头颈癌（HNC）是一种复杂的疾病，多种危险因素可能导致其进展。观察性研究表明，单纯疱疹病毒 (HSV) 可能与 HNC 风险相关。然而，它们之间的因果关系和方向仍不清楚。本研究根据最新的公共卫生数据和全基因组关联研究（GWAS），采用孟德尔随机化（MR）方法评估HSV感染与头颈癌之间的因果关系。数据。使用 IVW、加权中位数和 MR-Egger 估计因果效应。随后进行了反向 MR 分析。敏感性分析采用Cochrans Q检验、MR-Egger截距检验、留一分析、漏斗图。基因预测较高水平的HSV-1 IgG与HNC存在因果关系（OR=1.0019，95%CI=1.0003） -1.0036，p=0.0186，IVW）和口腔癌和口咽癌（OR=1.0018，95%CI=1.0004-1.0033，p=0.0105，IVW）。反向 MR 分析并未证明 HSV 和 HNC 之间存在反向因果关系。然而，HSV-2 感染与 HNC 数据和口咽癌数据没有因果关系。进行了敏感性分析，结果显示没有异质性和水平多效性。总的来说，HSV 感染与 HNC 风险增加之间存在显着关联，为了解这种恶性肿瘤的病因提供了宝贵的见解。需要进一步深入研究来验证这些发现并阐明其基础机制。版权所有 © 2024 Yan、Xiao、Gosau、Smeets、Feng、Burg、Fu 和 Friedrich。

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.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.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.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.Copyright © 2024 Yan, Xiao, Gosau, Smeets, Feng, Burg, Fu and Friedrich.