A New Brazilian Device for Cervical Cancer Screening: Acceptability and Accuracy of Self-sampling.

OBJECTIVE: To evaluate the accuracy and patient acceptability toward self-sampling using a new device - SelfCervix® - for detecting HPV-DNA. METHODS: A total of 73 women aged 25-65 who underwent regular cervical cancer screening from March to October 2016 were included. Women performed self-sampling followed by a physician-sampling, and the samples were analyzed for HPV-DNA. After that, patients were surveyed about their acceptability of self-sampling. RESULTS: HPV-DNA detection rate of self-sampling presented high accuracy and was similar to physician-collection. Sixty-four (87.7%) patients answered the acceptability survey. Most patients (89%) considered the self-sampling comfortable, and 82.5% preferred self-sampling to physician-sampling. The reasons cited were time-saving and convenience. Fifty-one (79.7%) reported that they would recommend self-sampling. CONCLUSION: Self-sampling using the new Brazilian device SelfCervix® is not inferior in HPV-DNA detection rate compared with physician-collection, and patients are supportive of the method. Therefore, it might be an option to reach under-screened populations in Brazil.

OBJETIVO: Avaliar a acurácia e aceitabilidade da auto-coleta utilizando um novo coletor - SelfCervix® - para a detecção de DNA de HPV. MéTODOS: Foram incluídas no estudo 73 mulheres com idade entre 25­65 anos que realizaram seu rastreamento regular do câncer de colo do útero entre Março e Outubro de 2016. Estas mulheres realizaram a auto-coleta, seguida de coleta profissional e as amostras foram analisadas para a presença de DNA de HPV. Após, elas responderam um questionário sobre a experiência da auto-coleta. RESULTADOS: As taxas de detecção de DNA de HPV por auto-coleta foram altas e similares as da coleta profissional. Sessenta e quatro (87,7%) pacientes responderam o questionário de experiência. A maioria (89%) considerou a auto-coleta confortável, e 82,5% preferiram o método comparado a coleta profissional. As razões citadas foram economia de tempo e conveniência. Cinquenta e uma (79,7%) mulheres confirmaram que recomendariam a auto-coleta. CONCLUSãO: Auto-coleta utilizando o novo coletor desenvolvido no Brasil não é inferior na detecção de DNA de HPV quando comparada a coleta profissional, e apresenta uma boa aceitabilidade pelas mulheres. Desta maneira, pode ser uma opção para alcançar populações que não realizam o rastreamento padrão.

A New Brazilian Device for Cervical Cancer Screening: Acceptability and Accuracy of Self-sampling / Um Novo Dispositivo Brasileiro para Diagnóstico de Câncer Cervical: Aceitabilidade e Precisão da Autoamostragem

Abstract Objective To evaluate the accuracy and patient acceptability toward self-sampling using a new device - SelfCervix® - for detecting HPV-DNA. Methods A total of 73 women aged 25-65 who underwent regular cervical cancer screening from March to October 2016 were included. Women performed self-sampling followed by a physician-sampling, and the samples were analyzed for HPV-DNA. After that, patients were surveyed about their acceptability of self-sampling. Results HPV-DNA detection rate of self-sampling presented high accuracy and was similar to physician-collection. Sixty-four (87.7%) patients answered the acceptability survey. Most patients (89%) considered the self-sampling comfortable, and 82.5% preferred self-sampling to physician-sampling. The reasons cited were time-saving and convenience. Fifty-one (79.7%) reported that they would recommend self-sampling. Conclusion Self-sampling using the new Brazilian device SelfCervix® is not inferior in HPV-DNA detection rate compared with physician-collection, and patients are supportive of the method. Therefore, it might be an option to reach under-screened populations in Brazil.

Resumo Objetivo Avaliar a acurácia e aceitabilidade da auto-coleta utilizando um novo coletor - SelfCervix® - para a detecção de DNA de HPV. Métodos Foram incluídas no estudo 73 mulheres com idade entre 25-65 anos que realizaram seu rastreamento regular do câncer de colo do útero entre Março e Outubro de 2016. Estas mulheres realizaram a auto-coleta, seguida de coleta profissional e as amostras foram analisadas paraa presença de DNA de HPV. Após, elas responderam um questionário sobre a experiência da auto-coleta. Resultados As taxas de detecção de DNA de HPV por auto-coleta foram altas e similares as da coleta profissional. Sessenta e quatro (87,7%) pacientes responderam o questionário de experiência. A maioria (89%) considerou a auto-coleta confortável, e 82,5% preferiram o método comparado a coleta profissional. As razões citadas foram economia de tempo e conveniência. Cinquenta e uma (79,7%) mulheres confirmaram que recomendariam a auto-coleta. Conclusão Auto-coleta utilizando o novo coletor desenvolvido no Brasil não é inferior na detecção de DNA de HPV quando comparada a coleta profissional, e apresenta uma boa aceitabilidade pelas mulheres. Desta maneira, pode ser uma opção para alcançar populações que não realizam o rastreamento padrão.

Local and Systemic STAT3 and p65 NF-KappaB Expression as Progression Markers and Functional Targets for Patients With Cervical Cancer.

