologia em meio líquido de canal anal de mulheres brasileiras imunocompetentes com HPV genital de alto risco

Abstract Objective The purpose of this study was to compare the frequency of the occurrence of high-risk human papillomavirus (HPV) and abnormal anal cytology in immunocompetent women with and without HPV-induced genital lesions. Methods This analytical cross-sectional, observational study was conducted between July 2017 and December 2018 in a specialized outpatient clinic of a tertiary hospital in Fortaleza, CE. Fifty-seven immunocompetent women with and without genital intraepithelial lesions were assessed; they were divided into two groups: group 1 was comprised of women with HPV-associated genital lesions (n=26), and group 2 was comprised of those without HPV-associated genital lesions (n=31). Samples for liquidbased cytology and high-risk DNA-HPV polymerase chain reaction real-time tests were collected from the cervix and anus. All cases were evaluated using high-resolution anoscopy; biopsies were performed when required. The Fisher exact and chi-squared tests were applied for consolidated data in the contingency table, and the Student ttest and Mann-Whitney U-test for independent variables. Results Anal high-risk HPV infections were more frequent in group 1 (odds ratio [OR], 4.95; 95% confidence interval [CI], 1.34-18.3; p=0.012), along with concomitant highrisk HPV infections in the uterine cervix and the anus (OR 18.8; 95% CI, 2.20-160; p<0.001). The incidence of high-risk cervical HPV infection was associated with highrisk anal HPV infection (OR, 4.95; 95% CI, 1.34-18.3; p=0.012). There was no statistical difference concerning abnormal anal cytology or anoscopy between the groups, and no anal intraepithelial lesion was found in either group. Conclusion Immunocompetent women with HPV-associated genital lesions and high-risk cervical HPV were more likely to have high-risk anal HPV.

Resumo Objetivo O objetivo deste estudo foi comparar a frequência de papilomavírus humano (HPV) de alto risco e citologia anal anormal em mulheres imunocompetentes com e sem lesões genitais induzidas por HPV. Métodos Este estudo transversal analítico e observacional foi realizado entre julho de 2017 e dezembro de 2018 em um ambulatório especializado de um hospital terciário em Fortaleza, CE. Cinquenta e sete mulheres imunocompetentes com e sem lesões intraepiteliais genitais foram avaliadas. Foram divididas em dois grupos: grupo 1, composto por mulheres com lesões genitais associadas ao HPV (n=26) e grupo 2, composto pormulheres sem lesões genitais associadas ao HPV (n=31). Amostras para citologia em meio líquido e testes de reação em cadeia da polimerase em tempo real para DNA-HPV de alto risco foram coletadas do colo do útero e do ânus. Todos os casos foram avaliados por anuscopia de alta resolução; sendo realizada biópsia quando necessária. Os testes exatos de Fisher e qui-quadrado foram aplicados para dados consolidados na tabela de contingência; o teste t de Student e o teste U de Mann-Whitney foram aplicados para variáveis independentes. Resultados As infecções anais por HPV de alto risco forammais frequentes no grupo 1 (razão de chances [RC], 4,95; intervalo de confiança [IC] de 95%, 1,34-18,3; p=0,012), assim como infecções concomitantes por HPV de alto risco em colo uterino e ânus (RC 18,8; IC de 95%, 2,20-160; p<0,001). A incidência de infecção de HPV cervical de alto risco foi associada à infecção de HPV anal de alto risco (RC, 4,95; IC de 95%, 1,34-18,3; p=0,012). Não houve diferença estatística em relação à citologia anal anormal ou anuscopia entre os grupos, e não houve caso de lesão intraepitelial anal em nenhum dos grupos. Conclusão Mulheres imunocompetentes com lesões genitais associadas ao HPV e com HPV cervical de alto risco foram mais propensas a ter HPV anal de alto risco.

Anal High-risk HPV and Liquid-based Cytology of Immunocompetent Brazilian Women with Genital High-risk HPV.

OBJECTIVE: The purpose of this study was to compare the frequency of the occurrence of high-risk human papillomavirus (HPV) and abnormal anal cytology in immunocompetent women with and without HPV-induced genital lesions. METHODS: This analytical cross-sectional, observational study was conducted between July 2017 and December 2018 in a specialized outpatient clinic of a tertiary hospital in Fortaleza, CE. Fifty-seven immunocompetent women with and without genital intraepithelial lesions were assessed; they were divided into two groups: group 1 was comprised of women with HPV-associated genital lesions (n = 26), and group 2 was comprised of those without HPV-associated genital lesions (n = 31). Samples for liquid-based cytology and high-risk DNA-HPV polymerase chain reaction real-time tests were collected from the cervix and anus. All cases were evaluated using high-resolution anoscopy; biopsies were performed when required. The Fisher exact and chi-squared tests were applied for consolidated data in the contingency table, and the Student t-test and Mann-Whitney U-test for independent variables. RESULTS: Anal high-risk HPV infections were more frequent in group 1 (odds ratio [OR], 4.95; 95% confidence interval [CI], 1.34-18.3; p = 0.012), along with concomitant high-risk HPV infections in the uterine cervix and the anus (OR 18.8; 95% CI, 2.20-160; p < 0.001). The incidence of high-risk cervical HPV infection was associated with high-risk anal HPV infection (OR, 4.95; 95% CI, 1.34-18.3; p = 0.012). There was no statistical difference concerning abnormal anal cytology or anoscopy between the groups, and no anal intraepithelial lesion was found in either group. CONCLUSION: Immunocompetent women with HPV-associated genital lesions and high-risk cervical HPV were more likely to have high-risk anal HPV.

