Background: Epidermodysplasia verruciformis is a rare lifelong disease that has raised an enormous interest since it is a model of cutaneous genetic cancer induced by specific human papillomaviruses.
Observations: The interacting immunogenetic and environmental factors, especially UV irradiation, result in the inability of the patients' immune system to respond to epidermodysplasia verruciformis-specific human papillomaviruses. The local immunosuppression is an effect, at least in part, of the overproduction of tumor necrosis factor alpha and transforming growth factor beta1 and of the excessive formation of cis-urocanic acid.
Conclusions: Epidermodysplasia verruciformis is a model not only of cutaneous viral oncogenesis but also of local defense mechanisms in the progression of human papillomavirus-associated cancers.