Ricerc@Sapienza

Human papillomaviruses (HPVs) represent a large family of viral types associated with significant clinical disease of mucosal epithelium and oral and anogenital cancers. Increased evidences indicate that microbial imbalance may play a critical role in the development of multiple diseases, such as cancer, autoimmune conditions, and increased susceptibility to viral infection. However, to date few data are available on the complex interplay between persistent mucosal HPV infection, microbiota and cancer development. This project is focused on a comprehensive characterization of the role of oral and anogenital microenvironment in HPV driven cancer initiation and progression. Although HPV cancerogenesis has been thoroughly studied, its heterogeneous nature makes its understanding, prevention and proper treatment a remaining challenge in clinical settings. Through an integrative analysis of mucosal microbiota, HPV parameters (genotypes, E6/E7 mRNA expression and HPV genome integration), and type I/III interferon (IFN) signature, this pilot study will explore how microbiota mediate regulation of innate immune response in three different settings of HPV disease (oral, genital and anal), identifying predictive risk markers of precancerous mucosal lesions progression, and possibly therapeutic strategies to restore an healthy microenvironment. A clinical plus of the project is the focus on the HIV-1 risk group, men sex men (MSM), characterized by a high rate of HPV infection and anal cancer. Moreover, the IFN lambda production, which represents a key component of the mucosal immunity, has never been investigated in oral and anal HPV infection. This pilot study will provided first evidences on the functional implications of microbiota and host immune interactions in terms of risk assessment of HPV disease, opening new perspectives on the understanding of the potential effect of bacteria microbiota on IFN response, HPV persistence and cancerogenesis.