Microbiome in Head and Neck Squamous Cell Carcinoma

Recruiting

• Conditions: Lip Cancer; Pharynx Cancer; Head and Neck Cancer; Oral Cancer
• Interventions: Diagnostic Test: Metagenomic sequencing; Diagnostic Test: Metabolic analysis

• Registration Number: NCT05837221
• Lead Sponsor: University of Colorado, Denver

Brief Summary

This study aims to determine whether dysbiosis actively contributes to HNSCC and if so, the underlying molecular mechanisms.

Detailed Description

HNSCCis a lethal cancer with a 5-year survival rate below 50%. Although smoking, alcohol intake, and human papillomavirus (HPV) infection are linked to HNSCC, only a small proportion of individuals exposed to these factors develop cancer and not all cases progress. Thus, additional environmental or host factors must contribute to HNSCC. The Study Team and others have observed significant oral dysbiosis in human HNSCC cases, both before and after treatment. This study aims to determine whether dysbiosis actively contributes to HNSCC and if so, the underlying molecular mechanisms.

Study Timeline

• Study First Submitted: 2023-04-19
• Study First Submitted QC: 2023-04-19
• Study First Posted: 2023-05-01
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-12
• Last Update Posted: 2024-01-16
• Study Start: 2024-12
• Primary Completion: 2028-01
• Study Completion: 2030-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Subjects equal to or above the age of 18.
2. Patients who are seen and evaluated by a provider within the adult Otolaryngology clinic at the University of Colorado Health.
3. Patients that present with a diagnosis of OSCC.
4. An equal number of age-matched patients who are visiting the clinic for reasons other than OSCC diagnoses, as the control group.
5. Ability to understand and willingness to sign a written informed consent document

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Exclusion Criteria

1. Subjects under the age of 18 or over the age of 100
2. Subjects unwilling to particiapte

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Oral Squamous Cell Carcinoma Saliva Sample Group	Metagenomic sequencing	Saliva will be collected at least 30 minutes after subjects stop eating, drinking, chewing gum, and smoking. Subjects will be instructed to spit saliva into a collection tube. The saliva will be split into two aliquots, one that is immediately frozen at -80C and one that is mixed 1:1 with pre-reduced tryptic soy broth, L-cysteine, and glycerol then frozen at -80C to preserve the viability of microorganisms.
Oral Squamous Cell Carcinoma Saliva Sample Group	Metabolic analysis	Saliva will be collected at least 30 minutes after subjects stop eating, drinking, chewing gum, and smoking. Subjects will be instructed to spit saliva into a collection tube. The saliva will be split into two aliquots, one that is immediately frozen at -80C and one that is mixed 1:1 with pre-reduced tryptic soy broth, L-cysteine, and glycerol then frozen at -80C to preserve the viability of microorganisms.
Non Oral Squamous Cell Carcinoma Saliva Sample Group	Metagenomic sequencing	Saliva will be collected at least 30 minutes after subjects stop eating, drinking, chewing gum, and smoking. Subjects will be instructed to spit saliva into a collection tube. The saliva will be split into two aliquots, one that is immediately frozen at -80C and one that is mixed 1:1 with pre-reduced tryptic soy broth, L-cysteine, and glycerol then frozen at -80C to preserve the viability of microorganisms.
Oral Squamous Cell Carcinoma Stool Sample Group	Metagenomic sequencing	Stool collection methods may differ depending on the patient. The aim is to collect fresh stool samples, those that are available will be collected during the study visit. If a patient is unable to give a sample at the visit, samples may be collected at home using the OMNIgene-GUT and OMNImet-GUT kits (DNA Genotek, Inc.).
Non Oral Squamous Cell Carcinoma Stool Sample Group	Metagenomic sequencing	Stool collection methods may differ depending on the patient. The aim is to collect fresh stool samples, those that are available will be collected during the study visit. If a patient is unable to give a sample at the visit, samples may be collected at home using the OMNIgene-GUT and OMNImet-GUT kits (DNA Genotek, Inc.).
Non Oral Squamous Cell Carcinoma Saliva Sample Group	Metabolic analysis	Saliva will be collected at least 30 minutes after subjects stop eating, drinking, chewing gum, and smoking. Subjects will be instructed to spit saliva into a collection tube. The saliva will be split into two aliquots, one that is immediately frozen at -80C and one that is mixed 1:1 with pre-reduced tryptic soy broth, L-cysteine, and glycerol then frozen at -80C to preserve the viability of microorganisms.
Oral Squamous Cell Carcinoma Stool Sample Group	Metabolic analysis	Stool collection methods may differ depending on the patient. The aim is to collect fresh stool samples, those that are available will be collected during the study visit. If a patient is unable to give a sample at the visit, samples may be collected at home using the OMNIgene-GUT and OMNImet-GUT kits (DNA Genotek, Inc.).
Non Oral Squamous Cell Carcinoma Stool Sample Group	Metabolic analysis	Stool collection methods may differ depending on the patient. The aim is to collect fresh stool samples, those that are available will be collected during the study visit. If a patient is unable to give a sample at the visit, samples may be collected at home using the OMNIgene-GUT and OMNImet-GUT kits (DNA Genotek, Inc.).

Primary Outcome Measures

Name	Time	Method
Characterize human dysbiosis	Day 1	Stool and saliva samples will be collected from participants, allowing us to reproduce human dysbiosis and analyze whether HNSCC affects one's microbiome composition. Metagenomic sequencing will be conducted through use of DNA extraction, library generation and Illumina sequencing. At least 30 million paired-end 2x150bp metagenomic reads will be generated per sample using the Illumina NovaSeq platform.
Characterize human metabolomics	Day 1	Through our stool and saliva samples we will be able to characterize metagenomic and metabolic signatures in treatment naïve OSCC and non-OSCC patients. Metabolic analysis will be conducted using LC/MS-based metabolic analysis. A targeted approach will quantify a panel of 30 componds including Trp pathway products, while a non-targeted approach, when applied to both lipid and aqueous phase compounds, will profile relative changes in compounds that may influence host and metabolic and immune statuses.
Integrative multi-omic data analysis and biomarker discovery	Day 365	We expect to find that specific sets of microbial and host factors interact with each other to promote OSCC.

Secondary Outcome Measures

Name	Time	Method
Impact of human dysbiosis on OSCC development in mice	Day 10-Day 100	Freshly collected saliva and stool samples from 10 subjects of each treatment category will be used to reconstitute microbiota.
Monitor tumor size	Day 10-Day 100	Tumor size (both weight and size) will be monitored using Bli-imaging. These measures will be assessed between treatment groups by ANOVA or analysis of variance testing.

Trial Locations

Locations (1)

University of Colorado Cancer Center; 🇺🇸 Aurora, Colorado, United States