口服微生物组以及随后的头颈鳞状细胞癌的风险

口腔菌群可能参与头颈部鳞状细胞癌（HNSCC）的发展，但是目前的证据在很大程度上仅限于细菌16S amplicon测序或小型回顾性病例对照研究。测试口腔细菌和真菌微生物中的口腔细菌和真菌微生物是否与HNSCC开发的风险相关。流行病学队列，美国癌症学会预防研究II营养队列，前列腺，肺，结直肠癌和卵巢癌筛查试验以及南方社区队列研究。在5。1（3.6）年的随访期间，发现了前瞻性开发HNSCC的26名患者。以2：1的频率匹配，年龄，性别，种族和种族以及自口头样本收集以来的时间，以2：1的频率匹配选择，以2：1的频率匹配选择了对照参与者。数据分析是在2023年进行的。使用全基因组shot弹枪测序和口服真菌微生物组对口腔细菌微生物组进行表征，并使用内部转录的间隔测序来进行口服真菌微生物组。细菌和真菌分类群与HNSCC的关联是通过分析具有偏置校正的微生物组的组成来评估的。通过逻辑回归测试了与红色和橙色口腔病原体复合物的关联。 HNSCC风险的微生物风险评分是根据风险相关的微生物群计算的。主要结果是HNSCC发病率。该研究包括236名HNSCC病例参与者，平均（SD）年龄为60.9（9.5）年龄（9.5）年龄，在平均为5.1（3.6）年龄的女性中，妇女的随访时间为5.1（3.6）年，并具有485名匹配的对照参与者。基线时的总体微生物组多样性与随后的HNSCC风险无关；然而，发现13种口腔细菌与HNSCC的发展有差异化。该物种包括新确定的唾液，sanguinis链球菌和瘦素种类，以及属于β和伽马蛋白细菌的几种物种。红色/橙色牙周病原体复合物与HNSCC风险中等相关（优势比，每1 SD 1.06； 95％CI，1.00-1.12）。微生物风险评分（基于22种细菌创建）的1-SD增加与HNSCC风险增加50％有关（多元优势比，1.50； 95％CI，1.21-1.85）。没有发现与HNSCC风险相关的真菌分类单元。此病例对照研究产生了令人信服的证据，表明口腔细菌是HNSCC开发的危险因素。所鉴定的细菌和细菌复合物以及其他危险因素有望识别高风险个体以进行个性化预防HNSCC。

The oral microbiota may be involved in development of head and neck squamous cell cancer (HNSCC), yet current evidence is largely limited to bacterial 16S amplicon sequencing or small retrospective case-control studies.To test whether oral bacterial and fungal microbiomes are associated with subsequent risk of HNSCC development.Prospective nested case-control study among participants providing oral samples in 3 epidemiological cohorts, the American Cancer Society Cancer Prevention Study II Nutrition Cohort, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, and the Southern Community Cohort Study. Two hundred thirty-six patients who prospectively developed HNSCC were identified during a mean (SD) of 5.1 (3.6) years of follow-up. Control participants who remained HNSCC free were selected by 2:1 frequency matching on cohort, age, sex, race and ethnicity, and time since oral sample collection. Data analysis was conducted in 2023.Characterization of the oral bacterial microbiome using whole-genome shotgun sequencing and the oral fungal microbiome using internal transcribed spacer sequencing. Association of bacterial and fungal taxa with HNSCC was assessed by analysis of compositions of microbiomes with bias correction. Association with red and orange oral pathogen complexes was tested by logistic regression. A microbial risk score for HNSCC risk was calculated from risk-associated microbiota.The primary outcome was HNSCC incidence.The study included 236 HNSCC case participants with a mean (SD) age of 60.9 (9.5) years and 24.6% women during a mean of 5.1 (3.6) years of follow-up, and 485 matched control participants. Overall microbiome diversity at baseline was not related to subsequent HNSCC risk; however 13 oral bacterial species were found to be differentially associated with development of HNSCC. The species included the newly identified Prevotella salivae, Streptococcus sanguinis, and Leptotrichia species, as well as several species belonging to beta and gamma Proteobacteria. The red/orange periodontal pathogen complex was moderately associated with HNSCC risk (odds ratio, 1.06 per 1 SD; 95% CI, 1.00-1.12). A 1-SD increase in microbial risk score (created based on 22 bacteria) was associated with a 50% increase in HNSCC risk (multivariate odds ratio, 1.50; 95% CI, 1.21-1.85). No fungal taxa associated with HNSCC risk were identified.This case-control study yielded compelling evidence that oral bacteria are a risk factor for HNSCC development. The identified bacteria and bacterial complexes hold promise, along with other risk factors, to identify high-risk individuals for personalized prevention of HNSCC.