Beta Human Papillomaviruses Seropositivity and the Association With Cutaneous Squamous Cell Carcinoma—A Systematic Review and Meta‐Analysis

ABSTRACT Background Cutaneous squamous cell carcinoma (cSCC) is one of the most common nonmelanoma skin cancers, with increasing incidence globally. Beta genus human papillomaviruses (β‐HPVs), particularly in immunocompromised individuals, have been implicated in the development of cSCC. However, the strength of association between β‐HPV seropositivity and cSCC risk in the general population remains unclear. Objectives This study systematically evaluates and quantify the association between β‐HPV seropositivity and cSCC. Methods A systematic literature search was conducted across PubMed, Embase, Scopus and Cochrane Library up to January 2024. Eligible studies included case‐control and cohort designs that assessed β‐HPV seropositivity in individuals with and without cSCC. A random‐effects meta‐analysis was performed to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs) for overall and type‐specific β‐HPV subtypes. Heterogeneity and publication bias were assessed using the I ² statistic, Egger's and Begg's tests. Results Twenty studies ( n  = 5827 cSCC cases, n  = 5057 controls) were included. Overall β‐HPV seropositivity was associated with increased cSCC risk (pooled OR: 1.17, 95% CI: 1.12–1.22). Subgroup analysis showed significant associations for β1 and β2 species, but not for β3–β5. Type‐specific analysis identified HPV types 5, 8, 17, 20, 38, 49, 76 and 92 as significantly associated with cSCC. Conclusions This meta‐analysis supports an association between β‐HPV seropositivity and cSCC. These findings highlight the potential role of β‐HPV in skin carcinogenesis and underscore the need for further research on its clinical significance and detection methods.