E6/E7 expression of human papillomavirus types in cutaneous squamous cell dysplasia and carcinoma in immunosuppressed organ transplant recipients

Dang, Chantip; Koehler, Angelika; Forschner, T.; Sehr, Peter; Michael, K.; Pawlita, Michael; Stockfleth, Eggert; Nindl, Ingo

doi:10.1111/j.1365-2133.2006.07378.x

Cited by 68 publications

(46 citation statements)

References 39 publications

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“…Both SCC and BCC develop mostly on sun-exposed sites (Frost & Green, 1994), and some specific types of HPV, including HPV-5, HPV-8, HPV-20 and HPV-77, have been shown to be activated by UV radiation (Akgül et al, 2005;Massimi et al, 2008;Michel et al, 2006;Purdie et al, 1999;Storey et al, 1998). Evidence of UV-induced E6/E7 oncogenicity and transcriptional activity of E6/E7 oncogenes in NMSC has been found (Al Moustafa et al, 2004;Dang et al, 2006;Michel et al, 2006). Furthermore, differences in transforming activity potential between various cutaneous HPV types have been shown, providing further evidence for a role of cutaneous HPV in the development of NMSC (Massimi et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Human papillomavirus type spectrum in normal skin of individuals with or without a history of frequent sun exposure

Chen

McMillan

Antonsson

2008

Journal of General Virology

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Cutaneous human papillomavirus (HPV) has been widely detected in healthy skin. Previous studies have found that UV radiation can activate several HPV types, and a possible role for cutaneous HPV in the development of non-melanoma skin cancer has been suggested. This study investigated the prevalence and type-spectrum of cutaneous HPV in relation to UV radiation by studying forehead skin swab samples from 50 healthy males frequently exposed to the sun and 50 healthy males who were not frequently exposed to the sun. A questionnaire including ethnic background of the participants, history of cancers and a self-assessment of sun-exposure was also conducted and analysed. PCR with the FAP primer pair was carried out to detect HPV DNA in samples. HPV prevalence was higher in individuals who spent more time outdoors and in individuals with a history of skin cancers (P50.044 and P50.04, respectively). Furthermore, individuals wearing sunglasses as a means of sun protection had a lower prevalence of HPV (P50.018). Interestingly, HPV-76 was only detected in the group without frequent sun-exposure (P50.001). These results suggest that increased UV radiation exposure may be a factor leading to a difference in prevalence of cutaneous HPV types. INTRODUCTIONHuman papillomaviruses (HPVs) infect cutaneous and mucosal epithelia and are recognized as the causative agents of warts. It has recently become apparent that clinically normal skin harbours many different HPV types, and many of these HPV types have not been described previously (Antonsson et al., 2000(Antonsson et al., , 2003a Astori et al., 1998). Furthermore, it has been shown that asymptomatic HPV infections are acquired very early in infancy with a broad spectrum of HPV types (Antonsson et al., 2003b), and that the prevalence of HPV DNA in healthy skin increases with age (Antonsson et al., 2000). Moreover, cutaneous HPV infections on healthy skin have often been found to persist over time (Hazard et al., 2006). Many studies have also suggested a role for HPV in the carcinogenesis of non-melanoma skin cancer (NMSC). Squamous cell carcinoma (SCC) can metastasize, and is known as the unfavourable form of NMSC compared with basal cell carcinoma (BCC). Interestingly, BCCs are found approximately three times more frequently in immunocompetent individuals; however, in immunosuppressed organ-transplant recipients, SCCs are more prevalent (Pfister, 2003). It has been reported that more HPV types have been found in actinic keratosis and SCC skin lesions than in normal skin (Alotaibi et al., 2006), and a greater variety of HPV types have also been found in immunosuppressed individuals than in immunocompetent individuals (Harwood et al., 2004). Both SCC and BCC develop mostly on sun-exposed sites (Frost & Green, 1994), and some specific types of HPV, including HPV-5, HPV-8, HPV-20 and HPV-77, have been shown to be activated by UV radiation (Akgül et al., 2005;Massimi et al., 2008;Michel et al., 2006;Purdie et al., 1999;Storey et al., 1998). Evidence of UV-induced E6/E7 oncogenici...

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Section: Introductionmentioning

confidence: 99%

Human papillomavirus type spectrum in normal skin of individuals with or without a history of frequent sun exposure

Chen

McMillan

Antonsson

2008

Journal of General Virology

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“…Expression of the early genes of betapapillomaviruses from the viral promoter in basal epidermal layers during natural infection in humans usually remains below the detection limits of in situ hybridization or real-time RT-PCR (Dang et al, 2006;Haller et al, 1995). This can explain the much slower and less efficient oncogenesis in man.…”

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confidence: 99%

Spontaneous tumour development in human papillomavirus type 8 E6 transgenic mice and rapid induction by UV-light exposure and wounding

