© The Author 2006. Published by Oxford University Press.
CORRESPONDENCE |
Re: Human Papillomavirus Infection and Incidence of Squamous Cell and Basal Cell Carcinomas of the Skin
Affiliations of authors: Queensland Institute of Medical Research, Brisbane, Queensland, Australia (LH); Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands (LS, MCWF); Queensland Cancer Fund, Brisbane, Queensland, Australia (REN)
Correspondence to: Mariet C. W. Feltkamp, MD, PhD, Department of Medical Microbiology, Leiden University Medical Center, PO Box 9600, 2300-RC, Leiden, The Netherlands (e-mail: m.c.w.feltkamp{at}lumc.nl).
Human papillomaviruses (HPVs) cause cervical cancer and some other types of epithelial cancers. HPV types from the phylogenic beta genus (beta-PVs), formerly known as epidermodysplasia verruciformis–associated HPV types, are frequently detected in nonmelanoma skin cancers, especially in squamous cell carcinomas (SCCs). An etiologic relationship with beta-PV infection is suspected.
In recent years, a small number of epidemiologic studies investigated the association between beta-PV infection and the development of nonmelanoma skin cancer. In studies that assessed antibodies directed against beta-PV and in studies that assessed the presence of beta-PV DNA, overall beta-PV positivity was positively associated with SCC (1,2). In some cases, beta-PV type-specific associations were also found—e.g., with HPV8 (3). Associations with basal cell carcinomas were generally absent. The largest epidemiologic study of this kind was recently reported by Karagas et al. (4).
As discussed by Karagas et al., consideration of a possible causal relationship between beta-PV infection of the skin and SCC development should take into account the potential of this group of viruses to transform cells. Although independent oncogenic properties of HPV8 have been observed in transgenic mice, if any beta-PV is involved in carcinogenesis of skin, it probably also requires exposure to ultraviolet radiation of the affected skin. A possible mechanism might involve virus-induced inhibition of DNA repair and apoptosis after ultraviolet radiation–induced DNA damage, as previously described for HPV8 and HPV5, respectively (5,6). In table 4 of Karagas et al., epidemiologic evidence is presented that supports a joint effect of beta-PV infection and sun exposure in the development of SCC. In a stratified analysis according to beta-PV serostatus, the risk of SCC associated with sun-related factors, such as degrees of sunburn and number of lifetime sunburns, was consistently higher in beta-PV seropositive subjects than in seronegative subjects.
To elaborate on a possible joint effect of ultraviolet radiation and beta-PV infection, we conducted a similar analysis nested in an SCC case–control study (7) in Queensland, Australia. The results of this analysis are shown in Table 1. In this analysis, participants were categorized according to their beta-PV antibody status and known SCC risk factors, such as fair skin and high sun exposure. We found that the combined effect of beta-PV seropositivity and presence of a susceptible phenotype or high lifetime sun exposure resulted in a greater risk of SCC than either risk factor alone. These findings are in keeping with those of Karagas et al. and support the hypothesis that the presence of beta-PV enhances the effect of ultraviolet exposure. Future research in this area is needed to elucidate the association between ultraviolet radiation and beta-PV infection in the carcinogenesis of the skin and to uncover the mechanisms involved.
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NOTES
Editor's note: Karagas et al. declined an invitation to respond to this correspondence.
REFERENCES
(1) Harwood CA, Surentheran T, Sasieni P, Proby CM, Bordea C, Leigh IM, et al. Increased risk of skin cancer associated with the presence of epidermodysplasia verruciformis human papillomavirus types in normal skin. Br J Dermatol 2004;150:949–57.[CrossRef][Web of Science][Medline]
(2) Struijk L, Bouwes Bavinck JN, Wanningen P, van der Meijden E, Westendorp RGJ, Schegget JT, 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;121:1531–5.[CrossRef][Web of Science][Medline]
(3) Feltkamp MC, Broer R, di Summa FM, Struijk L, van der Meijden E, Verlaan BP, et al. Seroreactivity to epidermodysplasia verruciformis-related human papillomavirus types is associated with nonmelanoma skin cancer. Cancer Res 2003;63:2695–700.
(4) Karagas MR, Nelson HH, Sehr P, Waterboer T, Stukel TA, Andrew A, 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.
(5) Iftner T, Elbel M, Schopp B, Hiller T, Loizou JI, Caldecott KW, et al. Interference of papillomavirus E6 protein with single-strand break repair by interaction with XRCC1. EMBO J 2002;21:4741–8.[CrossRef][Web of Science][Medline]
(6) Jackson S, Storey A. E6 proteins from diverse cutaneous HPV types inhibit apoptosis in response to UV damage. Oncogene 2000;19:592–8.[CrossRef][Web of Science][Medline]
(7) Struijk L, Hall L, Van Der Meijden, Wanningen P, Bavinck JN, Neale R, et al. Markers of cutaneous human papillomavirus infection in individuals with tumor-free skin, actinic keratoses, and squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 2006;15:529–35.
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