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1/11. epidermodysplasia verruciformis treated using topical 5-aminolaevulinic acid photodynamic therapy.

    We describe a 65-year-old woman who had had wart-like lesions on the hands, lower arms and forehead for about 45 years. She had already had several basal cell carcinomas excised. Histological study, electron microscopy and in situ hybridization [human papilloma virus (HPV)-types 5/8/12/14/19-23/25/36] of skin biopsies confirmed a diagnosis of epidermodysplasia verruciformis (EV). Photodynamic therapy (PDT) was performed using a 20% 5-aminolaevulinic acid ointment applied for 6 h to the lesions and irradiating using an incoherent light source (lambda = 580-740 nm, 160 mW/cm2, 160 J/cm2). Following PDT, blistering and crusting of the lesions occurred, but these healed completely within 2-3 weeks without scarring, and the cosmetic result was excellent. Six months after PDT a skin biopsy was taken. in situ hybridization was positive for HPV type 8 in skin which was clinically and histologically normal. Twelve months after PDT a few lesions had recurred on the hands. Although permanent cure of EV cannot be achieved by any therapy at present and single lesions continue to appear in this patient, topical PDT might result in better control of HPV-induced lesions.
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2/11. Distinctive distribution of human papillomavirus type 16 and type 20 dna in the tonsillar and the skin carcinomas of a patient with epidermodysplasia verruciformis.

    BACKGROUND: epidermodysplasia verruciformis (EV) is a rare skin disease characterized by disseminated pityriasis versicolor-like or flat wart-like lesions and by the development of skin carcinomas. It is well established that specific cutaneous human papillomaviruses (EV-HPVs) are associated with both benign and malignant skin lesions in EV patients. However, little is known of the relationship between HPV and the mucosal lesions of EV patients. OBJECTIVES: To detect and identify HPV types associated with skin and mucosal lesions of an EV patient. PATIENT/methods: We investigated the skin carcinoma and the coexisting tonsillar carcinoma of a 41-year-old man with EV. Histopathologically, both lesions were squamous cell carcinomas. We analysed these two lesions by immunohistochemistry, in situ hybridization, and by molecular virology. RESULTS: Neither skin nor tonsillar lesions exhibited positivity for HPV capsid antigen by immunohistochemistry. By Southern blot hybridization, however, the skin carcinoma harboured 'EV-specific' HPV20 dna, while the tonsillar carcinoma harboured 'genital' HPV16 dna. In addition, in situ hybridization localized the respective viral dna in the corresponding lesion. CONCLUSIONS: The results indicate that EV-HPV could be responsible for the development of the skin carcinoma, but not the mucosal carcinoma in this patient.
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3/11. epidermodysplasia verruciformis in two half brothers with hiv infection.

    BACKGROUND: epidermodysplasia verruciformis (EV) is a rare disorder characterized by widespread flat and common verrucae. From 25% to 50% of EV cases are inherited, usually with an autosomal recessive pattern. An X-linked inheritance has also been reported. Many EV patients have a cellular immunity defect. hiv-associated lesions have been found to contain HPV-5, HPV-8, and HPV-20. OBJECTIVE: We describe two hiv-positive Hispanic maternal half brothers who presented with asymptomatic polyangular papules and plaques on the face, trunk, and extremities and which first appeared 4-5 years prior. The histopathology is consistent with EV. HPV-8 was detected by in situ hybridization. The patients were treated with topical imiquimod for two months without improvement. CONCLUSION: To our knowledge, this is the first reported case of epidermodysplasia verruciformis in hiv-positive pediatric patients.
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4/11. epidermodysplasia verruciformis-associated papillomavirus infection complicating human immunodeficiency virus disease.

    Three males infected with the human immunodeficiency virus (hiv) were noted to have extensive flat warts of the face and/or body. In two there were also pityriasis versicolor-like lesions. Biopsies showed foamy, basophilic, distended cytoplasm in granular layer keratinocytes, characteristic of the human papillomavirus types seen in epidermodysplasia verruciformis. dna hybridization techniques demonstrated the presence of HPV-type 8 in one patient and HPV 5 and 8 in another. patients with immune suppression due to hiv infection may demonstrate the clinical features of epidermodysplasia verruciformis with the same potentially oncogenic HPV types.
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5/11. Severe intractable common warts associated with human papillomavirus 2, 3 and 20.

    A 26-year-old male had had numerous common warts on the feet and hands since childhood. They had repeatedly undergone etretinate cryosurgery, always responding well to it. However, the warts reappeared. Human papillomavirus (HPV) 2, 3 and 20 were detected in the warts using Southern's blot hybridization technique with HPV dna. Histologically, the warts showed swollen, clear keratinocytes with vacuolated degeneration not found in common warts. The findings are presented in this paper.
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6/11. epidermodysplasia verruciformis. A case associated with primary lymphatic dysplasia, depressed cell-mediated immunity, and bowen's disease containing human papillomavirus 16 dna.

    epidermodysplasia verruciformis is a rare, often hereditary disease characterized by a generalized cutaneous infection with human papillomavirus (HPV), depressed cell-mediated immunity, and a propensity for transformation of the warty lesions to squamous cell carcinoma on primarily sun-exposed areas of the skin. A 37-year-old man with congenital lymphatic dysplasia and a history of squamous cell carcinoma of the groin and foot was observed by us to have edema of all four extremities, numerous flat warts, and pityriasis versicolor-like papules over the trunk and arms. Condylomatous lesions were noted in the groin and a periungual verrucous nodule on the thumb. Biopsies showed the trunk and arm lesions to be verrucae and the thumb lesion to be bowen's disease. Results of molecular hybridization studies from four lesions of the arms showed the presence of only HPV 3 dna; HPV 16-related dna was detected in the intraepidermal carcinoma on the thumb. Immunologic evaluation revealed anergy to routine skin testing, depressed mitogen-stimulated lymphocyte transformation, decreased B-lymphocyte count, and a severe reversal of the T-lymphocyte helper:suppressor ratio.
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7/11. epidermodysplasia verruciformis in a patient with Hodgkin's disease: characterization of a new papillomavirus type and interferon treatment.

