Detection of Merkel Cell Polyomavirus in Epidermodysplasia-Verruciformis-Associated Skin Neoplasms (original) (raw)
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European Journal of Clinical Microbiology & Infectious Diseases, 2019
Non-melanoma skin cancers (NMSC) share similar risk factors with other virus-related cancers, despite the lack of proved causal association between viral infection and NMSC development. We investigated the presence of Merkel cell polyomavirus (MCPyV), Epstein-Barr virus (EBV), and human papillomavirus (HPV) DNA in 83 NMSC fresh-frozen and 16 noncancerous skin biopsies and evaluated viral infection according to demographical data, histopathological diagnosis, and ultraviolet exposure. Our results showed that 75% of NMSC biopsies were positive for at least one out of three viruses, whereas only 38% of non-cancerous skin biopsies were positive (p = 0.02). Notably, HPV detection was frequent in NMSC (43%) and nearly absent (one sample, 6.7%) in non-cancerous biopsies (p = 0.007). MCPyV was associated with sites of higher exposure to ultraviolet radiation (p = 0.010), while EBV was associated with a compromised immune system (p = 0.032). Our study showed that HPV was strongly associated with NMSC while EBV and MCPyV with other risk factors. Though further studies are required to elucidate the role of viral infection in NMSC development and management, this study supports the possible role of oncogenic viruses in skin cancers, especially HPV.
British Journal of Dermatology, 2010
Background A novel polyomavirus, the Merkel cell polyomavirus (MCPyV), has recently been identified in Merkel cell carcinoma (MCC). Objectives To investigate the specificity of this association through the detection, quantification and analysis of MCPyV DNA in lesional and nonlesional skin biopsies from patients with MCC or with other cutaneous diseases, as well as in normal skin from clinically healthy individuals. Methods DNA was extracted from lesional and nonlesional skin samples of patients with MCC or with other cutaneous diseases and from normal-appearing skin of clinically healthy subjects. MCPyV DNA was detected by polymerase chain reaction (PCR) and quantified by real-time PCR. Additionally, the T antigen coding region was sequenced in eight samples from seven patients. Results MCPyV DNA was detected in 14 of 18 (78%) patients with MCC, five of 18 (28%) patients with other skin diseases (P = 0AE007) and one of six (17%) clinically healthy subjects. In patients with MCC, viral DNA was detected in nine of 11 (82%) tumours and in 10 of 14 (71%) nontumoral skin samples (P = 0AE66). MCPyV DNA levels were higher in MCC tumours than in nontumoral skin from patients with MCC, and than in lesional or nonlesional skin from patients with other cutaneous disorders. Signature mutations in the T antigen gene were not identified in the two MCC tumour specimens analysed. Conclusions High prevalence and higher levels of MCPyV DNA in MCC supports a role for MCPyV in tumorigenesis. However, the high prevalence of MCPyV in the nontumoral skin and in subjects without MCC suggests that MCPyV is a ubiquitous virus.
Archives of Dermatological Research, 2003
Skin cancers in both immunosuppressed and immunocompetent populations are associated with epidermodysplasia verruciformis human papillomavirus (EV-HPV) DNA. However, little is known about the prevalence of EV-HPVs in actinic keratoses in immunocompetent individuals. Actinic keratoses from 114 patients were classified as low-grade (n=76) or high-grade (n=38) according to the extent of histological atypia. HPV DNA was amplified from 54 frozen and 60 paraffin-embedded biopsy specimens by nested polymerase chain reaction (PCR) with several consensus and type-specific primers. PCR products were sequenced for typing. These results were compared with HPV detection in skin cancers (n=20) and Bowen's disease (n=18). A broad spectrum of EV-HPV types including oncogenic HPV5 and HPV8 and partially characterized sequences were detected in actinic keratoses and cutaneous cancers. In actinic keratoses a higher prevalence of EV-HPV DNA was found in frozen tissues than in formalin-fixed tissues (85% vs 67%). There was no difference between the low-and high-grade actinic keratoses either in terms of EV-HPV DNA prevalence or the results of serological study using HPV8 virus-like particles. The detection rate of EV-HPVs was lower in skin cancers and Bowen's disease. This would suggest involvement of EV-HPVs in the early stages of cutaneous oncogenesis.
Human papillomaviruses and non-melanoma skin cancer
Current Opinion in Infectious Diseases, 2002
Human papillomaviruses (HPVs) infect the squamous epithelium and can induce benign and malignant lesions. To date, more than 200 different HPV types have been identified and classified into five genera, α, β, γ, μ, and ν. While high-risk α mucosal HPVs have a wellestablished role in cervical carcinoma and a significant percentage of other anogenital tract and oral carcinomas, the biology of the cutaneous β HPVs and their contribution to non-melanoma skin cancer (NMSC) has been less studied. Although the association of β HPV infection with NMSC in patients with a rare, genetically determined condition, epidermodysplasia verruciformis has been well established, the role of β HPV infection with NMSC in the normal population remains controversial. In stark contrast to α HPV-associated cancers, the presence of the β HPV genome does not appear to be mandatory for the maintenance of the malignant phenotype. Moreover, the mechanism of action of the β HPV E6 and E7 oncoproteins differs from the β HPV oncoproteins.
