Role of human papillomavirus in cutaneous squamous cell carcinoma: A meta-analysis

Abstract

Background The role of HPV in cutaneous squamous cell carcinoma (cuSCC) is not well defined, with past studies showing conflicting results. Objective We sought to determine if there is a significant association between HPV and cuSCC and whether cuSCC from immunosuppressed patients are more likely to carry HPV than cuSCC from immunocompetent patients. Methods We performed a systematic review and abstracted data from articles that included: skin samples by biopsy, HPV detection by PCR, and a minimum of 10 cases and 10 controls. Pooled effect size and 95% confidence intervals were calculated using random effects meta-analysis using the inverse variance method. Results cuSCC were more likely to carry HPV than normal skin (pooled ES 3.43, 95% CI 1.97–5.98, p<0.0001) in all patients. An increase in HPV prevalence was found in tumors from immunosuppressed patients compared to immunocompetent patients (pooled ES 3.01, 95%CI 2.00–4.52, p<0.0001). Limitations The greatest limitation is the heterogeneity of the studies included. The association of higher HPV prevalence in SCC compared to normal skin does not imply causality. Conclusion These results contribute to evidence that HPV is associated with cuSCC. Higher HPV burden in tumors from immunosuppressed patients compared to immunocompetent patients may have therapeutic implications.

Epidemiology of de novo malignancies after solid-organ transplantation: Immunosuppression, infection and other risk factors

“…UV light may have a transient immunosuppressive effect on skin allowing HPV to evade the immune system. Its higher prevalence in SCC lesions could therefore be merely a marker and not a cause of immunosuppression [34].…”

Cutaneous squamous cell cancer (cSCC) risk and the human leukocyte antigen (HLA) system

“…For instance, HPV77, an α-papillomavirus thus far only detected in cutaneous lesions of immunosuppressed patients, contains a p53-DNA binding site. Once activated by UVR, p53 is thought to stimulate HPV77 promoter activity, leading to the production of E6 and E7 proteins that deregulate p53 and Rb tumor suppressor pathways [42]. In all of these cases, HPV in conjunction with UVR may promote cSCC pathogenesis.…”

“…In all of these cases, HPV in conjunction with UVR may promote cSCC pathogenesis. However, the exact role of HPV in cutaneous oncogenesis remains to be elucidated because HPV DNA has been found in normal skin samples from cSCC patients, though differential detection of β-HPV in tumors suggests that certain high-risk HPV types may be involved in cSCC pathogenesis [38,42]. HLA allele groups positively associated with cSCC in immunosuppressed patients may encode HLA protein with less efficiency in presenting tumor or HPV antigens, and conversely, HLA allele groups negatively associated with cSCC may encode HLA protein with greater efficiency in presenting tumor or HPV antigens.…”

HPV vaccination for prevention of skin cancer

“…8 Additionally, although still controversially discussed, meta-analysis of the current literature shows cumulative evidence that infection with certain cutaneous HPVs can be a cofactor for the development of NMSC, especially SCC. [9][10][11] The oncogenic potential of b-HPV infection (e. g. HPV5 and HPV8) in NMSC has been originally identified in patients suffering from the rare inherited disease Epidermodysplasia Verruciformis (EV), who are characterized by an increased susceptibility to cutaneous HPV infection. 12 These patients apparently display an inherent genetic predisposition, harboring autosomal recessive mutations in the EVER1 and EVER2 genes which have been linked to the disease.…”