Nonmelanoma skin cancer (NMSC) is the most common cancer type among Caucasians. The incidence of squamous cell carcinoma is 60-250 times higher in immunosuppressed organ transplant recipients when compared to the general population. An etiologic role of human papillomaviruses (HPV) from genus beta has been suggested for many years because of their well-documented carcinogenicity in patients with epidermodysplasia verruciformis (EV). In addition to the EV patients, their carcinogenic activity has been strengthened in recent years by refined epidemiologic studies and molecular biology, demonstrating oncogenic properties of beta HPV proteins in either keratinocyte cultures or transgenic mice. Viral protein expression has also been demonstrated in the hyperplastic edges of skin SCC or BCC and in premalignant lesions from renal transplant recipients by immunohistochemistry, where the expression of cellular proliferation markers was increased and extended to the suprabasal layers.
The proposed mechanisms of carcinogenesis indicate that beta HPV play a role in tumor initiation and progression, but are not necessary for tumor maintenance. A next-generation sequencing approach quite recently showed the genus gamma HPV197 to be commonly present in skin tumors. Proteomic analysis of its E6 and E7 associated cellular proteins revealed interesting candidates well known for oncogenic and tumor suppressor activities. This may indicate that gamma HPV deserve more attention than given in the past. Attempts are on the way to further elucidate oncogenic mechanisms and develop preventive and therapeutic vaccines against skin cancer and its precursors, including the use of animal models of infection. Two human polyomaviruses are currently linked to malignant and benign skin tumors.
The Merkel cell polyomavirus (MCPyV) has been identified in and cloned from Merkel cell carcinoma, a rather rare but very aggressive skin cancer with a high mortality rate. It is a cancer of the elderly and its incidence is strongly increased in immunocompromised individuals, such as transplant recipients and HIV-infected people. The Trichodysplasia spinulosa Polyomavirus (TSPyV) causes a very rare but rather disfiguring benign proliferative skin disease only in severely immunocompromised patients. For this virus there is a promising perspective of successful antiviral treatment. In summary, the project would deal with widely distributed cutaneous viruses from the families Papilloma- and Polyomaviridae, which are able to establish life-long persisting infections. These infections are frequently clinically inapparent in the general population but may give rise to skin cancer following immunosenescence in the aging skin and especially in the immunocompromised host. Loss of control in the context of immunosuppression dramatically increases the skin cancer incidence and leads to an eminent medical problem. The prospects of preventive vaccination currently raise considerable interest in public health institutions.
Nonmelanoma skin cancer (NMSC) is the most common cancer type among Caucasians. The incidence of squamous cell carcinoma is 60-250 times higher in immunosuppressed organ transplant recipients when compared to the general population. An etiologic role of human papillomaviruses (HPV) from genus beta has been suggested for many years because of their well-documented carcinogenicity in patients with epidermodysplasia verruciformis (EV). In addition to the EV patients, their carcinogenic activity has been strengthened in recent years by refined epidemiologic studies and molecular biology, demonstrating oncogenic properties of beta HPV proteins in either keratinocyte cultures or transgenic mice. Viral protein expression has also been demonstrated in the hyperplastic edges of skin SCC or BCC and in premalignant lesions from renal transplant recipients by immunohistochemistry, where the expression of cellular proliferation markers was increased and extended to the suprabasal layers.
The proposed mechanisms of carcinogenesis indicate that beta HPV play a role in tumor initiation and progression, but are not necessary for tumor maintenance. A next-generation sequencing approach quite recently showed the genus gamma HPV197 to be commonly present in skin tumors. Proteomic analysis of its E6 and E7 associated cellular proteins revealed interesting candidates well known for oncogenic and tumor suppressor activities. This may indicate that gamma HPV deserve more attention than given in the past. Attempts are on the way to further elucidate oncogenic mechanisms and develop preventive and therapeutic vaccines against skin cancer and its precursors, including the use of animal models of infection. Two human polyomaviruses are currently linked to malignant and benign skin tumors.
The Merkel cell polyomavirus (MCPyV) has been identified in and cloned from Merkel cell carcinoma, a rather rare but very aggressive skin cancer with a high mortality rate. It is a cancer of the elderly and its incidence is strongly increased in immunocompromised individuals, such as transplant recipients and HIV-infected people. The Trichodysplasia spinulosa Polyomavirus (TSPyV) causes a very rare but rather disfiguring benign proliferative skin disease only in severely immunocompromised patients. For this virus there is a promising perspective of successful antiviral treatment. In summary, the project would deal with widely distributed cutaneous viruses from the families Papilloma- and Polyomaviridae, which are able to establish life-long persisting infections. These infections are frequently clinically inapparent in the general population but may give rise to skin cancer following immunosenescence in the aging skin and especially in the immunocompromised host. Loss of control in the context of immunosuppression dramatically increases the skin cancer incidence and leads to an eminent medical problem. The prospects of preventive vaccination currently raise considerable interest in public health institutions.
