Oral Cancer Flashcards
Define: prevalence
Number of people with a disease at any one time
Define: incidence
Number of new cases over a time period (usually a year)
What is the expected trend of oral cancer cases (in comparison to other smoking related cancers)
Oral cancer is projected to increase (postulated for 2030 in the UK) whereas other smoking related cancers (lung, larynx for eg) is expected to decrease
What is the most common cancer found in the oral cavity?
90% are squamous cell carcinomas
What makes up the 10% of oral cancers that are not squamous cell carcinomas
Salivary gland, lymphomas, melanomas and sarcomas
Where does oral squamous cell carcinoma arise?
Surface lining epithelium of the oral cavity
What areas classify as oral cavity cancer proper?
Cancers confined to the oral cavity
What areas do not classify as oral cavity cancers?
Nasopharyngeal, oropharyngeal, hypopharyngeal - these are head and neck cancers
List countries which have high rates of lip and oral cavity cancers?
Melanesia (Papua New Guinea)
South central asia
Australia/NZ
Gender predilection for oral cavity and oropharyngeal cancer?
Males > females
HOWEVER - female cases are increasing
What is the limitation of research data showing the rise in oral cavity cancers?
Data accumulates figures for incidence and prevelance for both oral cavity cancer proper and oropharyngeal cancers (head and neck cancer) - therefore it is difficult to predict the incidence and prevalence of oral cavity cancer alone
Describe how the number of cases of oral cavity and oropharyngeal cancers in males are changing
Both are increasing in the UK (and decreasing in USA), however in 2013, oropharyngeal cancers overtook oral cavity cancers (There are now more cases of OP cancers - HPV?)
Describe the link between socioeconomic background and oral cancer
Strong association between the two
Describe the link between age and oral cancer
Mean age around 40
Worldwide increase in the proportion of cases occurring in pts BELOW 45 especially in females
Describe the mortality risk of lip and oral cavity cancer
Better prognosis than most including lung, liver and pancreas (18th) - 5 year mortality rate is around half
HOWEVER risk of mortality is increasing in the UK
How does the stage of oral cancer affect survival rate?
The lower the stage, the better the prognosis (5 year)
Define specialist workforce
People able to treat the disease - e.g. in the case of cancer, it would be surgeons, doctors and nurses who specialise in cancer treatment
What is the risk of second primary cancer with oral cancers oropharyngeal cancers?
Very high risk of second primary cancers - likely in the head and neck or the lungs
What are the MAJOR MODIFIABLE risk factors of oral cancer
Smoking Smokeless tobacco Betel quid habit Alcohol Sunlight (lip)
What are the unmodifiable risk factors of oral cancer
Age
Previous cancer
Genetic suscpetibility?
Immunodeficiency
How does the dose of smoking relate to the risk of oral cancer
Risk increases with the number of cigarettes smoked a day - very high risk with >20/day for >20 years
What is the risk of oral cancer in smokers compared to non smokers
30 times greater
Does the risk of oral cancer reduce once a smoker stops?
No - the risk reduces by 50% after 5 years
List the signs of a smoker
- White patches with red dots on the palate (these are inflamed minor SG)
- Hyperpigmentation or smokers keratosis
- Pigmentation of the mucosa (Reactive change)
- Nicotine stained teeth
Describe the risk of oral cancer with ecigs and vaping
- Unknown since they are both new
- Vape contains added chemicals thus carrying a potential risk
- Toxicity paper in 2016 indicated chemicals can cause cytotoxicity of epithelial cells thus incr in breakage of DNA strands
List the risks of shisa smoking
- Cross infection from sharing pipe - herpes or tb
- Carbon monoxide from the charcoal
- Tobacco risk?
How is smokeless tobacco used?
Tobacco is prepared and placed into the sulcus and is absorbed by the mucosa
List the names of smokeless tobacco
Betel quid, paan, gutka
What are the signs of use of smokeless tobacco?
