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Review
Management of the clinically N
0
neck in early-stage oral squamous
cell carcinoma (OSCC). An EACMFS position paper
Leandros V. Vassiliou
a
, Julio Acero
b
,
1
, Aakshay Gulati
c
,
1
, Frank H€
olzle
d
,
1
,
Iain L. Hutchison
e
, Satheesh Prabhu
f
,
1
, Sylvie Testelin
g
,
1
, Klaus-Dietrich Wolff
h
,
1
,
Nicholas Kalavrezos
i
,
*
,
1
a
Department of Oral and Maxillofacial Surgery, Royal Blackburn Hospital, Haslingden Road, Blackburn, UK
b
Department of Oral and Maxillofacial Surgery, Ramon y Cajal University Hospital, Alcala University, Madrid, Spain
c
Maxillofacial Unit, Queen Victoria Hospital, Holtye Road, East Grinstead, UK
d
Department of Oral and Maxillofacial Surgery, Aachen University Hospital, Aachen, Germany
e
Department of Oral &Maxillofacial Surgery, Barts Health NHS Trust, Saving FacesdThe Facial Surgery Research Foundation, London, UK
f
Division of Oral &Maxillofacial Surgery, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, UK
g
Department of Maxillo-Facial Surgery, University Hospital of Amiens, Amiens, France
h
Department of Oral and Maxillofacial Surgery, Technical University of Munich, University Hospital Rechts der Isar, Munich, Germany
i
Department of Head &Neck Surgery, University College London Hospital, London, UK
article info
Article history:
Paper received 23 May 2020
Accepted 20 June 2020
Available online 2 July 2020
Keywords:
Oral cavity
Oral squamous cell carcinoma
OSCC
Lymph node
Sentinel node
Depth of invasion
abstract
Metastasis of oral squamous cell carcinoma (OSCC) to the cervical lymph nodes has a significant impact
on prognosis. Accurate staging of the neck is important in order to deliver appropriate treatment for
locoregional control of the disease and for prognosis.
The management of the neck in early, low volume disease (clinically T
1
/T
2
oral cavity tumours) has
long been debated. The risk of occult nodal involvement in cT
1
/T
2
OSCC is estimated around 20e30%.
We describe the natural evolutionary history of OSCC and its patterns of spread and metastasis to the
local lymphatic basins. We discuss most published literature and studies on management of the clinically
negative neck (cN
0
). Particular focus is given to prospective randomized trials comparing the outcomes of
upfront elective neck dissection against the observational stance, and we summarize the results of the
sentinel node biopsy studies.
The paper discusses the significance of the primary tumour histological characteristics and specif-
ically the tumour's depth of invasion (DOI) and its impact on predicting nodal metastasis. The DOI has
been incorporated in the TNM staging highlighting its significance in aiding the treatment decision
making and this is reflected in world-wide oncological guidelines.
The critical analysis of all available literature amalgamates the existing evidence in early OSCC and
provides recommendations in the management of the clinically N
0
neck.
©2020 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights
reserved.
1. Introduction and Purpose
Oral squamous cell carcinoma (OSCC) is one of the most common
cancers globally with an estimated incidence of 275,000 new cases
annually (Mooreet al, 2000;Jemal et al., 2011;Montero and Patel,
2015;Warnakulasuriya, 2009;Chow, 2020). The disease is staged
based on the AJCC TNM system (Edgeet al, 2010;Aminet al, 2017).
Forty to fifty percent of patients with OSCC present with clinical
stage I or II disease (De Zinis et al., 2006; Shimizu et al., 2006). The
most common site of presentation is the oral tongue followed by
the floor of mouth (FOM) (Funk et al., 2002;Li et al., 2013;Shah
et al., 2019). In early oral cancer the rate of occult metastasis is
estimated between 20 and 40%. Nodal metastasis comprises the
most significant prognosticator with survival rates decreasing by as
much as 50% in N
1
disease (Amit et al., 2013;Kowalski et al., 2000).
*Corresponding author.Head &Neck Surgery, University College London Hos-
pital, 250 Euston Road, London, NW1 2PG, United Kingdom.
E-mail address: n.kalavrezos@nhs.net (N. Kalavrezos).
1
EACMFS Head &Neck Oncology Group.
