The Journal of Laryngology & Otology (2016), 130 (Suppl. S2), S83–S89.

GUIDELINE
© JLO (1984) Limited, 2016. This is an Open Access article, distributed under the terms of the Creative Commons
Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and
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doi:10.1017/S0022215116000499

Oral cavity and lip cancer: United Kingdom National

Multidisciplinary Guidelines

C KERAWALA1, T ROQUES2, J-P JEANNON3, B BISASE4

1
Head and Neck Unit, The Royal Marsden Hospital, London, 2Norfolk and Norwich University Hospitals NHS
Foundation Trust, Norwich, 3Department of Otolaryngology-Head and Neck Surgery, Guy’s and St Thomas’ NHS
Foundation Hospital Trust, King’s College, London, and 4Queen Victoria Hospital, East Grinstead, UK

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer
patients in the UK. It provides recommendations on the assessment and management of patients with cancer of
the oral cavity and the lip.

Recommendations
• Surgery remains the mainstay of management for oral cavity tumours. (R)
• Tumour resection should be performed with a clinical clearance of 1 cm vital structures permitting. (R)
• Elective neck treatment should be offered for all oral cavity tumours. (R)
• Adjuvant radiochemotherapy in the presence of advanced neck disease or positive margins improves control
rates. (R)
• Early stage lip cancer can be treated equally well by surgery or radiation therapy. (R)

Introduction to carcinogens such as tobacco or alcohol is thought

In order of decreasing frequency, malignant tumours of to be important. Carcinogenesis is a multistep process
the oral cavity affect the anterior two-thirds of the that involves over expression of oncogenes and inacti-
tongue, floor of mouth, buccal mucosa, retromolar vation of tumour suppressor genes. The p53 suppressor
trigone, hard palate and gingivae. Tumours of the lip gene has been identified as being important in oral
require separate consideration as their natural history cavity carcinomas in smokers. The presence of
differs from oral cavity disease. The overwhelming human papilloma virus (HPV) that expresses the p16
majority of oral cavity cancers are squamous cell car- oncoprotein in oral cavity carcinoma in non-smokers
cinomas (SCCs). Non-squamous cell tumours are pre- is of significant importance as the cancers tend to
dominantly of salivary gland origin and are discussed occur in younger patients. However, HPV-related
elsewhere in these guidelines. The heterogeneous disease does not appear as frequently in the oral
nature of oral cavity tumours, the functional and cos- cavity as it does in the oropharynx and appears not to
metic sequelae of their management and the frequent proffer as much of an improvement in prognosis.1
medical co-morbidities that co-exist in this patient The importance of epidermal growth factor receptor
group demand that treatment options should be consid- (EGFR) status in oral cavity carcinoma remains
ered by a multidisciplinary team before reaching a final unclear. Whilst over expression does appear to be
plan through consensus with the patient and carers. The related to poor prognosis, EGFR status does not yet
overall treatment intention, whether curative or pallia- appear to be correlated with response to targeted
tive, should be clearly communicated at the outset. molecular therapies such as cetuximab.
Within the diagnosis of oral cavity SCC, several
histological subtypes exist with different prognoses
Pathology
such as verrucous (better prognosis) and basaloid
Oral cavity (worse prognosis) carcinomas. Oral SCCs are classified
Carcinoma of the oral cavity may develop de novo or according to grade depending on several histopatho-
from a pre-malignant dysplastic lesion that appears logical features such as degree of keratinisation,
clinically as leukoplakia, erythroplakia or a combin- nuclear pleomorphism, cellular atypia and mitotic
ation of the two. In both instances, chronic exposure activity. They are divided into well, moderate and
S84 C KERAWALA, T ROQUES, J-P JEANNON et al.

