Background: Epidermodysplasia verruciformis (EV) is a rare genodermatosis that is characterized by susceptibility to infection with specific human papillomavirus (HPV) genotypes. Among polyomaviruses, the novel Merkel cell polyomavirus (MCPyV) has been found in different epithelial skin neoplasias. Objective: To examine whether EV is associated with cutaneous MCPyV infection. Methods: We used MCPyV-specific PCR to study skin neoplasms of 6 congenital EV patients and of 1 patient with acquired EV. Results: In all congenital EV patients, MCPyV DNA was found in carcinomas in situ, in invasive squamous cell carcinomas and in common warts. In 4 of these patients, the MCPyV-positive skin lesions were from different anatomic locations. In addition, 1 immunosuppressed patient suffering from acquired EV harbored MCPyV DNA in 2 common warts. In contrast, 7 normal skin samples tested negative for MCPyV DNA. Only 2 out of 24 carcinomas in situ (8.3%) and 2 out of 30 common warts (6.7%) from immunocompetent individuals were positive for MCPyV DNA. Conclusions: The strong association of EV-associated skin neoplasms with MCPyV suggests a unique susceptibility of EV patients to infections with MCPyV. Both MCPyV and EV-HPV may act as synergistic oncogenic cofactors in the development of EV-associated skin neoplasms.

1.
Lewandowsky F, Lutz W: A case of a previously undescribed skin disease (epidermodysplasia verruciformis) (in German). Arch Dermatol Syph 1922;141:193–203.
2.
Ramoz N, Rueda LA, Bouadjar B, Montoya LS, Orth G, Favre M: Mutations in two adjacent novel genes are associated with epidermodysplasia verruciformis. Nat Genet 2002;32:579–581.
3.
Harwood CA, Proby CM: Human papillomaviruses and non-melanoma skin cancer. Curr Opin Infect Dis 2002;15:101–114.
4.
Majewski S, Jablonska S: Do epidermodysplasia verruciformis human papillomaviruses contribute to malignant and benign epidermal proliferations? Arch Dermatol 2002;138:649–654.
5.
Gul U, Kilic A, Gonul M, Cakmak SK, Bayis SS: Clinical aspects of epidermodysplasia verruciformis and review of the literature. Int J Dermatol 2007;46:1069–1072.
6.
Häusermann P, Lutter S, Meigel W, Rufli T: The Lewandowsky-Lutz syndrome: the first description of epidermodysplasia verruciformis and three further cases from Basel (in German). Z Hautkr 2002;77:176–180.
7.
Orth G: Human papillomaviruses associated with epidermodysplasia verruciformis in non-melanoma skin cancers: guilty or innocent? J Invest Dermatol 2005;125:xii–xiii.
8.
Jablonska S, Dabrowski J, Jakubowicz K: Epidermodysplasia verruciformis as a model in studies on the role of papovaviruses in oncogenesis. Cancer Res 1972;32:583–589.
9.
Lane JE, Bowman PH, Cohen DJ: Epidermodysplasia verruciformis. South Med J 2003;96:613–615.
10.
Oliveira WR, Rady PL, Festa C, Rivitti EA, Tyring SK: Skin cancer in epidermodysplasia verruciformis patients from Brazil. J Eur Acad Dermatol Venereol 2006;20:1154–1156.
11.
Orth G: Genetics of epidermodysplasia verruciformis: insights into host defense against papillomaviruses. Semin Immunol 2006;18:362–374.
12.
Rogers HD, Macgregor JL, Nord KM, Tyring S, Rady P, Engler DE, Grossman ME: Acquired epidermodysplasia verruciformis. J Am Acad Dermatol 2009;60:315–320.
13.
Gewirtzman A, Bartlett B, Tyring S: Epidermodysplasia verruciformis and human papilloma virus. Curr Opin Infect Dis 2008;21:141–146.
14.
Feng H, Shuda M, Chang Y, Moore PS: Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008;319:1096–1100.
15.
Andres C, Belloni B, Puchta U, Sander CA, Flaig MJ: Prevalence of MCPyV in Merkel cell carcinoma and non-MCC tumors. J Cutan Pathol 2009, E-pub ahead of print.
16.
Mertz KD, Pfaltz M, Junt T, Schmid M, Fernández Figueras MT, Pfaltz K, Barghorn A, Kempf W: Merkel cell polyomavirus is present in common warts and carcinoma in situ of the skin. Hum Pathol 2010;41:1369–1379.
17.
Ridd K, Yu S, Bastian BC: The presence of polyomavirus in non-melanoma skin cancer in organ transplant recipients is rare. J Invest Dermatol 2009;129:250–252.
18.
Sastre-Garau X, Peter M, Avril MF, Laude H, Couturier J, Rozenberg F, Almeida A, Boitier F, Carlotti A, Couturaud B, Dupin N: Merkel cell carcinoma of the skin: pathological and molecular evidence for a causative role of MCV in oncogenesis. J Pathol 2009;218:48–56.
19.
Viscidi RP, Shah KV: Cancer: a skin cancer virus? Science 2008;319:1049–1050.
20.