Contents lists available at ScienceDirect
Journal of Cranio-Maxillo-Facial Surgery
journal homepage: www.jcmfs.com
https://doi.org/10.1016/j.jcms.2020.06.004
1010-5182/©2020 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
Journal of Cranio-Maxillo-Facial Surgery 48 (2020) 711e718
Metastatic spread to two or more lymph nodes is an indication
for adjuvant radiotherapy and if the tumour cells invade through
the capsule of the lymph node (extracapsular/extranodal spread)
additional chemotherapy should be administered to improve sur-
vival (Woolgar et al., 2003). A small T
1
OSCC of the anterior floor of
mouth that has metastasised bilaterally (N2) meets the criteria for
IV
A
stage. This accounts for an expected 5-year overall survival (OS)
of 34% and disease specific survival (DSS) of 52%, or less (Montero
and Patel, 2015;Shah et al., 2019;Saggi et al., 2018). It is there-
fore prudent to establish the nodal status of the neck not only for
prognosticating purposes, but most importantly for planning and
delivering adjuvant treatment in a timely manner.
The management of the clinically N
0
neck has long been
debated. The main policies that have been considered in managing
the neck in early oral cancer are the following:
1. Upfront elective neck dissection (END)
2. Watch and wait policy, and more recently
3. Sentinel node biopsy (SNB)
The purpose of this paper is to critically analyse the existing
literature and provide an evidence-based approach in the man-
agement of the neck in cT
1
/T
2
N
0
oral squamous cell carcinoma.
2. OSCC high risk characteristics and patterns of spread
Oral squamous cell carcinoma comprises a malignant disease of
epithelial origin in accordance with the principles of carcinogenesis
(Hanahan and Weinberg, 2011). Its natural course and patterns of
spread have been studied extensively (Brandwein-Gensler et al.,
2005;Woolgar et al., 1995).
Tumours with clinically aggressive features such as rapid and
endophytic growth are likely to histologically correlate with poor
differentiation, non-cohesive pattern of spread, perineural and/or
lymphovascular invasion and are more likely to metastasize early
(Woolgar and Scott, 1995). Alveolar (gingival), floor of mouth, and
retromolar OSCC penetrate into the bone directly through the
attachment points of Sharpey's fibres to the cortex (Brown et al.,
2002).
OSCC in previously untreated patients metastasises in the neck
following predictable patterns that correspond with the respective
lymphatic draining basins (Lindberg, 1972;Shah et al., 1990). The
predominant pattern of lymphatic spread resembles the shape of
an ‘inverted cone’(Woolgar, 2007). Aggressive or rapidly spreading
(fast-tracking) tumours may concomitantly affect several nodal
levels through ‘overflow’or ‘flushing’and ‘peppering’effects
(Woolgar, 1999,2007).
Asubsite approach applies in the prediction of lymphatic nodal
levels that may harbour occult metastases. Lateralised tumours,
such as buccal, gingival, retromolar and maxillary OSCC metastasise
first into ipsilateral levels I and IIa (Lindberg, 1972;Shah et al., 1990;
Woolgar, 2007;Boeve et al., 2017)(Fig. 1).
The more anterior the tumour is located the higher the likeli-
hood of Level I
A
involvement and the more posterior the higher the
chance of level IIa involvement. In buccal OSCC, the facial lymph
node is at risk (Agarwal et al., 2016).
Tongue OSCC predominantly spreads to levels I and II with a
small fraction (6e12%) of tumours metastasizing contralaterally or
bilaterally depending on the tumour's proximity to the midline
(Lindberg, 1972;Kowalski et al., 1999) and its histopathological
aggressiveness (Fan et al., 2011)(Fig. 2).
The more posterior the tongue tumour, the higher the chance of
level II
B
and contralateral nodal metastasis, due to higher lymphatic
interconnections posteriorly towards the base of tongue (Sharpe,
1981;Kowalski et al., 1999;Olzowy et al., 2011). Level II
B
was
involved in 5.4% of cN
0
OSCC cases only when other nodal levels
were positive (32.4%) (Lim et al., 2004). In a study with 45.8% rate of
occult neck metastases in cN
0
OSCC, 10.4% of level II
B
were
concomitantly involved (Elsheikh et al., 2005).
