Uterine POLE mutant endometrioid carcinoma combined with human papilloma virus-associated cervical adenocarcinoma: A case report and literature review / 北京大学学报(医学版)

Independent primary uterine and cervical adenocarcinoma are rare and difficult to identify their origins, which makes treatment decision difficult. A 46-year-old female with endometrioid carcinoma and adenocarcinoma, human papilloma virus (HPV)-associated of the uterine cervix was reported. The patient presented with increased menstrual flow, contact bleeding and watery leucorrhea for more than one year, and the imaging findings showed abnormal uterine morphology, irregular margins, and multiple abnormal signals in uterine cavity and myometrium, which suggested multiple leiomyomas of the uterus. The signal intensity in the right muscle layer was markedly enhanced, suggesting a smooth muscle tumor of uncertain malignant potential. A large number of cystic hypointensity was seen in the cervix, and multiple cysts were considered. The initial preoperative diagnosis was multiple leiomyoma of the uterus, and a hysterectomy operation was planned. During the operation, the uterus was sent for frozen sections. There was a mass in the endometrium of the fundus, with a soft grayish-red cut surface and a clear border with the myometrium, and there was a grayish-white nodule in the cervix with a hard grayish-white cut surface. The two masses were well demarcated from each other, and the distance between them was 30 mm. The result of the frozen sections indicated the malignant tumor of the endometrium, and the extended hysterectomy+pelvic lymphadenectomy+partial resection of the greater omentum was performed. After the operation, the paraffin sections were sent to the Department of Pathology of the Peking University Third Hospital for histochemistry, POLE gene sequencing and HPV RNAscope tests, and the final diagnosis was a synchronous endometrioid carcinoma (POLE-mutant according to the WHO classification) and an adenocarcinoma, HPV-associated of the uterine cervix. Now the patient had been treated with 2 cycles of chemotherapy and her condition was fine. Through the analysis of the histological, immunohistochemical and molecular detection results of this case, the importance of applying HPV RNAscope and TCGA molecular typing in the diagnosis of cervical adenocarcinomas and endometrial carcinomas was emphasized. At the same time, gynecologists should not blindly rely on intraoperative frozen sections, and should pay attention to preoperative pathological examination, and make appropriate operation methods according to the results in order to prevent passivity in the surgery.

Efetividade da marcação combinada de p16 e ki67 na referência de mulheres com citologia ASC-US ou LSIL para colposcopia / Effectiveness of combined p16 and ki67 labeling in the referral of women with ASC-US or LSIL cytology for colposcopy

