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Australian Dental Journal
The official journal of the Australian Dental Association
Australian Dental Journal 2013; 58:(1 Suppl): 85–94
doi: 10.1111/adj.12054
Minimum intervention dentistry in oral medicine
CS Farah,*† N Bhatia,*† K John,*† BW Lee*†
*UQ Centre for Clinical Research, The University of Queensland, Herston, Queensland, Australia.
†School of Dentistry, The University of Queensland, Brisbane, Queensland, Australia.
ABSTRACT
Oral medicine sits at the interface of medicine and dentistry. Minimum intervention dentistry (MID) borrows a medical
model of disease control by oral health professionals. As an oral physician, the oral medicine specialist practices MID on
a daily basis. With the advent of sophisticated early detection and diagnostic technology, and the growing understanding
of oral diseases at the microscopic and molecular levels, all oral health practitioners can contribute to the practice of oral
medicine from a MID perspective. MID in oral medicine allows the practice of comprehensive oral care where the
patient is fully engaged in their own healthcare, with the use of advanced diagnostic technology, the application of medicines and therapeutics depending on disease processes, important risk assessment of both the oral disease and the
affected patient with identification of those at high risk, monitoring of compliance, and patient recall. In this article we
highlight minimum intervention in oral medicine by exploring oral cancer as the most significant disease we encounter
and are involved with. Advances in patient care, particularly in relation to minimum intervention, are underpinned by
high calibre cutting edge translational research. It is this research that allows us to positively transform our patients’
lives.
Keywords: Minimum intervention dentistry, oral medicine, oral cancer, early detection.
Abbreviations and acronyms: AF = autofluorescence; CT = computerized tomography; HPV = human papillomavirus; IMRT = intensity modulated radiation therapy; IPCL = intrapapillary capillary loops; LED = light emitting diode; MID = minimum intervention dentistry; miRNA = microRNA; MRI = magnetic resonance imaging; NBI = narrow band imaging; OHT = oral health therapist; OSCC =
oral squamous cell carcinoma; PET = positron emission tomography; SNP = single nucleotide polymorphism.
INTRODUCTION
Minimum intervention dentistry – otherwise known
as MID – has been defined as a philosophy of professional care concerned specifically with three strategies,
namely: (1) disease risk assessment; (2) early disease
detection and diagnosis; and (3) minimally invasive
treatment.
Although this philosophy has mainly focused on
assessment and management of dental caries, minimum intervention in oral medicine is an equally developed strategy although it has received less widespread
attention, and has used different nomenclature and
terminology to define its activities over time. The definition of oral medicine, as approved by the Oral Medicine Academy of Australasia, is ‘The branch of
dentistry concerned with the diagnosis, prevention
and predominantly non-surgical management of medically-related disorders and conditions affecting the
oral and maxillofacial region, in particular oral mucosal disease and oro-facial pain, as well as the oral
health care of medically complex patients’. Given the
© 2013 Australian Dental Association
scope of conditions and diseases oral medicine specialists deal with, it could perhaps appear too difficult to
discuss minimum intervention strategies and philosophies that cover the broad aspects of this specialty.
Nevertheless, with the particular importance of minimum intervention as a paradigm shift in oral healthcare, and the near complete absence of open
discussion of issues pertinent to oral medicine in this
growing field of dentistry, here we highlight particular
aspects of oral medicine where minimum intervention
plays a prominent role.
It is interesting that minimum discussion has
occurred around the importance of MID in oral medicine, given that MID borrows a medical model of disease control by oral health professionals, and oral
medicine sits at the interface of medicine and dentistry.
As an oral physician, the oral medicine specialist practises MID on a daily basis. Here we argue that with
the advent of sophisticated early detection and diagnostic technology available in this field, and the growing understanding of oral diseases at the microscopic
and molecular levels, all oral health practitioners
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CS Farah et al.
can contribute to the practice of oral medicine from a
MID perspective.
MID in oral medicine allows the practice of comprehensive oral care where the patient is fully engaged
in their own healthcare, with the use of advanced
diagnostic technology, the application of medicines
and therapeutics depending on disease processes,
important risk assessment of both the oral disease
and the affected patient with identification of those at
high risk, monitoring of compliance, and patient
recall.
