Oral cancer Flashcards
What is the worldwide epidemiology of oral cancer?
It is the 6th most common cancer worldwide and the total cases are 263000. The frequency is 2%. The incidence is 3.9/100000. There are 128000 deaths (in 2008) and the death rate is 48%. There are parts of the world where oral cancer is the main type of cancer including Papa New Guinea. In India and Sri Lanka oral cancer is one of the main types of cancer.
What are the oral cancer England stats?
- Total cases - 6767
- Frequency - 2% of all cancers
- Incidence - males 12/100000 and females 7/100000
- Deaths - 2119
- 5 year survival - 58%, death rate is 31% (most likely an underestimate)
- For men it is the 10th most common cancer and 15th for women in the UK
Deaths from cancer are increasing. There are some regional differences in the UK for head and neck cancer. England has the lowest rate and Scotland has the highest rate.
For what people is the incidence of oral cancer increasing?
The problems are that it is increasing in incidence, younger people are getting it (age demographic is shifting) and there is little improvement in survival. The mouth cancer data from cancer research UK shows that there is a 32% increase in males over the last 10 years and a 33% increase in women. We are seeing more women with oral cancer and younger people.
Why has there only been a modest increase in survival in 50 years in the UK?
Patients present late and 70% of patients present with late stage disease. If you get metastasis then you are straight into late stage disease - stage IV and the prognosis halves. We want to diagnose patients early/precancer.
Look at table in notes.
Which types of oral cancer have the best and worst survival rates?
Cancer of the lip has the best survival rate as it is easiest to see. Oral cavity, tongue, oropharynx and hypopharynx have lower survival rates as they are more difficult to see.
What are the biggest risk factors for oral cancer?
Smoking and alcohol.
What is the aetiology of oral cancer?
It is multifactorial and there is no single factor identified. There is genetic predisposition in some but the main causes are environmental. Factors vary in different geographical regions or ethnic groups. There are inherited factors in oral cancer such as polymorphisms in genes involved in the metabolism of carcinogens and these have been linked to individual susceptibility:
- Tobacco - glutathione transferases
- Alcohol - alcohol dehydrogenase (ALDH2)
There are also risk factors associated. Social deprivation has an association.
What inherited cancer syndromes are associated with an increased risk of oral cancer?
- Li-Fraumeni
- Fanconi anaemia - 60% of these patients get oral cancer
- Xeroderma pigmentosum
What are the risk factors for oral cancer?
- Tobacco
- Alcohol
- Sunlight
- Infections - viruses, fungi, bacteria
- Diet and nutrition
What are the different types of tobacco use?
Smoking: - Cigarettes - Pipes - Cigars - Reverse smoking Smokeless: - Betel quid - paan - Snuff - Chewing tobacco
When is the risk of oral cancer with smoking greatest?
Tobacco has a definite relationship with oral cancer and the risk is greatest in heavy users (>25/day). Risk is greater if accompanied by alcohol use. There is a definite relationship of smokeless tobacco with oral cancer established by epidemiological studies and observation of lesions.
What is betel nut/paan?
Betel nut/paan is the seed of a palm tree and is used as a stimulant in some parts of the world. It is chopped up and wrapped in the leaves of a vine and coated with lime. It is often mixed with tobacco and spices. It is reportedly chewed by up to 600 million worldwide especially in South and Southeast Asia.
What are the effects of betel nut/paan?
- Self-reported energy boost, possible adrenaline release stimulated by alkaloids
- Traditional beliefs about health benefits but little clinical evidence
- Addictive
- Stains the teeth
- Linked with oral cancer
- Regular users 28 times more likely to develop oral cancer than others
How can alcohol cause oral cancer and what are the recommended alcohol limits?
Consumption of alcoholic drinks is a risk factor for oral cancer. Ethanol alone is not carcinogenic – may be how it is metabolised or some of the other additives. The amount of ethanol is more important than the type. The risk is greatest when accompanied by tobacco use. There is increasing importance in young patients. Recommended alcohol limits for men and women is 14 units – 6 pints of beer, 7 glasses of wine or 14 single shots of spirits.
How can UV cause oral cancer?
UV is an important cause of lip (skin) cancer (BCC, SCC, melanoma). UV light causes solar keratosis and dysplasia of the skin.
How can HPV cause oral cancer?