Objetivo: Analisar o desempenho do teste de Dupla Marcação (DM) por p16 e Ki67 em amostras de células cervicais para detecção de lesões precursoras do câncer do colo do útero, comparando-o à repetição imediata da citologia em mulheres com resultado de citologia de rastreamento ASC-US ou LSIL. Metodologia: Trata-se de um estudo transversal que recrutou 121 mulheres nas unidades de Atenção Primária de Saúde dos municípios de Palmas e Porto Nacional, em Tocantins, e da cidade do Rio de Janeiro, com citologia de rastreamento com resultado ASC-US ou LSIL. As mulheres foram referidas aos Serviços de Referência do Colo participantes em Tocantins e no Rio de Janeiro. As participantes realizaram o exame de colposcopia e coleta de espécime para Citologia em Meio Líquido (CML) e para DM para p16 e Ki67. Os resultados dos testes foram comparados ao padrão-ouro misto definido pela colposcopia, histologia (quando obtido espécime histológico) na avaliação inicial, ou citologia, colposcopia e histologia (quando obtido espécime histológico) no seguimento de pelo menos 12 meses, definindo as que tinham lesão precursora (NIC II ou NIC III) ou não. Resultados: Das 121 mulheres recrutadas, 76 mulheres foram consideradas para esta análise por terem pelo menos um exame de triagem realizado (CML ou DM por p16-Ki67) e conclusão diagnóstica. Dessas, 42 apresentavam exame prévio de ASC-US e 34 de LSIL. A maioria (86,8%) estava na faixa etária recomendada para o rastreamento (25 a 64 anos). Objetivo: Analisar o desempenho do teste de Dupla Marcação (DM) por p16 e Ki67 em amostras de células cervicais para detecção de lesões precursoras do câncer do colo do útero, comparando-o à repetição imediata da citologia em mulheres com resultado de citologia de rastreamento ASC-US ou LSIL. Metodologia: Trata-se de um estudo transversal que recrutou 121 mulheres nas unidades de Atenção Primária de Saúde dos municípios de Palmas e Porto Nacional, em Tocantins, e da cidade do Rio de Janeiro, com citologia de rastreamento com resultado ASC-US ou LSIL. As mulheres foram referidas aos Serviços de Referência do Colo participantes em Tocantins e no Rio de Janeiro. As participantes realizaram o exame de colposcopia e coleta de espécime para Citologia em Meio Líquido (CML) e para DM para p16 e Ki67. Os resultados dos testes foram comparados ao padrão-ouro misto definido pela colposcopia, histologia (quando obtido espécime histológico) na avaliação inicial, ou citologia, colposcopia e histologia (quando obtido espécime histológico) no seguimento de pelo menos 12 meses, definindo as que tinham lesão precursora (NIC II ou NIC III) ou não. Resultados: Das 121 mulheres recrutadas, 76 mulheres foram consideradas para esta análise por terem pelo menos um exame de triagem realizado (CML ou DM por p16-Ki67) e conclusão diagnóstica. Dessas, 42 apresentavam exame prévio de ASC-US e 34 de LSIL. A maioria (86,8%) estava na faixa etária recomendada para o rastreamento (25 a 64 anos). Oito mulheres (10,5%) apresentaram NIC II ou III como conclusão diagnóstica. Verificou-se que o teste da DM de p16 e Ki67 identificou um número maior de mulheres com um desses diagnósticos, encaminhando 50% das mulheres com ASC-US ou LSIL na citologia de rastreamento para colposcopia, mas deixando de identificar 50% dessas mulheres. Esse teste mostrou-se 2,5 vezes mais sensível do que o exame citopatológico de repetição imediata. Conclusão: O teste de DM por p16 e Ki67 se mostrou mais capaz de identificar mulheres com lesões precursoras com resultado citopatológico prévio ASC-US ou LSIL e sem aumento relevante de encaminhamentos para colposcopia em comparação à citologia de repetição imediata.(AU)

Objective: To access p16/Ki-67 double staining (DS) in cervical cells performance for detecting precursor lesions of cervical cancer, in comparison to immediate repetition of the liquid-based cervical cytology (LBCC) in women with screening cytology results of atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL). Methodology: This study recruited 121 women in primary health care units in Palmas and Porto Nacional, Tocantins, and in Rio de Janeiro, Brazil, with screening cytology showing ASC-US or LSIL. Women were addressed to the Cervical Referral Services (SRC) in each state and examined with colposcopy, LBCC and DS-p16/Ki-67. Histological results were available for women in which a cervical biopsy was obtained during initial evaluation or duringa follow-up up to 12 months, discerning cases with precursor lesions (CIN2 or CIN3) or not. Results: From the 121 recruited women, 76 screened positive in at least one exam (LBCC or DS-p16/Ki-67) and had a diagnostic conclusion. From these, 42 and 34 patients had previous ASC-US and LSIL exams, respectively. Most patients (86,8%) were within the recommended age group for screening in Brazil (25 to 64 years-old). CIN2-3 were found in 8 women (10,5%). DS-p16/Ki-67 identified a greater number of women with CIN2-3, addressing 50% of the women to colposcopy, but failing to detect these lesions in 50% of cases. DS-p16/Ki-67 was2,5x more sensitive than the immediate repetition of the LBCC. Conclusion: DS-p16/Ki-67 is more efficient to identify women with precursor lesions with screening cytopalotogical ASC-US or LSIL results, and without relevant increase in referring patients to colposcopy, in comparison to immediate repetition of the LBCC.(AU)

