Human papillomaviruses: shared and distinct pathways for pathogenesis

• HPVs infect epithelia cells and link their life cycles to differentiation.
• HPVs are grouped into five genera including alpha and beta viruses.
• Alpha HPVs cause anogenital cancers while beta HPVs are co-factors in skin cancers.
• DNA damage pathways are important for alpha HPV life cycle but not beta viruses.

Over 200 types of human papillomaviruses (HPV) have been identified that infect epithelial cells at different anatomic locations. HPVs are grouped into five genera with the alpha and beta viruses being the most commonly studied. Members of the alpha HPV genus infect genital epithelia and are the causative agents of many anogenital cancers. Beta HPVs infect cutaneous epithelia and have been suggested as co-factors in the development of non-melanoma skin cancers. Recent studies have shown that activation of DNA damage pathways is important for the productive life cycle of the alpha HPVs while the beta viruses suppress their activation. These differences likely contribute to the varying types of lesions and malignancies that are associated with these viruses.