Patch in the buccal sulcus
Heavily stained teeth
Where are hotspots for smokeless tobacco abuse
South Asia, India, Bangladesh and Pakistan
What is the most important effect of smokeless tobacco
Oral submucous fibrosis - OPMD
What is the risk of oral cancer with alcohol?
- Increased risk which is dose dependent
- Synergistic effect with smoking (heavy smoking and alcohol increases risk greater than both alone)
What are oral potentially malignant diseases?
Pre-existing lesions occurring in the oral cavity that have the potential for malignant change
List the main OPMD
- Dysplastic and non-dysplastic leukoplakia
- Erythroplakia
- Speckled leukoplakia
- oral submucous fibrosis
- Proliferative verrucous leukoplasia
- Chronic candidosis
- Lichen planus
- DLE
- Dyskeratosis congenita, fanconi anaemia
Which OPMD have the highest risk of malignant change?
- Proliferative verrucous leukoplakia - almost 100% risk
- Oral submucous fibrosis - 15-20%
- Erythroplakia
- Speckled leukoplakia
What is field change?
Clonal expansion of cells which harbor early, preneoplastic genetic lesions which predispose the tissue to tumour formation
What types of genetic changes are required to produce OPMD
Mutations or chromosomal changes e.g. deletions or duplications
- PI3K/AKT/mTOR, RAS/RAF/MAPK, JAK/STAT, WNT/βcatenin and/or TGF β pathways must occur in order to develop a cancer
Describe the regulation of pathways in OPMD and cancers
- OMPD - downregulated, indicating further genetic change is required to produce a cancer
- Cancer - upregulated
Aetiology of OPMD
- Tobacco
- Alcohol
- Genetics
- AI/idiopathic
- HPV?
- Candida?
List susceptibility factors for oral cancer
- Inherited mutations
- Carcinogens (cause mutations or chromosomal changes)
- Irritants and infections (Cause promotional changes through proliferation)
- Host response - degradation of epithelial cells
What are the two parts of risk assessing OPMD
- Clinical risk assessment
- Histological risk assessment
List the features of clinical risk assessment of OPMD
- Type of OPMD (some have higher risk)
- Site
- Colour
- Extent - larger increased risk
- Surface texture
- Habits
- Gender (f > m)
- Malnourished
- Time present/changes
- History of cancer
List the sites where OPMD have a greater malignant risk
- FOM
- Lateral or ventral tongue
- Tonsil
- Retromolar region
What type of surface texture of OPMD have a greater risk
Lumpy or spiky
If indurated it is probably a carcinoma already
How does colour relate to risk of OPMD
- Speckled lesions have the highest risk
What is assessed during histological risk assessment of OPMD
- Degree of dysplasia
- DNA ploidy
What is dysplasia?
Histological feature of premalignancy, epithelial dysplasia occurs when there are disturbances to epithelial proliferation (YOU CANNOT SEE DYSPLASIA CLINICALLY)
Why do we assess for dysplasia?
It is the best indicator for future malignant change
List the histological changes indicating epithelial dysplasia
- Loss of basal cell polarity
- > 1 layer with basaloid appearance
- Increase nuclear-cytoplasic ratio
- Drop shaped rete-ridges
- Irregular epithelial stratification
- Increase mitotic figures +/- abnormal form or present in the superficial epithelium
- Enlarged nucleoli
- Loss of cell adherence
Describe the degree of dysplasia and risk of malignant change
- Mild < mod < severe
the greater the dysplasia, the higher the risk of malignant change
What is DNA ploidy analysis?
Assessment of DNA content in tissues
What is the NORMAL result of a ploidy analysis?
- Diploid
- This means that the cells contain a complete set of chromosomes (2)
What is an ABNORMAL result of ploidy analysis which indicates malignancy
- Aneuploid
- This indicates abnormal number of chromosomes in the cells
What are the small peaks on an otherwise normal diploid result on a dna ploidy analysis?
