oral cancer

1. Cancer of the lower lip, oral mucosa,
tongue. Etiology, pathogenesis,
classification, clinic. Diagnosis and
treatment.

2. The oral cavity extends from the skin-vermilion
junctions of the anterior lips to the junction of
the hard and soft palates above and to the line
of circumvallate papillae below and is divided
into the following specific areas:
 Lip.
 Anterior two thirds of tongue.
 Buccal mucosa.
 Floor of mouth.
 Lower gingiva.
 Retromolar trigone.
 Upper gingiva.
 Hard palate.

6. 5-year survival for localized disease is 76%
5-year survival for metastatic disease is 19%

7. Austria
Brazil,
Goiania
Bulgaria
Belarus
Germany,
Hamburg
Germany,
Munich
Netherlands,
North
Ea
Switerland,
3
registries
USA,
California
USA,
Colorado
USA,
Illinois
Total
early
late
0
10
20
30
40
50
60
70
80
%
Proportion of early and late stages in oral cavity and oropharynx cancers,
males and females (excluding incomplete and missing stage information)
Proportion of Early and late stages*
* Early: TNM stage group I and II, Late: TNM stage group III and IV

35.  Erythroplakia is defined as a fiery red patch that
cannot be characterized either clinically or
pathologically as any other definable lesion.
These may appear as smooth, velvety, granular or
nodular lesions often with a well-defined margins
adjacent to normal looking mucosa.The soft palate,
the floor of mouth, the ventral surface of tongue
and the retromolar area are the most common sites
of involvement. Erythroplakia is more common
among middle aged to elderly persons and,
especially among men. The prevalence of these
lesions range from 0.02-0.83% in different regions.
Erythroplakia is strongly associated with tobacco
habits and alcohol drinking.

41.  Management:
 Management of oral erythroplakia focuses on the
prevention of malignant transformation and early
detection of occult malignancy. Persons with
erythroplakia should be advised to stop
tobacco/alcohol habits, and should be encouraged to
take a diet rich in vegetables and fruits. In view of the
high malignant potential of these lesions the
recommended treatment is surgical excision, including
laser . However, even after surgical excision, the
recurrences and development of malignancy at the
same site are high . In view of this, long-term follow-
up is essential even after surgical removal.

44. Leukoplakia
The term leukoplakia should be used only as a
clinically descriptive term meaning that the observer
sees a white patch that does not rub off, the
significance of which depends on the histologic
findings. Leukoplakia can range from hyperkeratosis to
an actual early invasive carcinoma or may only
represent a fungal infection, lichen planus, or other
benign oral disease.

45.  Management:
 The various approaches for the management of
leukoplakia include medical and surgical options:
Medical management
 Cessation of tobacco and alcohol use
 Topical application of retinoids
 Systemic treatment with Vitamin A, beta-
carotene, lycopene, isotretinoin, etc.
 Surgical management
 Conventional surgical excision
 Laser excision
 Photodynamic therapy
 Cryotherapy
 Electrocautery

48. Actinic Cheiloses represent actinic keratoses affecting
the lip vermilion. The lip becomes dry, cracked, scaly,
pale or white. Squamous epithelium of the lip
vermilion may be hyperplastic or atrophic, and shows
maturation disorder, varying degrees of keratinisation,
cytological atypia and increased mithotic activities.
Keratin may be accumulated and form surface plaque.
The underlying connective tissue usually shows
basophilic degeneration of collagen and elastosis. The
diagnosis is confirmed by biopsy. Localized lesions are
easily treated with cryotherapy or electrosurgery.
Extensive lesions require carbon dioxide laser or
scalpel vermilionectomy. Avoiding further exposure to
the sun and close follow-up is recommended.

