We investigated the effects of the human papillomavirus type 16 E5 oncogene on cellular gene expression in human epithelial cells using cDNA microarray. In a genome-wide microarray assay, the expression of 179 genes was found to be significantly altered due to E5 expression. The expression of lamin A/C was downregulated at protein level. The expression of protein kinase C-delta and phosphoinositide-3-kinase proteins was found to be upregulated. We also observed increased motility of E5-expressing cells. We conclude that the E5 protein affects several cellular pathways involved in cell adhesion, cell motility and mitogenic signaling. These alterations may together lead to inhibition of apoptosis and facilitate the establishment of persistent infection in the epithelium.