poorly differentiated carcinomas. However, tumour or erythroplakia).6 A non-healing ulcer is the most
grade is of limited prognostic value due to the hetero- common presentation. Advanced tumours can present
geneity within a tumour and sampling error. Several with invasion of neighbouring structures causing
other histopathological factors have been shown to be tooth mobility, trismus, sensory change, referred
of prognostic importance such as tumour thickness, otalgia and neck masses. The clinical presentation of
extra-capsular spread (ECS) of nodal metastasis2 and cancer of the lip is usually that of an exophytic,
patterns of invasion. Oral tongue SCC of greater than crusted lesion with variable invasion into underlying
4 mm tumour thickness is considered to represent a muscle (related to the size of the primary tumour).
>20 per cent risk of cervical lymph node metastatic The adjacent lip often shows features of actinic sun
involvement.3 Extra-capsular spread in cervical damage such as colour change, mucosal thinning and
lymph nodes is consistently associated with an various associated areas of leukoplakia.7
increased risk of local regional recurrence, distant
metastasis and decreased survival. The pattern of Assessment and staging
invasion in oral SCC appears to be important in deter-
Clinical examination
mining prognosis in that those cancers that have a non-
cohesive invasive front and/or peri-neurial invasion Clinical examination is useful in identifying new
appear to be associated with an increased risk of tumours and for surveillance after treatment. Given
loco-regional relapse.4 These pathological factors its importance in diagnosis and treatment planning, a
therefore supplement the tumour–node–metastasis systematic approach must be adopted to include the
classification and are now incorporated in pathological primary site and neck, with assessment of the index
datasets. tumour size as well as any potential invasion of local
structures. The examination should be preceded by a
Lip focused history to elucidate any potential co-morbid-
Cancer of the lip is the most common malignant tumour ities and social circumstances that may influence the
affecting the head and neck. Its clinical behaviour is choice of treatment.
similar to that of skin cancer. Incidence rates are
around 13.5 per 100 000 in Oceania, 12 per 100 000 Imaging considerations
in Europe and 12.7 per 100 000 in North America.5 Imaging of early stage tumours of the lip is usually not
The factors commonly cited as important in lip indicated. However, advanced tumours of the lip (par-
cancer are solar radiation, tobacco smoking and ticularly if they are adherent to the adjacent mandible)
viruses. About 90 per cent of tumours arise in the require computed tomography (CT) or magnetic reson-
lower lip with 7 per cent occurring in the upper lip ance imaging to allow complete staging and treatment
and 3 per cent at the oral commissure. planning with regard to resection margins which may
Squamous cell carcinoma is the commonest histo- of necessity include adjacent bone.
logical tumour type in lip cancers, followed by basal Oral cavity tumours are almost always staged with
cell carcinoma. The most common non-mucosal form cross-sectional imaging to include the chest where the
of lip cancer arises from tumours of the minor salivary demonstration of simultaneous pulmonary parenchy-
glands, with in converse to mucosal lip cancer the mal disease may influence curability.8,9 Sentinel node
upper lip being more commonly involved than the lymph node biopsy has been shown to be an effective
lower. method of assessment of the neck in early stage oral
cancers.10
Clinical presentation
The majority of SCCs (>95 per cent) of the oral cavity Pre-treatment staging
are presented as ulcers or masses. Early lesions can be Staging of primary cancer of the lip and oral cavity is
subtle and appear as flat, discoloured areas (leukoplakia similar and shown in Table I. T4 tumours of the lip
usually only invade the anterior mandible or maxilla
rather than other structures.
TABLE I
T STAGING FOR ORAL CAVITY TUMOURS
Management
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour Oral cavity
Tis Carcinoma in situ Although there is no randomised data exclusively com-
T1 Tumour 2 cm or smaller in greatest dimension
T2 Tumour larger than 2 cm but 4 cm or smaller in greatest paring the different treatment modalities available in
dimension the management of oral cavity cancer, non-surgical
T3 Tumour larger than 4 cm in greatest dimension clinical trials often present this subsite in combination
T4a Tumour invades the larynx, deep/extrinsic muscle of
tongue, medial pterygoid, hard palate or mandible with others in the head and neck. Two-year crude sur-
T4b Tumour invades lateral pterygoid muscle, pterygoid plates, vival rates are around 85 per cent for stage I disease, 70
lateral nasopharynx or skull base or encases carotid per cent for stage II disease11, 50 per cent for stage III
artery
disease and 40 per cent for stage IV disease.12
ORAL CAVITY AND LIP CANCER: UK GUIDELINES S85

