Restoration of the Oral Microbiota After Surgery for Head and Neck Squamous Cell Carcinoma Is Associated With Patient Outcomes

Abstract

ObjectiveTo evaluate the dynamics of the oral microbiome and associated patient outcomes following treatment of head and neck squamous cell carcinoma (HNSCC).Materials and MethodsThis was a prospective cohort study at a tertiary academic center in Hong Kong SAR of patients with head and neck squamous cell carcinoma evaluating the oral microbiome in pre- and postsurgery oral rinses (at 1, 3, and 6 months) with 16S rRNA gene V3–V4 amplicon sequencing.ResultsIn total, 76 HNSCC patients were evaluated. There was a significantly depressed alpha diversities of oral microbial communities observed in HNSCC oral rinse samples within the first 6 months post-surgery when compared to presurgery or healthy controls. Distant clustering between pre- and postsurgery was also observed (p < 0.022). Following treatment, eight oral bacterial genera showed a trend towards the restoration in the relative abundances that approximate healthy persons. In evaluating patient outcomes, the decreased relative abundance of three periodontal bacteria (Capnocytophaga, Prevotella 7, and Leptotrichia) and the increased relative abundance of two commensal bacteria (Streptococcus and Rothia) at 6 months postsurgery compared to presurgery showed a better 3-year disease-specific survival (a cutoff of Kaplan–Meier survival curve test p < 0.3 at 36 months). In particular, the postsurgery restoration of Prevotella 7 was statistically significant in the surveyed patients (survival rate of 84% vs. 56% at 36 months, p = 0.0065).ConclusionsOral microbiome dysbiosis associated with HNSCC is dynamic. These dynamics of the oral microbiome postsurgery are also associated with patient treatment and outcomes and may serve as potential biomarkers for patient management in HNSCC.

Oral Microflora in the Background of Oral Cancer: A Review

“…These patterns point to a post treatment shift in favor of bacterial populations that resemble healthy controls. It also reflects the previously observed reverse pattern of an increase in the relative abundance of Fusobacterium from healthy controls to patients with premalignant oral cavity lesions and lastly to patients with oral squamous cell carcinoma [25].…”

Effects of squamous cell carcinoma and smoking status on oropharyngeal and laryngeal microbial communities

“…12,13,22,34,[39][40][41] Interestingly, despite the widespread discussion of Fusobacterium as a marker for HNSCC, only two of the aforementioned seven publications mentioned Fusobacterium as either enriched in cancer patients or in cancer patients without metastases. 31,[40][41][42] Whereas different genera were reported as being enriched in the saliva of HNSCC there is agreement on some genera such as Neisseria, Rothia, or Porphyromona as characterizing healthy microbiota. An alternative to the use of saliva/oral rinse is the use of tissue biopsies, which may be compared either with an adjacent tissue and/or tissue from healthy controls.…”

“…On the first view various manuscripts are available to analyze the microbiota components that allow to differentiate between OPSCC or LSCC and the respective healthy microbiota. However, various authors analyze the effect of HNSCC on the oral microbiota (oral rinse or saliva) as proxy or biomarker and typically use patients suffering from oral or oropharyngeal cancer or even more general all kinds of HNSCC 12,13,22,34,39–41 …”

Oral microbiome as a new research-target for supportive care and precision oncology

“…HPV-positive HNC patients showed F. nucleatum enrichment in advanced tumour stages [28]. Post-surgical treatment, the oral rinse microbiota analysis showed that in patients with commensal bacteria reestablishment ( Streptococcus and Rothia ) and decrease of periodontal bacteria ( Capnocytophaga, Prevotella 7 , and Leptotrichia ), after 6-months of post-surgery had better disease-specific survival rates [24]. Patients with no history of OSCC have a higher abundance of Streptococcus, Granulicatella and Corynebacterium in the oral mucosa [22].…”

“…Fusobacteria at the treatment baseline was correlated with nonresponders [18]. Changes in the oral epithelium in vivo are strongly related to Socransky's red complex bacteria [19], mainly Porphyromonas gingivalis [14,20,21], Porphyromonas catoniae [22], and Fusobacterium nucleatum [23,24], for their immune-receptor upregulation and tight junction degradation capacity [25].…”