Human papillomavirus infection and induction of neoplasia: a matter of fitness

The aetiologic association between infection with certain human papillomavirus (HPV) types, high-grade squamous neoplasia, and cancer at different epithelial sites is well established. In this review we briefly discuss recent breakthroughs in the regulation of squamous epithelia in homeostasis and disease, and provide a view of how these discoveries modify our understanding of how HPV-induced neoplasia in squamous epithelia is triggered. Taken together, these observations highlight how HPVs have evolved the ability to inactivate the products of genes that are frequently mutated in non-HPV-associated pre-neoplasia and squamous cell carcinoma of sun-exposed skin, and introduce a Darwinian model of clonal evolution of HPV-infected cells. These concepts are considered against our current understanding of transformation zones where HPV-associated cancers occur more frequently, and other sites of non-productive (or abortive) HPV infection.