Frequency and Spectrum of HPV Types Detected in Cutaneous Squamous-Cell Carcinomas Depend on the HPV Detection System: A Comparison of Four PCR Assays

Meyer, Thomas; Arndt, R.; Christophers, Enno; Stockfleth, Eggert

doi:10.1159/000018489

Cited by 43 publications

(46 citation statements)

References 24 publications

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“…This difference could be explained by the fact that in our study a specific HPV38 set of primers was used rather than consensus and/or degenerate primers. Indeed, it has been shown that different PCR assays impact on the frequency and spectrum of cutaneous HPV types detected in skin lesions (33).…”

Section: Discussionmentioning

confidence: 99%

The E6 and E7 Proteins of the Cutaneous Human Papillomavirus Type 38 Display Transforming Properties

Caldeira¹,

Zehbe²,

Accardi³

et al. 2003

J Virol

168

214

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Several studies have suggested the involvement of cutaneous human papillomaviruses (HPVs) in the development of nonmelanoma skin cancers. Here we have characterized the in vitro properties of E7 proteins of three cutaneous HPV types, 10, 20, and 38, which are frequently detected in skin specimens. We show that HPV38 E7 is able to inactivate the tumor suppressor pRb and induces loss of G 1 /S transition control, a key event in carcinogenesis. In contrast, HPV10 and HPV20 E7 proteins do not display these in vitro transforming activities. We also show that the two early proteins E6 and E7 of HPV38 are sufficient to corrupt the cell cycle and senescence programs in primary cells, inducing active and long-lasting proliferation of primary human keratinocytes, the natural host cells. Our study shows that E6 and E7 of this cutaneous HPV type have transforming activity in primary human cells, suggesting a role for HPV38 infection in skin carcinogenesis. In further support of such a role, we detected HPV38 DNA in approximately 50% of nonmelanoma skin cancers, but only in 10% of healthy skin specimens (P < 0.001).Nonmelanoma skin cancer is the most frequently occurring malignancy in the Caucasian population (34,38,47). Although these cancers have a good prognosis and are not normally associated with mortality, an increasing incidence of other invasive cancers and cancer mortality following nonmelanoma skin cancers has been reported (17,24,28,29). Several lines of evidence suggest the involvement of an infective agent in the etiology of this condition. Patients suffering from a rare genetic immune suppression termed epidermodysplasia verruciformis and individuals under long-lasting immunosuppression are prone to develop these cancers (21,22,30,37). Epidermodysplasia verruciformis patients are highly susceptible to human papillomavirus (HPV) infections by a specific subgroup of cutaneous HPVs, the so-called epidermodysplasia verruciformis types (e.g., HPV5 and HPV8), that lead to extensive verrucosis of confluent flat warts (22,30,37). In approximately 30% of cases, the HPV lesions develop into multifocal squamous cell carcinomas.Supporting the infectious role of cutaneous HPV types in the tumorigenesis of nonmelanoma skin cancers is the fact that other members of the papillomavirus family are clearly oncogenic (55). Indeed, clinical, epidemiological, and molecular data have demonstrated that mucosal high-risk HPV types (e.g., high-risk HPV16 and HPV18) are the etiological agents of anogenital cancers as well as a subgroup of head and neck cancers (55). The early region of these HPV types encodes two oncoproteins, E6 and E7, which associate with and neutralize the cellular tumor suppressors p53 and retinoblastoma (pRb), respectively (32,36).Independent studies suggest that cutaneous HPV types may also be involved in the development of squamous cell carcinoma and basal cell carcinomas in the general population (6,7,14,43). These indications are based only on studies assessing viral DNA presence in skin tumors by PCR, which ha...

