E6/E7 expression of human papillomavirus type 20 (HPV-20) and HPV-27 influences proliferation and differentiation of the skin in UV-irradiated SKH-hr1 transgenic mice. (1/54)

The functional role of UV irradiation, in combination with the E6 and E7 proteins of the cutaneous human papillomavirus (HPV) types in the malignant conversion of benign papillomatous lesions, has not been elucidated. Transgenic SKH-hr1 hairless mice expressing HPV-20 and HPV-27 E6 and E7 proteins in the suprabasal compartment were generated and exposed to chronic UV irradiation. Histological and immunohistochemical examination of skin samples revealed enhanced proliferation of the epidermal layers and papilloma formation in both transgenic strains in comparison to what was observed with nontransgenic mice. Squamous cell carcinoma developed in the HPV-20 E6/E7 transgenic line as well as in the HPV-27 E6/E7 transgenic line. Several weeks after cessation of UV-B exposure, enhanced proliferation, as measured by BrdU incorporation, was maintained only in HPV-20 transgenic skin. Keratin 6 expression was increased in the transgenic mice throughout all cell layers. Expression of the differentiation markers involucrin and loricrin was reduced and disturbed. p63alpha expression was differentially regulated with high levels of cytoplasmic expression in clusters of cells in the granular layer of the skin in the transgenic lines 20 weeks after cessation of UV-B exposure, in contrast to uninterrupted staining in the nontransgenic lines. p53 was expressed in clusters of cells in nontransgenic and HPV-27 transgenic mice, in contrast to an even distribution in a higher number of cells in HPV-20 transgenic animals.  (+info)

Betapapillomaviruses frequently persist in the skin of healthy individuals. (2/54)

Infections with human papillomaviruses (HPVs) belonging to the genus Betapapillomavirus have been linked to the development of non-melanoma skin cancer. Although persistence is expected, systematic investigation of this aspect of betapapillomavirus (beta-PV) infection has not been conducted. This study investigated the prevalence and persistence of 25 known beta-PV types in the skin of immunocompetent individuals. Over a 2 year period, eight consecutive plucked eyebrow hair samples taken from 23 healthy individuals were analysed for the presence of beta-PV DNA. Using a recently published general beta-PV PCR and genotyping method, 61% of the individuals were beta-PV DNA positive for one or more types at intake, whereas during follow-up this percentage rose to 96%. HPV23 was the most frequently detected beta-PV type. Type-specific beta-PV DNA was detected over 6 months or longer in 74% of the individuals. In 57% of the individuals, DNA from multiple beta-PV types was detected simultaneously for 6 months or longer. When the detection intervals of all beta-PV type-specific infections in the study population were considered, a substantial proportion, 48%, lasted at least half a year. The consistent beta-PV patterns found over time in most individuals strongly suggested that beta-PV DNA detection in plucked eyebrow hairs reveals true beta-PV infection. If the minimum interval of detection was set at 6 months, persistent beta-PV infections were found in the majority of the study population (74%).  (+info)

Development of a sensitive and specific multiplex PCR method combined with DNA microarray primer extension to detect Betapapillomavirus types. (3/54)

Emerging lines of evidence indicate that the cutaneous human papillomavirus (HPV) types that belong to the genus Betapapillomavirus (beta HPV) are involved in the development of nonmelanoma skin cancer. Unlike the situation for mucosal HPV types, highly sensitive and reliable methods to identify characterized cutaneous HPV types in a single assay are limited. Here, we describe a novel one-shot method for the detection of all characterized beta HPV types, namely, HPV type 5 (HPV5), 8, 9, 12, 14, 15, 17, 19, 20, 21, 22, 23, 24, 25, 36, 37, 38, 47, 49, 75, 76, 80, 92, 93, and 96. This assay combines two different techniques: multiplex PCR using HPV type-specific primers for amplification of each E7 gene and array primer extension (APEX) for typing. This method has been validated using clinical samples which were analyzed simultaneously for the presence of cutaneous HPV types by two additional methods, i.e., the FAP59/64 PCR protocol and a commercially available PCR-reverse hybridization assay (PM-PCR RHA). Our data show good agreement between the results obtained with the multiplex PCR/APEX assay and the PM-PCR RHA method (overall HPV positivity of 92.2% for multiplex PCR/APEX assay versus 90.6% with the PM-PCR RHA) (kappa value, 50; 95% confidence interval, 13 to 88). In addition, the multiplex PCR/APEX assay showed higher sensitivity than the PM-PCR RHA did. This favorable feature and the high-throughput potential make this assay ideal for large-scale clinical and epidemiological studies aimed at determining the spectrum of cutaneous types in skin cancer.  (+info)

Cutaneous human papillomaviruses found in sun-exposed skin: Beta-papillomavirus species 2 predominates in squamous cell carcinoma. (4/54)

BACKGROUND: A spectrum of cutaneous human papillomaviruses (HPVs) is detectable in nonmelanoma skin cancers, as well as in healthy skin, but the significance that the presence of these types of HPV DNA has for the pathogenesis of skin cancer remains unclear. METHODS: We studied 349 nonimmunosuppressed patients with skin lesions (82 with squamous cell carcinomas, 126 with basal cell carcinomas, 49 with actinic keratoses, and 92 with benign lesions). After superficial skin had been removed by tape, paired biopsy samples--from the lesion and from healthy skin from the same patient--were tested for HPV DNA. Risk factors for HPV DNA were analyzed in multivariate models. RESULTS: Overall, 12% of healthy skin samples were positive for HPV DNA, compared with 26% of benign lesions, 22% of actinic keratoses, 18% of basal cell carcinomas, and 26% of squamous cell carcinomas. HPV DNA was associated with sites extensively exposed to the sun, both for the lesions (odds ratio [OR], 4.45 [95% confidence interval {CI}, 2.44-8.11]) and for the healthy skin samples (OR, 3.65 [95% CI 1.79-7.44]). HPV types of Beta-papillomavirus species 2 predominate in squamous cell carcinomas (OR, 4.40 [95% CI, 1.92-10.06]), whereas HPV types of Beta-papillomavirus species 1 are primarily found in benign lesions (OR, 3.47 [95% CI, 1.72-6.99]). CONCLUSIONS: Cutaneous HPV types are primarily detected at sites extensively exposed to the sun. HPV types of Beta-papillomavirus species 2, but not of species 1, are associated with squamous cell carcinoma.  (+info)

Genetic diversity of cutaneous human papillomaviruses. (5/54)

Human papillomaviruses (HPVs) of the genera Betapapillomavirus and Gammapapillomavirus are common on human skin. Sequencing of subgenomic amplicons of cutaneous HPVs has revealed a large number of novel putative HPV types within these genera. Phylogenetic analysis based on these amplicons revealed 133 putative HPV types with <90 % sequence identity to any known HPV type or to each other. As there are already 34 characterized HPV types described within the genera Betapapillomavirus and Gammapapillomavirus, they appear to be the most genetically diverse of the HPVs, apparently comprising at least 167 different HPV types.  (+info)

The E6 oncoproteins from human betapapillomaviruses differentially activate telomerase through an E6AP-dependent mechanism and prolong the lifespan of primary keratinocytes. (6/54)

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Beta-papillomavirus infection and skin cancer. (7/54)

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Beta-papillomaviruses and psoriasis: an intra-patient comparison of human papillomavirus carriage in skin and hair. (8/54)

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