Dysbiotic microbiota to complement TNM staging or HPV status for prognostic indication of head and neck cancer

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.