Tumours arising close to the midline such as the floor of mouth
(FOM) or the palate spread to levels I and II
A
with approximately 25%
probability of bilateral or contralateral nodal involvement (Lindberg,
1972 ;Shah et al., 1990;Kowalski et al., 1999)(Fig. 3).
In the majority of OSCC patients, level IV is only involved when
other neck levels are positive for metastasis. Byers et al. reported that
clinically N
0
OSCC metastasised to level IV in 15.8% of the cases,
where 5.5% accounted for true ‘skip metastases’(Byers et al., 1997).
Shah et al. reported 3% of level IV involvement in cN
0
OSCC (Shah
et al., 1990). True skip metastases to level IV account for 2% or less
of the cases, predominantly from tongue OSCC (Cariati et al., 2018;
Crean et al., 2003;Warshavsky et al., 2019). Level V in cN
0
oral cancer
is rarely involved (less than 1%) (Shah et al., 1990).
3. Approaches in the management of cN
0
OSCC
The management of the cN
0
neck in the oral cavity SCC has been
a matter of controversy and scientific debate for the past 4 decades
(Wei et al., 2006). Various imaging modalities including US, CT, MRI,
PET have aimed to underpin an evidence-based approach, however
large studies have demonstrated the limitation of any preoperative
imaging in accurately staging the clinically negative neck (Van den
Brekel et al., 1996;Ferlito et al., 2002).
Algorithmic models have also been introduced to aid with the
dilemma of observing (watchful wait policy) or treating the neck
prophylactically, with an acceptable threshold of 20% of probability
of occult metastasis to favour elective neck dissection (END) (Weiss
et al., 1994).
The observational stance in cN
0
cases was based on the
assumption that the neck can be therapeutically treated when and
if patients develop an early recognised regional N
1
failure, however
further studies showed that often the patients presented with N
2
or
Fig. 1. Predominant lymph node levels for metastasis of lateralised OSCC tumours) (Lindberg, 1972;Shah et al., 1990;Woolgar, 2007;Boeve et al., 2017;Broglie et al., 2013;Sharpe,
1981;Essig et al., 2012). The estimated probability is demonstrated in the circles; a. Buccal b. Gingival (alveolar) c. Retromolar d. Maxillary OSCC.
L.V. Vassiliou et al. / Journal of Cranio-Maxillo-Facial Surgery 48 (2020) 711e718712
N
3
disease ending with disappointing survival outcomes (Andersen
et al., 1996;Lydiatt et al., 1993).
The superiority of END in achieving better survival outcomes
has been demonstrated in numerous retrospective studies
(Vandenbrouck et al., 1980;Fakih et al., 1989;Franceschi et al.,
1993;Kligerman et al., 1994;Yuen et al., 1997;Beenken et al.,
1999;Yii et al., 1999;Huang et al., 2008;Tai et al., 2012;Feng
et al., 2014).
Substantial data with adequate power to seal the debate be-
tween the observational policy and upfront END in early stage OSCC
have been obtained by prospective randomised clinical studies
(Yuen et al., 2009;D'Cruz et al., 2015;Fasunla et al., 2011), with two
large scale studies published by Tata Memorial Centre in India and
Fig. 2. Predominant lymph node levels for metastasis of tongue SCC (Lindberg, 1972;Shah et al., 1990;Woolgar, 2007;Broglie et al., 2013;Sharpe, 1981;Kowalski et al., 1999;Cariati
et al., 2018;Crean et al., 2003;Elsheikh et al., 2005;Lim et al., 2004;Warshavsky et al., 2019). The estimated probability is demonstrated in the circles. Lateral view demonstrates
ipsilateral commonly affected neck levels. Front view demonstrates the rate of possible contralateral neck nodal involvement.
Fig. 3. Predominant lymph node levels for metastasis of OSCC arising in midline subsites (Lindberg, 1972;Shah et al., 1990;Woolgar, 2007;Broglie et al., 2013;Kowalski et al.,1999;
Capote-Moreno et al., 2010). The estimated probability is demonstrated in the circles; a. Floor of mouth (FOM) b. Palatal OSCC (oral side).