OBJETIVO: O objetivo deste estudo foi comparar a frequência de papilomavírus humano (HPV) de alto risco e citologia anal anormal em mulheres imunocompetentes com e sem lesões genitais induzidas por HPV. MéTODOS: Este estudo transversal analítico e observacional foi realizado entre julho de 2017 e dezembro de 2018 em um ambulatório especializado de um hospital terciário em Fortaleza, CE. Cinquenta e sete mulheres imunocompetentes com e sem lesões intraepiteliais genitais foram avaliadas. Foram divididas em dois grupos: grupo 1, composto por mulheres com lesões genitais associadas ao HPV (n = 26) e grupo 2, composto por mulheres sem lesões genitais associadas ao HPV (n = 31). Amostras para citologia em meio líquido e testes de reação em cadeia da polimerase em tempo real para DNA-HPV de alto risco foram coletadas do colo do útero e do ânus. Todos os casos foram avaliados por anuscopia de alta resolução; sendo realizada biópsia quando necessária. Os testes exatos de Fisher e qui-quadrado foram aplicados para dados consolidados na tabela de contingência; o teste t de Student e o teste U de Mann-Whitney foram aplicados para variáveis independentes. RESULTADOS: As infecções anais por HPV de alto risco foram mais frequentes no grupo 1 (razão de chances [RC], 4,95; intervalo de confiança [IC] de 95%, 1,34­18,3; p = 0,012), assim como infecções concomitantes por HPV de alto risco em colo uterino e ânus (RC 18,8; IC de 95%, 2,20­160; p < 0,001). A incidência de infecção de HPV cervical de alto risco foi associada à infecção de HPV anal de alto risco (RC, 4,95; IC de 95%, 1,34­18,3; p = 0,012). Não houve diferença estatística em relação à citologia anal anormal ou anuscopia entre os grupos, e não houve caso de lesão intraepitelial anal em nenhum dos grupos. CONCLUSãO: Mulheres imunocompetentes com lesões genitais associadas ao HPV e com HPV cervical de alto risco foram mais propensas a ter HPV anal de alto risco.

Comparative measurement of D- and L-lactic acid isomers in vaginal secretions: association with high-grade cervical squamous intraepithelial lesions.

PURPOSE: Identification of low-cost protocols to identify women at elevated susceptibility to develop cervical intra-epithelial abnormalities would aid in more individualized monitoring. We evaluated whether quantitation of the D- and L-lactic acid isomers in vaginal secretions could differentiate women with normal cervical epithelia from those with a low (LSIL) or high (HSIL) grade squamous intraepithelial lesion or with cervical cancer. METHODS: Vaginal samples, collected from 78 women undetgoing cervical colposcopy and biopsy, were tested for pH, bacterial composition by Gram stain (Nugent score) and concentrations of D- and L-lactic acid by a colorimetric assay. RESULTS: Subsequent diagnosis was 23 women with normal cervical epithelium, 10 with LSIL, 43 with HSIL and 2 with cervical cancer. Vaginal pH and Nugent score were comparable in all subject groups. The concentration of L-lactic acid, but not D-lactic acid, as well as the L/D-lactic acid ratio, were significantly elevated (p < 0.01) in women with HSIL and cervical cancer. CONCLUSION: Comparative measurement of vaginal D- and L-lactic acid isomers may provide a low-cost alternative to identification of women with an elevated susceptibility to cervical abnormalities.

Prevalence of Trichomonas vaginalis in women attended at a private laboratory / Prevalência de Trichomonas vaginalis em mulheres atendidas em um laboratório privado

Introduction: Sexually Transmitted Infections (STIs) are caused by viruses, fungi, bacteria, or other microorganisms, thus being a serious public health issue. Trichomonas vaginalis is the disease causative agent of trichomoniasis, a worldwide protozoan. The prevalence of trichomoniasis depends on some factors, including age, sexual activity, number of sexual partners, hygiene habits, among others. Objective: To evaluate the prevalence of Trichomonas vaginalis in gynecological cytology in a private laboratory in the city of Fortaleza, state of Ceará, Brazil. Methods: This is a retrospective, quantitative, and descriptive study carried out in a private laboratory in Fortaleza, state of Ceará. Data for the research, such as age, marital status, and symptoms, were collected from the patients' medical records as well as the prevalence of cases in liquid-based cytology (LBC) and conventional cytology (CC). Results: In 2019, 83 women were positive for trichomoniasis. The most prevalent age group was between 36 and 51 years old (41%), with an average of 39.9 years old. Regarding symptoms, 14 (16.8%) were asymptomatic and 41 (49.3%) had some symptom. Conclusion: The data obtained in this study describe the profile of women affected by Trichomonas vaginalis.

As infecções sexualmente transmissíveis são causadas por vírus, fungos, bactérias ou outros microrganismos, sendo assim um grave problema de saúde pública. O Trichomonas vaginalis, um protozoário presente em todo o mundo, é o agente etiológico causador da tricomoníase. A prevalência dessa doença depende de alguns fatores, incluindo idade, atividade sexual, números de parceiros sexuais, hábitos de higiene, entre outros. Objetivo: Avaliar a prevalência de Trichomonas vaginalis, em citologia ginecológica em um laboratório privado em Fortaleza, Ceará, Brasil. Métodos: Trata-se de estudo retrospectivo, quantitativo e descritivo realizado em laboratório privado em Fortaleza. Os dados para a pesquisa, como idade, estado civil, sintomas, foram retirados de prontuários das pacientes, assim como a prevalência de casos em citologia em meio líquido e CO. Resultados: No ano de 2019, 83 mulheres apresentaram positividade para tricomoníase. A faixa etária mais prevalente foi a de 36 a 51 anos (41%), ficando com a média de 39,9 anos. Em relação aos sintomas, 14 (16,8%), apresentaram-se assintomáticas e 41 (49,3%) apresentaram algum sintoma. Conclusão: Os dados obtidos neste estudo descrevem o perfil das mulheres acometidas pelo Trichomonas vaginalis.

