Abstract
Human papillomaviruses (HPV) are increasingly recognised as important human carcinogens. The best established association with human malignancy is that of high-risk mucosal HPV types and anogenital cancer. HPV-induced transformation of anogenital epithelia has been the subject of intense research which has identified the cellular tumour suppressor gene products, p53 and pRB, as important targets for the viral oncoproteins E6 and E7 respectively. Certain HPV types are also strongly associated with the development of non-melanoma skin cancer in the inherited disorder epidermodysplasia verruciformis (EV). However, in contrast with anogenital malignancy the oncogenic mechanisms of EV-HPV types remain uncertain, and there appears to be a crucial additional requirement for ultraviolet radiation. Cutaneous HPV types in the general population are predominantly associated with benign viral warts, but a role in non-melanoma skin cancer has recently been postulated. Polymerase chain reaction based HPV detection techniques have shown a high prevalence of HPV DNA, particularly in skin cancers from immunosuppressed patients and to a lesser extent in malignancies from otherwise immunocompetent individuals. No particular HPV type has yet emerged as predominant, and the role of HPV in cutaneous malignancy is unclear at present. It remains to be established whether HPV plays an active or purely a passenger role in the evolution of non-melanoma skin cancer.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bayle-Lebey P., Labadie F., Basset-Seguin N., Bazex J. Carcinomes cutanés et papillomavirus 5. Révélation lors d'une photochimiothérapie UVA prolongée. Ann Dermatol Venereol. 1994;121(6-7):496–498. [PubMed] [Google Scholar]
- Berger T. G., Sawchuk W. S., Leonardi C., Langenberg A., Tappero J., Leboit P. E. Epidermodysplasia verruciformis-associated papillomavirus infection complicating human immunodeficiency virus disease. Br J Dermatol. 1991 Jan;124(1):79–83. doi: 10.1111/j.1365-2133.1991.tb03286.x. [DOI] [PubMed] [Google Scholar]
- Birkeland S. A., Storm H. H., Lamm L. U., Barlow L., Blohmé I., Forsberg B., Eklund B., Fjeldborg O., Friedberg M., Frödin L. Cancer risk after renal transplantation in the Nordic countries, 1964-1986. Int J Cancer. 1995 Jan 17;60(2):183–189. doi: 10.1002/ijc.2910600209. [DOI] [PubMed] [Google Scholar]
- Blessing K., McLaren K. M., Benton E. C., Barr B. B., Bunney M. H., Smith I. W., Beveridge G. W. Histopathology of skin lesions in renal allograft recipients--an assessment of viral features and dysplasia. Histopathology. 1989 Feb;14(2):129–139. doi: 10.1111/j.1365-2559.1989.tb02123.x. [DOI] [PubMed] [Google Scholar]
- Boyle J., MacKie R. M., Briggs J. D., Junor B. J., Aitchison T. C. Cancer, warts, and sunshine in renal transplant patients. A case-control study. Lancet. 1984 Mar 31;1(8379):702–705. doi: 10.1016/s0140-6736(84)92221-9. [DOI] [PubMed] [Google Scholar]
- Chan S. Y., Delius H., Halpern A. L., Bernard H. U. Analysis of genomic sequences of 95 papillomavirus types: uniting typing, phylogeny, and taxonomy. J Virol. 1995 May;69(5):3074–3083. doi: 10.1128/jvi.69.5.3074-3083.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cooper K. D., Androphy E. J., Lowy D., Katz S. I. Antigen presentation and T-cell activation in epidermodysplasia verruciformis. J Invest Dermatol. 1990 Jun;94(6):769–776. doi: 10.1111/1523-1747.ep12874631. [DOI] [PubMed] [Google Scholar]
- Frost C. A., Green A. C. Epidemiology of solar keratoses. Br J Dermatol. 1994 Oct;131(4):455–464. doi: 10.1111/j.1365-2133.1994.tb08544.x. [DOI] [PubMed] [Google Scholar]
- Hardie I. R., Strong R. W., Hartley L. C., Woodruff P. W., Clunie G. J. Skin cancer in Caucasian renal allograft recipients living in a subtropical climate. Surgery. 1980 Feb;87(2):177–183. [PubMed] [Google Scholar]
- Hartevelt M. M., Bavinck J. N., Kootte A. M., Vermeer B. J., Vandenbroucke J. P. Incidence of skin cancer after renal transplantation in The Netherlands. Transplantation. 1990 Mar;49(3):506–509. doi: 10.1097/00007890-199003000-00006. [DOI] [PubMed] [Google Scholar]