Cells undergoing cell division cycle (they contain double the dna therefore they appear as smaller peaks alongside the large diploid peak)
What are the aims of biopsies?
- Identify or exclude a specific diagnosis
- Assess dysplasia and map it to plan tx
- Assess invasion
- DNA ploidy analysis
- Baseline for follow up
- Pt communication
What is the difference between dysplasia and cancer?
- Cancer involves invasion, metastases and molecular changes
How is HPV transmitted?
Skin to skin contact - mainly through sexual contact
How many types of HPV are there?
over 100
Which subtypes of HPV are identified in oropharyngeal cancers?
Hpv 16 and 18
Hpv 33 to a lesser degree
*rmbr there are different subtypes which cause genital cancers
How are the subtypes of hpv classified?
Based on risk - e.g. cause malignant neoplasms (high risk) or benign neoplasms (low risk)
What % of healthy population have hpv 16 and 18 present in their saliva?
25% test positive - it only becomes an issue when hpv infection becomes persistent
List sites commonly affected by HPV-positive oropharyngeal cancer
- Originates at the base of the tonsillar crypt (not the surface)
- Base of the tongue
- Has a predilection for Waldeyer’s ring
Why is HPV cancer very difficult for dentists to screen?
- It originates at the base of the tonsillar crypt and there are no surface changes even in advanced changes
- difficult to assess oropharynx without a fibre-optic probe
What makes up Waldeyer’s ring?
- Pharyngeal tonsil
- Tubal tonsil
- Palatine tonsil
- Lingual tonsil
What are the risk factors for HPV positive cancers
- > 26 total lifetime partners
- > 6 oral sex partners
- Higher income and educated = higher risk
Link between smoking and alcohol and HPV cancers
Inverse correlation - most are non-smokers
Alcohol possibly has an inverse correlation too but evidence is insufficient
What is the main risk factor for HPV oral cancers
High number of oral sex partners
Demographic for HPV positive oral cancers
Caucasian males, 50-55, well educated and high income
What are the presenting signs for HPV positive oral cancers
Neck lumps (50%) Variable oral lesions (15%) - includes retrmolar area, diffuse redness on depression of the tongue
Describe the prognosis of HPV oral cancers with HPV-negative oral cancers
- HPV positive oral cancers have a better prognosis (around 90% 5 year survival compared with 40%)
List the reasons why the prognosis of HPV positive cancers is better than HPV negative cancers
- Low rates of secondary primary cancer
- Less cumulative genetic mutations compared to HPV negative
- Pt factors - Younger, lack of comorbidity, usually non-smokers
- HPV positive responds well to radiotherapy
Compare HPV negative and HPV positive oral cancers
Site - Neg - FOM, lat tongue, retromolar area / Pos - tonsi, base of tongue, waldeyers ring
Age - Neg - 58-60 / Pos - 52-56
Incidence - Neg - decreasing / Pos - increasing
Risk factors - Neg - tobacco, alcohol / Pos - oral sex
Prognosis - Neg - <40% 5 year / Pos - 90% 5 year
What type of cancer is on the rise due to HPV?
- Oropharyngeal cancers
- It plays a minimal role for oral cavity cancer proper
List the categories of cancer treatments
Curative Salvage Palliative Neoadjuvant Adjuvant
What is the purpose of curative treatment
- Aims to cure patient
- there is usually one shot at curative tx
What is the purpose of salvage treatment
- Form of tx given after the patient does not respond to the first treatment
What is palliative care?
