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Dr. Yogesh Belagali
Medical Advisor- Oncotherapeuitcs
CANCERS OF THE ORAL CAVITY
TYPES
Malignant epithelial tumors
 Squamous cell carcinoma
 Verrucous carcinoma
 Basaloid squamous cell carcinoma
 Papillary squamous cell carcinoma
 Spindle cell carcinoma
 Acantholytic squamous cell carcinoma
 Adenosquamous carcinoma
 Carcinoma cuniculatum
 Lymphoepithelial carcinoma
Benign epithelial tumors
 Papillomas
 Squamous cell papillomA and verruca vulgaris
 Condyloma acuminatum
 Focal epithelial hyperplasia
 Granular cell tumour
 Keratoacanthoma
TYPES
SALIVARY GLAND TUMOURS
Salivary gland carcinomas
 Acinic cell carcinoma
 Mucoepidermoid carcinoma
 Adenoid cystic carcinoma
 Polymorphous low-grade adenocarcinoma
 Basal cell adenocarcinoma
 Epithelial-myoepithelial carcinoma
Salivary gland carcinomas
 Clear cell carcinoma
 Cystadenocarcinoma
 Mucinous adenocarcinoma
 Oncocytic carcinoma
 Salivary duct carcinoma
 Myoepithelial carcinoma
 Carcinoma ex pleomorphic adenoma
SALIVARY GLAND TUMOURS
Salivary gland adenomas
 Pleomorphic adenoma
 Myoepithelioma
 Basal cell adenoma
 Canalicular adenoma
 Duct papilloma
 Cystadenoma
SALIVARY GLAND TUMOURS
Soft Tissue Tumors
 Kaposi sarcoma
 Lymphangioma
 Ectomesenchymal chondromyxoid tumour
 Focal oral mucinosis
 Congenital granular cell epulis
SALIVARY GLAND TUMOURS
EPIDEMIOLOGY IN INDIA
 Accounts for over 30% of all cancers in the
country
• Globocan 2008
EPIDEMIOLOGY- WORLD
SQUAMOUS CELL
CARCINOMA(SCC)
 Definition- An invasive epithelial neoplasm with
varying degrees of squamous differentiation
and a propensity to early and extensive lymph
node metastases, occurring predominantly in
alcohol and tobacco-using adults in the 5th and
6th decades of life.
 Etiology-
 Tobacco smoking & alcohol
 Tobacco chewing
 Human Papilloma Virus (HPV) infection
MACROSCOPIC APPEARANCE
MICROSCOPIC APPEARANCE
• Moderately differentiated SCC.
•Cells formlarge anastomosing
areas in which keratin pearls are
formed.
•Main component consists of cells
with pronounced cytonuclear atypia
•Well-differentiated SCC
•Characterized by abundant
formation of keratin pearls.
 Poorly differentiated SCC.
 Cells with atypical nuclei and a small rim of
eosinophilic cytoplasm form strands and small
nests.
MICROSCOPIC APPEARANCE
SIGNS & SYMPTOMS
 Small oral and oropharyngeal SCC are often
asymptomatic or may present with vague symptoms
 Red lesions, mixed red and white lesions, or white
plaques.
 Mucosal growth, pain and ulceration
 Referred pain to the ear
 Malodour from the mouth
 Difficulty with speaking, opening the mouth, chewing
 Pain with swallowing
DIAGNOSIS
 Physical examination- Visual inspection and
palpation of all mucosal surfaces, bimanual
palpation of the floor of the mouth and clinical
assessment of the neck for lymph node
involvement.
 Biopsy- Confirmatory test
 Fine needle aspiration cytology
 Routine pan endoscopy
 Three-dimensional imaging with computed
tomography (CT) and magnetic resonance
imaging (MRI)
LYMPHOEPITHELIAL CARCINOMA
 Definition- Lymphoepithelial carcinoma (LEC) is
a poorly differentiated squamous cell carcinoma
(SCC) or undifferentiated carcinoma,
accompanied by a prominent reactive
lymphoplasmacytic infiltrate.
