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Molecular Diagnostics

Development of a non-invasive exhaled breath test for the diagnosis of head and neck cancer



Improving the ability to identify early-stage head and neck squamous cell carcinoma (HNSCC) can improve treatment outcomes and patient morbidity. We sought to determine the diagnostic accuracy of breath analysis as a non-invasive test for detecting HNSCC.


Standardised breath samples were collected from 181 patients suspected of HNSCC prior to any treatment. A selected ion flow-tube mass spectrometer was used to analyse breath for volatile organic compounds. Diagnosis was confirmed by histopathology. A binomial logistic regression model was used to differentiate breath profiles between cancer and control (benign disease) patients based on mass spectrometry derived variables.


In all, 66% of participants had early-stage primary tumours (T1 and T2) and 58% had regional node metastasis. The optimised logistic regression model using three variables had a sensitivity and specificity of 80% and 86%, respectively, with an AUC for ROC curve of 0.821 (95%CI 0.625–1.0) in the testing cohort.


Breath analysis for non-invasive diagnosis of HNSCC appears to be practical and accurate. Future studies should be conducted in a primary care setting to determine the applicability of breath analysis for early identification of HNSCC.

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Author information




N.D. takes full responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: N.D., D.W., E.O., R.Y. Acquisition, analysis and interpretation: N.D., T.G., R.Y. Drafting of paper: N.D., R.Y. Critical revision of the paper for intellectual content: N.D., C.W., D.W., E.O., R.Y. Statistical analysis: N.D. Obtained funding: N.D., E.O., R.Y. Administrative: C.W. Study supervision: E.O., R.Y. No conflicts of interest were reported by any of the authors.

Corresponding author

Correspondence to Nuwan Dharmawardana.

Ethics declarations

Ethics approval and consent to participate

Ethical approval (HREC reference number HREC/16/SAC/70) was obtained from Southern Adelaide Local Health Network Human Ethics Committee with site-specific approvals for Flinders Medical Centre and Royal Adelaide Hospital, Adelaide, South Australia. Informed consent was obtained from all participants prior to sample collection. Local and international guidelines were followed as per the Declaration of Helsinki for research involving human participants.

Data availability

Modelling data are provided in this manuscript as well as in supplementary tables. Deidentified raw data is available upon request.

Competing interests

The authors declare no competing interests.

Funding information

Dr Dharmawardana was funded by the Garnett Passé and Rodney Williams Memorial Foundation—Academic Surgeon Scientist Research Scholarship. Associate Professor Ooi and Dr Yazbeck were funded by the Australia and New Zealand Head and Neck Cancer Society Foundation. Dr Yazbeck was also supported by the Catherine Marie Enright Kelly Research Fellowship.

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Dharmawardana, N., Goddard, T., Woods, C. et al. Development of a non-invasive exhaled breath test for the diagnosis of head and neck cancer. Br J Cancer 123, 1775–1781 (2020).

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