- Supporting the patient with needs - including relief of symptoms, improve QOL, control side effects of treatment
List the modes of cancer treatment
Surgery
Chemotherapy
Radiotherapy (External beam, brachytherapy)
Targeted therapy (Immunotherapies, anti EGFR, tyrosine kinase inhibitors)
Multimodality treatment
Holistic treatment
List the general steps of cancer diagnosis to monitoring
- Diagnose
- Assess extent (stage and grade)
- Recommend ideal tx
- Assess comorbidities
- Educate, understand, consent
- Dietetics and speech
- Active tx
- Surveillence
- Manage recurrence and second primary caners
- Survivorship
What is survivorship
Management of pts who survive cancers - need to cope with the side effects for the rest of their lives
What % of pts sent to the 2 week referral have cancer
3%
What are the NICE guidelines for referral of a pt to a 2 week cancer pathway
- Unexplained ulceration in the oral cavity lasting >3 weeks
- Persistent and unexplained lump in the neck
- Lump on the lip or oral cavity or a red or red/white patch in the oral cavity consistent with erythroplakia or erythroleukoplasia (if assessed by a dentist)
How is staging and grading carried out?
- Imaging e.g. CT, MRI, PET, USS
- Biopsies for grading, mapping biopsies or FNA or neck nodes
What stage and grading system is commonly used?
TMN (tumour size, metastases and nodes metastases)
What are the scores for N in the TMN grade/stage
N0 - no regional lymph node mets
N1 - mets in a single node, 3cm max diameter without extranodeal extension
N2a - same as N1 but with extranodal extension
pN2b - mts in multiple ipsilateral nodes <6cm max diameter without extranodal extension
pN2c - mets in bilateral or contralteral nodes, <6cm max dia without extranodal extension
N3a - mets in node >6cm without extranodal
N3b - mets >3cm dia with extranodal extension
What are the scores for T in TMN
Tis - dysplasia only (in situ)
T1 - tumour <2cm dimension and <5mm depth of invasion
T2 - tumour <2cm with 5-10mm invasion OR 2-4cm with up to 10mm
T3 - >4cm or >10mm invasion
T4a - invades cortical bone of the mandible or max sinus, or invades skin on the face
T4b - invades masticator space, pterygoid plates, skunn base or encases internal carotid
What is the TNM for stage 1 cancer?
T1 N0 M0
What is the TNM for stage 2 cancer?
T2 N0 M0
What is the TNM for stage 3 cancer?
T3 N0 M0
T1-3 N1 M0
What is the TNM for stage 4 cancer
T4a N0/1 M0 T1-4 N2 M0 Any T N3 M0 T4b any N M0 Any T any N M1
What is an occult metastases
Mets that cannot be detected
What type of oral cancer is prone to occult mets
Tongue cancer as it is prone to early mets
What is the risk of treating oral cancers without treating the neck too?
- Risk of leaving behind occult mets in the neck therefore there is a risk of recurrence
What is the purpose of a sentinel node biopsy?
- It traces the path from the tumour to the nodes to determine the closest node that the tumour drains into
- (indicates the node most likely to have mets so it can be investigated)
What is neoadjuvant radiotherapy
Aims to reduce tumour size before surgery
What is adjuvant radiotherapy
Redcue change of tumour recurrence after surgery
What types of cancers can be treated with radiotherapy alone? which ones cannot?
- Head and neck cancers respond well to RT alone
- ORAL cancers cannot be treated with radiotherapy alone (except HPV positive oropharyngeal)
How does radiotherapy work?
Ionising radiation (most use xrays and gamma rays) The radiation is produced via photons and electrons mainly (small amount via protons, neutrons and ion beams)
How does the radiation kill cancer cells?
Via RT induced cell death (lethal damage to DNA and mitotic cell death or direct killing via apoptosis)
What type of dose is used in radiotherapy?
Sublethal dose (cancer cells are more sensitive to the RT than healthy cells, and healthy cells have the ability to repair themselves)
What are the aims of RT
- Achieve local tumour control via delivery of a curative dose to the tumour (and keeping dose to adjacent tissues as low as possible - follow dose limits )
How is the dose of RT reduced whilst still keeping it high enough to achieve the aims?
- Delivery of small fractions (sessions) over a period of time to limit the dose and prevent overloading
What is the purpose of multi-leaf collimators?