    A new human papillomavirus (HPV) was discovered in disseminated, macular, pityriasis versicolor-like lesions on the skin of the neck, face, scalp, and pubic region of a 42-year-old male suffering from Hodgkin's disease. Histopathology revealed features characteristic of epidermodysplasia verruciformis (ev). In contrast to classical ev, the lesions were almost exclusively seen in previously irradiated and UV-exposed skin areas. Papillomavirus capsid antigen was demonstrated with the genus-specific antiserum and the patient's serum, which had IgM and IgG antibody titers. HPV dna was isolated from biopsies and cloned into the vector pIC20H. It proved to be related to ev-associated viruses, showing 23% cross-hybridization with dna of the closest relative HPV14. The new HPV type was named HPV46. The genome was physically mapped and colinearly aligned with HPV8 dna to establish its gene organization. Interferon treatment of the patient did not significantly change the clinical picture nor was the concentration of viral dna per lesion affected. However, no virus capsid antigen was detectable after starting treatment.
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8/11. Human papillomavirus type 38 isolated from patients with epidermodysplasia verruciformis.

    A new type of human papillomavirus (HPV), HPV-38b, was isolated from patients with epidermodysplasia verruciformis and was molecularly cloned. This HPV was shown by hybridization experiments to have almost no sequence homology with other types of reported HPVs, but did show homology with HPV-38, which was recently isolated from a melanoma. A physical map and a rough genetic map of the organization of this HPV are presented.
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9/11. Detection of human papillomavirus (HPV) type 47 dna in malignant lesions from epidermodysplasia verruciformis by protocols for precise typing of related HPV DNAs.

    Our discovery of human papillomavirus type 47 (HPV47) in benign lesions from a patient suffering from epidermodysplasia verruciformis prompted us to examine whether the viral dna also resided in malignant lesions from the same patient. By using newly devised protocols for amplifying a group of epidermodysplasia verruciformis-associated HPV DNAs by PCR and differentially identifying them by reverse-phase dot blot hybridization, we demonstrated that HPV47 dna, but not other HPV DNAs of the group, was abundant (about 10(3) copies per diploid amount of cell dna) in DNAs prepared from three carcinomas. Using dna from one of these carcinomas, we also confirmed that dna of HPV5, HPV14, or HPV21, detected in significant amounts in DNAs from benign lesions from the patient, were present only in negligible amounts or not at all. The results suggest the involvement of HPV47 dna in tumorigenesis. Furthermore, we demonstrated by the Southern technique that most, if not all, of the HPV47 dna consists of either a unit (or a nongrossly deleted unit) length of the viral genome carrying no (or no gross) internal rearrangements or tandem repeats. This and other results obtained by this technique indicated that a considerable amount of the viral dna resides as a circular monomer a unit length of the viral genome in carcinoma cells, while the remainder reside as catenanes, concatemers, or both. The concatemers were considered more likely to be replicated without integration into cellular dna than to be integrated, because no bands for the corresponding fragments including integration sites were detected by treatment with restriction enzymes that would have produced such fragments.
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10/11. Detection of new human papillomavirus sequences in skin lesions of a renal transplant recipient and characterization of one complete genome related to epidermodysplasia verruciformis-associated types.

    Human papillomavirus (HPV) dna, originally isolated from patients suffering from the skin disease epidermodysplasia verruciformis (EV), and a growing number of related sequences have recently been detected in a high percentage of benign and malignant skin lesions of both immunosuppressed and immunocompetent people. HPV L1 dna fragments (374-389 bp long) from a solar keratosis and a squamous cell carcinoma (SCC) of a renal transplant recipient were amplified, cloned and sequenced. In 54 clones, six different HPV sequences were identified. One of these six corresponded to the known type HPV-8 and two (RTRX3 and RTRX7) have been described previously in cutaneous lesions of immunosuppressed patients. The remaining three sequences were different from all known HPV types: an HPV-9-related sequence (77.4% identity), an RTRX2-related sequence (82.6% identity), and an HPV-22-related sequence (83.7% identity). These three sequences, representing putatively new HPV types, were named RTRX8, RTRX9 and RTRX10, respectively. RTRX7 was found in the majority of clones from both lesions. The complete genome of RTRX7 (7731 bp) was cloned as six overlapping subgenomic fragments, generated by nested PCR with dna extracts from the SCC. RTRX7 showed a genome organization typical of HPVs associated with EV. The L1 dna sequence differed by 15% from the corresponding region of its closest known relative, HPV-12; thus, RTRX7 can be regarded as a new HPV type. RTRX7 dna could not be detected by Southern blot hybridization with the homologous probe, indicating that the dna concentration was below one copy per 10 cells in the investigated SCC.
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