dysplasia and oral cancer Flashcards
what is used to define oral cancer
classification
International Classification of Disease for Oncology
ICD-O
Many different sites
* Makes comparison difficult
* Makes epidemiology difficult
* Makes treatment planning difficult
Congregated into
* OC – oral cavity cancer
* OP – oropharyngeal cancer
epidemiology of oral cancer
BDJ Ref Vol 225 No. 9 (November 9 2018) - useful
2 distinct disease patterns
* Oral Cavity Cancer (OCC)
* Oro-Pharyngeal Cancer (OPC)
each have Different populations, outcomes, risks
Female: Male divide
Country divide
Change over time – male predominency reduce
INHANCE
The International Head and Neck Cancer Epidemiology Consortium (INHANCE)
Collaboration of research groups of large epidemiological (case-control) studies
Investigating the risk factors for head and neck cancer including (separately) oral cavity and oropharyngeal cancer subsites
* 35 studies – 25,000 patients, 37,000 controls
oral cavity cancer
prevalance
2.5 per 100,000 pop (2012)
Almost HALF (48.7%) in south central Asia
Male 2:1 Female
Incidence not increasing worldwide
* Decreasing in men, increasing in women
* Linked to reduction in tobacco use (falling in men, rising in women)
Scottish Cancer Registry
* 10% increase 2001-2012
* Unclear why
common/high risk sites for oral cavity cancer
6
Floor of the mouth
Lateral border of the tongue
Retromolar regions
Soft and hard palate
Gingivae
Buccal mucosa
tongue and tonsillar area
It is well known that there are geographic and regional differences in the intraoral distribution of oral cancer
red highlighted area represents ~20% of the mouth, but ~70% of oral cancers are found here
3 specific sites are more predisposed to developing SSC in drinkers and smokers - FOM, lateral border of the tongue, soft palate
Don’t ignore others
oral cancer sites division
red highlighted area represents ~20% of the mouth, but ~70% of oral cancers are found here
oro-phayngeal cancer
prevalance
1.4 per 100,000 pop
Most in North America and south central Asia
Male 4.8:1 Female
More males than females, significant difference
Rates rapidly rising, especially in High Income areas (North America)
* Linked to rising HPV epidemic
Scottish Cancer Registry
* 85% increase 2001-2012 – highest increase for any cancer
OCC and OPC trends
OCC slowly increase (red dash line)
OPC biggest rise over last period (Red line)
5 key risk factors for oral cancer
smoking
drinking alcohol
both smoking and drinking
betel quid (paan)
socieoeconomic status
smokers who don’t drink oral cancer risk
Smokers who don’t drink x2 risk (compared to nonsmokers who don’t drink)
* Increases with quantity, duration and frequency of tobacco use
* Fewer cigarettes for longer duration worse than high number, short term
* Smoking risks were generally greater for larynx cancer
drinking alcohol oral cancer risk
Drinkers (3-4 drinks/day) x2 risk (same as smokers who don’t drink)
* Never smoked population
* Frequency more important than duration – more drinks each day key
* alcohol drinking for oral cavity and pharyngeal cancers
smoking and drinking alcohol oral cancer risk
Smoke and Drink x5 risk
* Increases with frequency and duration of smoking and alcohol consumption
* No safe lower limit
betel quid (paan) use oral cancer risk
x3 risk
mixture of substances including areca nut with or without tobacco wrapped in a betel leaf and placed in the mouth
socioeconomic statis oral cancer risk
x2 risk (SIMD 4/5)
* Even without other risk factors
* Key factor in many other diseases
* Same risk as smoking
* More likely to smoke and/or drink too- compound
* Low educational attainment
3 things that may impact oral cancer risk - but not yet certain currently
Family History
* 1st degree relative with H&N cancer may be important
Oral Health
* Early data suggests poor oral health may be associated with an increased cancer risk – small effect
Sexual Activity
* a slight increased risk for oropharyngeal cancer with:
* six or more lifetime sexual partners
* four or more lifetime oral sex partners
* early age (<18 years) of sexual debut (INHANCE)
* Probably link to HPV
benefits of stopping smoking and alcohol
INHANCE
Demonstrable benefits of quitting smoking were identified within one to four years after stopping smoking
* Quicker
* Smoker prevention more important when time limit on social health intervention (compared to drink)
risks reduced and reached a similar level to those who had never smoked after 20 years of quitting.
