oral cavity malignancy recent ppt.pptx

oral cavity malignancy

1. Malignancies of Oral Cavity, Lip, Tongue Dr Sumer Yadav Plastic and reconstructive surgeon [email protected]

2. [email protected]

3. Pre-Malignant Lesions/conditions Leukoplakia - chronic, white, verrucous plaque with histologic atypia Severity linked to the duration and quantity of tobacco and alcohol use Occur anywhere in the oral cavity Lip, tongue, or floor of the mouth lesions are prone for progression to SCC Erythroplakia - non-inflammatory erythematous plaque Analagous to intra-oral erythroplasia of Queyrat or SCC in situ Biopsies - severe dysplasia and areas of frank invasion [email protected]

4. Leukoplakia [email protected]

5. Erythroplakia [email protected]

6. Pre-Malignant Lesions… Submucous fibrosis generalized white discoloration of oral mucosa with progressive fibrosis, painful mucosal atrophy and restrictive fibrotic bands individuals who chew betel quid, a concoction of tobacco, lime, areca nut and betel leaves Ultimately leads to trismus, dysphagia and severe xerostomia 5 - 10 % progress to SCC [email protected]

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8. Cancerous lesion of Lips& Oral cavity Lips –SCC, Melanoma, BCC(rare) Oral cavity: -- scc: 9/10 incidence --verrucous ca: <5% low grade, slow growing rarely metastasizes with tendency to invade deep tissue. [email protected]

9. Cancerous lesion of Lips& Oral cavity Minor salivary gland tumor: -in the glands lining the oral cavity -adenoidcystic ca, mucoepidermoid ca, adenocarcinoma. -Sarcoma [email protected]

10. [email protected]

11. Incidence Globally >300,000 people diagnosed/year Eighth most common malignancy India –upto 40% of all malignancies M>F Raising trend 6-7 th decade Most of the people are dying because of ignorance [email protected]

12. INCIDENCE Demographic and clinical profile of oral squamous cell carcinoma patients: a retrospective study ( Shenoi R, Sharma BK, et.al, Indian J Cancer. 2012 Jan;49(1):21-6: Most common site: mandibular alveolus Major cause: tobacco chewing Majority of patients presented in stage III Majority presented within 6 months of onset [email protected]

13. Risk Factors Tobacco: About 90% of people with oral cavity and oropharyngeal cancer use tobacco Alcohol: Drinking alcohol strongly increases a smoker's risk of developing oral cavity and oropharyngeal cancer. Ultraviolet light: More than 30% of patients with cancers of the lip have outdoor occupations associated with prolonged exposure to sunlight. Irritation: Long-term irritation to the lining of the mouth caused by poorly fitting dentures [email protected]

14. Risk Factors Cont… Poor nutrition: A diet low in fruits and vegetables is associated with an increased risk Mouthwash: Some studies have suggested that mouthwash with a high alcohol content Human papillomavirus (HPV) infection: Immune system suppression : Age: The likelihood of developing oral and oropharyngeal cancer increases with age, especially after age 35. Gender: Oral and oropharyngeal cancer is twice as common in men as in women [email protected]

15. How tobacco affects Tobacco smoke contains >4000 chemicals, at least 60 shown to be carcinogens. Smoke less tobacco: main form: chewing, snuff at least 28 carcinogens found in smokeless form [email protected]

16. Relative Risk factors for Oral Cancers Habit Relative Risk % None Betel nut Chewing Smoking only Betel chewing + Tobacco chewing Betel chewing + Smoking Betel+Tobacco+smoking 1% 4% 3-6% 8-15% 4-25% 20% [email protected]

17. How Alcohol affects Chronic alcohol exposure results in increased cancer incidence in animal model. Acetaldehyde , reactive oxygen species- main mutagen Acetaldehyde: directly binds to DNA, alters methyl transfer leading to hypomethylation leading to alerted gene products Alcohol promotes cytochrome P450- which increases activation of procarcinogens( tobacco, alcohol). Alcohol can act as solvent facilitating entry of carcinogens into cells [email protected]