Allow us to conform the beam and change the angle to face the target to give a higher dose to the tumour without affecting adjacent cells
What is clinical delineation?
Process where target volumes and organs around the tumour are identified and risk assessed - they map out the adjacent structures to avoid important areas (mapping the dose)
How long does RT appt take? how often?
- 5-7min per appt and carried out daily monday-friday for 3-7 weeks depending on the cancer type and patient
When do side effects of RT usually start? when do they settle?
Acute toxicity - 1-2 weeks post initiation of tx
Late toxicity - 3 months after start of treatment
What is acute toxicity to radiotherapy?
- Side effects occuring 2-3 weeks from the start of tx and settle within 4-6 weeks of start of tx
- They are present to a degree in all patients and usually affects rapid turnover tissue (mucous membranes)
List the symptoms of acute toxicity
- Loss of taste or metallic taste
- dry mouth
- dysphagia and true weight loss
- Patchy, haemorrhagic or confluent mucositis
- Thick, stringy saliva or secretions which makes pts feel nauseous
- Erythema, dry, peeling or moist skin
What is late toxicity to RT?
- Symptoms occuring >3months post RT
- Tends to be permanent and progressive
- 5-10% develop severe toxicity
List the symptoms of late toxicity
Skin - odema, fibrosis, atrophy, dipigmentation or telangiectasia
- SG - xerostomia (radiation caries)
- Spinal cord - Lhermittes syndrome
- Ear - chronic otitis externa or deafness
- Laryngeal - cartilage necrosis or hoarse voise
- Muscle and joints - trismus, shoulder pain or neck striggnesss
What is the main side effect of RT of concern to dentists?
- Osteoradionecrosis of the jaw
- Xerostomia and radiation caries
- Mucositits
Compare RT mucositis and chemotherapy mucositits
RT - lasts longer (3-12 weeks) and is generally more severe
Chemo - lasts 3-12 days and is less severe
Describe the management of mucositis
- Oral hygiene
- Topical agents - saline rinses, difflam, oxetacine mouthwash (painkiller)
- Analgesics (paracetamol, co-codamol or opiates)
- Nutritional support and oral fluid intake - may need feeding tube
- Swallowing exercises
- Smoking and alcohol cessation
How to manage thick, stringy saliva as a side effect of RT?
- Sodium bicarbonate mouthwash or hygrogen peroxide
- Saline rinse or nebuliser
- Steam inhalations
- Antiemetics
What mouthwashes are contraindicated for RT mucositis
- Alcohol containing moutwashes - it will sting
- CHX mouthwash
Tx of post-RT mucositis due to an infection
- Antifungals given as soon as diagnosis is made - fluconazole 100mg for 7-14 days
- NOTE: prophylaxis nystatin is no longer given
Tx of RT xerostomoa
- Artificial saliva sprays
- Never goes back to normal flow - needs long term management, freq visits etc
What is osteoradionecrosis
Bone death due to radiation commonly affecting the mandible
List the role of the dentist before patients receive high dose RT
- Poor prognosis teeth are removed
- Perio health stabilised
- Fluoride therapy initiated
Who is at risk of ORN?
- Anyone who has had RT- the risk is there for life and someone who has had RT should have XLA under specialist care - never in practice
What stage of cancer is indicated for surgery (reconstructive surgery)?
All stages - however later spages may need RT or chemotherapy as an adjunct
What are the main morbities associated withreconstructive surgery for oral and oropharyngeal caners?
Speech and swallowing difficulties
What is the importance of the neck in oral and oropharyngeal surgery?
- Risk of occult disease so there may be elective neck dissection (lymph node dissection)
List the levels of the nodes int the neck
Level I - submental and submandibular Level II - Upper internal jugular nodes Level III - middle internal jugular nodes Level IV - lower internal jugular nodes Level V - posterior triangle nodes
What nodes are oral cavity cancers most likely to drain to?
IIa > I > III > IV
Rarely to level 5
