RESUMO
BACKGROUND: Oral squamous cell carcinoma (SCC) is associated with oral microbial dysbiosis. In this unique study, we compared pre- to post-treatment salivary microbiome in patients with SCC by 16S rRNA gene sequencing and examined how microbiome changes correlated with the expression of an anti-microbial protein. RESULTS: Treatment of SCC was associated with a reduction in overall bacterial richness and diversity. There were significant changes in the microbial community structure, including a decrease in the abundance of Porphyromonaceae and Prevotellaceae and an increase in Lactobacillaceae. There were also significant changes in the microbial community structure before and after treatment with chemoradiotherapy, but not with surgery alone. In patients treated with chemoradiotherapy alone, several bacterial populations were differentially abundant between responders and non-responders before and after therapy. Microbiome changes were associated with a change in the expression of DMBT1, an anti-microbial protein in human saliva. Additionally, we found that salivary DMBT1, which increases after treatment, could serve as a post-treatment salivary biomarker that links to microbial changes. Specifically, post-treatment increases in human salivary DMBT1 correlated with increased abundance of Gemella spp., Pasteurellaceae spp., Lactobacillus spp., and Oribacterium spp. This is the first longitudinal study to investigate treatment-associated changes (chemoradiotherapy and surgery) in the oral microbiome in patients with SCC along with changes in expression of an anti-microbial protein in saliva. CONCLUSIONS: The composition of the oral microbiota may predict treatment responses; salivary DMBT1 may have a role in modulating the oral microbiome in patients with SCC. After completion of treatment, 6 months after diagnosis, patients had a less diverse and less rich oral microbiome. Leptotrichia was a highly prevalent bacteria genus associated with disease. Expression of DMBT1 was higher after treatment and associated with microbiome changes, the most prominent genus being Gemella Video Abstract.
Assuntos
Carcinoma de Células Escamosas , Microbiota , Neoplasias Bucais , Humanos , Neoplasias Bucais/terapia , Estudos Longitudinais , RNA Ribossômico 16S/genética , Microbiota/genética , Saliva/microbiologia , Bactérias/genética , Proteínas de Ligação ao Cálcio , Proteínas de Ligação a DNA , Proteínas Supressoras de TumorRESUMO
OBJECTIVE: Approximately one-third of advanced head and neck squamous cell carcinomas (HNSCCs) recur within 2 years of treatment. Due to ease of collection, saliva is of interest to monitor changes that correlate with treatment. Previously this was a challenge due to xerostomia after conventional radiation. The emergence of gland-sparing radiation has made it possible to collect saliva post-treatment. This study investigated changes in cytokines in saliva pre- and post-treatment to provide foundational knowledge for future studies exploring the use of saliva to monitor treatment response. STUDY DESIGN: Pre- and post-treatment saliva was evaluated for 8 cytokines by multiplex assay and enzyme-linked immunosorbent assay. RESULTS: In oropharyngeal HNSCC, secretion of epidermal growth factor (EGF), GROα (Growth-regulated protein alpha), interleukin (IL)-1α, IL-ß, IL-6, IL-8, tumor necrosis factor-α, and vascular endothelial growth factor increased significantly post-treatment. In additional patients, significant increases of GR-α and IL-6 were validated, but EGF showed no change. CONCLUSIONS: The uniqueness of this study is its comparison of salivary cytokines from HNSCC patients pre- and post-treatment.
Assuntos
Carcinoma de Células Escamosas/terapia , Citocinas/metabolismo , Neoplasias de Cabeça e Pescoço/terapia , Saliva/química , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVES: One of the main normal tissue toxicities in head and neck radiation oncology is xerostomia. In several studies, reduced radiation dose to the salivary glands has been shown to diminish the effects of gland dysfunction. However, no clear guidelines exist to define the anatomic location of the involved glands on cross-sectional imaging in a pragmatic manner. This study presents an anatomic, computed tomography (CT)-based definition of the major and minor salivary glands. METHODS: On the basis of information from normal structure anatomy, the location of major and minor salivary glands was identified and translated into a cross-sectional CT-based description of the salivary glands. RESULTS: The major salivary glands include the parotids and submandibular glands. The minor salivary glands are presented as a part of a surrogate structure (the Minor Oral Including Sublingual Salivary Tissue target), including the minor glands located in the oral mucosa of the tongue, hard and soft palate, buccal mucosa, and inner surface of the lips. CONCLUSIONS: Clinical implementation of CT-based delineations of the salivary glands according to the proposed guideline should reduce interobserver variability. This may lead to an improved understanding of the relationship between radiation dose and volume and effects on salivary function.