Association between hepatitis C and B viruses and head and neck squamous cell carcinoma

doi:10.1016/j.jcv.2019.104209

Journal of Clinical Virology

Volume 121, December 2019, 104209

https://doi.org/10.1016/j.jcv.2019.104209 Get rights and content

Highlights

•
The influence of HCV and HBV infection on HNSCC is unclear.
•
We conducted a matched case-control study in patients with HNSCC.
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Patients with HNSCCs presented with HCV and HBV infection more often than controls.

Abstract

Background

Hepatitis B and C viruses are known to be carcinogenic and have been associated with the development of non-Hodgkin’s lymphoma as well as hepatocellular carcinoma. The incidence of head and neck cancer is increasing worldwide, and early diagnosis is vital in order to achieve good oncological outcomes.

Objectives

To investigate the association between chronic hepatitis B and C infection, and head and neck squamous cell carcinoma (HNSCC).

Study design

We performed a retrospective case control study with 774 head and neck squamous cell carcinoma (HNSCC) patients undergoing treatment, and 1518 cancer-free controls undergoing hernia surgery. Hepatitis B and C serologies were tested prior to treatment, and cases and controls were age- and sex-matched before analysing rates of infection.

Results

HNSCC patients were more likely than controls to have evidence of chronic hepatitis B (OR = 2.76; CI 95 %, 1.64–4.64) and hepatitis C (OR = 2.59; 95 % CI, 1.46–4.60) infection. No substantial association was found between hepatitis B and C infection and other known risk factors for head and neck cancer.

Conclusions

These findings suggest a positive association between both hepatitis B and hepatitis C chronic infection, and HNSCC. More work is needed to establish a causal role, however an awareness of the possibility of increased risk of HNSCC may lead to earlier diagnosis and better outcomes in patients with hepatitis B and C.

Section snippets

Background

In 2020, head and neck cancer (HNC) is expected to affect approximately 833,000 and 151,000 new patients worldwide and in Europe, respectively [1]. HNC includes a heterogeneous group of tumors; more than 90 % are squamous cell carcinoma (HNSCC) and about 70 % originate in the oral cavity, pharynx, and larynx [2]. Hepatitis B (HBV) and hepatitis C (HCV) viruses are carcinogenic pathogens associated with the development of hepatocellular carcinoma and non-Hodgkin’s lymphoma [3]. Furthermore, HCV

Objectives

The aim of this case-control study is to investigate the association between HCV/HBV infection an HNSCC risk in Italy, using a cancer-free comparison group.

Study design

After obtaining local ethics committee approval (n. 671/CE Marca), we enrolled 774 HIV-negative patients aged ≥18 years treated for HNSCC between 2000 and 2018. A control group of 1518 cancer-free patients aged ≥18 years undergoing hernioplasty (groin, hypogastric, umbilical, para-umbilical, anterior abdominal wall) was selected from hospital records. In both cases and controls, HBV and HCV serologies were tested before treatment. Previous cancer diagnoses resulted in exclusion from the control

Results

The 774 HNSCC patients tested for HCV and HBV antibodies during the study period included 106 oral cavity (13.7 %), 202 oropharynx (26.1 %), 83 hypopharynx (10.7 %) and 383 larynx (49.5 %).

The prevalence of anti-HCV antibodies (aHCV) was much higher among cancer cases (3.49 %) than controls (1.34 %; p < 0.01), resulting in a 2.5-fold higher HNSCC risk (95 % CI 1.46–4.60) among HCV infected people (Table 1). Similarly, HBsAg prevalence was higher among cases than controls (4.52 % and 1.29 %;

Discussion

This study is the largest case-control study reporting a statistically significant association between HNSCC and infection with HCV and HBV. These findings are clinically relevant and add evidence that HBV and HCV infections are associated with HNSCC with a similar magnitude as the already well recognized association with B-cell non-Hodgkin’s lymphoma [3,10].

Our results support the association between oral cavity SCC and HCV despite ongoing debate in the contemporary literature [11]. This

Funding

None.

Ethical approval

Not required.

Author contributions

PBR, DB, JP, SD have made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data;

VB, EV have made substantial contributions to acquisition of data and analysis

DB, JF, AM, MCDM, GS have been involved in drafting the manuscript or revising it critically for important intellectual content; PBR, RR, SD, DB, JP Agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of

Declaration of Competing Interest

None declared.

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Cited by (9)

HCV infection and the risk of head and neck cancer: A meta-analysis
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Citation Excerpt :
Giving the low number of studies, results should be interpreted with caution; indeed, the HKSJ estimates reported wider confidence intervals (Supplementary Fig. 1) and pooled RR was no longer significant for laryngeal cancer (RR = 2.55; 95% CI: 0.35–18.61). Influence analysis revealed that the pooled RR was no longer statistically significant when we excluded the study by Donà et al. (RR = 2.28) [12] or the one by Mahale et al. [19] (RR = 1.82). Conversely, when the study by Amin et al. [3] was ruled out, the pooled RR climbed to 3.76 (95% CI: 2.29–6.16).
Recent evidence has consistently suggested a role for HCV in the etiology of head and neck squamous cell carcinoma (HNSCC), but the conclusions of these studies have often been limited by small sample size. Therefore, a meta-analysis was performed to summarize present evidence on the association between HCV infection and HNSCC. After screening citations from literature search, eight observational studies investigating the association between HCV and cancer(s) of either oral cavity, oropharynx, hypopharynx or larynx were included. For each cancer site, risk ratios from individual studies were displayed in forest plots; pooled risk ratios (RR) and corresponding confidence intervals (CI) were calculated. A significant association was found between HCV infection and cancers of the oral cavity (RR = 2.13; 95%: 1.61–2.83), oropharynx (RR = 1.81; 95% CI: 1.21–2.72), and larynx (RR = 2.57; 95% CI: 1.11–5.94). A similar picture emerged for hypopharyngeal cancer, though this result did not fully reach statistical significance because of the small number of available studies (RR = 2.15; 95% CI: 0.73–6.31). These findings remained similar after exclusion of patients with HIV co-infection. Our results highlighted the importance of surveillance of the upper aerodigestive tract in patients with known chronic HCV infections in order to enable HNSCC early diagnosis. In addition, they could be a reminder of the possibility of undiagnosed HCV infection to the clinicians treating HNSCC.
The association of HBV infection and head and neck cancer: a systematic review and meta-analysis
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Associations of Head and Neck Cancer with Hepatitis B Virus and Hepatitis C Virus Infection
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Survival outcomes of patients with head and neck squamous cell cancer with hepatitis B virus infection: An analysis from an endemic tertiary center
2023, Cancer Medicine
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2023, Current Molecular Pharmacology
Hepatitis B virus infection: An insight into the clinical connection and molecular interaction between hepatitis B virus and host extrahepatic cancer risk
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¹: The first two Authors contributed equally to the paper.

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Short communicationAssociation between hepatitis C and B viruses and head and neck squamous cell carcinoma

Highlights

Abstract

Background

Objectives

Study design

Results

Conclusions

Section snippets

Background

Objectives

Study design

Results

Discussion

Funding

Ethical approval

Author contributions

Declaration of Competing Interest

Eur. J. Cancer

J. Hepatol.

Clin. Liver Dis.

Oral Oncol.

Oral Oncol.

Multiple cancers of the head and neck

Maedica

Biological agents. Volume 100 B. A review of human carcinogens

IARC Monogr. Eval. Carcinog. Risks Hum.

The oncologic burden of hepatitis C virus infection: a clinical perspective

CA Cancer J Clin.

Short communication
Association between hepatitis C and B viruses and head and neck squamous cell carcinoma