The global rise of non-communicable diseases (NCDs) presents an urgent public health challenge, particularly in regions undergoing rapid economic and demographic transitions. Guangdong Province, China’s most populous and economically advanced region, is experiencing a substantial and accelerating burden of NCDs. However, large-scale, population-based cohorts from this region remain scarce, limiting insights into region-specific disease determinants and prevention strategies. The Guangdong Biobank Cohort (GDBC) was established in 2017, enrolling 35,081 participants aged 40–84 years from urban and rural areas of Zhongshan City in the Pearl River Delta. At baseline, comprehensive data on 346 variables—including lifestyle, environmental exposures, medical histories, physical examinations, and laboratory profiles—were collected via a cloud-based member management information system (MMIS), alongside blood and saliva samples for biobanking. A sub-cohort underwent genome-wide genotyping (N = 2,530) and oral microbiome profiling via 16 S rRNA sequencing (N = 2,049). During dynamic follow-up, 44.2

Background: Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a distinct, Epstein-Barr virus (EBV)-associated subtype of non-small cell lung cancer (NSCLC) that occurs primarily in Asian populations. Despite its endemic distribution and distinctive clinicopathological features, the inherited susceptibility underlying pLELC remains undefined. Methods: We conducted a two-stage genome-wide association study (GWAS) of pLELC in Southern China, comprising discovery and independent validation cohorts with 771 cases and 7,162 cancer-free controls. We integrated GWAS findings with expression quantitative trait loci (eQTL)-informed gene-based association analysis (OTTERS and E-MAGMA) to identify susceptibility genes. We also compared the genetic architecture of pLELC with that of common NSCLC subtypes and other EBV-associated cancers. Findings: Three independent SNPs were associated with pLELC risk, including rs9357133 (OR 1·73, 95% CI 1·52-1·98, P=2·22×10-16) and rs145570027 (OR 0·33, 95% CI 0·25-0·42, P=1·08×10-18) at the HLA locus and rs3834970 (OR 1·44, 95% CI 1·26-1·65, P= 5·06×10-8) at 17q21·32. eQTL-informed gene-based analyses identified 15 susceptibility ge nes, including HLA class I genes (HLA-A/E/F/G) and SNX11. Lower expression of these genes was associated with reduced immune cell infiltration, higher intra-tumoral EBV transcription burden, and increased pretreatment CRP and NLR levels. Genetic comparison revealed that pLELC shared an HLA-driven immune susceptibility with nasopharyngeal carcinoma, while diverging from classical NSCLC by lacking typical smoking- and tumorigenesis-related susceptibility genes. Crucially, it presented a non-HLA susceptibility component characterized by SNX11, which distinguished pLELC from classical NSCLC subtypes and other EBV-associated cancers. Interpretations: This study delineates the inherited genetic architecture of pLELC, revealing an immune-driven etiology anchored by the HLA region, with SNX11 identified as a unique non-HLA susceptibility locus. These findings provide novel insights into the host genetic basis of this rare EBV-associated lung cancer.FundingNoncommunicable Chronic Diseases-National Science and Technology Major Project and National Natural Science Foundation of China.

The current Epstein–Barr virus (EBV) antibody-based screening strategy for nasopharyngeal carcinoma (NPC) has been used for years. However, its low positive predictive value (PPV) often leads to unnecessary diagnostic procedures. Thus, further triage strategies are needed. Saliva EBV DNA methylation and viral load were explored as noninvasive triage tools for NPC detection in this study. Saliva samples were collected from 621 NPC patients and 642 healthy controls recruited in Guangdong Province, China, between 2011 and 2014. The EBV DNA methylation and viral load were measured by real-time PCR, and the diagnostic performance was assessed for each biomarker individually and in combination using a logistic regression model. A simulation model was developed to evaluate the efficiency of a stepwise screening strategy integrating serum EBV antibody testing and saliva EBV DNA testing. Compared with the controls, EBV load was decreased while DNA methylation was increased in the saliva of NPC patients (both P < 0.0001). The area under the curve (AUC) values for saliva EBV DNA methylation and viral load in distinguishing patients from controls were 0.865 (95