What influence does vaginal microbiota have on human papillomavirus nfection? / Que influência a microbiota vaginal tem sobre a infecção por Papilomavírus humano?

Introduction: The human body is colonized by trillions of microbial cells, called the microbiota. The microbiome is defined as microbial cells and their genomes. Vaginal microbiota, especially lactic acid bacteria (mainly Lactobacillus sp.), seem to play a critical role in the prevention of various urogenital diseases such as bacterial vaginosis, fungal infections, sexually transmitted diseases, urinary tract infections, and human papillomaviridae (HPV) infections. Changes in the vaginal microbiome contribute to the development of precancerous cervical lesions. Objective: To evaluate studies associating the vaginal microbiota with HPV, including the risk and persistence of infection and evolution to squamous intraepithelial lesions of the cervix. Methods: A systematic review was conducted based on articles published between September 2011 and September 2019, using the following keyword combinations: "HPV [All Fields] AND "microbiota" [MeSH Terms] OR "microbiota" [All Fields] OR "microbiome" [All Fields])." The keyword search was performed in the MEDLINE, Latin American, and Caribbean Literature in Health Sciences (Lilacs), Cochrane Library, Highwire Stanford, and Embase databases. Results: In total, 239 original articles published between 2011 and 2019 were found in the researched databases on microbiome/microbiota and HPV. After exclusion, only six articles remained. Conclusion: There is a relationship between HPV and the cervicovaginal microbiota, but the mechanism of this influence cannot be specified.

Introdução: O corpo humano é colonizado por trilhões de células microbianas, denominadas microbiota. Microbioma é definida como células microbianas e seus genomas. A microbiota vaginal, especialmente as bactérias produtoras de ácido lático (principalmente Lactobacillus sp.), parece desempenhar um papel crítico na prevenção de várias doenças urogenitais, como a vaginose bacteriana, infecções fúngicas, doenças sexualmente transmissíveis, infecções do trato urinário e infecção pelo Papilomavírus humano (HPV). As alterações no microbioma vaginal parecem contribuir para o desenvolvimento de lesões cervicais pré-cancerosas. Objetivo: Avaliar estudos que associem a microbiota vaginal ao risco de infecção por HPV, sua persistência e evolução para lesões escamosas intraepiteliais do colo do útero. Métodos: Esta é uma revisão sistemática desenvolvida com base em artigos publicados entre setembro de 2011 e setembro de 2019, usando as seguintes combinações de palavras-chave: "HPV" [Todos os Campos] AND ("microbiota" [Termos MeSH] OU "microbiota" [Todos os Campos] OU "microbioma" [All Fields]) nas bases de dados MEDLINE, Latin American and Caribean Health Sciences Literature (Lilacs), Cochrane Library, Highwire Stanford e Embase. Resultados: Entre 2011 e 2019, foram encontrados 239 artigos originais nas bases de dados pesquisadas sobre microbioma/microbiota e HPV. Desse total, após o uso dos critérios de exclusão, restaram apenas seis artigos. Conclusão: Existe uma relação entre o HPV e a microbiota cervicovaginal, mas não foi possível especificar qual mecanismo está envolvido.

HPV infection and endometriosis: a systematic review and meta-analysis / Infecção por HPV e endometriose: uma revisão sistemática e meta-análise

Introduction: Recent research has focused on the role of persistent ascending bacterial infections and Sexually Transmitted Infections (STI) as an associated factor of endometriosis. Indeed, some studies investigated the possible role of HPV in endometriosis, but this topic remains inconclusive. Objective: The present study aims to meta-analyze research that assessed the presence of HPV infection in patients with endometriosis. Methods: MEDLINE, Embase, Scopus, LILACS, Cochrane Library, and OpenGrey were searched until February 10th, 2020. Search terms included "endometriosis" and "HPV" without language restrictions. Pooled relative risks and 95% confidence interval (95%CI) were calculated, and heterogeneity was assessed with I-squared (I2 ). Results: The meta-analysis with low heterogeneity found a twice as much relative risk in women exposed to HPV in relation to the unexposed control. Conclusion: The results indicate that HPV could be a risk factor for the development of endometriosis

Introdução: Pesquisas recentes enfocaram o papel das infecções bacterianas ascendentes persistentes e das infecções sexualmente transmissíveis (IST) como um fator associado à endometriose. De fato, alguns estudos investigaram o possível papel do HPV na endometriose, embora o tópico permaneça inconclusivo. Objetivo: O presente estudo tem como objetivo meta-analisar pesquisas que avaliaram a presença de infecção por HPV em pacientes com endometriose. Métodos: Foram realizadas buscas nas bases MEDLINE, Embase, Scopus, LILACS, Biblioteca Cochrane e OpenGrey até 10 de fevereiro de 2020. Os termos de pesquisa incluíram "endometriose" e "HPV" sem restrição de idioma. Riscos relativos agrupados e intervalo de confiança de 95% (IC 95%) foram calculados, e a heterogeneidade foi avaliada com I-quadrado (I2 ). Resultados: A meta-análise com baixa heterogeneidade encontrou um risco relativo duas vezes maior em mulheres expostas ao HPV em relação ao controle não exposto. Conclusão: Os resultados indicam que o HPV pode ser um fator de risco para o desenvolvimento de endometriose.

HPV infection and endometriosis: a systematic review and meta-analysis / Infecção por HPV e endometriose: uma revisão sistemática e metanálise

Introduction: Recent research has focused on the role of persistent ascending bacterial infections and sexually transmitted infections (STI) as a factor associated to endometriosis. Indeed, some studies investigated the possible role of HPV in endometriosis, but this topic remains inconclusive. Objective:The present study aims to meta-analyze research that assessed the presence of HPV infection in patients with endometriosis. Methods: MEDLINE, Embase, Scopus, LILACS, Cochrane Library, and OpenGrey were searched until February 10th, 2020. Search terms included "endometriosis" and "HPV" without language restrictions. The combined relative risks and 95% confidence interval (95%CI) were calculated, and heterogeneity was assessed with I-square (I2 ). Results: Meta-analysis with low heterogeneity found a relative risk of twice as much in women exposed to HPV in relation to the unexposed control. Conclusion: Results indicate that HPV could be a risk factor for developing endometriosis.

