Presence of HPV with overexpression of p16INK4a protein and EBV infection in penile cancer-A series of cases from Brazil Amazon.

BACKGROUND: In Brazil, penile cancer (PC) is not uncommon. The highest incidence of PC is in the North and Northeast of the country. In addition to phimosis, the Human Papillomavirus (HPV) and Epstein-Baar Virus (EBV) infections are also related as risk factors for PC. The overexpression of p16INK4a is a surrogate sensitive marker of HPV infection in PC. OBJECTIVES: To correlate p16INK4a overexpression and HPV infection status with EBV infection in a series of PC patients from the Amazon region. METHODS: Tumor tissues from 47 PC cases were analyzed for the presence of HPV and EBV DNA by PCR. All PC patients were diagnosed between 2013 and 2018 at a public reference cancer center hospital in Manaus, Amazonas-Brazil. HPV was genotyped using E7 HPV16/HPV18 type-specific real-time PCR and the PapilloCheck® HPV-Screening assay. p16INK4a expression was evaluated by immunohistochemistry using the automated Ventana® BenchMark Ultra. RESULTS: The mean age of patients at the time of diagnosis was 57.4 years ±SD 17.8 ranging from 20 to 90 years old. Most of the patients (64%) came from rural areas of the Amazonas State. Thirty patients had phimosis (64%). Among the patients with phimosis, 43% (13/30) underwent circumcision, three during childhood and 10 in adulthood. 60% of the patients were smokers or ex-smokers. HPV infection was observed in 45% (21/47) of cases. HPV16 was detected in 13 patients (61%). Other HPV types detected were HPV 6, 11, 42, 51, 53, 68 and 44/55. EBV infection was observed in 30% (14/47) of the patients with PC. Co-infection with HPV and EBV was observed in 28% (6/21) cases. p16INK4a was only investigated in 26 samples. The p16INK4a overexpression was observed exclusively in HPV 16 positive cases and four HPV negative cases. In the survival analysis, the follow-up time was 35.4 months/patient. The mortality rate during the follow up time was 38%. CONCLUSIONS: p16INK4a positivity presented a high correlation to HPV 16 DNA detection, reinforcing its use as a surrogate marker for HPV-driven cancers. Infection with EBV was quite frequent and its role in epithelial penile oncogenesis needs to be demonstrated.

Avaliação da segurança e eficácia da abiraterona e enzalutamida pré e pós-quimioterapia no tratamento de pacientes com câncer de próstata metastático castração-resistente: revisão sistemática / Assessment of safety and treatment capacity and pre-treatment and post-treatment chemotherapy without treatment of patients with castration-resistant metastatic prostate cancer: systematic review