Endometrial cancer (EC) incidence is rising globally, yet diagnosis still depends on invasive procedures, which limit accessibility and delay early detection. A noninvasive, accurate, and accessible diagnostic assay is urgently needed to enable early EC detection. In this multicenter diagnostic study across six hospitals in China (May 2021 - May 2026), we integrated whole-epigenome methylation profiling of 1,211 datasets followed by targeted bisulfite sequencing of 367 samples to identify EC-specific urine DNA methylation biomarkers. A qPCR-based urinary methylation assay (Urine-qEC) targeting three genes, VWC2, ZNF132, and ZSCAN12, was subsequently developed and validated in a cross-sectional multicenter cohort (n = 587). Urine hypermethylation signatures exhibited concordance with EC tumors and significantly diminished after tumor resection. The Urine-qEC assay achieved an AUC of 0.976 (89.4

BACKGROUND:Nasopharyngeal carcinoma is an aggressive malignancy originating from the nasopharyngeal mucosa and associated with genetic factors. Many nasopharyngeal carcinoma susceptibility loci have been identified by genome-wide association studies (GWASs), but their underlying functional insights are largely unexplained. RESULTS:A meta-GWAS including 5073 nasopharyngeal carcinoma patients and 5860 controls from nasopharyngeal carcinoma endemic areas identifies a total of 863 significant SNPs, including SNPs at a novel locus 3p24.1 (rs56365817; nearby genes: CMC1/EOMES). By integrating the GWAS signals with single-cell and bulk profiles, we find nasopharyngeal carcinoma susceptibility robustly associated with T cells in different methods and datasets. In nasopharyngeal carcinoma-associated cell type, we identify 234 putative susceptibility genes (81.62% of them novel), mainly enriched in immune-related biological processes. Five putative causal genes are prioritized. We perform in-depth bioinformatic analysis and functional experiments for EOMES, finding that the nasopharyngeal carcinoma-risk alleles of four functional SNPs upregulate EOMES expression by promoting the activity of regulatory elements in T cells, and EOMES participates in nasopharyngeal carcinoma tumorigenesis via regulation of CD8+ T cell exhaustion in the tumor microenvironment. CONCLUSIONS:This study uncovers novel nasopharyngeal carcinoma susceptibility genes and their functional cell types, which improves the understanding of nasopharyngeal carcinoma genetic etiology.

Objectives:Sleep health and other lifestyle behaviours are gaining increasing attention in public health, particularly for cancer prevention, but a comprehensive assessment is lacking. Methods:The study included 380,042 UK Biobank participants. A healthy sleep score was constructed based on five sleep factors: chronotype, sleep duration, insomnia, snoring, and daytime dozing. A healthy lifestyle score was constructed based on four lifestyle factors: smoking, alcohol consumption, diet and physical activity. The effect of healthy sleep and lifestyle on cancer risk was examined by Cox proportional hazard models. Results:Both healthy sleep and lifestyle patterns were significantly associated with a reduced risk of overall cancer and specific cancer sites. Participants with healthy sleep and lifestyle patterns had a lower risk of overall cancer (HR = 0.72, 95% CI = 0.68-0.77), liver cancer (HR = 0.53, 95% CI = 0.31-0.90), bladder cancer (HR = 0.61, 95% CI = 0.47-0.79), lung cancer (HR = 0.22, 95% CI = 0.19-0.27), and colorectal cancer (HR = 0.80, 95% CI = 0.66-0.96) compared to those with unhealthy patterns. Conclusion:Our findings highlight the importance of public health education and interventions to improve sleep and other lifestyle behaviours for cancer prevention.

Familial aggregation is common in nasopharyngeal carcinoma (NPC), yet the impact of oral microbiome dysbiosis on this occurrence remains largely unexplored. We recruit 127 families (649 members, 1-5 patients each) and a case-control cohort of 337 individuals, validating findings in an additional cohort of 995 individuals. Significant microbial similarity is observed among family members, with family factors contributing most to microbiome variation, followed by cigarette smoking, age, and gender. Among multi-NPC families, especially those with three or more patients, we identify three NPC-enriched taxa with notable heritability, including Gemella sp. (heritability, h2 = 53.1%), Lautropia mirabilis (h2 = 38.8%), and Streptococcus sp. (h2 = 38.0%). Heritable bacteria present a markedly higher heritability in families with increased clustering of NPC and form closely interacting networks, suggesting their role in NPC familial aggregation. These findings open up possibilities for identifying high-risk individuals, enhancing clinical surveillance, and developing personalized prevention and treatment approaches of NPC through microbiome-based strategies.