- Harwood C. A., Spink P. J., Surentheran T., Leigh I. M., Hawke J. L., Proby C. M., Breuer J., McGregor J. M. Detection of human papillomavirus DNA in PUVA-associated non-melanoma skin cancers. J Invest Dermatol. 1998 Jul;111(1):123–127. doi: 10.1046/j.1523-1747.1998.00240.x. [DOI] [PubMed] [Google Scholar]
- Hirt L., Hirsch-Behnam A., de Villiers E. M. Nucleotide sequence of human papillomavirus (HPV) type 41: an unusual HPV type without a typical E2 binding site consensus sequence. Virus Res. 1991 Mar;18(2-3):179–189. doi: 10.1016/0168-1702(91)90017-p. [DOI] [PubMed] [Google Scholar]
- Iftner T., Bierfelder S., Csapo Z., Pfister H. Involvement of human papillomavirus type 8 genes E6 and E7 in transformation and replication. J Virol. 1988 Oct;62(10):3655–3661. doi: 10.1128/jvi.62.10.3655-3661.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kiyono T., Nagashima K., Ishibashi M. The primary structure of major viral RNA in a rat cell line transfected with type 47 human papillomavirus DNA and the transforming activity of its cDNA and E6 gene. Virology. 1989 Dec;173(2):551–565. doi: 10.1016/0042-6822(89)90567-9. [DOI] [PubMed] [Google Scholar]
- Ko C. B., Walton S., Keczkes K., Bury H. P., Nicholson C. The emerging epidemic of skin cancer. Br J Dermatol. 1994 Mar;130(3):269–272. doi: 10.1111/j.1365-2133.1994.tb02920.x. [DOI] [PubMed] [Google Scholar]
- Kripke M. L., Morison W. L., Parrish J. A. Systemic suppression of contact hypersensitivity in mice by psoralen plus UVA radiation (PUVA). J Invest Dermatol. 1983 Aug;81(2):87–92. doi: 10.1111/1523-1747.ep12542071. [DOI] [PubMed] [Google Scholar]
- London N. J., Farmery S. M., Will E. J., Davison A. M., Lodge J. P. Risk of neoplasia in renal transplant patients. Lancet. 1995 Aug 12;346(8972):403–406. doi: 10.1016/s0140-6736(95)92780-8. [DOI] [PubMed] [Google Scholar]
- Majewski S., Jabłońska S. Epidermodysplasia verruciformis as a model of human papillomavirus-induced genetic cancer of the skin. Arch Dermatol. 1995 Nov;131(11):1312–1318. [PubMed] [Google Scholar]
- Maurer T. A., Christian K. V., Kerschmann R. L., Berzin B., Palefsky J. M., Payne D., Tyring S. K., Berger T. G. Cutaneous squamous cell carcinoma in human immunodeficiency virus-infected patients. A study of epidemiologic risk factors, human papillomavirus, and p53 expression. Arch Dermatol. 1997 May;133(5):577–583. [PubMed] [Google Scholar]
- May M., Grassmann K., Pfister H., Fuchs P. G. Transcriptional silencer of the human papillomavirus type 8 late promoter interacts alternatively with the viral trans activator E2 or with a cellular factor. J Virol. 1994 Jun;68(6):3612–3619. doi: 10.1128/jvi.68.6.3612-3619.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Milburn P. B., Brandsma J. L., Goldsman C. I., Teplitz E. D., Heilman E. I. Disseminated warts and evolving squamous cell carcinoma in a patient with acquired immunodeficiency syndrome. J Am Acad Dermatol. 1988 Aug;19(2 Pt 2):401–405. doi: 10.1016/s0190-9622(88)70187-5. [DOI] [PubMed] [Google Scholar]
- Nataraj A. J., Wolf P., Cerroni L., Ananthaswamy H. N. p53 mutation in squamous cell carcinomas from psoriasis patients treated with psoralen + UVA (PUVA). J Invest Dermatol. 1997 Aug;109(2):238–243. doi: 10.1111/1523-1747.ep12319764. [DOI] [PubMed] [Google Scholar]
- Orth G. Epidermodysplasia verruciformis: a model for understanding the oncogenicity of human papillomaviruses. Ciba Found Symp. 1986;120:157–174. doi: 10.1002/9780470513309.ch11. [DOI] [PubMed] [Google Scholar]
- Rees J. Genetic alterations in non-melanoma skin cancer. J Invest Dermatol. 1994 Dec;103(6):747–750. doi: 10.1111/1523-1747.ep12412256. [DOI] [PubMed] [Google Scholar]
- Rübben A., Baron J. M., Grussendorf-Conen E. I. Demonstration of human papillomavirus type 16-related DNA and absence of detectable p53 gene mutations in widespread cutaneous squamous cell carcinomas after oral psoralen with UV-A treatment. Arch Dermatol. 1996 Oct;132(10):1257–1259. doi: 10.1001/archderm.1996.03890340123032. [DOI] [PubMed] [Google Scholar]
