Microbiome in Head and Neck Squamous Cell Carcinoma

Role of Human Microbiome in Head and Neck Cancer

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

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer; Oral Cancer; Pharynx Cancer; Lip Cancer
• Intervention / Treatment: Diagnostic test: Metagenomic sequencing; Diagnostic test: Metabolic analysis

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 Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Ijeoma Eleazu, Pharm.D; Phone Number: (303) 724-6550; Email: ijeoma.eleazu@cuanschutz.edu
• Study Contact Backup: Name: Kristi Engle Folchert; Phone Number: (303) 724-9528; Email: kristi.englefolchert@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Cancer Center
      • Contact: Ijeoma Eleazu, Pharm.D; Phone Number: 303-724-6550; Email: ijeoma.eleazu@cuanschutz.edu
      • Principal Investigator: Shi-Long Lu, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

We aim to enroll 60 patients total - 30 with oral squamous cell carcinoma (OSCC) who are treatment naïve, and 30 who are non-OSCC control patients, who will be age matched to their OSCC counterparts. Estimates show that Dr. Goddard's practice sees approximately 3 treatment naïve OSCC cases per month. We estimate that we can enroll 30-40 of these cases and an equal number of controls in the first 18 months of this study.

Description

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Oral Squamous Cell Carcinoma Saliva Sample Group; 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.	Diagnostic test: Metagenomic sequencing; Shotgun metagenomic sequencing will characterize cancer-associated changes in microbial functional capacity and species/strain-level taxonomic profiles. Metagenomics will provide data on microbial functional capacity along with broader taxonomic classifications.; Diagnostic test: Metabolic analysis; Metabolic analysis will be conducted using LC/MS-based metabolic analysis. A targeted approach will quantify a panel of 30 compounds 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
Non Oral Squamous Cell Carcinoma Saliva Sample Group; 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.	Diagnostic test: Metagenomic sequencing; Shotgun metagenomic sequencing will characterize cancer-associated changes in microbial functional capacity and species/strain-level taxonomic profiles. Metagenomics will provide data on microbial functional capacity along with broader taxonomic classifications.; Diagnostic test: Metabolic analysis; Metabolic analysis will be conducted using LC/MS-based metabolic analysis. A targeted approach will quantify a panel of 30 compounds 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
Oral Squamous Cell Carcinoma Stool Sample Group; 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.).	Diagnostic test: Metagenomic sequencing; Shotgun metagenomic sequencing will characterize cancer-associated changes in microbial functional capacity and species/strain-level taxonomic profiles. Metagenomics will provide data on microbial functional capacity along with broader taxonomic classifications.; Diagnostic test: Metabolic analysis; Metabolic analysis will be conducted using LC/MS-based metabolic analysis. A targeted approach will quantify a panel of 30 compounds 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
Non Oral Squamous Cell Carcinoma Stool Sample Group; 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.).	Diagnostic test: Metagenomic sequencing; Shotgun metagenomic sequencing will characterize cancer-associated changes in microbial functional capacity and species/strain-level taxonomic profiles. Metagenomics will provide data on microbial functional capacity along with broader taxonomic classifications.; Diagnostic test: Metabolic analysis; Metabolic analysis will be conducted using LC/MS-based metabolic analysis. A targeted approach will quantify a panel of 30 compounds 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize human dysbiosis	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.	Day 1
Characterize human metabolomics	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.	Day 1
Integrative multi-omic data analysis and biomarker discovery	We expect to find that specific sets of microbial and host factors interact with each other to promote OSCC.	Day 365

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of human dysbiosis on OSCC development in mice	Freshly collected saliva and stool samples from 10 subjects of each treatment category will be used to reconstitute microbiota.	Day 10-Day 100
Monitor tumor size	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.	Day 10-Day 100

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Shi-Long E Lu, MD, PhD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: April 19, 2023
• First Submitted That Met QC Criteria: April 19, 2023
• First Posted (Actual): May 1, 2023

Study Record Updates

• Last Update Posted (Actual): January 16, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Mouth Diseases; Lip Diseases; Head and Neck Neoplasms; Mouth Neoplasms; Pharyngeal Neoplasms; Lip Neoplasms
• Other Study ID Numbers: 23-0016.cc; P50CA261605 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No