Human papillomavirus (HPV) productive infection has been long considered to be restricted to the squamous epithelium. However, we have demonstrated that both HPV type 16 (HPV-16) and type 31b (HPV-31b) productively replicate in a trophoblast cell line, 3A. Trophoblasts are an important cell type, as these are the cells of the placenta that directly contact maternal tissues. There are a number of studies that suggest that HPV infection may be found commonly in placental material and might be linked with spontaneous abortions. This chapter describes the preparation and transfection of HPV genomes into 3A cells, suggests ways to analyze viral replication and transcription, and describes how to assay the effect of HPV infection on the ability of the trophoblasts to bind endometrial cells.