ReviewHuman papillomaviruses and skin cancer
Introduction
The association between human papillomavirus (HPV) infection and squamous cell neoplasia of the lower genital tract is now well established with many lines of good evidence supporting a causative relationship. The role of HPVs in the development of cutaneous malignancy is not as definite, but nevertheless, there is emerging evidence to suggest that they have a potentially important part to play in the process of skin carcinogenesis.
Section snippets
Epidermodysplasia verruciformis
Cancer-associated skin HPV types were first discovered in patients with the rare condition of epidermodysplasia verruciformis. Those affected have a mild but demonstrable defect of cell-mediated immune responses and develop warty and scaly areas of skin, especially on sun-exposed sites, in their childhood and early adult life (Majewski and Jablonska, 2001). Most will also have squamous cell carcinomas (SCCs) of the skin appearing before the age of 40 and in many cases, the skin malignancies can
Molecular
Many studies have examined the skin lesions in immunosuppressed individuals and also immunocompetent people for the presence and type of HPV DNA. Early work with renal transplant patients using DNA extraction and restriction enzyme analysis has been superceded by the application of sensitive PCR DNA amplification using degenerate primer sets to increase the detection of many different types (reviewed in Harwood and Proby, 2002). Cutaneous HPVs of the EV or EV-related and putative new EV-related
Biological effects of EV and EV-related HPVs
The presence of certain HPVs within skin cancers is, by itself, not a proof of causative association, and the finding of the same types of viral DNA in normal skin and hair follicles of both immunosuppressed and immunocompetent individuals weakens the possibility of a direct neoplastic effect. If cutaneous HPVs contribute to the process of carcinogenesis, they must, in some way, influence the normal cellular processes. The list of ways in which genital high-risk types interact with cellular
Genetic variation in susceptibility to HPV-associated skin cancer
Mutations within the p53 gene are extremely common in many cancers including skin cancers (Padlewska et al., 2001). The p53 gene occurs in two common polymorphisms involving the amino acid at codon 72 which may occur either as arginine or proline and it has been shown that the E6 from the high-risk genital HPVs is able to degrade the arginine/arginine homozygous form much more efficiently than the proline/proline form (Storey et al., 1998). In spite of little evidence that the interaction
Conclusion
Until more is understood about the precise role of HPVs in the development of skin cancers, there is no obvious antiviral approach to the prevention or treatment of such lesions. The use of an animal model for investigation into the mechanisms of tumour formation with HPV 16 has been very fruitful and could usefully be extended to examine the EV HPVs. For the present, patients who are immunosuppressed for years should receive detailed information about the risks of skin cancer, and ideally be
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Cited by (39)
HPV-associated diseases
2014, Clinics in DermatologyPapillomavirus and cancer
2013, Revue Francophone des LaboratoiresDiseases associated with human papillomavirus infection
2013, VirologyCitation Excerpt :While β-HPV are ubiquitous and most cause in-apparent infections in the general population, a few types are associated with squamous cell carcinomas (SCC) in EV patients. HPV 5 and 8 account for 90% of the tumours with HPV 14, 17, 20 and 47 accounting for the remainder (Sterling, 2005). Most EV patients will develop SCC before the age of 40 on sun-exposed sites and the tumours are locally destructive.
TP53 Arg72Pro polymorphism and skin cancer risk: A meta-analysis
2011, Journal of Investigative DermatologyCitation Excerpt :Third, the lack of original data, including data on genotypes and environmental risk factors, from the included studies limited our further evaluation of potential gene–environment interactions, especially the interaction between infection with human papillomavirus and TP53 Arg72Pro polymorphism, which was investigated in several studies (Dokianakis et al., 2000; O’Connor et al., 2001; Cairey-Remonnay et al., 2002; McGregor et al., 2002; Gustafsson et al., 2004; Queille et al., 2007). However, unlike human papillomavirus infection in cervical carcinoma, the role of this virus in the etiology of skin cancer remains controversial (Sterling, 2005). Nevertheless, a more precise analysis should be conducted if individual data are available.
Exposure profiles and human papillomavirus infection in skin cancer: An analysis of 25 genus β-types in a population-based study
2008, Journal of Investigative DermatologyCitation Excerpt :Although genus β-type HPVs have been frequently detected in non-melanoma skin cancers (NMSC) in immunosuppressed individuals, very little is known about the presence of the virus in immunocompetent individuals. Epidemiologic studies have detected associations between markers of β-HPV infection and SCC, but not basal cell carcinoma (BCC) (Harwood and Proby, 2002; Pfister, 2003; Sterling, 2005; Karagas et al., 2006), suggesting a potential etiological role in SCC. However, the presence of HPV DNA in eyebrow pluckings was found to be nearly ubiquitous (Boxman et al., 2000).
Human papillomavirus and associated cancers: Epidemiological aspects
2008, Revue Francophone des Laboratoires