Papillomaviruses replicate exclusively in [[keratinocyte]]s. Keratinocytes form the outermost layers of the skin, as well as some [[mucous membrane|mucosal surfaces]], such as the inside of the cheek or the walls of the vagina. These surface tissues, which are known as stratified [[squamous epithelium|squamous epithelia]], are composed of stacked layers of flattened cells. The cell layers are formed through a process known as [[cellular differentiation]], in which keratinocytes gradually become specialized, eventually forming a hard, crosslinked surface that prevents moisture loss and acts as a barrier against pathogens. Less-differentiated keratinocyte stem cells, replenished on the surface layer, are thought to be the initial target of productive papillomavirus infections. Subsequent steps in the viral life cycle are strictly dependent on the process of keratinocyte differentiation. As a result, papillomaviruses can only replicate in body surface tissues.{{cn}}