Recent and future advances in technology used for
early detection of oral mucosal pathology and the
rapid development of point-of-care oral-based diagnostics, will put the oral health professional centre
stage in the management of chronic oral diseases such
as oral precancerous and cancerous conditions. However, these advancements will also call on significant
understanding of risk, assessment of that risk, and the
use of saliva, and other oral fluids and tissues for
monitoring of disease and disease risk. Fundamentally,
this necessitates upskilling the oral health workforce
and comprehensive utilization of oral health professionals such as oral health therapists (OHTs). Oral
health therapists are uniquely positioned to assist in
the long-term maintenance of oral medicine conditions, many of which are chronic in nature, given
their training in health promotion and provision of
preventive clinical services. Indeed, one can argue that
with the development of point-of-care oral-based
diagnostics, both dentists and OHTs need to be even
more familiar and competent with systemic diseases
affecting their patients and the ramifications of detection and potential diagnosis of these conditions using
technology. This is not as futuristic as it might seem.
MID in oral medicine supports the argument that
OHTs need to be better utilized in the context of oral
health prevention and health promotion, and that
dentists need to view themselves more as oral ‘physicians’ and less as oral ‘surgeons’ or indeed oral ‘engineers’. With the future of ‘personalized medicine’
upon us, it is vital that all oral health practitioners
engage with MID as it lies at the heart of personalized
medicine, particularly in the context and framework
of oral medicine.
Many oral diseases or oral manifestations of systemic diseases could be used to highlight the application of MID in oral medicine. These include, but are
not limited to, oral cancer and potentially malignant
mucosal pathology; head and neck cancer treatment
and long-term dental follow-up; mucocutaneous diseases; tooth erosion and salivary dysfunction; temporomandibular joint disorders and orofacial pain
conditions. Inasmuch as disease processes can be used
to highlight MID in oral medicine, technology can
also be used to frame this philosophy in everyday
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practice. Autofluorescence (AF) imaging, narrow band
imaging (NBI), oral spectroscopy, exfoliative brush
biopsy,
endoscopy/endomicroscopy,
point-of-care
saliva-based diagnostic, cone beam volumetric tomography, molecular diagnostics, cancer stem cell therapy,
and molecular imaging are but some of these varied
technologies at different stages of penetration and performance in oral medicine which are important to the
true practice of MID in oral medicine.
At the heart of MID in oral medicine though, is an
appreciation of people rather than diseases or technology, and proper training in disease recognition/
diagnosis. ‘People’ in this context though does not
only pertain to health practitioners, but more importantly to the patients we serve, consult, diagnose, care
for, manage, treat and educate. There can be no real
patient and disease risk assessment without a fundamental engagement with the patient at risk. There
cannot be minimum intervention without an understanding of risk factors, lifestyle risks, genetic risks,
health behaviour management strategies, the importance of monitoring and long-term maintenance and
compliance. Patient engagement and education is core
to MID in oral medicine as it is in minimum intervention broadly. Long gone are the days where the
practitioner dispenses treatment or a script for medication without truly engaging the patient and explaining the need, mode of operation, expected outcomes,
and adverse effects of therapeutics. And long gone are
the days where a patient is referred for diagnostic
services without truly comprehending the expected
outcomes, health risks and benefits. If MID in oral
medicine is to grow and flourish, and if oral medicine
as a specialty is to do the same, then practitioner and
patient engagement and education are paramount.
From our perspective, MID in oral medicine highlights an opportunity for integrated comprehensive
oral healthcare where the oral medicine specialist,
dentist, oral health therapist and others work as a
team to deliver healthcare of the highest standard,
through a well-formulated treatment plan that is executed based on accurate diagnostic information, and
delivered in accordance with an evidence-based
agenda at precise time points for distinct benefits.
In the context set above, we will explore these
concepts as they apply to the most important and
deadly of oral diseases: oral cancer. Here we will use
oral cancer as an example to highlight the practical
aspects of MID in oral medicine. We will reflect on
early detection technology such as AF and NBI,
molecular and salivary diagnostics, and molecular
imaging in head and neck cancer. In doing so, we will
highlight personalized medicine in the context of oral
cancer and also the shifting aetiology, changes to our
understanding of the pathogenesis, and management
strategies for this important disease.