L.V. Vassiliou et al. / Journal of Cranio-Maxillo-Facial Surgery 48 (2020) 711e718 713
the UK (D'Cruz et al., 2015;Hutchison et al., 2019). In the former
landmark randomised controlled trial (RCT), D'Cruz et al. demon-
strated the significant DFS and OS benefit (DFS 69.5% and OS 80% in
the END groups as opposed to DFS of 45.9% and OS of 67.5% in the
observation and therapeutic ND group, respectively) in early-stage
OSCC patients that underwent upfront elective neck dissection
(D'Cruz et al., 2015). The UK nation-wide trial is published along
with a meta-analysis and a concurrent real-world cohort and
further emphasises the benefits of upfront END even with small
cT1N0 disease. It also compares END with the SNB approach, which
is perceived as a primarily diagnostic approach (Hutchison et al.,
2019). The impact of the RCTs in the field has resonated in further
large-scale meta-analyses (Abu-Ghanem et al., 2016;Ren et al.,
2015;Oh et al., 2020;Cai et al., 2020)(Table 1).
There is consensus that the extent of the END should be in the
form of a selective I-IV neck dissection, as this is equally effective
than more extensive, but morbid, types of ND (MRND, RD) (Huang
et al., 2008), as long as there is a minimum yield of 18 lymph nodes
(Ebrahimi et al., 2014;Zenga et al., 2019).
4. Sentinel node biopsy (SNB)
During the conflict between the observational management of
the cN
0
neck and the upfront elective neck dissection the concept of
sentinel node biopsy has emerged as a compromise between the
two polarised stances.
This approach essentially involves preoperative injection of a
radiotracer (nanocolloid labelled with Technetium 99 m,
99m
Tc) at
the tumour site (submucosal tumour periphery), followed by
planar lymphoscintigraphy in conjunction with SPECT/CT (single-
photon emission computed tomography combined with low-dose
CT) to localise the draining lymph nodes (Civantos et al., 2010;
Den Toom et al., 2015;Schilling et al., 2015). Intraoperative ad-
juncts, such as visual blue dye, or fluorescence, alongside a gamma
probe/Geiger meter-detection, aid further in tracing the echelon
node that theoretically drains the site of the primary tumour
(Civantos et al., 2010;Den Toom et al., 2015;Schilling et al., 2015).
The latter should be the first lymph node to harbour occult
metastasis. The protocol of SNB dictates that if the sentinel lymph
node is found positive for metastasis then a formal neck dissection
should be carried out (Civantos et al., 2010).
The inspiration for SNB originally stems from breast cancer,
where axillary lymphadenectomy bears detrimental side-effects
(lymphoedema and functional complications for the upper limb),
hence the need for lesser invasive staging procedures (Pesek et al.,
2012).
Conceptually fascinating, the SNB utilises and promotes modern
imaging technologies and as expected has attracted marked
research interest. Numerous units have published data on the
diagnostic accuracy of this method in head and neck cancer (Broglie
et al., 2013;Den Toom et al., 2015;Kovacs et al., 2009;Samant,
2014;Pedersen et al., 2016;Moya-Plana et al., 2018;Loree et al.,
2019). The SNB topic has been studied in multi-centre trials
(Civantos et al., 2010;Schilling et al., 2015;Miura et al., 2017;Ross
et al., 2004)(Table 2). The false negative ratio (FNR) ratio varies
from 5% to 27% (Pedersen et al., 2016;Milenovic et al., 2014) and is
borderline acceptable (14%) in large scale studies (Schilling et al.,
2015).
The ability to accurately identify the echelon node appears to be
site-specific, with FOM tumours displaying higher false negative
rates (usually due to “shine-through”artefact) in the range of 25%
(Civantos et al., 2010;Milenovic et al., 2014;Alvarez et al., 2014).
There is very little evidence to date about the usefulness of SNB in
maxillary cancer (Boeve et al., 2017) and the current stance favours
elective neck dissection as recurrences (all T-stage maxillary tu-
mours) affect the contralateral neck in high ratio (45.5%) (Joosten
et al., 2017).
Lymphoscintigraphy could be useful in identifying the sentinel
node in cases of bilateral or contralateral drainage (12e20%)
depending on the proximity to the midline (approximately 2% of
occult metastasis to the contralateral site) (Broglie et al., 2013;
Schilling et al., 2015), or in cases of previously treated neck where
the lymphatic drainage is expected to be altered (Flach et al., 2012).