Introdução: A pesquisa recente enfocou o papel de infecções por bactéria ascendente persistente e infecções sexualmente transmissíveis (IST) como um dos fatores associados à endometriose. Na verdade, alguns estudos investigaram o possível papel do HPV na endometriose, mas esse tópico permanece inconclusivo. Objetivo: O presente estudo tem como objetivo fazer uma metanálise de pesquisas que avaliaram a presença de infecção por HPV em pacientes com endometriose. Métodos: As bases de dados MEDLINE, Embase, Scopus, LILACS, Biblioteca Cochrane e OpenGrey foram pesquisadas até 10 de fevereiro de 2020. Os termos de pesquisa incluíram "endometriose" e "HPV" sem restrições de idioma. Os riscos relativos combinados e intervalo de confiança de 95% (IC95%) foram calculados, e a heterogeneidade foi avaliada usando o I-quadrado (I2 ). Resultados: A metanálise com baixa heterogeneidade encontrou um risco relativo duas vezes maior em mulheres expostas ao HPV em relação ao controle não exposto. Conclusão: Os resultados indicam que o HPV pode ser um fator de risco para o desenvolvimento de endometriose.

The frequency of in Pap smear and liquid-based cytology (SurePath ) between 2013 and 2018 in a reference laboratory in Fortaleza, Brazil / Frequência de Trichomonas vaginalis no exame de Papanicolaou e citologia em base líquida (SurePathTM) entre 2013 e 2018 em um laboratório de referência em Fortaleza, Brasil

Introduction: Trichomonas vaginalis (Tv) is a parasite responsible for the most frequent non-viral sexually transmitted infection and causes more than 250 million new cases around the world each year. Frequently, Tv is identified in cervical cancer screening. Objective: To assess the frequency of Tv identified on cytology between 2013 and 2018 in a private Laboratory at Fortaleza, Brazil. Methods: Cases from the files of a laboratory in Fortaleza, Brazil, were searched for diagnoses of Tv on cytology (Pap smear and SurePathTM [SP]) between 2013 and 2018, and the frequency of infection in each year, as well as differences between the years, were calculated. A linear regression test was performed to analyze the relationship between time and infection with a 95% confidence interval. The research was approved by an ethics committee. Results: The mean age of the patients was 35.9 (+12.5) years in the Pap smear group and 33.4(+11.9) years in the liquid-based cytology group. Tv was diagnosed in 281 of 207,863 patients (0.14%) (113 [0.12%] in the Pap smear group and 168 [0.15%] in SP cytology). Assessing year by year differences, it was observed that Tv was identified on cytology in 36 of 33,193 in 2013 (0.1%) (Pap smear=19/ 19,734 [0.1%]; SP=17/ 13,459 [0.13%], 50 of 34,661 in 2014 (0.14%) (Pap smear=22/ 16,358 [0.13%]; SP=28/ 18,303 [0.15%]), 34 of 33,623 in 2015 (0.1%) (Pap smear=10/ 14,501 [0.07%]; SP=24/ 19,122 [0.13%]), 29 of 34,492 in 2016 (0.1%) (Pap smear=9/ 15,629 [0.06%]; SP=20/ 18,863 [0.1%]), 52 of 35,446 in 2017 (0.15%) (Pap smear=22/ 15,948 [0.14%]; SP=30/ 19,498 [0.15%], and 80 of 36,448 in 2018 (0.22%) (Pap smear=31/ 15,408 [0.2%]; SP=49/ 21,040 [0.23%]). Conclusion: There was a tendency towards increased frequency of Tv diagnosis in the gynecologic cytology group (Pap smear or SP), mainly in the last year, reflecting what is observed using more sensitive methods.

Introdução: Trichomonas vaginalis (Tv) é um parasita responsável pela infecção sexualmente transmissível não viral mais frequente e incidindo em mais de 250 milhões de novos casos a cada ano no mundo. Frequentemente, o Tv é identificado no rastreamento citológico do câncer de colo do útero. Objetivo: Avaliar a frequência de Tv identificada por citologia entre 2013 e 2018 em um laboratório privado em Fortaleza, Brasil. Métodos: Foram pesquisados casos dos prontuários de um laboratório em Fortaleza, Brasil, para dianóstico de Tv por citologia (exame de Papanicolaou ou SurePathTM [SP]) entre 2013 e 2018, e foram calculados a frequência da infecção a cada ano bem como as diferenças entre eles. Um teste de regressão linear foi aplicado para analizar a relação entre o tempo e a infecção com intervalo de confiança de 95%. A pesquisa foi aprovada pelo comitê de ética. Resultados: A idade média das pacientes foi 35.9 (+12.5) anos na citologia convencional (CC) e 33.4 (+11.9) anos no grupo de citologia em meio líquido. Tv foi diagnosticada em 281 de 207.863 pacientes (0,14%) (113 [0,12%] no grupo de CC e 168 [0,15%] no grupo de SP). Avaliando ano a ano, foi observado que o Tv foi identificado em 36 de 33.193 em 2013 (0,1%) (CC=19/ 19.734 [0,1%]; SP=17/ 13.459 [0,13%], 50 de 34.661 em 2014 (0,14%) (CC=22/ 16.358 [0,13%]; SP=28/ 18.303 [0,15%]), 34 de 33.623 em 2015 (0,1%) (CC=10/ 14.501 [0,07%]; SP=24/ 19.122 [0,13%]), 29 de 34.492 em 2016 (0,1%) (CC=9/ 15.629 [0,06%]; SP=20/ 18.863 [0,1%]), 52 de 35.446 em 2017 (0,15%) (CC=22/ 15.948 [0,14%]; SP=30/ 19.498 [0,15%], e 80 de 36.448 em 2018 (0,22%) (CC=31/ 15.408 [0,2%]; SP=49/ 21.040 [0,23%]). Conclusão: Há a tendência de aumento na frequência de diagnóstico de Tv na citologia (Papanicolaou ou SP), principalmente no último ano, refletindo o que já tem sido observado por métodos mais sensíveis.

