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An Update on Oral Cancers
Leo PangBSc (Med), MB BS, FRACS (OHNS)
Royal North Shore Hospital
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OverviewOral Cavity and Oropharyngeal CancersSquamous Cell Carcinoma most common (90%)AnatomyDIAGNOSISInvestigationsTreatment Options
Surgery, Chemotherapy, RadiotherapyPREVENTATIVE STRATEGIES
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Oral Cavity Cancer Overview
30% of all Head and Neck cancersMost present late (68% Stage 3 and 4)Surgery remains primary treatment modalityHPV status is of prognostic significanceEarly detection improves survivalOverall survival for oral cancers improving
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AnatomyOral Cavity (7 subsites)
Lip (30%)Tongue (20-50%)Floor of mouth (30%)Alveolar Ridge (<10%)Buccal Mucosa (<5%)Retromolar Trigone (<5%)Hard Palate (<1%)
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Diagnosis History
Local Symptoms Changes in fit of denture Oral/ dental pain Bleeding
Regional Symptoms Halitosis Trismus Dysphagia, odynophagia, dysarthria Otalgia Facial paraesthesia Neck mass and pain
Systemic Symptoms Weight loss
General medical history Tobacco and alcohol usage
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DiagnosisHistology
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InvestigationsCT Head, Neck, Chest with
IV contrastFluoro-deoxy-D-glucose
(FDG) Positron Emission Tomography Sensitivity 90% Specificity 95%
US Guided FNA Neck nodesMRIHistology
HPV + p16
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Surgery Radiotherapy
Chemotherapy
• Still primary treatment modality• Resection and Reconstruction• Extent of Resection• N0 Necks
• Sentinel Nodes?
• Adjuvant treatment modality• Margins, differentiation, size,
depth, invasion• Neck nodes: no, size,
extracapsular spread
• Adjuvant treatment modality• Presence of extracapsular spread
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Novel Treatment Options?Targeted therapyImmunotherapyPhototherapy
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Oropharyngeal Cancer Overview
Little is known about the disease-specific cumulative survival rate and factors affecting it among patients with oropharyngeal cancer
81.9% present Stage 3 and 4Historically treated with radical surgeryCurrent treatment is concurrent ChemoRTNo Level 1 evidence to compare surgery vs CRTChanging demographicsSlow paradigm shift towards surgical treatment
Laser, Da Vinci Robot
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Anatomy
5 subsitesSoft palateTonsillar fossaeBase of tongueOropharyngeal wallsVallecula
(Cummings 2010)
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AnatomyBoundaries
Superior – Hard Palate
(Netter 2003)
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AnatomyBoundaries
Anterior – Palatoglossal Arch, Hard/Soft Palate Border
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AnatomyBoundaries
Lateral – Tonsillar fossa, lateral pharyngeal wall
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AnatomyBoundaries
Posterior – Posterior pharyngeal wall
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AnatomyBoundaries
Inferior – Level of Hyoid Bone
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AnatomyBase of Tongue
Circumvallate papillae (anteriorly)
Pharyngoepiglottic fold (posteriorly)
Glossoepiglottic fold (posteriorly)
Lingual tonsils are lateral
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Epidemiology Relatively uncommon
Fewer than 1% of all new cancers Comprises 10-12% of head and neck malignancies
Squamous cell carcinoma (SCCA) accounts for 90% of oropharyngeal malignancies Peak incidence in 6th or 7th decades of life Tobacco and alcohol are synergistic risk factors Increasing incidence in 4th and 5th decades of life
Changing demographics Younger adults, equal gender distribution Good performance status Nonsmokers, but possible association with marijuana use Orogenital sexual practices
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Human Papilloma Virus (HPV)
High-risk HPV, type 16 Types 16 and 18 involved with cancer of genital tract Associated with 45-70% of oropharyngeal SCCA (Cohen 2011)
Integration of genome into host cell nucleus Express E6 and E7 oncoproteins Inactivate tumor-suppressant p53 and retinoblastoma protein Associated with p16-positivity
Histology Predominantly poorly differentiated SCCA Basaloid background Correlated with HPV- and p16-positivity (Mendelsohn 2010)
No increase in lymphovascular or perineural invasion Highly predictive of lymph node metastasis (h
ttp://
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Human Papilloma Virus (HPV)
Retrospective review of oropharyngeal SCCA (Ang 2010)
HPV-positive in 206 out of 323 with stage III or IV disease (63.8%) Improved 3-year overall survival (82.4% vs. 57.1%) Improved 3-year progression-free survival (73.7% vs. 43.4%)HPV-positive conveys 58% reduction in death
HPV-positivity is favorable prognostic factor (Ihloff 2010)
Meta-analysis of 8 studies between 2000 and 2010 HPV-positive tumors generally respond well to treatment