There is good evidence for the role of HPV in oropharynx (tonsil and base of tongue) cancer and some evidence of oral lesions. HPV 16 and 18 have been implicated. HPV is associated with about 60% of OPSCC cases in the UK. HPV related oropharyngeal SCC has a younger patient demographic without traditional risk factors. They often present with lymph node metastases. The prognosis is good with chemoradiotherapy but the advantage is lost if also a smoker. There is a vaccination.
How can candida cause oral cancer?
It has an association with oral cancer development. Candida can produce carcinogens from nicotine and alcohol. It can often infect pre-malignant lesions. Candida leukoplakia (CHC) is often non-homogenous and dysplastic.
What genes are associated with oral cancer?
- Oncogenes - differing oncogenes activated, geographical variations, no clear relationship with disease
- Tumour suppressor genes - P53 mutation or inactivation, many other genes
- Viral component - HPV
What are the stages of development of oral cancer?
There is a multistage carcinogenesis in oral cancer. The stages are initiation, induction and progression. You start with a normal cell and there are multiple genetic events (inherited and environmental factors) which lead to precancer. There are further multiple genetic events leading to cancer. The window is longer between normal cell and precancer so this is when we want to act.
What is field change?
Field change is a concept which involves field cancerisation which is the area of abnormal mucosa. If you only treat the lesion you can see you leave behind an area of abnormal mucosa which you cannot see which may lead to additional lesions. All/most of the oral mucosa is abnormal but not necessarily clinically or on histology. Subsequent tumours may develop in the ‘field’ of abnormal mucosa or may be completely different. You can get recurrence by leaving behind some tumour, or from the field or from another field. It is therefore important that oral cancer patients (or precancer) are carefully followed up after treatment.
What is a precancerous lesion?
A precancerous lesion is a morphologically altered tissue in which cancer is more likely to occur than in its apparently normal counterpart. The preferred term is now potentially malignant. There are two lesions which are leukoplakia and erythroplakia.
What is Leukoplakia?
The WHO definition of leukoplakia is a white patch that cannot be rubbed off and cannot be characterised clinically or histologically as any other disease and that is not associated with any physical or chemical causative agent except the use of tobacco.
What is the epidemiology of Leukoplakia?
Epidemiology of leukoplakia: no good registration schemes so no figures. Most precancer studies have looked at leukoplakia. The prevalence ranges from 0.9-26.9% and depends on the size of study and the population studied. The worldwide prevalence is 2.6% from a recent systematic review. A study of over 2000 patients in dental practice in the UK showed a prevalence of 2.8%.
What is the difference between homogenous and and non-homogenous leukoplakia?
Homogenous leukoplakia is flat and plaque like and uniformly white. Non-homogeneous leukoplakia has variation in colour or texture. It also includes speckled, exophytic, nodular, verruciform.
5% of leukoplakias become malignant in 5 years. Homogenous ones are 1-5% and non-homogenous is 20%. Red areas in the leukoplakia are worrying.
What are the indicators of malignant potential?
- Site – lateral border of tongue, ventral tongue, floor of mouth, anterior tonsil to lateral part of soft palate
- Colour – red patches higher risk
- Texture – thicker areas and variations in thickness high risk
- Presence of candida (seen in biopsy)
- Degree of dysplasia (biopsy – histology)
What is erythroplakia?
Erythroplakia WHO definition is a red patch on the oral mucosa which cannot be characterised clinically or histologically as due to any other condition. The use of the term erythroplakia varies. The prevalence is unknown but much less common than leukoplakia, but a much larger malignant potential than leukoplakia. It often shows severe dysplasia or CiS. It may be the earliest clinical sign of invasive SCC. Often already cancerous when biopsied – 25%.
What can the histology of leukoplakia show?
It can range from:
- Hyperkeratosis with no dysplasia
- Hyperkeratosis with dysplasia (mild, moderate, severe)
- Carcinoma in situ
- Squamous cell carcinoma
What is epithelial dysplasia?
Epithelial dysplasia is a collective term used to embrace a number of individual atypical features. It is graded as mild, moderate or severe on extent/degree of atypical features so it is ‘subjective’. It is a pre-malignant state with an increased risk of cancer development. Severe dysplasia involving the full epithelial thickness is called carcinoma in situ.
What are the architectural and cytological features of atypia in the epithelium?
