Accurate clinical staging of oral squamous cell cancer can be quite difficult to achieve especially if nodal involvement is identified. Radiologically-assisted clinical staging is more accurate and informs the clinician of loco-regional and distant metastasis

A Leslie

Aidan Adams

Aviva Petrie

Colin Hopper

Hani Radhi

Jacqueline Callear

Jesuloba Abiola

JP Shah

JV Bagan

Kartic Rajaram

M Noguchi

P Garzino-Demo

P Held

P Sureshkannan

Panagiotis Kafas

PM Specenier

R Mazeron

S Jank

S Warnakulasuriya

SC Hodder

SK Mukherji

Syedda Abbas

Tahwinder Upile

W Jerjes

Waseem Jerjes

Y Anzai

English

PubMed

Crossref

RESEARCH Open AccesscTNM vs. pTNM: the effect of not applyingultrasonography in the identification of cervicalnodal diseaseWaseem Jerjes1,2,3*, Tahwinder Upile4,5, Hani Radhi2*, Aviva Petrie6, Jesuloba Abiola1, Aidan Adams3,Jacqueline Callear3, Panagiotis Kafas7, Syedda Abbas5, Kartic Rajaram3 and Colin Hopper1,5AbstractAccurate clinical staging of oral squamous cell cancer can be quite difficult to achieve especially if nodalinvolvement is identified. Radiologically-assisted clinical staging is more accurate and informs the clinician of loco-regional and distant metastasis.In this study, we compared clinical TNM (cTNM) staging (not including ultrasonography) to pathological TNM(pTNM) staging in 245 patients presenting with carcinoma of the oral cavity and the oro-pharyngeal region.Tumour size differences and nodal involvement were highlighted. US reports of the neck were then added to theclinical staging and results compared.Tumour size was clinically underestimated in 4 T1, 2 T2 and 2 T3 oral diseases. Also 20 patients that were reportedas nodal disease free had histological proven N1 or N2 nodal involvement; while 3 patients with cTNM showingN1 disease had histologically proven N2 disease.Overall the agreement between the 2 systems per 1 site was 86.6% (Kappa agreement = 0.80), per 2 sites 90.0%(Kappa agreement = 0.68) and per 3 sites 90.5% (Kappa agreement 0.62).An accurate clinical staging is of an utmost importance. It is the corner stone in which the surgical team build thesurgical treatment plan and decide whether an adjuvant therapy is required to deal with any possible problemthat might arise. The failure to achieve an accurate staging may lead to incomplete surgical planning and henceunforeseen problems that may adversely affect the patient’s survival.BackgroundThe development of modern imaging techniques hassignificantly altered the treatment and management ofhead and neck malignancies. Important treatment deci-sions that were once made intra-operatively are nowmade preoperatively by means of advanced imaging, i.e.computed tomography (CT) and magnetic resonanceimaging (MRI) [1].MRI has been proved superior to CT, on account ofits coronal and sagittal slice orientation enabling notonly a better demonstration of findings, but alsoimproved tumour detection and staging [2]. Also whenit comes to T-staging, MRI is overall more accuratethan CT. However, if degraded images and T1 tumoursare excluded, the techniques are comparable. MRI isoversensitive for recurrent disease. For Nodal staging,MRI was found comparable to CT [3]. Although CTand MRI allow detection of abnormally enlarged nodesor necrotic nodes, neither borderline-sized nodes with-out necrosis nor extra-capsular spread are reliably differ-entiated from reactive or normal nodes in patients withhead and neck cancer [4].Accurate clinical staging of pathologies involving theoral and oro-pharyngeal-laryngeal regions can be quitedifficult to achieve, especially if nodal disease isinvolved. The current practice worldwide when it comesto clinically staging tumours identified in these areasusually involve carrying out a thorough clinical examina-tion of the head and neck region followed by radiologi-cal investigations. The latter usually involve carrying out* Correspondence: waseem_wk1@yahoo.co.uk; hani_hadi79@hotmail.com1UCL Department of Surgery, University College London, London, UK2Oral and Maxillofacial Surgery Unit, AL-Mustansirya University, Baghdad, IraqFull list of author information is available at the end of the articleJerjes et al. Head & Neck Oncology 2012, 4:5http://www.headandneckoncology.org/content/4/1/5© 2012 Jerjes et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.PUBLISHER’S NOTE: Based on the information available to BioMed Central, this article was apparently handled by Waseem Jerjes, the first author of the article and Editor-in-Chief of the journal at that time. The article states that ‘All applications were accompanied by multidisciplinary team recommendation, ethical approval and informed patient consent.’ UCL’s investigation concluded that this study was a retrospective analysis of data which would be classed as clinical audit and not a research study. Mr Hopper agreed it was a mistake on the part of the authors to state the analysis had ethical approval and informed consent. Mr Hopper has published a correction (https://www.oapublishinglondon.com/article/740).an MRI of the head and neck, or a CT scanning if bonyinvasion is anticipated (i.e. edentulous patients). Therest of the clinical staging involve a CT scanning of thechest and the upper abdomen to rule out any tumourspread to the pulmonary or hepato-pancreato-biliaryorgans [5].In most of the centres in the developed world, anultrasonography (US) imaging of the neck is carried outto identify any nodal involvement which cannot be iden-tified by other imaging modalities (i.e. MRI or CT);unfortunately the lack of expertise in the developingworld stops the application of US technology. US is areliable and valuable tool for metastatic lymph nodescreening in head and neck cancer patients. It is acheap, non-invasive, easy-to-handle and cost-effectivediagnostic method [6].This has lead many centres around the world tochange its practice to include US as part of clinical sta-ging process for any patient who presents with patholo-gical lesion in the head and neck. Furthermore, theadvances in cytological sciences allowed fine needleaspiration of neck nodes under US-guidance andallowed identification of reactive lymph nodes prior tosurgery. A study identified US, with or without FNAC,as an accurate (86%), sensitive (92%) and specific (83%)technique for the preoperative assessment of lymphnode metastases in patients with SCC [7]. In anotherstudy, US (for all levels) yielded a sensitivity of 71%, anda specificity of 87%, while CT showed a sensitivity of32% and a specificity of 96%. The sensitivity of USdecreased from level I to level IV, whereas the specificityincreased from level I to level IV [8].In this short communication, we retrospectively com-pared clinical TNM (cTNM) staging (not including US)to pathological TNM (pTNM) staging in patients pre-senting with carcinoma of the oral cavity and the oro-pharyngeal region. Tumour size differences and nodalinvolvement were highlighted. US reports of the neckwere then added to the clinical staging and resultscompared.Materials & methodsIn this retrospective analytic study, we looked at cTNMstaging and pTNM staging of 245 patients with oral andpharyngeal squamous cell carcinoma who underwenttreatment at the UCLH Head and Neck Centre, Londonfrom 2001 to 2006.The patients’ data were entered onto proformas, whichwere validated and checked by interval sampling. Thefields included a range of clinical, operative and histo-pathological variables related to disease staging. Allapplications were accompanied by multidisciplinaryteam recommendation, ethical approval and informedpatient consent.In this short communication, the cTNM staging wasachieved through clinical examination of the head andneck region and MRI, or CT scan when indicated, andno US scan of the neck. This was compared to pTNMtrying to identify any underestimation in tumour size ormissed cervical nodal disease. Agreement between bothstaging systems were assessed per anatomical site. Then,US reports were added to the cTNM staging and resultscompared again.Statistical analysisThe outcomes of the categorical clinic-pathological vari-ables (cTNM and pTNM) were summarised as frequen-cies and percentages for the whole group of patients.Kappa score agreement, with its standard error, was cal-culated to compare cTNM and pTNM for primary, sec-ondary and tertiary sites; also was applied to per 1 site,per 2 sites and per 3 sites.ResultsTable 1 highlights the cTNM and the pTNM staging ofthe cohort involved in this study. Tumour size was clini-cally underestimated in 4 T1, 2 T2 and 2 T3 oral dis-eases. Also 20 patients that were reported as nodaldisease free had histological proven N1 or N2 nodalinvolvement; while 3 patients with cTNM showing N1disease had histologically proven N2 disease (Table 1).When the US data was added to the cTNM staging, nodifferences were identified in nodal disease assessment.Agreement on anatomical sites between cTNM andpTNM, as well as kappa scores, are highlighted in Table2. The agreement between cTNM (without US) andpTNM when assessing the tongue was 95.7%, FOM86.6%, buccal mucosa 82.9%, retromolar area 75.0% andtonsils 91.7%. This may be due to the fact that deep andposterior oral structures