REVIEW
Australian Dental Journal 2002;47:(4):284-289
Current concepts in the management of oral squamous cell
carcinoma
KR Spencer,* JW Ferguson,* D Wiesenfeld*
Abstract
This paper focuses on how patients with oral
squamous cell carcinoma (SCC) are assessed and
managed once they have been referred for specialist
care. Current and future treatment options are
presented and basic management principles are
discussed. It is our hope that this will enable the
general dental practitioner to gain insight into the
process and reasoning behind the multidisciplinary
treatment of these complex cases.
Key words: Oral cancer, treatment, current concepts.
(Accepted for publication 9 January 2002.)
INTRODUCTION
The oral cavity is the most common site for
squamous cell carcinoma of the upper aero digestive
tract with over 750 new intra-oral squamous cell
carcinomas registered in Australia each year.1 Early
diagnosis is essential to ensure an optimal outcome: the
role of dental practitioners in the early detection and
referral of patients with any suspicious lesion cannot be
overstated.
In addition to discussing assessment and
investigation, this paper reviews the principles of
management of patients with oral squamous cell
carcinoma (SCC), subsequent to their referral to a
specialist unit.
Initial assessment and diagnosis
When a patient is referred to a specialist centre for
management of oral SCC, a comprehensive history and
physical examination will be undertaken, and
radiological investigations performed to assess the
extent of the primary lesion and to identify any local or
distant spread. Confirmation of the diagnosis of oral
SCC is made by pathologic examination following
incisional biopsy. Investigations such as vital staining
with toludine blue,2 fluorescence imaging3 and
*Department of Surgery, The Royal Melbourne Hospital, and School
of Dental Science, The University of Melbourne.
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fluorescence photography4 have all been suggested as
adjunctive screening tests prior to biopsy. However,
they are of little practical benefit in assessing patients
with oral SCC and definitive diagnosis must always be
based on histological examination. The patient is then
seen in a multi-disciplinary clinic. This clinic includes
oral and maxillofacial, ear, nose and throat and plastic
surgeons whose combined expertise is required for the
complex treatment planning and subsequent resection
and reconstruction. It also includes radiotherapists who
are able to offer organ preservation techniques, as well
as post-operative radiotherapy. Other essential
personnel include a maxillofacial prosthodontist, a
speech pathologist, a nutritionalist and a
physiotherapist along with other allied health and
nursing staff. After the patient has been seen and
assessed by all of the clinic staff, the case is discussed
and an individualized treatment plan is formulated.
Clinical and radiological assessment is used to
determine the extent of disease, and is commonly
expressed as staging. The most widely used staging
system is the Tumour, Node, Metastasis (TNM) system
conceived by the International Union against Cancer
(UICC) in 1987 and modified in 1997.5,6 Within this
system, Tumour (T) is assessed as the maximum
diameter of the tumour, Node (N) the number and
distribution of metastases in the regional lymph nodes,
Metastasis (M) the presence or not of distant
metastases (Table 1). Staging of the disease provides an
objective standardized assessment to aid planning,
facilitating the exchange of information and
determining the prognosis and potential for cure.7
Assessment of the primary lesion
Oral SCC can invade deeply into adjacent tissues
such as the tongue and floor of mouth, as well as bone,
primarily via the alveolar crest.8 Accurate clinical
assessment is therefore supplemented by imaging
studies that normally include an orthopantomogram
(OPG) and a computerized tomogram (CT). A
magnetic resonance imaging (MRI) scan will provide
supplementary information when the extent of invasion
into the soft tissues can not be clinically determined, or
there is the question of tumour spread along nerves.
Australian Dental Journal 2002;47:4.
Table 1. Clinical staging of oral squamous cell
carcinoma6
Tumour
T1 Greatest diameter ≤2cm
T2 Greatest diameter 2 to 4cm
T3 Greatest diameter >4cm
T4 Invades adjacent structures
Nodes
N0 No clinically positive nodes
N1 Single ipsilateral node <3cm
N2a Single ipsilateral node 3 to 6cm
N2b Multiple ipsilateral nodes ≤6cm
N2c Bilateral or contralateral nodes ≤6cm
N3 Node >6cm
Metastasis
M0 No distant metastasis
M1 Distant metastasis
Clinical staging
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage III T1 N1 M0
T2 N1 M0
T3 N0, N1 M0
Stage IVA T4 N0, N1 M0
Stage IVB Any T N2,N3 M0
Stage IVC Any T Any N M1

Some authorities recommend a bone scan to look for

evidence of bone involvement,9,10 although this is not
common practice.