General principles operative time. Adoption of a Mohs-type technique

Surgery. Factors such as fitness for anaesthesia, pre- where the whole of the resection bed is mapped out
vious cancer treatment and patient choice as well as the is impractical given the size of the average intra-oral
skill mix and resources available to the treating team resection. Intra-operative tumour tissue marking has
must be considered.13,14 There are a number of been attempted with agents such as toluidine-blue but
different options available under the broad banner of this has limited value in marginal clearance because
surgery: conventional surgery, laser surgery, thermal of high false positive rates.17 Where bony resection is
surgery and photodynamic therapy (PDT).15 Curative required, the assessment is largely based upon clinical
surgery for cancer of the oral cavity involves resection and radiological findings.18 Intra-operative techniques
of tumour with an appropriate safety margin and subse- such as periosteal stripping however remain reliable.
quent reconstruction of the tissues in order to maintain Frozen section of cancellous bone can be used to
function. The size and location of the primary tumour guide the extent of the resection.
determine the need or otherwise for adjuncts such as Cervical lymphadenectomy in the form of elective
temporary tracheostomy and access procedures. Many neck dissection offers improved overall and disease-
tumours in the anterior aspect of the oral cavity can free survival compared with therapeutic neck dissec-
be accessed via the transoral route. This is ideal, tion for the majority of oral cancers with recent
since in so doing the circumferential muscular sphinc- evidence suggesting advantages even for tumours less
ter is maintained and scars avoided. However, as than 4 mm in thickness.19 Sentinel node lymph node
tumours increase in size and become more posteriorly biopsy may be indicated for small (T1 and T2)
placed, a controlled resection may only be possible cancers since a negative sentinel node biopsy can
by performing either a lingual release or resorting avoid the morbidity of neck dissection and may be
to lip-split and mandibulotomy. There are several more cost-effective.10
options for the lip skin incision with some form of Z-
plasty being desirable to both disguise and lengthen
the scar, thus preventing post-operative wound contrac-
Recommendations
tion and distortion to the vermilion border. • Surgery remains the mainstay of management
Effective tumour ablation is achieved by ensuring for oral cavity tumours (R)
good visibility which in turn is dependent on appropri-
• Tumour resection should be performed with a
ate access. In order to maximise the chances of achiev-
clinical clearance of 1 cm vital structures
ing complete tumour resection with a clear margin of
permitting (R)
normal tissue, both visual inspection and palpation
must be employed. The method of ablation, be it • Elective neck treatment should be offered for
scalpel, laser, diathermy or coblation, is a matter of per- all oral cavity tumours (R)
sonal preference. For small, superficial lesions laser
vaporisation may be employed although this often
does not permit accurate histological assessment of Radiotherapy ± chemotherapy. In the oral cavity,
the adequacy of resection and so may compromise primary radiochemotherapy is less commonly utilised
decisions surrounding the need or otherwise for than other head and neck sites. However, it should be
adjuvant treatments. Lasers and thermal techniques, considered in selected patients. Concurrent radioche-
whilst reducing the amount of intra-operative bleeding, motherapy combines platinum-based chemotherapy
can cause histological artefact and morphological with external beam radiotherapy (EBRT) to 70 Gy.
distortion of tissue margins. Coblation involves the While the most recognised concurrent chemotherapy
generation of bipolar radio-frequency waves. Tissue regimen is cisplatin 100 mg/m2 three weekly,
temperatures of around 60 °C ensue, much lower than varying doses and schedules are acceptable practice,
temperatures generated by conventional diathermy. as is substitution by carboplatin. Patients undergoing
Although this is claimed to reduce post-operative radiochemotherapy require speech, swallow and
pain, the technique has been associated with increased dietetic support, in both the acute and long-term
levels of haemorrhage in certain head and neck sites. setting. Patients who are excluded from platinum-
The primary aim of surgery in oral cavity cancer is based chemotherapy may be considered for EBRT
tumour resection with a clinical clearance of ideally with cetuximab under National Institute for Health
1 cm (vital structures permitting). ‘Close’ margins and Care Excellence guidance. Neo-adjuvant chemo-
(defined as a histopathological margin of less than therapy with taxanes, cisplatin and 5-fluro-uracil
5 mm) mean further surgery or adjuvant radiotherapy (TPF) is a potent combination in advanced, inoperable
(RT) and should be discussed by the multidisciplinary disease in fit patients, if followed by concurrent
team. The use of intra-operative frozen sections to radiochemotherapy.
assist marginal clearance is controversial.16 Although External beam radiotherapy is not usually recom-
the accuracy is good in histological terms, they can mended as the primary curative treatment in oral
give a false sense of security and invariably prolong cavity tumours because the significant morbidity of
S86 C KERAWALA, T ROQUES, J-P JEANNON et al.

