Postmenopausal Vaginal Microbiome and Microbiota.

The ovulatory cycle has a significant influence on the microbial composition, according to the action of estrogen and progesterone on the stratified squamous epithelium, due to an increase in epithelial thickness, glycogen deposition, and influence on local immunology. The 16S rRNA gene amplification and pyrosequencing study demonstrated that healthy women have community state types (CST), classified as; type "L," with a predominance of Lactobacillus crispatus, type II, with a predominance of Lactobacillus gasseri, type III, where Lactobacillus iners predominates, and type V with a predominance of Lactobacillus jensenii. Type IV does not identify lactobacilli but a heterogeneous population of bacteria. There seems to be a relationship between increased vaginal bacterial diversity and poverty of lactobacilli with the complaining of vaginal dryness. With menopause, there appears to be a reduction in lactobacilli associated with higher serum levels of follicle-stimulating hormone (FSH) and lower estrogen levels. The evaluation of Gram-stained vaginal smears in postmenopause women must take into account the clinical-laboratory correlation. We should observe two meanly possibilities, atrophy with few bacterial morphotypes, without inflammatory, infiltrate (atrophy without inflammation), and atrophy with evident inflammatory infiltrate (atrophy with inflammation or atrophic vaginitis). The relationship between the microbiome and postmenopausal vulvovaginal symptoms seems to be related to the bacterial vaginal population. However, more robust studies are needed to confirm this impression.

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.

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

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

Greater expression of the human leukocyte antigen-G (HLA-G) and interleukin-17 (IL-17) in cervical intraepithelial neoplasia: analytical cross-sectional study / Aumento da expressão do antígeno leucocitário humano-G (HLA-G) e interleucina-17 (IL-17) em neoplasia intraepitelial cervical: estudo transversal analítico

CONTEXT AND OBJECTIVE:Impaired local cell immunity seems to contribute towards the pathogenesis and progression of cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms promoting its progression remain unclear. Identification of new molecular markers for prognosis and diagnosis of early-stage CIN may aid in decreasing the numbers of CIN cases. Several novel immunoregulatory molecules have been discovered over the past few years, including the human leukocyte antigen G (HLA-G), which through interaction with its receptors exerts important tolerogenic functions. Several lines of evidence suggest that T-helper interleukin-17 (IL-17)-producing cells (Th17 cells) may play a role in antitumor immunity. However, recent reports have implicated Th17 cells and their cytokines in both pro and anti-tumorigenic processes. The aim of the study was to evaluate the roles of HLA-G and Th17 in the immunopathogenesis of CIN I.DESIGN AND SETTING:Analytical cross-sectional study with a control group using 58 cervical specimens from the files of a public university hospital providing tertiary-level care.METHODS:We examined HLA-G and IL-17 expression in the cervical microenvironment by means of immunohistochemistry, and correlated these findings with clinical and pathological features.RESULTS:There was a greater tendency towards HLA-G and IL-17 expression in specimens that showed CIN I, thus suggesting that these molecules have a contribution towards cervical progression.CONCLUSION:These findings suggest that HLA-G and IL-17 expression may be an early marker for assessing the progression of cervical lesions.

CONTEXTO E OBJETIVO:A deficiência na imunidade celular localizada parece contribuir para a patogênese e progressão das neoplasias intraepiteliais cervicais (NIC), no entanto, ainda não está totalmente esclarecido o mecanismo molecular fundamental nesse processo de progressão. A identificação de novos marcadores moleculares de prognóstico e diagnóstico das NIC em estágios precoces pode ajudar a diminuir a quantidade de casos de NIC. Várias novas moléculas com função imunorregulatória foram descobertas nos últimos anos, inclusive o antígeno leucocitário humano G (HLA-G), que, através de interação com os receptores, tem importantes funções tolerogênicas. Diversas linhas de evidência sugerem que as células T-ajudantes produtoras de interleucina-17 (IL-17, células Th17), podem desempenhar um papel na imunidade antitumoral. Porém, recentes relatos implicaram as células Th17 e suas citocinas tanto em processos pro- quanto anti-tumorigênicos. O objetivo do estudo foi avaliar o papel do HLA-G e Th17 na imunopatogênese das NIC I.TIPO DE ESTUDO E LOCAL:Estudo transversal analítico com grupo controle em 58 espécimes cervicais dos arquivos de um hospital universitário público com assistência prestada no nível terciário.MÉTODOS:Avaliamos a expressão de HLA-G e IL-17 por imunoistoquímica no microambiente cervical, associando esses achados com as características clínico-patológicas.RESULTADOS:Houve tendência aumentada da expressão de HLA-G e IL-17 em espécimes que apresentaram NIC I, sugerindo que essas moléculas têm contribuição na progressão cervical.CONCLUSÃO:Estes resultados sugerem que a expressão do HLA-G e da IL-17 pode ser um marcador precoce para avaliar a progressão das lesões cervicais.