18. Role of HPV in Oral SCC Role of human papilloma virus in the oral carcinogenesis: an Indian perspective (Chocolatewala NM, et.al. J Cancer R Ther. 2009 Apr-Jun;5(2):7-17). Association strongest for Oropharynx, specially cancer of tonsils followed by base of tongue. High risk HPV-16 predominate type. Commonly affects younger age groups , male, non smokers. Better outcomes, more responsive to RT, higher survival rate. [email protected]

19. INHERITED RISK FACTORS Defective DNA repair mechanism: xeroderma pigmentosa, ataxia telangiectasia, bloom syndrome, fanconi syndrome Tumor suppressor gene(p53) defect: Li Fraumeni syndrome. [email protected]

20. INHERITED RISK FACTORS Relationship between ABO blood groups and oral cancer (Jaleel BF, et. al. Indian J Dental Research 2012 Jan;23(1):7-10: found that people with blood group A had 1.46 times higher risk of developing oral cancer as compared with other blood group. [email protected]

21. INHERITED RISK FACTORS Allergies and risk of head and neck cancer (Michaud DS, et.al. Cancer Causes Control. 2012 Aug;23(8):1317-22. Epub 2012 Jun 19). Case control study Allergies have heightened Th2 immunity Had a 19% lower risk of HNSCC. Statistically significant for oropharyngeal cancer. HPV status does not confound or modify associations with allergies. [email protected]

22. MOLECULAR BIOLOGY Cytogenetic : chromosomes 3,5,8,11,17,18. Tumor suppressor genes inactivation: p16,p21,p53,RB gene. Proto-oncogene activation: cyclinD1/PRADD1. Growth factors /receptors overexpression: EGF,EGF-R,TGF-ɑ,HER-2/ neu,FGF,FGF -R,PDGF). [email protected]

23. MOLECULAR BIOLOGY RAS family oncogene. Telomeres, telomerase, cell senescence Tumor immunology(role of TIL, CTL, IL-2/4/6) Tumor invasion and metastasis:(endothelial proliferation:PGE2,TGF β ,FGF,VEGF),MMP [email protected]

24. MOLECULAR PROGRESSION MODEL OF HNSCC CARCINOGENESIS Normal squamous mucosa EGF, EGFR Overexpression Squamous hyperplasia Telomerase activation p16 inactivation Dysplasia PRAD-1 amplification 3p deletion p53 inactivation Carcinoma in-situ 4q, 5q, 8p, 13q deletion Invasive carcinoma Matrix metalloproteinase Over-expression Metastasis [email protected]

25. DNA changes P53, p16, Ki67 immunoexpression in oral scc ( Dragomir LP, et.al, Rom jo morph embry 2012; 53(1)89-93: positivity index- increased for p16 tumor invasion- identified with p53, Ki67. Study highlights value of immunostain for p16 in identifying dysplastic lesion Predictive importance of p53, Ki16 markers in identifying aggressive form of tumour. [email protected]

26. DNA CHANGES Immunohistochemical p53, Ki16, hTERT in oral scc( Abraho AC et.al.Brazil oral research 2011 Jan-Feb;25(1):34-41: p53 positivity in 93.3% of PMD, 43.3% of OSCC, 80% OEH. [email protected]

27. Site of oral cavity Tongue : 35% Floor of mouth: 30% Lower alveolus: 15% Buccal mucosa: 10% Upper alveolus/hard palate: 8% RMT: 2% Lips: lower-93%, upper-5%, commissure- 2% [email protected]

28. Symptoms a sore in the mouth that does not heal (most common symptom) pain in the mouth that doesn't go away (also very common) a persistent lump or thickening in the cheek a persistent white or red patch on the gums, tongue, tonsil, or lining of the mouth a sore throat or a feeling that something is caught in the throat that doesn't go away Increased salivation [email protected]

29. More Symptoms difficulty chewing or swallowing difficulty moving the jaw or tongue swelling of the jaw that causes dentures to fit poorly or become uncomfortable loosening of the teeth or pain around the teeth or jaw voice changes a lump or mass in the neck weight loss persistent bad breath [email protected]

