From HPV infection to oncogenesis: A brief review of the complex immunobiological events

This article reviews the natural history of HPV infection covering key aspects of cell biology, virology and immunology. The oncogenic HPV lifecycle is characterised by infection in basal cells of anogenital epithelia with virus production dependent on epithelial differentiation and virions produced only in terminally differentiated cells. Natural control of an oncogenic type HPV infection depends on appropriate activation of innate immune mechanisms leading to stimulation of adaptive immunity in the form of specific T cells against viral proteins such as E2, E6 and E7 which can ef- fect clearance of the virally infected cells. Neutralising antibodies are detected in about 50% of women who have cleared such infections but are not necessarily protective against future infection by the same HPV type and are never therapeutic. In addition, the stealthy lifecycle of the virus which causes little or damage and no viraemia as well as various viral im- mune evasion strategies sometimes allows the virus to avoid immune detection providing for persistent infection which is the major risk factor for development of intraepithelial neoplasia. Oncogenic HPV infection is necessary but insufficient for development of a cervical cancer and additional genetic changes are acquired over time through selection including those that allow for immune escape from immune surveillance.