are a challenge during clinicalexamination as well as the dental artifacts that couldarise during scanning which affects staging of peri-den-tal tumours (Table 2).Overall the agreement between the 2 systems per 1site was 86.60% (Kappa agreement = 0.80), per 2 sites90.0% (Kappa agreement = 0.68) and per 3 sites 90.48%(Kappa agreement 0.6182), (Table 2).DiscussionCancers of the oral cavity and oro-pharyngeal region arethe sixth most common cancers in the world. Unfortu-nately the incidence continues to rise with moderatesurvival rates, despite the recent advances in surgeryand radiotherapy [9-11]. Oral squamous cell carcinoma(OSCC) continues to affect more males than femaleswith a ratio of 1.5-1. Diagnosis is usually at the fifth orsixth decade of life. However there is increase in thetrend of oral cancer affecting young people under theJerjes et al. Head & Neck Oncology 2012, 4:5http://www.headandneckoncology.org/content/4/1/5Page 2 of 4age of 45 years reaching to about 6%. Oral cancer hasbeen found to be higher in ethnic minorities in otherdeveloped countries [9-11]. The most common oral sitesto be affected with SCC include the lateral border of thetongue, ventral tongue and floor of mouth. In the Asianpopulation, the buccal mucosa is commonly affecteddue to betel quit/tobacco chewing habits [9-11].The tumour size is one of the most important factorsaffecting prognosis. This usually affects the clinician’sability to decide between ablative surgery, radiotherapy,chemotherapy, photodynamic therapy or just proceed topalliative care which could include a combination of anyof the above therapies. Also, it is well documented thatincreased tumour size is related to local and regionaldisease spread, higher recurrence rates and poor prog-nosis [11-15].Loco-regional spread to the cervical chain complicatestreatment options and worsen the outcome. Several fac-tors have been known to influence local and regionaltumour spread to the lymphatics and they includetumour primary site and thickness, double DNA aneu-ploidy, poorly differentiated tumours, infiltrating-typeinvasive front and perineural and peri/endovascularinvasion. Distant tumour spread occurs most commonlyin uncontrolled local and regional disease and nodal dis-ease [11-15].The influence of the histological grading as a prognos-tic factor in oral squamous cell carcinoma have beenassessed in several studies and found to be a significantpredictor of local and regional failure as well as tumourrecurrence. Positive close tumour margins are usuallyassociated with high risk of local recurrence and have anegative effect on survival [11-15].An accurate clinical staging is of an utmost importance.It is the corner stone in which the surgical team build thesurgical treatment plan and decide whether an adjuvanttherapy is required to deal with any possible problem thatmight arise (i.e. impossible to achieve negative marginsnear vital neurovascular structure or managing distant dis-ease causing pulmonary haemorrhage prior to surgery).The failure to achieve an accurate staging may lead toincomplete surgical planning and hence unforeseen pro-blems that may adversely affect the patient, leading tohigher morbidity and mortality.It is debatable that inaccurate registration of nodalinvolvement during the clinical TNM staging is unlikelyto affect the patient’s prognosis. Histo-pathologicalTable 1 The cTNM and the pTNM staging of the cohort involved in this studycTNM (with no US) Frequency (%) pTNMFrequency (%)Tumour size underestimated Nodal disease missedT1N0M0 107 (43.7) 96 (39.2) 2 (T2) 5 (N1), 3 (N2)T2N0M0 36 (14.7) 32 (13.1) 1 (T3) 5 (N1), 1 (N2)T3N0M0 20 (8.2) 18 (7.3) 2 (T4) 1 (N1)T4N0M0 45 (18.4) 42 (17.1) - 4 (N1), 1 (N2)T1N1M0 10 (4.1) 13 (5.3) 2 (T2)T2N1M0 12 (4.9) 16 (6.5) 1 (T3) 1 (N2)T3N1M0 9 (3.7) 10 (4.1) - 2 (N2)T4N1M0 6 (2.4) 10 (4.1) - -T1N2M0 0 (0.0) 3 (1.2) - -T2N2M0 0 (0.0) 2 (0.8) - -T3N2M0 0 (0.0) 2 (0.8) - -T4N2M0 0 (0.0) 1 (0.4) - -The table also identifies the number of patients with underestimated tumour size and missed nodal diseaseTable 2 Agreement on anatomical sites between cTNMand pTNM, as well as kappa scoresTotal Agreement Kappa Std. Err ofkappaPrimary Tongue 47 95.74% 0.94 0.07FOM 82 86.59% 0.82 0.05Retromolararea12 75.00% 0.69 0.12Buccalmucosa70 82.86% 0.77 0.06Lower lip 7 85.71% 0.79 0.20Gingiva 7 85.71% 0.81 0.20Hard palate 3 100.00% 1.00 0.58Soft palate 4 100.00% 1.00 0.36Tonsils 12 91.67% 0.88 0.17Overall 245 87.35% 0.83 0.03Secondary Tongue 12 75.00% 0.00 0.00FOM 15 100.00% 1.00 0.26Gingiva 16 93.75% 0.82 0.25Tonsils 3 66.67% 0.00 -Tertiary Buccalmucosa6 100.00% 1.00 