Human papillomaviruses and skin cancer

doi:10.1016/j.jcv.2004.11.018

Journal of Clinical Virology

Volume 32, Supplement, March 2005, Pages 67-71

https://doi.org/10.1016/j.jcv.2004.11.018 Get rights and content

Abstract

Cutaneous epidermodysplasia verruciformis (EV)-associated human papillomaviruses (HPVs) are found frequently in skin cancers especially in immunosuppressed people. They are also detectable in the normal skin and hair follicles of a proportion of individuals who have no immune defect. The available evidence to link HPVs causally with skin carcinogenesis is not conclusive, but includes epidemiological, molecular and immunological studies.

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 Early work with renal transplant patients using DNA extraction and restriction enzyme analysis has been superceded by the application of sensitive PCR DNA amplification using degenerate primer sets to increase the detection of many different types (reviewed in Harwood and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 Dermatology
Nearly 200 distinct human papilloma viruses (HPVs) have now been recognized, and each is associated with a specific set of clinical lesions. They are associated with a spectrum of diseases, from benign verrucae vulgares and condylomata acuminata to the malignancies of the cervix, vulva, anus, and penis. Disease associated with HPV can be divided into skin and mucosal lesion of the genital and extragenital regions. The relationship between HPV and nonmelanoma skin cancer (NMSC) is important clinically, because NMSC is the most common form of malignancy among fair-skinned populations. HPVs have also been detected in skin tags, lichen sclerosus, seborrheic keratoses, actinic keratoses, epidermal cysts, psoriatic plaques, and plucked hairs, but cutaneous HPV can be found on healthy skin.
Papillomavirus and cancer
2013, Revue Francophone des Laboratoires
Plus 120 de types de papillomavirus humains (HPV) infectent l’homme. Ces virus qui sont strictement épithéliotropes ont soit un tropisme cutané, soit un tropisme muqueux. Les HPV à tropisme muqueux, retrouvés essentiellement au niveau des muqueuses ano-génitales sont responsables de l’infection sexuellement transmissible la plus fréquente, touchant la majorité des individus sexuellement actifs. Une quinzaine de ces HPV présentent un pouvoir oncogène marqué (high-riskHPV: HR-HPV) et on peut considérer que ces virus sont responsables de près de 5 % des cancers humains. C’est le virus HPV16 qui est de loin le plus fréquemment impliqué. Le cancer le plus fréquemment associé à HPV est le cancer du col de l’utérus, pratiquement tous les cancers du col étant induits par HPV. D’autres cancers touchant la sphère génitale (vagin, vulve, pénis) peuvent être associés dans une moindre proportion aux HR-HPV. Ces virus sont également impliqués dans les cancers de l’anus et dans certains cancers des voies aérodigestives supérieures, le cancer de l’amygdale en particulier. Les HPV cutanés peuvent être détectés chez pratiquement tous les individus et le rôle de ces virus dans les cancers cutanés est moins évident. Toutefois, certains types tels que HPV5 et HPV8 sont associés à des carcinomes cutanés chez les sujets atteints d’épidermodysplasie verruciforme, et ils paraissent également jouer un rôle dans le développement de cancer cutané non-mélanome plus particulièrement chez des sujets immunodéprimés. La prévention des cancers humains associés à HPV concerne essentiellement le cancer du col et fait appel d’une part au dépistage et d’autre part à la vaccination.
More than 120 types of human papillomavirus (HPV) infect humans. These viruses are strictly epitheliotropic and present either a skin tropism or a mucosal tropism. The mucosal-tropic HPV, that mainly infect the ano-genital mucosa, represent the most common sexually transmitted infection worldwide, affecting the majority of sexually active individuals. About fifteen types of mucosal-tropic HPV have a marked oncogenic potential, they are called high-risk HPV (HR-HPV) and it is considered that these viruses are responsible for nearly 5% of human cancers. HPV16 is by far the HR-HPV most frequently involved. The cancer most frequently associated with HPV is the cervical cancer, virtually all these cancers being induced by HPV. Other cancers in the genital area (vagina, vulva, penis) can be associated, to a lesser extent, to HR-HPV. These viruses are also involved in cancers of the anus as well as in certain cancers of the upper aerodigestive tract, the cancer of the tonsils being the most frequent. Skin-tropic HPV can be detected in almost all individuals. The role of these viruses in skin cancers is less clear. However some skin-tropic HPV types such as HPV5 and HPV8 are associated with skin cancer in patients with epidermodysplasia verruciformis, and they also appear to play a role in the development of non-melanoma skin cancers, especially in immunocompromised patients. Prevention of human cancers associated with HPV, which mainly concerns cervical cancer, is based on screening and on HPV vaccination.
Diseases associated with human papillomavirus infection
2013, Virology
Citation 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.
Human papillomaviruses (HPVs) are ubiquitous, well adapted to their host and cleverly sequestered away from immune responses. HPV infections can be productive, subclinical or latent in both skin and mucosa. The causal association of HPV with cervical cancer, and increasingly with rising numbers of squamous cell carcinomas at other sites in both men and women, is increasingly recognised, while the morbidity of cutaneous HPV lesions, particularly in the immunosuppressed population is also significant. This chapter sets out the range of infections and clinical manifestations of the consequences of infection and its persistence and describes why HPVs are both highly effective pathogens and carcinogens, challenging to eliminate.
