The Experts below are selected from a list of 1164 Experts worldwide ranked by ideXlab platform
Stefania Jablonska - One of the best experts on this subject based on the ideXlab platform.
-
Epidermodysplasia verruciformis as a model of human papillomavirus-induced genetic cancer of the skin. Arch Dermatol 1995;131
2013Co-Authors: Stefania Jablonska, Jan Dabrowski, Kazimierz Jakubowicz, Contact The Aacr PublicationsAbstract:Epidermodysplasia verruciformis is a skin disease caused by a generalized infection by verruca virus in which the verrucous lesions usually change into tumors, most frequently Bowen's carcinoma. Lesions from a case in which papovavirus was evident were transmitted to a healthy person, the virus being found in cell nuclei in the wart lesions and also in lesions with some signs of atypia. This fulfilled the condition for recognition of the virus, demonstrated by electron microscopy, as being causatively involved in the verrucous lesions in Epidermodysplasia verruciformis and also in the initiation of the morbid process. The virus could not be demonstrated in lesions showing distinct signs of cancer
-
High prevalence of Epidermodysplasia verruciformis-associated human papillomavirus DNA in actinic keratoses of the immunocompetent population
Archives of Dermatological Research, 2003Co-Authors: Herbert Pfister, Pawel G Fuchs, Stefania Jablonska, Slawomir Majewski, Iwona Pniewska, Magdalena MalejczykAbstract: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.
-
do Epidermodysplasia verruciformis human papillomaviruses contribute to malignant and benign epidermal proliferations
Archives of Dermatology, 2002Co-Authors: Slawomir Majewski, Stefania JablonskaAbstract:The aim of this review is to present new data on Epidermodysplasia verruciformis (EV) and EV human papillomaviruses (HPVs), regarded previously as specific to the disease. Recently introduced highly sensitive molecular methods for virologic studies allow detection of EV HPVs in non-EV populations. In this article, we present the most recent findings on EV and EV HPVs, which shed new light on a possible contribution of EV viruses to malignant and benign epidermal proliferation. We discuss the significance of EV HPV DNA detection in premalignant cutaneous lesions and nonmelanoma skin cancers; however, direct evidence for the causative role of EV HPV is still not available. In psoriasis, a high frequency of EV HPV-5 and other EV HPVs in the skin and the presence of specific HPV-5 antibodies strongly suggest expression of EV HPV proteins in this extensive epidermal proliferation. Epidermodysplasia verruciformis HPV-5 may also be transiently expressed in epidermal repair processes, whereas in psoriasis there is a continuous epidermal proliferation that could result in persistent viral expression. A potential contribution of EV HPVs to the pathogenesis of psoriasis is also supported by the recently disclosed co-localization of susceptibility loci for psoriasis and EV in the same region of chromosome arm 17qter; however, specific genes for both conditions are still not identified.
-
Mutation and Abnormal Expression of the p53 Gene in the Viral Skin Carcinogenesis of Epidermodysplasia verruciformis
Journal of Investigative Dermatology, 2001Co-Authors: Kamila Padlewska, Nicolas Ramoz, Stefania Jablonska, Odile Croissant, Patricia Cassonnet, Guy Riou, Michel Barrois, Slavomir Majewski, Gerard OrthAbstract:Patients suffering from Epidermodysplasia verruciformis are prone to nonmelanoma skin cancers, due to an inherited abnormal susceptibility to the oncogenic human papillomavirus type 5. Genotoxic sunlight ultraviolet B radiations are likely to be a cofactor. Lesions of two human-papillomavirus-type-5-infected Epidermodysplasia verruciformis patients collected during an 8 y period were retrospectively studied for p53 mutations in exons 5 through 8 by a polymerase chain reaction single-strand conformation polymorphism technique and/or by DNA sequencing of amplified exons. Mutations were detected in 11 of 26 (42.3%) specimens, including five (62.5%) squamous cell carcinomas, three (33.3%) Bowen's carcinomas in situ, two (40%) actinic keratoses, and one (33%) benign lesion. The nine mutations characterized by sequencing were shown to be missense and to affect mutational hotspots in human cancers. Five were C-->T transitions at dicytidine sites considered as ultraviolet signature mutations. Two were transversions (C-->G and C-->A) at dicytidine sites and two were C-->T transitions at nondipyrimidine sites. A marked p53 immunoreactivity was disclosed in 72.7% of 11 invasive carcinomas, 55.6% of nine carcinomas in situ, 37.5% of eight actinic keratoses, and one of three benign lesions. This includes 81.8% of 11 specimens with a p53 mutation but also 50% of 14 specimens with no mutation detected. A dysfunction of the p53 gene is thus likely to play a part in Epidermodysplasia verruciformis carcinogenesis, either due to ultraviolet-B-induced p53 mutations, as in nonmelanoma skin cancers in the general population, or involving other mutagens or mechanisms. The part played by human papillomavirus type 5 proteins expressed in Epidermodysplasia verruciformis keratinocytes remains to be determined.