Proceedings of the National Academy of Sciences, 1982
DNA extracted from squamous cell carcinomas from patients with the chronic wart disease syndrome, epidermodysplasia verruciformis, was analyzed for the presence of human papillomavirus (HPV)-specific DNA sequences by Southern blot hybridization analysis. Employing an HPV probe obtained by molecular cloning of viral DNA purified from benign warts from these patients, we have unequivocally identified HPV-specific nucleotide sequences in squamous cell carcinomas from these patients. Restriction endonuclease mapping indicated that the DNA present in the carcinomas was of the same type (type 5) as that found in the benign tumors from these patients and was present as unintegrated, free viral DNA. Moreover, we have demonstrated the presence of HPV-5 DNA in a subcutaneous metastatic tumor from one of these patients. This latter observation essentially eliminates the possibility that the HPV-5 DNA present in the malignant tumors in these patients resulted from cross-contamination from an adjacent benign warty lesion. In addition to wildtype HPV-5 DNA, both the primary and metastatic carcinomas analyzed also contained an HPV-5 DNA species lacking approximately 20% of the HPV-5 DNA genome. These subgenomic forms of HPV-5 DNA could not be detected in benign papillomas from these patients.
Human papillomavirus and the development of non-melanoma skin cancer
Journal of Clinical Pathology, 1999
Human papillomaviruses (HPV) are increasingly recognised as important human carcinogens. The best established association with human malignancy is that of high-risk mucosal HPV types and anogenital cancer. HPV-induced transformation of anogenital epithelia has been the subject of intense research which has identified the cellular tumour suppressor gene products, p53 and pRB, as important targets for the viral oncoproteins E6 and E7 respectively. Certain HPV types are also strongly associated with the development of non-melanoma skin cancer in the inherited disorder epidermodysplasia verruciformis (EV). However, in contrast with anogenital malignancy the oncogenic mechanisms of EV-HPV types remain uncertain, and there appears to be a crucial additional requirement for ultraviolet radiation. Cutaneous HPV types in the general population are predominantly associated with benign viral warts, but a role in non-melanoma skin cancer has recently been postulated. Polymerase chain reaction based HPV detection techniques have shown a high prevalence of HPV DNA, particularly in skin cancers from immunosuppressed patients and to a lesser extent in malignancies from otherwise immunocompetent individuals. No particular HPV type has yet emerged as predominant, and the role of HPV in cutaneous malignancy is unclear at present. It remains to be established whether HPV plays an active or purely a passenger role in the evolution of non-melanoma skin cancer.
Pathogens
Oncogenic viruses are recognized to be involved in some cancers, based on very well-established criteria of carcinogenicity. For cervical cancer and liver cancer, the responsible viruses are well-known (e.g., HPV, HBV); in the case of skin cancer, there are still many studies which are trying to identify the possible viral etiologic agents as principal co-factors in the oncogenic process. We analysed scientific literature published in the last 5 years regarding mechanisms of carcinogenicity, methods of detection, available targeted therapy, and vaccination for Merkel cell polyomavirus, and beta human papillomavirus types, in relation to skin cancer. This review is targeted at presenting the recent findings which support the involvement of these viruses in the development of some types of skin cancers. In order to optimize the management of skin cancer, a health condition of very high importance, it would be ideal that the screening of skin cancer for these two analysed viruses (MCPy...
Human papillomavirus-associated tumors of the skin and mucosa
Journal of the American Academy of Dermatology, 1997
This review discusses diseases of the lower genital tract in which the presence of human papillomavirus (HPV) DNA is well documented. We discuss epidemiologic, clinical, and experimental data supporting a causative role for HPV in mucosal malignancies, with emphasis on the role of viral and host factors in their pathogenesis. Of special interest is the recently discovered association of cutaneous tumors with HPVs, previously known only for tumors in epidermodysplasia verruciformis 0EV). The frequent detection of EV-specific or EVrelated HPVs in immunosuppressed persons and in cutaneous mmol~ in the general population supports the importance of EV as a model of cutaneous oncogenesis. We also discuss recent serologic findings based on enzyme-linked immunosorbent assay results with the use of vimslike particles. This is important both for detection of present or past HPV infection and for epidemiologic and immunologic studies. Novel therapeutic modalities for HPV tumors and prospects for prophylactic and therapeutic vaccination are presented. (J Am Acad Dermatol 1997;36:659-85.) Learning objective: At the conclusion of this learning activity, participants should be able to recognize the clinical characteristics of the most common malignant disorders associated with high-risk mucosal HPVs or cutaneous and EV-related HPVs. Participants should also be familiar with epidemiologic data on HPV-associated tumors and with basic concepts of the role of HPV genes and host factors in cutaneous and mucosal oncogenesis.
Cancer Research, 1997
Epidermodysplasia verruciformis (EV) Is regarded as a model for cutaneous oncogenesis associated with specific human papillomaviruses (HPVs). Because genital HPV-associated carcinogenesis is a very long lasting process requiring 20â€"30 years and epidemiological studies of this type for HPV-assoclated skin cancers are impossible in such a rare disease as EV, we observed for up to 20 years EV patients having surgery for carcinomas with consecutive autografts from uninvolved and non-sun exposed skin. We noticed the appearance of premalignant and malignant changes around the grafts, whereas within the grafted skin, only benign macular lesions started to develop several years after transplantation.