Hepatitis C Virus Infection Associated with Oral Potentially Malignant Disorder, Oral Cancer, and Liver Diseases

Background/Objectives: While smoking, areca nut chewing, and alcohol are established risk factors, Hepatitis C virus (HCV) infection has emerged as a potential risk for oral neoplasia. This study explores any association of HCV infection with oral potentially malignant disorder (OPMD) and oral cancer, following adjustment for HCV-related liver disease in a large screening cohort. Methods: Data from 37,720 participants in the Changhua Community-Based Integrated Screening Program (2005–2014) with smoking or areca nut use history were analyzed. OPMD and cirrhosis were identified at screening, while oral and liver cancers were diagnosed during follow-up. Information on demographics, lifestyle, and clinical factors, including chronic and active HCV infection, was collected. Multinomial logistic regression was used to assess associations between HCV status and disease outcomes. Results: The prevalence of hepatitis C viremia was higher in the OPMD group (4.4%) and oral cancer group (3.3%) compared to the screen-negative group (2.7%), and highest in the cirrhosis/liver cancer group (23.3%). The odds ratios of OPMD and oral cancer were 1.59 (95% CI: 1.20–2.01) and 1.22 (95% CI: 0.67–2.23), respectively, in subjects with hepatitis C viremia compared to those without. After adjusting for confounding factors, individuals with hepatitis C viremia were at increased risk of OPMD by 50% (aOR = 1.50; 95% CI: 1.17–1.92) but not a statistically significant elevated risk for oral cancer (aOR = 1.09; 95% CI: 0.59–2.01), which was possibly attenuated due to HCV-related liver disease (aOR = 11.59; 95% CI: 8.33–16.13). Conclusions: HCV infection may act as an early risk factor for OPMD, though its progression to oral cancer may occur alongside the risk of HCV-related liver diseases. Including HCV status in screening may aid early detection and secondary prevention of oral cancer in high-risk groups.