© 2013 Australian Dental Association
MID in oral medicine
DISEASE RISK ASSESSMENT
Molecular and salivary diagnostics
Populations at high risk of developing oral cancer are
predominantly older, male, heavy users of alcohol and
tobacco, often associated with a poor diet and low
socio-economic status. Human papillomavirus (HPV)
has emerged as a major aetiological factor, creating a
new and enlarging subset of head and neck cancers,
predominantly arising from the tonsil, base of tongue
and oropharynx. With the increase in the incidence of
HPV-related oral squamous cell carcinoma (OSCC),
the demographics of the typical high risk patient are
likely to change as these lesions are diagnosed at
younger ages than non-HPV related SCC. Since the
prevalence of disease is higher in high risk groups,
risk assessment should be focused on these populations in order to better utilize human resources, but
also to affect better outcomes for the populations
involved.
HPV-related OSCC has emerged as a new and
growing subset of head and neck cancers, with HPV
status greatly influencing clinical features and prognosis.1 The aetiology and epidemiology of this group is
different to that of non-HPV related OSCC and management of this disease should be customized so as to
effectively treat patients, improving the prognosis and
patients’ quality of life. In order to achieve this, on
par with current scientific knowledge, it is important
to profile the molecular pathogenic mechanisms
underlying HPV-related OSCC, to aid in early diagnosis and appropriate treatment. It has been shown that
16–62% of OSCC develop from potentially malignant
oral leukoplakia.2
A potentially malignant lesion is defined as ‘a morphologically altered tissue in which cancer is more
likely to occur than in its normal counterpart’ – i.e.
the lesion itself can undergo malignant transformation. Leukoplakia and erythroplakia are examples of
potentially malignant lesions. Leukoplakia is the most
common potentially malignant lesion of the oral cavity and may be clinically homogenous or non-homogenous, nodular or speckled, including Candidaassociated lesions and proliferative verrucous leukoplakia. Erythroplakia carries the greatest threat of
malignant transformation, with 50% of cases already
being malignant at the time of diagnosis. Dysplastic
lesions may be graded histologically as mild, moderate
or severe; however, this is highly subjective with low
interpersonal and intrapersonal reproducibility. Dysplasia is considered to be ‘the histopathological
expression of genomic and molecular alterations in a
field of keratinocytes’ with a reported prevalence of
5% to 25% of epithelial dysplasia in oral leukoplakia.3
© 2013 Australian Dental Association
HPV has been detected in 26.2% of leukoplakia
with dysplasia and other precancerous intraepithelial
oral cancers.4 Up to 30% of oral leukoplakia may
recur,5 and oral cancer may develop in 12% of treated sites of leukoplakia.6 It is clear that some treated
leukoplakias will recur or undergo malignant transformation, but there are no current diagnostic methods,
clinical, histological, or molecular, to predictably
identify these cases.4
HPV-related OSCC is non-keratinizing and more
common in non-smoking and non-drinking 40–60 year
old males, a category distinctly separate to non-HPV
related OSCC, and has been termed a sexually
transmitted disease.1,7 The viral particle gains access
into the basal cells (consisting of stem cells and
transit-amplifying cells) through microabrasions of the
epithelial tissue.8 The stem cells need to be infected for
the infection to be maintained since it is these cells that
continuously divide to replace the lost superficial layer
cells through desquamation.8 The viral early genes are
expressed while the keratinocyte is in the basal or
parabasal layer, while the late genes are expressed as
the keratinocyte reaches the upper spinous, stratified
or cornified layers.9 Persistent infection, which the
host immune system has been incapable of clearing,
has been deemed a causal factor for cervical cancer.10
The reason for the presence of HPV DNA in the
oropharynx has been attributed to changing sexual
behaviour, multiple sexual partners, and earlier sexual
debut.11
MicroRNAs (miRNAs) have emerged with a great
potential as diagnostic and therapeutic aids. miRNAs
belong to a family of small, non protein-coding RNAs
that have been shown to regulate up to 60% of all
mRNAs.12 To date, there are 2042 mature miRNAs
and 1600 precursor miRNAs.13 In normal function,
miRNAs control important cellular processes such as
cell division, differentiation and apoptosis14 in a network of interlaced processes that are tightly controlled
and coordinated with large co-expression patterns.15
However, in cancer these networks are reprogrammed,
forming smaller, disjointed networks that form cliques
with over or under-expression of miRNAs. These
miRNAs may function either as oncogenes that drive
tumour growth or as tumour-suppressor genes that
normally serve as protective mechanisms against carcinogenesis but are down-regulated, allowing tumour
initiation and progression.16
miRNA expression dysregulation is central in its
role in carcinogenesis. miRNAs involved in cancers
are frequently located in genomic loci known to be
fragile,17 with chromosomal alterations shown to
affect miRNA levels and carcinogenesis.18 Single
nucleotide polymorphisms (SNPs) in the miRNA gene
have also been shown to cause aberrant miRNA formation and under/over expression.19
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miRNAs in saliva are thought to be derived from
tumour tissues through studies which reported
decreases in miRNA levels following cancer resection
surgery.20,21 However, there is a gap in our knowledge comparing miRNA expression profiles in
tumour tissues to that in saliva. There are currently
nearly 45 miRNAs that have been quantified as being
involved in oral cancer. The discovery of miRNAs
and its role in cancer has allowed a greater understanding of the molecular basis of oral cancer tumourigenesis. Although the field is relatively new, it is
maturing at a rapid pace, with continual refinements
in research methodology allowing for more comparable data to be found.