Sentinel node positivity or ‘upgrade’of the neck status rate
varies from 8.7% (N ¼103) (Kovacs et al., 2009) to 38% (N ¼111) in
SNB studies (Broglie et al., 2013), further necessitating formal neck
dissection. The latter reveals additional positive lymph nodes
(upstaging the disease to pN
2
or pN
3
) in approximately 20% of the
otherwise clinically staged as N
0
cases (Broglie et al., 2013;Den
Toom et al., 2015;Pedersen et al., 2016;Moya-Plana et al., 2018;
Loree et al., 2019;Milenovic et al., 2014;Rigual et al., 2013). All SNB
studies demonstrate lower survival outcomes in the SNB positive
patients (OS range 38%e71% in SNB positive patients).
Cost-effectiveness reports demonstrate that although SNB is
cost-effective in SNB negative cases, the cost in SNB positive cases
raises significantly (Hernando et al., 2016).
Therefore, despite the evidence that SNB benefits true pN
0
early-stage OSCC patients by sparing them from the potential
morbidity of ND, the technique might prove disadvantageous for N
(þ) patients, as it is not therapeutic for this group and exposes
those patients to two operative procedures, potentially delaying
the delivery of adjuvant treatment.
It becomes prudent to attempt to predict the SNB result and
therefore reserve this approach for patients who are not at high risk
of occult nodal disease (Sawant et al., 2017). In two large SNB co-
horts, Pedersen et al. (N ¼253) (Pedersen et al., 2016) and Moya-
Table 1
Prospective Randomised Trials and Meta-Analyses on END vs Observation.
TYPE OF STUDY Year N Subsite of
Primary
Outcome
Prospective Randomised Trials
Vandenbrouck
et al.
1980 75 All No Statistical difference END vs
Observation
Fakih et al. 1989 70 Tongue In favour of END
Kligerman et al. 1994 67 Tongue/FOM In favour of END
Yuen et al. 2009 71 Tongue No Statistical difference END vs
Observation
D'Cruz et al. 2015 596 Tongue/FOM/
Buccal
In favour of END
Hutchison et al.
(SEND)
2019 250 All In favour of END
Meta-Analyses
Fansula et al. 2011 283 All In favour of END
Ren et al. 2015 779 All In favour of END
Abu-Ghanem
et al.
2016 3244 All In favour of END
Hutchison et al.
(SEND)
2019 958 All In favour of END
Cai et al. 2020 5705 All In favour of END
Oh et al. 2020 1317 Tongue/FOM/
Buccal
In favour of END
Table 2
Multi-centre SNB trials.
Year N Subsite of Primary % SNB(þ) FNR
Civantos et al. 2010 140 Tongue/FOM 28% Tongue: 10%
FOM: 25%
Schilling et al.
(SENT)
2015 415 All 26% 14%
Miura et al. 2017 57 Tongue/FOM/Alveolus 17.8% 9.1%
L.V. Vassiliou et al. / Journal of Cranio-Maxillo-Facial Surgery 48 (2020) 711e718714
Plana et al. (N ¼229) (Moya-Plana et al., 2018) reported statistically
significant association between sentinel node positivity and pri-
mary tumour characteristics such as T-stage, grade of differentia-
tion, perineural invasion, lymphovascular involvement and tumour
thickness or depth of invasion (DOI). Based on the aforementioned
criteria, Pedersen et al. stratified the primary OSCC tumours in low-
and high-risk for occult lymph node metastasis, reporting a rate of
12% and 70% respectively (Pedersen et al., 2016).
5. Primary (index) tumour depth of invasion and its
significance to predict nodal metastasis
The propensity of OSCC to metastasize has been linked to its
vertical growth in a manner comparable with the Breslow thickness
in malignant melanoma (Breslow, 1979). The vertical dimension of
a tumour's growth can be measured by its thickness or its depth of
invasion (DOI).
Although the terms tumour's thickness and tumour's depth of in-
vasion (DOI) have often been interchangeably used in the literature,
they are not synonymous (Moore et al., 1986;Lydiatt et al., 2017);
#Tumour thickness represents the vertical dimension of the
tumour measured from the deepest point of invasion to its
mucosal surface.
#Depth of invasion (DOI) is measured from the deepest point of
invasion to the basement membrane of the most normal adjacent
mucosa (Moore et al., 1986;Lydiatt et al., 2017).
