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An Update on Oral Cancers. Leo Pang BSc (Med), MB BS, FRACS (OHNS) Royal North Shore Hospital. Overview. Oral Cavity and Oropharyngeal Cancers Squamous Cell Carcinoma most common (90%) Anatomy DIAGNOSIS Investigations Treatment Options Surgery, Chemotherapy, Radiotherapy

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An update on oral cancers

An Update on Oral Cancers

Leo Pang

BSc (Med), MB BS, FRACS (OHNS)

Royal North Shore Hospital


Overview
Overview

  • Oral Cavity and Oropharyngeal Cancers

  • Squamous Cell Carcinoma most common (90%)

  • Anatomy

  • DIAGNOSIS

  • Investigations

  • Treatment Options

    • Surgery, Chemotherapy, Radiotherapy

  • PREVENTATIVE STRATEGIES


Oral cavity cancer overview
Oral Cavity Cancer Overview

  • 30% of all Head and Neck cancers

  • Most present late (68% Stage 3 and 4)

  • Surgery remains primary treatment modality

  • HPV status is of prognostic significance

  • Early detection improves survival

  • Overall survival for oral cancers improving


Anatomy
Anatomy

  • Oral Cavity (7 subsites)

    • Lip (30%)

    • Tongue (20-50%)

    • Floor of mouth (30%)

    • Alveolar Ridge (<10%)

    • Buccal Mucosa (<5%)

    • RetromolarTrigone (<5%)

    • Hard Palate (<1%)


Diagnosis
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


Diagnosis1
Diagnosis

  • Histology


Investigations
Investigations

  • CT Head, Neck, Chest with IV contrast

  • Fluoro-deoxy-D-glucose (FDG) Positron Emission Tomography

    • Sensitivity 90%

    • Specificity 95%

  • US Guided FNA Neck nodes

  • MRI

  • Histology

    • HPV + p16


  • Adjuvant treatment modality

  • Margins, differentiation, size, depth, invasion

  • Neck nodes: no, size, extracapsular spread

Surgery

Radiotherapy

Chemotherapy

  • Adjuvant treatment modality

  • Presence of extracapsular spread


Novel treatment options
Novel Treatment Options?

  • Targeted therapy

  • Immunotherapy

  • Phototherapy


Oropharyngeal cancer overview
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 4

  • Historically treated with radical surgery

  • Current treatment is concurrent ChemoRT

  • No Level 1 evidence to compare surgery vs CRT

  • Changing demographics

  • Slow paradigm shift towards surgical treatment

    • Laser, Da Vinci Robot


Anatomy1
Anatomy

  • 5 subsites

    • Soft palate

    • Tonsillar fossae

    • Base of tongue

    • Oropharyngeal walls

    • Vallecula

(Cummings 2010)


Anatomy boundaries
AnatomyBoundaries

  • Superior – Hard Palate

(Netter 2003)


Anatomy boundaries1
AnatomyBoundaries

  • Anterior – Palatoglossal Arch, Hard/Soft Palate Border


Anatomy boundaries2
AnatomyBoundaries

  • Lateral – Tonsillar fossa, lateral pharyngeal wall


Anatomy boundaries3
AnatomyBoundaries

  • Posterior – Posterior pharyngeal wall


Anatomy boundaries4
AnatomyBoundaries

  • Inferior – Level of Hyoid Bone


Anatomy base of tongue
AnatomyBase of Tongue

  • Circumvallate papillae (anteriorly)

  • Pharyngoepiglottic fold (posteriorly)

  • Glossoepiglottic fold (posteriorly)

  • Lingual tonsils are lateral


Epidemiology
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
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

(http://www.pubcan.org)


Human papilloma virus hpv1
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


Oropharyngeal cancer lymphatic drainage
Oropharyngeal CancerLymphatic Drainage

(http://imaging.consult.com)

(AJR 2008; 191:W299-306)

(http://emedicine.medscape.com)


Diagnosis2
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
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 cancer staging
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 cancer staging1
Oropharyngeal CancerStaging

  • T, tumor

  • N, node

  • M, metastasis

  • Mx: distant metastasis cannot be evaluated

  • M0: no distant metastasis

  • M1: distant metastasis present


Investigations1
Investigations

  • CT Head, Neck, Chest with IV contrast

  • Fluoro-deoxy-D-glucose (FDG) Positron Emission Tomography

  • US Guided FNA Neck nodes

  • MRI

  • Histology

    • HPV + p16


Ct scan
CT Scan

(Radiograhics 2011; 31:339-54)

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

Invasion of medial pterygoid muscle


Ct scan1
CT Scan

(Radiograhics 2011; 31:339-54)

Encasement of carotid artery

Involvement of foramen ovale


Surgery

Radiotherapy

  • Concurrent chemotherapy and radiotherapy (CRT) considered mainstays of treatment

  • Organ Preservation

Chemotherapy


Treatment
Treatment

  • Concurrent 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 strategies
Preventative Strategies

  • 81.9% Stage 3 or 4at presentation

  • 90.9% Tonsil or Tongue Base

  • Significant drop in survival from Stage 1/2 (95%) to Stage 3/4 (70%)

  • Secondary Prevention is key to early detection and improved survival

  • Planned Free Oral Cancer Screening Day


References
References

Ang 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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