Detection of human papillomavirus in esophageal papillomas: systematic review and meta-analysis

Abstract

Since first suggested (in 1982), etiological role for human papillomavirus (HPV) in esophageal papillomas has aroused increasing interest. The objective of this study was to perform systematic review and formal meta-analysis of the literature reporting on HPV detection in esophageal squamous cell papillomas (ESCP). Literature was searched through May 2012. The effect size was calculated as event rates (95% CI), with homogeneity testing using Cochran's Q and I(2) statistics. Meta-regression was used to test the impact of study-level covariates (HPV detection method, geographic origin) on effect size, and potential publication bias was estimated using funnel plot symmetry. Thirty nine studies were eligible, covering 427 ESCPs from different geographic regions. Altogether, 132 (30.9%) cases tested HPV positive; effect size 0.375 (95% CI 0.319-0.434) using the fixed-effects (FE) model and 0.412 (95% CI 0.295-0.540) using the random-effects model. In meta-analysis stratified by (i) HPV detection technique and (ii) geographic study origin, the between-study heterogeneity was not significant (p = 0.071 and p = 0.105, respectively). In meta-regression, HPV detection method (p = 0.260) and geographic origin (p = 0.436) were not significant study-level covariates accounting for the heterogeneity in HPV prevalence. Some evidence for publication bias was found only for PCR-based studies, with a marginal impact on summary effect size estimates. In sensitivity analysis, all meta-analytic results were robust to all one-by-one study removals. In stratified meta-analysis and formal meta-regression, the variability in HPV detection rates in ESCPs is not explained by the HPV detection method or geographic origin of the study.