Association Between Hepatitis B Surface Antigen Positivity and Tumor Incidence: A Large Prospective Cohort Study in Southern China
5 affiliations
- 1Department of Medical Statistics, School of Public Health, Sun Yat-sen Global Health Institute, Center for Health Information Research, Sun Yat-sen University, Guangzhou 510080, China
- 2Center for Public Health and Epidemic Preparedness and Response, Peking University Beijing 100191, China
- 3Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
- 4Key Laboratory of Epidemiology of Major Diseases, Peking University, Ministry of Education, Beijing 100191, China
- 5Guangzhou Joint Research Center for Disease Surveillance and Risk Assessment, Sun Yat-sen University, Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China
Abstract
Background: Hepatitis B virus (HBV) infection is a major global health concern and has been implicated in carcinogenesis. However, evidence regarding the association between hepatitis B surface antigen (HBsAg) positivity and the risk of overall and site-specific tumors remains limited. This study aimed to investigate the association between HBsAg positivity and tumor incidence in a large prospective cohort. Methods: This prospective cohort study included 538,573 participants recruited in southern China between 2009 and 2015. Newly recorded tumor diagnoses were identified by linkage to a hospital discharge database available through December 2022. Missing covariate values were addressed using five multiple imputations, and propensity score matching was performed separately within each dataset. Cox model estimates were combined using Rubin’s rules. Time-varying and landmark analyses were also performed. Results: Baseline HBsAg positivity was associated with increased risks of all-site tumors (pooled hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.79–2.27), digestive system malignancies (pooled HR, 4.28; 95% CI, 3.51–5.22), and benign tumors (pooled HR, 1.52; 95% CI, 1.27–1.82). Strong associations were observed for liver and intrahepatic bile duct malignancies (pooled HR, 15.49; 95% CI, 8.99–26.67) and hepatocellular carcinoma (pooled HR, 19.78; 95% CI, 7.19–54.44). In contrast, the association with extrahepatic digestive system malignancies was not statistically significant. The associations generally attenuated over follow-up but persisted after excluding tumor events recorded within the first 1 and 2 years. Stronger associations with all-site tumors were observed among men and participants aged ≥45 years. Conclusions: Baseline HBsAg positivity was associated with an increased risk of overall and site-specific tumors, particularly digestive system malignancies. The associations were stronger among men and older adults. These findings support further clinical evaluation of HBsAg-positive individuals and guideline-based liver cancer surveillance when clinically indicated.
Related
- Incidence of mother-to-child transmission of hepatitis B virus and associated factors in Addis Ababa, Ethiopia: a prospective cohort study
- Life’s Essential 8 moderates the association between Occupational Hazard Index and the incidence of hypertension among steelworkers: a prospective cohort study
- Association between the cholesterol-high-density lipoprotein-glucose index and the incidence of new-onset diabetes in patients with chronic gastrointestinal diseases: A prospective cohort study.
- Spatial epidemiology of hepatitis C in Khenchela Province, Algeria: identifying HCV incidence hotspots and implications for regional public health
- A methodological exploration of monthly incidence rate of hepatitis B in China: a time series and machine learning analysis
BibTeX
@article{wen2026association,
title = {{Association Between Hepatitis B Surface Antigen Positivity and Tumor Incidence: A Large Prospective Cohort Study in Southern China}},
author = {Qilan Wen and Yu Wang and Yikun Chang and Jinwei Chen and Na Cao and Xin Sun and Yuantao Hao and Wangjian Zhang and Zhicheng Du},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18213445},
url = {https://www.mdpi.com/2072-6694/18/21/3445},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Association Between Hepatitis B Surface Antigen Positivity and Tumor Incidence: A Large Prospective Cohort Study in Southern China
AU - Qilan Wen
AU - Yu Wang
AU - Yikun Chang
AU - Jinwei Chen
AU - Na Cao
AU - Xin Sun
AU - Yuantao Hao
AU - Wangjian Zhang
AU - Zhicheng Du
PY - 2026
DA - 2026/10/25
JO - Cancers
DO - 10.3390/cancers18213445
UR - https://www.mdpi.com/2072-6694/18/21/3445
AB - Background: Hepatitis B virus (HBV) infection is a major global health concern and has been implicated in carcinogenesis. However, evidence regarding the association between hepatitis B surface antigen (HBsAg) positivity and the risk of overall and site-specific tumors remains limited. This study aimed to investigate the association between HBsAg positivity and tumor incidence in a large prospective cohort. Methods: This prospective cohort study included 538,573 participants recruited in southern China between 2009 and 2015. Newly recorded tumor diagnoses were identified by linkage to a hospital discharge database available through December 2022. Missing covariate values were addressed using five multiple imputations, and propensity score matching was performed separately within each dataset. Cox model estimates were combined using Rubin’s rules. Time-varying and landmark analyses were also performed. Results: Baseline HBsAg positivity was associated with increased risks of all-site tumors (pooled hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.79–2.27), digestive system malignancies (pooled HR, 4.28; 95% CI, 3.51–5.22), and benign tumors (pooled HR, 1.52; 95% CI, 1.27–1.82). Strong associations were observed for liver and intrahepatic bile duct malignancies (pooled HR, 15.49; 95% CI, 8.99–26.67) and hepatocellular carcinoma (pooled HR, 19.78; 95% CI, 7.19–54.44). In contrast, the association with extrahepatic digestive system malignancies was not statistically significant. The associations generally attenuated over follow-up but persisted after excluding tumor events recorded within the first 1 and 2 years. Stronger associations with all-site tumors were observed among men and participants aged ≥45 years. Conclusions: Baseline HBsAg positivity was associated with an increased risk of overall and site-specific tumors, particularly digestive system malignancies. The associations were stronger among men and older adults. These findings support further clinical evaluation of HBsAg-positive individuals and guideline-based liver cancer surveillance when clinically indicated.
SN - 2072-6694
ER -