49.  Tumor grading is recommended using
Broder classification (Tumor Grade [G]):
 G1: well differentiated.
 G2: moderately well differentiated.
 G3: poorly differentiated.
 G4: undifferentiated.
 No statistically significant correlation
between degree of differentiation and the
biologic behavior of the cancer exists;
however, vascular invasion is a negative
prognostic factor

54.  a. Tobacco
b. Alcohol
c. Dietary factors
An association between diet and oral cancer has long been suggested . A well-
established and quantifiable protective effect of a diet rich in fruits and vegetables
has been shown in several studies . A meta-analysis of various studies showed
28% decreased risk per 50g of non-starchy vegetables and 24% decreased risk per
50 g of citrus fruits consumed per day with a dose–response relationship .
d. Poor oral hygiene
Several studies have identified a role of poor oral hygiene (frequency of brushing
and/or poor dentition) in oral carcinogenesis even after adjustment for tobacco and
alcohol consumption . An inverse relationship has been observed with frequency of
brushing the teeth and oral cancer . Studies have shown higher acetaldehyde levels
in the saliva of those who smoke and use alcohol with poor oral hygiene .
e. HPV infection
Numerous studies have investigated the prevalence of HPV in oral cancer tissues.
HPV DNA was detected in about 25% of cancers of oral cavity . Recent studies
indicate that HPV infection, particularly with high-risk oncogenic types 16 and 18,
plays a role in the progression to oral cancer . The transmission of HPV to the oral
cavity is poorly understood. Sexual transmission has been suggested by some
authors. HPV DNA is more frequently seen in the biopsy specimens of patients with
oral cancer who practiced oral sex . However, other studies have found no
correlation between oral sex and oral cancer . The role of HPV infection in oral
cancer is not clear.

55. f. Chronic trauma
Several studies have shown that the presence of a chronic sore from
ill-fitting dentures or sharp teeth is a risk factor for oral cancer. This
is significant even after adjustment for tobacco and alcohol.
g. Mouth wash
Chronic use of alcohol-containing mouthwash is considered a risk
factor. However, not many studies support this association.
h. Mate
Mate is a tea-like beverage consumed in certain parts of South
America. It is brewed from the dried leaves of the perennial tree Ilex
paraguarensis. Drinking hot mate is associated with oral
carcinogenesis.
i. Solar radiation
Ultraviolet radiation is an important risk factor for lip cancer.
Individuals engaged in outdoor work such farming, fishing or postal
delivery are at higher risk.
j. Immunosuppression
Increased incidence of oral cancer is seen in immunocompromised
individuals. Carcinomas of the lip have been reported in a number of
kidney transplant patients receiving immunosuppressive medications,
and oral cancers have been reported in young HIV seropositive
patients.
k. Genetic factors
A genetic predisposition has been suggested for oral cancer risk.
Studies have found that individuals with polymorphisms
inGSTM1 and CYP1A1 are at a genetically higher risk of oral cancer,

61. Table 1. Primary Tumor (T)a
Enlarge
TX
Primary tumor cannot be assessed.
T0 No evidence of primary tumor.
Tis Carcinoma in situ.
T1 Tumor ≤2 cm in greatest dimension.
T2 Tumor >2 cm but ≤4 cm in greatest dimension.
T3 Tumor >4 cm in greatest dimension.
T4a Moderately advanced local disease.
b
(Lip) Tumor invades through cortical bone, inferior alveolar
nerve, floor of mouth, or skin of face, chin or nose.
(Oral cavity) Tumor invades adjacent structures only (e.g.,
through cortical bone [mandible or maxilla] into deep
[extrinsic] muscle of tongue [genioglossus, hyoglossus,
palatoglossus, and styloglossus], maxillary sinus, or skin of
face).
T4b Very advanced local disease.
Tumor invades masticator space, pterygoid plates, or skull base
and/or encases internal carotid artery.

62. NX Regional lymph nodes cannot be assessed.
N0 No regional lymph node metastasis.
N1 Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest
dimension.
N2 Metastasis in a single ipsilateral lymph node, >3 cm but ≤6 cm in
greatest dimension.
Metastases in multiple ipsilateral lymph nodes, none >6 cm in greatest
dimension.
Metastases in bilateral or contralateral lymph nodes, none >6 cm in
greatest dimension.
N2a Metastasis in single ipsilateral lymph node, >3 cm but ≤6 cm in
greatest dimension.
N2b Metastases in multiple ipsilateral lymph nodes, none >6 cm in greatest
dimension.
N2c Metastases in bilateral or contralateral lymph nodes, none >6 cm in
greatest dimension.
N3 Metastasis in a lymph node >6 cm in greatest dimension.