-
a possible vertical transmission of human papillomavirus genotypes associated with Epidermodysplasia verruciformis
Journal of Investigative Dermatology, 1998Co-Authors: Michel Favre, Gerard Orth, Slavomir Majewski, Nando De Jesus, Magdalena Malejczyk, Stefania JablonskaAbstract:Epidermodysplasia verruciformis (EV) is characterized by an abnormal genetic susceptibility to a group of related human papillomavirus (HPV) genotypes, including the oncogenic HPV5 and HPV8. The mode of transmission of these viruses remains unknown. In view of the rare incidence of EV, we had a unique opportunity to perform a virologic study of the amniotic fluid and placenta from an EV patient infected with HPV5, HPV8, several other EV HPV, and HPV3. The child was born by cesarean section and the amniotic fluid specimen was taken prior to rupture of membranes. Analysis of the amniotic fluid and placenta specimens by a nested polymerase chain reaction method, using degenerate EV HPV primers or type-specific HPV primers, disclosed the presence of the variants of EV HPV5, HPV8, HPV24, and HPV36, and of HPV3 detected in the skin lesions of the patient. HPV5, HPV8, HPV24, and HPV3 were also detected in the placenta. No viral sequences were detected in peripheral blood mononuclear cells collected 2 y and 6 mo before cesarean section, rendering an hematogenous transmission unlikely. The same HPV variants were also detected in cervical scrapes taken from the patient, which may suggest an ascending infection of the placenta. This first report of the detection of EV HPV in amniotic fluid, placenta, and cervical scrapes from an EV patient renders vertical transmission of EV HPV likely.
Stephen K. Tyring - One of the best experts on this subject based on the ideXlab platform.
-
a novel approach to the classification of Epidermodysplasia verruciformis
International Journal of Dermatology, 2018Co-Authors: Simo Huang, Peter L. Rady, Daniel J Lewis, Stephen K. TyringAbstract:Background Epidermodysplasia verruciformis (EV) is a rare genodermatosis that causes disseminated eruptions of hypo- or hyperpigmented macules and wart-like papules that can coalesce and scale. It is uniquely characterized by an increased susceptibility to specific human papillomavirus (HPV) genotypes. Classically, EV is associated with mutations of the EVER1/TMC6 and EVER2/TMC8 genes. The term "acquired" Epidermodysplasia verruciformis was coined to describe an EV-like syndrome that can develop in patients with a compromised immune system. Recent discoveries of other genes implicated in EV, including RHOH, MST-1, and CORO1A, have complicated the classification of EV and EV-like syndromes. Methods We review the available data on Epidermodysplasia verruciformis in the literature in order to propose a new classification system to encompass current and future developments on EV and EV-like syndromes. Results We propose classifying EV into: (1) classic genetic EV, (2) non-classic genetic EV, and (3) acquired EV. Conclusion The proposed categorization scheme provides a simple and logical way to organize the different cases of EV that have been described in the literature. This system organizes EV by its cause, allowing for a better understanding of the disease and helps differentiate EV from other causes of generalized verrucosis.