TP53 Arg72Pro polymorphism and skin cancer risk: A meta-analysis
2011, Journal of Investigative Dermatology
Citation 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.
The TP53 gene has an important role in the protection of cells from DNA damage due to UV exposure, and sequence variation in the gene may alter skin cancer susceptibility. To examine the association between the TP53 Arg72Pro polymorphism and skin cancer risk, we undertook a meta-analysis of 15 case–control studies involving 6,362 subjects. The quality of the studies was assessed according to a predefined scale. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were assessed for association using a random-effects model. Overall, no evidence of association was observed between TP53 genotypes and the risk of skin cancer in any genetic model (Arg/Arg vs. Pro/Pro: OR=1.05, 95% CI: 0.71–1.55; Arg/Pro vs. Pro/Pro: OR=0.92, 95% CI: 0.68–1.24; Arg/Arg+Arg/Pro vs. Pro/Pro: OR=0.97, 95% CI: 0.70–1.35; Arg/Arg vs. Arg/Pro+Pro/Pro: OR=1.15, 95% CI: 0.91–1.46). Stratified analyses according to ethnicity and quality score of the studies also detected no significant association in any subgroup. Furthermore, no effect of this polymorphism on subtype of skin cancer, such as melanoma, squamous cell carcinoma, and basal cell carcinoma, was observed. In conclusion, this meta-analysis suggests that the TP53 Arg72Pro polymorphism may have little involvement in skin cancer susceptibility.
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 Dermatology
Citation 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).
An increasing number of studies report that genus β human papillomaviruses (HPVs) are associated with skin cancer, with suggestions of specificity for squamous cell carcinoma (SCC) of the skin. We have conducted a systematic examination of HPV DNA in tumors from immunocompetent hosts, including SCC and basal cell carcinoma (BCC), using a highly sensitive methodology and population-based samples to test the hypothesis that a differential prevalence of β-HPVs exists between SCC (n=101) and BCC (n=101) tumors. When testing for all known β-HPV types, we found no significant difference in HPV prevalence between the two histologies. However, SCC lesions were significantly more likely to be infected with HPV genus β-species 1 (includes types 5 and 8), than BCC samples (P=0.01); this difference was not observed for any other species. A histologic difference was also observed for those HPV types previously reported to be important in skin cancer (P=0.003). SCC samples showed a higher rate of infectivity (that is, were positive for multiple types) than BCC tumors (P=0.02). These data highlight the potential importance of various genus β-HPV types, in particular genus β-species 1 in SCC, and support the hypothesis of a behavioral difference of the virus within the two major histological skin cancers.
Human papillomavirus and associated cancers: Epidemiological aspects
2008, Revue Francophone des Laboratoires
Les papillomavirus humains (HPV) sont des virus épithéliotropes qui infectent la peau et les muqueuses. La transmission interhumaine a lieu essentiellement par contact direct. Les HPV à localisation génitale sont transmis par voie sexuelle et ils sont la cause la plus fréquente d’infections sexuellement transmissibles (IST). L’incidence annuelle des infections génitales à HPV est de l’ordre de 30 % chez les jeunes adultes, dans les années qui suivent l’entrée dans la vie sexuelle. La prévalence du portage de HPV au niveau cervical est de l’ordre de 30 % chez les femmes de 20-25 ans ; elle diminue ensuite pour rester généralement inférieure à 10 % chez les femmes de plus de 30-35 ans. Les HPV à haut risque (HR-HPV) sont associés au développement de lésions cancéreuses. Ces HR-HPV sont retrouvés dans pratiquement 100 % des cancers du col de l’utérus et dans une proportion variable d’autres cancers génitaux ou de l’oropharynx. Les HR-HPV de type 16 et 18 sont retrouvés à l’échelle mondiale dans environ 70 % des cancers liés aux HPV. La distribution des autres types de HR-HPV peut varier d’une région à l’autre du monde.
Une prévalence accrue des infections HPV et des lésions précancéreuses et cancéreuses est observée chez les femmes infectées par le VIH.
La diffusion à grande échelle des vaccins préventifs devrait dans le futur modifier l’épidémiologie de ces virus et des cancers associés, le cancer du col en particulier.
Human papillomaviruses (HPV) are epitheliotropic viruses that cause skin and mucosa infections. Inter-human transmission mainly occurs through direct contact. Genital HPV represent the most frequent aetiology of sexually transmitted infections (STI) worldwide. Annual incidence of infections with genital HPV is about 30 % in young adults, during the years following the beginning of sexual activity. The prevalence of cervical HPV infection is about 30 % in women of 20-25 years of age with a subsequent decrease to less than 10 % in women above 30-35 years of age.
High-risk HPV (HR-HPV) are associated with the development of cancerous lesions. HR-HPV are involved in virtually all cases of cervical cancer and in a variable proportion of other genital cancers and of head and neck cancers. HR-HPV types 16 and 18 are involved in about 70 % of the HPV-related cancers worldwide, although some regional variations may be observed in the distribution of other HR-HPV types.
Prevalence of HPV infection and associated precancerous and cancerous lesions are higher in HIV-infected women compared with HIV-uninfected women.
In the future, the large-scale diffusion of prophylactic vaccines should modify the epidemiology of HPV and associated cancers, in particular cervical cancer.

