An Update on Oral Cancers

Leo PangBSc (Med), MB BS, FRACS (OHNS)

Royal North Shore Hospital

OverviewOral Cavity and Oropharyngeal CancersSquamous Cell Carcinoma most common (90%)AnatomyDIAGNOSISInvestigationsTreatment Options

Surgery, Chemotherapy, RadiotherapyPREVENTATIVE STRATEGIES

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

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%)

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

DiagnosisHistology

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

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

Novel Treatment Options?Targeted therapyImmunotherapyPhototherapy

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

Anatomy

5 subsitesSoft palateTonsillar fossaeBase of tongueOropharyngeal wallsVallecula

(Cummings 2010)

AnatomyBoundaries

Superior – Hard Palate

(Netter 2003)

AnatomyBoundaries

Anterior – Palatoglossal Arch, Hard/Soft Palate Border

AnatomyBoundaries

Lateral – Tonsillar fossa, lateral pharyngeal wall

AnatomyBoundaries

Posterior – Posterior pharyngeal wall

AnatomyBoundaries

Inferior – Level of Hyoid Bone

AnatomyBase of Tongue

Circumvallate papillae (anteriorly)

Pharyngoepiglottic fold (posteriorly)

Glossoepiglottic fold (posteriorly)

Lingual tonsils are lateral

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

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

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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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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

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

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

Oropharyngeal CancerStaging

T, tumor

N, node

M, metastasis

Mx: distant metastasis cannot be evaluated

M0: no distant metastasis M1: distant metastasis present

InvestigationsCT Head, Neck, Chest

with IV contrastFluoro-deoxy-D-glucose

(FDG) Positron Emission Tomography

US Guided FNA Neck nodes

MRIHistology

HPV + p16

CT Scan

Invasion of pre-epiglottic fat (i.e. laryngeal involvement)

Invasion of medial pterygoid muscle

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CT Scan

Encasement of carotid artery

Involvement of foramen ovale

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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

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

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

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.

Thank you