treatment limits radiation dose and therefore cure

rates. Severe mucositis of the treated volume during Recommendation
and immediately after treatment is inevitable and
will affect function and nutrition. Long-term pain is • Adjuvant radiochemotherapy in the presence
a common sequelae if high enough radiation doses of advanced neck disease or positive margins
to cure primary tumours are used while osteoradione- improves control rates (R)
crosis of the mandible is a particular risk when
irradiating the oral cavity. External beam radiother-
apy alone can be used to treat the neck prophylactic- Recurrent cancer. Patients with locally recurrent disease
ally after excision of a small primary without a neck should be fully restaged and assessed for consideration
dissection. Brachytherapy as sole treatment or as a of curative treatment in the form of repeat surgery, pos-
boost after EBRT can produce cure rates equivalent sible EBRT or brachytherapy if available. Palliative RT
to those in surgical series. As the radiation dose is may be used, either over short fractionation schedules
concentrated in the tumour tissue more effectively or split course, for patients with advanced and inoper-
than with EBRT, higher doses and fewer long-term able disease, or those who are not fit for a more toxic,
side effects can be achieved. Brachytherapy requires radical approach. Palliative chemotherapy should be
specific expertise which is not widely available in the considered for inoperable, recurrent and or metastatic
UK. disease, when possible patients should be offered
Adjuvant RT improves local control and overall sur- entry to clinical trials.
vival when added to surgery in locally advanced
cancers. It should be considered in all patients with Reconstruction following surgical ablation of oral cavity
larger T3 or T4 tumours, where there is ECS or tumours. There is a plethora of retrospective series
N2–3 neck disease. Other poor prognostic factors reporting technique and outcome of a wide range of
such as grade or peri-neurial invasion may also reconstructive techniques for the repair of defects
inform the decision.4 The morbidity of radiation to following ablation for oral cavity tumours.22,23
the primary site in the oral cavity means the benefits However, there are no randomised controlled trials.
and side effects should be carefully considered with The literature suffers from a wide range of heteroge-
each individual patient. neous factors introducing bias including tumour sites,
Concomitant chemotherapy improves the effective- stages, patient variables, operators, surgical techniques,
ness of adjuvant RT – more so in oral cavity tumours study designs, small numbers, lack of clarity for treat-
than in other primary sites of the upper aerodigestive ment intention and the reporting of different outcome
tract – and should always be considered in patients measures.
over 71 years old with relevant histological features Reconstructive options include local flaps, regional
when RT is discussed.20 However, it increases the pedicled flaps and microvascular free tissue transfer
acute and late morbidity of treatment. In patients with discussed elsewhere in the guidelines.24 Hard tissues
incurable disease, a short course of palliative RT may may be reconstructed using free autologous bone
help to improve local symptoms. Palliative chemother- grafts but more commonly involve the use of free
apy with platinum-based drugs and 5FU or capecita- tissue transfer from iliac crest, fibula, radius or scapula.
bine can also be considered to help symptoms and
improve survival. Lip
General principles. Early stage cancer can be treated
equally well by surgery or radiation therapy. The
Early stage cancer. Early stage tumours (T1 and small
five-year crude survival rates for surgical treatment
T2) can be adequately treated with either surgery or
are about 75–80 per cent for T1 to T2 tumours, drop-
brachytherapy. Treatment choice may be influenced
ping to 40–50 per cent for T3 and T4 tumours. The
by tumour size, location, depth of invasion, proximity
primary lymphatic drainage of the lower lip is to sub-
to bone, growth patterns including differentiation,
mental and submandibular level cervical lymph
neck nodal disease and access to services.
nodes. Neck dissection is generally not performed in
the absence of clinically suspicious cervical lymph
Advanced stage cancer. For advanced disease, stages III nodes as more than 5 per cent of patients are likely to
and IV (T3, T4 N0 and T1–4 N1), traditional manage- develop recurrence in the neck following treatment of
ment includes surgical resection, neck dissection, the primary lesion. The presence of cervical nodes at
reconstruction and post-operative RT. The latter presentation is a poor prognostic indicator. Small
should be offered to at least 60 Gy equivalent and opti- lesions are managed by simple surgical excision and
mally start within 6 weeks of surgery. In fit patients primary closure. Equally good results can be achieved
under the age of 71, adjuvant radiochemotherapy up with fractionated EBRT or brachytherapy. External
to 66 Gy with concurrent platinum-based chemother- beam radiotherapy using electrons or orthovoltage
apy should be considered for those with positive surgi- photons minimises dose to the oral cavity so that muco-
cal margins and/or ECS.21 sitis occurs only on the treated lip.
ORAL CAVITY AND LIP CANCER: UK GUIDELINES S87