Cervical cancer, which main etiologic factor is Human Papillomavirus (HPV) infection, continues to be a burden for public health systems in developing countries. Our laboratory has been working with the hypothesis that signals generated in the tumor microenvironment can modulate local and systemic immune responses. In this context, it would be reasonable to think that tumors create pro-tumoral bias in immune cells, even before they are recruited to the tumor microenvironment. To understand if and how signaling started in the tumor microenvironment can influence cells within the tumor and systemically, we investigated the expression of key proteins in signaling pathways important for cell proliferation, viability, immune responses and tolerance. Besides, we used detection of specific phosphorylated residues, which are indicative of activation for Akt, CREB, p65 NFκB, and STAT3. Our findings included the observation of a significant STAT3 expression increase and p65 NFκB decrease in circulating leukocytes in correlation with lesion grade. In light of those observations, we started investigating the result of the inhibition of STAT3 in a tumor experimental model. STAT3 inhibition impaired tumor growth, increased anti-tumor T cell responses and decreased the accumulation of myeloid cells in the spleen. The concomitant inhibition of NFκB partially reversed these effects. This study indicates that STAT3 and NFκB are involved in immunomodulatory tumor effects and STAT3 inhibition could be considered as therapy for patients with cervical cancer.

Lactate secreted by cervical cancer cells modulates macrophage phenotype.

Cervical cancer continues to be a public health problem in developing countries. Previous studies have shown that cervical cancer cells display markers of aerobic glycolysis, indicating that these tumors are likely to secrete lactate. Mostly, lactate is recognized as a molecule capable of suppressing immune responses, through inhibition of T cells, Mϕs, and dendritic cells. We and others have previously shown that Mϕs are frequent cells infiltrating cervical cancers with the ability to inhibit antitumor immune responses and promote tumor growth through angiogenesis. Here, we have tested the hypothesis that lactate, secreted by cervical cancer cells, can modulate Mϕ phenotype. First, we showed higher lactate plasma concentrations in patients with increasing cervical lesion grades, with maximum concentration in the plasma of cancer patients, which supported our hypothesis. We then inhibited lactate production in tumor cell spheroids established from cervical cancer derived cell lines, using the lactate dehydrogenase inhibitor, oxamate, prior to co-culture with monocytes. Lactate mediated part of the crosstalk between tumor cells and Mϕs, promoting secretion of IL-1ß, IL-10, IL-6, and up-regulation of hypoxia induced factor-1α expression, and down-regulation of p65-NFκB phosphorylation in Mϕs. We also showed that Mϕs from co-cultures treated with oxamate were better inducers of T cell activation. Of note, experiments performed with inhibition of the monocarboxylate transporters rendered similar results. Our data confirms the hypothesis that lactate, secreted by cervical tumor cells, influences the phenotype of tumor Mϕs, promoting a suppressive phenotype.

B lymphocytes can be activated to act as antigen presenting cells to promote anti-tumor responses.

Immune evasion by tumors includes several different mechanisms, including the inefficiency of antigen presenting cells (APCs) to trigger anti-tumor T cell responses. B lymphocytes may display a pro-tumoral role but can also be modulated to function as antigen presenting cells to T lymphocytes, capable of triggering anti-cancer immune responses. While dendritic cells, DCs, are the best APC population to activate naive T cells, DCs or their precursors, monocytes, are frequently modulated by tumors, displaying a tolerogenic phenotype in cancer patients. In patients with cervical cancer, we observed that monocyte derived DCs are tolerogenic, inhibiting allogeneic T cell activation compared to the same population obtained from patients with precursor lesions or cervicitis. In this work, we show that B lymphocytes from cervical cancer patients respond to treatment with sCD40L and IL-4 by increasing the CD80+CD86+ population, therefore potentially increasing their ability to activate T cells. To test if B lymphocytes could actually trigger anti-tumor T cell responses, we designed an experimental model where we harvested T and B lymphocytes, or dendritic cells, from tumor bearing donors, and after APC stimulation, transplanted them, together with T cells into RAG1-/- recipients, previously injected with tumor cells. We were able to show that anti-CD40 activated B lymphocytes could trigger secondary T cell responses, dependent on MHC-II expression. Moreover, we showed that dendritic cells were resistant to the anti-CD40 treatment and unable to stimulate anti-tumor responses. In summary, our results suggest that B lymphocytes may be used as a tool for immunotherapy against cancer.

Partial vaginal expulsion of a leiomyosarcoma.

Uterine sarcomas are an uncommon and heterogeneous group of tumors that account for 3-7% of the malignant neoplasms of the uterus and approximately 1% of all malignant tumors of the female genital system. The main clinical manifestations are abnormal uterine bleeding in pre- or postmenopausal women. Pelvic pain, abdominal distension, urinary urgency, and profuse and fetid leukorrhea are other frequent complaints. The authors present a case of a 48-year-old patient that was in amenorrhea for 2 years, who sought treatment for vaginal bleeding. On physical examination, the abdomen was distended, painful in the hypogastrium and upon examination of the external genitalia, it was observed the exteriorization of an amorphous "mass". The patient was submitted to uterine curettage. The results of the histological examination revealed leiomyosarcoma. Staging workup showed an enlarged uterus with endometrial lesion, and non-calcified pulmonary nodules. The patient underwent a pan-hysterectomy and chemotherapy, and is under oncologic treatment. The authors call attention for the unusual form of presentation of this entity.

Tumor filóides / Phyllodes tumor

O Tumor Filódes é neoplasia mamária pouco freqüente, com crescimento rápido, chegando a ser volumoso. Seu diagnóstico por imagem torna difícil a suspeita de benignidade ou malignidade. A punção aspirativa com agulha fina (PAAF) não é recomendada por alguns autores, sendo melhor indicada a "core biopsy". O tratamento de escolha é o cirúrgico, não havendo consenso na literatur quanto à melhor técnica. A tendência atual é individualizar o tratamento, levando-se em consideração fatores como diâmetro tumoral, volume mamário, extensão da doença, tipo histológico e, até, a vontade da própria paciente. Relatamos três casos ilustrando a moléstia estudada