B20.
Oral (squamous) cancer (molecular and pathological characteristics) Salivary gland
adenomas
• Mostly squamous cell carcinomas
• About half result in death within 5 years and most have already metastasized by the
time the primary lesion has been discovered
• Tend to occur late in life and rarely before the age of 40.
Risk Factors for Oral Cancer
Leukoplakia, erythroplakia - risk of transformation in leukoplakia 3-25%
Tobacco use - best established influence, particularly pipe smoking and smokeless
tobacco
HPV, 16 & 18 - identified by molecular probes in 30-50% of cases; probably have a
role in a subset of cases
Alcohol abuse - weaker influence than tobacco use, but the two habits interact to
greatly increase risk.
Protracted irritation - weakly associated
Clinical Features
These lesions may cause local pain or difficulty in chewing, but many are relatively
asymptomatic and so the lesion is ignored
A significant number are not discovered until beyond cure
Overall 5 year survival rates after surgery and adjuvant radiation and chemotherapy
are about 40% for cancers of the base of the tongue, pharynx, and floor of the
mouth without lymph node metastasis, compared with less than 20% for those with
lymph node metastasis
When these cancers are discovered at an early stage, 5 year survival can exceed 90%
Morphology
3 predominant sites of origin of oral cavity carcinomas are (in order of frequency)
the 1) vermilion border of the lateral margins of the lower lip, 2) floor of the mouth,
and 3) lateral borders of the mobile tongue.
early lesions appear as pearly white to gray, circumscribed thickenings of the mucosa
closely resembling leukoplakic patches
they may grow in an exophylic fashion to produce readily visible and palpable
nodular and
eventually fungating lesions, or may assume an endophytic, invasive pattern with
central necrosis to create a cancerous ulcer.
SCC’s are usually moderately to well-differentiated keratinizing tumors
before lesions become advanced it may be possible to identify epithelial atypia,
dysplasia, or carcinoma in situ in the margins, suggesting origin from leukoplakia or
erythroplakia
spread to regional nodes is present at time of initial diagnosis only rarely with lip
cancer, in about 50% of cases of tongue cancer, and in more than 60% of those with
cancer of floor of the mouth
More remote spread to tissues or organs in the thorax or abdomen is less common
than extensive regional spread.
Lecture Notes
extremely large (can be)
extremely high frequency and death in Hungary with rapid increase in mortality
overwhelming incidence in men
5 year survival - 35%
more frequent under 40
Etiology
smoking, alcohol (a good solvent for absorption of carcinogens and adducts) → enhance
each other’s effects
alcohol - a good solvent for absorption of carcinogens and adducts, therefore easily
absorbed -
DNA adducts also formed.
categorized 1-5: 1 = carcinogenic material, 2 = probably, 5 = not carcinogenic
Cigarette Smoke
acetaldehydes → metabolite of alcohol → has an effect on oral squamous epithelia.
acetaldehyde induce DNA adduct formation after alcohol consumption in oral squamous
epithelium - 100 X’s
Poor oral hygiene → diff. bacteria can enhance the effect of different bacteria.
pipe smokers → cancer of lip vs. oropharyngeal cancer
Major forms
Macroscopically there are 3 major forms:
Exophytic → cauliflower like, protruding lesion.
Endophytic → surface only slightly elevated, tumor projects more deeply, e.g.. cervical
cancer
Ulcerated → tumorous lesion with central part ulcerated.
TMN - staging
T1 → diameter </= 2 cm
T2 → 2-4 cm
T3 → 4 cm
T4→ more than 4 cm and local invasion
N1 → ipsilateral, solitary, diameter max. 3 cm
N2a → ipsilateral, solitary, 3-6 cm
N2b → multiple, ipsilateral, max. 6 cm
N2c → bilateral, or contralateral, max. 6 cm
N3 → any LN, > 6 cm
• Level of lymph nodes is also important - lower levels: worse prognosis!
M1 - distant metastasis (rare; mainly lung)
Major Molecular Changes
P16 inactivation (tumor suppressor gene)
P53 inactivation (tumor suppressor gene)
Cyclin D1 amplification
PTEN inactivation
Oral Cancer
long process → several decades
normal ➔ mild dysplasia ➔ intermediate dysplasia ➔ severe dysplasia/cancer cell in
situ, entire thickness, BM intact
early recognition of premalignant lesions is important
80% of malignant changes during oral cancer development
loss of heterozygosity (LOH), loss of chrom. 9p21 LOH, p16 inactivation - normal function
is to inhibit CDK4 - if inactive it is continuously active and keeps proliferating (1st step to
cancer formation - pancreatic and oral), 3p21, 17p13 LOH - p53 mutation (50%
normal ➔ hyperplasia ➔ dysplasia (mild and severe) ➔ carcinoma
Verrucous Carcinoma
variant of squamous carcinoma
elderly men
etiology = smoking, HPV
exophytic, irregular, warty
mainly mandibular crest
slow proliferation, growing expansively
good prognosis (rare lymph node metastasis, not distant metastasis)
Preneoplastic Conditions
more frequently undergo malignant transformation than the corresponding normal
tissues → increased cancer risk
oral cancers: 10-60% are preceded by premalignant lesions → 1/3 cases develop de
novo
leukoplakia: 3-6% is transformed over a ten year period
leukoplakia with severe dysplasia: 40%
proliferative verrucous leukoplakia: 70%
erythroplakia (carcinoma in situ): 50% become invasive
Other Neoplasms
melanoma
Kaposi’s sarcoma
Plasmocytoma
Different Metastasizing Capacity
Lip = low metastasis
Palate= generally low metastasis
Other intraoral tumors= submandibular, jugular L.N
Midline tumors = frequent bilateral metastasis
