Aetiology, epidemiology, clinical and pathological features of oral cancer Flashcards
What does oral cancer involve and not involve?
The oropharynx but NOT the salivary glands
Epidemics of oral cancer?
16th most common cancer worldwide Head and neck = 6th most common Cases - 355,000 Males: 5.8/100,000 Females: 2.3/100,000 Deaths 177000 Death rate 50%
Where is oral cancer most common?
Sri-Lanka
Oral cancer in England?
Cases: 7587 including the pharynx
4379 true oral cavity
3% of all cancers
Males: 20.1/100,000
Females: 9.3/100,000
Deaths 2427
5yr survival 58%
Are oral cancer deaths increasing or decreasing/
Increasing
Problems with oral cancer?
Increasing incidence
Younger patients
Little improvement in survival - only a modest increase in survival in 50yrs
Who does oral cancer most commonly affect?
A disease of older men typically - 60s and 70s - heavy smoker
But now more women have it and it is more common in younger populations - 40-49 yr olds
Why is the oral cancer death rate so high?
Pt’s present late so survival is poor
Stage III and stage IV presentation = late/advanced stage disease
The location of the cancer can vary the survival rate, list the highest to lowest survival rates per location
Lip = high 5 yr survival rate Oral cavity Tongue Oropharynx Hypotharynx = Lowest
Aetiology of oral cancer?
Multifactorial:
- No single factor identified
- Genetic predisposition in some (rare)
- Environmental
Factors vary in different locations and ethnic groups
Inherited factors in oral cancer?
Polymorphisms in genes involved in the metabolism of carcinogens have been linked to individual susceptibility:
- Tobacco - glutathione transferases = carcinogens stay for longer than they should
- Alcohol - Alcohol dehydrogenase (ALDH2)
An increased risk of oral cancer is associated with a number of inherited cancer syndromes:
- Li-fraumeni - abnormal P53
- Fanconi anaemia
- Xeroderma pigmentosum
Risk factors for oral cancer?
Tobacco Alcohol Sunlight Infections - Viruses (human papilloma virus) - Fungi (chronic hyperplastic candidosis has a 25% risk of becoming malignant) - Bacteria Diet and nutrition
What tobacco use can cause oral cancer?
Smoking tobacco
- Cigarettes
- Pipes
- Cigars
- Reverse smoking
- Definite relationship with oral cancer
- Risk is greatest in heavy users >20/day
- Risk is greater if accompanied by alcohol use
Smokeless tobacco
- Betal quid (paan)
- Snuff
- Chewing tobacco
- Definite relationship with oral cancer established by epidemiological studies, observation of lesions
- Risk is greatest in heavy users
- Risk is greater if with smoking or alcohol
Areca/betal nut/paan chewing features?
Used as a stimulant
Common in SE Asia
Stains teeth and linked with oral cancer
Alcohol as a risk factor of oral cancer?
Risk factor of oral cancer
- Ethanol alone is not carcinogenic
- Amount of ethanol more important than type
Risk is greatest with tobacco
Increasing importance in young pts
Recommended units of alcohol per week?
14 units per week for men and women
= 6 pints of beer
= 7 glasses of wine
= 14 shots of spirit
What can UV cause?
Lip (skin) cancer (BCC, mostly SCC, melanoma)
UV light causes solar keratosis and dysplasia of the skin
Viruses causing oral cancer?
HPV Good evidence for role in oropharynx - Some evidence in oral lesions HPV 16 and 18 have been implicated HPV associated with about 60% of OPSCC cases in UK
HPV related oropharyngeal SCC features?
Younger pt demographic
- Less traditional risk factors (pt’s who do not smoke)
Often present with LN metastases - may not see it in mouth (lymph node exam and ask if pt noticed any lumps)
Prognosis is good (chemoradiotherapy)
- Advantage lost is also a smoker
Effects of vaccination of HPV vaccine will hopefully reduce or eventually irradicate this cancer
Histology of HPV-OPSCC?
p16 marker is used as a surrogate for HPV infection
Candida and oral cancer?
Candida infection has an association with oral cancer development
Evidence:
- Candida can produce carcinogens from nicotine and alcohol
- Candida often infect pre-malignant lesions
- Candida leukoplakia (CHC) is often non-homogenous and dysplastic
Social deprivation and oral cancer?
More deprived = most likely to have cancer
Oral cancer genetics?
Oncogenes
- Differing oncogenes activated
- Geographical variations
- No clear relationship with disease
Tumour suppressor genes
- p53 mutation or inactivation - linked to HPV
Viral component - what role does HPV play in OSCC?
Multistage carcinogenesis of oral cancer?
Initiation (Normal cell) - Induction when multiple genetic events occur (due to inherited and environmental factors) - causes pre-cancer cells
Progression - multiple genetic events = cancer cells
What is field change in oral cancer?
