Prevalencia y genotipicación de virus papiloma humano vaginal y cervical en trabajadoras sexuales de un centro de salud sexual en la zona Norte de Santiago, Chile / Prevalence and genotypes of cervical and vaginal HPV in female sex workers attending a Sexual Control Centre, North Area of Santiago, Chile

INTRODUCCIÓN: En Chile, el cáncer de cuello uterino (CCU) es la segunda causa de muerte por neoplasias malignas en la mujer. El principal agente causal es el virus papiloma humano (VPH). Comparando con la población general, los o las trabajadoras(es) sexuales (TS) tienen alto riesgo de adquirir VPH. OBJETIVO: Analizar la prevalencia y genotipos del VPH cervical y vaginal en TS que se atienden en un Centro de Salud Sexual de Santiago, Chile. Pacientes y MÉTODO: Se realizó un estudio transversal en 97 mujeres TS, de 19 a 70 años de edad. Se obtuvieron dos muestras por paciente, una de exocérvix y otra de paredes vaginales. El ADN de VPH fue identificado por reacción de polimerasa en cadena (RPC) y su genotipo fue investigado para 32 tipos de VPH. RESULTADOS: La prevalencia de VPH global fue de 45%, observándose portación cervical en 41,2% y vaginal en 36,1%, con una coinfección de 32%. El 63% de las muestras tenía genotipos de alto riesgo. Los VPH de alto riesgo más frecuentes fueron el VPH 66 (12%), VPH 58 (9,3%), seguidos por VPH 16, VPH 59 y VPH 82 con igual frecuencia (8% c/u). Treinta y dos mujeres (43%) fueron infectadas con genotipos múltiples. CONCLUSIÓN: El VPH es una infección frecuente entre las TS. Este es el primer estudio en Chile sobre prevalencia y genotipos de VPH en TS.

BACKGROUND: In Chile, cervical cancer is the second leading cause of death from malignancy in women. The main causal agent of cervical cancer is the human papillomavirus (HPV). Compared with the general population, sex workers (SW) are at increased risk of acquiring HPV. AIM: To analyze the prevalence and genotypes of cervical and vaginal HPV in female SW attending a Sexual Control Centre. METHODS: A cross-sectional study was carried out on 97 women (19-70 years old). Two samples were taken per patient, one from exocervix and the other from vaginal walls. HPV DNA. was identified by polymerase chain reaction (PCR) and genotyping using specific probes for 32 types of HPV. RESULTS: The overall frequency of HPV was 45%, 41.2% in cervical carrier and 36.1% in vaginal carrier, 32% were co-infected, 63% of HPV were high-risk genotypes. The most frequent high-risk HPV was HPV 66 (12%), HPV 58 (9.3%), followed by HPV 16, HPV 59 and HPV 82 with the same frequency (8% each one). Thirty two (43%) of females were infected with multiple genotypes. CONCLUSION: HPV is frequent infection among SW. This is the first study in Chile on the prevalence and genotypes of HPV in sex workers.

Vasohibin-2 promotes proliferation and metastasis of cervical cancer cells by regulating epithelial-mesenchymal transition / 南方医科大学学报

OBJECTIVE@#To explore the role of vasohibin-2 (VASH2) in regulation of proliferation and metastasis of cervical cancer cells.@*METHODS@#We analyzed the differentially expressed genes between cervical cancer cells with flotillin-1 overexpression and knockdown by RNA-seq combined with analysis of public databases. The expression levels of VASH2 were examined in normal cervical epithelial cells (HcerEpic), cervical cancer cell lines (HeLa, C-33A, Ca ski, SiHa and MS751) and fresh cervical cancer tissues with different lymph node metastasis status. We further tested the effects of lentivirus-mediated overexpression and interference of VASH2 on proliferation, migration, invasion and lymphatic vessel formation of the cervical cancer cells and detected the expression levels of key epithelial-mesenchymal transition (EMT) markers and TGF-β mRNA.@*RESULTS@#RNA-seq and analysis of public databases showed that VASH2 expression was significantly upregulated in cervical cancer cells exogenously overexpressing flotillin-1 (P < 0.05) and downregulated in cells with flotillin-1 knockdown (P < 0.05), and was significantly higher in cervical cancer tissues with lymph node metastasis than in those without lymph node metastasis (P < 0.01). In cervical cancer cell lines Ca Ski, SiHa, and MS751 and cervical cancer tissue specimens with lymph node metastasis, VASH2 expression was also significantly upregulated as compared with HcerEpic cells and cervical cancer tissues without lymph node metastasis (P < 0.05). Exogenous overexpression of VASH2 significantly promoted proliferation, migration, invasion and lymphatic vessel formation of cervical cancer cells, whereas these abilities were significantly inhibited in cells with VASH2 knockdown (P < 0.05). The cervical cancer cells overexpressing VASH2 showed significant down- regulation of e-cadherin and up- regulation of N-cadherin, Vimentin and VEGF-C, while the reverse changes were detected in cells with VASH2 knockdown (P < 0.05). TGF-β mRNA expression was significantly up-regulated in cervical cancer cells overexpressing VASH2 and down-regulated in cells with VASH2 knockdown (P < 0.001).@*CONCLUSION@#Flotillin-1 may participate in TGF-β signaling pathway-mediated EMT through its down-stream target gene VASH2 to promote the proliferation, migration, invasion and lymphatic vessel formation of cervical cancer cells in vitro.