Neoplasia intraepitelial escamosa cervical de alto grau: abordagem ambulatorial / High-grade cervical intraepithelial neoplasia: outpatient approach

As neoplasias intraepiteliais cervicais correspondem a alterações identificadas por rastreamento citológico cervical e estudo histológico, pós-biópsia incisional guiada por colposcopia ou procedimento diagnóstico excisional. Podem ser tratadas com abordagens conservadoras e procedimentos excisionais. A vacinação anti-HPV e o tratamento excisional oportuno constituem, respectivamente, prevenção primária e secundária contra o câncer do colo uterino.(AU)

Cervical intraephitelial neoplasms correspond to changes identified by cervical citological screening and histological study, post-incisional biopsy guided by colposcopy or excisional diagnostic procedure. They can be treated with conservative approaches and excision procedures. Anti-HPV vaccination and timely excional treatment are primary and secondary prevention against cervical cancer, respectively.(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.

Infección por virus del papiloma humano en mujeres del Cantón Cañar, Ecuador / Human papillomavirus infection among women from Cañar Canton in Ecuador

Introducción: Existen pocos estudios sobre la circulación del virus del papiloma humano en mujeres ecuatorianas, particularmente residentes en el Cantón Cañar. Objetivo: Determinar la circulación del virus del papiloma humano, las alteraciones en la citología cérvico-vaginal de mujeres cañaríes y el comportamiento de algunas variables sociodemográficas y clínico-epidemiológicas. Métodos: Estudio analítico de corte transversal desde julio 2017-septiembre 2018. Se colectaron células cervicouterinas de 100 mujeres entre 15 y 55 años de edad para determinar la infección viral y alteraciones citológicas. Se investigó la asociación entre variables sociodemográficas y clínico-epidemiológicas con la infección viral. Resultados: El 51 por ciento (51/100) de las mujeres examinadas resultó positivo al virus, con predominio de los genotipos oncogénicos. El genotipo 31 fue el más frecuente (56,9 por ciento; 29/51), seguido por el genotipo 58 (43,1 por ciento; 22/51). Las mujeres mayores de 50 años, tenían una probabilidad menor de estar infectadas (3,9 por ciento; 2/51). La probabilidad de infección fue mayor en mujeres solteras, con antecedentes de infecciones de transmisión sexual, que padecían procesos cervicales inflamatorios, y en las fumadoras. La infección con genotipo 66 estuvo asociada al uso de anticonceptivos hormonales (53,3 por ciento; 8/15); p= 0,045, RP= 3,08 IC95 por ciento (1,00-9,46). Se obtuvo el 97 por ciento de citologías negativas para malignidad; no se diagnosticaron casos con lesiones de alto grado. Conclusiones: La elevada prevalencia de infección con genotipos oncogénicos en contraste con la baja frecuencia de citologías positivas, indica la necesidad de implementar programas eficientes para la detección precoz del cáncer cervicouterino en la población del Cañar y divulgar campañas de educación sexual y reproductiva(AU)

Introduction: Few studies are available about the circulation of human papillomavirus among Ecuadorian women, particularly those from Cañar Canton. Objectives: Determine the circulation of human papillomavirus, alterations in the cervical-vaginal cytology of women from Cañar Canton, and the behavior of some sociodemographic and clinical-epidemiological variables. Methods: An analytical cross-sectional study was conducted from July 2017 to September 2018. Cervical cells were collected from 100 women aged 15-55 years to determine viral infection and cytological alterations. An analysis was performed of the relationship of sociodemographic and clinical-epidemiological variables to viral infection. Results: Of the women examined, 51 percent; (51/100) tested positive for the virus, with a predominance of oncogenic genotypes. Genotype 31 was the most common (56.9 percent;; 29/51), followed by genotype 58 (43.1 percent; 22/51). Women aged over 50 years had a lesser probability of being infected (3.9 percent;; 2/51). Infection probability was greater among single women, with a history of sexually transmitted infections, who suffered from inflammatory cervical processes, and smokers. Infection by genotype 66 was associated to the use of hormonal contraceptives (53.3 percent;; 8/15); p= 0.045, PR= 3.08 CI95 percent; (1.00-9.46). Of the sample cytologies, 97 percent; were negative for malignancy; no case was diagnosed of high-grade lesions. Conclusions: The high prevalence of infection by oncogenic genotypes, as opposed to the low frequency of positive cytologies, points to the need to implement efficient programs aimed at early detection of cervical cancer in the population of Cañar Canton, as well as sexual and reproductive education campaigns(AU)