In contrast, the risk effects associated with quitting heavy alcohol consumption take 20 years to begin to emerge.
SE status compared to smoking/alcohol oral cancer risk
SE status is on a par with smoking and alcohol in terms of magnitude (two-fold increased risk)
* specifically low educational attainment and low income.
These risks were not fully explained by smoking and alcohol consumption (‘the cause of the cause’)
* have a more direct effect associated with socioeconomic circumstances
diet and oral cancer risk
There is limited new evidence in relation to dietary factors beyond confirming that a high intake of fresh fruits and vegetables were associated with reducing by half the oral cancer risk
obesity was not associated with an increased oral cancer risk
* young people (aged 30-years or less) oral cancer was more likely in those who self-reported a low body mass index (BMI)
potentially malignant disorders examples
4
White lesions (leukoplakia)
Red lesions (erythroplakia)
Lichen planus
* Candidal Leukoplakia
* Chronic Hyperplastic Candidiasis
Oral Submucous Fibrosis
leukoplakia
white pathc that cannot be rubbed off and not attributable to any other disease
PMD
erythroplakia
red patch that is not attributable to any other disease
(more commonly attributed to malignancy - could indicated vascular change)
PMD
what are eryth- and leuko- and erytholeuko- plakia
clincial descriptions
oral cancer in white lesions
incidence 0.2 - 4%
* wide variation in different populations
* Reliability of data not clear
malignant change
* varied reports, most under 4%
* period prevalence
3.2.5% in 10 years, 4% in 20 years
biopsy where possible to assess dysplasia
do oral carcinomas occur from normal or abnormal mucosa?
most oral caricnoms in the UK arise arise in initially clinically normal mucosa
Most cancer in high incidence areas (e.g. India) from potentially malignant lesions
Worldwide leukoplakia is 50 to 100 times more likely to progress to cancer than clinically normal mucosa
* Consider whole mouth not just area of white lesion
biopsy where possible to assess dysplasia
oral cancer in red lesions
much less frequent than leukoplakia
much higher risk of cancer
greater dysplasia risk
* Up to 50% already be carcinoma
no good follow-up studies available
dysplasia based on
2
cellular atypia
epithelial architectural organisation
categorisation for dysplasia
Mild, moderate, severe, carcinoma-in-situ
New categorisation
* Low grade, high grade, carcinoma-in-situ
* Clearer definitions – better guidance on tx needed
CHECK
categorisation for dysplasia
Mild, moderate, severe, carcinoma-in-situ
New categorisation
* Low grade, high grade, carcinoma-in-situ
* Clearer definitions – better guidance on tx needed
CHECK
grading of oral mucosa dysplasia
histologically
based on cytological and architectural changes
* not all features needed for dysplasia to be occuring
* more features present, the higher the grade of dysplasia reported
possible cytological changes to indicate dysplasia
8
changes in indivdual cells reflecting abnormal DNA content in the nucleus, failure to mature and keratinise correctly and inc proliferation
- abnormal variation in nuclear size
- abnormal variation in nuclear shape
- abnormal variation in cell shape
- abnormal variation in cell size
- inc/altered nuclear-cytoplasmic ratio
- atypical mitosis figures
- inc number and size of nucleoli (prominent nucleoli)
- nuclear hyperchormoatism
possible architectural changes to indicate dysplasia
8
changes in the organisation of maturation and normal layering of the epithelium
- irregular epithelial stratification
- loss/disturbed of polarity of basal cells
- drop-shaped rete ridges
- inc and abnormal mitoses
- premature keratinisation in single cells
- abnormal keratinisation
- keratin pearls within rete ridges
- loss of epithelial cell cohesion and adhesion
low grade dysplasia
- Easy to identify that the tumour originates from squamous epithelium
- Architectural change into lower third
- Cytological atypia or dysplasia may not be prominent
- Shows a considerable amount of keratin production
- Evidence of stratification
- Well formed basal cell layer surrounding the tumour islands
- Tumour islands are usually well defined and are often continuous with the surface epithelium
- Invasion pattern with intact large branching rete pegs ‘pushing’ into underlying CT
(Where there is architectural change into middle third, depending on the level of cytological atypia will be classified into low grade or high grade)
high grade dysplasia
- Show little resemblance to a normal squamous epithelium
- Architectural change upper third
- Usually show considerable atypia
- Invade in a non-cohesive pattern with fine cords, small islands and single cells infiltrating widely through the CT
- Mitotic figures are prominent and many may be abnormal
Degree of differentiation is widely used to predict prognosis and shows a significant correlation to survival.