0.41Gingiva 7 71.43% 0.00 0.00Per 1 site - 194 86.60% 0.80 0.04Per 2 sites - 30 90.00% 0.68 0.16Per 3 sites - 21 90.48% 0.62 0.20Jerjes et al. Head & Neck Oncology 2012, 4:5http://www.headandneckoncology.org/content/4/1/5Page 3 of 4grading would rectify the error and the patient wouldundergo an adjuvant therapy (i.e. radiation) that wouldbe delivered anyway in the postoperative phase.In this short communication, we highlighted the sig-nificant differences between cTNM and pTNM whenUS is not used in assessing for cervical nodal disease.Author details1UCL Department of Surgery, University College London, London, UK. 2Oraland Maxillofacial Surgery Unit, AL-Mustansirya University, Baghdad, Iraq.3Leeds Institute of Molecular Medicine, School of Medicine, University ofLeeds, Leeds, UK. 4Chase Farm & Barnet NHS Trust, Enfield, UK. 5Head & NeckUnit, University College London Hospital, London, UK. 6Biostatistics Unit, UCLEastman Dental Institute, London, UK. 7Department of Oral Surgery andRadiology, School of Dentistry, Aristotle University, Thessalonica, Greece.Authors’ contributionsAll authors have contributed intellectually and to the writing of thismanuscript. AP: contributed to the statistical analysis of this study. Allauthors read and approved the final manuscript.Competing interestsThe authors declare that they have no competing interests.Received: 11 January 2012 Accepted: 12 March 2012Published: 12 March 2012References1. Mukherji SK, Castelijns J, Castillo M: Squamous cell carcinoma of theoropharynx and oral cavity: how imaging makes a difference. SeminUltrasound CT MR 1998, 19(6):463-475.2. Held P, Langnickel R, Breit A: CT and MRI in tumors of the mouth andoropharynx-comparison of methods with reference to fast and ultra-fastMR pulse sequences. Laryngorhinootologie 1993, 72(11):521-531.3. Leslie A, Fyfe E, Guest P, Goddard P, Kabala JE: Staging of squamous cellcarcinoma of the oral cavity and oropharynx: a comparison of MRI andCT in T- and N-staging. Comput Assist Tomogr 1999, 23(1):43-49.4. Anzai Y, Brunberg JA, Lufkin RB: Imaging of nodal metastases in the headand neck. J Magn Reson Imaging 1997, 7(5):774-783.5. Jerjes W, Upile T, Petrie A, Riskalla A, Hamdoon Z, Vourvachis M,Karavidas K, Jay A, Sandison A, Thomas GJ, Kalavrezos N, Hopper C:Clinicopathological parameters, recurrence, locoregional and distantmetastasis in 115 T1-T2 oral squamous cell carcinoma patients. HeadNeck Oncol 2010, 2:9.6. Sureshkannan P, Vijayprabhu , John R: Role of ultrasound in detection ofmetastatic neck nodes in patients with oral cancer. Indian J Dent Res2011, 22(3):419-423.7. Hodder SC, Evans RM, Patton DW, Silvester KC: Ultrasound and fine needleaspiration cytology in the staging of neck lymph nodes in oralsquamous cell carcinoma. Br J Oral Maxillofac Surg 2000, 38(5):430-436.8. Jank S, Robatscher P, Emshoff R, Strobl H, Gojer G, Norer B: The diagnosticvalue of ultrasonography to detect occult lymph node involvement atdifferent levels in patients with squamous cell carcinoma in themaxillofacial region. Int J Oral Maxillofac Surg 2003, 32(1):39-42.9. Bagan JV, Scully C: Recent advances in Oral Oncology 2007:epidemiology, aetiopathogenesis, diagnosis and prognostication. OralOncol 2008, 44(2):103-108.10. Warnakulasuriya S: Global epidemiology of oral and oropharyngealcancer. Oral Oncol 2009, 45(4-5):309-316.11. Noguchi M, Kinjyo H, Kohama GI, Nakamori K: Invasive front in oralsquamous cell carcinoma: image and flow cytometric analysis withclinicopathologic correlation. Oral Surg Oral Med Oral Pathol Oral RadiolEndod 2002, 93(6):682-687.12. Garzino-Demo P, Dell’Acqua A, Dalmasso P, Fasolis M, La TerraMaggiore GM, Ramieri G, Berrone S, Rampino M, Schena M:Clinicopathological parameters and outcome of 245 patients operatedfor oral squamous cell carcinoma. J Craniomaxillofac Surg 2006,34(6):344-350.13. Shah JP, Gil Z: Current concepts in management of oral cancer–surgery.Oral Oncol 2009, 45(4-5):394-401.14. Mazeron R, Tao Y, Lusinchi A, Bourhis J: Current concepts of managementin radiotherapy for head and neck squamous-cell cancer. Oral Oncol2009, 45(4-5):402-408.15. Specenier PM, Vermorken JB: Current concepts for the management ofhead and neck cancer: chemotherapy. Oral Oncol 2009, 45(4-5):409-415.doi:10.1186/1758-3284-4-5Cite this article as: Jerjes et al.: cTNM vs. pTNM: the effect of notapplying ultrasonography in the identification of cervical nodal disease.Head & Neck Oncology 2012 4:5.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitJerjes et al. Head & Neck Oncology 2012, 4:5http://www.headandneckoncology.org/content/4/1/5Page 4 of 4