Epstein-Barr virus (EBV) has been implicated in several human cancers, but its broader cancer risk remains unclear. We investigated the association between EBV VCA-IgA antibody levels and cancer risk in two large prospective cohorts from Southern China, comprising 73,939 adults. During around 8-10 years follow-up, 964 and 1026 incident cancer cases were identified in the Zhongshan and Wuzhou cohorts. VCA-IgA seropositivity was associated with higher age-standardized incidence rates for total cancer significantly. In pooled analyses, VCA-IgA seropositive individuals had higher risks of total cancer (HR 4.88, 95% CI: 2.84-8.37), lung cancer (1.76, 1.23-2.54), liver cancer (1.70, 1.10-2.63), nasopharyngeal carcinoma (26.05, 11.77-57.65), and lymphoma (3.20, 1.46-6.99) compared to seronegative individuals. The associations showed an increased dose-response pattern, and keep persistent even up to ten years prior to diagnosis. The population-attributable risk percentage for total cancer due to VCA-IgA seropositivity is estimated at 7.8%. These findings provide prospective evidence that EBV seropositivity is associated with increased risks of multiple cancers. This association results in a heightened attributed cancer burden in Southern China.

Background Oral microbiome has been associated with various cancers, including nasopharyngeal carcinoma (NPC), but its role in cancer treatment and prognosis remains largely unknown. This study aims to address the dynamic changes in oral microbiome following cancer treatment and their prognostic implications in NPC patients.Patients and Methods Unstimulated whole saliva samples were collected from 23 NPC patients before and after treatment, with an average of 2.8 samples per patient, and post-treatment saliva samples were collected from additional 13 NPC patients that enrolled after treatment. Following DNA extraction and purification, the salivary microbiome was assessed by 16S rRNA gene amplicon sequencing targeting the V4 hypervariable region.Results Alpha-diversity of oral microbiome decreased progressively after treatment and during follow-up, and the beta-diversity of post-treatment samples differed significantly from the pre-treatment ones (R2 = 0.032, p < 0.001). Among patients free of disease progression, 31 oral taxa were identified that changed significantly in abundances after treatment, with 8 increasing and 23 decreasing. The declining taxa included two previously reported NPC-enriched bacteria, Lautropia mirabilis and Capnocytophaga sputigena. In contrast, in the only recurrent case, the abundances of the two bacteria did not decrease, but remained at high levels or even increased until recurrence occurred.Conclusion NPC treatment can cause persistent decline in microbial diversity of salivary microbiome and abundances of NPC-associated bacteria, and candidate bacteria could be an explanatory factor for NPC prognosis and deserve intensive research.

Genome-wide association studies (GWASs) have pinpointed many susceptibility loci for Hodgkin Lymphoma (HL), but their underlying biological mechanisms remain unclear. Utilizing GWAS data from the UK Biobank and FinnGen, along with expression quantitative trait loci (eQTL) statistics from the Genotype-Tissue Expression (GTEx) and the eQTL Catalogue, we carried out a large-scale gene-level association study using Omnibus Transcriptome Test with Expression Reference Summary data (OTTERS), and gene-based analysis with eQTL Multi-marker Analysis of Genomic Annotation (E-MAGMA). We identified sixteen susceptibility genes for HL (FDR < 0.01), primarily immune-related, including HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB1, HLA-DRB5, HLA-DMA, and HLA-DPB1, alongside genes involved in apoptosis, RNA processing, transcriptional regulation, and signal transduction. We identified five novel plausible genes, including HLA-DMA, HLA-DPB1, LSM2, AAR2, and NOTCH4. These findings highlight the role of the exogenous antigen presentation pathway in HL, shedding light on potential mechanisms.

