Abstract 3326: Mucositis, candidiasis, and associations with the oral microbiome in treatment naive patients with oropharyngeal cancer
Authors: Pierce Christine M. , Hogue Stephanie , Paul Shirlene , Hong Bo-Young , Silva Wildson Vieira da , Gomez Maria F. , Giuliano Anna R. , Caudell Jimmy J. , Weinstock George M. 
Published: August 2019

Abstract
Purpose: Oropharyngeal cancer (OPC) incidence continues to increase dramatically in the US. Accumulating evidence suggests that oral microbiota (communities of microorganisms that reside in the oral cavity) may influence cancer treatment-related toxicities. We sought to examine the composition and diversity of oral microbiota in OPC patients prior to treatment, and identify associations between oral microbiota and subsequent development of oral mucositis (inflammation of mucous membranes) and candidiasis (fungal infection with Candida yeast).
Methods: 60 newly diagnosed, treatment naïve, OPC patients were recruited from Moffitt Cancer Center (2015-2017). Patients provided mouthwash-based oral gargles before starting chemoradiation or radiation. DNA was isolated using the QIAGEN DNeasy PowerSoil kit, and the V1-V3 region of the bacterial 16S rRNA gene was sequenced. An operational taxonomic unit table was generated and Ribosomal Database Project Classifier used to assign taxonomy. The development of oral mucositis (no/mild vs. severe) and candidiasis (no vs. yes) during treatment was abstracted from medical records. Comparisons of bacterial relative abundance (Mann Whitney U), alpha diversity (Chao1, Shannon, and Simpson), and beta diversity (Bray-Curtis) were performed in R and its extension (Phyloseq).
Results: Of 60 OPC patients, 65% were stage IV, 48% tonsillar and 42% base of tongue, and 40% never smokers. Pre-treatment levels of genus Klebsiella and class Gammaproteobacteria were significantly greater in the oral cavity of patients who had no/mild mucositis vs. those who developed severe mucositis (p&lt;0.04). Genera Atopobium and Mogibacterium, as well as families Coriobacteriaceae and Clostridiales Incertae Sedis, were significantly more abundant in patients who did not develop oral candidiasis compared to those who did (p&lt;0.04). Oral bacterial alpha diversity (intra-subject) was higher in patients who developed vs. did not develop severe mucositis, and lower in patients who developed vs. did not develop candidiasis during treatment. Analyses of beta diversity (inter-subject) showed that the microbial community structures were not significantly different by mucositis or candidiasis development.
Conclusions: Microbiome profiling may hold promise as a prognostic biomarker of treatment-related toxicities. Several potentially predictive taxa were identified to be differentially abundant in OPC patients who subsequently developed oral mucositis or candidiasis. Future analyses will evaluate the role of oral microbial resilience (the rate of recovery after disturbance) using oral specimens collected 3 mo. after treatment. Translational research focused on understanding how oral microbiota influence local immune and inflammatory responses may aid in the development of microbiota-based interventions to minimize adverse events.
Citation Format: Christine M. Pierce, Stephanie Hogue, Shirlene Paul, Bo-Young Hong, Wildson Vieira da Silva, Maria F. Gomez, Anna R. Giuliano, Jimmy J. Caudell, George M. Weinstock. Mucositis, candidiasis, and associations with the oral microbiome in treatment naive patients with oropharyngeal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3326.