Head & Neck Oncology

cTNM vs. pTNM: the effect of not applying ultrasonography in the identification of cervical nodal disease

Springer - Publisher Connector

RESEARCH Open Access
cTNM vs. pTNM: the effect of not applying
ultrasonography in the identification of cervical
nodal disease
Waseem Jerjes1,2,3*, Tahwinder Upile4,5, Hani Radhi2*, Aviva Petrie6, Jesuloba Abiola1, Aidan Adams3,
Jacqueline Callear3, Panagiotis Kafas7, Syedda Abbas5, Kartic Rajaram3 and Colin Hopper1,5
Abstract
Accurate clinical staging of oral squamous cell cancer can be quite difficult to achieve especially if nodal
involvement is identified. Radiologically-assisted clinical staging is more accurate and informs the clinician of loco-
regional and distant metastasis.
In this study, we compared clinical TNM (cTNM) staging (not including ultrasonography) to pathological TNM
(pTNM) staging in 245 patients presenting with carcinoma of the oral cavity and the oro-pharyngeal region.
Tumour size differences and nodal involvement were highlighted. US reports of the neck were then added to the
clinical staging and results compared.
Tumour size was clinically underestimated in 4 T1, 2 T2 and 2 T3 oral diseases. Also 20 patients that were reported
as nodal disease free had histological proven N1 or N2 nodal involvement; while 3 patients with cTNM showing
N1 disease had histologically proven N2 disease.
Overall the agreement between the 2 systems per 1 site was 86.6% (Kappa agreement = 0.80), per 2 sites 90.0%
(Kappa agreement = 0.68) and per 3 sites 90.5% (Kappa agreement 0.62).
An accurate clinical staging is of an utmost importance. It is the corner stone in which the surgical team build the
surgical treatment plan and decide whether an adjuvant therapy is required to deal with any possible problem
that might arise. The failure to achieve an accurate staging may lead to incomplete surgical planning and hence
unforeseen problems that may adversely affect the patient’s survival.
Background
The development of modern imaging techniques has
significantly altered the treatment and management of
head and neck malignancies. Important treatment deci-
sions that were once made intra-operatively are now
made preoperatively by means of advanced imaging, i.e.
computed tomography (CT) and magnetic resonance
imaging (MRI) [1].
MRI has been proved superior to CT, on account of
its coronal and sagittal slice orientation enabling not
only a better demonstration of findings, but also
improved tumour detection and staging [2]. Also when
it comes to T-staging, MRI is overall more accurate
than CT. However, if degraded images and T1 tumours
are excluded, the techniques are comparable. MRI is
oversensitive for recurrent disease. For Nodal staging,
MRI was found comparable to CT [3]. Although CT
and MRI allow detection of abnormally enlarged nodes
or necrotic nodes, neither borderline-sized nodes with-
out necrosis nor extra-capsular spread are reliably differ-
entiated from reactive or normal nodes in patients with
head and neck cancer [4].
Accurate clinical staging of pathologies involving the
oral and oro-pharyngeal-laryngeal regions can be quite
difficult to achieve, especially if nodal disease is
involved. The current practice worldwide when it comes
to clinically staging tumours identified in these areas
usually involve carrying out a thorough clinical examina-
tion of the head and neck region followed by radiologi-
cal investigations. The latter usually involve carrying out
* Correspondence: waseem_wk1@yahoo.co.uk; hani_hadi79@hotmail.com
1UCL Department of Surgery, University College London, London, UK
2Oral and Maxillofacial Surgery Unit, AL-Mustansirya University, Baghdad, Iraq
Full list of author information is available at the end of the article
Jerjes et al. Head & Neck Oncology 2012, 4:5
http://www.headandneckoncology.org/content/4/1/5
© 2012 Jerjes et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
PUBLISHER’S NOTE: Based on the information available to BioMed Central, this article was apparently handled by Waseem Jerjes, the first author of the article 
and Editor-in-Chief of the journal at that time. The article states that ‘All applications were accompanied by multidisciplinary team recommendation, ethical approval 
and informed patient consent.’ UCL’s investigation concluded that this study was a retrospective analysis of data which would be classed as clinical audit and not 
a research study. Mr Hopper agreed it was a mistake on the part of the authors to state the analysis had ethical approval and informed consent. Mr Hopper has 
published a correction (https://www.oapublishinglondon.com/article/740).
an MRI of the head and neck, or a CT scanning if bony
invasion is anticipated (i.e. edentulous patients). The
rest of the clinical staging involve a CT scanning of the
chest and the upper abdomen to rule out any tumour
spread to the pulmonary or hepato-pancreato-biliary
organs [5].
In most of the centres in the developed world, an
ultrasonography (US) imaging of the neck is carried out
to identify any nodal involvement which cannot be iden-
tified by other imaging modalities (i.e. MRI or CT);
unfortunately the lack of expertise in the developing
world stops the application of US technology. US is a
reliable and valuable tool for metastatic lymph node
screening in head and neck cancer patients. It is a
cheap, non-invasive, easy-to-handle and cost-effective
diagnostic method [6].
This has lead many centres around the world to
change its practice to include US as part of clinical sta-
ging process for any patient who presents with patholo-
gical lesion in the head and neck. Furthermore, the
advances in cytological sciences allowed fine needle
aspiration of neck nodes under US-guidance and
allowed identification of reactive lymph nodes prior to
surgery. A study identified US, with or without FNAC,
as an accurate (86%), sensitive (92%) and specific (83%)
technique for the preoperative assessment of lymph
node metastases in patients with SCC [7]. In another
study, US (for all levels) yielded a sensitivity of 71%, and
a specificity of 87%, while CT showed a sensitivity of