-
acquired Epidermodysplasia verruciformis associated with human papilloma virus type 14 in a small bowel transplanted child a case report
Pediatric Dermatology, 2016Co-Authors: D Derek O Hirschman, Peter L. Rady, Stephen K. Tyring, M Joselin D Tacastacas, M Kevin D Cooper, M Kord D HondaAbstract:A 3-year-old African American girl taking sirolimus and tacrolimus for a small bowel transplantation presented with hypopigmented macules and papules throughout her trunk. A biopsy diagnosed Epidermodysplasia verruciformis (EV) that was found to be associated with human papillomavirus (HPV) type 14 according to polymerase chain reaction analysis. There are few cases of acquired EV in the setting of organ transplantation. Although there is no standardized treatment for acquired EV, prevention and surveillance for transformation to squamous cell carcinoma are primary concerns.
-
Cornoid Lamella-Like Structures in HIV-Associated Epidermodysplasia verruciformis: A Unique Histopathologic Finding.
The American Journal of dermatopathology, 2015Co-Authors: Courtney Champagne, Stephen K. Tyring, Lindsey Moore, Ross B. Reule, Jonathan A. Dyer, Peter Rady, Jeffrey P. NorthAbstract:Epidermodysplasia verruciformis (EV) is an uncommon inherited skin condition with increased vulnerability to widespread infection by certain human papillomavirus types, resulting in extensive verruca plana-like papules coalescing to large confluent plaques. Since the AIDS epidemic starting in the 1980s, an acquired type of EV has been described in patients infected with human immunodeficiency virus. The histopathologic features of EV consist of papillated epidermal hyperplasia with hypergranulosis and a distinct bluish-gray color in the large human papillomavirus-infected keratinocytes in the stratum granulosum. The authors present a case of HIV-associated EV with a unique histopathologic finding of multiple cornoid lamella-like structures. To the authors' knowledge, this finding has not been previously described in the literature.
-
homozygosity for the c 917a t p n306l polymorphism in the ever2 tmc8 gene of two sisters with Epidermodysplasia verruciformis lewandowsky lutz originally described by wilhelm lutz
Dermatology, 2011Co-Authors: Andreas W Arnold, Stephen K. Tyring, Bettina Burger, Erwin Kump, Alexander Rufle, Werner Kempf, Peter Hausermann, Peter ItinAbstract:Background: Epidermodysplasia verruciformis Lewandowsky-Lutz (EV) is a rare genodermatosis, characterised by development of numerous verrucous skin lesions caused by specific genoty
-
Epidermodysplasia verruciformis after cutaneous t cell lymphoma periungual presentation
Dermatology Online Journal, 2010Co-Authors: Jonathan E Cutlan, Stephen K. Tyring, Rashid M Rashid, Carlos A Torrescabala, Valencia ThomasAbstract:Epidermodysplasia verruciformis (EV) has several clinical presentations and has been reported in various states of immune deregulation. We report the unique presentation of this disease as a pigmented periungual macule in a patient with a previous history of immune deregulation related to cutaneous lymphoma. A literature review did not reveal any previous reports of EV in patients with cutaneous T-cell lymphoma.
Slawomir Majewski - One of the best experts on this subject based on the ideXlab platform.
-
the ever genes the genetic etiology of carcinogenesis in Epidermodysplasia verruciformis and a possible role in non Epidermodysplasia verruciformis patients
Postepy Dermatologii I Alergologii, 2016Co-Authors: Agnieszka Kalinskabienias, Cezary Kowalewski, Slawomir MajewskiAbstract:In recent years, the two adjacent novel EVER1 and EVER2 genes have been identified, whose mutations are responsible for the development of Epidermodysplasia verruciformis (EV). Epidermodysplasia verruciformis is a rare, autosomal recessive genodermatosis associated with increased risk of skin carcinoma. Up to now 7 mutations in the EVER1 gene and 5 mutations in the EVER2 gene have been identified only in EV. It was also determined that the EVER genes belong to a novel gene family, the transmembrane channel-like (TMC) family, and are responsible for properly functioning zinc homeostasis. These observations have given new insights into EV pathogenesis.
