title: Association Between β-Genus Human Papillomavirus and Cutaneous Squamous Cell Carcinoma in Immunocompetent Individuals-A Meta-analysis.
abstract: Existing epidemiological evidence remains controversial regarding the association between β-genus human papillomavirus (β-HPV) and cutaneous squamous cell carcinoma (cSCC) in immunocompetent individuals.
  
  
  
  We aimed to clarify this association and evaluate type-specific β-HPV involvement.
  
  
  
  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."
  
  
  
  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.
  
  
  
  We first assessed the heterogeneity among study-specific ORs using the Q statistic and I2 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Internal Medicine, The University of Texas Health Science Center, University of Texas Medical School at Houston, Houston.
authors.forename: Jad
authors.initials: J
authors.lastname: Chahoud
authors.affiliation: Department of Management Policy and Community Health, The University of Texas School of Public Health, Houston.
authors.forename: Adele
authors.initials: A
authors.lastname: Semaan
authors.affiliation: Department of Biostatistics, The University of Texas School of Public Health, Houston.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Biostatistics, The University of Texas School of Public Health, Houston.
authors.forename: Ming
authors.initials: M
authors.lastname: Cao
authors.affiliation: Department of General Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Alyssa G
authors.initials: AG
authors.lastname: Rieber
authors.affiliation: Department of Dermatology, The University of Texas Medical School at Houston, Houston.
authors.forename: Peter
authors.initials: P
authors.lastname: Rady
authors.affiliation: Department of Dermatology, The University of Texas Medical School at Houston, Houston.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Tyring
mesh_terms: D000328:Adult; D052686:Betapapillomavirus / Q000302:isolation & purification; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D007121:Immunocompetence; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000821:virology*