这项嵌套式病例-对照研究是在NIH-AARP饮食与健康研究中进行的，旨在前瞻性探究口腔微生物组与头颈癌（HNC）的关系。研究共识别了56例HNC患者和112个对照组成对匹配的个体。从诊前口腔漱洗样本提取DNA，并进行全基因组Shotgun宏基因组测序，以测量总体口腔微生物。应用ITS2基因qPCR方法检测真菌的存在，并在ITS2基因qPCR阳性样本中进行ITS2基因测序。我们计算了分类和功能的α-多样性和β-多样性指标。通过有条件逻辑回归模型和MiRKAT，比较了红色复合物（例如，牙龈卟啉单胞菌）和/或橙色复合物（例如，核酸拟杆菌）牙周病原体的存在和相对丰度。 α-多样性微生物生态的参与者患HNC风险降低的不具统计学意义。MiRKAT模型的β-多样性在HNC患者和对照组之间没有差异（所有p> 0.05）。红色复合物牙周病原体（OR = 0.51, 95％CI = 0.26-1.00）、橙色复合物（OR = 0.38, 95％CI = 0.18-0.83）和两种复合物的病原体（OR = 0.32, 95％CI = 0.14-0.75）的相对丰度与HNC风险降低有关。与对照组相比，口腔真菌的存在也与HNC风险降低密切相关（OR = 0.39, 95％CI = 0.17-0.92）。更高的分类α-多样性、口腔真菌的存在以及包括红色复合物和橙色复合物牙周病原体在内的多种微生物物种的存在或相对丰度，均与HNC风险降低有关。需要更大样本量的未来研究以评估这些关联。

This nested case-control study in the NIH-AARP Diet and Health Study was carried out to prospectively investigate the relationship of oral microbiome with head and neck cancer (HNC).56 incident HNC cases were identified, and 112 controls were incidence-density matched to cases. DNA extracted from pre-diagnostic oral wash samples was whole-genome shotgun metagenomic sequenced to measure the overall oral microbiome. ITS2 gene qPCR was used to measure the presence of fungi. ITS2 gene sequencing was performed on ITS2 gene qPCR positive samples. We computed taxonomic and functional alpha-diversity and beta-diversity metrics. The presence and relative abundance of groups of red-complex (e.g., Porphyromonas gingivalis) and/or orange-complex (e.g., Fusobacterium nucleatum) periodontal pathogens were compared between cases and controls using conditional logistic regression models and MiRKAT.Participants with higher taxonomic microbial alpha-diversity had a non-statistically significant decreased risk of HNC. No case-control differences were found for beta diversity by MiRKAT model (all p > 0.05). A greater relative abundance of red-complex periodontal pathogens (OR = 0.51, 95 % CI = 0.26-1.00), orange-complex (OR = 0.38, 95 % CI = 0.18-0.83), and both complexes' pathogens (OR = 0.32, 95 % CI = 0.14-0.75), were associated with reduced risk of HNC. The presence of oral fungi was also strongly associated with reduced risk of HNC compared with controls (OR = 0.39, 95 % CI = 0.17-0.92).Greater taxonomic alpha-diversity, the presence of oral fungi, and the presence or relative abundance of multiple microbial species, including the red- and orange-complex periodontal pathogens, were associated with reduced risk of HNC. Future studies with larger sample sizes are needed to evaluate these associations.Published by Elsevier Ltd.