-
seroreactivity of 38 human papillomavirus types in Epidermodysplasia verruciformis patients relatives and controls
Journal of Investigative Dermatology, 2010Co-Authors: Kristina M Michael, Michel Favre, Herbert Pfister, Slawomir Majewski, Tim Waterboer, Marisa Gariglio, Michael PawlitaAbstract:Epidermodysplasia verruciformis (EV) is a rare recessive genodermatosis characterized by high susceptibility to infections with human papillomaviruses (HPVs) of genus beta. Knowledge about seroreactivity against HPV in these patients and their first-degree relatives is scarce. Using multiplex serology, we analyzed antibodies to 38 HPV types from five genera in 32 EV patients, 22 first-degree relatives, and 64 and 44 age- and sex-matched, non-related, healthy controls, respectively. EV patients showed higher seroprevalences than non-related controls with statistically significant odds ratios (ORs) for 5 of 10 investigated alpha (OR range 6.9–21.3), all 16 beta (OR range 12.3–61.3), 3 of 9 gamma (OR range 6.4–11.7), and 1 of 2 mu HPVs (OR 5.8). In comparison to their relatives, antibodies in EV patients were significantly more prevalent for 4 of 16 beta HPVs (OR range 12.5–25.6), but for none of the other genera. A significantly increased seroprevalence in relatives compared with their controls was only seen for HPV 5 (OR 22.1). The considerably elevated HPV seroprevalence in EV patients, especially for beta papillomaviruses (PVs), reflects the high viral load described for these individuals. Whether the observed differences between relatives and healthy controls depend on heterozygosity for EV-associated alleles requires further investigation.
-
High prevalence of Epidermodysplasia verruciformis-associated human papillomavirus DNA in actinic keratoses of the immunocompetent population
Archives of Dermatological Research, 2003Co-Authors: Herbert Pfister, Pawel G Fuchs, Stefania Jablonska, Slawomir Majewski, Iwona Pniewska, Magdalena MalejczykAbstract: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.
-
do Epidermodysplasia verruciformis human papillomaviruses contribute to malignant and benign epidermal proliferations
Archives of Dermatology, 2002Co-Authors: Slawomir Majewski, Stefania JablonskaAbstract:The aim of this review is to present new data on Epidermodysplasia verruciformis (EV) and EV human papillomaviruses (HPVs), regarded previously as specific to the disease. Recently introduced highly sensitive molecular methods for virologic studies allow detection of EV HPVs in non-EV populations. In this article, we present the most recent findings on EV and EV HPVs, which shed new light on a possible contribution of EV viruses to malignant and benign epidermal proliferation. We discuss the significance of EV HPV DNA detection in premalignant cutaneous lesions and nonmelanoma skin cancers; however, direct evidence for the causative role of EV HPV is still not available. In psoriasis, a high frequency of EV HPV-5 and other EV HPVs in the skin and the presence of specific HPV-5 antibodies strongly suggest expression of EV HPV proteins in this extensive epidermal proliferation. Epidermodysplasia verruciformis HPV-5 may also be transiently expressed in epidermal repair processes, whereas in psoriasis there is a continuous epidermal proliferation that could result in persistent viral expression. A potential contribution of EV HPVs to the pathogenesis of psoriasis is also supported by the recently disclosed co-localization of susceptibility loci for psoriasis and EV in the same region of chromosome arm 17qter; however, specific genes for both conditions are still not identified.
-
skin autografts in Epidermodysplasia verruciformis human papillomavirus associated cutaneous changes need over 20 years for malignant conversion
Cancer Research, 1997Co-Authors: Slawomir Majewski, Stefania JablonskaAbstract: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 20-30 years and epidemiological studies of this type for HPV-associated 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. Thus, skin HPV-associated carcinogenesis appears to be a very slow process comparable to the genital carcinogenesis associated with high risk HPVs.
Herbert Pfister - One of the best experts on this subject based on the ideXlab platform.