 Etiology-Epstein- Burr Virus
 Clinical Features - Intra-oral mass, which may
be ulcerated
PAPILLOMAS
 Definition- Localised hyperplastic exophytic and
polypoid lesions of hyperplastic epithelium with a
verrucous or cauliflower-like morphology
 Etiology- HPV infection
ORAL CAVITY MANAGEMENT
 Radiation
 Surgery
 Combined therapy
TREATMENT OF EARLY DISEASE
Surgical Excision
 Management of choice
 Excellent cure rates with minimum morbidity
Radiotherapy (Interstitial or External)
 Equally effective as surgery for the treatment of
early disease
 Long-term sequelae including xerostomia,
dysphagia and osteoradionecrosis are major
limitations
 Requires daily therapy for 6–7 weeks
 Reserved for those patients who are unable to
undergo surgery
UICC/AJCC STAGING FOR
ADVANCED ORAL CAVITY
CANCER
 Small Tumor with neck metastasis
 T1-T2, N2-3
 Tumor < 4 cm with 2 or more cervical metastasis,
one or more contralateral cervical metastases, or
cervical metastasis > 3cm
PRIMARY SURGERY + RADIATION
INDICATED FOR ADVANCED ORAL
CAVITY CANCER
 Low local control for primary radiotherapy for
advanced oral cavity (30-40%) and poor survival
(25%)
 Increased local control with surgery +
radiotherapy (60%) and improved survival (55%)
 Zelefsky et al, Head Neck. 1990 Nov-Dec;12(6):470-5
 Local control significantly improved for locally
advanced T3, T4 oral cancers using surgery +
postoperative radiotherapy vs. primary RT
 Fein et al. Head Neck. 1994 Jul-Aug;16(4):358-65
SURGICAL APPROACHES
 Transoral
 Visor
 Lip Split with or without mandibulotomy
 Lip Split with Mandibulectomy
SURGICAL APPROACHES
 Transoral and Visor Approaches
 Cosmetic but may limit exposure
 Lip Splitting
 Modest cosmetic disadvantage with excellent
posterior exposure for mandibulotomy
 Paramedian or midline mandibulotomy
 Avoidance of alveolar nerve
SURGICAL APPROACHES
CAVEATS
 Approach determined before incision and
mandibulectomy or mandibulotomy
 Accurate assessment of bone erosion, involvement of neural
structures
SURGICAL RESECTION
ADVANCES
 Reconstruction
 Reconstruction
 Free Tissue Transfer
 Mandibular reconstruction (fibula, scapula, etc.)
 Soft tissue/tongue (radial forearm, rectus
abdominus, lateral thigh, etc.)
 Resection is rarely limited by size or extent of
tumor
CONTRAINDICATIONS TO
RESECTION
T4b: invasion of masticator space,
pterygoid plates, skull base, or
carotid encasement
Patient perception of
quality of life
SURGICAL EXCISION
 To achieve a complete resection of the tumor with
free margins
 In cases where there are positive or close
margins (tumor within 5 mm of the surgical
margin), surgical re-resection is recommended
 In cases where a re-resection is performed and
evidence of microscopically positive margins
remains or if resection cannot be reliably
performed, radiation therapy directed at the
primary site should be considered.
MANAGEMENT OF TUMORS
INVADING MANDIBLE
 A marginal or a segmental resection
 Tumor invasion of the periosteum or cortical
bone, without invasion of the medullary cortex,
can be appropriately managed with a marginal
resection.
 Tumors that erode into the medullary canal,
however, require a segmental resection
 Postoperative external beam radiation is
mandatory for tumors that invade mandible
MANAGEMENT OF TUMORS INVADING
THE BUCCAL MUCOSA
 Buccal cancer comprises10% of oral cavity
cancers
 It commonly arises from pre-existing leukoplakia.
 In early disease, surgical excision can usually be
accomplished transorally
 Advanced tumors may require a midline
labiotomy incision.
MANAGEMENT OF TUMORS
INVOLVING THE HARD PALATE
 Superficial lesions of the palatal mucosa are best
managed with a wide surgical resection including
the underlying palatal periosteum
CLINICAL EVIDENCE
Primary Surgical Therapy Followed by
Postoperative Chemotherapy and Radiation
I: EORTC Bernier et al. NEJM 2004
 Previously untreated SCC, all head and neck sites,
n=167, 5 year median follow up
 100 mg/m2 cisplatinum day 1, 22, 43 during
postoperative irradiation or postoperative radiation
alone
Primary Surgical Therapy Followed by
Postoperative Chemotherapy and Radiation:
EORTC Bernier et al. NEJM 2004
 pT3 or pT4, any N, except T3N0 of the larynx,
with negative resection margins
 pT1 or T2, N2 or N3
 T1 or T2 and N0 or N1 with pathological
extranodal spread, positive resection margins,
perineural involvement, or vascular tumor
embolism
 Oral cavity or oropharyngeal tumors with involved
lymph nodes at level IV or V
EORTC Bernier et al. NEJM 2004
 The overall survival rate 53% vs 40%, p=0.02
 Locoregional failure 18% vs. 31%, p=0.007
 Severe (grade 3 or higher) adverse effects 41%
vs. 21% p=0.001
Postoperative Chemoradiation for
Advanced Head and Neck Cancer
 Clear advantage in locoregional control
 Survival advantage
 Difference in enrollment criteria may suggest survival
advantage for locally aggressive tumors without
significant nodal disease
New Trials : Molecular Targeted
Therapy, EGF Inhibitors
Bonner, et al, NEJM, 2005
Radiation only Cetuximab+RT p-value
Patients randomized 213 211
Median survival
- Two-year survival
- Three-year survival
28 mo
55%
44%
54 mo
62%
57%
0.02 (log-rank test)
Grade 3/4 mucositis 52% 55% 0.50 (Fisher's exact)
Grade 3/4 infusion
reaction
- 3% 0.01 (Fisher's exact)
Grade 3/4 skin reaction 18% 34%
0.0003 (Fisher's
exact)
CONCLUSIONS
 Early disease (stages I–II) is generally curable
with single modality therapy.
