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| The International Transplant Skin Cancer Collaborative is our sister organization in North-America and Australia. |
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Epidemiology of human papillomavirus (HPV) infection, ultraviolet (UV) radiation in relation to non-melanoma skin cancer (EPI-HPV-UV-CA)
Introduction
The EPI-HPV-UV-CA project is granted by the EC (QLK2-CT-2002-01179) to studying the role of human papillomavirus infection and ultraviolet exposure in the development of skin cancer in organ transplant recipients and immunocomptent individuals. Many SCOP members are involved in this project (Jan Nico Bouwes Bavinck, Mariet Feldkamp, Eggert Stockfleth, Ingo Nindl, Sylvie Euvrard, Luigi Naldi, and Charlotte Proby).
Summary of the project
Non-melanoma skin cancers (squamous cell and basal cell carcinoma) are the most frequent malignant tumors of man. The etiology of skin cancer is still under debate. Recent reports demonstrated a high prevalence of human-papillomavirus (HPV)-DNA in non-melanoma skin cancers. The etiologic role of some HPV types in the development of cervical cancer is well established. HPV types probably also play a role in head and neck cancers. The identification of HPV in skin cancer may indicate a similar key role in the pathogenesis of skin tumors, which would raise prospects of prevention by vaccination and provide targets for therapeutic options. This proposal is the first unified initiative of nine European institutions in Northern (Leiden and Delft, The Netherlands; Berlin, Cologne and Heidelberg, Germany; London, United Kingdom) and Southern Europe (Bergamo and Rome, Italy; Lyon, France) and one in Australia (Brisbane, Queensland), each disposing of a long-standing expertise in the field of papillomavirus research and/or epidemiology of skin cancer to study the role of HPV in skin cancer oncogenesis.
Objectives
The objective is to clarify the role of HPV infections in the development of non-melanoma skin cancer in relation to sunlight exposure by combining methods of modern epidemiology and molecular biology. Specifically we will study: (i) the kinetics of HPV infection in organ-transplant recipients (ii) the effect of immunosuppression on HPV load, by measuring the viral load around and at different time points after organ transplantation (iii) the association of HPV infection with skin cancer in relation to exposure to sunlight by comparing Northern Europe with Southern Europe and Australia (iv) the presence of high-risk HPV types by using newly to develop HPV-DNA typing systems, and (v) the question whether all malignant cells contain at least one HPV genome, by determining the HPV load in histopathologically precisely defined skin cancers.
Description of the work
The consortium has designed five large epidemiological studies to answer these specific questions, two in organ transplant recipients and three in immunocompetent individuals. Three institutes located in Northern Europe and three in Southern Europe are participating to make an optimal use of European diversity regarding sun exposure. Participation of Australia adds an extra dimension to this proposal, since Australia is the continent with the highest sun exposure and skin cancer incidence in the world. Outcome for HPV infection will be serology and HPV DNA detection in hairs plucked from eyebrows. Serological assays provide the most accurate measurement of previous exposures to infections with HPV types. Serology is also of great value for the diagnosis of current HPV infections. The definition of specific high-risk HPV serotypes for skin cancer utilizing already available and novel serological methods is an important goal of our studies.
Until now, HPV DNA typing is performed by the amplification of the viral nucleic acid (polymerase chain reaction) followed by sequencing of the amplimers. The disadvantage of this approach is that the technique is obviously labor-intensive and, therefore, not easily usable for large numbers of samples. This method is not usable without additional procedural steps for the detection of multiple infections especially when HPV types are present with a relative abundance of below 20%. The identification of the potentially oncogenic HPV types is only feasible when novel HPV typing systems are developed. The consortium, therefore, will make use of a newly to develop HPV-DNA typing system, allowing the simultaneous detection of all relevant HPV types also in complex mixtures of HPV types: PCR-reverse hybridization line-probe assay (LiPA).
Milestones and expected results
As a result of this program we expect to be able in three years to make a founded statement on the possible association between human papillomavirus infection and the development of non-melanoma skin cancer and to define virus types (if any) presenting special risk factors with or without the influence of UV-exposure. If human papillomavirus infection is involved in skin cancer oncogenesis this would raise the possibility of skin cancer prevention by anti-viral intervention.
Additional information can be obtained from the B and C forms and the technical annex. Interested persons can download the questionnaires.
Jan Nico Bouwes Bavinck, co-ordinator EPI-HPV-UV-CA project
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| Please make sure to pay attention to this actual New England Journal paper on skin cancer in organ transplant recipients by SCOP Vice President Dr Sylvie Euvrard, Lyon, France.
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