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.

EBV is classified as the group I human carcinogen and is associated with multiple cancers, including NPC. The interplays between the microbiota and oncovirus in cancer development remain largely unknown.

The dysbiosis of oral microbiota is linked to numerous diseases and is associated with personal lifestyles, such as alcohol drinking. However, there is inadequate data to study the effect of alcohol drinking on oral microbiota from the Chinese population. Here, we profiled the oral microbiota of 150 healthy subjects in the Chinese population by 16S rRNA gene sequencing. The results showed that drinkers had significantly higher alpha diversity than non-drinkers. A significant difference in overall microbiota composition was observed between non-drinkers and drinkers. Additionally, using DESeq analysis, we found genus Prevotella and Moryella, and species Prevotella melaninogenica and Prevotella tannerae were significantly enriched in drinkers; meanwhile, the genus Lautropia, Haemophilus and Porphyromonas, and species Haemophilus parainfluenzae were significantly depleted in drinkers. PICRUSt analysis showed that significantly different genera were mainly related to metabolism pathways. The oxygen-independent pathways, including galactose, fructose and mannose metabolism pathways, were enriched in drinkers and positively associated with genera enriched in drinkers; while the pyruvate metabolism pathway, an aerobic metabolism pathway, was decreased in drinkers and negatively associated with genera enriched in drinkers. Our results suggested that alcohol drinking may affect health by altering oral microbial composition and potentially affecting microbial functional pathways. These findings may have implications for better understanding the potential role those oral bacteria play in alcohol-related diseases.

Various biomarkers targeting cell-free DNA (cfDNA) and circulating proteins have been tested for pan-cancer detection. Oncofetal chondroitin sulfate (ofCS), which distinctively modifies proteoglycans (PGs) of most cancer cells and binds specifically to the recombinant Plasmodium falciparum VAR2CSA proteins (rVAR2), is explored for its potential as a plasma biomarker in pan-cancer detection. To quantitate the plasma ofCS/ofCSPGs, we optimized an ELISA using different capture/detection pairs (rVAR2/anti-CD44, -SDC1, and -CSPG4) in a case-control study with six cancer types. We show that the plasma levels of ofCS/ofCSPGs are significantly higher in cancer patients (P values, 1.2 × 10⁻² to 4.4 × 10⁻¹⁰). Validation studies are performed with two independent cohorts covering 11 malignant tumors. The individuals in the top decile of ofCS-CD44 have more than 27-fold cancer risk (OR = 27.8, 95%CI = 18.8–41.4, P = 2.72 × 10⁻⁶²) compared with the lowest 20%. Moreover, the elevated plasma ofCS-CD44 could be detected at the early stage of pan-cancer with strong dose-dependent odds risk prediction.

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.

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% CI = 0.61–0.76). When compared to a model constructed solely from clinical factors, including tumor stage, lymphatic metastasis, and perineural invasion, the predictive accuracy significantly improved with the addition of the MRS, resulting in a C-index rising to 0.77 (P = 2.33 × 10⁻⁵). Our findings suggest that oral microbiota biomarkers may contribute to personalized CRC monitoring strategies, their implementation in clinical surveillance necessitates confirmatory studies.