Atypical Squamous Cells: Cytopathological Findings and Correlation with HPV Genotype and Histopathology.

OBJECTIVE: We aimed to assess potential associations between atypical squamous cell (ASC) subgroups: ASC-US (undetermined significance) and ASC-H (cannot exclude high-grade squamous intraepithelial lesion), regarding cytomorphological features, high-risk (HR) human papillomavirus (HPV) testing, and histological outcomes in a sample of Brazilian women. STUDY DESIGN: Cross-sectional study which evaluated 1,346 liquid-based cytologies between January 2010 and July 2016 with ASC results. ASC-US and ASC-H were analyzed for frequency, diagnostic criteria, and cytological findings and compared with HR-HPV tests and histological outcomes. RESULTS: Enlarged nucleus was the most frequent ASC-US criterion, but alternative criteria were present in 20% of the total cases. No ASC-US criteria were associated with histological outcomes or HR-HPV positivity. Parakeratosis, corneal pearl, giant cells, and binucleation were strongly associated with ASC-US while hyperkeratosis was associated with high-grade squamous intraepithelial lesions (HSIL) or a superior outcome. HR-HPV was positive in 64.39% of ASC-US and 65.38% of ASC-H. HSIL or superior outcomes also occurred in 13.33% of ASC-US and 64.71% of ASC-H cases. CONCLUSION: Alternative criteria for ASC-US were relatively frequent. Reactive cellular changes suggestive of atypias were more abundant in ASC-US. Although ASC-H is associated with worse histological outcomes, no differences in HPV positivity were found in comparison to ASC-US.

Management of Atypical Squamous Cell Cases: A Prospective Study of Women seen at a Private Health Service in Northeastern Brazil.

OBJECTIVE: To assess the management chosen by gynecologists after atypical squamous cells (ASCs) cytology results, and to evaluate the outcomes of these cases in Brazilian women. METHODS: A prospective observational study evaluated the initial management offered by the gynecologist in the case of 2,458 ASCs cytology results collected between January of 2010 and July of 2016. The outcomes of the cytology, high-risk human papilloma virus (HR-HPV) test and histology were compared in two subgroups: atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H). RESULTS: In many cases of ASC-US (36.97%) and ASC-H (40.50%), no clinical actions were taken. Cytology was the most frequent follow-up chosen, including for cases of ASC-H, which goes against the conduct recommended in the national guideline. In women over 30 years of age, the period of time elapsed between an ASC-US result and a new cytology was in 13.03 months, in disagreement with the national guideline recommendations (p < 0.0001). Negative for intraepithelial lesions or malignancy (NILM) cytologic (p = 0.0026) and histologic (p = 0.0017) results in the follow-up were associated with prior ASC-US, while negative results for ASC-H were cytologically (p < 0.0001) and histologically associated with high-grade squamous intraepithelial lesion (HSIL) (p < 0.0001). Two invasive cervical carcinomas (ICCs) were found in the follow-up for ASC-H, and there was a statistically significant association (p = 0.0341). A positive HR-HPV test was associated with ASC-H (p = 0.0075). CONCLUSION: The data suggest that even for a population of Brazilian women assisted at private clinics, the national guidelines recommendations for ASCs results are not followed.

OBJETIVO: Avaliar a conduta adotada por ginecologistas após resultados citológicos apresentando células escamosas atípicas (ASCs) e os desfechos destes casos em mulheres brasileiras. MéTODOS: Um estudo observacional prospectivo avaliou o manejo clínico inicial do ginecologista nos casos de 2.458 resultados citológicos apresentando ASCs coletados entre janeiro de 2010 e julho de 2016. Os respectivos desfechos citológicos, histológicos e de detecção do papilomavírus humano (HPV) foram comparados entre os subgrupos células escamosas atípicas de significado indeterminado (ASC-US) e células escamosas atípicas não podendo excluir lesão intraepitelial de alto grau (ASC-H). RESULTADOS: Nenhuma conduta foi adotada em 36,97% de citologias do tipo ASC-US e 40,5% do tipo ASC-H. A conduta mais escolhida foi a repetição da citologia, inclusive para acompanhamento de ASC-H, o que contraria as diretrizes nacionais. O tempo de realização de uma nova citologia para resultado do tipo ASC-US em mulheres com mais de 30 anos de idade foi de 13,03 meses, também em desacordo com as diretrizes (p < 0,0001). Resultados negativos para lesão intraepitelial ou neoplasia maligna (NILM), tanto citológicos (p = 0,0026) como histológicos (p = 0,0017), foram associados a ASC-US, enquanto que resultados negativos para lesões intraepiteliais escamosas de alto grau (HSILs), citológicos (p < 0,0001) e histológicos, foram associados a ASC-H (p < 0,0001). Dois carcinomas cervicais invasivos foram encontrados durante o acompanhamento para ASC-H e uma associação estatisticamente significante foi estabelecida (p = 0,0341). Um teste de HR-HPV positivo foi associado a ASC-H (p = 0,0075). CONCLUSãO: Os dados sugerem que mesmo para uma população de mulheres brasileiras atendidas em clínicas privadas, as recomendações das diretrizes clínicas nacionais para resultados citológicos apresentando ASCs não são seguidas.