This distinction is important and separates ‘thick’, exophytic
tumours from ulcerated, ‘endophytic’and highly invasive carci-
nomas. In this section however we make reference to the terms
‘thickness’and ‘DOI’with respect to their original use in the refer-
enced articles.
Initial studies linked the metastatic potential of OSCC with the
tumour thickness (Mohit-Tabatabai et al., 1986;Spiro et al., 1986).
Subsequent studies substantiated these findings and further
demonstrated site-specific differences in tumour thickness cut-offs
(Woolgar and Scott, 1995;Kligerman et al., 1994;Sheahan et al.,
2003;Urist et al., 1987;Po Wing Yuen et al., 2002).
The tumour thickness threshold for FOM tumours beyond which
the incidence of nodal metastasis rises over 20%, therefore indi-
cating benefit from prophylactic/staging neck dissection is 1.5 mm
(Mohit-Tabatabai et al., 1986;Balasubramanian et al., 2014). The
threshold for tongue OSCC is set at 4e5 mm (Woolgar and Scott,
1995;Balasubramanian et al., 2014).
Further research on the field has clarified that it is the tumour's
depth of invasion (DOI) that reflects more accurately its penetrative
and infiltrative potential as opposed to its thickness (Moore et al.,
1986).
Pentenero et al. and numerous reports showed positive corre-
lation between DOI and nodal metastasis (Pentenero et al., 2005;
Garzino-Demo et al., 2016;Melchers et al., 2012).
The strong correlation of either the tumour's thickness (cut-off
4 mm) or DOI with nodal metastasis has been demonstrated clearly
in the randomised control trial of D'Cruz et al. (D'Cruz et al., 2015)
and has been highlighted in a large-scale SNB study (N ¼253) by
Pedersen et al. (2016).
A summary of the critical tumour thickness and DOI beyond
which tumour metastasis becomes more likely is demonstrated in
Table 3.
All recent data suggest that the DOI is a better predictive
parameter in comparison to thickness and the accepted DOI
threshold beyond which the risk of nodal metastasis increases is
1.5 mm for FOM tumours and 4 mm for the rest of the oral cavity
OSCC (Lydiatt et al., 2017).
The high prognostic significance of a tumour's DOI in staging the
OSCC as well as predicting nodal metastasis and dictating the
management of the neck has been reflected in the recent 8
th
AJCC
classification update (Aminet al, 2017). The latter quoted the re-
ports of Spiro et al. (1986) and Ebrahimi et al. (2019). Oral cavity
tumours with DOI of 5 mm and above are staged as T2 and with
10 mm and above T3, irrespective of the tumour's surface diameter,
acknowledging the significance of the vertical dimension of tumour
growth in conjunction to the traditionally measured ‘maximum
diameter’(Edgeet al, 2010).
Current research is focusing on optimising and improving the
ability to accurately measure the tumour's DOI with preoperative
imaging (Brouwer de Koning et al., 2019;Tarabichi et al., 2019;Lam
et al., 2004;Yesuratnam et al., 2014).
Apart from the DOI, other index tumour characteristics such as
perineural invasion and pattern of infiltration (non-cohesive) have
also been shown to correlate with positive nodal metastasis (pre-
diction) potentially driving a future approach of individualised
tumour risk-profiling (Sawant et al., 2017). Recent studies reveal
that perineural invasion is a result of complex tumour molecular
mechanisms and that is a reliable reflection of aggressive tumour
biology (Galmiche et al., 2020;Saidak et al., 2020).
6. Existing worldwide guidelines
Although a significant proportion of OSCC patients present at an
early stage of the disease, it is of interest to note that there is
globally a lack of consensus amongst the published guidelines on
the management of the cN
0
neck.
In Europe, the EHNS-ESMO-ESTRO guidelines do not provide
explicit recommendation for the management of early (Stage I and
II) OSCC and to the authors’best awareness have not been updated
since the last AJCC classification upgrade (Gregoire et al., 2010). The
German guidelines written by Wolff et al. strongly favour upfront
elective neck dissection regardless of the T stage of the tumour
(Wolff et al., 2012).
