AIM: To look for the evidence of human papilloma virus (HPV) infection in esophageal squamous cell carcinomas (ESCC) and to investigate the potential role and epidemiology of HPV infection in the pathogenesis of esophageal carcinomas in Henan emigrants.METHODS: Papilloma virus (PV) and HPV were determined by UltrasensiveTM S-P immunohistochemistry (IHC)and in situ hybridization (ISH) in esophageal carcinoma tissues (82.cases) and the normal mucosa (40 cases).RESULTS: IHC revealed that the positive rate of PV was 75.0%, 68.18% and 72.5% respectively while the HPV (16/18-E6) positive rate was 45.0%, 36.36%, 37.5%,respectively in esophageal carcinoma tissue specimens from Henan emigrants,the local citizens and patients in Hubei Cancer Hospital. The PV and HPV (16/18-E6) were negative in all normal esophageal mucosa specimens. No correlation was found between HPV in esophageal squamous cell carcinoma tissues and in grade 1-3 esophageal squamous cell carcinoma cells. In situ hybridization showed that the HPV (16/18) DNA positive rate was 30.0%, 31.8%, 25.0%, respectively in the 3 groups of samples. No positive hybridization signal was found in 40 normal esophageal mucosa specimens. The positive rate of HPV (16/18) DNA in the esophageal carcinoma specimens was significantly higher than that in normal mucosa specimens (P＜ 0.05). The positive rate was not different among the 3 groups of esophageal carcinoma tissue specimens (P＞0.05).CONCLUSION: HPV infection is high in esophageal carcinoma of Henan emigrants, local residents and patients in Hubei Cancer Hospital. HPV is closely related with esophageal squamous cell carcinoma. HPV infection may play an important role in esophageal squamous cell carcinoma.