(Where there is architectural change into middle third, depending on the level of cytological atypia will be classified into low grade or high grade)
carcinoma-in-situ
Theoretical concept
Cytologically malignant but not invading through basement membrane
Abnormal architecture
* Full thickness (or almost full)
* Severe cytological atypia
Mitotic abnormalities frequent
4 histological prognostic factors
Pattern of Invasion
Depth of Invasion
Perineural Invasion
Invasion of Vessels
pattern of invasion
histological prognostic factor
Bulbous rete pegs infiltrating at same level is considered of a better prognosis than widely infiltrating small islands and single cells
depth of invasion
histological prognostic factor
risk of metastases for a tumours greater than 4mm was 4x greater than for a tumour less than 4mmm
perineural invasion
histological prognositc factor
seen in up to 60% of OSCCs but is most significant when a tumour is seen within a large nerve at a site some distance from the main tumour mass
invasion of vessels
histological prognositc factor
widely thought to be associated with lymph node metastaes and a poor prognosis
multi stage promotion
from normal to PMD to OCC
process takes time
can happen at different stages at different parts of mouth depening on what environmental stimuli playing a role
field cancerisation concept
Multiple primaries possible over time
up to 15 to 20 in some patients
Concept of “field cancerisation”
high cancer risk in 5cm radius of original primary - that’s most of the mouth/pharynx
synchronous or metachronous lesions
* Can occur at the same time as the primary or at later times
Need to follow up for rest of life as at risk of another oral cancer
oral cancer staging
clinical
mutliple variable for clinical staging
site
size (T)
spread (N&M)
TNM
oral cancer staging
Tumour
Nodes
Metasis
oral cancer prognosis
1/3 patients present at stage I/II
* Stage I - 80% cure rate early lesion
* Stage II – 65% cure rate
stage 4 is much more advanced condition
* 5 year survival <50%, cure <30%
If untreated, with metastases, survival is about 4 months
dysplasia lesion detection is best – excision just before malignant good chance of success
tx options for oral cancer
Surgery, Radiotherapy and Chemo/Immunotherapy all used
* Choice will depend on patient choice and health/prognosis
* Tumour location, size and nutitional status all important
For resectable tumours, primary surgery offers the best outcome
* Post surgical radiotherapy or chemotherapy
lip cancer
location
aetiology
behaviour and prognosis
Lower lip
* non-healing ulcer or swelling
Aetiology
* Sunlight UV-B
* smoking
Behaviour
* slow growth
* local invasion
* rarely metastasise to nodes
Good prognosis as early detection
oral cancer detection/screening
5 options currently
HPV16 screening
Toluidene blue
* false positive in inflammatory lesions
* ? 50 % false negatives (highlights area of trauma and infection too)
* good for invasive disease, but usually clinically evident
VELscope
* Autofluorescence of tissues with blue light
* Loss of fluorescence equates to ‘change’
* Change may be cancer but can be other changes
* Causes for loss of fluorescence isn’t clear
* Published work ‘thin’
May well work, but evidence not yet adequate
Photodynamic Diagnosis (PDD)
* UV light attracted to area of change
The most cost effective and reliable screening tool is the experienced dental practitioner.
current debate/ethical qs around oral cancer screening
Benefits vs Harm
Undetected lesions vs False positive
Cost of Screening vs Cost of disease
Cost of Screening vs Disability from disease
oral cancer in primary care
Dentist has opportunity for PRIMARY PREVENTION in patients attending for regular oral care
Dentist must be familiar with and competent in:
* Smoking cessation advice
* Alcohol reduction advice
* Healthy diet promotion
Part of General CPD requirement now
There is a GDC expectation that a dentist will do this as part of ‘good patient care’ rather than any particular remuneration
summary of oral cancer management as GPD
Can present at ANY age in ANY patient
Dentist has to make decision about their referral threshold for potentially malignant lesions
Monitor with photographs and education
* Remove local factors where ulcer may be due to trauma, then review
2 WEEK RULE for referral to clinic for the hospital
* Patient must be initially seen within this time
* 62 day referral to treatment time for cancer patients
