The question of the effect of anti-TNF-alpha in skin carcinogenesis is especially relevant in view of the increased use of these drugs for the treatment of autoinflammatory immune diseases. Since ultraviolet radiation and human papillomavirus are involved in skin carcinogenesis, we wished to investigate the effect of TNF-alpha antagonists on the UVB-induced apoptosis of keratinocytes infected by HPV38. Our results indicate that anti-TNF agent, infliximab, does not contribute to the survival of HPV38-transduced keratinocytes with UVB-induced DNA damages. 1. Introduction Tumor necrosis factor-alpha (TNF-α) is one of the main mediators of skin and mucosa inflammation and has a potent antiproliferative effect on normal epithelial cells. Numerous studies indicate that TNF-α may influence the fate of HPV-infected cells and suggest that HPV-mediated TNF resistance is a key event in the multistep process leading to cervical cancer [1]. Although several epidemiological studies have reported an increased risk of nonmelanoma skin cancer in patients treated with anti-TNF agents, the relationship remains uncertain [2]. The question of the effect of anti-TNF-α in skin carcinogenesis is, thus, especially relevant in view of the increased use of these drugs for the treatment of autoinflammatory immune diseases. Besides ultraviolet (UV) irradiation which is the most important risk factor involved in the development of NMSC, cutaneous beta-HPV infection is also considered as an important cofactor [3]. Similar to the high-risk alpha mucosal HPV types, E6 and E7 oncoproteins from certain beta-HPV types target p53- and pRb-regulated pathways and display transforming activities. In particular, E6 and E7 from the beta HPV38 are able to immortalize keratinocytes that are natural hosts of the virus [4, 5]. To our knowledge, there are no available data on the interactions between cutaneous HPV infection and anti-TNF agents. Since anti-TNF agents are also associated with an increased risk of viral infections [6], we wished to investigate the effect of an anti-TNF-α agent, infliximab, on the UVB-induced apoptosis of keratinocytes infected by HPV38. 2. Materials and Methods HaCaT keratinocytes and HaCaT keratinocytes transduced with empty vector pLXSN and with pLXSN-HPV38 E6/E7 vector [7] were UVB irradiated (10？mJ/cm2) to induce apoptosis. To assess the role of TNF-α, 100？ng/mL of TNF-α (Sigma Aldrich, Saint Quentin Fallavier, France) and 20？μg/mL of infliximab (MSD, France) were added after UVB irradiation. Apoptosis was evaluated by flow cytometry (annexin V/propidium iodide
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