Document Type

Journal Article

Date of this Version

12-2016

Embargo Date

12-15-2017

Comments

Chahoud J, Semaan A, Chen Y, Cao M, Rieber AG, Rady P, Tyring SK. Association Between β-Genus Human Papillomavirus and Cutaneous Squamous Cell Carcinoma in Immunocompetent Individuals—A Meta-analysis. JAMA Dermatol. 2016;152(12):1354-1364. doi: dx.doi.org/10.1001/jamadermatol.2015.4530

Abstract

IMPORTANCE

Existing epidemiological evidence remains controversial regarding the association between β-genus human papillomavirus (β-HPV) and cutaneous squamous cell carcinoma (cSCC) in immunocompetent individuals.

OBJECTIVE

We aimed to clarify this association and evaluate type-specific β-HPV involvement.

DATA SOURCES

We performed a systematic literature search of MEDLINE and EMBASE for studies in humans through June 18, 2014, with no restriction on publication date or language. The following search terms were used: “human papillomavirus” and “cutaneous squamous cell carcinoma or skin squamous cell carcinoma or cSCC or nonmelanoma skin neoplasms.”

STUDY SELECTION

Articles were independently assessed by 2 reviewers. We only included case-control or cohort studies, in immunocompetent individuals, that calculated the odds ratio (OR) for cSCC associated with overall and type-specific β-HPV.

DATA EXTRACTION AND SYNTHESIS

We first assessed the heterogeneity among study-specific ORs using the Q statistic and I 2 statistic. Then, we used the random-effects model to obtain the overall OR and its 95% CI for all studies as well as for each type of HPV. We also tested and corrected for publication bias by 3 funnel plot–based methods. The quality of each study was assessed with the Newcastle Ottawa Scale.

MAIN OUTCOMES AND MEASURES

Pooled ORs and 95% CIs for overall β-HPV and HPV types 5, 8, 15, 17, 20, 24, 36, and 38 association with skin biopsy proven cSCC. RESULTS Seventy-nine articles were assessed for eligibility; 14 studies met inclusion criteria for the meta-analysis and included 3112 adult immunocompetent study participants with cSCC and 6020 controls. For all detection methods, the overall association between β-HPV and cSCC was significant with an adjusted pooled OR (95% CI) of 1.42 (1.18-1.72). As for the type-specific analysis, types 5, 8, 15, 17, 20, 24, 36, and 38 showed a significant association with adjusted pooled ORs (95% CIs) of 1.4 (1.18-1.66), 1.39 (1.16-1.66), 1.25 (1.04-1.50), 1.34 (1.19-1.52), 1.38 (1.21-1.59), 1.26 (1.09-1.44), 1.23 (1.01-1.50), and 1.37 (1.13-1.67) respectively. Our subgroup analysis in studies using only serology for HPV detection showed a significant association between overall β-HPV and HPV subtypes 5, 8, 17, 20, 24, and 38 with an increased risk of cSCC development.

CONCLUSIONS AND RELEVANCE

This study serves as added evidence supporting β-HPV as a risk factor for cSCC in healthy individuals. The subgroup analysis highlights this significant association for HPV 5, 8, 17, 20, and 38, which may help to direct future prevention efforts

Keywords

Papillomavirus, Carcinoma, Immunocompetent

Available for download on Friday, December 15, 2017

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Date Posted: 30 June 2017

This document has been peer reviewed.