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)

In vivo and ex vivo dermoscopy of lesions from implantation of human papillomavirus in tattoos: report of two cases

Abstract The number of individuals with tattoos has been increasing worldwide, alongside with reports of complications varying from reactions to the injected pigments to infections caused by agents inoculated in the pigmentation process. The diagnosis of such unwanted events can be obtained through complementary non-invasive methods, preserving the maximum of the tattoo design. The authors present two cases of patients with warts on tattooing, and correlate their clinical aspects to in vivo and ex vivo dermoscopy, and to the findings in the histopathological examination, aiming to determine patterns that aid the diagnosis of these lesions without performing biopsy.

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.

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.

Importancia del sistema de Bethesda en el diagnóstico citológico de lesiones precancerosas del cérvix / The importance of Bethesda system in the cytological diagnosis of the cervix pre-cancerous lesions

RESUMEN El cáncer cérvico uterino, causa alrededor de 250 000 muertes anuales en el mundo y alrededor de 400 en Cuba, a pesar del esfuerzo que realiza el MINSAP, a través del Programa de Pesquisaje. Con el mismo se puede obtener el diagnóstico de lesiones precursoras del cáncer de cuello uterino, este diagnóstico citológico se realiza en Cuba a través del método de Richard y Barron que demuestra que existe un progreso citológico aparente hasta llegar al cáncer, que comienza con neoplasia intraepitelial (NICI a NICIII y carcinoma in situ), hasta finalmente el cáncer invasor. Por otro lado existe el método de Bethesda que responde casi todas las interrogantes que la citología plantea para su enfrentamiento, evidentemente los mayores aportes y revisiones se enfocan al manejo de las citologías atípicas de significado incierto, ya que no sólo presentan un mayor número de posibles evaluaciones, sino que representan el mayor porcentaje de citologías alteradas y la inclusión del VPH en las lesiones de bajo grado. En Cuba todavía se clasifica por el método de Richard y no se utiliza el Bethesda. Por la alta incidencia de esta entidad el propósito de este trabajo es emitir consideraciones sobre la implementación del sistema de Bethesda en el diagnóstico citológico de lesiones precancerosas del cérvix.

ABSTRACT The cervical-uterine cancer causes almost 250 000 death a year around the world and around 400 in Cuba in spite of the efforts made by the Public Health Ministry through the Screening Program. With it, the diagnosis of lesions that are predecessors of the cervical cancer could be reached. This cytological diagnosis is carried out through the Richard and Barron method, showing that there is an apparent cytological progress leading to the cancer that begins with intraepithelial neoplasia (NICI and NICIII and carcinoma in-situ) and ends in the invasive cancer. From the other hand there is the Bethesda methods answering to all the questions cytology ask for confronting it. Obviously the biggest contributions and reviews are focused in the management of the atypical cytologies with uncertain significance since they not only have a higher number of possible evaluations, but also represent the highest percent of the altered cytologies and the inclusion of the HPV in low grade lesions. The classification in Cuba is still made by the Richard method and the Bethesda one is not used. Due to the high incidence of this entity, the aim of this article is exposing considerations on the implementation of the Bethesda system in the cytological diagnosis of cervix pre-cancerous lesions.