Clinical examination may be supplemented by an
examination under anaesthetic (EUA) of the upper
aerodigestive tract, particularly when the patient
presents with a tumour that has spread beyond the oral
cavity such that the full extent of the lesion cannot be
assessed whilst the patient is awake. Panendoscopy
may also be performed as part of the initial workup as
Fig 1. Cervical lymph nodes.
Australian Dental Journal 2002;47:4.
Fig 2. Lymph node levels I-V. Spread from a tumour (T) is typically
to the upper levels first.
some patients may have synchronous tumours at sites
further along the aerodigestive tract. However, in the
absence of symptoms or signs suggesting a second
tumour this is not universally done.
Assessment of the neck
Lymphatic drainage in the head and neck is to the
deep cervical lymph nodes, which lie along the length of
the internal jugular vein (Fig 1). The most commonly
used system for describing their location is the
Memorial Hospital system which divides the lymph
nodes into five levels.11 Level I nodes lie in the
submandibular triangle (the area bounded by the
anterior and posterior bellies of the digastric muscle
and the inferior border of the mandible), levels II, III,
IV are the nodes that lie around the upper, middle and
lower parts of the internal jugular vein respectively.
Level V nodes are in the posterior triangle bounded by
the clavicle, posterior border of the
sternocleidomastoid muscle and the trapezius muscle.
Lymph flows from the upper to the lower nodes and
therefore lymph node metastasis from oral SCC usually
occurs in a predictable fashion, involving the lymph
node levels in the upper neck first (Fig 2).
The status of cervical lymph nodes at presentation is
an extremely important prognostic factor in oral
squamous cell carcinoma. The presence of metastasis in
a cervical lymph node, in a patient with oral SCC,
decreases the chance of long-term control by 50 per
cent when compared to with patients who have similar
primary tumours without nodal metastasis.12
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 Because the prognosis is influenced by the presence
of secondary disease in the neck, an accurate
assessment of the neck is essential. As the overall
accuracy of clinical assessment by palpation of neck
nodes is approximately 71 per cent,13 CT or MRI scans
of the neck are performed to supplement the clinical
examination. Lymph nodes larger than 1cm, or nodes
showing evidence of central necrosis, are reported as
pathological on CT or MRI scan. However, node size
cannot accurately predict histology. Enlarged nodes
may represent benign reactive hyperplasia, while
normal sized nodes (less than 1cm), may contain
metastatic deposits.14
Positron emission tomography (PET) is a sensitive
imaging technique, which may identify the presence of
malignant deposits, by virtue of detecting the increased
metabolism associated with tumours. Thus, non-
enlarged lymph nodes that contain metastatic disease,
but are negative according to MRI and CT, may be
detected by PET,15 and where available, PET can be a
useful adjunctive investigation.
Assessment for metastasis
Chest radiography, full blood examination and liver
function tests may be used to screen for metastatic
disease. If a patient has symptoms or signs, or an
abnormal result suggesting metastatic spread, then
further investigations including a chest CT, liver
ultrasound and bone scan are indicated.
Principles of management
Palliative care is offered to patients who either have
incurable disease, or are medically unfit to be subjected
to potentially curative treatment. Pain relief,
chemotherapy and sometimes radiotherapy or surgery
may be useful for these patients, who will be assessed
and managed by a palliative care team.
Currently, surgery and radiotherapy are the two
treatment options available with curative potential, and
may be used alone or in combination. Surgery will
involve complete excision of the tumour along with a
surrounding margin of normal tissue, and, where
indicated, some or all of the ipsilateral and occasionally
contra lateral cervical lymph nodes.
Radiotherapy preferentially kills dividing cells, and
for those patients treated by radiotherapy, the aim is to
kill every cancer cell. Both the primary tumour and the
regional lymph nodes can be included in the treatment
field. A full course of radiotherapy is typically
expressed in the usual units as being about 60 Grey
(Gy) (1 Gy=100 rads), which is fractionated into 30
daily doses of 2 Gy each over six weeks. Radiotherapy
has the advantage of organ preservation and is
currently the primary modality used to treat some cases
of tonsillar, soft palate, and pharyngeal SCC. However,
significant and potentially disabling side effects may
follow the use of radiotherapy in the head and neck
region, including mucositis, xerostomia, and
osteoradionecrosis.