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Section: Discussionmentioning

confidence: 99%

The E6 and E7 Proteins of the Cutaneous Human Papillomavirus Type 38 Display Transforming Properties

Caldeira¹,

Zehbe²,

Accardi³

et al. 2003

J Virol

168

214

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“…28 The finding that viral load in cutaneous tumors was 1 HPV DNA/ 20-5000 tumor cells, pointed out that not every tumor cell harbours HPV genome. 11,25,29 This finding explains that why we need highly sensitive detection techniques to show HPV DNA in the lesions. It was reported that HPV could not be detected with degenerate PCR and other techniques in up to 40% of cutaneous warts which were known to develop as a consequence of active infection with HPV.…”

Section: Discussionmentioning

confidence: 99%

“…30 Due to the low viral load in tumor cells, the frequency and spectrum of HPV detected by different techniques with different sensitivities show a great diversity. 25 In PCR technique, while degenerate primers enable detection of a broad range of HPV types with limited sensitivity for different HPV types, nondegenerate primers allow detection of only small subset of HPV types but with high sensitivity. 25 To detect all HPVpositive cases, several degenerate PCR primers should be combined with multiple nondegenerate PCR primers, each of which is specific for different HPV types.…”

Section: Discussionmentioning

confidence: 99%

“…3,20,21,23,24 Despite no HPV type has emerged specifically to be associated with skin cancer, beta HPV types have been detected predominantly in the lesions. 3,13,18,[25][26][27] The establishment of the relationship between the NMSC and HPV provide a basis for not only the preventive measures like vaccination but also improvement of antiviral/antitumor treatment. Characterization of HPV types that are significantly related with skin cancer is important especially for development of vaccine against these tumors.…”

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confidence: 99%

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The Role of Human Papillomaviruses in the Development of Non-Melanoma Skin Cancers

Keseroglu¹,

İlter²,

Rota³

et al. 2013

Turkiye Klinikleri J Med Sci

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A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Non-melanoma skin cancers (NMSC) represent the most frequent cancers among the Caucasian population worldwide. The possibility of the involvement of human papillomavirus (HPV) in the development of these cancers is suggested by several studies. The purpose of this study is to evaluate the presence of various types of HPV in NMSC lesions of immunocompetent patients. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : Biopsies taken from NMSC and non-sun exposed healthy skin from each of 32 immunocompetent patients were analysed for presence of HPV DNA by a polymerase chain reaction (PCR) using degenerate primers which can detect a broad spectrum of HPV types. R Re es su ul lt ts s: : HPV DNA was detected in one of 21 basal cell carcinomas, from one of two actinic keratosis and from none of 8 squamous cell carcinomas, and none of the control biopsy specimens. It was thought that in addition to factors associated with Turkish population, the specimens which were found to be HPV negative did not harbor HPV DNA, or although tissues harbor HPV DNA, it was not detected with the technique we used because of low viral load. C Co on nc cl lu us si io on n: : We could not show an association between HPV infection and NMSC by using real-time PCR technique. Our data suggest that the use of MY09/MY11 primer pairs alone in PCR technique is not sufficient to evaluate the HPV prevalence in NMSC. We thought that studies with more patients and using more sensitive detection techniques which will be developed in the future are needed to show a significant association between HPV and NMSC development.K Ke ey y W Wo or rd ds s: : Skin neoplasms; betapapillomavirus; polymerase chain reaction Ö ÖZ ZE ET T A Am ma aç ç: : Melanom dışı deri kanserleri (MDDK) dünya çapında beyaz ırkta en sık görülen kanserlerdir. Human papillomavirüslerin (HPV) bu kanserlerin gelişimine katkıda bulunuyor olabileceği birçok çalışmada öne sürülmüştür. Bu çalışmanın amacı, bağışıklık sistemi normal hastalardaki MDDK lezyonlarında farklı HPV tiplerinin mevcudiyetini değerlendirmektir. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Bağışıklık sistemi normal 32 hastanın her birinin MDDK ve güneş görmeyen sağlıklı derilerinden alınan biyopsiler, HPV tiplerinin geniş bir spektrumunu saptayabilen dejenere primerlerin kullanıldığı polimeraz zincir reaksiyonu (PZR) ile incelendi. B Bu ul lg gu ul la ar r: : HPV DNA, 21 bazal hücreli karsinomun 1 tanesi ve 2 aktinik keratozun 1 tanesinde saptanırken, 8 yassı hücreli karsinom ve kontrol deri örneklerinin hiçbirinde HPV DNA saptanmadı. Bu durumun, Türk toplumuyla ilişkili faktörlere ek olarak, HPV negatif olarak bulunan numunelerin HPV DNA içermemesine veya bu dokular HPV DNA içeriyor olmasına rağmen, viral yükün düşük olması nedeniyle bizim kullandığımız yöntemle saptanamamış olmasına bağlı olabileceği düşünüldü. S So on nu uç ç: : Biz çalışmamızda real-time PZR tekniği kullanarak MDDK ve HPV enfeksiyonu arasında ilişki gösteremedik. MDDK'de HPV pr...

