Human Papillomavirus Infection and Esophageal Squamous Cell Carcinoma: A Case–Control Study

Abstract

BACKGROUND: The risk factors for esophageal squamous cell carcinoma (ESCC) in the high-incidence areas of China remain unclear. METHODS: A total of 300 patients with ESCC and 900 controls matched for age and sex were enrolled in Anyang (China), a high-risk area for ESCC in China. In tumor tissue of the cases and in esophageal biopsies of controls, the presence of human papillomavirus (HPV) DNA was assessed by an SPF1/GP6(+)-mediated PCR followed by sequencing. The presence of serum antibody against the HPV-16 E7 oncoprotein was assessed by use of the ELISA. ORs with 95% confidence intervals (CI) were calculated via unconditional logistic regression models. RESULTS: The presence of HPV in the esophagus (OR, 6.4; 95% CI, 4.4-9.2) was associated with increased risk of ESCC. Moreover, infection with "oncogenic" types of HPV (OR, 10.3; 95% CI, 6.3-16.8) was more strongly associated with ESCC than other types of HPV (OR, 2.4; 95% CI, 1.4-4.2). The presence of HPV-16 (OR, 12.8; 95% CI, 7.6-21.7) was particularly strongly associated with ESCC. In addition, a higher proportion of cases than controls had serum antibodies against HPV-16 E7 (OR, 6.1; 95% CI, 3.7-10.0). CONCLUSION AND IMPACT: This study provides the strongest epidemiologic evidence to date in support of the important role of HPV in the development of ESCC in high-incidence areas of China.