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Human papilloma virus (HPV) has been detected in some upper aerodigestive tract tumors, but the correlation between HPV and these tumors is not well understood. There is also some controversy regarding this correlation because a large variation in the prevalence of HPV in these tumors has been reported. To discuss the impact of HPV infection on upper aerodigestive tract tumors, this review estimated systematically the prevalence and risk of HPV in upper aerodigestive tract tumors from studies published between 1982 and 2012. In total, 418 articles were selected, which included 273 studies on the head and neck and 145 studies on esophageal squamous cell carcinoma. The overall prevalence of HPV in the 5,467 head and neck squamous cell carcinoma specimens was 36.3%. HPV was detected more frequently in the Americas (40%), than in Asia (38.6%), Europe (32%), or others regions (30.5%). The prevalence of HPV was significantly higher in oropharyngeal (48.5%) than in oral (32.5%), laryngeal (30.7%), and unselected head and neck squamous cell carcinoma (33.3%) (P < 0.001). The pooled prevalence of HPV in the 6,912 esophageal squamous cell carcinoma cases was 38.9% and it was significantly higher in China (44%) versus other regions (31.3%) (P < 0.05). Meta-analysis showed that head and neck and esophageal squamous cell carcinoma are associated with HPV infection (combined OR: 3.58, OR for head and neck and esophageal squamous cell carcinoma: 4.20). These findings suggest that HPV might be linked etiologically to the development of some upper aerodigestive tract tumors., (Copyright © 2013 Wiley Periodicals, Inc.)