63. M0 No distant metastasis.
M1 Distant metastasis.
Stage T N M
0 Tis N0 M0
I T1 N0 M0
II T2 N0 M0
III T3 N0 M0
T1 N1 M0
T2 N1 M0
T3 N1 M0
IVA T4a N0 M0
T4a N1 M0
T1 N2 M0
T2 N2 M0
T3 N2 M0
T4a N2 M0
IVB Any T N3 M0
T4b Any N M0
IVC Any T Any N M1

67.  The mechanism of spread from the
primary site to lymph nodes is almost
always by embolism.
 The main routes of lymph node drainage
are into the first station nodes (i.e.,
buccinator, jugulodigastric,
submandibular, and submental).
 Sites close to the midline often drain
bilaterally.
 Second station nodes include the parotid,
jugular, and the upper and lower posterior
cervical nodes.

70. Dental or doctor examinations
oSores found on lip, tongue, or around mouth
oUlcers or bleeding in the mouth
 Tests used to confirm findings
o Incisional biopsy
o Orthopantomogram
o X-rays, CT scans, MRI scans can be done to
determine if the cancer metastisized
 Determination of the stage
o Early Cancer
o Advanced Cancer

71.  Toluidine blue (TB) staining is an adjunct and
not a substitute to visual examination. TB
staining has been shown to aid in the detection
and diagnosis of oral precancers and cancers.
TB staining provides better demarcation of
malignant/dysplastic areas, so as to identify the
site for biopsy. TB staining has been shown to
identify lesions with molecular changes
associated with increased risk of progression of
oral precancer to oral cancer

72. Oral exfoliative cytology is another commonly used
adjunct to oral visual inspection. The major
limitations of this technique are high false-
negative rates and smaller number of exfoliated
cells identified in the smear. The use of a
cytobrush as a sampling device has improved
the technique, providing adequate good-quality
specimens for interpretation. By brushing, it is
possible to reach the deeper layers of the oral
mucosa where squamous intraepithelial
neoplasia begins. The biological characteristics
of the oral epithelial cells obtained can be
evaluated using the following additional
methods: computer-assisted image analysis,
DNA cytometry, immununo histochemistry,
monolayer cytology and molecular biological
analysis.

73. The diagnosis is confirmed by biopsy.
The specimen is taken from the clinically
most suspicious area, avoiding necrotic
or grossly ulcerated areas, and more than
one biopsy site may need to be chosen.

74. Open lymph node biopsy is
carried out only when the lesion cannot
be identified by aspiration biopsy or in
patients with suspected lymphoma.

75.  Nx: Regional lymph nodes cannot be
assessed.
 N0: No regional lymph node metastases.
 N1: Single ipsilateral lymph node, < 3 cm

76.  N2a: Single ipsilateral lymph node 3 to 6
cm
 N2b: Multiple ipsilateral lymph nodes >
6 cm
 N2c: Bilateral or contralateral nodes >
6cm
 N3: Metastases > 6 cm

77. Patients with SCC of the oral cavity or
oropharynx have a risk of multiple primary
tumours in the pharynx or larynx, as
well as in the tracheobronchial region and
oesophagus so routine panendoscopy is
often performed to evaluate these sites.

78. The sentinel node
is the first draining lymph node from a tumour. It
is assumed that if the sentinel node can be
shown to be free from tumour, then the
lymphatic basin is free from tumour and neck
dissection is not required.
Sentinel nodes are identified by a combination of
lymphoscintigraphy and injection of blue dye in
the tumour bed and then sampling draining
nodes identified.

79.  Chemiluminescent illumination is used as a
diagnostic aid in the detection of oral precancers
and cancers. In this technique,
chemiluminescent light is used to visualize the
oral cavity after rinsing the mouth with 1%
dilute acetic acid. This highlight dysplastic white
lesions as acetowhite regions. Chemiluminescent
light improves the identification, evaluation and
monitoring of white oral mucosal lesions.
However its usefulness in discriminating benign,
inflammatory, potentially malignant or malignant
oral lesion remains uncertain . This can be used
as an adjunct following standard visual
examination to provide additional information.

