Lecture notes for medical students

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2. Learning Objectives

3. Learning Objectives
1. Introduction & History
2. Relevant Anatomy, Physiology
3. Aetiology
4. Pathophysiology
5. Pathology
6. Classification
7. Clinical Features
8. Investigations
9. Management
10. Prevention
11. Guidelines
12. Take home messages

4. Introduction & History.
•

5. Introduction & History.
• Aka. OSCC Oral Squamous Cell
Carcinoma.
• Mouth (oral) cancer is a major neoplasm
worldwide and accounts for most head and
neck cancers.
• It theoretically should be largely
preventable or detectable at an early stage
but it is not.
• Approximately 90% of oral cancers are
SCC,

6. Introduction & History.
• Seen typically on the lateral border of the
tongue, oropharynx, and floor of the mouth,
• as a red lesion (erythroplakia), white lesion
(leukoplakia), or a mix of the two
(erythroleukoplakia) with an ulcer.

7. Aetiology

8. Aetiology
• Idiopathic
• Congenital/ Genetic
• Nutritional Deficiency/excess
• Traumatic
• Infections /Infestation
• Autoimmune
• Neoplastic (Benign/Malignant)
• Degenerative / lifestyle
• Iatrogenic
• Psychosomatic
• Poisoning/ Toxins/ Drug induced

9. Aetiology
• Idiopathic
• Congenital/Genetic
• Traumatic
• Infections /Infestation
• Autoimmune
• Neoplastic (Benign/Malignant)
• Degenerative
• Iatrogenic

10. Aetiology
• Multifactorial and strongly related to
lifestyle, mostly habits and diet (particularly
tobacco alone or in combination with betel,
and alcohol use.
• Ca. oropharynx, possible due to human
papillomavirus (HPV).
• Immune defects or immunosuppression,
defects of carcinogen metabolism, or
defects in DNA-repair enzymes underlie
some cases of SCC.
• Sunlight exposure predisposes to lip cancer.

11. Aetiology
• Tobacco and alcohol use
• Betel-quid chewing and oral snuff
• diet low in fresh vegetables and fruits
• human papillomaviruses (HPVs)
• Cigarette smoking:
• Oral health
• Mouthwash use: The effect of the alcohol in
mouthwash appears to be similar to that of
alcohol used for drinking,

12. Aetiology
• oral submucous fibrosis
• oral lichen planus
• lupus erythematosus
• dyskeratosis congenita
• Fanconi anemia).

13. Pathophysiology

14. Pathophysiology
• The genetic aberrations involving
chromosomes 9, 3, 17, 13, and 11.
• Inactivated TSGs (Tumor Supressor Genes)
especially P16, and TP53 in western
countries
• Overexpressed oncogenes,
especially PRAD1 and Harvey ras (H-ras).
In Indians.
• Defective Carcinogen-metabolizing
enzymes

15. Pathophysiology
• Defective Carcinogen-metabolizing enzymes –
– alcohol dehydrogenase type 3 genotypes
– Cytochrome P450
– GSTM1 has a decreased capacity to detoxify
tobacco carcinogens.
– N-acetyl transferase NAT1*10 genotypes.
• Defective DNA repair genes has also been found
to underlie some OSCCs.
• An immune deficiency state may predispose one
to a higher risk of developing OSCC, especially
lip cancer.

16. Pathology
•

17. Pathology
• nests and islands of squamous cells invading the
underlying connective tissue.
• aberrant keratinization, forming whorls of keratin
within
• Poorly differentiated OSCC consists of sheets of
cells showing extreme pleomorphism, giant
nuclei, and multiple and bizarre mitoses difficult
to distinguish from other malignancies,
particularly poorly differentiated lymphoma or
melanoma.
• mmunocytochemical markers such as keratins,
common leukocyte antigen, and melanoma-
specific antibodies

18. Clinical Features
•

19. Clinical Features
• Demography
• Symptoms
• Signs
• Prognosis
• Complications

20. Demography

21. Demography
• The oral cavity is one of the 10 most
frequent sites of cancer internationally.
• OSCC is particularly common in the
developing world, mostly in older males.
• In parts of India, oral cancer can represent
more than 50% of all cancers.
• The prevalence of lip cancer appears to be
decreasing, but the prevalence of intraoral
cancer appears to be rising in many
countries, especially in younger people and
women.

22. Demography
• Race -higher (by approximately 50%) in
blacks compared with whites.
• More in males but equalising.
• occurs in middle-aged and older persons.
However, in recent years, an increase in
younger patients

23. 7Warning Signs of Cancer
.

