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Review
. 2014 Apr;70(4):621-629.
doi: 10.1016/j.jaad.2014.01.857.

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

Jennifer Wang  1 , Bishr Aldabagh  2 , Justin Yu  3 , Sarah Tuttleton Arron  4
Affiliations
Review

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

Jennifer Wang et al. J Am Acad Dermatol. 2014 Apr.

Abstract

Background: The role of human papillomavirus (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 polymerase chain reaction, 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-appearing skin (pooled effect size [ES] 3.43, 95% confidence interval 1.97-5.98, P < .0001) in all patients. An increase in HPV prevalence was found in tumors from immunosuppressed patients compared with immunocompetent patients (pooled ES 3.01, 95% confidence interval 2.00-4.52, P < .0001).

Limitations: The greatest limitation is the heterogeneity of the studies included. The association of higher HPV prevalence in squamous cell carcinoma compared with normal-appearing 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 with immunocompetent patients may have therapeutic implications.

Keywords: cutaneous squamous cell carcinoma; human papillomavirus; immunocompetence; immunosuppression; meta-analysis; skin cancer.

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Conflict of interest statement

The authors report no potential conflicts of interest

Figures

Fig 1
Fig 1
Flow chart of the search strategy and selection criteria
Fig 2
Fig 2
Funnel plot with pseudo 95% confidence intervals for tumor versus normal (Hypothesis 1) showing no evidence of publication bias (Egger’s p=0.23).
Fig 3
Fig 3
Pooled effect size and 95% confidence intervals for tumor versus normal (Hypothesis 1), showing that SCC were more likely to carry HPV than normal skin (pooled ES 3.43, 95% CI 1.97–5.98, p<0.0001). I2 and Q statistics showed significant evidence of heterogeneity in the published studies (I2=76.0%, Q = 66.65 (d.f. = 16) p <0.0001).
Fig 4
Fig 4
Pooled effect size and 95% confidence intervals for immunosuppressed tumors versus immunocompetent tumors (Hypothesis 2), showing that SCC from immunosuppressed patients are more likely to carry HPV than SCC from immunocompetent patients (pooled ES 3.01, 95%CI 2.00–4.52, p<0.0001). I2 and Q statistics showed minimal evidence of heterogeneity (I2=28.4%, Q = 15.37 (d.f. = 11) p = 0.17).
Fig 5
Fig 5
Funnel plot with pseudo 95% confidence intervals for immunosuppressed tumors versus immunocompetent tumors (Hypothesis 2) showing no evidence of publication bias (Egger’s p=0.78).
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