-
seroreactivity of 38 human papillomavirus types in Epidermodysplasia verruciformis patients relatives and controls
Journal of Investigative Dermatology, 2010Co-Authors: Kristina M Michael, Michel Favre, Herbert Pfister, Slawomir Majewski, Tim Waterboer, Marisa Gariglio, Michael PawlitaAbstract:Epidermodysplasia verruciformis (EV) is a rare recessive genodermatosis characterized by high susceptibility to infections with human papillomaviruses (HPVs) of genus beta. Knowledge about seroreactivity against HPV in these patients and their first-degree relatives is scarce. Using multiplex serology, we analyzed antibodies to 38 HPV types from five genera in 32 EV patients, 22 first-degree relatives, and 64 and 44 age- and sex-matched, non-related, healthy controls, respectively. EV patients showed higher seroprevalences than non-related controls with statistically significant odds ratios (ORs) for 5 of 10 investigated alpha (OR range 6.9–21.3), all 16 beta (OR range 12.3–61.3), 3 of 9 gamma (OR range 6.4–11.7), and 1 of 2 mu HPVs (OR 5.8). In comparison to their relatives, antibodies in EV patients were significantly more prevalent for 4 of 16 beta HPVs (OR range 12.5–25.6), but for none of the other genera. A significantly increased seroprevalence in relatives compared with their controls was only seen for HPV 5 (OR 22.1). The considerably elevated HPV seroprevalence in EV patients, especially for beta papillomaviruses (PVs), reflects the high viral load described for these individuals. Whether the observed differences between relatives and healthy controls depend on heterozygosity for EV-associated alleles requires further investigation.
-
high β hpv dna loads and strong seroreactivity are present in Epidermodysplasia verruciformis
Journal of Investigative Dermatology, 2009Co-Authors: Valentina Delloste, Sonke Weissenborn, Herbert Pfister, Barbara Azzimonti, Marco De Andrea, Michele Mondini, Elisa Zavattaro, Giorgio Leigheb, Kristina M Michael, Tim WaterboerAbstract:Epidermodysplasia verruciformis (EV) is a rare disease, characterized by cutaneous warts and associated with a strong predisposition to β-genus human papillomavirus (HPV). Earlier studies reported high copy numbers of HPV-DNA in nearly all skin tumors from EV patients, but neither HPV replication status in non-lesional skin nor anti-HPV seroreactivity in these patients have been reported yet. We therefore performed a comprehensive viral load analysis for the more common β-HPV types on skin samples and plucked eyebrow hairs from four EV patients treated at our dermatology department. The results clearly demonstrate that they carry a multiplicity (up to eighteen types) of β-HPV genotypes in both skin sites. Worthy of note, a high intrapatient concordance for specific types between hair bulbs and skin biopsies was observed and the same β-PV profile was maintained over time. Viral load analysis revealed a load range between less than one HPV-DNA copy per 100 cells to more than 400 HPV-DNA copies per cell in both eyebrow hairs and skin proliferative lesions. Evaluation of seroreactivity to β-HPV types in the four EV patients revealed that antibodies against the 16 β-HPV were significantly more prevalent and showed higher titers than in the controls.
-
High prevalence of Epidermodysplasia verruciformis-associated human papillomavirus DNA in actinic keratoses of the immunocompetent population
Archives of Dermatological Research, 2003Co-Authors: Herbert Pfister, Pawel G Fuchs, Stefania Jablonska, Slawomir Majewski, Iwona Pniewska, Magdalena MalejczykAbstract: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.