 Surgery is preferable in most cases
 Advanced disease (stages III–IV) is best
managed with multimodality therapy, generally
with surgery followed by radiotherapy particularly
for high-risk primary lesions
 Adjuvant chemoradiotherapy to the neck is
indicated for N2 or greater disease.
REFERENCES
 Genden EM,Ferlito A et al. Contemporary management
of cancer of the oral cavity. Eur Arch Otorhinolaryngol
(2010) 267:1001–1017.
 Cancela M, Voti L, Guerra-Yi M, Chapuis F, Mazuir M,
Curado MP (2010) Oral cavity cancer in developed and
in developing countries: population-based incidence.
Head Neck (in press)
 Hashibe M, Brennan P, Chuang SC et al. Interaction
between tobacco and alcohol use and the risk of head
and neck cancer: pooled analysis in the International
Head and Neck Cancer Epidemiology Consortium.
Cancer Epidemiol Biomarkers Prev. 1999, 18:541–550
REFERENCES
 Hennessey PT, Westra WH, Califano JA (2009)
Human papillomavirus and head and neck squamous
cell carcinoma: recent evidence and clinical
implications. J Dent Res 88:300–306
 Chaturvedi AK, Engels EA, Anderson WF, Gillison ML
(2008) Incidence trends for human papilloma virus-
related and -unrelated oral squamous cell carcinomas
in the United States. J Clin Oncol 26:612–619
 Smeets SJ, Hesselink AT, Speel EJ, Haesevoets A,
Snijders PJ (2007) A novel algorithm for reliable
detection of human papillomavirus in paraffin
embedded head and neck cancer specimen. Int J
Cancer 121:2465–2472

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Cancers of the Oral Cavity

  • 1. Dr. Yogesh Belagali Medical Advisor- Oncotherapeuitcs CANCERS OF THE ORAL CAVITY
  • 2. TYPES Malignant epithelial tumors  Squamous cell carcinoma  Verrucous carcinoma  Basaloid squamous cell carcinoma  Papillary squamous cell carcinoma  Spindle cell carcinoma  Acantholytic squamous cell carcinoma  Adenosquamous carcinoma  Carcinoma cuniculatum  Lymphoepithelial carcinoma
  • 3. Benign epithelial tumors  Papillomas  Squamous cell papillomA and verruca vulgaris  Condyloma acuminatum  Focal epithelial hyperplasia  Granular cell tumour  Keratoacanthoma TYPES
  • 4. SALIVARY GLAND TUMOURS Salivary gland carcinomas  Acinic cell carcinoma  Mucoepidermoid carcinoma  Adenoid cystic carcinoma  Polymorphous low-grade adenocarcinoma  Basal cell adenocarcinoma  Epithelial-myoepithelial carcinoma
  • 5. Salivary gland carcinomas  Clear cell carcinoma  Cystadenocarcinoma  Mucinous adenocarcinoma  Oncocytic carcinoma  Salivary duct carcinoma  Myoepithelial carcinoma  Carcinoma ex pleomorphic adenoma SALIVARY GLAND TUMOURS
  • 6. Salivary gland adenomas  Pleomorphic adenoma  Myoepithelioma  Basal cell adenoma  Canalicular adenoma  Duct papilloma  Cystadenoma SALIVARY GLAND TUMOURS
  • 7. Soft Tissue Tumors  Kaposi sarcoma  Lymphangioma  Ectomesenchymal chondromyxoid tumour  Focal oral mucinosis  Congenital granular cell epulis SALIVARY GLAND TUMOURS
  • 8. EPIDEMIOLOGY IN INDIA  Accounts for over 30% of all cancers in the country • Globocan 2008
  • 10. SQUAMOUS CELL CARCINOMA(SCC)  Definition- An invasive epithelial neoplasm with varying degrees of squamous differentiation and a propensity to early and extensive lymph node metastases, occurring predominantly in alcohol and tobacco-using adults in the 5th and 6th decades of life.  Etiology-  Tobacco smoking & alcohol  Tobacco chewing  Human Papilloma Virus (HPV) infection
  • 12. MICROSCOPIC APPEARANCE • Moderately differentiated SCC. •Cells formlarge anastomosing areas in which keratin pearls are formed. •Main component consists of cells with pronounced cytonuclear atypia •Well-differentiated SCC •Characterized by abundant formation of keratin pearls.
