Pathogenic infections have been associated with cancer worldwide. About 18-20% of the malignancies have been attributed to infections, such as Helicobacter pylori, Fusobacterium, human papillomaviruses (HPV), hepatitis virus, Epstein–Barr virus (EBV)/human herpes virus (HHV) 4 viruses, and others. However, lack of understanding of the underlying mechanism to establish causality of pathogenic infections to carcinogenesis lends itself to want of further research. Here, we propose to systematically elucidate pathogens associated with human oral cancer using the in-house developed Cancer Pathogen Detector tool, and characterize their role in carcinogenesis using in vitro and in vivo model systems by integrating the changing global landscape of co-occurring mutations and chromatin activation states. This study would further the understanding of the underlying cellular functions in context of its complex interactions with infectious agents through epigenomics. The identification of newer oncogenic infectious agents along with its concomitant effect of the genome and epigenome of the host cell – in state of transformation-- would lead to the molecular understanding of oncogenic mechanisms, better sub-classification of disease according to etiology, understanding of the role of pathogens in disease progression, prevention of associated cancers by immunization or public health measures, and to develop specific targeted treatments.