Evidence for the Association of Human Papillomavirus Infection and Cutaneous Squamous Cell Carcinoma in Immunocompetent Individuals

Masini, Cinzia; Fuchs, Pawel G.; Gabrielli, Fabrizio; Stark, Sabine; Sera, Francesco; Ploner, Miriam; Melchi, C.F.; Primavera, Grazia; Pirchio, Giulio; Picconi, Orietta; Petasecca, Pierpaolo; Cattaruzza, Maria Sofia; Pfister, Herbert; Abeni, Damiano

doi:10.1001/archderm.139.7.890

Cited by 112 publications

(106 citation statements)

References 37 publications

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“…In addition, the prevalence of antibodies against any b-HPV type was higher among men than among women, although the result reported here was not statistically significant. 15,16 Overall, there was no difference in HPV seropositivity between patients with incident SCC and controls after adjusting for age, sex and geographical location. This was found both in analyses looking at single infection and multiple infections and is in contrast to serological results reported from prospective studies of cervical intraepithelial neoplasia (CIN) or cancer of the uterine cervix.…”

Section: Discussionmentioning

confidence: 93%

A prospective pilot study of antibodies against human papillomaviruses and cutaneous squamous cell carcinoma nested in the Oxford component of the European Prospective Investigation into Cancer and Nutrition

Casabonne

Michael

Waterboer

et al. 2007

Intl Journal of Cancer

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In a prospective pilot study nested in the EPIC-Oxford cohort, we examined the seroprevalence of antibodies against the L1 antigen of 38 human papilloma virus (HPV) types among 39 cases of cutaneous squamous cell carcinoma (SCC) for whom plasma was collected prior to diagnosis (incident) and 80 controls. Fifteen cases having already developed SCC at blood collection (prevalent) were also tested. There were no statistically significant differences in the seroprevalence of antibodies against any of the HPV types examined between incident cases and controls, nor was there a difference in the seroprevalence of multiple infections. However, consistent with results from published case-control studies, the seroprevalence of many b-HPV types was higher among prevalent cases than among either incident cases or controls. For example the seroprevalence of antibodies against HPV-8 was 20% (16/80) in controls, 23% (9/39) among incident cases and 40% (6/15) among prevalent cases. Among the incident cases only, the seroprevalence was 16% (5/32) among those for whom blood was collected 181 months prior to diagnosis, but 57% (4/7) among those for whom diagnosis was within 18 months of blood collection, a pattern seen for many of the HPV types. This might suggest that if HPV is involved in the aetiology of SCC, the process occurs close to the time of diagnosis, or that the antibody response observed in people with SCC is a consequence of tumor formation. Further and larger prospective studies are needed to clarify the role of HPV in the aetiology of cutaneous SCC. ' 2007 Wiley-Liss, Inc.Key words: Epidemiology; human papillomavirus (HPV); serology; cutaneous squamous cell carcinoma (SCC); prospective case-control Nonmelanoma skin cancer (NMSC), comprising basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in a ratio of about five to one, is the most commonly diagnosed cancer in white populations. Established risk factors include exposure to solar ultra-violet radiation and, for SCC in particular, immunosuppression, such as that experienced by organ transplant recipients.1-4 In addition, there is some evidence of an association between certain human papillomaviruses (such as HPV types 5 and 8) and the development of cutaneous SCC (but not basal).5 To date, more than 118 papillomaviruses have been completely described, of which about a hundred infect humans. 6 The alpha types, particularly HPV-16, 18, 33 and 45, are well established causes of cancer of the uterine cervix; the viral E6 and E7 proteins are associated with the degradation of tumor suppressors p53 and pRb, respectively. 7A role for HPV in the aetiology of skin cancers is uncertain, although evidence of possible molecular mechanisms is emerging with HPV probably working as a co-factor with ultraviolet radiation early in the development of SCC. 8Most studies of HPV and cutaneous SCC have used HPV-DNA detection methods to examine the association. Because of the high sensitivity of PCR methods and the ubiquity of HPV, previously unknown types are often identified...

