1. Oral Precancerous Lesions!
Dr. Juma Alkhabuli
​BDS, MDentSci, MFDS RCPS (Glasg), FICD, PhD Assoc Prof and Chair of Basic Dental Sciences Dept. RAK College of Dental Sciences, UAE

2. Oral Cancer Facts Oral Cancer ? 1998-2007 #8 most common cancer
300,000 NC/WW
35,000
in USA
7.600
Death
40,000 EU
Total = 246 cases
24% (n=58)/ national
40% (n=23)/ tongue
Oral Cancer
UAE ?
India
70,000
children starting smoking in India
90% are
SCC
6.6/
3.1/
5y survival
60%

3. Risk Factors
Tobacco
Alcohol
Human Papilloma Virus

4. Probably, smoking is the single most preventable cause of death
Tobacco
Probably, smoking is the single most preventable cause of death

5. Smoking Smokeless tobacco
Cigar
Chewable
Pipes
Cigarettes
Snuff

6. What are the ingredients of tobacco?
Tar: Black sticky substance used to pave roads
Insecticide: Nicotine
Car exhaust: Carbon monoxide
Finger nail polish remover: Acetone
Toilet cleaner: Ammonia
Batteries chemicals: Cadmium
Alcohol: Ethanol
Rat poison: Arsenic
Lighter fluid: Butane
More than 4000
Deadly
Chemicals
Plus
carcinogens

7. Alcohol OC is 6x > than in non-alcohol consumer
75%-80% of Pt with OC consume alcohol
Reduce the cytoplasmic area
Reduce cellular endocytosis
↑ Penetration of carcinogens into mucosa

8. Human Papilloma virus (HPV)
Implicated in oral cancer
> 120 types
HPV Types; HPV-16,-18
< 5th decade, white people
Recent studies indicate that HPV 16 is implicated in Oral cancer- sexually transmitted HPV-16, 18, 31, 45
Genital warts(condyloma accuminatum) associated with type 6 and 11 HPV
HPV related appear to occur on the tonsillar area, the base of the tongue and the oropharynx, and non-HPV positive tumors tend to involve the anterior tongue, floor of the mouth, the mucosa that covers the inside of the cheeks and alveolar ridges (the ridge area in which the teeth reside).  HPV related appear to occur on the tonsillar area, the base of the tongue and the oropharynx, and non-HPV positive tumors tend to involve the anterior tongue, floor of the mouth, the mucosa that covers the inside of the cheeks and alveolar ridges (the ridge area in which the teeth reside). 
Non smoking group
The fastest growing group

9. Cancer biology Alcohol Tobacco Theoretical model P53 pRb EGFR P 27
Nitrosamines
Aro. compounds
O2 F. radicals
P53
pRb
EGFR
Cyclin D
Polimorphisms of DNA repair genes and metabolic enzymes
P 27
P 16
VEGF
VEGFR
Telomerase
Cyclin D=single nucleotide polymorphism- associated with high susceptibility to oral cancer
E6, E7 are protein complexes released by HR HPV and bind to p53 and Rb, respectively and deactivate them and the cells divide uncontrollably
SCCs have been reported in HCVirus +ve pt. and in Lichen planus BV
EGFR
MMP-2
MMP-9
Robust angiogenesis
Hyperplasia
or mild
dysplasia
Normal
epithelium
Severe dysplasia /CIS
Invasive SCC

10. Features of epithelial dysplasia
Drop-shaped rete ridges
Nuclear hyperchromatism
Nuclear pleomorphism and altered N/C ratio
Excess mitotic activity
Loss of polarity of cells
Deep cell keratinization
Loss of intercellular adherence
Disordered or loss of differentiation

11. Classification of Epithelial dysplasia
Based on: Barnes et al, 2005, Bouquot et al, 2006

12. Nomenclatures of PC Lesions
Pre-cancer
Precursor lesions
Pre-malignant
Intra epithelial neoplasia
Potentially malignant
Used to describe clinical presentations that may have a potential to become cancer
Latest WHO monograph on H&N tumours (2005) uses the term “epithelial precursor lesions”

13. Oral Precancerous Lesions
WHO classification (1978)
Precancerous conditions
The working group of the WHO classified the clinical presentation of the oral cavity that are recognized as “precancerous” be classified into two broad groups; conditions and lesions
Precancerous
lesions
Generalized state associated with significantly increased risk of cancer
Lichen planus
Submucous fibrosis
Actinic keratosis
DL erythematosus
A morphologically altered tissue in which oral cancer is more likely to occur than in its normal counterpart
Leukoplaia
Erythroplakia
Palatal lesions (in reverse smoking)

14. Cont’d Previous terms were based on:
“Oral precancer” has clinically diverse appearances
The origin of a malignancy in the mouth of a patient with precancer would correspond with the site of precancer
In precancerous conditions, cancer may arise in any anatomical site of the mouth

15. The current concept/ view
The term “potentially malignant disorders” as it coveys that not all lesions and conditions described under this term may transform to cancer
Also, it reflects their wide spread anatomical distribution
In a patient harbouring precancerous lesion, the clinically “normal ” appearing mucosa may have dysplasia on the contralateral anatomic side (Thompson, 2002) OR molecular aberrations at other sites suggestive of a pathway to malignant transformation (Bremmer, et al; 2005)
Therefore, cancer could arise in apparently normal tissue
Therefore, the current Working Group of the WHO:
Do not favour subdividing the oral precancer to lesions and conditions
The consensus view is to refer to all clinical presentations that carry a risk of cancer under the term “ Potentially malignant disorders”