Analysis of the application values of different combination schemes of liquid-based cytology and high-risk human papilloma virus test in the screening of high-grade cervical lesions

The aim of this study was to explore the value of different combination schemes of liquid-based cytology (LBC) and high-risk human papilloma virus (HPV) test in the screening of high-grade (≥CIN 2) cervical lesions. From 5727 women who had undergone examinations with LBC and high-risk HPV test, 1884 patients with positive results of either or both LBC and HPV test were included in this study and underwent cervical biopsy. Based on the pathological examination results, comparisons of the assessment indicators of all diagnostic tests were made, and the application values of LBC and high-risk HPV test and different combination schemes of the two in the screening of high-grade (≥CIN II) cervical lesions were estimated. Compared with the single test method, the sensitivity and negative predictive value of the combination scheme of LBC+HPV (with one positive result) were increased significantly (98.7% and 99.7%), but the specificity (60.8%) and accuracy rate (65.4%) dropped significantly (P<0.05). The sensitivity of LBC+HPV (with two positive results) was the lowest (80.7%), but the specificity and accuracy rate were the highest (83.5% and 83.1%, P<0.05). Z test showed that differences in the screening efficiency of four schemes were not statistically significant (P>0.05). Both LBC and HPV test were effective methods in the screening of high-grade cervical lesions; combination of the two tests did not improve the screening efficiency, but the scheme of LBC+HPV (with two positive results) significantly increased the sensitivity and negative predictive value, which was of better cost-benefit value.

¿Permiten la citología, el genotipado y la anoscopia de alta resolución establecer un protocolo para la detección precoz del carcinoma epidermoide de canal anal en población de riesgo? / Do cytology, genotyping, and high resolution anoscopy allow to establish a protocol for early detection of squamous cell carcinoma of the anal canal in risk population?

Introducción: El cáncer anal ha experimentado un aumento de incidencia en los últimos años. Está mediado por el VPH y precedido de cambios precancerosos planteando la posibilidad de dirigir los esfuerzos preventivos hacia los grupos de alto riesgo. Sigue siendo controvertida la indicación de cribado y los métodos de detección ideales. Objetivo: Validar las pruebas de cribado implementadas en la actualidad comparadas con la biopsia como "gold standard". Material y Métodos: Estudio transversal con recogida de datos prospectiva, en una cohorte de hombres VIH+ que tienen sexo con hombres, pertenecientes al Hospital Gregorio Marañón e Infanta Leonor en un periodo de 2 años. Resultados: Se seleccionaron 179 pacientes con 286 visitas a la consulta de screening en las que se llevaron a cabo 3 pruebas de cribado en paralelo (citología anal, genotipado del VPH y anoscopia de alta resolución (AAR) con toma de biopsia dirigida sobre zona sospechosa o aleatoria). La sensibilidad y especificidad para la detección de displasia de alto grado y cáncer y su grado de concordancia con la biopsia fue la siguiente: citología 3,23%/94,43% (k: 0,03), genotipado de VPH de alto riesgo 90,32%/27,45% (k: 0,05), AAR 32,26%/87,45 (k: 0, 17) siendo el rendimiento diagnóstico de las tres pruebas muy bajo. Conclusión: La citología presenta un rendimiento diagnóstico muy bajo comparado con el genotipado que representa el mayor. A la luz de nuestros resultados, los protocolos clínicos tal y como vienen desarrollándose en la actualidad deberían de ser abandonados.

Introduction: The incidence of anal cancer has increased in recent years. It is mediated by HPV and preceded by precancerous changes, raising the possibility of directing preventive efforts towards high-risk groups. The indication of screening remains controversial and which methods would be the ideal ones. Objective: To validate the screening tests established actually, comparing it with the biopsy considered as the "gold standard". Materials and Methods: A cross-sectional study was performed, with prospective data collection in a cohort of VIH+ patients, who have male homosexual anal relations, belonging to Gregorio Marañón and Infanta Leonor Hospitals in a period of 2 years. Results: A total of 179 patients were selected with 286 visits to the screening Outpatient Clinic in which 3 parallel screening tests were performed (anal cytology, HPV genotyping and high resolution anoscopy (AAR) with a biopsy directed on a suspicious or random area). The sensitivity and specificity for the detection of high-grade dysplasia and cancer and their degree of agreement with the biopsy was as follows: cytology 3.23%/94.43% (k: 0.03), high HPV genotyping. risk 90.32%/27.45% (k: 0.05), AAR 32.26%/87.45 (k: 0, 17), the diagnostic accuracy of the three tests being very low. Conclusion: Cytology shows a very low diagnostic accuracy compared to the genotype that represents the highest one. In light of our results, clinical protocols as they are currently being developed should be abandoned.