Apoptotic and autophagic death union by Thuja occidentalis homeopathic drug in cervical cancer cells with thujone as the bioactive principle / 中西医结合学报

OBJECTIVE@#"Multi-targeting" drugs can prove fruitful to combat drug-resistance of multifactorial disease-cervical cancer. This study envisioned to reveal if Thuja homeopathic mother tincture (MT) and its bioactive component could combat human papillomavirus (HPV)-16-infected SiHa cervical cancer cells since it is globally acclaimed for HPV-mediated warts.@*METHODS@#Thuja MT was studied for its antiproliferative and antimigratory properties in SiHa cells followed by microscopic determination of reactive oxygen species (ROS) generation by 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) staining and loss in mitochondrial membrane potential (MtMP) by rhodamine 123 (Rh123) staining. Apoptosis and autophagy inductions were studied by acridine orange/ethidium bromide (AO/EB) staining and immunoblot analyses of marker proteins. The bioactive component of Thuja MT detected by gas chromatography-mass spectrometry was studied for antiproliferative and antimigratory properties along with in silico prediction of its cellular targets by molecular docking and oral drug forming competency.@*RESULTS@#Thuja MT showed significant antiproliferative and antimigratory potential in SiHa cells at a 50% inhibitory concentration (IC50) of 17.3 µL/mL. An increase in DCFDA fluorescence and loss in Rh123 fluorescence prove that Thuja MT acted through the burst of ROS and loss in MtMP respectively. AO/EB-stained cells under the microscope and immunoblot analyses supported Thuja-induced cellular demise via dual pathways-apoptosis and autophagy. Immunoblots showed cleavage of caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1) along with upregulation of Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B)-II, and p62 proteins. Hence, the apoptotic cascade followed a caspase-3-dependent pathway supported by PARP-1 cleavage, while autophagic death was Beclin-1-dependent and mediated by accumulation of LC3BII and p62 proteins. Thujone, detected as the bioactive principle of Thuja MT, showed greater anti-proliferative and anti-migratory potential at an IC50 of 77 µg/mL, along with excellent oral drug competency with the ability for gastrointestinal absorption and blood-brain-barrier permeation with nil toxicity. Molecular docking depicted thujone with the strongest affinity for mammalian target of rapamycin, phosphoinositide 3-kinase, and protein kinase B followed by B-cell lymphoma 2, murine double minute 2 and adenosine monophosphate-activated protein kinase, which might act as upstream triggers of apoptotic-autophagic crosstalk.@*CONCLUSION@#Robust "multi-targeting" anticancer potential of Thuja drug and thujone for HPV-infected cervical cancer ascertained its therapeutic efficacy for HPV infections.

Prevalence and frequencies of human papilloma virus types in adenocarcinoma in situ of the uterine cervix / 中华病理学杂志

Objective: To examine the prevalence and frequencies of human papillomavirus (HPV) genotypes in cervical adenocarcinoma in situ (AIS). Methods: The cases of cervical AIS with concurrent tests of cytology and HPV typing from January 2007 to February 2020 in the Obstetrics and Gynecology Hospital of Fudan University were collected and analyzed. Results: A total of 478 cases of cervical AIS were obtained. The average age of the patients was 39.4 years (range, 19-81 years). The largest age group was 30-39 years (44.8%), followed by 40-49 years (34.7%). Among the 478 patients, 355 underwent high-risk HPV (hrHPV) testing and had a hrHPV-positive rate of 93.8%. Of the 355 patients, 277 also underwent HPV typing and were mostly positive for either or both HPV16 and HPV18 (93.1%), with 55.6% positive for HPV18 and 48.7% positive for HPV16. Among the 478 cases, 266 cases (55.6%) were diagnosed with both AIS and squamous intraepithelial lesion (SIL), while 212 cases (44.4%) were diagnosed with only AIS. Patients infected with HPV16 in the AIS and SIL group significantly outnumbered those in the AIS alone group (P<0.05). Moreover, the rate of positive cytology was 55.9% (167/299 cases), while that of negative cytology was 44.1% (132/299). Among the 109 patients with negative cytology results and co-tested hrHPV, there were 101 HPV-positive cases (92.7%), of which 88 cases were subject to HPV typing and showed an HPV16/18 positive rate of 94.3% (83/88 cases). Conclusions: The combination of HPV typing and cytological screening can maximize the detection rate of cervical AIS, and should continue to be utilized, ideally on a larger scale, in the future.

Cervical mesonephric adenocarcinoma: A case report of a rare gynecological tumor from embryological remains of the female genital tract / Adenocarcinoma mesonéfrico cervical: Relato de caso de um tumor ginecológico raro de restos embriológicos do trato genital feminino

Abstract Introduction Malignant mesonephric tumors are uncommon in the female genital tract, and they are usually located where embryonic remnants of Wolffian ducts are detected, such as the uterine cervix. The information about these tumors, their treatment protocol, and prognosis are scarce. Case report A 60-year-old woman with postmenopausal vaginal bleeding was initially diagnosed with endometrial carcinoma. After suspicion co-testing, the patient underwent a loop electrosurgical excision of the cervix and was eventually diagnosed with mesonephric adenocarcinoma. She was subjected to a radical hysterectomy, which revealed International Federation of Gynecology and Obstetrics (FIGO) IB1 stage, and adjuvant radiotherapy. The follow-up showed no evidence of recurrence after 60 months. Conclusion We present the case of a woman with cervical mesonephric adenocarcinoma. When compared with the literature, this case had the longest clinical follow-up without evidence of recurrence, which reinforces the concept that these tumors are associated with a favorable prognosis if managed according to the guidelines defined for the treatment of patients with cervical adenocarcinomas. Though a rare entity, it should be kept in mind as a differential diagnosis for other cervical cancers.