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

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

Greater expression of the human leukocyte antigen-G (HLA-G) and interleukin-17 (IL-17) in cervical intraepithelial neoplasia: analytical cross-sectional study.

CONTEXT AND OBJECTIVE: Impaired local cell immunity seems to contribute towards the pathogenesis and progression of cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms promoting its progression remain unclear. Identification of new molecular markers for prognosis and diagnosis of early-stage CIN may aid in decreasing the numbers of CIN cases. Several novel immunoregulatory molecules have been discovered over the past few years, including the human leukocyte antigen G (HLA-G), which through interaction with its receptors exerts important tolerogenic functions. Several lines of evidence suggest that T-helper interleukin-17 (IL-17)-producing cells (Th17 cells) may play a role in antitumor immunity. However, recent reports have implicated Th17 cells and their cytokines in both pro and anti-tumorigenic processes. The aim of the study was to evaluate the roles of HLA-G and Th17 in the immunopathogenesis of CIN I. DESIGN AND SETTING: Analytical cross-sectional study with a control group using 58 cervical specimens from the files of a public university hospital providing tertiary-level care. METHODS: We examined HLA-G and IL-17 expression in the cervical microenvironment by means of immunohistochemistry, and correlated these findings with clinical and pathological features. RESULTS: There was a greater tendency towards HLA-G and IL-17 expression in specimens that showed CIN I, thus suggesting that these molecules have a contribution towards cervical progression. CONCLUSION: These findings suggest that HLA-G and IL-17 expression may be an early marker for assessing the progression of cervical lesions.

Uterine cervical ectopy during reproductive age: cytological and microbiological findings.

Cervical ectopy is common in adolescents, pregnant women, and those taking high doses of estrogen-containing contraceptives. The majority of cases have spontaneous reversion, but some cases can be persistent. Studies suggested that the adequacy of a Pap smear could be affected and there is an increased risk cervical infections. This study is a cross-sectional study conducted from December 2009 to February 2011 with 457 women with cervical ectopy and 736 without ectopy. Cervical samples were collected in vials for analysis by ThinPrep cytology (Hologic, Marlborough, MA). The Mann-Whitney test and Fisher's exact test (95% CI) were applied. The study was approved by the ethics committee of the Federal University of Ceará. The mean ages of the study group and control group were 28.7 (±14.8) and 33.6 (±7.5) years old, respectively (P < 0.0001). Negative diagnosis for malignancy and intraepithelial lesion was present in 399 (87%) cases and 705 (96%) in the study and control groups, respectively (P < 0.0001). Shift in the flora suggestive of bacterial vaginosis (BV) was observed more frequently in the study group: 74 (16.2%) than in the control group: 86(11.7%) (P = 0.017). The differences among the other morphotypes showed no significance. The smears were atypical in 12.7% (58/457) of the patients from the study group and in 4.2% (31/736) in the control group (P < 0.001; RR = 3 [2.033-4.712]). The association between ectopy and inflammatory cytology, the presence of the shift in the flora suggestive of BV and cytological atypia is evident.

Qual deve ser o rastreamento de doenças infecciosas em casos de perda gestacional recorrente?: [revisão] / What should be the screening of infectious diseases in cases of recurrent pregnancy loss?: [review]

A perda gravídica de repetição ocorre em cerca de 1 a 2% das gestações, e em cerca de em 2% das vezes tem quadros infecciosos como agentes etiológicos. A necessidade de rastreio de causa infecciosa tem sido muito discutida na literatura. Com objetivo de avaliar o que se conhece sobre esta necessidade, foi realizada uma revisão sistemática de trabalhos em inglês, português e espanhol em bases de dados do Pubmed, Highwire, Lilacs e biblioteca Cochrane. Observou-se que, de todos os agentes, o mais estudado foi a Chlamydia trachomatis, em especial seu efeito imunológico tardio. Outros agentes têm sido associados ao aborto habitual, no entanto, as infecções bacterianas, virais e parasitárias podem interferir na evolução da gestação, mas não parece ser uma causa significante de aborto de repetição. O valor do rastreio parece ser limitado na investigação de perda gravídica de repetição fora de um episódio infeccioso agudo. No entanto, mais estudos se fazem necessários, em especial para avaliar efeitos tardios, como das infecções por Chlamydia trachomatis.

The recurrent pregnancy loss occurs in about 1-2% of pregnancies, and in about 2% the etiology would be infectious. The need for tracking infectious causes has been much discussed in the literature. In order to evaluate what is known about this need, we conducted a systematic review of papers in English, Portuguese and Spanish on this subject available in the databases of Pubmed, Highwire, Lilacs and Cochrane Library. Chlamydia trachomatis was mostly studied, especially with regard to its late immunological effect. Other agents have been associated with habitual abortion; however, bacterial infections, viral and parasitic diseases can interfere with the course of gestation, but does not seem to be a significant cause of recurrent abortion. The value of screening seems to be limited for the investigation of recurrent pregnancy loss if acute infection does not occur. However, further studies are needed, especially to evaluate late effects such as infections by Chlamydia trachomatis.