32% and a specificity of 96%. The sensitivity of US
decreased from level I to level IV, whereas the specificity
increased from level I to level IV [8].
In this short communication, we retrospectively com-
pared clinical TNM (cTNM) staging (not including US)
to pathological TNM (pTNM) staging in patients pre-
senting with carcinoma of the oral cavity and the oro-
pharyngeal region. Tumour size differences and nodal
involvement were highlighted. US reports of the neck
were then added to the clinical staging and results
compared.
Materials & methods
In this retrospective analytic study, we looked at cTNM
staging and pTNM staging of 245 patients with oral and
pharyngeal squamous cell carcinoma who underwent
treatment at the UCLH Head and Neck Centre, London
from 2001 to 2006.
The patients’ data were entered onto proformas, which
were validated and checked by interval sampling. The
fields included a range of clinical, operative and histo-
pathological variables related to disease staging. All
applications were accompanied by multidisciplinary
team recommendation, ethical approval and informed
patient consent.
In this short communication, the cTNM staging was
achieved through clinical examination of the head and
neck region and MRI, or CT scan when indicated, and
no US scan of the neck. This was compared to pTNM
trying to identify any underestimation in tumour size or
missed cervical nodal disease. Agreement between both
staging systems were assessed per anatomical site. Then,
US reports were added to the cTNM staging and results
compared again.
Statistical analysis
The outcomes of the categorical clinic-pathological vari-
ables (cTNM and pTNM) were summarised as frequen-
cies and percentages for the whole group of patients.
Kappa score agreement, with its standard error, was cal-
culated to compare cTNM and pTNM for primary, sec-
ondary and tertiary sites; also was applied to per 1 site,
per 2 sites and per 3 sites.
Results
Table 1 highlights the cTNM and the pTNM staging of
the cohort involved in this study. Tumour size was clini-
cally underestimated in 4 T1, 2 T2 and 2 T3 oral dis-
eases. Also 20 patients that were reported as nodal
disease free had histological proven N1 or N2 nodal
involvement; while 3 patients with cTNM showing N1
disease had histologically proven N2 disease (Table 1).
When the US data was added to the cTNM staging, no
differences were identified in nodal disease assessment.
Agreement on anatomical sites between cTNM and
pTNM, as well as kappa scores, are highlighted in Table
2. The agreement between cTNM (without US) and
pTNM when assessing the tongue was 95.7%, FOM
86.6%, buccal mucosa 82.9%, retromolar area 75.0% and
tonsils 91.7%. This may be due to the fact that deep and
posterior oral structures are a challenge during clinical
examination as well as the dental artifacts that could
arise during scanning which affects staging of peri-den-
tal tumours (Table 2).
Overall the agreement between the 2 systems per 1
site was 86.60% (Kappa agreement = 0.80), per 2 sites
90.0% (Kappa agreement = 0.68) and per 3 sites 90.48%
(Kappa agreement 0.6182), (Table 2).
Discussion
Cancers of the oral cavity and oro-pharyngeal region are
the sixth most common cancers in the world. Unfortu-
nately the incidence continues to rise with moderate
survival rates, despite the recent advances in surgery
and radiotherapy [9-11]. Oral squamous cell carcinoma
(OSCC) continues to affect more males than females
with a ratio of 1.5-1. Diagnosis is usually at the fifth or
sixth decade of life. However there is increase in the
trend of oral cancer affecting young people under the
Jerjes et al. Head & Neck Oncology 2012, 4:5
http://www.headandneckoncology.org/content/4/1/5
Page 2 of 4
age of 45 years reaching to about 6%. Oral cancer has
been found to be higher in ethnic minorities in other
developed countries [9-11]. The most common oral sites
to be affected with SCC include the lateral border of the
tongue, ventral tongue and floor of mouth. In the Asian
population, the buccal mucosa is commonly affected
due to betel quit/tobacco chewing habits [9-11].
The tumour size is one of the most important factors
affecting prognosis. This usually affects the clinician’s
ability to decide between ablative surgery, radiotherapy,
chemotherapy, photodynamic therapy or just proceed to
palliative care which could include a combination of any
of the above therapies. Also, it is well documented that
increased tumour size is related to local and regional
disease spread, higher recurrence rates and poor prog-
nosis [11-15].
Loco-regional spread to the cervical chain complicates
treatment options and worsen the outcome. Several fac-
tors have been known to influence local and regional
tumour spread to the lymphatics and they include
tumour primary site and thickness, double DNA aneu-
ploidy, poorly differentiated tumours, infiltrating-type
invasive front and perineural and peri/endovascular
invasion. Distant tumour spread occurs most commonly
in uncontrolled local and regional disease and nodal dis-
ease [11-15].
The influence of the histological grading as a prognos-
tic factor in oral squamous cell carcinoma have been
assessed in several studies and found to be a significant
predictor of local and regional failure as well as tumour
recurrence. Positive close tumour margins are usually
associated with high risk of local recurrence and have a
negative effect on survival [11-15].
An accurate clinical staging is of an utmost importance.
It is the corner stone in which the surgical team build the
surgical treatment plan and decide whether an adjuvant
therapy is required to deal with any possible problem that
might arise (i.e. impossible to achieve negative margins
near vital neurovascular structure or managing distant dis-
ease causing pulmonary haemorrhage prior to surgery).
The failure to achieve an accurate staging may lead to
incomplete surgical planning and hence unforeseen pro-
blems that may adversely affect the patient, leading to
higher morbidity and mortality.
It is debatable that inaccurate registration of nodal