Management of atypical squamous cell cases: A prospective study of women seen at a private health service in northeastern Brazil / Conduta em casos de células escamosas atípicas: um estudo prospectivo de mulheres atendidas pelo serviço de saúde privado no nordeste do Brasil

Abstract Objective To assess the management chosen by gynecologists after atypical squamous cells (ASCs) cytology results, and to evaluate the outcomes of these cases in Brazilian women. Methods A prospective observational study evaluated the initial management offered by the gynecologist in the case of 2,458 ASCs cytology results collected between January of 2010 and July of 2016. The outcomes of the cytology, high-risk human papilloma virus (HR-HPV) test and histology were compared in two subgroups: atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H). Results In many cases of ASC-US (36.97%) and ASC-H (40.50%), no clinical actions were taken. Cytology was the most frequent follow-up chosen, including for cases of ASC-H, which goes against the conduct recommended in the national guideline. In women over 30 years of age, the period of time elapsed between an ASC-US result and a new cytology was in 13.03 months, in disagreement with the national guideline recommendations (p< 0.0001). Negative for intraepithelial lesions or malignancy (NILM) cytologic (p = 0.0026) and histologic (p = 0.0017) results in the follow-up were associated with prior ASC-US, while negative results for ASC-H were cytologically (p< 0.0001) and histologically associated with high-grade squamous intraepithelial lesion (HSIL) (p< 0.0001). Two invasive cervical carcinomas (ICCs) were found in the follow-up for ASC-H, and there was a statistically significant association (p = 0.0341). A positive HR-HPV test was associated with ASC-H (p = 0.0075). Conclusion The data suggest that even for a population of Brazilian women assisted at private clinics, the national guidelines recommendations for ASCs results are not followed.

Resumo Objetivo Avaliar a conduta adotada por ginecologistas após resultados citológicos apresentando células escamosas atípicas (ASCs) e os desfechos destes casos em mulheres brasileiras. Métodos Um estudo observacional prospectivo avaliou o manejo clínico inicial do ginecologista nos casos de 2.458 resultados citológicos apresentando ASCs coletados entre janeiro de 2010 e julho de 2016. Os respectivos desfechos citológicos, histológicos e de detecção do papilomavírus humano (HPV) foram comparados entre os subgrupos células escamosas atípicas de significado indeterminado (ASC-US) e células escamosas atípicas não podendo excluir lesão intraepitelial de alto grau (ASC-H). Resultados Nenhuma conduta foi adotada em 36,97% de citologias do tipo ASC-US e 40,5% do tipo ASC-H. A conduta mais escolhida foi a repetição da citologia, inclusive para acompanhamento de ASC-H, o que contraria as diretrizes nacionais. O tempo de realização de uma nova citologia para resultado do tipo ASC-US em mulheres com mais de 30 anos de idade foi de 13,03 meses, também em desacordo com as diretrizes (p< 0,0001). Resultados negativos para lesão intraepitelial ou neoplasia maligna (NILM), tanto citológicos (p = 0,0026) como histológicos (p = 0,0017), foram associados a ASC-US, enquanto que resultados negativos para lesões intraepiteliais escamosas de alto grau (HSILs), citológicos (p< 0,0001) e histológicos, foram associados a ASC-H (p< 0,0001). Dois carcinomas cervicais invasivos foram encontrados durante o acompanhamento para ASC-H e uma associação estatisticamente significante foi estabelecida (p = 0,0341). Um teste de HR-HPV positivo foi associado a ASC-H (p = 0,0075). Conclusão Os dados sugerem que mesmo para uma população de mulheres brasileiras atendidas em clínicas privadas, as recomendações das diretrizes clínicas nacionais para resultados citológicos apresentando ASCs não são seguidas.

Atypical Squamous Cells in Liquid-Based Cervical Cytology: Microbiology, Inflammatory Infiltrate, and Human Papillomavirus-DNA Testing.

OBJECTIVE: The aim of this study was to assess the correlation between atypical squamous cells (ASC) and inflammatory infiltrate and vaginal microbiota using cervical liquid-based cytological (SurePath®) and high-risk human papillomavirus (HR-HPV) tests. STUDY DESIGN: A cross-sectional study was conducted using a 6-year database from a laboratory in Fortaleza (Brazil). Files from 1,346 ASC cases were divided into subgroups and results concerning inflammation and vaginal microorganisms diagnosed by cytology were compared with HR-HPV test results. RESULTS: An absence of specific microorganisms (ASM) was the most frequent finding (ASC of undetermined significance, ASC-US = 74%; ASC - cannot exclude high-grade squamous intraepithelial lesion, ASC-H = 68%), followed by bacterial vaginosis (ASC-US = 20%; ASC- H = 25%) and Candida spp. (ASC-US = 6%; ASC-H = 5%). Leukocyte infiltrate was present in 71% of ASC-US and 85% of ASC-H (p = 0.0040), and in these specific cases HR-HPV tests were positive for 65 and 64%, respectively. A positive HR-HPV test was relatively more frequent when a specific microorganism was present, and Candida spp. was associated with HR-HPV-positive results (p = 0.0156), while an ASM was associated with negative HR-HPV results (p = 0.0370). CONCLUSION: ASC-US is associated with an absence of inflammation or vaginosis, while ASC-H smears are associated with Trichomonas vaginalis and inflammatory infiltrate. A positive HR-HPV is associated with Candida spp. in ASC cytology.

Inflammatory cells in liquid-based cytology smears classified as bacterial vaginosis.

