Human papillomaviruses (HPVs) are highly prevalent giving rise to both benign and malignant lesions why they are classified as high- and low-risk viruses. In this study we selected one low-risk (HPV 11) and two high-risk (HPV 16 and -45) types for genomewide miRNA analysis to investigate possible common and distinct features in the expression profiles. For this purpose we developed a cell culture model system in HaCaT cells for expression of the viral genomes under standardized conditions. We identified 25 miRNAs which were differentially regulated in two or three HPV types where 13 miRNAs were in common for all three types. Among the miRNAs identified, miR-125a-5p, miR-129-3p, miR-363, and miR-145 are related to human cancers. Noteworthy, miR-145 is found upregulated in the miRNA profiles of both high-risk HPV types. For selected differentially expressed miRNAs in HPV 16 predicted miRNA target transcript involved in signal transduction, RNA splicing and tumor invasive growth were validated by qRT-PCR. In addition, our results imply that the early 3' untranslated region (3'UTR) of the three HPV genomes were not a target for miRNA regulation.