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The choice of whether to observe or treat the
clinically “negative” neck, as well as treatment of the
neck using radiotherapy versus surgery, remains
controversial. August et al.16 contend that clinical
observation is inadequate, as neck nodes originally
assessed as normal are subsequently clinically detected,
often with disease that has spread beyond the lymph
node capsule. Shah and Andersen12 advocates surgical
management for the negative neck but argues that
tumours of the maxillary gingivae, hard palate, and
lips, have such a low rate of occult metastasis that
elective treatment of the neck is not necessary.
Surgery has always had a dominant role in
management of the patient with a palpable lymph node
in the neck, and the term neck dissection applies to such
treatment. Undertaken in combination with the
excision of the primary tumour, the surgeon carefully
dissects out the cervical lymph nodes whilst identifying
and preserving the surrounding vital structures, hence
the term for this part of the operation which is known
as a neck dissection. The original operation of radical
neck dissection for management of the “positive” neck
as described by Crile17 involved removal of all deep
cervical lymph nodes (levels I-V) as well as the
accessory nerve, internal jugular vein and
sternocleidomastoid muscle.
Modifications to preserve some of the anatomical
structures, including the accessory nerve, internal
jugular vein, and sternocleidomastoid muscle, have
since been advocated, in order to reduce the morbidity
associated with this procedure. Thus the so called
modified radical neck dissection (MRND) has become
the standard for surgical management of the neck. In
patients with a clinically negative neck, the upper nodal
levels (levels I-III) are most at risk for metastasis, and
therefore a selective neck dissection, which removes
only these upper levels of lymph nodes, may be
performed and is described as a supra-omohyoid neck
dissection.12
Decisions about the use of post-operative
radiotherapy must consider both the primary lesion
and the neck. When factors relating to the primary site
(large primary tumour, positive or close margins,
perineural or lymph and vascular space invasion)
dictate the use of radiotherapy, the neck should be
included in the field. When factors associated with the
primary tumour do not alone provide an indication for
radiotherapy, the decision will be based on the
pathologic findings in the neck dissection specimen. In
the patient whose neck nodes have been demonstrated
histologically to be disease-free, radiotherapy is not
indicated.18 Multiple positive nodes, or the presence of
tumour spread beyond the lymph node capsule, are
absolute indications for radiotherapy.
When radiotherapy is to be combined with surgery,
most surgeons prefer the radiotherapy to be provided
post-operatively. Surgery involving irradiated tissues is
more difficult to perform as radiotherapy causes the
tissues to fibrose and become “woody”. Irradiated
Australian Dental Journal 2002;47:4.
 Clinically and radiologically negative neck
Observation Irradiation Selective neck dissection
(upper lymph nodes)
Single positive node Multiple positive nodes
or extracapsular spread
± on pathological examination
Primary requires irradiation Post-operative radiotherapy
to the neck
Multiple nodes or
extracapsular spread on
pathological examination
Comprehensive neck dissection
(all lymph nodes)
Clinically positive neck
Fig 3. Management of the neck in oral SCC.
tissues are also much slower to heal (Fig 3).
Chemotherapy, or the use of cytotoxic drugs, usually in
various combinations to kill tumour cells has not been
particularly successful in the treatment of patients with
oral SCC and is not regarded as a current primary
treatment modality other than for palliative care.
However, recent trials reporting the use of
chemotherapy combined with radiotherapy and surgery
in patients with advanced disease have shown
encouraging early results,19,20 and may have a role in
future treatment.
Reconstruction and rehabilitation
There are many options for the reconstruction and
rehabilitation of the oral cavity and the decision of
which option to use is a very important aspect of the
initial treatment planning process. Working closely
with the maxillofacial prosthodontist before surgery
enables the surgical team to appreciate what will be
required for each individual case. This combined
treatment planning is essential for the success of the
prosthetic aspect and ultimate goal of dental
rehabilitation.
Post-maxillectomy defects may be managed by either
surgical reconstruction or provision of a prosthesis,
although there is continuing controversy about the
most appropriate method of rehabilitation in any
particular case21 with the indications for either being
relative. The decision to obturate or reconstruct a
defect must take into account the patient’s prognosis,
the size of the defect, prosthetic constraints, and the
ability of the patient to cope post-operatively.