Architectural features:
- Irregular epithelial stratification
- Loss of basal cell polarity
- Drop shaped rete processes
Cytological features:
- Increased numbers of mitotic figures
- Cellular and nuclear pleomorphism (variety in shape and size)
- Nuclear hyperchromatism (ploidy) - staining too darkly as too much DNA in cells
- Individual cell keratinisation
- Loss of intercellular adherence - cells break apart
What are the differences between mild, moderate and severe dysplasia?
See images in notes.
Mild dysplasia shows all changes in the basal third. It is mostly cytology rather than architecture. In moderate dysplasia there are architecture changes into the middle third. In severe dysplasia there are changes in the upper third and there will be numerous mitoses/mitotic figures through full thickness (white halos). These should only be seen in the basal layer.
What is carcinoma in situ?
Carcinoma in situ is malignant but not invasive. There is abnormal architecture in full thickness of viable cell layers. It is pronounced cytological atypia – mitotic abnormalities frequent.
What percentage of leukoplakia shows dysplasia on biopsy?
20-50%. It is 20% for homogenous and 50% for non-homogenous.
What can happen with a dysplastic lesion?
- Progress to malignancy - 20%
- Regress - 20%
- No change - 40%
- Increase in size - 20%
What are the high and low risk areas of the mouth?
High risk 80% - Lateral margins of tongue - Floor of mouth - Retromolar, soft palate and fauces Lower risk: - Gingiva - Buccal mucosa - Labial mucosa - Hard palate Look at images in notes.
What techniques and technology can be used in diagnosis and prediction of oral cancer?
- A thorough and systematic examination
- Mucosal stains e.g. toluidine blue (orascreen), areas that are abnormal have more DNA and stain blue, many conditions will stain blue e.g. lichen planus so not very specific
- Imaging systems e.g. veloscope - blue excitation light shone on oral mucosa, when normal it gives green fluorescence, abnormal will not fluoresce. The main problem is specificity, it will tell you something is wrong but not whether it is serious or not so not that helpful
- Brush biopsy (cytobrush) - a technique for sampling cells of a lesion, painful and requires LA, atypical and malignant cells are found in the basal layer so need to get it to that layer, cytological assessment, lab on a chip - modified brush used to take sample then place a chip and use biomarkers, place in machine and it tells you whether there is dysplasia, DNA image cytometry
What are the potentially malignant conditions?
- Chronic hyperplastic candidosis
- Actinic keratosis
- Submucous fibrosis
- Lichen planus
What is chronic hyperplastic candidosis?
It is classically present at the angle of the mouth, histologically epithelium is hyperplastic with long rete processes, chronic inflammatory processes underneath, candida hyphae purple lines extending into surface. Treat candida with (fluconazole) and then reassess lesion, further biopsy if concern.
What is actinic keratosis?
It is a rough scaly patch from exposure to the sun often seen on the lips.
What is submucous fibrosis?
It is predominantly seen in Indians and other Asians. It is associated with areca nut use (paan). The precise mechanism is still uncertain. Once it develops there is no regression and no effective treatment. There is a reported risk of malignant transformation 2.3-7.6%. In the initial stages you get fibrosis of the oral mucosa. When the patient opens the mucosa blanches and they cannot open properly. You will see brown staining, red and white patches. Histologically there is fibrosis in underlying tissue, epithelium is atrophic with atypia (dysplasia) and lots of collagen.
What is lichen planus?
There are erosive/atrophic forms e.g. on the lateral surface of the tongue or gingiva there is a significant risk of developing oral cancer. Reticular forms are less likely.
What are the signs of oral cancer?
You get keratosis, dysplasia and then carcinoma. The signs are:
- Persistent ulcer
- Persistent white, red or mixed patch
- Exophytic mass
- Fixation of tissue
- Induration
- Sensory/motor deficit
- Tooth movement/mobility
- Lymph node enlargement/fixation
What are the symptoms of oral cancer?
- None
- Soreness/irritation
- Paraesthesia/anaesthesia
- Disruption of function
- Dysphagia
- Often advanced when you see symptoms
Patients will often have no symptoms. Diagnosis is through a good incisional biopsy.
What are the types of oral cancer?
