Smellprints in lung Cancer; the role of ENose in diagnosis and Treatment (SCENT):
part 4. Diagnostic value of the eNose in Head and Neck Cancer

Rationale: Head and neck cancer (HNC) is the fifth most common cancer worldwide
and the most common neoplasm in central Asia and accounts about for 2 to 3% in
U.S.A. mortality. HNC encompasses a variety of cancers, mostly (>90%) squamous
cell cancers (HN SCCs), arising from a variety of sites from oral cavity,
including lips, to larynx. The clinical presentation of HNC varies with the
primary site. Patient delay especially holds true for the deeper regions like
pharynx and larynx. In general dentists and general practitioners are the first
to be consulted when symptoms occur and lack experience. In the ideal situation
a rapid non invasive diagnostic test with high (especially negative)
predictive value would be of great value if available for dentist and GP.
Easy access to such a tool might lead to a diagnostic step in earlier phase of
the disease with better prognosis and prevent medical overconsumption. The
evolving field of exhaled breathmarkers might offer new opportunities in this
respect.
Exhaled breath contains a complex mixture of several hundreds of volatile
organic compounds (VOCs) . This could be established by gas chromatography and
mass spectrometry (GC-MS). It has been shown that distinct biochemical markers
have been found in the exhaled breath of patients with lung and breast
cancer that could be discriminated from those of controls, suggesting that VOC
analysis might be used as a non invasive marker of these cancers. After the
introduction of electronic noses, the sampling of exhaled breath and its
VOC-pattern (*breathprint*) has become readily available (*breatheomics*) based
on pattern recognition without analyzing the individual molecular components,
which potentially suffices for diagnostic objectives. The first studies by a
sensor array in detecting lung cancer have demonstrated promising diagnostic
accuracy showing that VOC patterns analysed by an electronic nose
discriminated patients with Non Small Cell Lung Cancer from COPD patients as
well as healthy controls. In our SCENT study 1 and 2 the diagnostic value of
eNose is being investigated in lung cancer and breast cancer.
In analogy with lung cancer there is evidence that HNCs can be discriminated by
VOCs from a recent study of Schmtuzhard and colleagues with proton transfer
reaction-mass spectrometry, where 42 different VOCs were found showing a
statistically significant difference between the carcinoma group and the
control groups. Maybe the electronic nose technique could be that rapid non
invasive screening tool in HNSCC.
Therefore in the present study, we hypothesize that an electronic nose can
discriminate the VOC pattern in exhaled breath between patients with Head and
Neck Cancer from healthy controls.

The primary objective of this study is:
to examine the difference in VOC pattern of exhaled air (breathprint) between
patients with histology-confirmed diagnosis of head and neck squamous cell
carcinoma (HNSCC) and healthy controls.
The secondary objectives are to investigate:
a. Whether the eNose can discriminate the breathprint of patients with HNSCC
from patients with lung cancer and mamma carcinoma, included in SCENT study 1
and 2.
b. Whether the eNose can discriminate between the breathprints of patients with
adenocarcinoma (NSCLC, mamma carcinoma) and squamous cell carcinoma (NSCLC,
HNSCC).
c. Whether the eNose can discriminate between the breathprints of HNSCC
patients before and after resection.

Open observational, case control study. In addition a (short) longitudinal
observational study in the resection-only-subgroup.

Patients and controls will visit the pulmonary function department one time.
Participants refrain from eating, drinking and smoking 3 hours prior to the
test. They first complete a questionnaire obtaining information about medical
history , smoking status and actual medical condition and then proceed with an
exhaled breath collection: exhaled vital capacity (VC) manoeuvre will be
performed after breathing for 5 minutes through a mouthpiece. Then spirometry
will be done. These investigations are part of the routine pulmonary function
testing and are safe procedures. Total investigation time will be less than 20
minutes. eNose testing might contribute to a simple non invasive diagnostic
process in future in patients with HNC.