Human Papillomavirus Infection Is Associated with Decreased Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients: Taiwan Nationwide Matched Cohort Study
by
, , and
Sung-Shuo Kao
1,2,3,†, 
Chia-Jung Li
4,5
,
James Cheng-Chung Wei
6,7,8,
Cheng-Li Lin
9,
Renin Chang
6,10,† and
Yao-Min Hung
11,12,* 1
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
2
Kaohsiung Veterans General Hospital Pinging Branch, Pingtung 91245, Taiwan
3
School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
4
Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
5
Institute of BioPharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
6
Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
7
Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
8
Graduate Institute of Integrated Medicine, China Medical University, Taichung 40402, Taiwan
9
Management Office for Health Data, China Medical University Hospital, Taichung 40402, Taiwan
10
Department of Emergency Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
11
Department of Internal Medicine, Kaohsiung Municipal United Hospital, Kaohsiung 80457, Taiwan
12
College of Health and Nursing, Meiho University, Pingtung 91202, Taiwan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2022, 14(5), 1289; https://doi.org/10.3390/cancers14051289
Submission received: 15 January 2022
/
Revised: 17 February 2022
/
Accepted: 18 February 2022
/
Published: 2 March 2022
(This article belongs to the Section Infectious Agents and Cancer)
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.
Keywords:
human papillomavirus; HPV; hepatitis C virus; HCV; hepatocellular carcinoma; HCC; cohort