Mertz KD, Junt T, Schmid M, Pfaltz M, Kempf W: Inflammatory monocytes are a reservoir for Merkel cell polyomavirus. J Invest Dermatol 2010;130:1146–1151.
21.
Giraud G, Ramqvist T, Ragnarsson-Olding B, Dalianis T: DNA from BK virus and JC virus and from KI, WU, and MC polyomaviruses as well as from simian virus 40 is not detected in non-UV-light-associated primary malignant melanomas of mucous membranes. J Clin Microbiol 2008;46:3595–3598.
22.
Harwood CA, Spink PJ, Surentheran T, Leigh IM, de Villiers EM, McGregor JM, Proby CM, Breuer J: Degenerate and nested PCR: a highly sensitive and specific method for detection of human papillomavirus infection in cutaneous warts. J Clin Microbiol 1999;37:3545–3555.
23.
Shuda M, Arora R, Kwun HJ, Feng H, Sarid R, Fernández-Figueras MT, Tolstov Y, Gjoerup O, Mansukhani MM, Swerdlow SH, Chaudhary PM, Kirkwood JM, Nalesnik MA, Kant JA, Weiss LM, Moore PS, Chang Y: Human Merkel cell polyomavirus infection. 1. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors. Int J Cancer 2009;125:1243–1249.
24.
Kean JM, Rao S, Wang M, Garcea RL: Seroepidemiology of human polyomaviruses. PLoS Pathog 2009;5:e1000363.
25.
Tolstov YL, Pastrana DV, Feng H, Becker JC, Jenkins FJ, Moschos S, Chang Y, Buck CB, Moore PS: Human Merkel cell polyomavirus infection. 2. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays. Int J Cancer 2009;125:1250–1256.
26.
Lazarczyk M, Cassonnet P, Pons C, Jacob Y, Favre M: The EVER proteins as a natural barrier against papillomaviruses: a new insight into the pathogenesis of human papillomavirus infections. Microbiol Mol Biol Rev 2009;73:348–370.
27.
Asgari MM, Kiviat NB, Critchlow CW, Stern JE, Argenyi ZB, Raugi GJ, Berg D, Odland PB, Hawes SE, de Villiers EM: Detection of human papillomavirus DNA in cutaneous squamous cell carcinoma among immunocompetent individuals. J Invest Dermatol 2008;128:1409–1417.
28.
Oliveira WR, Sotto MN, Festa C, Rady P, Tyring SK: Merkel cell polyomavirus in Merkel cell carcinoma from a Brazilian epidermodysplasia verruciformis patient. J Am Acad Dermatol 2010;62:889–890.
29.
Lazarczyk M, Pons C, Mendoza JA, Cassonnet P, Jacob Y, Favre M: Regulation of cellular zinc balance as a potential mechanism of EVER-mediated protection against pathogenesis by cutaneous oncogenic human papillomaviruses. J Exp Med 2008;205:35–42.
30.
Foulongne V, Dereure O, Kluger N, Molès JP, Guillot B, Segondy M: Merkel cell polyomavirus DNA detection in lesional and nonlesional skin from patients with Merkel cell carcinoma or other skin diseases. Br J Dermatol 2010;162:59–63.
31.
Majewski S, Jablonska S: Possible involvement of epidermodysplasia verruciformis human papillomaviruses in the immunopathogenesis of psoriasis: a proposed hypothesis. Exp Dermatol 2003;12:721–728.
32.
Weissenborn SJ, Höpfl R, Weber F, Smola H, Pfister HJ, Fuchs PG: High prevalence of a variety of epidermodysplasia verruciformis-associated human papillomaviruses in psoriatic skin of patients treated or not treated with PUVA. J Invest Dermatol 1999;113:122–126.
33.
Tomfohrde J, Silverman A, Barnes R, Fernández-Vina MA, Young M, Lory D, Morris L, Wuepper KD, Stastny P, Menter A, et al: Gene for familial psoriasis susceptibility mapped to the distal end of human chromosome 17q. Science 1994;264:1141–1145.
34.
Ramoz N, Taïeb A, Rueda LA, Montoya LS, Bouadjar B, Favre M, Orth G: Evidence for a nonallelic heterogeneity of epidermodysplasia verruciformis with two susceptibility loci mapped to chromosome regions 2p21–p24 and 17q25. J Invest Dermatol 2000;114:1148–1153.
35.
Dolei A, Pietropaolo V, Gomes E, di Taranto C, Ziccheddu M, Spanu MA, Lavorino C, Manca M, Degener AM: Polyomavirus persistence in lymphocytes: prevalence in lymphocytes from blood donors and healthy personnel of a blood transfusion centre. J Gen Virol 2000;81:1967–1973.
36.
Shuda M, Feng H, Kwun HJ, Rosen ST, Gjoerup O, Moore PS, Chang Y: T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus. Proc Natl Acad Sci USA 2008;105:16272–16277.
37.
Fredericks DN, Relman DA: Sequence-based identification of microbial pathogens: a reconsideration of Koch’s postulates. Clin Microbiol Rev 1996;9:18–33.
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