Emerging evidence links oral-derived gut microbes to colorectal cancer (CRC) development, but CRC prognosis-related microbial alterations in oral remain underexplored. In a retrospective study of 312 CRC patients, we examined the oral microbiota using 16S rRNA gene full-length amplicon sequencing to identify prognostic microbial biomarkers for CRC. Neisseria oralis and Campylobacter gracilis increased CRC progression risk (HR = 2.63 with P = 0.007, HR = 2.27 with P = 0.001, respectively), while Treponema medium showed protective effects (HR = 0.41, P = 0.0002). A microbial risk score (MRS) incorporating these species effectively predicted CRC progression risk (C-index = 0.68, 95

Background and Objectives: The accurate discrimination between patients with and without cancer using their cell-free DNA (cfDNA) is crucial for early cancer diagnosis. The end-motifs of cfDNA serve as significant cancer biomarkers, offering compelling prospects for cancer diagnosis. This study proposes EM-DeepSD, a signal decomposition deep learning framework based on cfDNA end-motifs, which is aimed at improving the accuracy of cancer diagnosis and adapting to different sequencing modalities. Materials and Methods: This study included 146 patients diagnosed with cancer and 122 non-cancer controls. EM-DeepSD comprises three core modules. Initially, it utilizes a signal decomposition module to decompose and reconstruct the input end-motif profiles, thereby generating multiple regular subsequences that optimize the subsequent modeling process. Subsequently, both a machine learning module and a deep learning module are employed to improve the accuracy of cancer diagnosis. Furthermore, this paper compares the performance of EM-DeepSD with that of existing benchmarked methods to demonstrate its superiority. Based on the EM-DeepSD framework, we developed the EM-DeepSSA model and compared it with two benchmarked methods across different cfDNA sequencing datasets. Results: In the internal validation set, EM-DeepSSA outperformed the two benchmark methods for cancer diagnosis (area under the curve (AUC), 0.920; adjusted p value < 0.05). Meanwhile, EM-DeepSSA also exhibited the best performance on two independent external testing sets that were subjected to 5-hydroxymethylcytosine sequencing (5hmCS) and broad-range cell-free DNA sequencing (BR-cfDNA-Seq), respectively (test set-1: AUC = 0.933; test set-2: AUC = 0.956; adjusted p value < 0.05). Conclusions: In summary, we present a new framework which can achieve high classification performance in cancer diagnosis and which is applicable to different sequencing modalities.

BACKGROUND:Colorectal cancer (CRC) is a major global public health issue, with over 1.8 million new cases and 881,000 deaths in 2018. This study aims to explore the application of integrating microbiome and transcriptome analysis in the diagnosis of colorectal adenocarcinoma (COAD), focusing on its potential in identifying cancer biomarkers and predicting disease progression. METHODS:By utilizing COAD transcriptome and microbiome data from TCGA, diversity and differential expression analyses were conducted to identify microbiome composition differences between primary tumors (PT) and solid tissue normal (STN) samples, and the role of mRNA in prognosis. Mediation analysis was used to identify interactions between microbiome, transcriptome, in COAD tumors. The Multi-Omics Graph convolutional NET works (MOGONET) framework was employed to combine these data for COAD tumor prediction. RESULTS:Significant changes in microbiome composition and specific mRNA expression patterns were closely related to COAD development. It was observed that the Simplex virus genus can mediate the abundance of the BRAF transcripts, thereby affecting the risk of COAD. The MOGONET model demonstrated high accuracy in predicting COAD tumors, achieving 0.977 accuracy, 0.988 F1 score, and 1.0 AUROC. CONCLUSION:Integrating microbiome and transcriptome analysis shows significant potential in COAD diagnosis and prognostic assessment. These findings provide important insights for further clinical applications and cancer treatment strategies.

Objectives: This study aims to investigate the potential mediators for ethnic disparity in cervical cancer 5-year mortality and identify potential patients affected by ethnic disparities. Methods: The cohort study analyzed 56,374 cervical cancer patients from the Surveillance, Epidemiology, and End Results (SEER) 17 database (2000–2019). The primary and secondary outcome were the 5-year mortality of cervical cancer patients for all causes and cervical cancer-specific death, respectively. Cox and competing risks models were applied to identifying prognostic factors for 5-year cervical cancer all-cause mortality and specific death, respectively. Potential mediators for ethnic disparity were analyzed using multiple mediation analyses. Results: NHB patients had a 49% higher risk of 5-year mortality than NHW patients, while Hispanic and API patients showed a 19% and 12% decreased risk, respectively. Mediation analyses revealed that clinical stage and surgery predominately contributed to NHW-NHB prognosis disparities, with an indirect effect proportion of 29.6% and 26.7% for all-cause mortality and 34.2% and 26.7% for disease-specific death, respectively. No significant mediation effect was observed for other ethnic disparities. Compared to NHW patients, the inferior prognosis of NHB patients was observed mainly for localized and regional cancer, receiving hysterectomy, and, especially, adenocarcinomas. Conversely, the superior prognosis of Hispanic and API patients was observed in the no surgery subgroup and mainly for squamous cell carcinomas. Conclusions: Delayed diagnosis and a lack of surgery are key contributors to the prognosis discrepancy between NHB and NHW patients. More attention should be paid to NHB patients with cervical adenocarcinoma to narrow the disparity.