BACKGROUND: Bacterial vaginosis (BV) remains an enigmatic question. The term "osis" instead of "itis" is used because commonly, there are no inflammatory process associated with BV. However, leukocytes are often observed in it. METHODS: In a transversal study, we evaluated 1178 cases with diagnosis of BV by liquid-based cytology (more than 20% of clue cells), attended in general gynecologic private clinic. Depending of the presence of more than five leukocytes on average per field in immersion objective (1000×), the cases were divided in two groups: few or no leukocytes (< 5 leukocytes per field) (BV) and with leukocytes (≥ 5 leukocytes per field) (BV-L). The Fisher exact and Student t tests was applied to a confidence interval of 95%. The project was approved by the Ethic Committee of Federal University of Ceará, Brazil. RESULTS: The age between the groups was the only different socio-demographic variable. The assessment of vaginal discharge aspect had no characteristic aspect. Colposcopy findings suggesting colpitis and ectopy were more frequent in the group of BV-L, 7.1% and 6.9%, respectively. The study of the microbiology demonstrated in the BV-L group, more frequently co-occurrence of Candida sp (15.1%) than in BV group (1.5%) (P < .0001). The cellular atypia was present more frequently in the BV-L (9.6%) than in BV (5.7%) (P = .0116). CONCLUSION: The presence of leukocytes in BV (or BV-L) may suggest a mixed infection, ectopy influencing the vaginal milieu and even epithelial atypia.

Frequência sazonal de vaginose bacteriana e Candida sp em esfregaços citológicos de laboratório privado na cidade de Fortaleza entre 2012 e 2015 / Sazonal frequency of Bacterial vaginosis and Candida sp in Pap smears observed in a private laboratory in Fortaleza, Brazil, from 2012 to 2015

As mais frequentes queixas ginecológicas estão associadas a infecções genitais, que afetam a microbiota vaginal, ou seja, vaginites e vaginoses. A vaginose bacteriana (VB) é caracterizada por uma mudança da microbiota vaginal de bactérias aeróbias para anaeróbias. Já a candidíase vulvovaginal (CVV) é um distúrbio ocasionado pelo crescimento anormal de fungos do tipo leveduras na mucosa do trato genital feminino. Objetivo: Identificar a frequência de VB e Candida sp em exames citológicos (Papanicolaou) em uma cidade no nordeste do Brasil, conforme os meses do ano em um período de quatro anos. Métodos: Estudo de frequência da identificação de VB e Candida sp em exames de citologia oncótica do banco de dados do Laboratório Professor Eleutério em Fortaleza entre os anos de 2012 e 2015. Resultados: Os casos avaliados tinham entre 14 e 54 anos, média de 34,7 anos. Em 2012, o mês de agosto teve maior frequência de VB (62,96%), e o mês de março teve a maior frequência de Candida sp (42,35%). No ano de 2013, VB foi mais prevalente em setembro (61,98%) e Candida sp em agosto (47,26%). Já em 2014, o mês de junho teve maior frequência VB (60,47%), e setembro maior frequência de Candida sp (43,30%). Em 2015, foi abril o mês em que mais se detectou VB (60,30%) e em junho, Candida sp (41,85%). Conclusão: A frequência de VB foi maior que a de Candida sp nos quatro anos. Os meses com maior frequência de patógenos identificados foram os de junho, agosto e setembro, no entanto não houve grandes modificações entre a distribuição durante todo o ano.

The most frequent gynecological complaints are associated with genital infections, which affect the vaginal microbiota, i.e., vaginitis and vaginosis. Bacterial vaginosis (BV) is characterized by a change of the vaginal microbiota from aerobic bacteria to anaerobic bacteria. Vulvovaginal candidiasis (VVC) is a disorder caused by the abnormal growth of yeast type fungi in the mucosa of the female genital tract. Objective: To identify the frequency of BV and Candida sp in Pap (Papanicolaou) smears in a city of Northeastern Brazil, according to the months of the year for a period of four years. Methods: Study of the frequency of the identification of BV and Candida sp in the oncotic cytology tests carried out in the Professor Eleutério Laboratory database in the city of Fortaleza from 2012 to 2015. Results: The average age of the evaluated cases was 34.7 years, varying from 14 to 54 years of age. In 2012, August was the month with a higher frequency of BV (62.96%), and the month of March had the highest frequency of Candida sp (42.35%). In 2013, BV was more prevalent in September (61.98%) and Candida sp in August (47.26%). In 2014, however, the month of June showed most often BV (60.47%) and September had a higher frequency of Candida sp (43.30%). In 2015, it was April the month in which BV was most detected (60.30%), and in June, Candida sp (41.85%). Conclusion: The frequency of bacterial vaginosis was higher than that of Candida sp during four years. The months with the highest frequency of identified pathogens were June, August and September; however, there were no major changes throughout the year.

Liquid-based cytology and HPV DNA testing using intra-anal specimens from HIV-negative women with and without genital HPV-induced lesions.

BACKGROUND: Screening for anal cancer using cytology has not been considered in immunocompetent women. The aim of this study was to identify cytological atypia and human papillomavirus (HPV) DNA in intra-anal specimens from human immunodeficiency virus (HIV)-negative women with and without genital HPV lesions. METHODS: This study was a cross-sectional analysis of 142 women who were negative for the HIV: 80 with genital lesions that were associated with HPV and 62 without HPV-induced lesions. The women were evaluated at the Federal University of Ceará from October 2011 to June 2012. The statistical analysis included the Fisher exact test and the odds ratio (CI 95%). RESULTS: Atypical anal cytology was observed in 24 (29.3%) patients in the study group and in 11 (17.8%) patients in the control group. In cases with at least two sites of HPV-associated lesions, 12 (41.4%) presented atypical cytology (P = 0.0220; OR = 2.7621, 1.1579-6.5889). When the practice of anal sex was evaluated, atypical cytology was observed in 22/43 (34%) [P = 0.0214; OR = 2.519, 1.146-5.534]. HPV DNA was detected in 17/27 (63%) cases with at least two sites of lesions (P = 0.0293, OR = 2.4855, 1.0960-5.6367). In the 33 cases who presented positive HPV DNA test results, the liquid-based cytology results were atypical (P = 0.0212, OR = 2.8, 1.1665-6.7208). CONCLUSION: Based on the results, liquid-based cytology may be used to detect intra-anal lesions, especially among women who have a history of anal intercourse or who have genital HPV-associated lesions at multiple sites.

