Interaction Between Ultraviolet Radiation and Human Papillomavirus

  • Alan Storey
  • Mark Simmonds
Part of the Cancer Treatment and Research book series (CTAR, volume 146)

Human papillomaviruses (HPV) are small double-stranded DNA viruses that predominantly form hyperproliferative lesions in mucosal and cutaneous epithelial tissues and are strictly epitheliotropic. More than 120 different types have been characterised based on DNA sequence homology [1]. The association between HPV and cervical cancer has been well documented,with 99% of cervical tumours containing HPV DNA [2]. The expression of E6 and E7 proteins of high-risk anogenital types, such as HPV 16 and 18, has been linked with the subsequent degradation of both p53 and pRb, respectively, and the constitutive expression of both viral proteins in anogenital tumours is required to maintain this transformed state [3].


Basal Cell Carcinoma Organotypic Culture Skin Tumour Primary Human Keratinocytes Squamous Cell Dysplasia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    de Villiers EM, Fauquet C, Broker TR. Classification of papillomaviruses. Virology 2004; 324:17–27.PubMedCrossRefGoogle Scholar
  2. 2.
    Scheurer ME, Tortolero-Luna G, Alder-Storthz K. Human papillomavirus infection: biology, epidemiology, and prevention. Int J Gynecol Cancer 2005; 15:727–46.PubMedCrossRefGoogle Scholar
  3. 3.
    Finzer P, Aguilar-Lemarroy A, Rosl F. The role of human papillomavirus oncoproteins E6 and E7 in apoptosis. Cancer Lett 2002; 188:15–24.PubMedCrossRefGoogle Scholar
  4. 4.
    Karagas MR, Nelson HH, Sehr P, et al. Human papillomavirus infection and incidence of squamous cell and basal cell carcinomas of the skin. J Natl Cancer Inst 2006; 98:389–95.PubMedCrossRefGoogle Scholar
  5. 5.
    Termorshuizen, F, Feltkamp MCW, Struijk L, et al. Sunlight exposure and (sero)prevalence of epidermodysplasia verruciformis-associated human papillomavirus. J Invest Dermatol 2004; 122:1456–62.PubMedCrossRefGoogle Scholar
  6. 6.
    Harwood CA, Surentheran T, McGregor JM, Spink PJ, et al. Human papillomavirus infection and non-melanoma skin cancer in immunosuppressed and immunocompetent individuals. J Med Virol 2000; 61:289–97.PubMedCrossRefGoogle Scholar
  7. 7.
    Gillet LC, Scharer OD. Molecular mechanisms of mammalian global genome nucleotide excision repair. Chem Rev 2006; 106:253–76.PubMedCrossRefGoogle Scholar
  8. 8.
    Dixon K, Koprash E. Genetic alterations and DNA repair in human carcinogenesis. Semin Cancer Biol 2004; 14:441–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Fridman JS, Lowe SW. Control of apoptosis by p53. Oncogene 2003; 22:9030–40.PubMedCrossRefGoogle Scholar
  10. 10.
    Jans J, Garinis GA, Wouter S, et al. Differential role of basal keratinocytes in UV-induced immunosuppression and skin cancer. Mol Cell Biol 2006; 26:8515–26.PubMedCrossRefGoogle Scholar
  11. 11.
    Hebner CM, Laimins LA. Human papillomaviruses: basic mechanisms of pathogenesis and oncogenicity. Rev Med Virol 2006; 16:83–97.PubMedCrossRefGoogle Scholar
  12. 12.
    Caldeira S, Zehbe I, Accardi R, et al. The E6 and E7 proteins of the cutaneous human papillomavirus type 38 display transforming properties. J Virol 2003; 77:2195–206.PubMedCrossRefGoogle Scholar
  13. 13.
    Nataraj AJ, Trent JC, Ananthaswamy HN. p53 gene mutations and photocarcinogenesis. Photochem Photobiol 1995; 62:218–30.PubMedCrossRefGoogle Scholar
  14. 14.
    Accardi R, Dong W, Smet A. Skin human papillomavirus type 38 alters p53 functions by accumulation of ▵Np73. EMBO Rep 2006; 3:334–40.CrossRefGoogle Scholar
  15. 15.
    Giampieri S, Garcia-Escuerdo R, Green J, et al. Human papillomavirus type 77 E6 protein selectively inhibits p53-dependent transcription of proapoptoic genes following UV-B radiation. Oncogene 2004; 23:5864–70.PubMedCrossRefGoogle Scholar
  16. 16.
    Malkin D, Li FP, Strong LC, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 1990; 250:1233–38.PubMedCrossRefGoogle Scholar
  17. 17.
    Ren ZP, Hedrum A, Ponten F, et al. Human epidermal cancer and accompanying precursors have identical p53 mutations different from p53 mutations in adjacent areas of clonally expanded non-neoplastic keratinocytes. Oncogene 1996; 12:765–73.PubMedGoogle Scholar
  18. 18.
    Hussein MR. Ultraviolet radiation and skin cancer: molecular mechanisms. J Cutan Pathol 2005; 32:191–205.PubMedCrossRefGoogle Scholar
  19. 19.
    Griffiths GJ, Dubrez L, Morgan CP, et al. Cell damage-induced conformational changes of the pro-apoptotic protein Bak in vivo precede the onset of apoptosis. J Cell Biol 1999; 144:903–14.PubMedCrossRefGoogle Scholar