Saliva biopsy of nasopharyngeal carcinoma (NPC) has been developed in our latest study, indicating the application of oral sampling in NPC detection. Further exploration of the potential for self-sampling from the oral cavity is necessary. A total of 907 various samples from oral cavity, including saliva (n = 262), oropharyngeal swabs (n = 250), oral swabs (n = 210), and mouthwash (n = 185), were collected. Epstein‒Barr virus (EBV) DNA methylation at the 12,420 bp CpG site in EBV genome from the repeat-copy W promoter (Wp) region and at the 11,029 bp CpG site in the single-copy C promoter (Cp) region were simultaneously detected in these samples. A significant increase in EBV methylation, no matter at Wp or Cp region, was found in all types of samples from NPC patients. However, EBV DNA methylation in saliva and oropharyngeal swab showed a better diagnostic performance in detecting NPC. The combination of these two sample types and two markers could help to improve the detection of NPC. Our study further explored the optimal self-sampling methods and detection target in the detection of NPC and may facilitate the application of EBV DNA methylation detection in a home-based large-scale screening of NPC.

Background As an oncovirus, EBV is associated with multiple cancers, including solid tumors and hematological malignancies. EBV methylation plays an important role in regulating tumor occurrence. However, the EBV methylation profiles in EBV-associated tumor tissues are poorly understood. Results In this study, EBV methylation capture sequencing was conducted in several different tumor tissue samples, including NPC, EBVaGC, lung LELC and parotid LELC. Besides, EBV capture sequencing and following qMSP were performed on nasopharyngeal brushing samples from NPC and nasal NKTCL patients. Our results showed that the EBV genome among different types of tumors displayed specific methylation patterns. Among the four types of tumors from epithelial origin (NPC, EBVaGC, lung LELC and parotid LELC), the most significant differences were found between EBVaGC and the others. For example, in EBVaGC, all CpG sites within 1,44,189–1,45,136 bp of the EBV genome sequence on gene RPMS1 were hyper-methylated compared to the others. Differently, significant differences of EBV CpG sites, particularly those located on gene BILF2, were observed between NPC and nasal NKTCL patients in nasopharyngeal brushing samples. Further, the methylated level of BILF2 was further detected using qMSP, and a diagnostic model distinguishing NPC and nasal NKTCL was established. The AUC of the model was 0.9801 (95% CI 0.9524–1.0000), with the sensitivity and specificity of 98.81% (95% CI 93.63–99.94%) and 76.92% (95% CI 49.74–91.82%), respectively. Conclusions Our study reveals more clues for further understanding the pathogenesis of EBV, and provides a possibility for distinguishing EBV-related tumor by detecting specific EBV CpG sites.

Background and purpose: Radiation-induced brain injury (RBI) is a severe radiotoxicity for nasopharyngeal carcinoma (NPC) patients, greatly affecting their long-term life quality and survival. We aim to establish a comprehensive predictive model including clinical factors and newly developed genetic variants to improve the precision of RBI risk stratification.Materials and methods: By performing a large registry-based retrospective study with magnetic resonance imaging follow-up on RBI development, we conducted a genome-wide association study and developed a polygenic risk score (PRS) for RBI in 1189 NPC patients who underwent intensity-modulated radiotherapy. We proposed a tolerance dose scheme for temporal lobe radiation based on the risk predicted by PRS. Additionally, we established a nomogram by combining PRS and clinical factors for RBI risk prediction.Results: The 38-SNP PRS could effectively identify high-risk individuals of RBI (P = 1.42 x 10(-34)). Based on genetic risk calculation, the recommended tolerance doses of temporal lobes should be 57.6 Gy for individuals in the top 10 % PRS subgroup and 68.1 Gy for individuals in the bottom 50 % PRS. Notably, individuals with high genetic risk (PRS > P50) and receiving high radiation dose in the temporal lobes (D0.5CC > 65 Gy) had an approximate 50-fold risk over individuals with low PRS and receiving low radiation dose (HR = 50.09, 95 %CI = 24.27-103.35), showing an additive joint effect (Pinteraction < 0.001). By combining PRS with clinical factors including age, tumor stage, and radiation dose of temporal lobes, the predictive accuracy was significantly improved with C-index increased from 0.78 to 0.85 (P = 1.63 x 10(-2)).Conclusions: The PRS, together with clinical factors, could improve RBI risk stratification and implies person-alized radiotherapy.