-
high prevalence of a variety of Epidermodysplasia verruciformis associated human papillomaviruses in psoriatic skin of patients treated or not treated with puva
Journal of Investigative Dermatology, 1999Co-Authors: Sonke Weissenborn, Reinhard Hopfl, F Weber, Hans Smola, Herbert Pfister, Pawel G FuchsAbstract:Epidermodysplasia verruciformis-associated human papillomaviruses and in particular human papillomavirus type 5 were recently shown to be highly prevalent in psoriatic skin. We have analyzed lesional skin from 54 psoriasis patients for infections with genital-specific and Epidermodysplasia verruciformis-specific human papillomaviruses to define the spectrum of involved human papillomavirus types and to test if it is influenced by psoralen ultraviolet A therapy. Using polymerase chain reaction analysis we could detect human papillomavirus sequences in skin lesions of 83% of the tested patients. In contrast, human papillomavirus-DNA was only demonstrated in 19% of skin samples from 42 dermatologically healthy, immunocompetent individuals. Sequence analysis of the polymerase chain reaction amplimers revealed 14 human papillomavirus types, all belonging to the Epidermodysplasia verruciformis or Epidermodysplasia verruciformis-related papillomaviruses. Only in one case we identified sequences related to those of genital viruses, which, however, represented a putatively new human papillomavirus type. The most prevalent human papillomavirus type in our patient series was human papillomavirus type 36, found in 62% of the patients positive for human papillomavirus-DNA, followed by human papillomavirus type 5 (38%) and human papillomavirus type 38 (24%). Multiple infections with two to five different human papillomavirus types could be detected in skin samples of 63% of the analyzed patients. The overall human papillomavirus detection rate did not differ significantly between patients which have been subjected to psoralen ultraviolet A photochemotherapy or solely treated with topical preparations (77 vs 89%). Human papillomavirus type 5, however, could be detected significantly more frequent in lesions of psoralen ultraviolet A-treated patients (p
-
prevalence of antibodies against virus like particles of Epidermodysplasia verruciformis associated hpv8 in patients at risk of skin cancer
Journal of Investigative Dermatology, 1998Co-Authors: Sabine Stark, Pawel G Fuchs, Jan Nico Bouwes Bavinck, Athanasios K Petridis, Shinje Ghim, Bennett A Jenson, G Gross, Eggert Stockfleth, Herbert PfisterAbstract:There is increasing evidence for widespread occurrences of infection with Epidermodysplasia verruciformis-related human papillomaviruses, both in the general population and in immunosuppressed patients. In order to test for the prevalence of antibodies directed against the native L1 epitopes exposed on the surface of the virions, we have established an IgG-specific enzyme-linked immunosorbent assay with L1 virus-like particles of the Epidermodysplasia verruciformis-specific human papillomavirus 8 as antigen to screen 567 representative serum samples from the general population and immunosuppressed/dermatologic patients. Among healthy European donors (n = 210), 7.6% were found to be seropositive. In a group of renal transplant recipients (n = 185) the antibody prevalence was elevated to 21.1%, irrespective of the presence or absence of skin cancer. High positivity rates could be detected among (i) immunocompetent patients with nonmelanoma skin tumors (45.6%, n = 79) and (ii) Psoralene/UVA treated psoriasis patients (42.9%, n = 42). In contrast, anti-human papillomavirus 8-virus-like particle antibodies were found in only 6.8% of Hodgkin lymphoma patients (n = 44).
Gerard Orth - One of the best experts on this subject based on the ideXlab platform.
-
host defenses against human papillomaviruses lessons from Epidermodysplasia verruciformis
Current Topics in Microbiology and Immunology, 2008Co-Authors: Gerard OrthAbstract:Epidermodysplasia verruciformis (EV) is a rare, autosomal recessive genodermatosis associated with a high risk of skin carcinoma (MIM 226400). EV is characterized by the abnormal susceptibility of otherwise healthy patients to infection by specific, weakly virulent human papillomaviruses (HPVs), including the potentially oncogenic HPV-5. Inactivating mutations in either of the related EVER1/TMC6 and EVER2/TMC8 genes cause most EV cases. New insights in EV pathogenesis have been gained from the following recent observations: (1) EV-specific HPVs (betapapillomaviruses) are defective for an important growth-promoting function encoded by an E5/E8 gene present in other HPVs, and inactivation of EVER proteins may compensate for the missing viral function; (2) the transmembrane viral E5/E8 and cellular EVER proteins interact both with the zinc transporter ZnT1, and are likely to modulate zinc homeostasis. EV may thus represent a primary deficiency in intrinsic, constitutive immunity to betapapillomaviruses, or constitute a primary deficiency in innate immunity (or both). Keratinocytes, the home cells of HPVs, are likely to play a central role in both cases. An important issue is to establish which cellular genes involved in intrinsic and innate antiviral responses play a part in the outcome of infections with other HPV types, such as genital oncogenic HPVs.