- Shamanin V., Glover M., Rausch C., Proby C., Leigh I. M., zur Hausen H., de Villiers E. M. Specific types of human papillomavirus found in benign proliferations and carcinomas of the skin in immunosuppressed patients. Cancer Res. 1994 Sep 1;54(17):4610–4613. [PubMed] [Google Scholar]
- Shamanin V., zur Hausen H., Lavergne D., Proby C. M., Leigh I. M., Neumann C., Hamm H., Goos M., Haustein U. F., Jung E. G. Human papillomavirus infections in nonmelanoma skin cancers from renal transplant recipients and nonimmunosuppressed patients. J Natl Cancer Inst. 1996 Jun 19;88(12):802–811. doi: 10.1093/jnci/88.12.802. [DOI] [PubMed] [Google Scholar]
- Sheil A. G., Flavel S., Disney A. P., Mathew T. H. Cancer development in patients progressing to dialysis and renal transplantation. Transplant Proc. 1985 Apr;17(2):1685–1688. [PubMed] [Google Scholar]
- Steger G., Pfister H. In vitro expressed HPV 8 E6 protein does not bind p53. Arch Virol. 1992;125(1-4):355–360. doi: 10.1007/BF01309654. [DOI] [PubMed] [Google Scholar]
- Storey A., Thomas M., Kalita A., Harwood C., Gardiol D., Mantovani F., Breuer J., Leigh I. M., Matlashewski G., Banks L. Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature. 1998 May 21;393(6682):229–234. doi: 10.1038/30400. [DOI] [PubMed] [Google Scholar]
- Studniberg H. M., Weller P. PUVA, UVB, psoriasis, and nonmelanoma skin cancer. J Am Acad Dermatol. 1993 Dec;29(6):1013–1022. doi: 10.1016/0190-9622(93)70283-y. [DOI] [PubMed] [Google Scholar]
- Ullrich S. E. Systemic immunosuppression of cell-mediated immune reactions by a monofunctional psoralen plus ultraviolet A radiation. Photodermatol Photoimmunol Photomed. 1991 Jun;8(3):116–122. [PubMed] [Google Scholar]
- Weinstock M. A., Coulter S., Bates J., Bogaars H. A., Larson P. L., Burmer G. C. Human papillomavirus and widespread cutaneous carcinoma after PUVA photochemotherapy. Arch Dermatol. 1995 Jun;131(6):701–704. [PubMed] [Google Scholar]
- Woodworth C. D., Doniger J., DiPaolo J. A. Immortalization of human foreskin keratinocytes by various human papillomavirus DNAs corresponds to their association with cervical carcinoma. J Virol. 1989 Jan;63(1):159–164. doi: 10.1128/jvi.63.1.159-164.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Young A. R. Photocarcinogenicity of psoralens used in PUVA treatment: present status in mouse and man. J Photochem Photobiol B. 1990 Jun;6(1-2):237–247. doi: 10.1016/1011-1344(90)85093-c. [DOI] [PubMed] [Google Scholar]
- Ziegler A., Leffell D. J., Kunala S., Sharma H. W., Gailani M., Simon J. A., Halperin A. J., Baden H. P., Shapiro P. E., Bale A. E. Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancers. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4216–4220. doi: 10.1073/pnas.90.9.4216. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Jong-Tieben L. M., Berkhout R. J., Smits H. L., Bouwes Bavinck J. N., Vermeer B. J., van der Woude F. J., ter Schegget J. High frequency of detection of epidermodysplasia verruciformis-associated human papillomavirus DNA in biopsies from malignant and premalignant skin lesions from renal transplant recipients. J Invest Dermatol. 1995 Sep;105(3):367–371. doi: 10.1111/1523-1747.ep12320803. [DOI] [PubMed] [Google Scholar]
- de Villiers E. M. Human pathogenic papillomavirus types: an update. Curr Top Microbiol Immunol. 1994;186:1–12. doi: 10.1007/978-3-642-78487-3_1. [DOI] [PubMed] [Google Scholar]
- de Villiers E. M., Lavergne D., McLaren K., Benton E. C. Prevailing papillomavirus types in non-melanoma carcinomas of the skin in renal allograft recipients. Int J Cancer. 1997 Nov 4;73(3):356–361. doi: 10.1002/(sici)1097-0215(19971104)73:3<356::aid-ijc9>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
- zur Hausen H. Papillomavirus infections--a major cause of human cancers. Biochim Biophys Acta. 1996 Oct 9;1288(2):F55–F78. doi: 10.1016/0304-419x(96)00020-0. [DOI] [PubMed] [Google Scholar]