Biomedical Engineering Reference
In-Depth Information
22.3
Applications of saliva for early detection of ischemic heart
disease and in head and neck cancers
In this section, we will highlight a case study where saliva as a biological medium has been applied
to diagnose IHD and head and neck squamous cell carcinoma (HNSCC) at an early stage.
22.3.1
Salivary C-reactive protein levels as a proxy to diagnose ischemic heart
disease
C-reactive protein (CRP) is a marker of inflammation. CRP is a member of the class of acute-phase
reactants that mediates innate and adaptive immunity
[92]
. It is produced by the hepatocytes in
response to a variety of inflammatory cytokines
[93]
and may rise rapidly by as much as 1000-fold
or more after an acute inflammatory stimulus
[94]
. CRP has been shown to be an independent
predictor of cardiovascular events, and this biomolecule has also been proven to add prognostic
value to cardiovascular risk
[11,12]
.
We found that salivary CRP concentrations in 55 healthy volunteers ranged from 50.6 to
872.4 pg/mL. Using ranked statistical methods the derived reference interval in a healthy popula-
tion was
824 pg/mL. The mean CRP level in the saliva of healthy human volunteers was
285 pg/mL and in cardiac patients was 1680 pg/mL (P
,
,
0.01). Analysis of CRP concentrations in
paired serum and saliva samples from cardiac patients gave a positive correlation (r
2
0.84,
5
P
0.001) (see
Figure 22.2
).
,
22.3.2
Salivary DNA methylation as a proxy to diagnose head and neck cancer
HNSCC is the fifth most common cancer in men with an incidence of about 780,000 new cases per
year worldwide
[95]
. Despite advances in therapy, its prognosis has not markedly improved in the
past 20 years
[96]
. This is mainly caused by the late diagnosis of HNSCC, when cancer cells may
have metastasized to other parts of the body. HNSCC can affect the nasal passages, sinuses, mouth,
throat, larynx (voice box), swallowing passages, salivary glands, and thyroid gland and arise from
the surface epithelium. Tobacco use is a major risk factor for this type of cancer, and smoking kills
over 1,000,000 people a year, causing 30% of all cancer-related deaths in western societies. Yet,
one in three people worldwide is addicted to nicotine. In addition, 30% of HNSCC are a direct result
of human papillomavirus (HPV) infections
[97]
. Of all HPV types, the high-risk strains HPV16 and,
to a lesser extent, HPV18 are most commonly identified in oral squamous cell cancer biopsies
[98]
.
22.3.2.1
Current clinical work flow for head and neck cancer
HNSCC detection is currently based on an expert clinical examination of the upper aerodigestive
tract and histologic analysis of suspicious areas, but it may be undetectable in hidden sites, such as
crypts of the tongue base or tonsils.
22.3.2.2
Current unmet clinical need in head and neck cancer patient management
At present, there are no early detection/screening tests for head and neck cancers. At the time of
diagnosis of HNSCC, in 80% of the patients cancer cells may have already metastasized into other
parts of the body, resulting in a low 5-year survival rate.