30. Patient Workup History Clinical examination Investigations [email protected]

31. Patient Workup Investigations : Primary: photographs incisional biopsy FNAC Orthopantogram CXR ECG Routine blood investigations [email protected]

32. Patient Workup Investigations: for staging - CT face + neck ± CT chest - MRI - USG of neck or primary ± USG guided FNAC of suspicious lymphadenopathy - PET [email protected]

33. INVESTIGATIONS FOR RECONSTRUCTION Allen’s test of vascular supply to hand if a radial forearm flap anticipated. MRA of leg vessels if composite fibula reconstruction anticipated. Colour Doppler of chest , abdomen if DCIA(deep circumflex iliac artery) free flap anticipated Dental impression for all maxillary tumours [email protected]

34. STAGING OF THE DISEASE American joint committee on cancer: T , N , M Tx- primary tumour cannot be assessed T0- No evidence of primary tumour T1- ≤ 2cm in greatest dimension T2- 4cm < 2cm> in greatest dimension T3- > 4cm in greatest dimension [email protected]

35. STAGING OF THE DISEASE T4a- Oral cavity: tumour invades through cortical bone, into deep(extrinsic) muscle of tongue, maxillary sinus or skin. Lips: cortical bone, inferior alveolar nerve, floor of mouth, skin i.e. chin or nose. T4b- involves masticator space, pterygoid plates, skull base and/or encases internal carotid artery [email protected]

36. STAGING OF THE DISEASE N stage: Nx- regional lymph nodes can not be assessed. N0- no regional lymph node metastasis. N1- metastasis in a single ipsilateral lymph node ≤ 3cm in greatest dimension. N2a- metastasis in a single ipsilateral LN > 3cm but < 6cm in greatest dimension. [email protected]

37. STAGING OF THE DISEASE N2b- metastasis in multiple ipsilateral LNs, none > 6cm in greatest dimension. N2c- metastasis in B/L or C/L LNs, none > 6 cm. N3- metastasis in a LN > 6 cm in greatest dimension M stage: Mx- cannot be assessed, M0- no distant metastasis, M1- distant metastasisi. [email protected]

38. Stage Grouping Stage 0 Tis N0 M0 Stage I T1 N0 M0 Stage II T2 N0 M0 Stage III T1, T2 N1 M0 T3 N0, N1 M0 Stage IV A T1, T2, T3 N2 M0 T4a N0, N1, N2 M0 Stage IV B Any T N3 M0 T4b Any N M0 Stage IV C Any T Any N M1 [email protected]

39. TREATMENT Treatment goals: to eradicate primary tumor and LN metastasis, to maintain function, cosmetic reconstruction Factors affecting choice of treatment: tumor factor patient factor resource factor [email protected]

40. Treatment Goals for Cancer of the Oral Cavity • Cure of cancer • Preservation or restoration of form and function • Avoid or minimize sequelae of treatment • Prevent second primary cancers Palliation Restore cosmesis Minimise morbidity and mortality [email protected]

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42. TUMOR FACTORS AFFECTING TREATMENT • Site • Size (T stage) • Location • Multiplicity • Proximity to bone • Pathological features • Histology, grade, depth of invasion, tumor type • Status of cervical lymph nodes • Previous treatment [email protected]

43. TREATMENT Patient factors: age, general medical condition, performance status, occupation, lifestyle(smoking/drinking) socioeconomic considerations previous treatment [email protected]

44. TREATMENT Physician factors: surgery, radiotherapy, chemotherapy nursing & rehabilitation services, dental, prosthetics, support services [email protected]

45. Treatment Surgery Radiotherapy Chemotherapy Immunotherapy Targeted therapy Gene therapy [email protected]

46. Treatment of Choice Stage I , II: single modality treatment is effective and preferable. Stage III , IV: multimodal therapy is essential [email protected]

