Característica sociodemográfica, epidemiológica, clínica e o viroma de pacientes com câncer de pênis do Estado do Amazonas

Abstract

Penile cancer is not an uncommon neoplasm in developing countries. Brazil appears among the countries with high incidence - particularly in the North and Northeast. The etiology of this neoplasm appears to be multifactorial; phimosis, retention of smegma, inflammatory processes, zoophilia, smoking, infection with oncogenic viruses such as Human papillomavirus (HPV) and Epstein-Barr virus (EBV) may be associated with the onset of cancer. The application of next generation sequencing (NGS) is a promising strategy in the discovery of potentially oncogenic virus in tumor tissue. Objectives: In order to understand the profile of penile cancer patients in the region, this study aimed to describe the sociodemographic, behavioral, clinical and viroma characteristics of penile cancer patients treated at a public oncology referral hospital in Manaus, Amazonas - Brazil. Methods: Forty-seven patients diagnosed with penile cancer from 2013 to 2018 were included in the study. Initially screening for oncogenic viruses (HPV and EBV) was performed by PCR. For the viral study by metagenomics we used the protocol NetoVIR - Novel enrichment technique of VIRomes. 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 patients had phimosis and come from the interior of the state of Amazonas or from other states (64% and 77%, respectively). 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. 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%. Thirteen patients with penile cancer non-HPV/EBV-associated were submitted viral metagenomic analysis. Bioinformatics analysis of high-throughput sequencing for virus detection combined two existing workflows which resulted in a range of 190-2,232 reads (< 0.1%) by Kraken and 458,189 – 1,277,735 reads (~6%) by Kaiju – RVDB. Interestingly, between 10-70% of the sequences remained unclassified, suggesting the potential of high throughput metagenomic sequencing studies, such as ours, to identify new microorganisms possibly related to cancer. Conclusions: Penile carcinogenesis has heterogeneous etiology and could be assigned HPV infection or molecular mechanisms independent of HPV. In this study, 27% (13/47) patients with penile cancer non-HPV/EBV-associated were analyses by NGS. Most of the DNA sequencing was found to represent unclassified sequences. As the bioinformatics analysis showed ~99% sequences to map against the human genome, it becomes possible to assess multiple genetic alterations and maybe to predict of outcome in penile cancer.