High-risk mucosal HPV types associated with squamous cell carcinoma on the nose tip in an immunocompetent young man

Abstract: The oncogenic role of high-risk HPV in anogenital, head and neck, and cervical cancer is well recognized, but not in skin cancer in the general population. Some authors have demonstrated their appearance mainly on the hands and feet, particularly in the area of the nail bed, which could be due to contamination with HPV types from anogenital regions. Here, we describe a case of genital HPV associated with SCC on the nose tip in an immunocompetent young man, which was confirmed by histopathological findings and in situ hybridization. The importance of this report is to highlight the potential role of HPV in the etiology of skin cancer in an immunocompetent individual.

Cáncer orofaríngeo y virus del papiloma humano en cabeza y cuello: relaciones fisiopatológicas y epidemiológicas / Oropharyngeal carcinoma and papiloma virus in head and neck: phisiopathological and epidemiological relations

Resumen El Virus del Papiloma Humano (VPH) es una enfermedad diagnóstico frecuente, transmitida por contacto entre piel y mucosas. Se han descrito múltiples relaciones etiológicas con neoplasias en órganos del sistema genital y reproductor y a nivel de cabeza y cuello. Éste se ha agrupado y caracterizado mediante análisis filogenéticos y en su secuencia de nucleótidos y aminoácidos. EL VPH progresa por las capas de epitelio de piel o mucosa induciendo malignización celular. El diagnóstico se realiza mediante diversas técnicas de PCR o de hibridación in situ. El carcinoma orofaríngeo es una patología neoplásica con una presentación clínica variada. Su asociación a VPH es inmunohistoquímicamente detectable, y se asocia a una presentación más frecuente en jóvenes, en hombres, con una localización anatómica mejor definida, y con una expresión clínica más florida y temprana. Actualmente se ha documentado un incremento en los casos de carcinoma orofaríngeo a pesar del descenso de su principal factor de riesgo; el tabaquismo. Su incidencia y mortalidad continúan siendo relativamente bajas en comparación con otros tumores en cabeza y cuello. Este incremento se ha asociado etiológicamente a la infección de VPH con subtipos de mayor riesgo de malignidad como el VPH 16 y 18. A nivel nacional existen diferencias estadísticas con respecto a los datos foráneos, sin embargo la cantidad de estudios realizados en nuestra población y los sesgos asociados al subregistro de la enfermedad son un factor importante a tomar en cuenta. Es necesario realizar una mayor cantidad de estudios en la población costarricense para determinar el comportamiento real de esta enfermedad y su relación etiológica con el carcinoma de orofaringe en nuestro país.

Abstract The Human Papilloma Virus (HPV) is a frequently diagnosed sexually transmitted disease, transmitted by contact between skin and mucous membranes. There are multiple etiological relationships between HPV infections and neoplasms in organs of the reproductive and genital system and at head and neck. Those belonging to HPV have been grouped and characterized by phylogenetic analysis and by its sequence of nucleotides and amino acids. HPV progresses through the layers of skin or mucosal epithelium inducing malignant transformation in these cells. The diagnosis of this infection is performed using various techniques of PCR and in situ hybridization. Oropharyngeal carcinoma is a neoplastic disease with a varied clinical presentation. Its association with HPV is detectable by immunohistochemic methods. It's also associated more frequent with young people, men, presentation with a better defined anatomic location and an earlier clinical expression. Currently it has been documented an increase in cases of oropharyngeal carcinoma despite the fall of their main risk factor; smoking. Its incidence and mortality continue to be relatively low in comparison with other head and neck tumors. This increase has etiologically been associated with HPV infection; and with subtypes of increased risk of malignancy such as HPV 16 and 18; as with changes in the behavior of the disease. National statistics differ from the foreign data, however the low amount of studies in our population and the biases associated with underreporting of the disease are an important factor to take into account. It is necessary to perform a greater number of studies in the Costa Rican population to determine the actual behavior of this disease and its etiological relation to carcinoma of the oropharynx.