47. TREATMENT SURGERY: Early stage T1/2No tumor: Wide excision +/ - ND High risk of locoregional recurrent (40%) Management of No Neck : High incidence of occult metastasis in the clinically No Neck (15-43%) Controversy : Observation or Surgery/Radiation Depend on primary site. Should be have minimal morbidity ELND if risk of occult meta >20%. (SND/SOHND). Locally advanced tumor: Combined modality treatment [email protected]

48. Classification of ND 1991 Classification: RND Modified RND Selective ND: Supraomohyoid Lateral Posterolateral Anterior Extended ND 2001 Classification: RND Modified RND Selective ND (SND): SND (L.I-III/IV) SND (L.II-IV) SND (L.II-V) SND (L.VI) Extended ND Proposed by American HN Society and AAOHNS [email protected]

49. Selective neck dissection Modified RND type 1,2,3. [email protected]

50. Standard treatment options for management of lymph node: Radiation therapy alone or neck dissection: N1 (0–2 cm). N2b or N3; all nodes smaller than 2 cm. (A combined surgical and radiation therapy approach should also be considered.) Radiation therapy and neck dissection: N1 (2–3 cm), N2a, N3. Surgery followed by radiation therapy, indications for which are as follows: Multiple positive nodes. Contralateral subclinical metastases. Invasion of tumor through the capsule of the lymph node. N2b or N3 (one or more nodes in each side of the neck, as appropriate, >2 cm). Radiation therapy prior to surgery: Large fixed nodes. [email protected]

51. SURGICAL APPROACHES Trans-oral approach Lower cheek approach Upper cheek approach mandibulotomy Visor flap [email protected]

52. Surgical approach depends on • Tumor size • Tumor site • Tumor location • Proximity to mandible or maxilla • Need for neck dissection • Need for reconstructive surgery [email protected]

53. Factors predicting positive margin Large tumour. Perineural spread. Vascular permeation. Noncohesive invasive front Cervical metastasis [email protected]

54. Carcinoma tongue [email protected]

55. Carcinoma tongue Tongue functions Taste Mastication swallowing Speech intimacy [email protected]

56. Carcinoma tongue Pathological types 1. nonhealing ulcer 2. proliferative growth with everted edge 3. indurated variety with frozen tongue 4. fissure variety [email protected]

57. Carcinoma tongue - clinical Bleeding ulcer Pain Ankyloglossia Dysarticulation Dysphagia Fetor oris Neck nodes [email protected]

58. Carcinoma tongue- surgery Wide local excision – CIS Partial glossectomy Hemiglossectomy Total glossectomy Neck dissection Flap reconstruction- PMMC/DP/FREE ALT/FRFF [email protected]

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63. CARCINOMA LIP [email protected]

64. Oral competence Deglutition Articulation Expression of emotion Symbol of beauty Lip Function [email protected]

65. EPIDEMIOLOGY It is one of most common malignant tumor affecting head & neck Squamous cell Carcinoma is most common in India Factors affecting are : Solar radiation Tobacco smoking Viruses LIP CANCER [email protected]

66. Male:female ratio – 14:1 Lower lip > upper lip (solar radiation) 90% : lower lip 6%: oral commissure 4%: upper lip [email protected]

67. Lip should have sensation, motion, prevent drooling, permit speech & resonable cosmetic appearance. Full thickness skin flaps used whenever possible It should provide sufficient mucosa contiguous to commisure to avoid contracture Principles of lip repair [email protected]

68. FIGURE 2. Direct excision and repair of lower lip lesions. Lesions up to one half of the lip can be excised and repair primarily. Small lesions can be excised using the "V" excision, and can be angled to blend into the chin-lip crease. Larger lesions can be excised using a "W" pattern. The "W" avoids crossing the chin-lip crease and retains an adequate margin of tissue around the lesion inferiorly. The largest lesions can be excised as a rectangle and incisions made in the chin-lip crease to allow advancement of lateral lip tissue for closure. [email protected]

69. FIGURE 6. Abbe cross lip flap. (A) "V"-shaped incision diagramed around lower lip lesion and proposed upper lip flap outlined. (B) Lesion removed, flap rotated and sutured into defect. Flap is designed with height 1 to 2 mm greater than defect to be reconstructed [email protected]

