MICROBIOME REVEALS PRO-INFLAMMATORY BACTERIA AND FUNCTIONAL PATHWAYS IN HPV+ PENILE CARCINOMA

INTRODUCTION: Penile squamous cell carcinoma (SCCP) is a rare disease and more prevalent in developing countries, such as Brazil, and is linked to poor genital hygiene, which promotes the proliferation of microorganisms. Dysbiosis affects the local immune response, increases the risk of viral infection and can generate inflammatory processes. Current knowledge of the microbiota found in penile tissues is limited, and the bacterial diversity of SCC remains unknown. In this investigation, the microbiota associated with SCC and their potential role in tumor development and progression were evaluated. METHODS: The 16S rRNA gene was analyzed by next-generation sequencing in 19 tumors and their respective adjacent non-tumor tissues to perform taxonomic classification, analysis of the core microbiome, abundance and diversity of amplicon variant sequences (ASVs) and in silico functional prediction (p<0.05). RESULTS: In both tissues, the phyla Proteobacteria and Firmicutes, and the genera Alcaligenes and Fusobaterium, were the most prevalent. Tumors showed greater abundance of Fusobacteriota, Campylobacteria, and Fusobacterium (p=0.04, p=0.04, and p=0.039, respectively). Furthermore, beta diversity revealed a tendency towards the formation of two distinct groups when only advanced tumors (pT2 and pT3) were considered. Additionally, functional analysis identified 35 main related pathways, of which the top 3 are: chitinase, sucrose and inositol degradation. And 79.5% of SCC samples contained pro-inflammatory microorganisms. CONCLUSION: We described the first SCCP microbiome, which revealed an abundant and diverse microbiota and pathways that have also been associated with inflammation and carcinogenesis. Furthermore, we found specific ASVs in tumor and non-tumor tissues. Our data encourage further studies to better understand the role of these microorganisms in penile carcinogenesis, offering an opportunity for advances in diagnosis, prognosis and early therapy.