Análise dos Motivos de Insatisfatoriedade dos Exames Histopatológicos do Colo do Útero no Sistema Único de Saúde, Brasil, 2014 a 2017 / Analysis of The Reasons for Unsatisfactory Cervical Histopathological Exams in the Unified Health System, Brazil, 2014 to 2017 / Análisis de las Causas de los Exámenes Histopatológicos Cervicales Insatisfactorios en el Sistema Único de Salud, Brasil, 2014 a 2017

Introdução: O câncer do colo do útero é ainda um importante problema de saúde pública no Brasil e no mundo. A qualidade dos exames de rastreio e de confirmação diagnóstica são fundamentais para que as ações de controle do câncer alcancem efetivo impacto sobre a mortalidade. Objetivo: Analisar as informações registradas no campo descritivo dos motivos da insatisfatoriedade dos exames histopatológicos do colo do útero. Método: Estudo descritivo com dados do Sistema de Informação do Câncer (SISCAN) de mulheres que realizaram exame histopatológico do colo do útero no Sistema Único de Saúde (SUS) no período de 2014 a 2017. Foram analisados 1.236 exames histopatológicos do colo do útero. Os motivos de insatisfatoriedade especificados no campo descritivo foram analisados, reclassificados e, quando pertinente, foram redistribuídos nos campos existentes para exames satisfatórios. Resultados: Foram classificados incorretamente como 'insatisfatório' 262 exames (21,2%), dos quais, 11,25% foram reclassificados como lesão de caráter benigno, 5,91% como lesão de alto grau, 1,46% como carcinoma, 0,24% como adenocarcinoma e 0,24% como adenocarcinoma in situ. Conclusão: O estudo demonstrou um percentual expressivo de erros nos laudos classificados como insatisfatórios no SUS, apontando a necessidade de capacitar profissionais que emitem laudo histopatológico de forma a evitar erros diagnósticos.

Introduction: Cervical cancer is still an important public health problem in Brazil and worldwide. The quality of screening and diagnostic confirmation tests are essential for cancer control actions to achieve an effective impact on mortality. Objective: The aim of this study was to analyze the information registered in the description field of the motives for the unsatisfactoriness of the histopathological exams of the cervix. Method: Descriptive study using data of the Cancer Information System (SISCAN) of women who underwent histopathological examination of the cervix in the Unified Health System (SUS) in the period from 2014 to 2017.1,236 histopathological examinations of the cervix were analyzed.The reasons for unsatisfactoriness specified in the description field were analyzed and reclassified and, when relevant, were reassigned to the existing fields for satisfactory exams. Results: 262 exams (21.2%) were incorrectly classified as 'unsatisfactory', in which 11.25% were reclassified as a benign lesion, 5.91% as a high-grade lesion, 1.46% as carcinoma, 0.24% as adenocarcinoma and 0.24% as adenocarcinoma in situ. Conclusion: The study showed a significant percentage of errors in reports classified as unsatisfactory in SUS, pointing out the need to train professionals who issue histopathological reports in order to avoid diagnostic errors.

Introducción: El cáncer de cuello uterino sigue siendo un importante problema de salud pública en Brasil y en todo el mundo. La calidad de las pruebas de cribado y las de confirmación diagnóstica son fundamentales para que las acciones de control del cáncer logren un impacto efectivo en la mortalidad. Objetivo: El objetivo de este estudio fue analizar la información registrada en el campo descriptivo de las razones de la insatisfacción de los exámenes histopatológicos del cuello uterino. Método: Estudio descriptivo que utilizó datos del Sistema de Información del Cáncer (SISCAN) de mujeres a las que se les realizó examen histopatológico cervicouterino en el Sistema Único de Salud (SUS) de 2014 a 2017. Se analizaron 1.236 exámenes histopatológicos cervicouterino. útero. Los motivos de insatisfacción especificados en el campo descriptivo se analizaron y reclasificaron y, cuando fue relevante, se redistribuyeron en los campos existentes de satisfacción con el examen. Resultados: 262 exámenes (21,2%) se clasificaron incorrectamente como 'insatisfactorios', en los que el 11,25% se reclasificó como lesión benigna, el 5,91% como lesión de alto grado, el 1,46% como carcinoma, 0,24 % como adenocarcinoma y 0,24% como adenocarcinoma in situ. Conclusión: El estudio mostró un porcentaje significativo de errores en informes calificados como insatisfactorios en el SUS, señalando la necesidad de formar profesionales que emitan informes histopatológicos para evitar errores diagnósticos.

