Influence of HPV infection in esophageal cancer: A systematic review and meta-analysis

Purpose: Literature has reported that there is similar to 22 % prevalence of high risk (HR)-human papillomavirus (HPV) subtypes in esophageal cancer (EC), the sixth most common cause of cancer related deaths in both genders worldwide. But, the association of HPV in the development of EC is still not clear. Methods: A systematic search on studies with HPV infection and EC was performed using Pub-Med and Science Direct database. A total of 1756 research articles were screened. A random-effect model was used to estimate the overall ODDs Ratio (ORs) and 95 % Confidence Interval (CI) through RevMan 5.3 software. Results: After stringent screening, 33 research articles were selected for meta-analysis following the PRISMA guidelines. Out of these 33 studies, 19 are case-control, 11 are cohort/ observational studies and 3 are cross-sectional studies which were analyzed for HPV infection and EC risk. In case-control studies, a significant association of HR-HPV 16 [3.59 (95 % CI: 2.60-4.96); p-value <0.00001] and HR-HPV 18 [2.25 (95 % CI: 1.31-3.87); p-value <0.00001] genotypes were observed with EC risk. The other HPV subtypes which include both HR and low risk HPV genotypes- 6, 11, 13, 17, 19, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73 and 82 [2.13 (95 % CI:1.36-3.32); p-value <0.04,] also showed a borderline significance with EC progression in case-control studies. Similarly, among the cohort studies, a significant association of HR-HPV 16 [1.20 (95 % CI: 0.84-1.72); p-value <= 0.00001] and HR-HPV 18 [1.33(95 % CI: 0.72-2.46); p-value = 0.0002] genotypes were observed. And in contrast, no significant association of HR-HPV 16 [1.12 (95% CI: 0.75-1.68); p-value = 0.12] genotype with EC development was observed in cross-sectional studies. Conclusions: The present meta-analysis unravelled that HR- HPV 16 and 18 infections may be a strong co-factor along with other confounding risk factors for the etiopathogenesis of EC.