The role of certain mucosal human papillomaviruses (HPV) such as HPV 16 in the development of cancer of the anogenital tract and of the head and neck is undisputed. In contrast, a connection between some of the cutaneous HPV types that belong to the species β of papillomaviruses and non-melanoma skin cancer is controversially discussed.
A major argument against an infectious etiology is the failure to detect at least one copy of the viral DNA per cancer cell as it is consistently found in case of HPV 16-related cancer. In fact, the β-HPV genomes are present only in one per 100 to 10,000 cells and are often less abundant than in healthy skin. These observations led to the hypothesis that the HPV proteins E6 and E7 are necessary during early stage of tumor development but during progression their transforming functions are being replaced by other carcinogens (e.g. UV in sunlight) and thus the genomes were lost from the tumor cells.     
To test this hypothesis we have developed models of transgenic mice that specifically express the genes E6 and E7 of the β-papillomaviruses 38 or 49 in the undifferentiated cells of the skin.  We were able to show that the animals develop skin lesions at chronically UV-irradiation skin areas that histologically resemble squamous cell carcinomas of the skin or their precursors (actinic keratosis) in humans.  In an ongoing study we investigate whether tumors are still developing when the expression of the transgene is interrupted by knock-out at different times during the experiment. 

Viarisio D, Mueller-Decker K, Kloz U, Aengeneyndt B, Kopp-Schneider A, Gröne HJ, Gheit T, Flechtenmacher C, Gissmann L, Tommasino M. 
E6 and E7 from beta HPV38 cooperate with ultraviolet light in the development of actinic keratosis-like lesions and squamous cell carcinoma in mice.
PLoS Pathog. 2011 Jul;7(7):e1002125. doi: 10.1371/journal.ppat.1002125. Epub 2011 Jul 14.

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