Larger lesions of the lip require more consideration lower lip reconstruction requires either large cheek
with regard to reconstruction techniques. The function- flaps to be advanced to repair the defect or the use of
al outcome of the repair with regard to lip sensitivity free tissue transfer. The common forms of cheek flap
and muscle function also needs to be taken into consid- include the bilateral Gillies fan flaps or the
eration. Whenever possible full thickness skin flaps Bernard–Webster cheek flap reconstruction. Free
(skin, muscle and mucosa) should be used. The repair tissue transfer is required for lip reconstruction when
should provide sufficient mucosa contiguous to the the total remaining lip or adjacent rotated tissue is
commissure to avoid contracture. Superficial field insufficient to create a reasonable circular stoma.
change lesions affecting the external vermilion of the
lip such as leukoplakia or actinic keratosis are best
managed via a lip shave and mucosal advancement. Recommendation
Various studies have shown that for small tumours
radiation therapy can achieve a cure rate equivalent • Early stage lip cancer can be treated equally
to that obtained surgically. However, the cosmetic well by surgery or radiation therapy (R)
results of EBRT to the lip are usually not as satisfactory
as surgical excision and repair. Surgical excision of
small lip tumours involves relatively minor surgery,
Upper lip. Similar to lower lip defects wedge excisions
often under local anaesthetic and may be therefore and advancement flaps can address upper lip defects
less burdensome for the patient than a course of RT.
which involve up to one half of the width of the
The lower lip is one of the few ideal sites for orthovol-
upper lip. Care should be taken to respect the relevant
tage therapy. Using a single anterior field a fractionated aesthetic subunits. Defects of less than a third in the
course of 50 Gy in 15 fractions over 3 weeks is admi-
midline can be closed primarily. Defects involving
nistered. Brachytherapy can produce good aesthetic
greater than half of the lip can be reconstructed with
results but is not widely available in the UK. cross-lip flaps from the lower lip. Peri-alar crescentic
Iridium192 can be used in the treatment of lip cancer.
advancement flaps can be used to disguise the advance-
Patients can be treated twice a day for 4–5 days with
ment of the upper lip when the advancement
a total radiation dose between 40 and 45 Gy in 8–10 encroaches to the medial part of the nose. For defects
fractions.
involving more than two-thirds of the lip, a Burow-
Diffenbach reconstruction can be performed. This
Lower lip. Small lesions invading into the adjacent flap replaces upper lip defects by utilisation of laterally
muscle are amenable to a wedge excision. The excision based advancement flaps. Bilateral peri-alar crescentic
can also be completed using a ‘W’ plasty or half ‘W’ excisions are required to provide adequate advance-
plasty to avoid the inferior aspect of the excision ment. The various reconstructive options are identified
encroaching on the crease line of the chin. If the dimen- in Table III.
sions of the lip resection require the introduction of Most large series in the literature show that the
tissue to minimise functional problems and microsto- majority of patients have small lesions without palpable
mia, then this may be by means of Abbe, Abbe- cervical metastases although the incidence of syn-
Estlander or Karapandzic flaps. The Estlander modifi- chronous cervical metastases increases as the size of
cation of the cross-lip flap is used to reconstruct the the primary tumour increases. The local recurrence
oral commissure. The Karapandzic flap is useful for rate is low due to the relative ease of surgical excision.
defects involving more than two-thirds of the lower Even re-excision because of local failure leads to
lip, where the defect is in the midline. The main advan- salvage in 75–80 per cent of cases.
tage of the Karapandzic flap is that the nerve and blood
supply is retained and the underlying orbicularis Developing therapeutic regimens
muscle rotated so that a sensate functional lip recon- Neoadjuvant chemotherapy with TPF followed by
struction results. The various reconstructive options surgery and then RT is accruing evidence in other
are identified in Table II. With larger defects of the primary sites. Radio chemotherapy with the addition

