The Use of Selected Ion Flow Tube-Mass Spectrometry Technology to Identify Breath Volatile Organic Compounds for the Detection of Head and Neck Squamous Cell Carcinoma: A Pilot Study

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common form of cancer worldwide, with approximately 630,000 new cases diagnosed each year. The development of low-cost and non-invasive tools for the detection of HNSCC using volatile organic compounds (VOCs) in the breath could potentially improve patient care. The aim of this study was to investigate the feasibility of selected ion flow tube mass spectrometry (SIFT-MS) technology to identify breath VOCs for the detection of HNSCC. Materials and Methods: Breath samples were obtained from HNSCC patients (N = 23) and healthy volunteers (N = 21). Exhaled alveolar breath samples were collected into FlexFoil® PLUS (SKC Limited, Dorset, UK) sampling bags from newly diagnosed, histologically confirmed, untreated patients with HNSCC and from non-cancer participants. Breath samples were analyzed by Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS) (Syft Technologies, Christchurch, New Zealand) using Selective Ion Mode (SIM) scans that probed for 91 specific VOCs that had been previously reported as breath biomarkers of HNSCC and other malignancies. Results: Of the 91 compounds analyzed, the median concentration of hydrogen cyanide (HCN) was significantly higher in the HNSCC group (2.5 ppb, 1.6–4.4) compared to the non-cancer group (1.1 ppb, 0.9–1.3; Benjamini–Hochberg adjusted p < 0.05). A receiver operating curve (ROC) analysis showed an area under the curve (AUC) of 0.801 (95% CI, 0.65952–0.94296), suggesting moderate accuracy of HCN in distinguishing HNSCC from non-cancer individuals. There were no statistically significant differences in the concentrations of the other compounds of interest that were analyzed. Conclusions: This pilot study demonstrated the feasibility of SIFT-MS technology to identify VOCs for the detection of HNSCC.

A Literature Review of the Potential Diagnostic Biomarkers of Head and Neck Neoplasms

“…The increase in ethanol was also found in head and neck squamous cell carcinoma (HNSCC) patients by Gruber et al, next to 2-propenenitrile and undecane ( 40 ), which discriminated patients from healthy controls and even patients with benign conditions with 77% sensitivity and 90% specificity. Hydrogen cyanide was found to be increased in the breath of HNSCC patients compared to controls using SIFT-MS and allowed discrimination with 91% sensitivity and 76% specificity ( 52 ).…”

Exhaled breath analysis in the diagnosis of head and neck cancer

“…In oral squamous cell carcinoma, a recent study used EBA and found three compounds (benzaldehyde, 3,7‐dimethylundecane, and butyl acetate) that have a relationship with pathological parameters of these cancers . The methods used for EBA of HNC patients so far include gas chromatography‐mass spectrometry, various nanomaterial‐based sensors and chemical ionization mass spectrometry …”

“…Recent research has analyzed exhaled breath to aid in early detection of HNC . An early attempt to analyze exhaled breath for diagnosis of HNC was conducted by Hakim et al (2011) who used breath gas testing with an artificial nose based on gold nanoparticle sensors.…”

Breath methane to hydrogen ratio as a surrogate marker of intestinal dysbiosis in head and neck cancer

“…Exhaled breath hydrogen and methane have been previously investigated as non-invasive, real-time surrogate markers of the fermentation status of the large bowel 9 , and changes in these exhaled compounds have been linked to colorectal cancer 10 and functional gastrointestinal disorders 11 . Breath volatile organic compounds (VOC) have also recently demonstrated promise as non-invasive biomarkers of HNSCC 12 .…”

“…and changes in these exhaled compounds have been linked to colorectal cancer 10 and functional gastrointestinal disorders 11 . Breath volatile organic compounds (VOC) have also recently demonstrated promise as non-invasive biomarkers of HNSCC 12 .…”