Saliva is an attractive medium for oral cancer biomarker detection due to the non-invasive nature of
collection and the fact that it is in constant contact
with the oral epithelium.22 Previous research into saliva as a source for biomarkers focused on proteomics,23 which has proved to be difficult for a myriad
of reasons. However, salivary miRNA has been found
to be remarkably stable, and able to resist degradation
much better than non-salivary miRNA.
The use of saliva as a biomarker may potentially
allow for non-invasive salivary diagnostics to be conducted for oral cancer, providing another tool that the
clinician may employ in the detection of these lesions
and their precursors. It is anticipated that the discovery of comparable miRNA signatures in saliva and in
tumour tissues, as well as changes in salivary miRNA
signatures will allow the development of non-invasive
salivary diagnostic biomarker panels.
Given the rapid speed with which our understanding
of the role of HPV in oral/oropharyngeal cancers is
developing, the explosion of new molecular targets to
assay, and the developing pace of saliva-based point
of care diagnostics, it is no wonder that a radical
re-think/paradigm shift is occurring in the way we
approach oral cancer risk assessment. With this new
information that is available to us, there is more
responsibility on us as a profession to educate our
patients about the emerging role of oral sexual behaviour as a means for transmission of HPV, and to undertake sexual histories. Although saliva based diagnostic
tests are available for determining HPV genotypes in
the ease of the dental surgery (OraRisk® HPV Salivary
Diagnostic Test, OralDNA Labs), the usefulness of
these in patient management is yet to be determined.
EARLY DISEASE DETECTION AND DIAGNOSIS
Early detection technology
The poor prognosis for oral malignancies can largely
be attributed to the late diagnosis of these cancers. Patients with a delayed diagnosis of oral or
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oropharyngeal carcinoma are 30% more likely to
present with an advanced stage tumour compared to
those without a delayed diagnosis.24–26 There is a significant decrease in prognosis with a more advanced
TNM stage at initial presentation. The five-year survival rates for Stage I and II tumours are 85% and
66% respectively, while the survival rates decrease for
Stage III and IV tumours to 41% and 9%.27
Alarmingly, almost half of all oral cancers are diagnosed at Stage III or IV.24 As such, emphasis is being
placed on increased public awareness and earlier
detection of oral cancer to improve patient survival
rates. It is well established that the majority of oral
cancers are preceded by potentially malignant lesions.
However, many of these same lesions may remain
benign in nature or resemble other benign mucosal
abnormalities. Leukoplakia and erythroplakia are the
most common lesions to precede oral cancer although
others such as oral lichen planus and submucous
fibrosis may also progress to malignancy. Current
practice for the detection of malignant or potentially
malignant lesions involves a visual and tactile mucosal
examination under an incandescent overhead light by
a dental practitioner. White or red lesions exhibiting
induration or fixation may be indicative of malignancy.28 These lesions are typically referred to an oral
medicine specialist for biopsy and a definitive diagnosis. A conventional oral examination may not necessarily detect or identify all potentially malignant or
malignant lesions. While screening programmes to
identify malignant lesions have been trialled, their
cost-effectiveness in the general population is uncertain and the onus has fallen on primary care providers
to screen patients for such lesions.29–32
A number of diagnostic aids have recently been
developed to assist the general dental and medical
practitioner in detecting premalignant and malignant
lesions, and to differentiate these from benign lesions.
