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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
slide10
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

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

slide32
Early Cancers in selected patients
  • Transoral Laser
  • Transoral Robotic Surgery (TORS)
  • ?Emerging role

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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