O câncer de próstata é no mundo e no Brasil. Alguns pacientes são diagnosticados em fase avançada um problema de saúde pública com alta prevalência ou progridem para tal após o tratamento inicial. Na fase do câncer de próstata metastático castração resistente (CPMCR), o emprego do acetato de abiraterona (AA) e enzalutamida (ENZ) surgem como alternativas de tratamento. O objetivo da tese foi sintetizar as evidências científicas disponíveis, através de uma revisão sistemática (RS), sobre a segurança e eficácia do AA e ENZ empregados em homens com CPMCR antes e após a quimioterapia. Procurou-se também avaliar os mesmos atributos das tecnologias em idosos com idade ≥ 75 anos e pacientes com metástase visceral. Foram pesquisadas cinco bases de dados bibliográficas eletrônicas ­ Medline, Embase, Lilacs, Scopus, Web of Science ­ e duas bases de registros de ensaios clínicos - CENTRAL e ClinicalTrials. Foram utilizados descritores do Medical Subject Headings (MeSH) e termos livres correspondentes ao problema de saúde e às tecnologias de interesse, combinados com uso dos operadores booleanos AND e OR, sem restrição inicial de idioma. Foram incluídos artigos no período de janeiro de 2006 a dezembro de 2018. Todas as etapas da RS foram realizadas por dois revisores independentes. A qualidade metodológica foi avaliada utilizando-se a ferramenta da Colaboração Cochrane. Foram identificadas 9.465 referências, sendo que apenas 29 artigos seguiram para fase de análise dos textos completos. Na segunda fase, apenas 12 estudos foram incluídos, com seis correspondentes a ensaios clínicos fase III originais, quatro contemplando o uso da AA (dois utilizando AA antes da QT e outros dois após-QT) e dois com utilização de ENZ (um antes da QT e um após a QT). Outros seis estudos trataram da análise de subgrupos, idade > 75 anos e com presença de metástase visceral. A sobrevida global e o tempo livre de progressão radiológica mostraram resultados favoráveis ao uso de AA e ENZ, inclusive em indivíduos na faixa etária com mais de 75 anos e com presença de metástase visceral com ganho de sobrevida de aproximadamente quatro meses. Os medicamentos evidenciaram baixas taxas de eventos adversos de graus moderados e graves, não havendo diferença estatística em relação ao uso do placebo em relação a eventos adversos grau V (entre 3,5 e 3,7%), e na taxa de descontinuidade do tratamento, ao redor de 6 a 8%. Ambos os medicamentos AA e ENZ evidenciaram benefícios similares. A despeito dos resultados favoráveis, estes apoiam-se em poucos ECCR fase III, o que deve ser levado em conta em decisões de eventual incorporação ao Sistema Único de Saúde

Prostate cancer is a public health problem with high prevalence worldwide and in Brazil. Some patients are diagnosed at an advanced stage or progress to it after initial treatment. In the phase of castration resistant metastatic prostate cancer (CPMCR), the use of abiraterone acetate (AA) and enzalutamide (ENZ) appear as treatment alternatives. The aim of the thesis was to synthesize the available scientific evidence through a systematic review (SR) on the safety and efficacy of AA and ENZ employed in men with CPMCR before and after chemotherapy (QT). We also sought to evaluate the same attributes of technologies in the elderly aged ≥ 75 years and patients with visceral metastasis. We searched five electronic bibliographic databases - Medline, Embase, Lilacs, Scopus, Web of Science - and two clinical trial record databases - CENTRAL and ClinicalTrials. Medical Subject Headings (MeSH) descriptors and free terms corresponding to the health problem and the technologies of interest were used, combined with the use of AND and OR boolean operators, without initial language restriction. Articles were included from January 2006 to December 2018. All stages of RS were performed by two independent reviewers. Methodological quality was assessed using the Cochrane Collaboration tool. 9,465 references were identified, and only 29 articles went to the full text analysis phase. In the second phase, only 12 studies were included, with six corresponding to original phase III clinical trials, four contemplating the use of AA (two using AA before QT and two after QT) and two using ENZ (one before QT and one after QT). Another six studies dealt with subgroup analysis, age> 75 years and visceral metastasis. Overall survival and time-free radiological progression showed favorable results for the use of AA and ENZ, even in individuals over 75 years of age and visceral metastasis with a survival gain of approximately four months. The drugs showed low rates of moderate and severe adverse events, with no statistical difference regarding placebo use compared to grade V adverse events (between 3.5 and 3.7%), and treatment discontinuation rate. , around 6 to 8%. Both AA and ENZ drugs showed similar benefits. Despite the favorable results, they are supported by few phase III ECCRs, which should be taken into account in decisions of eventual incorporation into the Unified Health System

Prevalence of and risk factors for penile infection by high-risk human papillomavirus among men infected with HIV.