  • 13.  Poorly differentiated SCC.  Cells with atypical nuclei and a small rim of eosinophilic cytoplasm form strands and small nests. MICROSCOPIC APPEARANCE
  • 14. SIGNS & SYMPTOMS  Small oral and oropharyngeal SCC are often asymptomatic or may present with vague symptoms  Red lesions, mixed red and white lesions, or white plaques.  Mucosal growth, pain and ulceration  Referred pain to the ear  Malodour from the mouth  Difficulty with speaking, opening the mouth, chewing  Pain with swallowing
  • 15. DIAGNOSIS  Physical examination- Visual inspection and palpation of all mucosal surfaces, bimanual palpation of the floor of the mouth and clinical assessment of the neck for lymph node involvement.  Biopsy- Confirmatory test  Fine needle aspiration cytology  Routine pan endoscopy  Three-dimensional imaging with computed tomography (CT) and magnetic resonance imaging (MRI)
  • 16. LYMPHOEPITHELIAL CARCINOMA  Definition- Lymphoepithelial carcinoma (LEC) is a poorly differentiated squamous cell carcinoma (SCC) or undifferentiated carcinoma, accompanied by a prominent reactive lymphoplasmacytic infiltrate.  Etiology-Epstein- Burr Virus  Clinical Features - Intra-oral mass, which may be ulcerated
  • 17. PAPILLOMAS  Definition- Localised hyperplastic exophytic and polypoid lesions of hyperplastic epithelium with a verrucous or cauliflower-like morphology  Etiology- HPV infection
  • 18. ORAL CAVITY MANAGEMENT  Radiation  Surgery  Combined therapy
  • 19. TREATMENT OF EARLY DISEASE Surgical Excision  Management of choice  Excellent cure rates with minimum morbidity Radiotherapy (Interstitial or External)  Equally effective as surgery for the treatment of early disease  Long-term sequelae including xerostomia, dysphagia and osteoradionecrosis are major limitations  Requires daily therapy for 6–7 weeks  Reserved for those patients who are unable to undergo surgery
  • 20. UICC/AJCC STAGING FOR ADVANCED ORAL CAVITY CANCER  Small Tumor with neck metastasis  T1-T2, N2-3  Tumor < 4 cm with 2 or more cervical metastasis, one or more contralateral cervical metastases, or cervical metastasis > 3cm
  • 21. PRIMARY SURGERY + RADIATION INDICATED FOR ADVANCED ORAL CAVITY CANCER  Low local control for primary radiotherapy for advanced oral cavity (30-40%) and poor survival (25%)  Increased local control with surgery + radiotherapy (60%) and improved survival (55%)  Zelefsky et al, Head Neck. 1990 Nov-Dec;12(6):470-5  Local control significantly improved for locally advanced T3, T4 oral cancers using surgery + postoperative radiotherapy vs. primary RT  Fein et al. Head Neck. 1994 Jul-Aug;16(4):358-65
  • 22. SURGICAL APPROACHES  Transoral  Visor  Lip Split with or without mandibulotomy  Lip Split with Mandibulectomy
  • 23. SURGICAL APPROACHES  Transoral and Visor Approaches  Cosmetic but may limit exposure  Lip Splitting  Modest cosmetic disadvantage with excellent posterior exposure for mandibulotomy  Paramedian or midline mandibulotomy  Avoidance of alveolar nerve
  • 24. SURGICAL APPROACHES CAVEATS  Approach determined before incision and mandibulectomy or mandibulotomy  Accurate assessment of bone erosion, involvement of neural structures
  • 25. SURGICAL RESECTION ADVANCES  Reconstruction  Reconstruction  Free Tissue Transfer  Mandibular reconstruction (fibula, scapula, etc.)  Soft tissue/tongue (radial forearm, rectus abdominus, lateral thigh, etc.)  Resection is rarely limited by size or extent of tumor
  • 26. CONTRAINDICATIONS TO RESECTION T4b: invasion of masticator space, pterygoid plates, skull base, or carotid encasement Patient perception of quality of life
  • 27. SURGICAL EXCISION  To achieve a complete resection of the tumor with free margins  In cases where there are positive or close margins (tumor within 5 mm of the surgical margin), surgical re-resection is recommended  In cases where a re-resection is performed and evidence of microscopically positive margins remains or if resection cannot be reliably performed, radiation therapy directed at the primary site should be considered.