Light based systems have been developed for this purpose,33–36 although these, on the whole, have not proven to be beneficial in providing the practitioner with
useful information to assist in identification or diagnosis of suspicious lesions. Microlux/DLTM (AdDent Inc)
is a handheld battery operated light emitting diode
(LED) white light device which can be used on
patients for assessment of an oral lesion. McIntosh
et al. have used this device following a conventional
oral examination under incandescent overhead light
for examination of suspicious oral mucosal lesions.37
While lesion visibility was enhanced compared to a
regular incandescent light, Microlux/DLTM did not
help uncover any new lesions or alter the provisional
diagnosis or biopsy site. It was also poor in helping
discriminate between benign and malignant or potentially malignant lesions. A LED headlight displayed
similar properties to Microlux/DLTM in increasing
© 2013 Australian Dental Association
MID in oral medicine
lesion visibility and allowed for an even greater field
of view. They found that white light was more beneficial compared to routine incandescent operatory light
in the detection of oral mucosal lesions and have been
advocating more widespread use of LED headlights
for examination of oral mucosal pathology since.
In contrast to devices that utilize white light and
the properties of reflectance, several diagnostic aids
utilize the features of AF. These include handheld
devices designed for use in dental practice such as
VELScopeTM (LED Dental Inc)35 and IdentafiTM (StarDental)33 and endoscopic devices such as the Wolf
Diagnostic Auto-fluorescence Endoscope. These
devices use AF to differentiate benign mucosa from
malignant and potentially malignant lesions. They
typically emit blue/violet light in the 400–460 nm
wavelength range, causing the oral mucosa to fluoresce due to the presence of intrinsic fluorophores,
collagen and cross-links between collagen.38 The AF
profile of a tissue is altered by absorption and scattering events in the tissue. Normal oral mucosa is associated with a pale green fluorescence while abnormal
tissue is associated with a loss of AF in this wavelength, largely due to changes in the concentration of
fluorophores and structural modifications such as
increased epithelial thickness, altered collagen content
and nuclear size distribution.38 These visual changes
can be used in vivo to differentiate normal oral
mucosa from dysplasia, carcinoma in situ and invasive
carcinoma.39 AF has also proven to be a valuable tool
in demarcating margins of established tumours where
the malignant tissue may extend beyond what is
otherwise clinically visible.40
Only recently have trials become available evaluating the use of AF in a clinical environment. Mehrotra
et al. reported the detection of 11 cases of dysplasia
and 1 case of oral cancer of which 6 demonstrated
loss of AF providing a sensitivity of 50%.41 Among
the 144 benign lesions evaluated, 88 lesions demonstrated a loss of AF giving an overall specificity of
38.9% and a positive predictive value of 6.4%. Awan
et al. conducted a prospective study evaluating the
accuracy of AF compared to a clinical and subsequently histological exam at specialist oral medicine
clinics.42 When correlated with histology, 44 lesions
proved to be dysplastic of which only 7 retained AF,
giving a sensitivity of 84.1%. However, the specificity
was relatively low at 15.3% with 61 out of the 72
non-dysplastic lesions also exhibiting some loss of AF.
A similar study by Scheer et al. on a high risk population reported a sensitivity and specificity of 100% and
80.8% respectively.43 The authors found that lesions
presented along a spectrum ranging from marked
decrease in AF to an increase in fluorescence.
While the above studies evaluated the diagnostic
capabilities and accuracy of AF without taking into
© 2013 Australian Dental Association
account clinical characteristics in the diagnosis, it
should be remembered that the main function of these
devices is to be an adjunctive aid to, rather than a
replacement for, a conventional oral examination. For
this reason, Farah et al. prospectively evaluated what
additional benefits AF provided when used in conjunction with an oral examination by oral medicine specialists.44 The accuracy of a conventional oral
examination, an AF examination, and both in combination were compared. In addition, the study evaluated whether AF altered the biopsy site or provisional
diagnosis. They also tested for diascopic fluorescence
of lesions with those displaying complete blanching
on pressure being deemed negative for loss of AF. A
histopathological gold standard was used. While the
diagnostic accuracy increased with the use of AF in
conjunction with clinical examination, the rate of
false positives also increased. This confirmed findings
from previous trials on the poor diagnostic accuracy
of AF findings without proper clinical interpretation.42,43
AF enhanced the visualization of 34.74% of lesions
and helped uncover 5 clinically occult lesions of
which one was moderately dysplastic. Further, the use
of AF altered the provisional diagnosis in 22 cases
and altered the biopsy site of 4 lesions. It was
observed that blanching of lesions was difficult to perform accurately, and partial blanching in particular
may complicate interpretation. Like Scheer et al.,
Farah et al. expressed concerns regarding clinical
interpretation and stated that advanced knowledge of
mucosal pathology was required to accurately interpret the findings of AF.43,44
The study by Farah et al. showed that although AF
could provide useful information to assist in the identification and diagnosis of lesions when used in conjunction with a conventional oral examination under
white light, its use may be more suitable to a specialist oral oncology setting due to the difficulties in accurate interpretation of findings, without proper training
and skill.