All/most of the oral mucosa is abnormal - but not necessarily clinically or on histology
Common genetic abnormalities
Subsequent tumours may develop in the field of abnormal mucosa or may be completely different
= If you treat just the lesion you can see, you may leave behind an area of abnormal epi = develop another lesion
Define precancerous lesions/potentially malignant
A morphologically altered tissue in which cancer is more likely to occur than in its apparently normal counterpart
= Preferred term is now “potentially malignant”
Name the 2 types of lesions
Leukoplakia
Erythroplakia
Leukoplakia WHO definition?
A white patch that cannot be rubbed off and cannot be characterised clinically or histologically as another other disease…
…and that is not associated with any physical or chemical causative agent except the use of tobacco
If can be rubbed off - probs candida
Epidemiology of leukoplakia?
0.9-26.9%
Depends on size of study and population studied
Woldwide prevalence - 2.6%
In UK - 2.8%
Homogenous leukoplakia - what does it look like?
Flat and plaque like, uniformly white
UNIFORM in colour (white) = lots of keratin on surface and texture
Non-homogenous leukoplakia features?
Variation in colour and texture - NOT uniform
Also includes: speckled (can have a red background with white speckles), exophytic nodular, verruciform
What percentage of leukoplakias becomes malignant in 5yrs?
5% become malignant in 5 yrs
- Homogeneous 1-5%
- Non-homogeneous 20%
Indicators of malignant potential with leukoplakia?
Site - high risk: - Floor of mouth - Ventral of tongue - Lateral borders of tongue - Anterior papilla of the tonsil Colour - RED areas in a lesion Texture - variations in thickness have higher risks of progression Presence of candida - higher risk Degree of dysplasia
Erythroplakia WHO definition?
A red patch on the oral mucosa which cannot be characterised clinically or histologically as due to any other condition
Erythroplakia features?
Use of term varies (erosive/specked lesion)
Prevalence unknown but less than leukoplakia
Has a higher malignant potential than leukoplakia
Often shows severe dysplasia or CiS
May be the earliest clinical sign of invasive SCC
Leukoplakia histology?
Ranges from: Hyperkeratosis with no dysplasia Hyperkeratosis with dysplasia - Mild, mod, severe Can already be cancerous: Carcinoma-in-Situ or SSC
What is epithelial dysplasia?
A collective term used to embrace a number of individual atypical features
Graded as mild/mod/severe on extent/degree of atypical features - subjective
A premalignant-state with an increased risk of cancer development
Severe dysplasia involving the full epithelial thickness = carcinoma in situ
What are you looking at in the epithelium regarding atypia dysplasia?
Architectural features:
- Irregular epithelial stratification
- Loss of basal cell polarity
- Drop shaped rete processes
Cytological features
- Increased number of mitotic figures
- Cellular and nuclear pleomorphism
- Nuclear hyperchromatism
- Individual cell keratinisation
- Loss of intercellular adherence
Mild dysplasia features?
Architecture: Changes in lower 3rd
Cytology: mild atypia
Moderate dysplasia?
Changes into middle 3rd - looks jumbled, cells look darker, bumpy rete processes
Moderate atypia
Severe dysplasia?
Changes in upper 3rd - almost the full thickness of the epithelium
Severe atypia and numerous mitoses, abnormally high
Carcinoma in situ (term not used much any more) features?
Malignant but not invasive Abnormal architecture - Full thickness of viable cell layers Pronounced cytological atypia - Mitotic abnormalities frequent
Looks like cancer but cannot see invasion
What percentage of leukoplakias show dysplasia on biopsy?
20-50% may show dysplasia on biopsy
- Homogeneous 20%
- Non-homogeneous 50%
What percentage of dysplastic lesions progress to malignancy, regress, no change or increase in size?
Progress to malignancy - 20%
Regress - 20%
No change - 40%
Increase in size - 20%
High risk sites?
Lateral margins of tongue
Floor of mouth
Retromolar, soft palate and fauces
Low risk sites?
Gingiva
Buccal mucosa
Labial mucosa
Hard palate
How to manage potentially malignant lesions?
- Systemic examination
- Screening tools: - Provisional clinical diagnosis
- Biopsy
- Definable lesion - manage accordingly
- Eliminate possible cause (good response - definable lesion - manage accordingly OR no response = no definable lesion - dysplasia or no dysplasia = tx, observation and follow up
- No obvious cause - no definable lesion, dysplasia or no dysplasia = tx, observation, follow up
Techniques/technology in diagnosis and prediction?
A thorough and systemic examination
Mucosal stains e.g. Toluidene blue
Imaging systems
Brush biopsy - cytology assessment, lab-on-a-chip (uncomfortable - may as well take biopsy)
DNA image cytometry
OraScreen stains abnormal epithelium blue (but lots of other lesions stain blue e.g. lichen planus)
VELscope - light on normal mucosa, not on abnormal mucosa
Z-scan = passes electrical current into tissue - how it passes the tissue tells you about its structure - used routinely
Potentially malignant conditions examples?