24. 7Warning Signs of Cancer
1. Change in bowel or bladder habits.
2. A sore that does not heal.
3. Unusual bleeding or discharge.
4. Thickening or lump in the breast or
elsewhere.
5. Indigestion or difficulty in swallowing.
6. Obvious change in a wart or mole.
7. Nagging cough or hoarseness.

25. History
• Some OSCCs arise in apparently normal
mucosa, but many are preceded by
premalignant disorders-
– Erythroplakia (red patch) 90%
– Leukoplakia (white patch) –rare chance.
– Erythroleukoplakia (red and white patch)
– Verrucous leukoplakia.
– Speckeled leukoplakia.

26. Symptoms

27. Symptoms
• A red lesion (erythroplakia)
• A granular ulcer with fissuring or raised
exophytic margins
• A white or mixed white and red lesion
• An indurated lump/ulcer (ie, a firm
infiltration beneath the mucosa)
• A nonhealing extraction socket
• A lesion fixed to deeper tissues or to
overlying skin or mucosa
• Cervical lymph node enlargement,

28. Symptoms
• Early carcinomas may not be painful
• later, they may cause pain and difficulty
with speech and swallowing.

29. Signs

30. Signs
• The most common sites tongue, mainly the
lateral and ventrolateral aspects, and the
floor of the mouth.
• Ulcers, red or white areas, lumps, or
fissures.
• Red oral lesions usually are more dangerous
than white oral lesions.
• Erythroplakia is a red and often velvety
lesion, which, unlike leukoplakias, may not
form a plaque but is level with or depressed
below the surrounding mucosa

31. Signs
• Lesions always must be palpated after
inspection to detect induration and fixation
to deeper tissues.
• Some OSCC can also appear as a white
patch.
• Late OSCC may manifest as an exophytic
lesion or an area of ulceration with
induration
• A typical malignant ulcer is hard with
heaped-up and often everted or rolled edges
and a granular floor,

32. Signs
• RULE Any single lesion that persists more
than 3 weeks, especially if red, ulcerated, or
a lump, especially with induration (ie, the
RULE mnemonic) should be regarded with
suspicion and a histopathological diagnosis
established.

33. Signs
•

34. Signs
•

35. Signs
•

37. Signs
• Second primary tumors are additional
primary carcinomas (synchronous tumors)
present in as many as 10-15% .
• From 30-80% of patients with oral cancer
have metastases in the cervical lymph nodes
at presentation.
• Later, dissemination to the lungs, liver, or
bones may occur.

38. Prognosis

39. Prognosis
• Depends on stage.
• 5-year survival rate for oral and pharyngeal
cancers is approximately 66%.
• Lip carcinomas generally has the best 5-
year survival rate (88%)
• floor of mouth has the worst (54%).
• HPV-positive tumors tend to respond better
to chemotherapy and/or radiation therapy
compared with those with HPV-negative
tumors

40. Prognosis
• When OSCC is fatal, it almost always is
either because of failure to control the
primary tumor or because of nodal
metastases. Death resulting from distant
metastasis is unusual.

41. Investigations

42. Investigations
• Laboratory Studies
– Routine
– Special
• Imaging Studies
• Tissue diagnosis
– Cytology
• FNAC
– Histology
– Germ line Testing and Molecular Analysis
• Diagnostic Laparotomy.

43. Investigations
• Laboratory Studies
– Routine
– Special
• Imaging Studies
• Tissue diagnosis
– Cytology
• FNAC
– Histology

44. Investigations in Malignancy
•

45. Investigations in Malignancy
• For diagnosis
• For staging
• For Screening
• For Monitoring

46. Diagnostic Studies
Imaging Studies

47. Diagnostic Studies
Imaging Studies
• X-Ray
• USG
• CT
• Angiography
• MRI
• Endoscopy
• Nuclear scan PET CT Scan.

48. Diagnostic Studies
Imaging Studies
• Photography for monitoring the clinical
state and site of premalignant lesions.
• Chest radiography and endoscopy
synchronous second primary tumors
• Jaw radiography (often rotating
pantomography) may show invasion
• USG Abd.
• CT Chest
• PET scan

49. Diagnostic Studies
Histopathology
• Punch biopsy Avoid excisional biopsy
• Always take a biopsy specimen of the red
lesions if both red and white lesions are
present
• Guided biopsy by vital staining-
– Staining with toluidine blue followed by a rinse
with 1% acetic acid and then saline
– Various light sources are becoming available to
help delineate areas for biopsy

50. Differential Diagnosis

51. Differential Diagnosis
• Actinic Keratosis
• Erythroplasia
• Lichen Planus
• Lichenoid lesions
• Mucosal Candidiasis
• Traumatic lesion

52. TNM Classification
• .

53. TNM Classification
Primary tumor
• T0 - No primary tumor
• Tis - Carcinoma in situ
• T1 - Tumor 2 cm or smaller
• T2 - Tumor 4 cm or smaller
• T3 - Tumor larger than 4 cm
• T4 - Tumor larger than 4 cm and deep
invasion to muscle, bone, or deep structures
.

