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Background: Microbiota has been found associated with the incidence of head and neck cancers (HNCs), however, the association of microbiota with the prognosis of HNCs remains unknown. In the present study, the relationship between tumoral microbiata and survival was examined. The prognosis predictive value of tumoral microbiota to complement classic TNM staging and Human Papillomavirus (HPV) status was also investigated.
Results: We conducted a retrospective study including 158 primary tumors using 16S rRNA sequencing. The tumoral microbiota in the HNC patients with poor prognosis were significantly different from that of the patients with good prognosis. A greater abundance of Schlegelella or Methyloversatilis was characterized in HNC patients with poor prognosis and a greater abundance of Lactobacillus or Bacillus was characterized in HNC patients with good prognosis. Strikingly, the microbial dysbiosis index (MDI), the ratio of above poor and good prognosis associated genera, was strongly associated with overall survival [hazard ratio (HR) 3.24; 95% confidence interval (CI), 1.88 to 5.59; P < 0.001] and disease free survival (HR 2.11; 95% CI, 1.34 to 3.34; P = 0.001), independently of age, TNM staging, differentiation and HPV status. Intriguingly, the combination of the MDI and HPV status significantly improved the prognostic performance of HPV status (AUC of 0.719 and 0.581 respectively, P = 0.024). Moreover, the MDI showed higher risk for overall survival in the late stage patients (HR 3.35; 95% CI, 1.73 to 6.49; P < 0.001) compared with the early stage patients (HR 2.41; 95% CI, 1.00 to 5.84; P = 0.051).
Conclusion: Together, the MDI could serve as an applicable indicator of the prognosis of HNCs, and complements the predictive values of TNM staging and HPV status. Moreover, the findings of the higher risk of the MDI in the late stage patients supply directions for future studies that microbial modulation might be valuable in survival improvement of HNCs, especially for the late stage patients.
Keywords
Microbiota, Head and neck cancer, 16s rRNA, Next-generation sequence, Microbial Dysbiosis, Human Papillomavirus, Prognostic indication
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This is a list of supplementary files associated with this preprint. Click to download.
- AdditionalFile1TableS1Baseline.docx
Additional file 1: Table S1 Patients and clinic-pathologiccharacteristics.
- AdditionalFile2TableS2TableS3.docx
Additional file 2: Table S2 Indices of alpha diversities between the head and neck cancer patients. Table S3 Epidemiological associations between micriobiota and head and neck cancer
- AdditionalFile2TableS3.pdf
(we also attached a PDF version of Table S3 to show the way we would like to present.)
- AdditionalFile3Supplementaryfiguresandlegends.pdf
Additional file 3: Figure S1. Time dependent ROC analysis of observed species and differentially abundant taxa. Figure S2. Univariate Cox regression of observed species, differential taxa, characteristics and overall or disease free survival. Figure S3. Association of reported HNC incidence associated taxa with overall or disease free survival. Figure S4. Profiles and compositions of tumoral microbiota in patients with clinic-pathological characteristics. Figure S5. Profiles and compositions of tumoral microbiota in patients with clinic-pathological characteristics-continued. Figure S6. Differentially abundant taxa identified amongst distinct prognoses or clinic-pathological characteristics.
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 21 Sep, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Microbiota has been found associated with the incidence of head and neck cancers (HNCs), however, the association of microbiota with the prognosis of HNCs remains unknown. In the present study, the relationship between tumoral microbiata and survival was examined. The prognosis predictive value of tumoral microbiota to complement classic TNM staging and Human Papillomavirus (HPV) status was also investigated.
Results: We conducted a retrospective study including 158 primary tumors using 16S rRNA sequencing. The tumoral microbiota in the HNC patients with poor prognosis were significantly different from that of the patients with good prognosis. A greater abundance of Schlegelella or Methyloversatilis was characterized in HNC patients with poor prognosis and a greater abundance of Lactobacillus or Bacillus was characterized in HNC patients with good prognosis. Strikingly, the microbial dysbiosis index (MDI), the ratio of above poor and good prognosis associated genera, was strongly associated with overall survival [hazard ratio (HR) 3.24; 95% confidence interval (CI), 1.88 to 5.59; P < 0.001] and disease free survival (HR 2.11; 95% CI, 1.34 to 3.34; P = 0.001), independently of age, TNM staging, differentiation and HPV status. Intriguingly, the combination of the MDI and HPV status significantly improved the prognostic performance of HPV status (AUC of 0.719 and 0.581 respectively, P = 0.024). Moreover, the MDI showed higher risk for overall survival in the late stage patients (HR 3.35; 95% CI, 1.73 to 6.49; P < 0.001) compared with the early stage patients (HR 2.41; 95% CI, 1.00 to 5.84; P = 0.051).
Conclusion: Together, the MDI could serve as an applicable indicator of the prognosis of HNCs, and complements the predictive values of TNM staging and HPV status. Moreover, the findings of the higher risk of the MDI in the late stage patients supply directions for future studies that microbial modulation might be valuable in survival improvement of HNCs, especially for the late stage patients.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
- AdditionalFile1TableS1Baseline.docx
Additional file 1: Table S1 Patients and clinic-pathologiccharacteristics.
- AdditionalFile2TableS2TableS3.docx
Additional file 2: Table S2 Indices of alpha diversities between the head and neck cancer patients. Table S3 Epidemiological associations between micriobiota and head and neck cancer
- AdditionalFile2TableS3.pdf
(we also attached a PDF version of Table S3 to show the way we would like to present.)
- AdditionalFile3Supplementaryfiguresandlegends.pdf
Additional file 3: Figure S1. Time dependent ROC analysis of observed species and differentially abundant taxa. Figure S2. Univariate Cox regression of observed species, differential taxa, characteristics and overall or disease free survival. Figure S3. Association of reported HNC incidence associated taxa with overall or disease free survival. Figure S4. Profiles and compositions of tumoral microbiota in patients with clinic-pathological characteristics. Figure S5. Profiles and compositions of tumoral microbiota in patients with clinic-pathological characteristics-continued. Figure S6. Differentially abundant taxa identified amongst distinct prognoses or clinic-pathological characteristics.
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