involvement during the clinical TNM staging is unlikely
to affect the patient’s prognosis. Histo-pathological
Table 1 The cTNM and the pTNM staging of the cohort involved in this study
cTNM (with no US) Frequency (%) pTNM
Frequency (%)
Tumour size underestimated Nodal disease missed
T1N0M0 107 (43.7) 96 (39.2) 2 (T2) 5 (N1), 3 (N2)
T2N0M0 36 (14.7) 32 (13.1) 1 (T3) 5 (N1), 1 (N2)
T3N0M0 20 (8.2) 18 (7.3) 2 (T4) 1 (N1)
T4N0M0 45 (18.4) 42 (17.1) - 4 (N1), 1 (N2)
T1N1M0 10 (4.1) 13 (5.3) 2 (T2)
T2N1M0 12 (4.9) 16 (6.5) 1 (T3) 1 (N2)
T3N1M0 9 (3.7) 10 (4.1) - 2 (N2)
T4N1M0 6 (2.4) 10 (4.1) - -
T1N2M0 0 (0.0) 3 (1.2) - -
T2N2M0 0 (0.0) 2 (0.8) - -
T3N2M0 0 (0.0) 2 (0.8) - -
T4N2M0 0 (0.0) 1 (0.4) - -
The table also identifies the number of patients with underestimated tumour size and missed nodal disease
Table 2 Agreement on anatomical sites between cTNM
and pTNM, as well as kappa scores
Total Agreement Kappa Std. Err of
kappa
Primary Tongue 47 95.74% 0.94 0.07
FOM 82 86.59% 0.82 0.05
Retromolar
area
12 75.00% 0.69 0.12
Buccal
mucosa
70 82.86% 0.77 0.06
Lower lip 7 85.71% 0.79 0.20
Gingiva 7 85.71% 0.81 0.20
Hard palate 3 100.00% 1.00 0.58
Soft palate 4 100.00% 1.00 0.36
Tonsils 12 91.67% 0.88 0.17
Overall 245 87.35% 0.83 0.03
Secondary Tongue 12 75.00% 0.00 0.00
FOM 15 100.00% 1.00 0.26
Gingiva 16 93.75% 0.82 0.25
Tonsils 3 66.67% 0.00 -
Tertiary Buccal
mucosa
6 100.00% 1.00 0.41
Gingiva 7 71.43% 0.00 0.00
Per 1 site - 194 86.60% 0.80 0.04
Per 2 sites - 30 90.00% 0.68 0.16
Per 3 sites - 21 90.48% 0.62 0.20
Jerjes et al. Head & Neck Oncology 2012, 4:5
http://www.headandneckoncology.org/content/4/1/5
Page 3 of 4
grading would rectify the error and the patient would
undergo an adjuvant therapy (i.e. radiation) that would
be delivered anyway in the postoperative phase.
In this short communication, we highlighted the sig-
nificant differences between cTNM and pTNM when
US is not used in assessing for cervical nodal disease.
Author details
1UCL Department of Surgery, University College London, London, UK. 2Oral
and Maxillofacial Surgery Unit, AL-Mustansirya University, Baghdad, Iraq.
3Leeds Institute of Molecular Medicine, School of Medicine, University of
Leeds, Leeds, UK. 4Chase Farm & Barnet NHS Trust, Enfield, UK. 5Head & Neck
Unit, University College London Hospital, London, UK. 6Biostatistics Unit, UCL
Eastman Dental Institute, London, UK. 7Department of Oral Surgery and
Radiology, School of Dentistry, Aristotle University, Thessalonica, Greece.
Authors’ contributions
All authors have contributed intellectually and to the writing of this
manuscript. AP: contributed to the statistical analysis of this study. All
authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Received: 11 January 2012 Accepted: 12 March 2012
Published: 12 March 2012
References
1. Mukherji SK, Castelijns J, Castillo M: Squamous cell carcinoma of the
oropharynx and oral cavity: how imaging makes a difference. Semin
Ultrasound CT MR 1998, 19(6):463-475.
2. Held P, Langnickel R, Breit A: CT and MRI in tumors of the mouth and
oropharynx-comparison of methods with reference to fast and ultra-fast
MR pulse sequences. Laryngorhinootologie 1993, 72(11):521-531.
3. Leslie A, Fyfe E, Guest P, Goddard P, Kabala JE: Staging of squamous cell
carcinoma of the oral cavity and oropharynx: a comparison of MRI and
CT in T- and N-staging. Comput Assist Tomogr 1999, 23(1):43-49.
4. Anzai Y, Brunberg JA, Lufkin RB: Imaging of nodal metastases in the head
and neck. J Magn Reson Imaging 1997, 7(5):774-783.
5. Jerjes W, Upile T, Petrie A, Riskalla A, Hamdoon Z, Vourvachis M,
Karavidas K, Jay A, Sandison A, Thomas GJ, Kalavrezos N, Hopper C:
Clinicopathological parameters, recurrence, locoregional and distant
metastasis in 115 T1-T2 oral squamous cell carcinoma patients. Head
Neck Oncol 2010, 2:9.
6. Sureshkannan P, Vijayprabhu , John R: Role of ultrasound in detection of
metastatic neck nodes in patients with oral cancer. Indian J Dent Res
2011, 22(3):419-423.
7. Hodder SC, Evans RM, Patton DW, Silvester KC: Ultrasound and fine needle
aspiration cytology in the staging of neck lymph nodes in oral
squamous cell carcinoma. Br J Oral Maxillofac Surg 2000, 38(5):430-436.
8. Jank S, Robatscher P, Emshoff R, Strobl H, Gojer G, Norer B: The diagnostic
value of ultrasonography to detect occult lymph node involvement at
different levels in patients with squamous cell carcinoma in the
maxillofacial region. Int J Oral Maxillofac Surg 2003, 32(1):39-42.
9. Bagan JV, Scully C: Recent advances in Oral Oncology 2007:
epidemiology, aetiopathogenesis, diagnosis and prognostication. Oral
Oncol 2008, 44(2):103-108.
10. Warnakulasuriya S: Global epidemiology of oral and oropharyngeal
cancer. Oral Oncol 2009, 45(4-5):309-316.
11. Noguchi M, Kinjyo H, Kohama GI, Nakamori K: Invasive front in oral
squamous cell carcinoma: image and flow cytometric analysis with
clinicopathologic correlation. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 2002, 93(6):682-687.
12. Garzino-Demo P, Dell’Acqua A, Dalmasso P, Fasolis M, La Terra
Maggiore GM, Ramieri G, Berrone S, Rampino M, Schena M:
Clinicopathological parameters and outcome of 245 patients operated
for oral squamous cell carcinoma. J Craniomaxillofac Surg 2006,
34(6):344-350.
13. Shah JP, Gil Z: Current concepts in management of oral cancer–surgery.
Oral Oncol 2009, 45(4-5):394-401.
14. Mazeron R, Tao Y, Lusinchi A, Bourhis J: Current concepts of management
in radiotherapy for head and neck squamous-cell cancer. Oral Oncol
2009, 45(4-5):402-408.
15. Specenier PM, Vermorken JB: Current concepts for the management of
head and neck cancer: chemotherapy. Oral Oncol 2009, 45(4-5):409-415.
doi:10.1186/1758-3284-4-5
Cite this article as: Jerjes et al.: cTNM vs. pTNM: the effect of not
applying ultrasonography in the identification of cervical nodal disease.
Head & Neck Oncology 2012 4:5.
Submit your next manuscript to BioMed Central
and take full advantage of: 
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at 
www.biomedcentral.com/submit
Jerjes et al. Head & Neck Oncology 2012, 4:5
http://www.headandneckoncology.org/content/4/1/5
Page 4 of 4


