CANCERS OF THE ORAL CAVITY

Dr. Yogesh BelagaliMedical Advisor- Oncotherapeuitcs

CANCERS OF THE ORAL CAVITY

TYPESMalignant epithelial tumorsSquamous cell carcinoma Verrucous carcinoma Basaloid squamous cell carcinomaPapillary squamous cell carcinoma Spindle cell carcinoma Acantholytic squamous cell carcinoma Adenosquamous carcinoma Carcinoma cuniculatum Lymphoepithelial carcinoma

Benign epithelial tumorsPapillomasSquamous cell papillomA and verruca vulgarisCondyloma acuminatumFocal epithelial hyperplasiaGranular cell tumourKeratoacanthoma TYPES

SALIVARY GLAND TUMOURS

Salivary gland carcinomasAcinic cell carcinoma Mucoepidermoid carcinoma Adenoid cystic carcinoma Polymorphous low-grade adenocarcinoma Basal cell adenocarcinomaEpithelial-myoepithelial carcinoma

Salivary gland carcinomasClear cell carcinoma Cystadenocarcinoma Mucinous adenocarcinoma Oncocytic carcinoma Salivary duct carcinomaMyoepithelial carcinoma Carcinoma ex pleomorphic adenoma

SALIVARY GLAND TUMOURS

Salivary gland adenomasPleomorphic adenoma Myoepithelioma Basal cell adenoma Canalicular adenoma Duct papilloma CystadenomaSALIVARY GLAND TUMOURS

Soft Tissue TumorsKaposi sarcoma Lymphangioma Ectomesenchymal chondromyxoid tumourFocal oral mucinosisCongenital granular cell epulisSALIVARY GLAND TUMOURS

EPIDEMIOLOGY IN INDIAAccounts 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 & alcoholTobacco chewingHuman 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 atypiaWell-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 & SYMPTOMSSmall 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 ulcerationReferred pain to the ear Malodour from the mouthDifficulty with speaking, opening the mouth, chewing Pain with swallowingBleedingWeight loss Neck swelling

DIAGNOSISPhysical 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 VirusClinical Features - Intra-oral mass, which may be ulcerated

PAPILLOMASDefinition- Localised hyperplastic exophytic and polypoid lesions of hyperplastic epithelium with a verrucous or cauliflower-like morphology Etiology- HPV infection

ORAL CAVITY MANAGEMENT RadiationSurgery Combined therapy

TREATMENT OF EARLY DISEASESurgical ExcisionManagement of choiceExcellent cure rates with minimum morbidityRadiotherapy (Interstitial or External) Equally effective as surgery for the treatment of early diseaseLong-term sequelae including xerostomia, dysphagia and osteoradionecrosis are major limitationsRequires daily therapy for 67 weeks Reserved for those patients who are unable to undergo surgery

UICC/AJCC STAGING FOR ADVANCED ORAL CAVITY CANCERSmall Tumor with neck metastasisT1-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 CANCERLow 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 RTFein et al. Head Neck. 1994 Jul-Aug;16(4):358-65

SURGICAL APPROACHES TransoralVisorLip Split with or without mandibulotomyLip Split with Mandibulectomy

SURGICAL APPROACHESTransoral and Visor ApproachesCosmetic but may limit exposureLip SplittingModest cosmetic disadvantage with excellent posterior exposure for mandibulotomyParamedian or midline mandibulotomyAvoidance of alveolar nerve

SURGICAL APPROACHESCAVEATSApproach determined before incision and mandibulectomy or mandibulotomyAccurate assessment of bone erosion, involvement of neural structures

SURGICAL RESECTION ADVANCESReconstructionReconstructionFree Tissue TransferMandibular 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 encasementPatient perception of quality of life

SURGICAL EXCISIONTo achieve a complete resection of the tumor with free marginsIn cases where there are positive or close margins (tumor within 5 mm of the surgical margin), surgical re-resection is recommendedIn 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 MANDIBLEA marginal or a segmental resectionTumor 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 resectionPostoperative external beam radiation is mandatory for tumors that invade mandible

MANAGEMENT OF TUMORS INVADING THE BUCCAL MUCOSABuccal 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 PALATESupercial 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 2004Previously untreated SCC, all head and neck sites, n=167, 5 year median follow up100 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 2004pT3 or pT4, any N, except T3N0 of the larynx, with negative resection marginspT1 or T2, N2 or N3 T1 or T2 and N0 or N1 with pathological extranodal spread, positive resection margins, perineural involvement, or vascular tumor embolismOral cavity or oropharyngeal tumors with involved lymph nodes at level IV or V

EORTC Bernier et al. NEJM 2004The overall survival rate 53% vs 40%, p=0.02 Locoregional failure 18% vs. 31%, p=0.007Severe (grade 3 or higher) adverse effects 41% vs. 21% p=0.001

Postoperative Chemoradiation for Advanced Head and Neck CancerClear advantage in locoregional controlSurvival advantageDifference in enrollment criteria may suggest survival advantage for locally aggressive tumors without significant nodal disease

New Trials : Molecular Targeted Therapy, EGF InhibitorsBonner, et al, NEJM, 2005Radiation onlyCetuximab+RTp-valuePatients randomized213211Median survival- Two-year survival- Three-year survival28 mo55%44%54 mo62%57%0.02 (log-rank test)Grade 3/4 mucositis52%55%0.50 (Fisher's exact)Grade 3/4 infusion reaction-3%0.01 (Fisher's exact)Grade 3/4 skin reaction18%34%0.0003 (Fisher's exact)

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CONCLUSIONSEarly disease (stages III) is generally curable with single modality therapy. Surgery is preferable in most casesAdvanced disease (stages IIIIV) 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.

REFERENCESGenden EM,Ferlito A et al. Contemporary management of cancer of the oral cavity. Eur Arch Otorhinolaryngol (2010) 267:10011017.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, 18:541550

REFERENCESHennessey PT, Westra WH, Califano JA (2009) Human papillomavirus and head and neck squamous cell carcinoma: recent evidence and clinical implications. J Dent Res 88:300306Chaturvedi 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 26:612619Smeets SJ, Hesselink AT, Speel EJ, Haesevoets A, Snijders PJ (2007) A novel algorithm for reliable detection of human papillomavirus in parafn embedded head and neck cancer specimen. Int J Cancer 121:24652472