  20. 20.
    Jackson S, Harwood C, Thomas M, et al. Role of Bak in UV-induced apoptosis in skin cancer and abrogation by HPV E6 proteins. Genes Dev 2000; 14:3065–73.PubMedCrossRefGoogle Scholar
  21. 21.
    Leverrier S, Bergamaschi D, Ghali L, et al. Role of HPV E6 proteins in preventing UVB-induced release of proapoptotic factors from the mitochondria. Apoptosis 2007; 12:549–560.PubMedCrossRefGoogle Scholar
  22. 22.
    Magal SS, Jackman A, Ish-Shalom S, et al. Downregulation of Bax mRNA and protein stability by the E6 protein of human papillomavirus 16. J Gen Virol 2005; 86:611–21.PubMedCrossRefGoogle Scholar
  23. 23.
    Vogt M, Butz K, Dymalla S, et al. Inhibition of Bax activity is crucial for the antiapoptotic function of the human papillomavirus E6 oncoprotein. Oncogene 2006; 25:4009–15.PubMedCrossRefGoogle Scholar
  24. 24.
    Jackson S, Ghali L, Harwood C, et al. Reduced apoptotic levels in squamous but not basal cell carcinomas correlate with detection of cutaneous human papillomaviruses. Br J Cancer 2002; 87:319–23.PubMedCrossRefGoogle Scholar
  25. 25.
    Storey A. Papillomaviruses: death-defying acts in skin cancer. Trends Mol Med 2002 8:417–21.PubMedCrossRefGoogle Scholar
  26. 26.
    Van Laethem A, Van Kelst S, Lippens S, et al. Activation of p38 MAPK is required for Bax translocation to mitochondria, cytochrome c release and apoptosis induced by UVB irradiation in human keratinocytes. FASEB 2004; 18:1946–48.Google Scholar
  27. 27.
    Giampieri S, Storey A. Repair of UV-induced thymine dimers is compromised in cells expressing the E6 protein from human papillomaviruses types 5 and 18. Br J Cancer 2004; 90:2203–9.PubMedGoogle Scholar
  28. 28.
    Iftner T, Elbel M, Schopp B, et al. Interference of papillomavirus E6 protein with single-strand break repair by interaction with XRCC1. EMBO J 2002; 21:4741–48.PubMedCrossRefGoogle Scholar
  29. 29.
    Jans J, Schul W, Sert Y-G, et al. Powerful skin cancer protection by a CPD-photolyase transgene. Curr Biol 2005; 15:105–15.PubMedCrossRefGoogle Scholar
  30. 30.
    Munger K, Phelps WC, Bubb V, et al. The E6 and E7 genes of the human papillomavirus type 16 are necessary and sufficient for transformation of primary human keratinocytes. J Virol 1989; 63:4417–21.PubMedGoogle Scholar
  31. 31.
    Boxman IL, Mulder LH, Noya F, et al. Transduction of the E6 and E7 genes of epidermodysplasia-verruciformis-associated human papillomaviruses alters human keratinocyte growth and differentiation in organotypic cultures. J Invest Dermatol 2001; 117:1397–404.PubMedCrossRefGoogle Scholar
  32. 32.
    Pfister H. Chapter 8: Human papillomaviruses and skin cancer. J Natl Cancer Inst Monogr 2003; 31:52–56.PubMedGoogle Scholar
  33. 33.
    Schaper ID, Marcuzzi GP, Weissenborn SJ, et al. Development of skin tumours in mice transgenic for early genes of human papillomavirus type 8. Cancer Res 2005; 65:1394–400.PubMedCrossRefGoogle Scholar
  34. 34.
    Dong W, Klotz U, Accardi R, et al. Skin hyperproliferation and susceptibility to chemical carcinogenesis in transgenic mice expressing E6 and E7 of human papillomavirus type 38. J Virol 2005; 23:14899–908.CrossRefGoogle Scholar
  35. 35.
    Michel A, Kopp-Schneider A, Zentgraf H, et al. 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. J Virol 2006; 22:11153–64.CrossRefGoogle Scholar
  36. 36.
    Akgul B, Garcia-Escuerdo R, Ghali L, et al. The E7 protein of cutaneous human papillomavirus type 8 causes invasion of human keratinocytes into the dermis in organotypic cultures of skin. Cancer Res 2005; 56:2216–23CrossRefGoogle Scholar
  37. 37.
    Struijk L, Bouwes Bavinck JN, Wanningen P, et al. Presence of human papillomavirus DNA in plucked eyebrow hairs is associated with a history of cutaneous squamous cell carcinoma. J Invest Dermatol 2003; 121:1531–35.PubMedCrossRefGoogle Scholar
  38. 38.
    Akgul B, Cooke JC, Storey A. HPV-associated skin disease. J Pathol 2006; 208:165–75.PubMedCrossRefGoogle Scholar
  39. 39.
    Dang C, Koehler, T, Forschner, P, et al. E6/E7 expression of human papillomavirus types in cutaneous squamous cell dysplasia and carcinoma in immunosuppressed organ transplant recipients. Br J Dermatol 2006; 155:129–36.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Alan Storey
    • 1
  • Mark Simmonds
    • 2
  1. 1.Molecular Oncology Department, Weatherall Institute for Molecular MedicineJohn Radcliffe Hospital, University of OxfordOxfordUnited Kingdom
  2. 2.Cancer Research UK Skin Tumour Laboratory Institute of Cell and Molecular ScienceUnited Kingdom

Personalised recommendations