Tipificación viral en el seguimiento de conización: rol pronóstico de la persistencia del HPV post cono con asa / Viral typing in conization monitoring: prognostic role of HPV persistence post cone with loop

RESUMEN Fundamento: La persistencia del virus papiloma posterior a la conización del cuello uterino, se ha considerado un factor de riesgo para la persistencia de lesiones intra epiteliales (LIE) causadas por virus papiloma. Para determinar la asociación entre persistencia de lesión cervical y la presencia del virus papiloma posterior a la conización del cuello uterino, se realizó un estudio observacional prospectivo en un grupo de 123 pacientes portadoras de lesiones intraepiteliales de alto grado (LIEAG) tratadas con conización. Material y métodos: Se siguieron a 123 pacientes portadoras de LIEAG, ingresadas a la Unidad de Patología Cervical entre Abril de 2013 y Abril de 2014, las que fueron seguidas por 2 años hasta Abril de 2016. Se realizó genotipificación antes, y entre 4 a 6 meses posterior a la conización. Los datos se tabularon considerando la edad, paridad, tipo de virus, persistencia de LIE, reconización o requerimiento de histerectomía posterior. Resultados: La mediana de la edad fue de 37 años, el 91% fueron multíparas, y solo el 9% fueron nulíparas. El 56% ingresó por NIE III y el 44% por NIE II. Los virus más frecuentes fueron el 16, 31,58, 52 y 56. La persistencia de virus papiloma se constató en el 37% de las pacientes conizadas. La persistencia de LIE se observó en el 27% de las pacientes que fueron positivas para virus papiloma posterior a la conización, en comparación a sólo el 5% en las que fueron negativas. Del total de pacientes positivas para virus papiloma posterior a la conización, 12 de ellas presentaron persistencia de lesión confirmadas histológicamente por biopsia cervical, 8 pacientes requirieron recono por LIE de alto grado, 2 pacientes fueron a histerectomía y en 2 casos se realizó seguimiento estricto por NIE I. Cuando la tipificación post cono fue negativa solamente 3 pacientes requirieron conización y en sólo una se realizó seguimiento estricto por NIE I. Conclusión: La persistencia del virus papiloma posterior a la conización se asocia a mayor persistencia de LIEAG, mayor frecuencia de reconización o histerectomía posterior.

ABSTRACT Backgroud: The persistence of papilloma virus after conization of the cervix has been considered a risk factor for the persistence of cervical intra epithelial lesion (CIN) caused by papilloma virus. Aim: In order to determine the association between cervical lesion persistence and the presence of papilloma virus after conization, a prospective observational study was performed in a group of 123 patients with intraepithelial lesions treated with conization. Material and methods: We followed 123 patients with high grade CIN who were admitted to the Cervical Pathology Unit, between April 2013 and April 2014; they were followed for 2 years until April 2016. Viral genotyping was done before, and among the 4 to 6 months after the LEEP. Data were tabulated considering age, parity, type of virus, persistence of CIN, reconization or requirement of posterior hysterectomy. Results: The median age was 37 years, 91% were multiparous, and only 9% were nulliparous. 56% had NIE III and 44% NIE II. The most frequent viruses were 16, 31, 58, 52 and 56. The persistence of papillomavirus was present in 37% of patients. The persistence of CIN was observed in 27% of patients who were positive for papilloma virus after conization, compared to only 5% in those who were negative. Of the total number of patients positive for papilloma virus, in 12 of them had intra epitelial lesions were confirmed by cervical biopsy, 8 patients required recone for high grade CIN, 2 patients underwent hysterectomy, and 2 patients underwent follows up strictly by CIN I. When post cone typing was negative only 3 patients required conization and only one was followed strictly by CIN I.