In the UK the 2016 NICE guidelines (National Collaborating
Centre for Cancer, 2016) suggest that SNB should be offered for
cT1-T2, N
0
OSCC tumours, referring to the 7
th
Edition of the
staging, prior to the incorporation of the DOI in the T-staging
system. The 2016 BAHNO guidelines (Kerawala et al., 2016)
distinguish the T1 and T2 tumours based on thickness and set a
cut-off of 4 mm above which elective neck dissection is recom-
mended, whereas for thinner tumours SNB is preferred. The
Scottish guidelines in the last update in 2006 favoured prophy-
lactic END for all oral cavity cN
0
tumours (S.I.G.N. 2006).
Examples from other countries and continents are similar with
the Japanese head and neck cancer guidelines highlighting the
controversy in managing the neck in early OSCC (Nibu et al., 2017),
whereas Canadian guidance published in 2015 accepts a 4 mm DOI
threshold, above which they favour elective ND (S.C.A.O.C.C. 2015).
The most concise and comprehensive guidelines globally are the
NCCN and ASCO guidelines (NCCN, 2019;Koyfman et al., 2019). The
former incorporates the DOI in an explicit evidence-based treat-
ment decision algorithm. The NCCN strongly suggests END for
tumour DOI 4 mm or above and reserves SNB only for thin OSCC of a
DOI up to 2 mm. For intermediate depth tumours the guideline
suggests correlation with other tumour and patient characteristics
pointing towards a more individualised approach (NCCN, 2019).
The ASCO guidelines favour upfront elective neck dissection and
also recommend a lowthreshold for elective surgical treatment of
the contralateral neck in tumours proximal to the midline
(Koyfman et al., 2019).
L.V. Vassiliou et al. / Journal of Cranio-Maxillo-Facial Surgery 48 (2020) 711e718 715
7. Recommended policy
Based on the current best available evidence we propose that
elective neck dissection should comprise the default mainstay
treatment of the cN
0
neck. Elective surgical management of the
neck has the following advantages:
1. Accurate staging; Selective neck dissection allows analysis of
all the nodal basins in the draining region of the primary tumour
and provides the most reliable means of staging.
2. Locoregional Control; END pre-empts the best opportunity
for locoregional control of the disease (prophylactic and thera-
peutic management).
3. Adjuvant treatment planning; Pathological assessment of the
regional lymph nodes allowing timely planning and delivery of
appropriate adjuvant therapy (RT or CRT).
The primary tumour depth of invasion (DOI) constitutes indis-
putably a key parameter in the evaluation of the risk for nodal
occult metastasis and the overall prognosis of the disease and it
should be taken under consideration in the treatment planning
(primary and adjuvant).
SNB risks de-escalating the therapeutic approach in high risk
cancers and should be reserved for carefully selected cases, when
nodal metastasis in unlikely to occur. SNB has a role in clinically
thin (less than 2 mm DOI) tongue, buccal and alveolar SCC while it
can also be considered in histologically “favourable”SCCs of
2e4 mm DOI. SNB should not be employed in FOM tumours due to
the inherent site-specific inaccuracies of the technique and its high
false negative ratio in this anatomical subsite.
FOM tumours should be considered high-risk for regional
failure and should be approached differently, due to the early
preponderance of tumours to spread (DOI 1.5 mm). In FOM OSCC
strong consideration for bilateral selective neck dissection must
be given.
Estimation of DOI preoperatively cannot always be guaranteed
with accuracy. Correlation with other clinical (site, endophytic
growth profile), radiological and histopathological (evidence of
poor differentiation, perineural invasion, lymphovascular spread,
non-cohesive pattern of infiltration from the initial biopsy spec-
imen) evidence is recommended, with a low threshold to embark
on END.
Future research should be targeted on more accurate profiling
of the primary tumours and assist in tailoring the extent of the
surgical management to decisively intercept the biological
aggressiveness of the disease. Lymphoscintigraphy and sentinel
node biopsy may be of value as a diagnostic mapping procedure,
and further research should be undertaken in its applicability in
tracing the nodal involvement in tumours proximal to the
midline and previously treated patients (recurrent or metachro-
nous disease) where altered or aberrant lymphatic drainage is
expected.
Competing interests
None declared.
Acknowledgements
The authors wish to thank Mr Francis Vassiliou for the graphic
design of the illustrations.
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