The risk of high-grade squamous intraepithelial lesions in women with low serum levels of vitamin A.

BACKGROUND: The progression of the cervical squamous intraepithelial lesion (SIL) is associated with many cofactors, and nutritional aspects are gradually assuming an important role in understanding the physiopathogenesis. OBJECTIVE: To assess the serum levels of retinol in women from a poor region of Brazil with a histological diagnosis of cervical high-grade SIL (HSIL). METHODS: A cross-sectional study was conducted in 62 women aged 14-48 years who had a cervical biopsy and were treated at the Federal University of Ceara in Fortaleza, Brazil. Serum retinol levels were measured in peripheral blood by a spectrophotometry technique. Values were categorized as subnormal (<20 µg/dl) or normal (≥20 µg/dl). Multivariate logistic regression was used to determine the association between serum levels of retinol and HSIL for a confidence interval of 95%. RESULTS: Twenty-six out of 62 women (42%) had a negative histopathological result for SIL and 36 (58%) were diagnosed with SIL (20 low SIL and 16 high SIL). The level of retinol was more frequently low in women with HSIL, but there was no statistical significance [p = 0.409, OR: 2.26 (0.33-15.59)]. CONCLUSION: There was no association between high SIL and low levels of retinol in peripheral blood.

Influence of human papillomavirus infection on the vaginal microbiome of women with immunocompetency / Influência da infecção por papillomavirus humano no microbioma vaginal de mulheres imunocompetentes

The influence of vaginal infections on the natural history of human papillomavirus (HPV) is still unclear. Objective: To determine if patientswith low-grade squamous intraepithelial lesions (LSILs) and HPV have more vulvovaginitis than patients with normal liquid-based cervical cytology whowere negative for HPV. Methods: This is a cross-sectional study including 322 patients who underwent cervical exams. One hundred and sixty-seven ofthese patients had LSILs on cervical cytology and were simultaneously hybrid capture 2 (HC2)-positive for HPV, and the remaining 155 patients were negative for malignancies and intraepithelial lesions by cytology and HC2-negative for HPV. The prevalence of vaginal infections in both groups was compared using the X2 test without Yates' correction. Results: Among the patients with HPV and LSILs, the most common vaginal infection was vaginosis(8.98%) compared to candidiasis (12.9%) in the patients without LSILs and HPV. No significant differences were found in the prevalence of vaginosisbetween the two groups (p=0.53). Candidiasis was statistically more prevalent in patients without LSILs and HPV (p<0.001). Conclusion: An associationwas found between the presence of Candida and the absence of HPV. Although vaginosis was more frequent among patients with LSILs and HPV, it wasnot statistically significant.

A influência das infecções vaginais na história natural do papillomavirus humano (HPV) ainda é incerta. Objetivo: Determinar se pacientes com lesões intraepiteliais escamosas de baixo grau (LIEBG) e HPV têm mais vulvovaginites que aquelas com citologia cervical em meio líquido normal e testes negativos para HPV. Métodos: Este é um estudo transversal, que incluiu 322 mulheres que fizeram exames de colo. Cento e sessenta e sete destas tinham LIEBG na citologia oncótica e foram simultaneamente positivas para HPV na captura híbrida 2 (CH2). As outras 155 tiveram citologias negativas para neoplasia intraepitelial e malignidade e eram CH2 negativas para HPV. A prevalência de infecção vaginal nos dois grupos foi comparada usando o teste do X2 sem correção de Yates. Resultados: Entre as pacientes com HPV e LIEBG, a infecção vaginal mais comum foi a vaginose (8,98%), enquantoque, no grupo sem LIEBG e sem HPV, foi a candidíase (12,9%). Nenhuma diferença estatisticamente significante foi encontrada na prevalência de vaginose entre os dois grupos (p=0,53). Candidíase foi estatisticamente mais prevalente nas pacientes sem LIEBG e HPV (p<0,001). Conclusão: Foi encontrada uma associação entre a presença de Candida e a ausência de HPV. Embora a vaginose tenha sido mais frequente em pacientes com LIEBG e HPV, esse dado não foi estatisticamente significante.

HPV-DNA hybrid capture test: influence of cellularity in penile samples.

OBJECTIVE: To evaluate if the cellularity of Hybrid Capture samples (Digene, São Paulo, Brazil) influences the results of HPV-DNA Hybrid Capture tests in men. STUDY DESIGN: We harvested material from penile scrapings for the Hybrid Capture HPV test. This material was then used to make cytologic smears, which we used to evaluate for the presence of nonnucleated squamous cells, nucleated squamous cells and glandular cells. The cellularity of nucleated squamous cells was classified as absent, low, moderate or high. Subsequently, we performed the Hybrid Capture test to identify the low and high risk of HPV and compared these results with the cytologic findings. We used the Fisher and odds ratio tests at CI of 95% to determine statistical significance. RESULTS: Of the 88 tests performed, 65 (74.0%) were negative for HPV-DNA and 23 (26.0%) were positive. Nucleated and nonnucleated squamous cells were absent on nine slides, all of which tested negative for HPV. When only nonnudcleated squamous cells were found, 20% of the cases were positive for HPV-DNA (p < 0.0001; OR = 26.185). The presence of nucleated squamous cells correlated with 33% HPV-DNA positivity (p < 0.0001, OR = 49.05). CONCLUSION: Assessing the presence of non-nucleated and nucleated squamous cells on cytologic smears prior to performing an HPV-DNA test is a useful tool for quality control in penile samples.