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“…5,[7][8][9][10] Acredita-se que cerca de 15% das neoplasias sejam de origem viral. Além do HPV, outros vírus são descritos como oncogenes, como o vírus da hepatite C e alguns herpes-vírus humanos (HHV).…”

Section: Introductionunclassified

Prevalência do herpes-vírus humano tipo 1 em neoplasias cutâneas epiteliais malignas

Ypiranga

Moraes

2009

An. Bras. Dermatol.

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Resumo: FUNDAMENTOS -O DNA viral pode atuar como oncogene, favorecendo o desenvolvimento de neoplasias, como as linfoides e da pele. Entre esses vírus, encontram-se alguns herpes-vírus humanos. OBJETIVO -Identificar a presença de DNA do herpes-vírus humano tipo 1 em neoplasias epiteliais pré-malignas, malignas e pele normal de indivíduos controle, avaliando seu papel na carcinogênese. MÉTODOS -Identificação, por reação em cadeia da polimerase, do DNA viral do tumor e pele sã de 41 pacientes e comparação com grupo controle, sem neoplasia. Análise estatística: Testes de Fisher e de McNemar. RESULTADOS -O vírus foi identificado em 20 indivíduos sem e em 21 com neoplasia. Destes últimos, 11 o expessaram apenas nas células tumorais. A diferença, entretanto, não foi estatisticamente significante. CONCLUSÕES -Parece não haver relação direta entre o encontro do DNA viral na pele sã e na pele tumoral. Sua presença pode facilitar o desenvolvimento da neoplasia ou apenas coincidir de se localizar onde esta já ocorreu. Palavras-chave: Herpes-vírus humano 1; Neoplasias cutâneas; Reação em cadeia de polimerase; Vírus oncogênicos Abstract: Background -Viral DNA may act as an oncogene, especially in skin and lymphoid organs. This group includes some human herpes virus. Objective -To identify human herpes virus type 1 DNA in pre-malignant and malignant skin samples of epithelial tumors comparing to normal skin to determine its role in carcinogenesis. Methods -Forty-one patients with epithelial tumors were submitted to biopsies from tumor and normal skin. The control group comprised 41 biopsies from patients with other dermatoses than cancer. After DNA extraction, polymerase chain reaction was performed to identify 199-bp band. The results were statistically evaluated by Fisher and McNemar tests. Results -The virus was identified in 20 subjects without cancer and in 21 with skin cancer. From these, 11 expressed it only in tumor cells. This difference was not significant. Conclusion -There seem to be no direct relation between viral findings in normal skin and skin cancer cells. It may act as a promoter or just coexist at the same site where a neoplastic transformation has already occurred.

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Frequency and Spectrum of HPV Types Detected in Cutaneous Squamous-Cell Carcinomas Depend on the HPV Detection System: A Comparison of Four PCR Assays

Cited by 43 publications

References 24 publications

The E6 and E7 Proteins of the Cutaneous Human Papillomavirus Type 38 Display Transforming Properties

The E6 and E7 Proteins of the Cutaneous Human Papillomavirus Type 38 Display Transforming Properties

The Role of Human Papillomaviruses in the Development of Non-Melanoma Skin Cancers

Prevalência do herpes-vírus humano tipo 1 em neoplasias cutâneas epiteliais malignas

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