A generalised state associated with a significantly increased risk of cancer
Chronic hyperplastic candidosis
Actinic keratosis
Submucous fibrosis
Lichen planus
Presentation of chronic hyperplastic candidosis?
Present at angles of mouth Can be white patch or mixed red and white patch Well defined Pre-malignant Candida hyphae purple in histology
How to treat chronic hyperplastic candidosis?
Treat candida
Assess lesion - if still concerned then rebiopsy it
Oral submucous fibrosis?
Predominantly seen in Indians and Asians
Associated with areca nut use (paan)
Precise mechanism uncertain
Once develops no regression and no effective tx
Risk of malignant transformation 2.3-7.6%
1st stage = fibrosis of oral mucosa, blanches when stretched
2nd stage = red and white patches on mucosa, cannot open mouth much, brown stains on teeth, buccal mucosa rigid and hard to touch
Oral submucous fibrosis histology?
Atrophic with atypia
Fibrosis
Oral lichen planus?
Lateral border of tongue common
White and red patches
May have matching lesion on other side
Symptoms of oral cancer?
None Soreness/irritation Paraesthesia/anaesthesia Disruption of function - Can they move their tongue? Swallow? Dysphagia
Signs of oral cancer?
Persistent ulcer Persistent white, red or mixed patch Exophytic mass Fixation of tissue Induration Firmness Sensory/motor deficit Tooth movement/mobility Lymph node enlargement/fixation
What percentage of oral cancers are in the high risk sites?
80%
Where to take a biopsy from?
The most worrying area
Some normal mucosa next to it
Biopsy is deep enough so you can see it’s full thickness
Types of oral cancer?
Squamous cell carcinoma - majority
Verrucous carcinoma
- Relatively low grade
- Rarely metastasises
- Tobacco/snuff use
- Exophytic surface
- Will gradually cover more and more of the oral surface
- Pushing invasive pattern
Others - both very aggressive
- Basaloid
- Spindle cell
Grading of oral cancer - why?
Gives an indication of prognosis
Helps differentiate tumours that may do well from tumours that may not
Done by the pathologist on biopsies
Well differentiated:
- Resembles cell of origin
- Expresses keratins
Moderately differentiation
- Majority
- Little bit of keratinisation
- Invading into underlying muscle
- Resembles cell of origin
Poorly differentiation
- Aggressive
- No keratin
- May not resemble cell of origin (anaplastic)
- Necrosis common
Staging of oral cancer?
TNM - tumour, nodes, metastases
- Local extension of disease
- T1-4
Important features in the primary tumour:
- Overall tumour size
- Invasion into muscle (tongue)
- Involvement of nerves/blood vessels
- Invasion into bone - tumour is growing into underlying CT = makes it malignant — >5mm has a worse prognosis as risk of lymph node metastases increases
- Perineural spread - involving small nerves at the advancing edge - extensive spread related to IAN may give RECURRENCE
- Tumour in vessels - lymphatics or blood vessels = risk of metastases
- Spread to bone: Makes it a T4 tumour - edentulous pts usually into gaps in cortex, in dentate pts via periodontal ligament
Effects of previous radiation?
Recurrence most frequent route through alveolar crest
Often multiple points of entry wherever tumour near bone
Extensive spread within bone = very aggressive tumour
What percentage of pts will have metastases to regional lymph nodes?
50%
Signs and symptoms of lymph node metastasis?
Painless enlargement (painful usually from infection) Rock hard mass Fixation - indicates tumour has spread from node into surrounding tissues
What location of oral SCC is most likely to lead to positive nodes (lymph node metastases)?
Vental tongue
Extranodal extension of cancer - what is this?
Tumour extends out of the node into soft tissues
This decreases survival by 50%
Haematogenous spread features?
Is a late event
Related to advanced disease and poor prognosis
Most commonly extends to lungs
Staging of oral cancer table
If any distant metastases = M1 = stage IVc NO = no lymphnodes N1 = lymph node 1 N2a = 2 lymph nodes etc
Prognosis of oral cancers?
Related to
- Site
- Grade
- Stage - Related to size (T) and spread (N and M)
- Extracapsular spread
- Multiple primaries - 15 to 20% - synchronous or metachronous
Management of oral cancer?
Confirm/establish diagnosis by biopsy Through clinical examination Imaging for extent of spread - MRI, potential CT of chest or PET scan Review at multidisciplinary team meeting Tx plan formulated: - Surgical excision and/or - Radiotherapy and/or - Chemotherapy - Palliation
Management in primary dental care?
Do NOT biopsy
Prompt referral
Refer to local oral and maxillofacial surgery department - 2 week target
Do not tell the pt they have cancer
Do tell them you are concerned and they should be seen by a specialist