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Section: Discussionmentioning

confidence: 93%

A prospective pilot study of antibodies against human papillomaviruses and cutaneous squamous cell carcinoma nested in the Oxford component of the European Prospective Investigation into Cancer and Nutrition

Casabonne

Michael

Waterboer

et al. 2007

Intl Journal of Cancer

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“…Except for HPV15, the bPV types that showed inhibitory effects on UVB-induced apoptosis have been associated with non-melanoma skin cancer in epidemiological studies Karagas et al, 2006;Masini et al, 2003;Struijk et al, 2003). This might indicate that the ability to inhibit UVB-induced apoptosis of keratinocytes is somehow associated with skin cancer development, and that particular bPV types may act as co-factors in carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Specific betapapillomaviruses associated with squamous cell carcinoma of the skin inhibit UVB-induced apoptosis of primary human keratinocytes

Struijk

Meijden

Kazem

et al. 2008

Journal of General Virology

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Epidemiological studies have shown an association between infections by specific betapapillomaviruses, such as human papillomavirus (HPV) types 5 and 8, and cutaneous squamous cell carcinoma (SCC). The role of betapapillomaviruses in the development of cutaneous SCC is, however, still enigmatic. The ability to inhibit UVB-induced apoptosis, as demonstrated for HPV5 in vitro, may be important in this respect, as survival of DNA-damaged and mutated cells increases the risk of transformation. The aim of this study was to assess whether inhibition of UVB-induced apoptosis is a general property of betapapillomaviruses and to identify apoptotic factors that are potentially involved in this process. Primary human keratinocytes transduced with E6 and E7 of selected betapapillomaviruses (HPV5, HPV8, HPV15, HPV20, HPV24 and HPV38) were characterized and subjected to UVB irradiation. HPV8-and HPV20-expressing keratinocytes in particular showed fewer signs of apoptosis, as demonstrated by lower levels of active caspase 3, less enzymic caspase activity and less DNA fragmentation. The observed inhibition of UVB-induced apoptosis was mediated by E6 and coincided with reduced steady-state expression of the pro-apoptotic protein Bax. In conclusion, E6 of HPV8 and HPV20 reduces the apoptotic responses upon UVB irradiation when expressed in primary human keratinocytes. Infections with HPV8 and HPV20 may therefore augment the carcinogenic effect of UV radiation and potentially contribute to oncogenic transformation of the skin.

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“…Finding markers of increased viral activity may help to elucidate the role of HPV in cutaneous carcinogenesis. HPV antibodies, present in about half of those who have evidence of eyebrow hair infection, have been associated with SCC risk in several case-control studies (12)(13)(14)(15)(16), possibly indicating the presence of more active virus. However, it is also possible that presence of skin cancer causes the generation of HPV antibodies and that reverse causality is responsible for this finding (17).…”

Section: Introductionmentioning

confidence: 99%

Human Papillomavirus Load in Eyebrow Hair Follicles and Risk of Cutaneous Squamous Cell Carcinoma

Neale

Weissenborn

Abeni

et al. 2013

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Beta-human papillomavirus (betaPV) may play a role in the development of cutaneous squamous cell carcinoma (SCC). However betaPV is highly prevalent, and it may only be people with a higher viral load who have increased risk of SCCs. We therefore examined the association between betaPV load and SCCs.Methods: We recruited 448 immunocompetent cases with SCCs and 464 controls from Italy and Australia and 497 immunosuppressed organ transplant recipients (OTR; 179 cases and 318 controls) from Europe. We used reverse hybridization to genotype 25 betaPV types in eyebrow hair follicles and determined the viral load for eight selected types using quantitative PCR. We used logistic regression to assess associations between type-specific and cumulative viral load and SCCs.Results: Australian and OTR participants in the highest cumulative load tertile were at significantly higher risk of SCCs than those in the lowest tertile. Those with more than four betaPV types in the high load tertile were at approximately three-fold increased risk of SCCs. In Australia, HPV23 and 36 loads were significantly associated with SCCs, with borderline associations for HPV5 and 38. In OTR, HPV8 and 38 loads were significantly associated and HPV20 and 36 were borderline. We found little evidence for an association between load and SCCs in Italy.Conclusions: High viral load may be associated with risk of cutaneous SCCs, with total load seemingly more important than the load of any specific type.Impact: Our findings lend weight to the hypothesis that HPV plays a role in skin carcinogenesis. Cancer Epidemiol Biomarkers Prev; 22(4); 719-27. Ó2013 AACR.

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Evidence for the Association of Human Papillomavirus Infection and Cutaneous Squamous Cell Carcinoma in Immunocompetent Individuals

Cited by 112 publications

References 37 publications

A prospective pilot study of antibodies against human papillomaviruses and cutaneous squamous cell carcinoma nested in the Oxford component of the European Prospective Investigation into Cancer and Nutrition

A prospective pilot study of antibodies against human papillomaviruses and cutaneous squamous cell carcinoma nested in the Oxford component of the European Prospective Investigation into Cancer and Nutrition

Specific betapapillomaviruses associated with squamous cell carcinoma of the skin inhibit UVB-induced apoptosis of primary human keratinocytes

Human Papillomavirus Load in Eyebrow Hair Follicles and Risk of Cutaneous Squamous Cell Carcinoma

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