A: CT and MRI in tumors of the mouth and oropharynx-comparison of methods with reference to fast and ultra-fast MR pulse sequences. Laryngorhinootologie

Clinicopathological parameters and outcome of 245 patients operated for oral squamous cell carcinoma. J Craniomaxillofac Surg

Current concepts for the management of head and neck cancer: chemotherapy. Oral Oncol

Current concepts in management of oral cancer–surgery. Oral Oncol

Current concepts of management in radiotherapy for head and neck squamous-cell cancer. Oral Oncol

Global epidemiology of oral and oropharyngeal cancer. Oral Oncol

Hopper C: Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients. Head Neck Oncol

Invasive front in oral squamous cell carcinoma: image and flow cytometric analysis with clinicopathologic correlation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod

JE: Staging of squamous cell carcinoma of the oral cavity and oropharynx: a comparison of MRI and CT in T- and N-staging. Comput Assist Tomogr

KC: Ultrasound and fine needle aspiration cytology in the staging of neck lymph nodes in oral squamous cell carcinoma. Br J Oral Maxillofac Surg

RB: Imaging of nodal metastases in the head and neck.

Role of ultrasound in detection of metastatic neck nodes in patients with oral cancer.

Scully C: Recent advances in Oral Oncology

Squamous cell carcinoma of the oropharynx and oral cavity: how imaging makes a difference. Semin Ultrasound CT MR

The diagnostic value of ultrasonography to detect occult lymph node involvement at different levels in patients with squamous cell carcinoma in the maxillofacial region. Int J Oral Maxillofac Surg

https://headandneckoncology.biomedcentral.com/track/pdf/10.1186/1758-3284-4-5?site=headandneckoncology.biomedcentral.com

cTNM vs. pTNM: the effect of not applying ultrasonography in the identification of cervical nodal disease

Abstract

Similar works

Full text

Available Versions

Crossref

Springer - Publisher Connector

Springer - Publisher Connector