Células glandulares atípicas: abordagem ginecológica / Atypical glandular cells: gynecological approach

As células glandulares atípicas representam 0,2% a 2,1% dos resultados dos testes de Papanicolaou. Mesmo com essa baixa prevalência, tem um significado importante no diagnóstico do câncer cervical e endometrial, tendo em vista que tais células e subcategorias, associadas à idade da paciente, podem prenunciar um número expressivo de doença intraepitelial, doença invasiva do endocérvix, endométrio e até neoplasias anexiais. E não se pode esquecer do importante número de resultados histológicos benignos, identificados no seguimento dessas pacientes, muitas vezes assintomáticas.(AU)

Atypical glandular cells represent 0,2% to 2,1% of Pap test results even with this low prevalence has an important significance in the diagnosis of cervical and endometrial cancer, considering that such cells and subcategories associated with the patient's age can predict a significant number of intraepithelial disease, invasive disease of the endometrium, endocervix and even adnexial neoplasms; no forgetting the important number of benign histological results, identified in the follow up of these patients, often asymptomatic.(AU)

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.

Analysis of conization results in patients undergoing hysterectomy for uterine adenocarcinoma / Análise dos resultados de conização nos pacientes submetidos a histerectomia por adenocarcinoma uterino

Abstract Objective To observe if the histopathological result of a conization performed after cervical adenocarcinoma in situ diagnosis is compatible with the histopathological analysis of a subsequent hysterectomy. Methods The present descriptive and observational research consisted of the analysis of the medical records of 42 patients who were diagnosed with in situ adenocarcinoma postconization. The analysis consisted of whether there was compatibility between the histopathological reports of conization and hysterectomy and if there was an association between adenocarcinoma in situ and another neoplasia (squamous disease). Interpretation of any immunohistochemistry reports obtained was also performed. In addition, clinical and epidemiological data were also analyzed. Results A total of 42 conizations were performed, 33 (79%) were cold knife conizations and 9 (21%) were loop electrosurgical excision procedures (LEEPs). Of the patients analyzed, 5 (10%) chose not to undergo subsequent hysterectomy to preserve fertility or were < 25 years old. Out of the 37 patients with adenocarcinoma in situ who underwent subsequent hysterectomy, 6 (16%) presented with residual disease. This findingprovedincompatiblewiththe finding of the conizations, which had ruled out invasive cancer. Conclusion The prevalence of adenocarcinoma in situ increased in the past years. There is still a large part of the medical literature that advocates the use of conservative treatment for this disease, even though it is common knowledge that it is a multifocal disease. However, the majority of studies advocate that hysterectomy should remain the preferred treatment for women who have already completed their reproductive purpose.

Resumo Objetivo Observar se o resultado proveniente de uma conização realizada após o diagnóstico de adenocarcinoma cervical in situ é compatível com a análise histopatológica da histerectomia. Métodos A pesquisa foi descritiva e observacional e consistiu na análise de prontuário de 42 pacientes que tiveram o diagnóstico de adenocarcinoma in situ obtidas por conização. Foram analisados se havia compatibilidade entre os laudos de conização e histerectomia, margens do cone, se havia associação com outra patologia (doença escamosa) e interpretação de eventuais laudos histoquímicos obtidos. Além disso, também foram analisados dados clínico-epidemiológicos. Resultados Foram realizadas 42 conizações, sendo 33 (79%) por cone clássico e 9 (21%) por cirurgia de alta frequência. Das pacientes analisadas, 5 (10%) não foram submetidas a histerectomia por desejarem manter a fertilidade ou por terem idade < 25 anos. Das 37 pacientes com adenocarcinoma in situ no exame prévio realizado e que foram submetidas à histerectomia posteriormente, 6 (16%) apresentaram doença residual após o procedimento cirúrgico, apresentando laudos do anatomopatológico pós-histerectomia incompatíveis com o achado na conização que atestava margens livres. Conclusão A prevalência do adenocarcinoma in situ vemaumentando cada vez mais. Ainda há uma grande parte da literatura que defende o uso do tratamento conservador para esta doença, mesmo sabendo que ela é uma doença multifocal e que pode estar presente mesmo em situações nas quais o anatomopatológico evidencie margens livres. Tendo em vista essas características, a maioria preconiza que a histerectomia continua a ser o tratamento preferencial nas mulheres que já completaram o seu intuito reprodutivo.

Avaliação do perfil de mulheres atendidas em centros de referência em saúde de Porto Alegre/RS e relação de alterações citológicas detectadas no exame citopatológico e a presença do HPV / Profile evaluation of women that attended reference health centers in Porto Alegre/RS and the relationship between cytological alterations detected in cytopathological examination and presence of HPV / Evaluación del perfil de las mujeres atendidas en los centros de referencia de salud de Porto Alegre / RS y la relación de las alteraciones citológicas detectadas en el examen citopatológico con la presencia de VPH

Justificativas e Objetivos: Câncer de colo de útero é considerado um problema de saúde pública mundial. Seu diagnóstico é realizado através do exame citopatológico (EC) e seu desenvolvimento relacionado à infecção pelo papilomavírus humano (HPV). Este estudo objetiva avaliar o perfil de mulheres atendidas em centros de referência em saúde de Porto Alegre, Rio Grande do Sul, assim como a relação de alterações observadas ao EC com presença do HPV. Métodos: Estudo transversal realizado em mulheres atendidas em unidades básicas de saúde e um ambulatório de referência de hospital público terciário, no período de julho de 2014 a janeiro de 2017. Coletaram-se amostras representativas da endo/ectocérvice para realização do EC e investigadas quanto à presença molecular do HPV. Resultados: Foram analisadas 169 mulheres com idade média entre 31 e 40 anos, das quais 125 (74%) informaram que a sexarca ocorreu na faixa de 15-20 anos e 37,9% relatou ter tido de três a cinco parceiros sexuais. Em relação ao EC, 71 (42%) apresentaram resultado negativo para lesão intraepitelial ou malignidade e 98 (58%) alguma anormalidade de células escamosas: 20 (11,8%) atipias; 22 (13%) lesão intraepitelial escamosa de baixo grau e 56 (32,6%) lesão intraepitelial de alto grau (HSIL). Cinquenta (29,6%) apresentaram positividade para HPV, destas 56,4% foram diagnosticadas com HSIL (p<0,01). Conclusão: Os resultados revelam alta frequência de HPV em amostras com alterações citopatológicas, em mulheres jovens e com grau de exposição ao HPV, reforçando a importância do papel da sua identificação precoce na investigação da carcinogênese cervical.(AU)