Background: The nasopharyngeal brush sampling can effectively collect samples from the nasopharynx. The blind brush sampling does not require the guidance of endoscopy, which is favorable for implementation and dissemination in the community. This study explored methylation markers for nasopharyngeal carcinoma (NPC) at both Epstein–Barr virus (EBV) and its host genome levels, aiming to construct a blind brushing diagnostic method. Methods: EBV DNA capture and methylation sequencing and GEO Illumina 450K methylation array data were used respectively for the discovery of EBV and host methylation markers. The diagnostic method was built in training cohort ( n = 347) and validated in an independent validation cohort ( n = 155). Results: A total of 1 EBV methylation marker (BILF2) and 6 host methylation markers (ITGA4, IMPA2, ITPKB, PI9, AMIGO2, and VAV3) were identified. Both EBV and host methylation markers were almost exclusively detected in NPC samples, with negligible detection in control samples. In validation cohort, the diagnostic method that included only the EBV BILF2 marker showed a sensitivity and specificity of 80.22% and 98.44%, respectively. When combining the EBV-derived marker BILF2 with the host-derived marker IMPA2, the diagnostic method’s sensitivity increased to 84.62%, while the specificity remained unchanged (IDI = 4.4%, P = 0.0419). Conclusion: Overall, the blind nasopharyngeal brushing diagnostic method, combining EBV and host methylation markers, showed great potential in NPC detection and could promote its application in nonclinical screening of NPC.

Plasma levels of oncofetal chondroitin sulfate (ofCS)-modified CD44 have emerged as a promising biomarker for multi-cancer detection. Here, we explored its potential to predict the survival of patients with lung cancer. A prospective observational cohort was conducted involving 274 newly diagnosed patients with lung cancer at the Sun Yat-sen University Cancer Center from 2013 to 2015. The plasma levels of ofCS-modified CD44 were measured, and Cox regression analysis was performed to assess the association between plasma-modified CD44 levels and overall survival (OS) as well as other prognostic outcomes. Prognostic nomograms were constructed based on plasma ofCS-modified CD44 levels to predict survival outcomes for patients with lung cancer. Patients with high expression ofCS-modified CD44 exhibited significantly worse outcomes in terms of OS (HR = 1.61, 95%CI = 1.13-2.29, p = 0.009) and progression-free survival (PFS). These findings were consistent across various analyses. The concordance index of the prognostic nomogram for predicting OS in both the training set and validation set were 0.723 and 0.737, respectively. Additionally, time-dependent receiver operating characteristic (ROC) curves showed that the nomogram could serve as a useful tool for predicting OS in patients with lung cancer. Plasma ofCS-modified CD44 may serve as an independent prognosis marker for patients with lung cancer. Further validation of its predictive value could enhance prognostic assessment and guide personalized treatment strategies for patients with lung cancer.

The presence of oral microbes in extra-oral sites is linked to gastrointestinal cancers. However, their potential ectopically colonization in the nasopharynx and impact on local cancer development remains uncertain. Our study involving paired nasopharyngeal-oral microbial samples from nasopharyngeal carcinoma (NPC) patients and controls unveils an aberrant oral-to-nasopharyngeal microbial translocation associated with increased NPC risk (OR = 4.51, P = 0.012). Thirteen species are classified as oral-translocated and enriched in NPC patients. Among these, Fusobacterium nucleatum and Prevotella intermedia are validated through culturomics and clonal strain identification. Nasopharyngeal biopsy meta-transcriptomes confirm these microbes within tumors, influencing local microenvironment and cytokine response. These microbes correlate significantly with the Epstein-Barr virus (EBV) loads in the nasopharynx, exhibiting an increased dose-response relationship. Collectively, our study identifies oral microbes migrating to the nasopharynx, infiltrating tumors, impacting microenvironments and linking with EBV infection. These results enhance our understanding of abnormal microbial communication and their roles in carcinogenesis.