16. Potentially malignant disorders
Leukoplakia
Clinical terminology
No specific histology
May show atrophy or acanthosis
May/may not demonstrate epithelial dysplasia
“The term leukoplakia should be used to recognize white plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer” (Warnakulasuria et al; 2007)

17. Cont’d
Leukoplakia
The consensus view of the working group is that dividing leukoplakia into homogenous and non homogenous is imprecise and of little value. Nevertheless, those with mixed white and red plaques (erythroleukoplakia)
should be recognized as having a higher risk.
Non-homogeneous
Speckled
Nodular
Verrucous
Proliferative verrocus (PVL)
High risk of malignant transformation
Homogeneous
Uniformly flat and thin
Exhibit shallow cracks on surface keratin
Low risk of malignant transformation
The distinction between the two types is purely clinical
The consensus view that dividing the leukoplakia into homogeneous and non-homogeneous groups is imprecise and of limited value. However,

18. Proliferative verrocus leukoplakia
Cont’d
Verrocus leukoplakia
Proliferative verrocus leukoplakia
Nodular leukoplakia
Speckled leukoplakia

19. Cont’d

20. Cont’d

21. Cont’d Diagnosis of Leukoplakia
A provisional diagnosis of leukoplakia is made when a white lesion at clinical examination can not be diagnosed as any other disease/disorder
Definitive diagnosis- is made after exclusion of any aetiological cause other than tobacco/areca nut use and Histopathology has not confirmed any other specific disorder

22. Differential diagnosis of leukoplakia
Cont’d
Differential diagnosis of leukoplakia
White sponge nevus
Frictional keratosis- if persistent biopsy
Chemical injury
Ac. pseudomembranous candidosis- S&C
Lichen planus- biopsy
Lichenoid reaction- biopsy
Discoid lupus erythematosus- biopsy
Hairy leukoplakia- Biopsy- ISH, specific/ demonstrate EBV

23. Cont’d Erythroplakia ! (erythroplasia) Differential diagnosis:
Desquamative gingivitis
Erythematous lichen planus
DL Erythematosus
Pemphigoids
Hypersensitivity reaction
Erythematosus candidiasis
kaposi sarcoma
Haemangioma
Red patch, can not characterized clinically/ histopathologically as any definable disease
Greatest potential for malignant transformation
Relatively uncommon on their own
Appear as flat with smooth or granular surface
To be differentiated from other lesions

24. Cont’d Palatal lesions in reverse smokers
Changes are noted on the palatal surface
Clinically appear as red, white or mixed lesions
History of reverse smoking makes diagnosis easy

25. Cont’d Oral submucous fibrosis Occur in Asia (particularly India)
Potentially malignant
Chronic disorder characterized by fibrosis of the lining mucosa:
Oral cavity
Upper 1/3 of the oesophagus
Difficult to diagnose in the early forms
Later, characterized by limitation of mouth opening, narrowing of oropharyngeal orifice and woody changes to mucosa and tongue
Early stages characterized by burning sensation exacerbated by spicy food

26. Cont’d Actinic keratosis Potentially malignant disorder of the lip
Lip vermilion clinicaly may show atrophy, ulceration or crusting
Histologically, atrophy, hyperplasia, keratinization, cytological atypia, increased mitotic activity, degenration of collagen and elastosis
Biopsy for definitive diagnosis

27. Cont’d
Lichen planus
Potential malignant transformation (%?), not more than 1%
Clinically, many forms
Erosive LP+old age+risk factors= likely MT (Fang et al; 2009)
Difficult to distinguish from lichenoid reaction/contact lichenoid
Biopsy for definitive diagnosis and FU
L. R.

28. Cont’d Discoid lupus erythematosus Ch AI disease of unknown aetiology
Diagnostic overlap with LP and erythroplakia
Potential malignant transformation (?)
The chances are more when DLE affects lip
Common in young female, sensitivity to light, butterfly malar redness, skin rash, polyarthritis, unexplained fever, renal insufficiency

29. Cont’d Hereditary disorders with increased risk Dyskeratosis congenita
Epidermolysis bullosa
Rare hereditary conditions
DC are x-linked and affects male
DC characterized by white plaques on dorsum of tongue- may be confused with leukoplakia
DC-White patch on tongue, nail atrophy or absence, eye lesion (lacrimation), pigmented areas on skin (features of geriatric changes), thrombocytopenia, anemia, testicular abnormality in male

30. Malignant transformation rate of microscopically diagnosed carcinoma in situ

31. Diagnosis of oral precancerous lesions
The diagnosis of oral precancer and cancer remains a challenge to the dental profession, particularly in detection, evaluation and management of early phase alterations or frank disease
Cytology
Biopsy
Use of detecting solution
A detailed history
A clinical Examination

32. Diagnosis of oral precancerous lesions
Special investigation
Visually Enhanced Lesion
Scope
VELSCOPE

33. Diagnosis of oral precancerous lesions
Special investigation

34. Diagnosis of Leukoplakia
White patch
Proper history and clinical examination to exclude any known condition/
disorder/disease
Provisional clinical diagnosis of leukoplakia
Other known disorder excluded
Other known disorder confirmed
Biopsy
Leukoplakia with dysplasia
Leukoplakia without dysplasia
Revise diagnosis
to other disorder/ disease
Adapted from: Warnakulasuriya et al; 2007

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Thanks