Effectiveness of Intensive Endoscopic Screening for Esophageal Cancer in China: A Community-Based Study.

Evidence is required to evaluate the effectiveness of population-level endoscopic screening for esophageal cancer (EC). In this study, 5,632 permanent residents aged 25-65 years from 6 villages in Hua County, Henan Province, China, were defined as the screening cohort and were offered intensive endoscopic screening. Residents of all 914 remaining villages in Hua County were included as the control cohort, and age-sex standardization was used to calculate the expected numbers of EC and upper gastrointestinal (GI) tract cancer cases and deaths in the screening cohort. The effectiveness of screening was assessed by comparing observed numbers of cases and deaths with expected numbers after 9-year follow-up of these screened subjects (2007-2016). In the screening cohort, 23 upper GI cancers (including 16 ECs) and 10 upper GI cancer deaths (including 5 EC deaths) were identified, and 47% (standardized incidence ratio = 0.53, 95% confidence interval (CI): 0.33, 0.87) and 66% (standardized mortality ratio = 0.34, 95% CI: 0.14, 0.81) reductions in cumulative EC incidence and mortality were found. For upper GI cancers, incidence and mortality were lowered by 43% (standardized incidence ratio = 0.57, 95% CI: 0.38, 0.86) and 53% (standardized mortality ratio = 0.47, 95% CI: 0.25, 0.88), respectively. This study showed that upper GI tract endoscopy is an effective population-level screening test for EC in high-risk regions.

Anti-HPV-E7 seropositivity and risk of esophageal squamous cell carcinoma in a high-risk population in China.

Results of previous serologic studies on the association of human papillomavirus (HPV) with esophageal squamous cell carcinoma (ESCC) have been inconsistent. From 2007 to 2010, the authors collected blood samples and relevant demographic data from 1435 patients with ESCC and 2071 age- and sex-matched normal controls from Anyang, China. HPV-16, 18 and 57 E7 antibodies were evaluated with the glutathione-S-transferase capture ELISA. The proportions of subjects who were positive for antibodies against these three HPV antigens in the case group were all significantly higher than those in the control group. In multivariate analysis, the presence of HPV-16 E7 antibody was associated with an increased risk of ESCC [odds ratio (OR) = 3.6, 95% confidence interval (CI): 2.5-5.0], whereas the presence of HPV-18 (OR = 1.1, 95% CI: 0.7-1.7) and HPV-57 (OR = 1.3, 95% CI: 0.9-1.9) antibodies were not significant after adjustment for HPV-16. In multiple cutoff value analysis, the lowest OR for HPV-16 was obtained with the standard cut point mean + 3 SD. This study provides serological evidence in support of HPV-16 infection playing a role in the occurrence of ESCC in a high-incidence area of China.

The Anyang Esophageal Cancer Cohort Study: study design, implementation of fieldwork, and use of computer-aided survey system.

BACKGROUND: Human papillomavirus (HPV) has been observed repeatedly in esophageal squamous cell carcinoma (ESCC) tissues. However, the causal relationship between HPV infection and the onset of ESCC remains unknown. A large cohort study focusing on this topic is being carried out in rural Anyang, China. METHODOLOGY/PRINCIPAL FINDINGS: The Anyang Esophageal Cancer Cohort Study (AECCS) is a population-based prospective endoscopic cohort study designed to investigate the association of HPV infection and ESCC. This paper provides information regarding the design and implementation of this study. In particular we describe the recruitment strategies and quality control procedures which have been put into place, and the custom designed computer-aided survey system (CASS) used for this project. This system integrates barcode technology and unique identification numbers, and has been developed to facilitate real-time data management throughout the workflow using a wireless local area network. A total of 8,112 (75.3%) of invited subjects participated in the baseline endoscopic examination; of those invited two years later to take part in the first cycle of follow-up, 91.9% have complied. CONCLUSIONS/SIGNIFICANCE: The AECCS study has high potential for evaluating the causal relationship between HPV infection and the occurrence of ESCC. The experience in setting up the AECCS may be beneficial for others planning to initiate similar epidemiological studies in developing countries.

Human papillomavirus infection and esophageal squamous cell carcinoma: a case-control study.

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.