Marcuzzi

Hufbauer

Kasper

et al. 2009

Journal of General Virology

101

118

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Cutaneous human papillomavirus type 8 (HPV8) is carcinogenic in patients with epidermodysplasia verruciformis. Transgenic mice with the complete early region (CER) of HPV8 spontaneously developed papillomas, dysplasia and squamous cell carcinomas of the skin. To characterize the role of individual early genes in carcinogenesis, the E6 and E6/E7 genes were expressed separately in transgenic mice. Nearly all HPV8-E6-positive mice spontaneously developed multifocal tumours, characterized by papillomatosis, hyperkeratosis and varying degrees of epidermal dysplasia. In 6 % of the cases, the tumours became malignant, comparable with HPV8-CER mice. Thus, in the murine epidermis, E6 is the major oncogene necessary and sufficient to induce spontaneous tumour development up to the level of squamous cell carcinoma. To evaluate the synergistic effects of UV light and wound healing, the skin of HPV8 mice was irradiated with UVA/UVB light or wounded with punch biopsies. These treatments induced papillomatosis in HPV8-CER and -E6 mice within 3 weeks. Irradiation with UVA alone did not induce papillomatosis and UVB alone had a weaker effect than UVA/UVB, indicating a synergistic role of UVA in UVB-induced papillomatosis. An HPV8 infection persisting over decades in interaction with sun burns and wound healing processes may be a relevant cause of skin cancer in humans.

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“…Two recent studies have reported on antibodies against E6 and E7 proteins. 18,19 We report here the results of a pilot study of the relationship between antibodies against HPV-L1 antigens for 38 HPV types in relation to SCC in apparently immunocompetent patients with plasma collected before or after the diagnosis of their skin tumor. We used biological samples and data from the Oxford component of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford).…”

mentioning

confidence: 99%

A prospective pilot study of antibodies against human papillomaviruses and cutaneous squamous cell carcinoma nested in the Oxford component of the European Prospective Investigation into Cancer and Nutrition

Casabonne

Michael

Waterboer

et al. 2007

Intl Journal of Cancer

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In a prospective pilot study nested in the EPIC-Oxford cohort, we examined the seroprevalence of antibodies against the L1 antigen of 38 human papilloma virus (HPV) types among 39 cases of cutaneous squamous cell carcinoma (SCC) for whom plasma was collected prior to diagnosis (incident) and 80 controls. Fifteen cases having already developed SCC at blood collection (prevalent) were also tested. There were no statistically significant differences in the seroprevalence of antibodies against any of the HPV types examined between incident cases and controls, nor was there a difference in the seroprevalence of multiple infections. However, consistent with results from published case-control studies, the seroprevalence of many b-HPV types was higher among prevalent cases than among either incident cases or controls. For example the seroprevalence of antibodies against HPV-8 was 20% (16/80) in controls, 23% (9/39) among incident cases and 40% (6/15) among prevalent cases. Among the incident cases only, the seroprevalence was 16% (5/32) among those for whom blood was collected 181 months prior to diagnosis, but 57% (4/7) among those for whom diagnosis was within 18 months of blood collection, a pattern seen for many of the HPV types. This might suggest that if HPV is involved in the aetiology of SCC, the process occurs close to the time of diagnosis, or that the antibody response observed in people with SCC is a consequence of tumor formation. Further and larger prospective studies are needed to clarify the role of HPV in the aetiology of cutaneous SCC. ' 2007 Wiley-Liss, Inc.Key words: Epidemiology; human papillomavirus (HPV); serology; cutaneous squamous cell carcinoma (SCC); prospective case-control Nonmelanoma skin cancer (NMSC), comprising basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in a ratio of about five to one, is the most commonly diagnosed cancer in white populations. Established risk factors include exposure to solar ultra-violet radiation and, for SCC in particular, immunosuppression, such as that experienced by organ transplant recipients.1-4 In addition, there is some evidence of an association between certain human papillomaviruses (such as HPV types 5 and 8) and the development of cutaneous SCC (but not basal).5 To date, more than 118 papillomaviruses have been completely described, of which about a hundred infect humans. 6 The alpha types, particularly HPV-16, 18, 33 and 45, are well established causes of cancer of the uterine cervix; the viral E6 and E7 proteins are associated with the degradation of tumor suppressors p53 and pRb, respectively. 7A role for HPV in the aetiology of skin cancers is uncertain, although evidence of possible molecular mechanisms is emerging with HPV probably working as a co-factor with ultraviolet radiation early in the development of SCC. 8Most studies of HPV and cutaneous SCC have used HPV-DNA detection methods to examine the association. Because of the high sensitivity of PCR methods and the ubiquity of HPV, previously unknown types are often identified...

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E6/E7 expression of human papillomavirus types in cutaneous squamous cell dysplasia and carcinoma in immunosuppressed organ transplant recipients

Abstract: Transcriptional activity of the E6/E7 oncogenes in AK and SCC suggests an active role of HPV in the lesion.

Cited by 68 publications

References 39 publications

Human papillomavirus type spectrum in normal skin of individuals with or without a history of frequent sun exposure

Human papillomavirus type spectrum in normal skin of individuals with or without a history of frequent sun exposure

Spontaneous tumour development in human papillomavirus type 8 E6 transgenic mice and rapid induction by UV-light exposure and wounding

A prospective pilot study of antibodies against human papillomaviruses and cutaneous squamous cell carcinoma nested in the Oxford component of the European Prospective Investigation into Cancer and Nutrition

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