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ReviewHuman papillomaviruses and skin cancer

Abstract

Introduction

Section snippets

Epidermodysplasia verruciformis

Molecular

Biological effects of EV and EV-related HPVs

Genetic variation in susceptibility to HPV-associated skin cancer

Conclusion

J Am Acad Dermatol

J Invest Dermatol

J Invest Dermatol

J Invest Dermatol

J Invest Dermatol

Hum Pathol

Virology

Virology

J Invest Dermatol

J Invest Dermatol

J Invest Dermatol

J Invest Dermatol

J Invest Dermatol

J Invest Dermatol

Prevalence and type spectrum of human papillomaviruses in healthy skin samples collected in three continents

J Gen Virol

Cutaneous squamous cell carcinoma and p53 codon 72 polymorphism: a need for screening?

Mol Carcinog

Persistence of human papillomavirus DNA in benign and (pre)malignant skin lesions from renal transplant recipients

J Clin Microbiol

Relation between skin cancer, humoral responses to human papillomaviruses, and HLA class II molecules in renal transplant patients

J Immunol

The presence of antibodies against virus-like particles of epidermodysplasia verruciformis-associated human papillomavirus type 8 in patients with actinic keratoses

Br J Dermatol

Antibodies to human papillomavirus type 5 are generated in epidermal repair processes

J Invest Dermatol

Review
Human papillomaviruses and skin cancer