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Microbial community structure and its shift after laryngectomy in laryngeal squamous cell carcinoma (LSCC) patients were investigated. Thirty swab samples of LSCC prior to laryngectomy (SLC), 18 samples after 1-weeks laryngectomy (SLCA1w), and 30 samples after 24-week laryngectomy (SLCA24w) from 30 LSCC patients were sourced. Microbial diversity was profiled through sequencing the V3-4 variable region of the 16S ribosomal ribonucleic acid (rRNA) gene. Quantitative real-time polymerase chain reaction (qPCR) was used to validate the V3-4 region of 16S rRNA sequence data. The community structure and function of throat microbiota were assessed by PICRUSt analysis. Both Alpha and Beta diversity results showed significant differences in the throat microbiota of LSCC patients before and after laryngectomy (P < 0.05). Drinking index of SLC group was positively associated with the genus abundance of Prevotella (P < 0.05). SLCA1w group had lower abundance of Fusobacterium, Leptotrichia, Lachnoanaerobaculum and Veillonella compared to the SLC group (P < 0.05). SLCA24w group had higher abundance of Streptococcus and Leptotrichia, as well as the lower abundance of Fusobacterium and Alloprevotella compared to the SLC group (P < 0.05). The different propensity of throat microbiome of SLC group could implicate human cancer signaling pathways evident through Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis (P < 0.05). Our study clarifies altered throat microbial community structure and function in LSCC patients during the perioperative period and post-operative recovery period. Importance Laryngeal squamous cell carcinoma greatly impacts patient's livelihood, and non-invasive ways for prognostic assessment is valuable in determining the effectiveness of laryngectomy. We set to study the microbial structure changes in throat before and after laryngectomy and found the gene functions of several throat bacteria to be associated with human cancer signaling pathways. Our findings may offer insights into the disease management of patients with laryngeal squamous cell carcinoma. We hope to provide a perspective in molecular mechanisms to improve the prognosis of laryngeal cancer treatment and to facilitate relevant research.

Objective: High levels of red cell distribution width (RDW) may be associated with adverse outcomes in patients with cancer. The purpose of the present study was to investigate the prognostic impact of pretreatment RDW levels on overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) in a large cohort of male laryngeal squamous cell cancer (LSCC) patients. Methods: A total of 809 LSCC patients who were treated between 2007 and 2011 at the Eye & ENT Hospital of Fudan University were enrolled and evaluated retrospectively. OS, CSS, and DFS were analyzed using the Kaplan–Meier method. To evaluate the prognostic significance of RDW levels, univariate, and multivariate Cox analyses were applied. Results: Higher pretreatment RDW levels were significantly associated with high death events, red blood cell count, hemoglobin, radiotherapy, operation therapy, and advanced tumor stage ( p < 0.05). From the univariate analysis, we observed that the higher (13.2–13.5%) and the highest (>13.5%) quartiles of RDW level were consistent factors for poor OS, CSS, and DFS in LSCC patients. In the multivariate analysis, after adjusting for confounding factors, the higher and highest quartiles of RDW levels were identified as independent prognostic factors in male LSCC patients. Conclusion: Higher pretreatment RDW levels were demonstrated to be associated with poor clinical outcome in male LSCC patients and might be novel markers for patient stratification in LSCC management.

Background Dysbiosis of the laryngeal microbiota has been demonstrated to the development of head and neck squamous cell carcinoma (HNSCC), but the association of Fusobacterium and Fusobacterium nucleatum (F. nucleatum) with DNA mismatch repair (MMR) and microsatellite instability (MSI) has not been investigated. Methods The abundance of Fusobacterium and F. nucleatum, the status of deficient MMR (dMMR) and MSI, and MMR‐related gene expression were analyzed in 171 HNSCC tissues, 61 paired para‐tumor tissues, and 60 vocal cord polyp tissues. The molecular mechanism of F. nucleatum and MMR‐related gene expression were investigated in two human HNSCC cell lines (Tu 686 and FD‐LSC‐1). Results Our results demonstrated that a high Fusobacterium abundance was detected in the HNSCC tissues and was exaggerated in the recurrent patients. We further found that a high Fusobacterium abundance was detected in the HNSCC tissues with dMMR and MSI. The Fusobacterium abundance was negatively correlated with the expression of MLH1, MSH2, and MSH6 in the HNSCC tissues. The Fusobacterium abundance was closely associated with the F. nucleatum abundance in the HNSCC tissues. F. nucleatum increased miR‐205‐5p expression to suppress MLH1, MSH2, and MSH6 expression via the TLR4‐ and MYD88‐dependent innate immune signaling pathway, resulting in dMMR, DNA damage, and cell proliferation in HNSCC. Conclusions F. nucleatum impacts HNSCC epigenetic changes in tissues with dMMR to promote DNA damage and cell proliferation by suppressing MMR‐related gene expression via the TLR4/MYD88/miR‐205‐5p signaling pathway, which is valuable in the development of efficient strategies for HNSCC prevention and treatment. LAY SUMMARY This study clearly indicates that Fusobacterium induced head and neck squamous cell carcinoma (HNSCC) aggressiveness to affect poor prognosis in HNSCC patients by epigenetic alteration of DNA mismatch repair (MMR) and microsatellite instability. Moreover, the research has shown that Fusobacterium nucleatum ( F. nucleatum ) impacts HNSCC epigenetic changes in tissues with deficient MMR to promote DNA damage and cell proliferation by suppressing MMRrelated gene expression via the TLR4/MYD88/miR‐205‐5p signaling pathway.

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Aims To analyze changes in oropharynx microbiota composition after receiving induced chemotherapy followed by surgery for hypopharyngeal squamous cell carcinoma (HPSCC) patients. Methods Clinical data and swab samples of 38 HPSCC patients (HPSCC group) and 30 patients with benign disease (control group, CG) were enrolled in the study. HPSCC group was stratified into two groups: induced chemotherapy group (IC) of 10 patients and non-induced chemotherapy group (nIC) of 28 patients. The microbiota from oropharyngeal membrane was analyzed through 16S rRNA sequencing. Results Alpha-diversity (Shannon and Ace indexes) and weighted UniFrac based beta-diversity severely decreased in the HPSCC group when compared with CG. In pre-operative comparisons, PCoA and NMDS analyses showed microbial structures in the IC group were more similar to CG than nIC. Both IC group and nIC group yielded significantly diverse post-operative communities in contrast to their pre-operative counterparts, evident by the decrease in genera Veillonella and Fusobacterium and increase in genera Streptococcus and Gemella. Given that post-operative oropharynx microbiota showed no difference between IC and nIC groups, the IC group showed less accumulation in anaerobic communities. The abundance of genera Fusobacterium, Parvimonas, Actinomyces were enhanced in the advanced stages (III/IV). Conclusions Oropharynx microbiota in the HPSCC group presents dysbiosis with low diversity and abundance. Induced chemotherapy is beneficial in adjusting the oropharynx microbial environment leading to fewer amounts of anaerobe accumulation after operation. Higher amounts of Fusobacterium in advanced stages (III/IV) may influence the progression of HPSCC.

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