80.  Fluorescence imaging is a process in which tissue is illuminated with a light
source, and images of the fluorescence produced in the tissue and altered
by absorption and scattering events are recorded using a camera. The
presence of disease changes the concentration of the fluorophores as well
as the light-scattering and absorption properties of the tissue. Use of
exogenous fluorophores (protoporphyrin IX) or autofluorescence have been
tried, but exogenous fluorophores has several disadvantages, such as
waiting for some time after the application of the fluorophore to reach the
tissues, and the residual photosensitivity following the procedure
temporarly affecting the individuals daily life; low specificity is another
drawback.
Autofluorescence of tissues is produced by fluorophores that naturally occur
in living cells after excitation with a suitable wavelength. In
autofluorescence imaging the tissue is illuminated with a light source and
images of the fluorescence produced are recorded using a camera.
Autofluorescence imaging is especially suitable for screening of
premalignant and early malignant oral lesions.
The autofluorescence spectroscopy system consists of a light source that
excites the tissue through a fibre; the fluorescence produced in the tissues
is analysed by a spectrograph. The recorded spectra can be saved to a
computer, which allows mathematical spectral analysis. Autofluorescence
spectroscopy is useful for distinguishing lesions from healthy oral mucosa
with a sensitivity above 80% and specificity above 60%. Scanning of the
complete oral cavity using point spectroscopy is impossible, and
autofluorescence imaging may be more appropriate and easy-to-use to
detect oral lesions. Autofluorescence imaging may be useful in detecting
lesions that are not easily noticed by visual inspection.

81.  Intraoral dental radiographs and pantomographs
may help in identifying the involvement of the
underlying bone. Computed tomography (CT)
and magnetic resonance image (MRI) scans give
more information about the local extent of the
disease and status of the lymph nodes. CT
scanning is useful in evaluating the involvement
of cortical bone, and MRI is superior in
evaluating the medullary bone and soft tissue
extent of the disease. MRI is more reliable than
CT scanning in identifying metastatic nodal
disease and extracapsular spread of tumour.
Such investigations are not mandatory for most
cases, but they may be useful in selected cases
where the additional details obtained may be
helpful in deciding and planning radical forms of
therapy for moderately advanced invasive
cancers.

83.  Fine needle aspiration cytology (FNAC) of the
enlarged lymph node is recommended in
patients without any obvious primary tumours.
In patients in whom fine needle aspiration is
non-diagnostic, an excision biopsy of the node is
advisable. In patients with enlarged cervical
(neck) lymph nodes with an obvious primary
tumour in the oral cavity or oropharynx,
the biopsy is always taken from the primary site
and not from the lymph node

88. Small Lesions of the Lip
Standard treatment options:
 Surgery.
 Radiation therapy.
 Surgery and radiation therapy produce
similar cure rates, and the method of
treatment is dictated by the anticipated
cosmetic and functional results.

89. Surgery alone.
Radiation therapy alone.
A combination of the above.
The choice of treatment is generally
dictated by the anticipated functional and
cosmetic results of the treatment.

90.  For lesions of the oral cavity, surgery must
adequately encompass all of the gross as well as
the presumed microscopic extent of the disease.
If regional nodes are positive, cervical node
dissection is usually done in continuity. With
modern approaches, the surgeon can
successfully ablate large posterior oral cavity
tumors and with reconstructive methods can
achieve satisfactory functional results.
Prosthodontic rehabilitation is important,
particularly in early-stage cancers, to assure the
best quality of life

91. Radiation therapy for lip and oral cavity cancers
can be administered by external-beam radiation
therapy (EBRT) or interstitial implantation alone,
but for many sites the use of both modalities
produces better control and functional results.
Small superficial cancers can be very
successfully treated by local implantation using
any one of several radioactive sources, by
intraoral cone radiation therapy, or by electrons.
Larger lesions are frequently managed using
EBRT to include the primary site and regional
lymph nodes, even if they are not clinically
involved. Supplementation with interstitial
radiation sources may be necessary to achieve
adequate doses to large primary tumors and/or
bulky nodal metastases