This study aimed to determine the prevalence of and risk factors for high-risk human papillomavirus (HPV) genital infection and precursor lesions of penile cancer among patients infected with human immunodeficiency virus (HIV). In total, 276 men with a mean age of 34.6 years were included. All participants were subjected to peniscopic examination under magnification, collection of genital exfoliated cells for detecting HPV types using Hybrid Capture, and biopsy surgery of clinically observable lesions and aceto-white areas for histopathological studies. The prevalence of high-risk HPV types was 43%. Peniscopicy showed clinically visible lesions or aceto-white areas in 75/276 participants (27%), of which genital warts were the most common (22/75; 29%). HIV-positive (HIV(+) ) men with CD4(+) T-cell counts <200 cells/mm(3) showed a higher prevalence of penile lesions. Multivariate logistic regression was applied to identify independent risk factors for high-risk HPV types. The results showed that high-risk HPV was associated with lower education level (OR = 1.89, 95% CI: 1.15-3.13), illicit drug use (OR = 1.80, 95% CI: 1.03-3.14), mulatto ethnicity (OR = 2.51, 95% CI: 1.38-4.54), heterosexual orientation (OR = 2.12, 95% CI: 1.30-3.47) symptomatic AIDS (OR = 2.80, 95% CI: 1.65-4.77), AIDS-associated opportunistic infections (OR = 2.92, 95% CI: 1.78-4.78), on HAART (OR = 2.91, 95% CI: 1.78-4.77), and CD4(+) T-cell count <200 cells/mm(3) (OR = 3.31, 95% CI: 1.84-5.96). Immunocompromised men were more susceptible to developing penile lesions associated with high-risk HPV types.

Clinical and laboratorial study of HPV infection in men infected with HIV.

OBJECTIVES: To determine the prevalence of precursor lesions of penile cancer, to establish the concordance of diagnostic techniques (PCR, Hybrid Capture (HC) and peniscopy with acetic acid 5%) in the diagnosis of Human Papilloma Virus (HPV) of the penis of men infected with HIV and to evaluate the influence of the immune status. PATIENTS, METHODS AND RESULTS: 276 men were studied, with a median age of 34.6 years. Prevalence of High Risk HPV, Low Risk HPV and infection with both, according to HC, was 43%, 32% and 22%, respectively. PCR showed 50% of positivity for HPV DNA. Peniscopy was positive in 27% of individuals. Peniscopy showed good specificity and low sensitivity for the detection of penile HPV, and low concordance with PCR. Men with white lesions had a 3.6 higher relative risk of positivity for HPV. The most common clinical lesion observed was vegetation, identified in 29% of patients. PCR and HC techniques showed high sensitivity for HPV DNA and there was an excellent correlation between them. Immunosuppressed individuals with CD4 < 200 cells/mm(3) had the highest prevalence of premalignant lesions that were observed in 10% of the studied individuals. CONCLUSIONS: Peniscopy was important for identification and treatment of subclinical lesions. PCR and HC techniques were sensitive methods for the detection of HPV DNA with high concordance. Severely immunosuppressed individuals showed a higher prevalence of pre-malignant lesions of the penis.

Clinical and laboratorial study of HPV infection in men infected with HIV

OBJECTIVES: To determine the prevalence of precursor lesions of penile cancer, to establish the concordance of diagnostic techniques (PCR, Hybrid Capture (HC) and peniscopy with acetic acid 5%) in the diagnosis of Human Papilloma Virus (HPV) of the penis of men infected with HIV and to evaluate the influence of the immune status. PATIENTS, METHODS AND RESULTS: 276 men were studied, with a median age of 34.6 years. Prevalence of High Risk HPV, Low Risk HPV and infection with both, according to HC, was 43%, 32% and 22%, respectively. PCR showed 50% of positivity for HPV DNA. Peniscopy was positive in 27% of individuals. Peniscopy showed good specificity and low sensitivity for the detection of penile HPV, and low concordance with PCR. Men with white lesions had a 3.6 higher relative risk of positivity for HPV. The most common clinical lesion observed was vegetation, identified in 29% of patients. PCR and HC techniques showed high sensitivity for HPV DNA and there was an excellent correlation between them. Immunosuppressed individuals with CD4< 200 cells/mm3 had the highest prevalence of pre-malignant lesions that were observed in 10% of the studied individuals. CONCLUSIONS: Peniscopy was important for identification and treatment of subclinical lesions. PCR and HC techniques were sensitive methods for the detection of HPV DNA with high concordance. Severely immunosuppressed individuals showed a higher prevalence of pre-malignant lesions of the penis.