-
genetics of Epidermodysplasia verruciformis insights into host defense against papillomaviruses
Seminars in Immunology, 2006Co-Authors: Gerard OrthAbstract:Epidermodysplasia verruciformis (EV) is a rare autosomal recessive genodermatosis associated with a high risk of skin carcinoma. EV results from an abnormal susceptibility to infection by specific human papillomavirus (HPV) genotypes (beta-papillomaviruses) which include the potentially oncogenic HPV5. EV-specific HPVs are considered as harmless for the general population. EV was recently found to be caused by invalidating mutations in two adjacent, related, novel genes, EVER1/TMC6 and EVER2/TMC8. EVER genes encode transmembrane proteins located in the endoplasmic reticulum, which are likely to function as modifiers of ion transporters or channels and to be involved in signal transduction. It was proposed that EV was a primary defect of innate immunity. Our hypothesis is that EVER proteins act as restriction factors for EV-specific HPVs in keratinocytes, and that EV represents a primary deficiency of intrinsic immunity against certain papillomaviruses.
-
human papillomaviruses associated with Epidermodysplasia verruciformis in non melanoma skin cancers guilty or innocent
Journal of Investigative Dermatology, 2005Co-Authors: Gerard OrthAbstract:Abbreviations: AK, actinic keratoses; EV, Epidermodysplasia verruciformis; HPV, human papillomavirus; ISH, in situ hybridization; NMSC, non-melanoma skin cancers; OTR, organ transplant recipients; SCC, squamous cell carcinomas; UVR, ultraviolet radiation
-
Mutations in two adjacent novel genes are associated with Epidermodysplasia verruciformis.
Nature Genetics, 2002Co-Authors: Nicolas Ramoz, Luisalfredo Rueda, Luzstella Montoya, Bakar Bouadjar, Gerard Orth, Michel FavreAbstract:Epidermodysplasia verruciformis (OMIM 226400) is a rare autosomal recessive genodermatosis associated with a high risk of skin carcinoma that results from an abnormal susceptibility to infection by specific human papillomaviruses (HPVs). We recently mapped a susceptibility locus for Epidermodysplasia verruciformis (EV1) to chromosome 17q25. Here we report the identification of nonsense mutations in two adjacent novel genes, EVER1 and EVER2, that are associated with the disease. The gene products EVER1 and EVER2 have features of integral membrane proteins and are localized in the endoplasmic reticulum.
-
Mutation and Abnormal Expression of the p53 Gene in the Viral Skin Carcinogenesis of Epidermodysplasia verruciformis
Journal of Investigative Dermatology, 2001Co-Authors: Kamila Padlewska, Nicolas Ramoz, Stefania Jablonska, Odile Croissant, Patricia Cassonnet, Guy Riou, Michel Barrois, Slavomir Majewski, Gerard OrthAbstract:Patients suffering from Epidermodysplasia verruciformis are prone to nonmelanoma skin cancers, due to an inherited abnormal susceptibility to the oncogenic human papillomavirus type 5. Genotoxic sunlight ultraviolet B radiations are likely to be a cofactor. Lesions of two human-papillomavirus-type-5-infected Epidermodysplasia verruciformis patients collected during an 8 y period were retrospectively studied for p53 mutations in exons 5 through 8 by a polymerase chain reaction single-strand conformation polymorphism technique and/or by DNA sequencing of amplified exons. Mutations were detected in 11 of 26 (42.3%) specimens, including five (62.5%) squamous cell carcinomas, three (33.3%) Bowen's carcinomas in situ, two (40%) actinic keratoses, and one (33%) benign lesion. The nine mutations characterized by sequencing were shown to be missense and to affect mutational hotspots in human cancers. Five were C-->T transitions at dicytidine sites considered as ultraviolet signature mutations. Two were transversions (C-->G and C-->A) at dicytidine sites and two were C-->T transitions at nondipyrimidine sites. A marked p53 immunoreactivity was disclosed in 72.7% of 11 invasive carcinomas, 55.6% of nine carcinomas in situ, 37.5% of eight actinic keratoses, and one of three benign lesions. This includes 81.8% of 11 specimens with a p53 mutation but also 50% of 14 specimens with no mutation detected. A dysfunction of the p53 gene is thus likely to play a part in Epidermodysplasia verruciformis carcinogenesis, either due to ultraviolet-B-induced p53 mutations, as in nonmelanoma skin cancers in the general population, or involving other mutagens or mechanisms. The part played by human papillomavirus type 5 proteins expressed in Epidermodysplasia verruciformis keratinocytes remains to be determined.