Background and Objectives: Cervical cancer is considered a worldwide public health problem. Its diagnosis is made through cytopathological examination and its development related to human papillomavirus (HPV) infection. This study aims to evaluate the profile of women treated at reference health centers in Porto Alegre, Rio Grande do Sul, as well as the relation of changes observed to cytopathological examination with the presence of HPV. Methods: This is a cross-sectional study carried out in women treated at basic health units and a referral clinic of a public tertiary hospital, from July 2014 to January 2017. Representative samples of the endo/ectocervix were collected to perform the cytopathological examination and investigated for the molecular presence of HPV. Results: 169 women with mean age between 31 and 40 years were analyzed, of whom 125 (74%) reported that the onset of sexual activity occurred in the 15-20 years age group, and 37.9% reported having had three to five sexual partners. In relation to cytopathological examination, 71 (42%) had a negative result for intraepithelial lesion or malignancy and 98 (58%) some squamous cell abnormality: 20 (11.8%) atypical; 22 (13%) low-grade squamous intraepithelial lesion and 56 (32.6%) high-grade intraepithelial lesion (HSIL). Fifty (29.6%) were positive for HPV, of which 56.4% were diagnosed with HSIL (p < 0.01). Conclusion: The results reveal a high frequency of HPV in samples with cytopathological changes, in young women and with a degree of exposure to HPV, reinforcing the importance of the role of its early identification in the investigation of cervical carcinogenesis.(AU)

Justificación y objetivos: El cáncer de cuello uterino se considera un problema de salud pública en todo el mundo. Su diagnóstico se realiza mediante el examen citopatológico (EC), y su desarrollo está relacionado con la infección por el virus del papiloma humano (VPH). Este estudio objetivó evaluar el perfil de mujeres atendidas en los centros de referencia en salud de Porto Alegre, Rio Grande do Sul (Brasil), así como la relación de las alteraciones observadas en el EC con la presencia del VPH. Métodos: Estudio transversal realizado en las mujeres atendidas por unidades de atención primaria y por una clínica ambulatoria de referencia del hospital público terciario en la ciudad de Porto Alegre, en el período de julio de 2014 a enero de 2017. Se recolectaron muestras representativas de endo/ectocérvice para realizar la CE, las cuales se clasificaron según el sistema Bethesda y se investigaron la presencia molecular del VPH. Resultados: Analizamos 169 mujeres con promedio de edad entre 31 y 40 años, de las cuales 125 (74%) informaron que el sexarche ocurrió en el rango de 15-20 años. La mayoría (37,9%) informó haber tenido de 3 a 5 parejas sexuales; y el 37,3% estaban usando anticonceptivos orales. Con respecto a la EC, 71 (42%) se clasificaron como negativos para lesión intraepitelial o malignidad; y el 98 (58%) tenían alguna anormalidad de células escamosas: 20 (11,8%) de atipias; 22 (13,0%) lesión intraepitelial escamosa de bajo grado y 56 (32,6%) lesión intraepitelial de alto grado (HSIL). La frecuencia de positividad del VPH encontrada fue de 50 (29,6%), de estas un 56,4% fueron diagnosticadas con HSIL (p<0,01). Conclusiones: Estos resultados revelan una alta frecuencia de VPH en muestras con alteraciones citopatológicas presentes en mujeres jóvenes con cierto grado de exposición al VPH, lo que refuerza la importancia de identificarse tempranamente en el análisis de la carcinogénesis cervical.(AU)

Description of referrals for colposcopy in a hospital in Brazil / Descrição dos encaminhamentos para colposcopia em um hospital no Brasil

Abstract Objective To describe the referral for colposcopy in a Hospital in Brazil and the relative frequency of patients who benefited from it, considering the correct indications for the examination and its final diagnoses. Methods A retrospective study was performed in the colposcopy service database of the Hospital Universitário de Taubaté, Taubaté, state of São Paulo, Brazil. The frequency validated in the analysis of the medical records of women referred for clinical indication or cytological alteration, attended from March 2015 to March 2017. The population selected and analyzed included 256 results that were correlated to the cytological, clinical data and the result of the colposcopy. Results Of the women referred, 45% presented out of the age of screening according to the guidelines of cervical cancer screening, 8.6% being adolescents and young adults < 25 years old, and 36.4% of the patients being ≥ 65 years old. A total of 50% of the patients had no indication of colposcopy, that is, normal cytologies, benign changes, ectopia, cervicitis, atypical squamous cells of indeterminate significance (ASC-US) and low-grade intraepithelial lesion (LSIL) without persistence and normal clinical appearance. A total of 39.84% who underwent colposcopy had high-grade lesion or cancer results, thus benefiting from the adequate referral. Conclusion Most (60.16%) of the patients referred to the colposcopy service did not benefit from the referral for results without changes, such as negative colposcopies, histologies with no cervical intraepithelial neoplasm (CIN) or only CIN 1, or were out of the age for screening. These findings therefore demonstrate a significant number of unnecessary and inadequate referrals.