70. FIGURE 6. Estlander cross lip flap. (A) "V"-shaped incision diagramed around lower lip lesion and proposed upper lip flap outlined. (B) Lesion removed, flap rotated and sutured into defect. Flap is designed with height 1 to 2 mm greater than defect to be reconstructed. [email protected]

71. Karapandzic flap, (A) Lower lip defect after resection of carcinoma. Proposed incisions outlined. (B) Incisions made through skin. Buccal branches of facial nerve and labial artery branches preserved to greatest extent possible. (C) Tissue advanced and defect closed. [email protected]

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73. RADIOTHERAPY Applications: - Radical : early tongue cancer - palliative : advanced total control not possible: 20Gy x5 daily fractions x 1 week. -combined therapy. -preoperative. -postoperative. [email protected]

74. POST-OP RT Indications: - presence of nodal disease with exptracapsular spread. -presence of involved surgical margin -excision margin less than 5mm. -stage III/IV. -perineural or vascular invasion. -poor differentiation. -oral cavity primary. -multicentric primary. ->4 nodes positive. -soft tissue invasion. -dysplasia or carcinoma insitu at resection margin. [email protected]

75. IMMUNOTHERAPY HPV Vaccines Estimated that 25% of HNSCC are HPV associated Tend to arise in younger patients Lingual and palatine tonsils Occur predominantly in non smoker/drinker Associated with a more favorable prognosis HPV viral oncogenes E6 and E7 are consistently expressed in HPV associated cancers Thought to integrate into the host DNA, and when expressed, bypass the regulation of cell proliferation Both protein and DNA vaccines targeting HPV DNA are currently in phase I and phase II trials [email protected]

76. TARGETED THERAPY Targeted therapy in head and neck cancer: state of the art 2007 and review of clinical applications ( Langer CJ. Cancer 2008 Jun 15;112(12):2635-45: -anti-EGFR monoclonal antibody( MoAb ) cetuximab first targeted therapy to be developed -single agent cetuximab confer clinical benefits in patient with cisplatin refractory metastatic disease. [email protected]

77. TARGETED THERAPY Molecular targeted therapies in head and neck cancer - An update of recent developments(Martin Goerner , et.al, Head & Neck Oncology 2010, 2:8): -anti-EGFR MoAbs :cetuximab , pantimumab , zalutumumab -EGFR targeted tyrosine kinase inhibitors: gefitinib , erlotinib - EGFR & HER-2 combined tyrosine kinase inhibitors: lapatinib , BIBW-2992. - VEGFR inhibitor: bevacicumab , sorafenib , sunitinib . [email protected]

78. GENE THERAPY Gene therapy for oral squamous cell carcinoma: An overview( TR Saraswathi , et.al, Indian J Dent Res. 2007 Jul-Sep;18(3):120-3) STRATEGIES: - gene addition therapy : reconstitution of wild type p-53 function with p-53 expressing adenovirus-> led to inhibition of SCC cell lines. - antisense RNA therapy: introducing a remedial gene that prevents expression of a specific defective gene: potential target E6 & E7 genes of HPV. - suicide gene therapy: introduction of a gene into a ce ll inabling a prodrug to be activated into an active cytotoxic drug. [email protected]

79. Recurrent lips & oral cavity cancer Surgery is preferred, if radiation was used initially. Surgery, radiation or combination if surgery used initially. Chemotherapy , but no increase in survival demonstrated. Other novel therapy method [email protected]

80. PROGNOSIS Location/thickness/depth of primary tumor Staging Type of histology Grading Presence of perineural spread Mandibular invasion Ln extension (Level, size, exptracapsular) Molecular markers (?) [email protected]

81. What happens after Treatment? Speech and Swallowing Therapy Follow-up tests Chemoprevention Watch for new symptoms General health considerations [email protected]

82. Summary Risk factors Premalignant lesions Sign and symptoms Investigations TNM staging and diagnosis Treatment plan Surgery Radiotherapy Chemotherapy Follow up [email protected]

83. THANKS [email protected]