54. TNM Classification
Lymphatic node involvement
• N0 - No nodes
• N1 - Single homolateral node smaller than 3
cm
• N2 - Nodes(s) homolateral smaller than 6
cm
• N3 - Nodes(s) larger than 6 cm and/or
bilateral

55. TNM Classification
• M0 - No metastasis
• M1 - Metastasis noted

56. TNM Classification
• Stage I - T1, N0, M0.
• Stage II -T2, N0, M0.
• Stage III :
– T3, N0, M0
– T1, T2, T3, N1, M0
• Stage IV :
– T4, N0, M0
– Any T, N2 or N3, M0
– Any T, any N, any M

57. Management

58. Management
• Surgery
• Radiotherapy
• Chemotherapy
• Targeted therapy

59. Management
• Oral squamous cell carcinoma (OSCC)
currently is treated largely by surgery
and/or irradiation.
• Photodynamic therapy and chemotherapy
have occasional applications
• There is an increased use of chemotherapy
including targeted therapy

60. Operative Therapy

61. Operative Therapy
• The goal of surgery for oral squamous cell
carcinoma (OSCC) is to remove the primary
tumor together with a margin of clinically
normal tissue.
• If at least one node has clinical signs of
invasion, a reasonable presumption is that
others may be involved and must be
removed by traditional radical neck
dissection.
• Reconstruction.

62. Operative Therapy
Advantages-
• Surgery provides complete tumor and
lymph node excision.
• A full histologic examination can be
performed for staging purposes and to help
predict prognosis and the need for adjuvant
radiotherapy.
• Surgery also provides another option of
treatment for radiotherapy-resistant tumors.

63. Operative Therapy
Disadvantages-
• Perioperative mortality and morbidity.
• aesthetic and functional defects.

64. Radiotherapy

65. Radiotherapy
• Advantages of radiotherapy
1. Normal anatomy and function are
maintained
2. General anesthesia is not needed.
• Disadvantages
1. adverse effects are common
2. Cure is uncommon, especially for large
tumors
3. Subsequent surgery is more difficult and
hazardous and survival is reduced further.

66. Radiotherapy:Adverse effects
• Short term complication- Oral mucositis
invariable
• Longer-term complications
1. dry mouth (xerostomia)
2. loss of taste
3. osteoradionecrosis (ORN) .of mandible.

67. Radiotherapy
1. External beam radiation (teletherapy),
which is commonly accompanied by
adverse effects,
2. Interstitial therapy

68. Interstitial therapy

69. Interstitial therapy
1. Brachytherapy- intrralesional
2. Plesiotherapy – Surface therapy
• causes fewer complications but is suitable
only for tumors that are smaller than 2 cm
and located in selected sites.

70. Targeted therapy
• Cetuximab and panitumumab.
• Cetuximab
• Erlotinib and gefitinib
• Lapatinib

71. cancer-prevention tips.

72. cancer-prevention tips.
• Don't use tobacco
• Avoid Alcohol
• Eat a healthy diet. ...
• Maintain a healthy weight and be physically
active. ...
• Protect yourself from the sun. ...
• Get vaccinated. ...
• Avoid risky behaviors. ...
• Get regular medical care.
• .

73. Prevention

74. Prevention
• Screening
• Risk reduction

75. Prevention
• Diet richer in vegetables and fruits
• Avoid Tobacco
• Avoid Betel nut, Paan, Gutkha
• Avoid alcohol consumption.
• Self examination.
• Good oral hygiene.

76. Early Detection

77. Early Detection
• Dental practitioners and dental care
professionals should remain vigilant for
signs of potentially malignant disorders and
oral cancer while performing routine oral
examinations.
• The mnemonic RULE
– Red
– Ulcerated
– Lump
– Extending for 3 or more weeks.
• Biopsy

78. Early Detection

79. Early Detection

80. Early Detection

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