BackgroundThe objectives of this study were to determine the minimum incidence of penile cancer in the poorest Brazilian state, and to describe the epidemiologic and clinical characteristics of patients diagnosed with the disease.MethodsA retrospective study of 392 patients diagnosed with penile cancer in the three most important referral center in the state was conducted during 2004–2014.ResultsThe age-standardized incidence was 6.15 per 100,000 and the crude annual incidence was 1.18 per 100,000. More than half (61.1%) of the tumors were histological grades 2 and 3, and 66.4% of tumors were classified as at least stage T2. The average age of patients was 58.6 ± 15.7 years (range, 18 to 103 years), with 20.8% of patients ≤40 years of age at diagnosis. The vast majority underwent penectomy (93%). Only 41.8% underwent lymphadenectomy, 58 patients (14.8%) received chemotherapy, and 54 patients (13.8%) received radiotherapy. Stage 3/4 and vascular invasion were statically significant at disease-free survival analysis.ConclusionThe state of Maranhão has the highest incidence of penile cancer in Brazil and globally. Tumors are locally advanced and at the time of diagnosis, and there is a high frequency among young individuals. Patients have a low socioeconomic status, making it difficult to complete treatment and receive appropriate follow-up.

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

factors, the diagnosis is delayed (Gao et al., 2016). Consequently, patients are usually diagnosed at an advanced stage, resulting in total or partial penectomy, and often present with regional lymph node metastasis and reduced survival (

Purpose Penile cancer is highly prevalent in low- and middle-income countries, with significant morbidity and mortality rates. The first Brazilian consensus provides support to improve penile cancer patients’ outcomes, based on expert’s opinion and evidence from medical literature. Methods Fifty-one Brazilian experts (clinical oncologists, radiation oncologists, urologists, and pathologists) assembled and voted 104 multiple-choice questions, confronted the results with the literature, and ranked the levels of evidence. Results Healthcare professionals need to deliver more effective communication about the risk factors for penile cancer. Staging and follow-up of patients include physical examination, computed tomography, and magnetic resonance imaging. Close monitoring is crucial, because most recurrences occur in the first 2–5 years. Lymph-node involvement is the most important predictive factor for survival, and management depends on the location (inguinal or pelvic) and the number of lymph nodes involved. Conservative treatment may be helpful in selected patients without compromising oncological outcomes; however, surgery yields the lowest rate of local recurrence. Conclusion This consensus provides an essential decision-making orientation regarding this challenging disease.