  • 28. MANAGEMENT OF TUMORS INVADING MANDIBLE  A marginal or a segmental resection  Tumor invasion of the periosteum or cortical bone, without invasion of the medullary cortex, can be appropriately managed with a marginal resection.  Tumors that erode into the medullary canal, however, require a segmental resection  Postoperative external beam radiation is mandatory for tumors that invade mandible
  • 29. MANAGEMENT OF TUMORS INVADING THE BUCCAL MUCOSA  Buccal cancer comprises10% of oral cavity cancers  It commonly arises from pre-existing leukoplakia.  In early disease, surgical excision can usually be accomplished transorally  Advanced tumors may require a midline labiotomy incision.
  • 30. MANAGEMENT OF TUMORS INVOLVING THE HARD PALATE  Superficial lesions of the palatal mucosa are best managed with a wide surgical resection including the underlying palatal periosteum
  • 32. Primary Surgical Therapy Followed by Postoperative Chemotherapy and Radiation I: EORTC Bernier et al. NEJM 2004  Previously untreated SCC, all head and neck sites, n=167, 5 year median follow up  100 mg/m2 cisplatinum day 1, 22, 43 during postoperative irradiation or postoperative radiation alone
  • 33. Primary Surgical Therapy Followed by Postoperative Chemotherapy and Radiation: EORTC Bernier et al. NEJM 2004  pT3 or pT4, any N, except T3N0 of the larynx, with negative resection margins  pT1 or T2, N2 or N3  T1 or T2 and N0 or N1 with pathological extranodal spread, positive resection margins, perineural involvement, or vascular tumor embolism  Oral cavity or oropharyngeal tumors with involved lymph nodes at level IV or V
  • 34. EORTC Bernier et al. NEJM 2004  The overall survival rate 53% vs 40%, p=0.02  Locoregional failure 18% vs. 31%, p=0.007  Severe (grade 3 or higher) adverse effects 41% vs. 21% p=0.001
  • 35. Postoperative Chemoradiation for Advanced Head and Neck Cancer  Clear advantage in locoregional control  Survival advantage  Difference in enrollment criteria may suggest survival advantage for locally aggressive tumors without significant nodal disease
  • 36. New Trials : Molecular Targeted Therapy, EGF Inhibitors Bonner, et al, NEJM, 2005 Radiation only Cetuximab+RT p-value Patients randomized 213 211 Median survival - Two-year survival - Three-year survival 28 mo 55% 44% 54 mo 62% 57% 0.02 (log-rank test) Grade 3/4 mucositis 52% 55% 0.50 (Fisher's exact) Grade 3/4 infusion reaction - 3% 0.01 (Fisher's exact) Grade 3/4 skin reaction 18% 34% 0.0003 (Fisher's exact)
  • 37. CONCLUSIONS  Early disease (stages I–II) is generally curable with single modality therapy.  Surgery is preferable in most cases  Advanced disease (stages III–IV) is best managed with multimodality therapy, generally with surgery followed by radiotherapy particularly for high-risk primary lesions  Adjuvant chemoradiotherapy to the neck is indicated for N2 or greater disease.
  • 38. REFERENCES  Genden EM,Ferlito A et al. Contemporary management of cancer of the oral cavity. Eur Arch Otorhinolaryngol (2010) 267:1001–1017.  Cancela M, Voti L, Guerra-Yi M, Chapuis F, Mazuir M, Curado MP (2010) Oral cavity cancer in developed and in developing countries: population-based incidence. Head Neck (in press)  Hashibe M, Brennan P, Chuang SC et al. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev. 1999, 18:541–550
  • 39. REFERENCES  Hennessey PT, Westra WH, Califano JA (2009) Human papillomavirus and head and neck squamous cell carcinoma: recent evidence and clinical implications. J Dent Res 88:300–306  Chaturvedi AK, Engels EA, Anderson WF, Gillison ML (2008) Incidence trends for human papilloma virus- related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol 26:612–619  Smeets SJ, Hesselink AT, Speel EJ, Haesevoets A, Snijders PJ (2007) A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer 121:2465–2472