92. Radiation mask used in treatment of throat cancer

97. Indications for post-operative radiotherapy:
 Positive resected margin
 Multiple involved nodes
 Extracapsular extension
 Perineural spread
 Lymphovascular emboli
 Locally advanced tumour regardless of margin

103. Prognostic Factors:Various factors associated with the primary tumour and regional nodes
have been found to be indicators of predicting treatment outcome.
Factors related to primary tumours:
Tumour size
The size of primary tumour affects both the choice and outcome of treatment. Large tumour
size has poor prognosis. However, recent reports indicate that the thickness of the tumour is
more important than the diameter in predicting nodal metastasis, local recurrences and
survival. The clinical appearance (ulcerative versus proliferative) and ratio of exo/endophytic
growths are also considered to be predictors of treatment outcome.
Tumour site
A gradual decrease in 5-year survival has been reported for tumours located more posteriorly
in the oral cavity. Nodal metastases are more common for tumours of the tongue,
retromolar area and oropharynx compared to lip and buccal mucosa.
Bone involvement
Infiltrating type bone involvement is associated with increased risk of local recurrences and
poor survival compared to an erosive type of bone involvement.
Skin involvement
Direct spread to the skin is an indicator of poor prognosis, and carcinoma en cuirasse, due to
lymphatic involvement of the skin, is more serious, indicative of a grave prognosis.
Lymphovascular and perineural invasion
The presence of lymphovascular and perineural invasion in the pathological specimen are
considered to be poor prognostic factors.
Invasive front grading
Several studies have shown a poor correlation between Broders/WHO histological grading and
treatment outcome. Invasive front grading is now found to be a more reliable predictor of
treatment outcome. Tumours with a non-cohesive invasive front have a poor outcome
compared to those with a well-defined tumour front.

104. Status of resected margins
The post-operative status of the mucosal margin, as well as of the deeper margins,
has significance in deciding adjuvant treatment and the treatment outcome.
According to UK guidelines, a margin of 5mm or more is clear, 1-5mm is close
and less than 1mm is considered as involved margin. Positive or close margins
have poor outcome compared to those with clear margins.
Histopathology
Verrucous carcinoma is a slow-growing type of squamous cell carcinoma with good
treatment outcome, whereas prognosis is poor for adenosquamous and basaloid
squamous cell carcinomas.
DNA ploidy status DNA ploidy status is an important predictor of overall and
relapse-free survival. The presence of DNA aneunploidy is considered to be a
predictor of regional metastasis.
 Prognostic factors related to the regional nodes:
 Presence or absence of metastasis
 Number of positive nodes
 Extracapsular spread
 Size of the metastatic deposit
 Anatomical level of involvement
 Laterality of positive nodes
 Embolisation/permeation of perinodal lymphatics
 Post-operative nodal stage

105. Chemotherapy
Typical chemotherapy agents are a combination
of paclitaxel and carboplatin.
Targeted therapy
Cetuximab is also used in the treatment of cancer.
Docetaxel-based chemotherapy has shown a very good
response in locally advanced head and neck cancer.
Taxotere is the only taxane approved by US FDA for Head
and neck cancer, in combination with cisplatin and
fluorouracil for the induction treatment of patients with
inoperable, locally advanced squamous cell carcinoma of
the head and neck.
While not specifically a chemotherapy, amifostine is often
administered intravenously by a chemotherapy clinic
prior to a patient's IMRT radiotherapy sessions.
Amifostine protects the patient's gums and salivary
glands from the effects of radiation

107.  Practice good oral hygiene
 Do not use tobacco products
 Do not drink alcohol
 Eat well balanced diet, increase
use of fruits and vegetables.
Increased Risk Reduced Risk
•Meats high in fat and
cholesterol
•Refined cereals and
sugar
•Rice
•Fruits
•Vegetables
•Fish