Cutaneous squamous cell carcinomas (cSCC) are among the most prevalent and costly cancers in Australia, yet the exact pathways enabling transformed keratinocytes to escape from immune surveillance and progress to SCC are still not known. In Human Papillomavirus (HPV) associated mucosal SCC, HPV transcripts contribute to immune suppression and hyperproliferation, thereby enabling cancer progression. Despite an association between HPV persistence in the epidermis and squamous cancer development, a causal link between HPV gene transcription and skin cancer initiation has not been shown to date, largely due to a lack of sensitive enough methodology to capture rare viral transcription events. Here, we describe a pipeline that enables us to detect and genotype transcriptionally active HPV genotypes in epithelial cells using single-cell RNA sequencing. A sample from an immunosuppressed patient was found to express HPV E5 and E6 genes, but not the commonly cancer-associated E7 oncogene. Ongoing work uses the presented workflow to screen SCC patient samples for HPV gene transcription, as well as investigate downstream signalling pathways and thus provide mechanistic links between virus life cycle and cancer progression.