Human Papillomavirus Infection Is Associated with Decreased Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients: Taiwan Nationwide Matched Cohort Study

SIMPLE SUMMARY: Previous studies have provided evidence suggesting a link between HCV and HPV-associated head and neck cancers. The epidemiological evidence of the relocated association between HPV and HCV-associated HCC is scarce. In the current study, from a secondary claim-based dataset, HPV infection is not associated with an increased risk of HCC in the CHC population. On the contrary, HPV infection seems to be associated with a lower risk of HCC development among patients with HCV infection. These findings suggest that the mechanism of association between procuring an HPV infection and reducing risk of HCC in the CHC population needs to be studied in detail in the future, with the opportunity to generate an intervention target that could delay the development of HCC. ABSTRACT: Background: Hepatitis C virus (HCV) has been shown to be associated with human papillomavirus (HPV)-positive head and neck cancers. However, studies regarding HPV infection and the risk of new-onset hepatocellular carcinoma (HCC) among chronic hepatitis C (CHC) patients are limited. We examined the risk of HCC in CHC patients with or without HPV infection. Methods: In total, 9905 CHC patients from 2000 to 2016 constituted the whole cohort. HPV was defined as being diagnosed after HCV. The CHC cohort with HPV (N = 1981) and age-, sex-, inception point-, comorbidity-, and medication-matched non-HPV (N = 7924) were followed up until HCC, death, or 2018. HCC patients were extracted from the Taiwan Registry for Catastrophic Illness Database. We adopted the propensity score match and inverse probability of treatment weighting (IPTW) to eliminate bias. Cox proportional hazard regression analyses were performed to calculate HCC risk. Results: After a full adjustment, HPV was not associated with HCC risk (aHR, 0.74; 95% CI, 0.58–0.96 in the main model, and aHR, 0.76; 95% CI, 0.66–0.87 in IPTW, respectively). Almost all subgroup analyses verified this finding (HRs < 1.0). Conclusions: Among CHC patients older than 18 years old, those with HPV infection were associated with a lower risk of subsequent HCC.