To determine the epidemiological, histopathological, and clinical characteristics of patients diagnosed with penile cancer in the Brazilian state of Maranhão, the region with the highest incidence worldwide. One hundred and sixteen penile cancer patients were interviewed from July 2016 to October 2018. The majority of patients lived in a rural area (57%), worked in farming (58%), had a low level of schooling or no schooling (90%), and were married or in a stable relationship (74%). The mean age was 60.4 ± 16.51 years (range, 23-93 years). Phimosis (66%), poor/moderate genital hygiene (73%), history of sexually transmitted infections (55%), and zoophilia (60%) were found in the majority of patients. Most patients had their first sexual encounter at 16.2 ± 2.8 years (range, 10-25 years), and 75% had >6 sexual partners. The most common initial symptom was pruritus (37%), and most patients waited to seek treatment (average time to treatment, 18.9 months; range, 2-84 months). Human papillomavirus (HPV)-related histologies were observed in 62% of patients. Most patients had histological grades II or III (87%), stage ≥T2 disease (84%), and lymphadenopathy at admission (42%). Penectomy was performed in 96% of patients. The population with penile cancer in the region of highest incidence in the world is marked by low socioeconomic status, high prevalence of HPV infection, and phimosis. The delay in seeking treatment is related to a very high rate of advanced cancer and aggressive surgical treatment. The high prevalence of young patients was also a striking feature.Penile cancer is uncommon in developed countries, and its incidence varies according to the demographic region and the circumcision status 1,2 . In the US and Europe, the age-standardized incidence rate (ASR) for 100,000 inhabitants is between 0.1 and 1.0 3 . However, in less developed countries, including some countries in South America, Asia, and Africa, the incidence is alarmingly high 1 . In uncircumcised males, the cumulative lifetime risk for cancer of the penis is higher compared to the general population, corresponding to 1 in 600 men in the US 2 . Brazil has a high incidence, and the state of Maranhão, located in the northeastern region of the country, has the highest incidence of penile cancer in the world (ASR of 6.1 cases per 100,000 inhabitants) 4 .The etiology of penile carcinoma remains unknown, and its mechanisms of development have not been completely elucidated. Phimosis, balanitis, smegma, precarious genital hygiene, smoking, history of sexually transmitted infections (STIs), and human papilloma virus (HPV) infection (present in approximately 50% of cases) are the main risk factors, and circumcision is an important protective factor 5-8 . Its incidence is higher in regions History of STIs 55 (40/73) Sexual history Age of first sexual encounter [mean (range)] 16.2 years (10-25 years) Zoophilia 60 (43/72) No. female partners Less than 6 25 (19/75) Between 6 and 10 17 (13/75) More than 10 58 (43/75) Duration of symptom [mean (range)] 18.9 months ...

The incidence of penile cancer (PeCa) is increasing worldwide, however, the highest rates are reported in underdeveloped countries. The molecular mechanisms that underly the onset and progression of these tumors are still unclear. Therefore, our goal was to determine the genome-wide copy number alterations and the involvement of human papiloma virus (HPV) (TP53 and RB1), inflammatory (COX2 and EGFR), and PI3K/AKT pathway (AKT1, AKT2, EGFR, ERBB3, ERBB4, PIK3CA, and PTEN) associated genes in patients with PeCa from a high incidence region in Brazil (Maranhão). HPV genotyping was performed by nest-PCR and genome sequencing, copy number alterations (CNAs) by array comparative genomic hybridization and gene copy number status, gene, and protein expression by quantitative polymerase chain reaction, reverse transcriptasequantitative polymerase chain reaction, and immunohistochemistry, respectively.HPV genotyping revealed one of the highest frequencies of HPV reported in PeCa, affecting 96.4% of the cases. The most common CNAs observed were located at the HPV integration sites, such as 2p12-p11.2 and 14q32.33, where Abbreviations: aCGH, array comparative genomic hybridization; CNA, copy number alteration; Cq, quantification cycle; FFPE, formalin-fixed paraffin-embedded; HPV, human papiloma virus;HrHPV, High risk HPV; IHCi, mmunohistochemistry; PCR, polymerase chain reaction; PeCa, penile cancer; qPCR, quantitative polymerase chain reaction; RT-qPCR, reverse transcriptase-quantitative polymerase chain reaction; TMA, tissue microarray. ADAM 6, KIAA0125, LINC00226, LINC00221, and miR7641-2, are mapped. Increased copy number of ERBB3 and EGFR genes were observed in association with COX2 and EGFR overexpression, reinforcing the role of the inflammatory pathway in PeCa, and suggesting anti-EGFR and anti-COX2 inhibitors as promising therapies for PeCa. Additionally, TP53 and RB1 messenger RNA downregulation was observed, suggesting the occurrence of other mechanisms for repression of these oncoproteins, in addition to the canonical HPV/TP53/RB1 signaling pathway. Our data reinforce the role of epigenetic events in abnormal gene expression in HPV-associated carcinomas and suggest the pivotal role of HPV driving CNAs and controlling gene expression in PeCa. K E Y W O R D Scarcinoma of the penis, genomic alterations, human papillomavirus, molecular markers

BackgroundOculosporidiosis (ocular rhinosporidiosis) accounts for 15% of cases of rhinosporidiosis, which is a chronic granulomatous disease and is endemic in India and Sri Lanka. In Brazil, the climatic and hydrographic similarities to these endemic areas and the presence of riverside populations contributes to an increase in the incidence of rhinosporidiosis particularly in the State of Maranhão. This study, therefore, aimed to identify the number of diagnosed cases of oculosporidiosis and describe its the clinical epidemiology, laboratory, histopathology, and therapeutic characteristics.MethodsThe study is descriptive, observational, and cross-sectional, and reports the prevalence and clinical epidemiological characteristics of oculosporidiosis in the State of Maranhão, Brazil. A retrospective analysis of the paper and electronic records for a period from 1999 to 2017 was conducted in the University Hospital of Federal University of Maranhão (HU-UFMA), located in the northeastern region of Brazil.ResultsThirty patients were diagnosed with rhinosporidiosis, eight of them had oculosporidiosis and seven of these met the criteria to be included in the study. Of the cases (23.3% of all 30), five were men (71.4%) and two women (28.5%), with an average age of 16.4 ± 15.6 years. In terms of race, four patients (57.1%) declared themselves white and three (42.9%) as brown. The north of the state, the mesoregion, had the most diagnosed cases accounting for 57.1% of the total. Left eye was the most affected site, reported in six patients (85.7%), while the conjunctiva was affected in all patients. Rhinosporidiosis and papilloma were the predominant diagnostic hypotheses (28.5 and 28.5%, respectively), followed by chronic scleritis, granuloma, and chalazion (14.25, 14.25, and 14.25%, respectively). All these cases were treated with lesion excision, and only two patients (28.5%) progressed with recurrence.ConclusionIt was verified that there was a male predominance, with only one eye reported as an infected site, with no bilateral involvement. The younger age group (between 1 and 2 years of age) was more affected by oculosporidiosis, and histopathological examination was necessary for a conclusive diagnosis.

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