Advanced primary associated with recurrence and death (Sedaghat 2009)
Studies needed to investigate impact of HPV vaccinations
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Oropharyngeal CancerLymphatic Drainage
(http://emedicine.medscape.com)(AJR
200
8; 1
91:W
299-
306)
(http
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)
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Diagnosis Local
Pain Bleeding Foreign Body Sensation
Regional Halitosis Trismus Dysphagia/odynophagia Otalgia Neck mass Voice changes Paraesthesia Neck Mass
Systemic Weight loss Loss of appetite
General Smoking/ETOH
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Staging
T tumor
N node
M metastasis
Tx: primary site cannot be evaluated T0: no evidence of carcinoma Tis: carcinoma in-situ T1: tumor < 2cm in greatest dimension T2: tumor 2-4cm in greatest dimension T3: tumor > 4cm in greatest dimension T4
T4a: invades larynx, deep/extrinsic tongue muscles, medial pterygoid, hard palate, or mandible
T4b: invades lateral pterygoid, pterygoid plates, lateral nasopharynx, skull base, or carotid
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Oropharyngeal CancerStaging
T, tumor
N, node
M, metastasis
Nx: lymph nodes cannot be evaluated N0: no evidence of nodal metastasis N1: single node involved, < 3cm N2
N2a: single node involved, 3-6cm N2b: multiple nodes involved unilaterally, < 6cm N2c: bilateral nodal involvement, < 6cm
N3: nodal involvement > 6cm
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Oropharyngeal CancerStaging
T, tumor
N, node
M, metastasis
Mx: distant metastasis cannot be evaluated
M0: no distant metastasis M1: distant metastasis present
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InvestigationsCT Head, Neck, Chest
with IV contrastFluoro-deoxy-D-glucose
(FDG) Positron Emission Tomography
US Guided FNA Neck nodes
MRIHistology
HPV + p16
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CT Scan
Invasion of pre-epiglottic fat (i.e. laryngeal involvement)
Invasion of medial pterygoid muscle
(Rad
iogr
ahic
s 20
11; 3
1:33
9-54
)
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CT Scan
Encasement of carotid artery
Involvement of foramen ovale
(Rad
iogr
ahic
s 20
11; 3
1:33
9-54
)
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Surgery Radiotherapy
Chemotherapy
• Early Cancers in selected patients
• Transoral Laser• Transoral Robotic Surgery
(TORS)• ?Emerging role
• Concurrent chemotherapy and radiotherapy (CRT) considered mainstays of treatment
• Organ Preservation
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TreatmentConcurrent chemotherapy and radiotherapy (CRT)
considered mainstays of treatment Organ preservation strategies Good local and regional control rates Meta-analysis (Blanchard 2011)
87 randomized trials between 1965 and 2000 Improved overall and disease-free survival with CTX Concomitant CTX more favorable than adjuvant or neoadjuvant CTX Applies to all head and neck SCCA, but statistical significance in oropharynx
and larynx
Note: Not level evidence comparing Surgery +/- RT vs CRT Unlikely to be proven
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Preventative Strategies81.9% Stage 3 or 4 at presentation90.9% Tonsil or Tongue BaseSignificant drop in survival from Stage 1/2 (95%)
to Stage 3/4 (70%)Secondary Prevention is key to early
detection and improved survivalPlanned Free Oral Cancer Screening Day
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ReferencesAng KK, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. NEJM 2010; 363:24-35.
Bailey BJ, Johnson, JT, Newlands SD, eds. Head and Neck Surgery – Otolaryngology, 4th Ed. Philadelphia: Lippincott, 2006. pp 12-3, 1673-88.
Bernier J, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. NEJM2004; 350:1945-52.
Blanchard P, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): a comprehensive analysis by tumour site. Radiother Oncol 2011; 100:33-40.
Cano ER, et al. Management of squamous cell carcinoma of the base of tongue with chemoradiation and brachytherapy. Head Neck 2009; 31:1431-8.
Cohen MA, et al. Transoral robotic surgery and human papillomavirus status: oncologic results. Head Neck 2011; 33:573-80.
Cooper JS, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. NEJM 2004; 350:1937-44.
Greene FL, et al, eds. AJCC Cancer Staging Atlas, 6th Ed. Chicago: Springer, 2006. pp 27-34.
Fein D, et al. Oropharyngeal carcinoma treated with radiotherapy: a 30 year experience. Int J Radiat Oncol Biol Phys 1996; 34:289-96.
Flint PW, et al, eds. Cummings Otolaryngology: Head and Neck Surgery, 5th Ed. Philadelphia: Mosby Elsevier, 2010. ch 8, 100.
Furness S, et al. Interventions for the treatment of oral cavity and oropharyngeal cancer: chemotherapy. Cochrane Database Syst Rev 2010; 9:CD006386.
Grant DG, et al. Oropharyngeal cancer: a case for single modality treatment with transoral laser microsurgery. Arch Otolaryngol Head Neck Surg 2009; 135:1225-30.
Henstrom DK, et al. Transoral resection for squamous cell carcinoma of the base of the tongue. Arch Otolaryngol Head Neck Surg 2009; 135:1231-8.
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Thank you