AF is able to differentiate between normal mucosa
and mucosal abnormalities; however, it is not highly
specific in detecting potentially malignant lesions, giving rise to a high rate of false positives. The sensitivity
varies among studies and this could be due to interoperator variability in what constitutes loss of AF. It
has been reported that there is a large spectrum of fluorescence, and more definitive criteria in what constitutes loss of AF may be required before this
technology can gain widespread use. Further, it is suggested that significant understanding of mucosal
pathology is required to make correct clinical interpretations of AF findings. This may be lacking in a
general dental practice although the onus is on us, as a
profession, to improve our detection and interpretation
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of mucosal changes for the benefit of our patients.
Overall, the evidence suggests that AF technology
has difficulty in differentiating benign lesions from
potentially malignant and malignant lesions, and a
significant level of training in its use and interpretation is required if it is to become a useful adjunctive
aid in general dental practice. In the meantime we
await the results of properly designed large scale
studies currently underway investigating its use by
general oral health practitioners.
To better differentiate between oral epithelial
lesions, a new device, IdentafiTM has been released utilizing the properties of both reflectance and AF
although clinical data is currently unavailable. IdentafiTM combines the essential properties of tissue reflectance and AF in one streamlined multi-spectral
handheld device. It consists of a white light source, a
violet light source and also an amber light source. Tissue is examined firstly with the white light source,
and then with the use of the clinician’s photosensitive
glasses, abnormal areas lose AF and appear dark
under violet light. The amber light is designed to help
with the visualization of tissue vasculature to assist in
the interpretation of abnormalities of the mucosa.
IdentafiTM is a small handheld battery-operated device,
which is used intraorally as opposed to the VELScopeTM which is used extraorally. At this stage no
results from large scale studies showing the utility of
IdentafiTM are available, although several of these are
currently underway in clinics around the world
including our own.
NBI is a newer endoscopic imaging modality that
applies 2 narrow bands of filtered light in the blue
(400–430 nm) and green (525–555 nm) spectrum to
only minimally penetrate the superficial mucosa and
mimic the waveform of haemoglobin to detect early
abnormal angiogenesis seen in premalignant and
malignant lesions. It has been shown to be superior to
white light in detecting head and neck cancers and
precancers,45,46 and it has also been used for surgical
margin detection but mainly in superficial head and
neck cancers.47
NBI has been reported to improve the sensitivity,
diagnostic accuracy, and negative predictive value for
the detection of early head and neck squamous cell
carcinomas compared with white light inspection.48
Well-characterized changes can be seen that correspond to an early increase in vascularization of lesions
of severe dysplasia or worse; these include intrapapillary capillary loops (IPCLs) and tortuosity of vessels.49
Nguyen et al. have used AF and NBI in patients
with head and neck cancer planned for panendoscopy
as part of their diagnostic workup. The aim was to
screen for additional lesions to the primary head and
neck cancer, and to determine how these had an
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impact on overall management. Furthermore, they
wanted to determine if the addition of NBI improved
the poor specificity of AF without influencing overall
sensitivity.
In the head and neck region there were 42 extra
biopsies taken because of abnormal AF or NBI findings. Histopathology of these showed 17 normal/
inflammatory lesions (40.5%), 1 mild dysplasia
(2.4%), 6 moderate dysplasias (14.3%), 11 severe
dysplasias (26.2%), and 7 carcinomas in situ
(16.7%).50 For lesions of moderate dysplasia or
worse, sensitivity of WL was 0.375 and the specificity
was 0.95. AF and NBI had the same sensitivity: 0.96.
The specificity of AF was 0.26, whereas for NBI it
was 0.79. Both AF and NBI were significantly more
sensitive than WL (p = 0.003). The specificities of WL
and NBI were not significantly different, with both
modalities being more specific than AF compared with
WL and NBI, respectively. In addition, there were 66
random biopsies that were negative for dysplasia or
malignancy and also negative at the time of AF and
NBI inspection. The results confirm that NBI is more
specific than AF without compromising sensitivity.