Mandibular reconstruction aims to restore or
maintain speech, swallowing and appearance. The most
versatile method of mandibular reconstruction is free
tissue transfer, where tissue is transferred complete with
isolated major blood vessels from one part of the body
Australian Dental Journal 2002;47:4.
to another, with restoration of circulation to the
transferred tissue achieved by joining the donor and
recipient flap vessels to local blood vessels. This
method of reconstruction has gained many advocates,
and iliac crest,22 radius23 and fibula24 tissue transfer are
well described. However, some patients are unsuitable
for such major reconstruction,25 particularly on medical
grounds, and in these cases titanium plates can
satisfactorily bridge small lateral defects although
preferably not including the chin.26
Anterior and large lateral mandibular defects are
difficult to reconstruct in those patients who are
unsuitable for bony reconstruction, and high failure
rates have been reported where plates have been used to
bridge these defects.26 Posterior lateral defects may
sometimes be left without any form of reconstruction,
with minimal morbidity, particularly in edentulous
patients. Soft tissue defects, such as in the tongue, soft
palate and cheeks should be reconstructed to minimize
scarring, deformity and subsequent interference with
function. Techniques include skin grafting for
superficial defects, loco-regional flaps such as buccal
mucosal island or temporalis flaps, and composite flaps
such as radial skin or pectoralis major flaps for larger
defects.
Oral rehabilitation may involve a number of
subsequent procedures, including placement of
titanium dental implants and fabrication of complex
fixed or removable prosthesises by a specialist
maxillofacial prosthodontist. Patients who have
undergone radiotherapy are prone to develop
xerostomia, and occasionally osteoradionecrosis.
Regular dental review is therefore essential to prevent
or manage such complications.
Following definitive treatment, all patients will
require close follow-up and must be assessed frequently
both clinically and radiologically, for tumour
recurrence. Subsequent to surgery and radiotherapy,
anatomical structures may be lost, distorted or even
unrecognizable, which makes early diagnosis of
renewed tumour growth difficult.
Recent studies have sought to identify markers of
malignancy to help detect tumour recurrence. A marker
is a substance that can be measured in the blood at an
increased level before there is clinical evidence of
recurrent tumour. Two relatively new tumour markers,
Cyfra 21-1 and tissue polypeptide specific antigen
(TPS), have recently been investigated and have shown
promise in early detection and treatment monitoring in
oral SCC.27
Future concepts in treatment
Photodynamic therapy is an experimental cancer
treatment modality. It involves the intravenous
injection of a photosensitizing agent that is selectively
retained by tumour cells. When the tumour is then
exposed to light of an appropriate wavelength, a
photochemical reaction occurs. The activated
photosensitizer reacts with oxygen, which subsequently
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damages the tumour cells. Several studies reporting the
use of photodynamic therapy in early carcinoma, and
as adjuvant intra-operative therapy for recurrent
tumors, have shown impressive response rates.28,29
Tumour cells are able to produce substances,
collectively termed tumour angiogenesis factors, which
encourage neovascularization or growth of new blood
vessels, a fundamental step in tumour growth and
metastasis.30 Tumour angiogenesis may provide a useful
target for therapy. However, recent animal research in
the use of anti-angiogenic substances in head and neck
cancer have shown mixed results.31,32
An ingenious treatment strategy currently being
researched is gene therapy. Inserting part of a herpes
simplex virus gene into cancer cells has been used to
sensitize tumours to the cytotoxic effects of the anti-
viral drug ganciclovir.33 Combination gene therapy
using several different genes, which can sensitize
tumours to various drugs, have also been shown to
cause significant tumour regression in mice.34
Apoptosis-inducing (cell self-destruction) therapy is
becoming a new strategy in cancer therapy, with
research into agents that can induce apoptosis of SCC
cells at various stages in the cell cycle.35
From a reconstructive aspect, there is currently active
research in the field of distraction osteogenesis, and this
process has been used to regenerate mandibular bone.
Originally described by Codivilla36 and used by
Ilizarov37 to reconstruct defects in long bones, bone
lengthening by gradual distraction makes use of the
body’s natural healing potential to produce bone in the
resultant gap.
Much has been learned in the past 50 years about oral
SCC, and new and ingenious strategies are being
developed to combat the disease. However, despite this
increase in knowledge, survival rates for patients
presenting with advanced disease have not improved
significantly. Early diagnosis is still the most important
factor in improving the prognosis. It is therefore the
responsibility of the dental profession to increase and
maintain its high level of its awareness and to actively
pursue the understanding of this disease to enable earlier
diagnosis, and hence improved outcomes.
AC K N OW L E D G E M E N T S
This paper was completed as partial fulfillment of
the requirements for the degree of MDSc at the
University of Melbourne, by the primary author.
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Address for correspondence/reprints:
Mr Kevin Spencer
5th Floor, 766 Elizabeth Street
Melbourne, Victoria 3000
Email: kspencer@omfs.com.au
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