Papillomaviruses can either infect cells, replicate, and induce cell death upon lysis (permissive cells) or infect cells and transform them rather than undergoing viral replication (non-permissive cells). In permissive cells, the virion attaches to specific surface receptors, enters the cell and is transported to the nucleus, where viral DNA is released. Early phase proteins such as E6 and E7 drive the cell into S phase, then use cellular DNA synthesis proteins such as DNA polymerase and thymidine kinase to replicate. After transcription of late viral RNAs for structural proteins, progeny virions are assembled in the nucleus. Host cell lysis then releases the viral particles.

In non-permissive cells or permissive cells infected with defective viral genomes, the tumor antigens are synthesized, and cellular DNA synthesis is stimulated, but late viral capsid genes are not expressed. Instead, the viral genome integrates randomly into the host chromosome. In human papillomaviruses, the E6 and E7 proteins bind p53 and RB, respectively, leading to immortalization. These transforming proteins produce altered host cell morphology, increased growth rate, loss of contact inhibition, and anchorage independence, all of which promote tumorigenicity.