Resumo Objetivo Descrever os encaminhamentos para colposcopia em um hospital no Brasil e a frequência relativa dos pacientes que foram beneficiados, considerando as indicações corretas para o exame e seus diagnósticos finais. Métodos Foi realizado um estudo retrospectivo no banco de dados do serviço de colposcopia do Hospital Universitário de Taubaté, Taubaté, SP, Brasil. A frequência validou em análise de prontuários de mulheres encaminhadas por indicação clínica ou alteração citológica, atendidas no período de março de 2015 a março de 2017. A população selecionada e analisada incluiu 256 resultados que estavam correlacionadas aos dados citológicos, clínicos e com o resultado da colposcopia. Resultados Das mulheres encaminhadas, 45% apresentaram-se fora da idade de rastreamento conforme as diretrizes de rastreio de câncer de colo uterino, sendo que 8,6% eram adolescentes e adultas jovens < 25 anos de idade e 36,4% das pacientes tinham idade ≥ 65 anos. Um total de 50% das pacientes não possuía indicação de colposcopia, ou seja, citologias normais, de alterações benignas, ectopia, cervicite, células escamosas atípicas de significado indeterminado (ASC-US) e lesão intraepitelial escamosa de baixo grau (LSIL) sem persistência e aspecto clínico normal. Um total de 39,84% das pacientes que realizaram a colposcopia tiveram resultados de lesão de alto grau ou câncer e, dessa forma, se beneficiaram com o encaminhamento adequado. Conclusão A maioria (60,16%) das pacientes encaminhadas para o serviço de colposcopia não se beneficiou com o encaminhamento, por resultados sem alterações como colposcopias negativas, histologias com ausência de neoplasia intraepitelial cervical (NIC) ou apenas NIC 1, ou estavam fora da idade de rastreamento. Esses achados demonstram, portanto, significativo número de encaminhamentos desnecessários e inadequados.

lncRNA OIP5-AS1 targets ROCK1 to promote cell proliferation and inhibit cell apoptosis through a mechanism involving miR-143-3p in cervical cancer

Opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) is one kind of cytoplasmic long non-coding RNA (lncRNA), which has been demonstrated to play a critical function in multiple cancers. However, the detailed mechanism of OIP5-AS1 in the regulation of cervical cancer progression is still obscure. Here, we demonstrated that lncRNA OIP5-AS1 was upregulated in cervical cancer and was correlated with poor prognosis by bioinformatics studies. OIP5-AS1 depletion inhibited cell proliferation and promoted cell apoptosis in cervical cancer cells. Furthermore, we clarified that ROCK1 was the downstream effector of OIP5-AS1 and OIP5-AS1 acted as a molecular sponge of miR-143-3p. Finally, we verified that OIP5-AS1 exerted its function in the regulation of cervical cancer progression via interacting with miR-143-3p to regulate ROCK1 expression. Our study revealed novel mechanisms about how lncRNA OIP5-AS1 executed its function in cervical cancer and thus provided potential therapeutic targets for the disease.

Premature mortality due to cervical cancer: study of interrupted time series / Mortalidade prematura por câncer de colo uterino: estudo de séries temporais interrompidas

ABSTRACT OBJECTIVE: To verify the effect of the Pact for Health on premature mortality (30-69 years) attributed to cervical cancer in Brazil and its macroregions, using interrupted time series analysis. METHODS: Segmented regression was used to assess "change in level" and "change in trend" in premature mortality rates attributed to cervical cancer considering the post-Pact period (2010-2018), controlling by the pre-Pact period (1998-2006). Understanding the triennium 2007-2009 as essential for the adoption and implementation of the policy, it was excluded from the main modeling, but assessed in the sensitivity analysis. RESULTS: From 1998 to 2018, there were more than 119,000 deaths due to cervical cancer in women aged 30 to 69 years in Brazil. The Northern region experienced the highest rates (> 20 per 100,000). Comparing with baseline (1998-2006), segmented regression showed a progressive increase in changing trend from cervical cancer deaths in Brazil as a whole (coefficient = 0.513; 95%CI 0.430 to 0.596) and in the Southeast region (coefficient = 0.515; 95%CI 0.358 to 0.674), South region (coefficient = 0.925; 95%CI 0.642 to 1.208), and Midwest region (coefficient = 0.590; 95%CI 0.103 to 1.077). The Northeast region presented the most promising effects with immediate reduction in change level (-0.635; 95%CI −1.177 to −0.092) and progressive reduction in the changing trend of premature deaths (coefficient= −0.151; 95%CI −0.231 to −0.007). CONCLUSIONS: Premature mortality rates due to cervical cancer are high in Brazil and its macroregions. This interrupted time series was not able to reveal the effectiveness of initiatives related to the Pact for Health on premature deaths from cervical cancer nationally and in all macroregions equally. The best results are restricted to the Northeast region.

