Original Research Volatile Organic Compounds in the Breath of Oral Squamous Cell Carcinoma Patients: A Pilot Study Otolaryngology– Head and Neck Surgery 1–7 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2017 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599817711411 http://otojournal.org Stefan Hartwig, MD, DMD* 1 , Jan D. Raguse, MD, DMD, PhD* 1 , Dorothee Pfitzner, DMD 3 , Robert Preissner, DSc, PhD 2 , Sebastian Paris, DMD, PhD 3 , and Saskia Preissner, DMD, PhD 3 Sponsorships or competing interests that may be relevant to content are dis- closed at the end of this article. Abstract Objective. To assess the feasibility of detecting signature vola- tile organic compounds in the breath of patients with oral squamous cell carcinoma. Study Design. Prospective cohort pilot study. Setting. University hospital. Subjects and Methods. Using gas chromatography and mass spectrometry, emitted volatile organic compounds in the breath of patients before and after curative surgery (n = 10) were compared with those of healthy subjects (n = 4). It was hypothesized that certain volatile organic compounds disap- pear after surgical therapy. A characteristic signature of these compounds for diseased patients was compiled and validated. Results. Breath analyses revealed 125 volatile organic com- pounds in patients with oral cancer. A signature of 8 com- pounds that were characteristic for patients with oral cancer could be detected: 3 from this group presented were absent after surgery. Conclusion. The presented results confirmed the hypothesis of an absence of cancer-associated volatile organic compounds in the breath after therapy. In this pilot study, we proved the fea- sibility of this test approach. Further studies should be initiated to establish protocols for usage in a clinical setting. Keywords head and neck cancer, oral cancer, volatile organic com- pounds, VOCs, volatile biomarker, breath test, GC/MS, recurrence Received February 24, 2017; revised April 7, 2017; accepted May 3, 2017. O ral squamous cell carcinoma (OSCC) is still a cancer with poor outcome despite new therapeutic regimens that have appeared within the past decade. Each year, approximately 300,000 new occurrences of OSCC are diagnosed worldwide and approximately 145,000 patients die. 1 Numerous advances in surgical and nonsurgi- cal therapies, such as microvascular reconstruction, multi- modal regimens, and innovations in systemic therapies, especially for patients with advanced disease, have been developed, but the prognosis remains poor. 2 Oral cancer is usually diagnosed in the advanced stages: at the time of initial diagnosis, approximately 50% of patients are already in an intermediate or advanced stage of the disease. 3 Oral symptoms are rarely attributed to cancer and seem harm- less to patients, 4 but the early diagnosis of OSCC is of funda- mental importance for prognosis. 5 As there is currently no established testing procedure other than clinical inspection, there is an urgent need for new diagnostic approaches. Necessary screening programs for people at high risk (smokers and/or heavy drinkers) or in the posttherapeutic phase for recurrence detection are key factors for prognosis and are difficult to implement and sustain. The posttherapeu- tic phase of recurrence detection is standardized in most countries and essentially based on, besides clinical examina- tion, the diagnostic sensitivity of imaging such as magnetic resonance imaging, computed tomography, or one of those coupled with positron emission tomography. 6-9 Blood-related biomarkers, such as circulating tumor cells or cancer-related metabolites, are still under investigation. Biochemical diagno- sis of tumor-specific factors (so-called tumor markers) is of great interest, but in tumors of the head and neck area, to date they have no relevance in the clinical routine. 10-12 1 Department of Oral and Maxillofacial Surgery/Clinical Navigation, Charite ´– Universita ¨tsmedizin Berlin, Berlin, Germany 2 Institute of Physiology, Structural Bioinformatics Group, Charite ´– Universita ¨tsmedizin Berlin, Berlin, Germany 3 Department of Operative and Preventive Dentistry, Charite ´– Universita ¨tsmedizin Berlin, Berlin, Germany * Contributed equally to this work. Corresponding Author: Saskia Preissner, DMD, PhD, Department of Operative and Preventive Dentistry, Charite ´–Universita ¨tsmedizin Berlin, Assmanshauser Str. 4-6, 14197 Berlin, Germany. Email: saskia.preissner@charite.de