Epidermodysplasia verruciformis human papillomaviruses in skin cancers and in the immunopathogenesis of psoriasis

Abstract

Epidermodysplasia verruciformis (EV), a rare genetic disease associated with specific human papillomaviruses (HPVs) and skin cancers, regarded as a model of cutaneous viral cancerogenesis, has raised recently an enormous interest in general medicine since EV HPVs, non contagious for normal population due to genetic restriction, were found in cutaneous precancers and cancers in the immunosuppressed and immunocompetent individuals. EV HPVs are quite unusual human papillomaviruses causing a rare genetic disease EV only in susceptible individuals. The recent epidemiological, immunological and immunogenetic studies disclosed that specific HPVs of this rare genetic disease play a substantial role in malignant and benign epidermal proliferations also in non EV patients. Patients with EV are immunotolerant towards own EV HPVs throughout the whole life, whereas the oncogenic types of EV HPVs induce cancers. In this review we present virological, immunological and immunogenetic data on epidermodysplasia verruciformis, including the most recent detection of two novel specific genes whose mutations are responsible for the disease. We discuss the involvement of EV HPVs in premalignancies and non melanoma skin cancers in the general population. The most interesting new finding was disclosure of a very high prevalence of potentially oncogenic types EV HPV5 and 8 in psoriasis. In spite of association with the same potentially oncogenic EV HPVs in EV and psoriasis and in spite of close localization of the two susceptibility loci on chromosomes 17qter and 2 in both diseases, these two disorders differ entirely in their pathogenesis, clinical, pathological, immunological and immunogenetic characteristics. We found that EV HPVs present in psoriatic keratinocytes may contribute to the complex immunopathogenesis of the disease, to the sustained T cell activation and self-perpetuation of the immune process. Since the patients have only partially alleviated genetic restriction to high risk EV HPVs these viruses are able to replicate in proliferating and differentiating psoriatic keratinocytes. The novel selective immunosuppressive therapies for psoriasis interfere with and block various stages of interconnected activation and proliferation of keratinocytes and closely linked EV HPVs.