The incidence of HPV associated oropharyngeal cancers (OPC) has been rising, making it one of the most common HPV related malignancies. The high-risk variant HPV16 accounts for up to 90% of HPV related OPC. In this study we aimed to uncover the interaction between two major ncRNA players in carcinogenesis, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). LncRNAs and miRNAs are described as independent master regulators; however, evidence suggests the two ncRNAs can interact with each other. We processed and analysed the RNA-sequencing data from TCGA of 49 Oropharyngeal patients to identify differential expressed (DE) lncRNAs, miRNAs and mRNAs between HPV16+ and HPV- tissues. We identified 1929 DE lncRNAs when comparing HPV16+ to HPV- OPC. The function of these lncRNAs have not previously been reported OPC and are unique to this study. Between the HPV16+ and HPV- OPC tissues there were 32 DE-miRNAs and 60 DE-mRNAs. Using an interactome analysis we explored the specific functions of these lncRNAs in relation to miRNA sponging and the impact of altered expression on the RNA axis, which includes: lncRNA/miRNA/mRNA. Nearly all our differentially expressed lncRNAs had the potential to bind to one or more DE-miRNA, impacting multiple miRNA targets. The DE-lncRNAs were linked to cellular pathways including cell cycle and proliferation, signal receptor binding and the PI3K-Akt signalling pathway, highlighting the critical role they play in HPV16 related OPC.Overall, we demonstrated that HPV16 does lead to altered expression of non-codingRNAs in OPC. Through an interactome analysis we identify novel lncRNA-miRNA interactions in HPV16+ OPC. We have described a unique lncRNA/miRNA/mRNA axis in HPV16 related OPC. These molecular interactions have the potential to be key targets of HPV16 and play an important role in HPV driven cancers.