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. 2024 Aug 5:15:1278327.
doi: 10.3389/fimmu.2024.1278327. eCollection 2024.

The role of herpes simplex virus infection in the etiology of head and neck cancer-a Mendelian randomization study

Ming Yan  1   2 , Li-Yuan Xiao  1 , Martin Gosau  2 , Ralf Smeets  2   3 , Hong-Chao Feng  1 , Simon Burg  2 , Ling-Ling Fu  1   2 , Reinhard E Friedrich  2
Affiliations

The role of herpes simplex virus infection in the etiology of head and neck cancer-a Mendelian randomization study

Ming Yan et al. Front Immunol. .

Abstract

Introduction: Head and neck cancer (HNC) is a complex disease, and multiple risk factors can lead to its progression. Observational studies indicated that herpes simplex virus (HSV) may be correlated with the risk of HNC. However, the causal effects and direction between them were still unclear.

Methods: This study utilized a Mendelian randomization (MR) approach for causality assessment between HSV infection and Head and neck cancer based on the latest public health data and Genome-Wide Association Study (GWAS) data. The causal effects were estimated using IVW, weighted median, and MR-Egger. A reverse MR analysis was subsequently performed. Cochrans Q test, MR-Egger intercept test, leave one out analysis, and the funnel plot were all used in sensitivity analyses.

Results: Genetically predicted higher level of HSV-1 IgG was causally related to HNC (OR=1.0019, 95%CI=1.0003-1.0036, p=0.0186, IVW) and oral and oropharyngeal cancer (OR=1.0018, 95%CI=1.0004-1.0033, p=0.0105, IVW). The reverse MR analysis did not demonstrate a reverse causal relationship between HSV and HNC. However, HSV-2 infection was not causally related to HNC data and oropharyngeal cancer data. Sensitivity analysis was performed and revealed no heterogeneity and horizontal pleiotropy.

Conclusion: Collectively, a significant association was noted between HSV infection and increased risk of HNC, providing valuable insights into the etiology of this malignancy. Further in-depth study is needed to validate these findings and elucidate the underpinning mechanisms.

Keywords: Mendelian randomization; causal effect; head and neck cancer; herpes simplex virus; hsv; oral and oropharyngeal cancer.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Experimental design and assumptions. (A) Three key assumptions of MR analysis. (B) Flow chart of experimental design.
Figure 2
Figure 2
Scanner plots for the two-sample Mendelian randomization analyses. (A) HSV-1 and head and neck cancer; (B) HSV-1 and Oral and oropharyngeal cancer; (C) HSV-2 and head and neck cancer; (D) HSV-2 and Oral and oropharyngeal cancer.
Figure 3
Figure 3
Plots of leave-one-out analyses for the two-sample Mendelian randomization analyses. (A) HSV-1 and head and neck cancer; (B) HSV-1 and Oral and oropharyngeal cancer; (C) HSV-2 and head and neck cancer; (D) HSV-2 and Oral and oropharyngeal cancer.
Figure 4
Figure 4
Funnel plots for the two-sample Mendelian randomization analyses. (A) HSV-1 and head and neck cancer; (B) HSV-1 and Oral and oropharyngeal cancer; (C) HSV-2 and head and neck cancer; (D) HSV-2 and Oral and oropharyngeal cancer.
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Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by a grant from the Foundation of Guiyang Science and Technology Bureau (No. [2018]1-56). MY was supported by the Merit Scholarship of Hamburg university for International Students (No.7238065). L-LF was supported by the Chinese Government Scholarship (CSC Scholarship) (No.202208520014).

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