A high prevalence of human papillomavirus 16 and 18 co-infections in cervical biopsies from southern Brazil

ABSTRACT HPV types 16 and 18 were studied in paraffin-fixed cervical biopsy collected in southern Brazil. HPV 16, HPV 18 and co-infection HPV 16/18 were identified in 10/57 (17.5%), 4/57 (7%) and in 43/57 (75.4%) samples, respectively. Southern Brazil has one of the highest prevalence rates of HPV 16/18 reported.

Pigmented Bowen's disease associated with high-risk HPV simulating melanoma of the hand

Abstract: Bowen's disease is an in situ squamous cell carcinoma of the skin with only 2% of pigmented cases reported. It is clinically characterized by papules and plaques of blackened surface that may be caused either by sun damage - usually in photoexposed areas in elderly individuals - or by human papillomavirus infection - usually in the anogenital region of young adults. Dermoscopic aspects of Bowen's disease are discussed for over a decade, but with no definitive criteria that would lead to a definitive diagnosis. We present a case of Bowen's disease affecting the finger of a 57-year-old Asian patient. The lesion clinically and dermoscopically simulated a melanoma. Histopathological findings suggested the diagnosis of pigmented Bowen's disease. Pigmented Bowen's disease should be considered a differential diagnosis of melanoma, since its clinical and dermoscopic criteria are unspecific. Histopathological examination remains the gold standard for the diagnosis of the disease.

Infección genital masculina por virus de papiloma humano / Male genital infection by human papiloma virus

El virus del papiloma humano (VPH) es una de las enfermedades de transmisión sexual más comunes. Puede afectar tanto el aparato genital masculino y femenino, como también el área perianal, ano, y diversas áreas de cabeza y cuello y otorrinolaringológicas, ya sea como lesiones benignas o como promotor de lesiones malignas. Las lesiones benignas por VPH en genitales masculinos se caracterizan fundamentalmente por la aparición de lesiones verrugosas, aunque también puede manifestarse mediante lesiones planas atípicas. En algunos casos hay ausencia de lesiones macroscópicamente visibles que pueden hacerse evidentes con la prueba de ácido acético. La biopsia de la lesión, su evaluación anatomopatológica y, sobre todo, la determinación de la existencia y el tipo de virus involucrado mediante PCR (reacción en cadena de la polimerasa) permiten confirmar el diagnóstico. En algunas ocasiones es necesario realizar una cistoscopia para diagnosticar lesiones intrauretrales y vesicales. Los tratamientos propuestos son muy variados y de eficacia dispar, desde las topicaciones y la electrocirugía o la criocirugía, hasta el empleo de la tecnología láser. La prevención con el uso de protección durante el acto sexual así como la educación sexual son fundamentales. En los últimos 10 años se ha implementado el uso de la vacuna para el VPH en niñas con el fin de disminuir la incidencia de lesiones de alto grado y de cáncer de cuello uterino, pero su indicación en varones es menos clara y aún no ha sido consensuada. (AU)

Human papiloma virus (HPV) is one of the most common sexual transmitted diseases. It can affect the male genitalia, as well as the perianal and anal regions and multiple areas of the head and neck and otorhinolaryngological structures, as benign lesiones or as a promoter of malignant lesions. Benign male genitalia lesions are characterized mainly by verrucous lesions, although flat atypical lesions can be found, as well as the abscence of macroscopic visible lesions that in some cases can become evident using the acetic acid test. Lesion biopsy, its histological evaluation, and the determination of the existence and type of virus using PCR (Polymerase Chain Reaction) can confirm the diagnosis. In some cases is necessary to do a cistoscopy to diagnose intraurethral and vesical lesions. Proposed treatments are varied and with a wide range of efficacy, from topications to electro or cryosurgery, and the use of laser technology. Sexual education and the use of sexual protection are essential in prevention. In the last 10 years the use of VPH vaccine in girls was widely spread, in order to decrease the incidence of high grade lesions and cervix cancer. Its indication in male patients is less clear and not yet consented among specialists. (AU)