RESUMO OBJETIVO: Verificar o efeito do Pacto Pela Saúde na mortalidade prematura (30-69 anos) atribuída a câncer de colo uterino no Brasil e nas suas macrorregiões, utilizando modelagem de séries temporais interrompidas. MÉTODOS: A regressão segmentada foi usada para avaliar "mudança de nível" e "mudança de tendência" das taxas de mortes prematuras por câncer de colo uterino no período pós-Pacto (2010-2018), controlando pelo período pré-Pacto (1998-2006). Entendendo o triênio 2007-2009 como essencial para adesão e implantação da política ele foi excluído da modelagem principal, mas avaliado na análise de sensibilidade. RESULTADOS: De 1998 a 2018, houve mais de 119 mil óbitos por câncer de colo uterino, em mulheres de 30 a 69 anos, no Brasil. A região Norte experimentou as taxas mais altas (> 20 por 100 mil). Comparando à linha de base (1998-2006), a regressão segmentada mostrou progressiva elevação das mortes por câncer de colo uterino no Brasil como um todo (coeficiente angular = 0,513; IC95% 0,430 a 0,596) e nas regiões Sudeste (coeficiente = 0,515; IC95% 0,358 a 0,674), Sul (coeficiente = 0,925; IC95% 0,642 a 1,208), e Centro-Oeste (coeficiente = 0,590; IC95% 0,103 a 1,077). A região Nordeste apresentou os efeitos mais promissores com redução imediata no nível (-0,635; IC95% −1,177 a −0,092) e redução progressiva na tendência de mortes prematuras (coeficiente= −0,151; IC95% −0,231 a −0,007). CONCLUSÕES: As taxas de mortalidade prematuras por câncer de colo uterino são altas no Brasil e nas suas macrorregiões. Esta série temporal interrompida não foi capaz de revelar efetividade das iniciativas relacionadas ao Pacto pela Saúde sobre as mortes prematuras por câncer de colo uterino nacionalmente e tampouco em todas as macrorregiões igualmente. Os melhores resultados estão restritos à região Nordeste.

Efficacy and safety of cryotherapy, cold cone or thermocoagulation compared to LEEP as a therapy for cervical intraepithelial neoplasia: Systematic review / Eficacia y seguridad de crioterapia, cono frio o termo-coagulación en comparación con LEEP como terapia para la neoplasia intraepitelial cervical: Revisión sistemática

ABSTRACT OBJECTIVES To determine the efficacy and safety of the use of cryotherapy, cold knife or thermocoagulation compared to Loop Electrosurgical Excision Procedure (LEEP) for the treatment of cervical intraepithelial neoplasia. METHODS Systematic review with meta-analysis of randomized controlled trials in women with cervical intraepithelial neoplasia undergoing treatment with cryotherapy, cold knife, or thermo-coagulation compared with LEEP, to estimate its efficacy and safety. The search was conducted on MEDLINE/PUBMED, Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus, until September 2018. RESULTS The total of 72 studies were identified, of which only 8 studies met the inclusion criteria. The treatment of CIN with cold knife decreases the risk of residual disease compared with LEEP (RR, 0.54, 95%CI, 0.30-0.96, p = 0.04). The management of premalignant lesions with cryotherapy, compared with LEEP, increases the risk of disease recurrence by 86% (RR, 1.86, 95%CI, 1.16-2.97, p = 0.01), increases the risk of infections (RR, 1.17, 95%CI, 1.08-1.28, p < 0.001) and reduces the risk of minor bleeding by 51% (RR, 0.49, 95%CI) %, 0.40-0.59, p ≤ 0.001). CONCLUSIONS The treatment of premalignant lesions of cervical cancer with cold knife reduces the risk of residual disease. Nevertheless, cryotherapy reduces the risk of minor bleeding in the 24 hours after treatment and increases the risk of recurrence of disease and infections.

RESUMEN OBJETIVOS Evaluar la eficacia y seguridad del uso de crioterapia, cono frio o termo-coagulación en comparación con el procedimiento de escisión electroquirúrgica en asa (LEEP) para el manejo de neoplasias intraepiteliales cervicales. MÉTODOS Revisión sistemática de ensayos controlados aleatorizados en mujeres con neoplasia intraepitelial cervical en tratamiento con crioterapia, cono frio, o termo coagulación y LEEP, para estimar su eficacia y seguridad. La búsqueda se realizó en MEDLINE/PUBMED, Registro Cochrane Central de Ensayos Controlados (CENTRAL) y Scopus, hasta setiembre de 2018. RESULTADOS Se identificaron 72 estudios, ocho cumplieron los criterios de inclusión. Cono frio disminuyó el riesgo de enfermedad residual en comparación con LEEP (RR 0,54; IC del 95%, 0,30-0,96, p = 0,04). Crioterapia en comparación con LEEP incrementó el riesgo de recurrencia de enfermedad en un 86,0% (RR 1,86; IC del 95%, 1,16-2,97, p = 0,01) con un tiempo de seguimiento de seis a 24 meses, y de infecciones (RR, 1,17; IC del 95%, 1,08-1,28, p < 0,001); pero redujo el riesgo de sangrado menor en un 51,0% (RR 0,49; IC del 95%, 0,40-0,59, p ≤ 0,001). CONCLUSIONES Cono frio reduce el riesgo de enfermedad residual. Sin embargo, la crioterapia reduce el riesgo de sangrado menor en las 24 horas posteriores al tratamiento e incrementa el riesgo de recurrencia de enfermedad y de infecciones.

