Association of human papillomavirus infections with cutaneous tumors in immunosuppressed patients

Meyer, Thomas; Arndt, R.; Nindl, Ingo; Ulrich, Claas; Christophers, Enno; Stockfleth, Eggert

doi:10.1111/j.1432-2277.2003.tb00278.x

Cited by 86 publications

(73 citation statements)

References 21 publications

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“…The viral loads in the HPV-positive patients were low, ranging from one viral copy per y35 000 cells to three copies per cell, a trend also observed by other groups (Bens et al, 1998;Meyer et al, 2001;Weissenborn et al, 2005). We found that SK lesions harboured higher amounts of virus than AK; however, due to the small number of observations, this finding requires further investigation.…”

Section: Discussionsupporting

confidence: 59%

Four novel human betapapillomaviruses of species 2 preferentially found in actinic keratosis

Vasiljević

Hazard

Dillner

et al. 2008

Journal of General Virology

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Recent studies have suggested an association between human papillomaviruses (HPVs), particularly species 2 members of the genus Betapapillomavirus, and squamous cell carcinoma (SCC) of the skin. As most of these viruses are uncharacterized, molecular characterization and epidemiology are needed to advance our understanding of their significance in carcinogenesis. This study determined the complete genomes of four betapapillomaviruses of species 2 from skin lesions designated , an isolate of an unpublished HPV type, and analysed their prevalence and viral loads in biopsies from SCC, actinic keratosis (AK), basal cell carcinoma, seborrhoeic keratosis and the healthy skin of 263 immunocompetent patients by HPV type-specific real-time PCR assays. Seventeen patients (6.5 %) harboured at least one of the four HPV types in their lesion, whereas seven patients (2.7 %) harboured one or more of the HPV types in healthy skin. Overall, the four viruses were more common in AK than in healthy skin (odds ratio 5.0, 95 % confidence interval 1.4-17.5), but the prevalence and viral loads were low. This characterization of expands the heterogeneity of members of species 2 of the genus Betapapillomavirus. However, as these types were found in only a few samples and in low amounts, a possible role in carcinogenesis remains elusive.

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Section: Discussionsupporting

confidence: 59%

Four novel human betapapillomaviruses of species 2 preferentially found in actinic keratosis

Vasiljević

Hazard

Dillner

et al. 2008

Journal of General Virology

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“…Cutaneous ␤-HPVs are less studied. While ␤-HPVs appear to be part of the normal "skin flora" and infections are often asymptomatic, they can cause cutaneous warts, which undergo malignant progression in patients suffering from the rare genetic disease epidermodysplasia verruciformis (EV) or in systemically immune-suppressed organ transplant patients, particularly in sun-exposed areas of the body (2)(3)(4)(5). ␤-HPVs may also contribute to nonmelanoma skin cancers (NMSCs) in patients with a normal immune system, but this has not been formally proven.…”

mentioning

confidence: 99%

The Human Papillomavirus Type 8 E6 Protein Interferes with NOTCH Activation during Keratinocyte Differentiation

Meyers

Spangle

Münger

2013

J Virol

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Cutaneous ␤-human papillomavirus (␤-HPV) E6 proteins inhibit NOTCH signaling by associating with the transcriptional coactivator MAML1. NOTCH has tumor suppressor activities in epithelial cells and is activated during keratinocyte differentiation. Here we report that HPV type 8 (HPV8) E6 subverts NOTCH activation during keratinocyte differentiation by inhibiting RBPJ/MAML1 transcriptional activator complexes at NOTCH target DNA. NOTCH inhibition impairs epithelial differentiation and may thus contribute to ␤-HPV replication and viral oncogenesis. Papillomaviridae are a large family of epitheliotropic viruses with double-stranded circular ϳ8-kb DNA genomes. More than 150 human papillomaviruses (HPVs) have been isolated (1). Some HPVs infect mucosal epithelia, whereas other HPVs infect cutaneous epithelial cells. HPV infections can be nonsymptomatic or cause hyperplastic skin lesions, commonly referred to as warts. Mucosal ␣-HPVs have been studied in great detail since some of these viruses, the "high-risk" HPVs, are the causative agents of cervical carcinoma as well as other anogenital cancers and oropharyngeal carcinomas. Cutaneous ␤-HPVs are less studied. While ␤-HPVs appear to be part of the normal "skin flora" and infections are often asymptomatic, they can cause cutaneous warts, which undergo malignant progression in patients suffering from the rare genetic disease epidermodysplasia verruciformis (EV) or in systemically immune-suppressed organ transplant patients, particularly in sun-exposed areas of the body (2-5). ␤-HPVs may also contribute to nonmelanoma skin cancers (NMSCs) in patients with a normal immune system, but this has not been formally proven.Cutaneous ␤-HPV E6 proteins have intrinsic transforming activities (6, 7) but do not associate with known cellular target proteins of high-risk mucosal ␣-HPV E6 proteins, including p53, UBE3A, and cellular PDZ proteins (8). Several groups have recently reported that the E6 proteins from HPV5, HPV8, and other ␤-HPVs can bind the NOTCH coactivator mastermind-like 1 (MAML1), thereby inhibiting NOTCH transcriptional programs (9-11). This is particularly interesting since NOTCH functions as a tumor suppressor in epithelial cells and mice with expression of a dominant negative MAML in basal epithelial cells develop squamous cell carcinoma (12). Since NOTCH signaling is important for cellular differentiation, we wanted to determine whether HPV8 E6 inhibits NOTCH signaling during keratinocyte differentiation. To experimentally address this issue, we generated populations of human keratinocytes immortalized with human telomerase reverse transcriptase (hTERT) (cl398) (13) and stably expressing amino-terminally hemagglutinin (HA)/FLAG epitopetagged HPV8 E6 (8E6-iHFKs) by lentiviral transduction. Vector-infected cells were generated as controls (C-iHFKs). To confirm the interaction of HPV8 E6 with components of the NOTCH transcriptional complex in these cells, we prepared lysates of 8E6-iHFKs and C-iHFKs in mammalian cell lysis buffer (MCLB; 50 mM Tris [pH 7.5], 150 mM...

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“…Weiterhin erwähnt wird in der Diskussion eine stattgehabte Therapie mit Chemotherapeutika in der Vorgeschichte der Patienten. Hier spielt neben dem immunsuppressiven Faktor der direkte kanzerogene Effekt dieser Medikamente eine Rolle (Hojo et al, 1999;Meyer et al, 2003 (Joseph et al, 1992;Weinstock, 1994). Bei Auftreten einer lokoregionären oder Fernmetastasierung kommt es zu einem relevanten Anstieg des Mortalitätsrisikos und zu einem…”

Section: % Wurde Für Die Lokalisation Am äUßeren Ohr Und In Der Perunclassified

Significance of parotid metastases of squamous cell carcinoma of scalp

2007

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Association of human papillomavirus infections with cutaneous tumors in immunosuppressed patients

Cited by 86 publications

References 21 publications

Four novel human betapapillomaviruses of species 2 preferentially found in actinic keratosis

Four novel human betapapillomaviruses of species 2 preferentially found in actinic keratosis

The Human Papillomavirus Type 8 E6 Protein Interferes with NOTCH Activation during Keratinocyte Differentiation

Significance of parotid metastases of squamous cell carcinoma of scalp

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