FIGURE 3.

Human papillomavirus (HPV) life cycle and cancer. Cartoon depicting normal stratified cervical epithelium (left), HPV-infected epithelium (center), and HPV-induced cancer (right). Epithelial layers are indicated on the far left, and HPV life cycle stages are indicated on the far right. Episomal genomes are shown as orange circles and integrated genomes are shown as orange stripes. (Left) Normal keratinocyte differentiation: basal cells divide and daughter cells migrate upward, beginning the differentiation process. As differentiation proceeds, cells exit the cell cycle. Fully keratinized squames slough off from the apical surface. (Middle) Productive HPV infection: HPV virions gain access to basal cells via microwounds. The viral genomes migrate to the nucleus, where they are maintained at ˜100 copies/cell. As daughter cells begin differentiation, viral genomes are amplified. Cell nuclei are retained and chromatin is activated to support viral DNA replication. (Right) Cancer: viral genomes often integrate into the host genome and E6/E7 expression is increased, leading to enhanced proliferation and the accumulation of cellular mutations. Cellular differentiation is lost, and cancerous cells invade into the dermal layer as well as into neighboring tissues (Langsfeld and Laimin, 2016).