- Squamous cell carcinoma (mostly)
- Verrucous carcinoma - relatively low grade, rarely metastasises, tobacco/snuff use, exophytic surface, ‘pushing’ invasive pattern, lots of recurrences, may develop into SCC at some point (image in notes)
- Others (histological subtypes, very aggressive, patients do badly) - basaloid, spindle cell
Why are cancers graded?
It gives an indication of prognosis. It helps differentiate tumours that may do well from tumours that may not. Grading is done by the pathologist on biopsies.
What are the different grades that can be given to a cancer?
- Well differentiated - resembles cell of origin, expresses keratins (differentiation), low grade
- Moderately differentiated (majority) - still epithelium with a little bit of keratinisation, resembles cell of origin, may produce some keratin, patients don’t tend to do well
- Poorly differentiated - no keratin (does not differentiate), may not resemble cell of origin (anaplastic), often there will be central necrosis, high levels of division, aggressive
What is TNM used for?
To assess the local extension of the disease. The important features in the primary tumour are:
- Overall tumour size
- Invasion into muscle (tongue etc)
- Involvement of nerves/blood vessels
- Invasion into bone
The surgeon will want to know how deep the lesion is. Once the lesion is greater than 5mm this has a worse prognosis as the risk of lymph node metastasis increases.
What is the sign of malignancy histologically?
Invasion of the epithelium into the underlying connective tissue. There will be islands of epithelium in the connective tissue.
Where can oral cancer spread to?
It is important to know where the cancer has spread to (muscle, floor of mouth, tongue, superficial spread, submandibular gland). We look at perineural spread so if the tumour is growing around nerves. It may use nerves as a scaffold to help it grow and spread. Extensive spread related to IAN may give recurrence. Tumours in vessels are important – lymphovascular invasion. This allows metastasis so is important. Spread into bone makes a tumour a T4 tumour even if small. If patient is edentulous it can travel through gaps in cortex and if dentate via the periodontal ligament. Patients with this wont do well.
What are the effects of previous irradiation on oral cancer?
- There are often multiple points of entry wherever tumour near bone
- Extensive spread within bone
- Most frequent route through alveolar crest
What are the signs and symptoms of lymph node metastasis and in what percentage does this occur?
50% of patients will have metastases to regional lymph nodes. The signs and symptoms are:
- Painless enlargement
- Rock hard mass
- Fixation - indicates tumour has spread from node into surrounding tissues
How does the tumour invade lymph nodes?
The tumour enters the lymph node by the subcapsular sinus via afferent lymphatics. Then there will be metastasis which will grow in the node.
What are the lymph nodes in the head and neck?
- Preauricular
- Submandibular
- Submental
- Upper jugular
- Mid jugular
- Lower jugular
- Upper posterior cervical
- Mid posterior cervical
- Lower posterior cervical
Look at images in notes.
What is extranodal extension? (extra-capsular spread)
When there is spread of carcinoma through the fibrous capsule of a lymph node into the surrounding soft tissues. It can be detected clinically due to fixation, tethering, skin invasion, cranial nerve defects (e.g. facial nerve in parotid gland), with radiological confirmation or pathologically. ENE is a new addition to the 8th edition of the TNM manual and confers a poor prognosis in oral cancer. ENE decreases 5 year survival by 50%. Less than 1cm - 23% EC spread, 2-3cm 53% and more than 3cm 74%.
What is haematogenous spread?
Haematogenous spread is what gives us M in TNM. It is a late event and is related to advanced disease and poor prognosis. It is most commonly to lungs.
What is the prognosis of oral cancer based on?
- Site – further back the worse the prognosis
- Grade – poorly differentiated is worse
- Stage
- Size T
- Spread N and M
- Extracapsular spread
- Multiple primaries (multiple cancers) – 15-20%
- Synchronous or metachronous
What is the management of oral cancer?
- Confirm/establish diagnosis by biopsy
- Thorough clinical examination
- Imaging for extent of spread (MRI and then CT scan of chest to check for spread), PET scan to trace where there is tumour around the body
- Review at multidisciplinary team meeting
- Treatment plan formulated
- Surgical excision and/or
- Radiotherapy and/or
- Chemotherapy
- Palliation
What is the general role of a radiologist in managing patients with oral cancer?
It falls into 3 distinct areas:
- Diagnosis - does the patient have imaging signs of cancer?
- Staging - how far has the cancer spread?
- Surveillance - has the cancer recurred after treatment?