TABLE II
RECONSTRUCTIVE OPTIONS FOR LOWER LIP DEFECTS TABLE III
RECONSTRUCTIVE OPTIONS FOR UPPER LIP DEFECTS
Defect size Procedure
Defect size Procedure
<1/2 Wedge excision
1/2 to 2/3 Karapandzic flap <1/2 Wedge excision
Abbe-Estlander flap 1/2–2/3 Peri-alar crescentic flap
>2/3 Bernard Burow Reverse Karapandzic flap
Gillies fan flap Abbe–Estlander flap
Webster flap >2/3 Burow–Diffenbach flap
Free flap Free flap
S88 C KERAWALA, T ROQUES, J-P JEANNON et al.

of targeted agents requires further evaluation. have been shown to have significant prognostic
Radiotherapy alone vs RT plus cetuximab in intermedi- value
ate cancers and the use of positron emission tomogra- • Post-operative adjuvant radiation or radiochemother-
phy–computed tomography to define the gross apy should be considered in the presence of
tumour volume and to assess response to non-surgical unfavourable disease factors.
treatments is the subject of ongoing research. Agents
such as palifermin and amifostine are under investiga-
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843–50 Address for correspondence:
22 Mucke T, Wolff KD, Wagenpfeil S, Mitchell DA, Holzle F. Cyrus Kerawala,
Immediate microsurgical reconstruction after tumor ablation pre- Head and Neck Unit,
dicts survival among patients with head and neck carcinoma. The Royal Marsden Hospital,
Ann Surg Oncol 2010;17:287–95 London, UK
23 Dziegielewski PT, Ho ML, Rieger J, Singh P, Langille M, Harris
JR et al. Total glossectomy with laryngeal preservation and E-mail: c.kerawala@googlemail.com