The Cutaneous Human Papillomavirus Types and Non-melanoma Skin Cancer
Veronique Bouvard, Anne-Sophie Gabet, Rosita Accardi, Bakary S. Sylla and Massimo Tommasino
from: Papillomavirus Research: From Natural History To Vaccines and Beyond (Edited by: M. Saveria Campo). Caister Academic Press, U.K. (2006)
Non-melanoma skin cancer (NMSC) is the most common form of malignancy in Caucasian adult populations. UV light is a key environmental risk factor for NMSC. The fact that impairment of the immune system increases the risk for development of skin cancers strongly suggests that infectious agents are also involved in their aetiology. The epitheliotropic human papillomaviruses (HPVs) are likely candidates, especially those classified in the genus beta of the HPV phylogenetic tree, also known as Epidermodysplasia verruciformis (EV) HPV types. Independent investigations have shown that the DNA of several EV HPV types is highly prevalent in NMSC of both immunocompromised and immunocompetent individuals. Despite this association, however, a direct role of the EV HPV types in the development of NMSC remains to be proven. Due to the lack of a universal protocol for detection of EV HPV types, many studies using various methods have found different spectra of HPV types in skin lesions. Thus, it is still not known whether, within the genus beta, certain HPV types are more prevalent than others in malignant skin lesions. In addition, EV HPVs appear to be highly ubiquitous, being commonly detected in healthy skin of both immunocompromised and immunocompetent individuals. Functional studies on mucosal high-risk HPV types have clearly demonstrated that the products of two early genes, E6 and E7, play a key role in the transformation of infected cells by disrupting the regulation of cell cycle and apoptosis. Very little is known about the biological properties of E6 and E7 of the majority of EV HPV types. Partial characterization of a limited number of skin HPV types (EV and non-EV) has revealed that also their E6 and E7 proteins have the ability to interfere with the regulation of apoptosis and cell cycle. These findings need confirmation in studies in which additional HPV types are included to establish the biological significance of these events. In conclusion, some cutaneous HPV types may be involved in skin cancer development. However, the initial functional data indicate that the molecular mechanisms leading to cellular transformation are different from those of mucosal HPV types. EV viruses may act only at early stages of carcinogenesis, by potentiating the deleterious effects of other carcinogens such as UV radiation. Further functional and epidemiological studies are required to evaluate this model read more ...