NBI inspection adds to WL and AF evaluation in
patients with head and neck cancer, and NBI
improves specificity and can have a direct positive
impact on patient management.
Given the excellent results observed in this study,
the usefulness of NBI is currently being assessed on
precancerous lesions in our oral medicine outpatient
clinic for assessment of new lesions, surveillance of
existing and previously removed lesions, and surgical
margin delineation. This technology promises more
than AF alone, and appears to suffer less from the
subjective interpretation of results, although skill in
utilizing the technology and interpretation of the
results is still paramount. Although this technology
may not find its way into general dental practice due
to the size of the equipment and the associated
expense, it is another example of advanced technology driving early detection and diagnosis in oral
medicine.
MINIMALLY INVASIVE TREATMENT
Head and neck cancer imaging
At present the most advanced and relevant multimodal system used in head and neck cancer imaging
is the combination of positron emission tomography
(PET) and computerized tomography (CT).51 However, the combination of the high soft tissue contrast
provided by magnetic resonance imaging (MRI) and
the molecular and metabolic information provided by
PET shows promise especially in the evaluation of
tumours of the head and neck.52
© 2013 Australian Dental Association
MID in oral medicine
PET with 18-F-flurodeoxyglucose (FDG) has shown
promising results for the assessment of lymph node
involvement in cancer, the identification of distant
metastasis and synchronous and metasynchronous
tumours, and the evaluation of tumour recurrence or
carcinoma of an unknown primary.52
MRI has several advantages compared with CT for
morphologic imaging in the head and neck region due
to the superior soft tissue contrast and fewer artefacts.
MRI also allows functional imaging such as the
assessment of perfusion with dynamic contrast
enhanced MRI.
Studies with sequential PET/MRI have shown that
patients with head and neck cancer would benefit
from additional high definition MRI sequences providing soft tissue characterization not possible with CT
images from traditional PET/CT scanners. The published data to date regarding image fusion, although
in its infancy, indicates that this is beneficial in the
evaluation of potential metastatic lymph nodes and in
assessment of recurrence of head and neck cancer.
However, PET can deliver more information than is
available from 18 FDG and can provide imaging biomarkers of specific biological processes, which may be
relevant for therapy planning, assessment of prognosis
and evaluation of the treatment response, beyond the
traditional applications in staging assessment of
tumour extent and metastatic spread.52, 53
Fully integrated PET/MRI systems allow for simultaneous whole-body PET and MRI imaging. This
allows the simultaneous acquisition of high resolution
PET and MRI images which is significantly beneficial
in head and neck cancer imaging given the complexity
of the anatomy of this region, and the soft tissue nature of its pathology.54 Simultaneous acquisition of
PET and MRI sequences is advantageous not only
because it decreases examination time compared to
sequential scanning, but also because PET/MRI
co-registration has the potential to be a useful tool in
the planning of image-based surgery and radiotherapy,
image-guided radiotherapy, and the determination of
the level of follow up in the treatment of head and
neck cancer.
Potential benefits of combined PET/MRI technology
in head and neck cancer management include, but are
not limited to:
(1) Usefulness and applicability of PET/MRI in head
and neck cancer staging and detection. PET is more
superior to clinical examination and CT in staging
primary tumour with similar sensitivity but higher
specificity.55 The sensitivity of PET is hampered by its
lower resolution than CT or MRI, but with the inclusion of hybrid PET/MRI, this should be resolved.
MRI is useful for determination of perineural spread,
and typically PET alone is unable to resolve these
because of partial volume averaging effects. The com© 2013 Australian Dental Association
bination of PET/MRI has the potential to improve
this. In addition to detection of primary disease, PET/
MRI has the potential to uncover unknown primary
tumours. The reported incidence of unknown primary
tumours in the head and neck area range between 3%
to 10% with negative clinical examination and CT
and/or MRI studies.56 Panendoscopy in combination
with FDG-PET has been shown to be valuable in the
work-up of such patients.
