A persistent human papillomavirus type 16 (HPV-16) infection is one of the highest risk factors for development of cervical cancer. The majority of all DNA viruses that establish persistence have evolved a highly organised gene expression program, often divided into clear early and late phases, which allows the virus to delay expression of the highly immunogenic structural proteins to a point when this is advantageous to the virus. In HPV-16, the switch from early to late gene expression includes a promoter switch as well as de-repression and activation of the late polyadenylation signal and late splice sites. Some splice sites are used solely by early mRNAs, others by early and late mRNAs and two splice sites are uniquely used by late mRNAs. We have reviewed published results on cellular RNA processing factors that regulate HPV-16 late gene expression.