Abstract: Objective To investigate the correlations of human papillomavirus (HPV) infection and esophageal squamous cell cancer (ESCC)/ gastric cardia adenocarcinoma (GCA) and clinical significance of p16INK4A expression in the tumorigenesis of esophageal/gastric cardia epithelium by concurrent cancers from esophagus and gastric cardia in the same patient (CC) from Linzhou,a high-incidence area for SCC in Henan. Methods HPV16-E6 DNA and expressions of p16INK4A were detected by polymerase chain reaction (PCR) and ABC immunohistochemistry in 17 surgically resected specimens with SCC, 17 specimens with GCA. Results The positive rate of HPV16-E6 DNA was 47% (8/17) in SCC, and 29% (5/17) in GCA, respectively, and HPV16-E6 DNA was observed simultaneously in 2 specimens of SCC and 2 GCA，respectively. The immunohistochemical stain for p16INK4A protein was observed both in SCC and GCA tissues with different degrees. The expression of p16INK4A protein was significantly higher in GCA than that in SCC (75% vs.25%, P＜0.05). Conclusion The consistent HPV infection in CC from the patients at same area suggests that HPV may be one of the common oncogenic factor for both SCC and GCA. HPV16, the high-risk type, may play an important role in the development of SCC and GCA. p16INK4A may be another candidate biomarker for screening of HPV-related GCA.