PET staging also has the significant benefit of yielding smaller tumour volumes and tends to be closely
correlated with the pathological specimen. There is a
significant advantage in coupling this with MRI, as
this might facilitate focused treatment options such as
intensity modulated radiation therapy (IMRT). In
addition, some patients with small tumour volumes
and stage exhibit aggressive growth patterns despite
appropriate therapy, and it is thought that the functional data from PET can be used to identify and
stratify these cases.57,58
(2) Assessment of sentinel lymph nodes. The combination of PET/MRI not only has the ability to localize
disease even in small subcentimetre nodes, but also
has the ability to alter planned neck dissection, and
monitor nodal involvement post-surgery/radiotherapy
in surveillance patients. The benefit of PET/MRI has
not been determined in N0 patients, and this requires
attention given the rates of occult nodal metastasis in
some head and neck cancer groups such as oral cavity. Early evidence supports superior performance of
PET over CT/MRI in nodal metastasis determination,
and up to 5.2% altered treatment planning based on
PET findings compared to CT/MRI in discordant
TNM staging. Extra-capsular nodal spread is another
important prognostic factor, which requires MRI
enhancement accompanied with PET to increase sensitivity and specificity, compared to PET alone, or even
contrast enhanced CT. In addition to detection of
nodal involvement in staging treatment, PET has a
role in post-treatment evaluation of nodal disease,
and appears to be beneficial in patients undergoing
radiochemotherapy.
(3) Correlation of biomarkers for head and neck cancer and resection margins. Autofluorescence and narrow band imaging have recently been introduced to
examine patients with head and neck cancer, and our
group has been the first to show conclusively that panendoscopy with narrow band imaging increases sensitivity and specificity of detection compared with white
light panendoscopy, but also improves surgical margin
delineation.50 PET has also more recently been shown
to be of value in detection of recurrence in up to 25%
of patients with clinically unsuspected disease. PET/
MRI can be useful in surveillance of patients post-surgery or radiation treatment. Given that the changes
noted under AF and NBI are limited to epithelium and
91
CS Farah et al.
superficial connective tissue, it is anticipated that coupling of these technologies with PET/MRI will allow
better determination of algorithms for detection of
superficial tumours, given the ability of PET to capture
metabolic rates in earlier detection of recurrent
tumour, even in clinically disease-free patients.
(4) Development of drug/molecular targets discovered
through next generation sequencing for possible radionuclide tracer development. We are currently undertaking genome wide sequencing of head and neck
tumours in an effort to produce a diagnostic molecular biomarker panel for early detection and more
accurate diagnosis. Molecular targets in head and
neck cancer, coupled with novel targeted anticancer
therapeutics, labelled with positron emitters could be
used to guide patient selection protocols, further drug
development, and hence advance efforts into personalized medicine. Use of non-FDG PET with emitters
such as zirconium-89 or gallium-68, coupled to monoclonal antibodies against target molecules, has great
potential in guiding both patient treatment and surveillance. PET imaging of tyrosine kinase inhibitors
may also prove useful.59
CONCLUSIONS
The concept of minimum intervention dentistry in the
context of oral medicine may seem foreign to some,
but in fact oral medicine specialists practise minimum
intervention daily. As oral diagnosticians we have a
duty of exploring the most effective and efficient early
detection approaches to unravel disease, and as oral
physicians we undertake minimally invasive interventions to affect positive outcomes for our patients, many
of whom live with chronic conditions that require regular care. Underlying this is a deep understanding of
disease risk, aetiopathogenesis, health behaviour patterns, and effective patient communication strategies.
In this article we have tried to highlight minimum
intervention in oral medicine by exploring oral cancer
as the most significant disease we encounter and are
involved with. Advances in patient care, particularly
in relation to minimum intervention, are underpinned
by high calibre cutting edge translational research. It
is this research that allows us to positively transform
our patients’ lives.
ACKNOWLEDGEMENTS
CSF would like to thank Dr Pauline Ford from the
UQ School of Dentistry for fruitful discussions while
conceptualizing this article, and Dr Anastasia Georgiou, Oral Medicine Specialist and President-Elect of
the Oral Medicine Academy of Australasia, for critical
review of the manuscript.
92
DISCLOSURE
The authors declare that they have no conflicts of
interest in relation to this work.
CSF is a registered specialist in Oral Medicine and
Oral Pathology, current President of the Oral Medicine Academy of Australasia, and Head of the Oral
Oncology Research Program at the UQCCR where he
undertakes clinical practice and research into head
and neck cancer early detection, diagnosis and imaging. NB, KJ and BWL are dental student members of
the Oral Oncology Research Program.
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Address for correspondence:
Associate Professor Camile Farah
Oral Medicine Specialist
UQ Centre for Clinical Research
The University of Queensland
Building 71/918
Royal Brisbane and Women’s Hospital Campus
Herston QLD 4029
Email: [email protected]
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