ß-Catenin: oncogenic role and therapeutic target in cervical cancer

Cervical cancer is a common and fatal malignancy of the female reproductive system. Human papillomavirus (HPV) is the primary causal agent for cervical cancer, but HPV infection alone is insufficient to cause the disease. Actually, most HPV infections are sub-clinical and cleared spontaneously by the host immune system; very few persist and eventually develop into cervical cancer. Therefore, other host or environmental alterations could also contribute to the malignant phenotype. One of the candidate co-factors is the ß-catenin protein, a pivotal component of the Wnt/ß-catenin signaling pathway. ß-Catenin mainly implicates two major cellular activities: cell-cell adhesion and signal transduction. Recent studies have indicated that an imbalance in the structural and signaling properties of ß-catenin leads to various cancers, such as cervical cancer. In this review, we will systematically summarize the role of ß-catenin in cervical cancer and provide new insights into therapeutic strategies.

Uterine cavity embryonal rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a rare solid tumor in childhood and adolescence. The higher incidence is predominant during the first two decades of life. According to the Intergroup RMS Study Group, the embryonal RMS (ERMS), botryoidal variant, constitutes a histological subtype characterized as a "grape-like" lesion of 2.0 cm to 9.5 cm. The treatment involves chemotherapy, surgery, and/or radiotherapy. We present the case of a 14-year-old female patient diagnosed with ERMS, botryoidal variant, which originated in the uterine cervix with vaginal externalization. The initial therapeutic approach comprised an initial prolapsed mass excision followed by Wertheim­Meigs surgery due to the tumor extension. No consensual protocol to ERMS treatment is found in the medical literature; however, a combined approach seems to offer a better result. The postoperative time period was uneventful and the patient followed an adjuvant therapy with vincristine, d-actinomycin, and cyclophosphamide. A comprehensive evaluation of the therapeutic options preserving the reproductive function­unfortunately not always possible­is part of a multi-disciplined care team concerning the pediatric patients.

Health-related quality of life in women with cervical cancer / Qualidade de vida relacionada à saúde em mulheres com câncer do colo do útero

Abstract Objective To analyze the factors associated with health-related quality of life (HRQoL) in women with cervical cancer (CC) in a single center in Rio de Janeiro, state of Rio de Janeiro, Brazil. Methods A cross-sectional study in women with a diagnosis of CC followed-up in the gynecology outpatient clinic of the Hospital do Câncer II (HCII, in the Portuguese acronym) of the Instituto Nacional de Câncer (INCA, in the Portuguese acronym). The data were collected from March to August 2015. Women with palliative care, communication/cognition difficulty, undergoing simultaneous treatment for other types of cancer, or undergoing chemotherapy and/or radiation therapy were excluded. For the evaluation of the HRQoL, a specific questionnaire for women with CC was used (Functional Assessment of Cancer Therapy - Cervix Cancer [FACT-Cx]). The total score of the questionnaire ranges from 0 to 168, with higher scores indicating a better HRQoL. Results A total of 115 women were included in the present study, with a mean age of 52.64 years old (standard deviation [SD] = 12.13). The domains of emotional (16.61; SD = 4.55) and functional well-being (17.63; SD = 6.15) were those which presented the worst scores. The factors that had an association with better HRQoL in women with CC were having a current occupation, a longer time since the treatment and diagnosis, and women who had undergone hysterectomy. Conclusion Considering the domains of HRQoL of the women treated for cervical cancer, a better score was observed in the domains of physical and social/family wellbeing. For most domains, better scores were found between those with a current occupation, with a longer time after the diagnosis and treatment, and among those who had undergone a hysterectomy.

Resumo Objetivo Analisar os fatores associados à qualidade de vida em mulheres com câncer de colo do útero tratadas em um hospital de referência no Rio de Janeiro, RJ, Brasil. Métodos Estudo transversal em mulheres com diagnóstico de câncer do colo do útero emseguimento ambulatorial no Hospital de Câncer II (HCII) do Instituto Nacional de Câncer (INCA). Os dados foram coletados no período de março a agosto de 2015. Foram excluídas as mulheres em cuidados paliativos, comdificuldade de comunicação/cognição, que estavam em tratamento simultâneo para outros tipos de câncer, ou em quimioterapia e/ou radioterapia. Para a avaliação da qualidade de vida relacionada à saúde, foi utilizado um questionário específico para mulheres com câncer de colo do útero (Avaliação Funcional da Terapia do Câncer - Câncer Cervical (FACT-Cx, na sigla em inglês). O escore total do questionário varia de 0 a 168, com escores mais altos indicando melhor qualidade de vida relacionada à saúde. Resultados Foram incluídas 115 mulheres com uma média de idade de 52,64 anos (desvio padrão [DP] = 12,13). Os domínios de questões emocionais (16,61; DP = 4,55) e de bem-estar funcional (17,63; DP = 6,15) foram os que apresentaram os piores escores. Os fatores que tiveram associação com melhor qualidade de vida relacionada à saúde em mulheres com câncer de colo do útero foram ocupação atual, maior tempo após o tratamento e diagnóstico, e mulheres que haviamsido submetidas a histerectomia. Conclusão Considerando os domínios da qualidade de vida relacionada à saúde de mulheres tratadas para câncer do colo do útero, foi observado melhor escore nos domínios de bem-estar físico e social. Para amaioria dos domínios, osmelhores escores foram observados entre aquelas com ocupação atual, com mais tempo após o diagnóstico e tratamento, além daquelas que se submeteram a histerectomia.