Sunlight Exposure and (Sero)Prevalence of Epidermodysplasia Verruciformis-Associated Human Papillomavirus
ÃLaboratory for Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands; wDepartment of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, Leiden,The Netherlands; zDepartment of Dermatology, Leiden University Medical Center, Leiden, The Netherlands; yDepartment of Health Risk Analysis and Toxicology, University of Maastricht, The Netherlands
Fabian Termorshuizen,Ã Mariet C.W. Feltkamp,w Linda Struijk,w Frank R. de Gruijl,z Jan Nico Bouwes Bavinck,z and Henk van LoverenÃy
Ultraviolet radiation (UVR) is associated with an increased riskof squamous cell carcinoma (SCC), which is in part due to immunomodulation. In addition, human papilloma virus (HPV), especially the epidermodysplasia verruciformis (EV)-associated types, may be involved. In view of the capacity of UVR to impair host resistance to infections, we investigated the relationship between solar exposure and the prevalence of cutaneous HPV. In a case-control study onskin cancer (320 controls and 156 patients) a lifetime-retrospective questionnaire on sun exposure was administered. The presence of DNA of HPV types 5, 8, 15, 20, 24, and 38 in plucked eyebrow hair and type-speciﬁc seroreactivity were assessed and analyzed in relation to estimated exposure. Sunburn episodes in the past, especially at age 13–20 y, appeared to be associated with an enhanced risk ofEV–HPV DNA positivity. In contrast, a higher lifetime sun exposure was associated with a lower risk of HPV infection. These results indicate that UVR at erythematogenic doses increases the risk of EV–HPV infection, possibly due to impaired host resistance to HPV and/or a direct effect of UVR on viral replication. The favorable association between lifetime sun exposure and HPV prevalence, however,underscores the enigmatic role of HPV in skin carcinogenesis.
Keywords: epidemiology/human papillomavirus/immunosuppression/squamous cell carcinoma/UVR exposure J Invest Dermatol 122:1456 –1462, 2004
Human papillomaviruses (HPVs) are associated with both benign and malignant proliferative skin disorders (Boxman et al, 2000, 2001; Zur Hausen, 2000; Feltkamp et al, 2003; Struijk et al, 2003). Aquarter of the HPV genotypes that are completely sequenced today belong to the so-called epidermodysplasia verruciformis (EV)-associated HPV types (De Villiers, 2001). These EV–HPV types have originally been found in skin lesions from patients with EV (Jablonska and Orth, 1985). EV patients develop multiple skin lesions on sun-exposed sites that often progress into squamous cell carcinoma (SCC).Recent studies indicate that EV–HPV types are not restricted to EV patients. Skin carcinomas in patients from the general population frequently contain EV–HPV (Pﬁster and Ter Schegget, 1997; Harwood and Proby, 2002). In immunosuppressed patients, such as renal transplant recipients, high incidences of skin carcinomas and keratotic skin lesions are found on sunexposed sites in conjunction with ahigh percentage of EV– HPV DNA positivity, suggesting that these phenomena are associated with an underlying impairment of the immune
Abbreviations: CHS, contact hypersensitivity; EV, epidermodysplasia verruciformis; HPV, human papillomavirus; OR, odds ratio; SCC, squamous cell carcinoma; UVR, ultraviolet radiation This work was carried out at Leiden, Leiden University Medical Center, TheNetherlands, and Bilthoven, National Institute of Public Health and the Environment (RIVM), The Netherlands.
system and may be causally linked with each other (Bouwes Bavinck et al, 1993; Shamanin et al, 1994; De Jong-Tieben et al, 1995; Berkhout et al, 2000). It is known that exposure to solar ultraviolet radiation (UVR) plays a pivotal role in the genesis of pre-malignant skin lesions and...