Malignancies of Oral Cavity, Lip, Tongue

Dr Sumer Yadav
Plastic and reconstructive surgeon
sumeryadav2004@gmail.com

Pre-Malignant Lesions/conditions
Leukoplakia - chronic, white, verrucous plaque with
histologic atypia
Severity linked to the duration and quantity of tobacco and alcohol
use
Occur anywhere in the oral cavity
Lip, tongue, or floor of the mouth lesions are prone for progression
to SCC
Erythroplakia - non-inflammatory erythematous plaque
Analagous to intra-oral erythroplasia of Queyrat or SCC in situ
Biopsies - severe dysplasia and areas of frank invasion

Leukoplakia

Erythroplakia

Pre-Malignant Lesions…
Submucous fibrosis
generalized white discoloration of oral mucosa with
progressive fibrosis, painful mucosal atrophy and
restrictive fibrotic bands
individuals who chew betel quid, a concoction of
tobacco, lime, areca nut and betel leaves
Ultimately leads to trismus, dysphagia and severe
xerostomia
5 - 10 % progress to SCC

Cancerous lesion of Lips& Oral
cavity
Lips –SCC, Melanoma, BCC(rare)
Oral cavity:
-- scc: 9/10 incidence
--verrucous ca: <5% low grade, slow growing rarely
metastasizes with tendency to invade deep tissue.

Cancerous lesion of Lips& Oral
cavity
Minor salivary gland tumor:
-in the glands lining the oral cavity
-adenoidcystic ca, mucoepidermoid ca,
adenocarcinoma.
-Sarcoma

Incidence
Globally >300,000 people diagnosed/year
Eighth most common malignancy
India –upto 40% of all malignancies
M>F
Raising trend
6-7th
decade
Most of the people are dying because of ignorance

INCIDENCE
Demographic and clinical profile of oral squamous
cell carcinoma patients: a retrospective study ( Shenoi
R, Sharma BK, et.al, Indian J Cancer. 2012 Jan;49(1):21-
6:
Most common site: mandibular alveolus
Major cause: tobacco chewing
Majority of patients presented in stage III
Majority presented within 6 months of onset

Risk Factors
Tobacco: About 90% of people with oral cavity
and oropharyngeal cancer use tobacco
Alcohol: Drinking alcohol strongly increases a
smoker's risk of developing oral cavity and
oropharyngeal cancer.
Ultraviolet light: More than 30% of patients
with cancers of the lip have outdoor occupations
associated with prolonged exposure to sunlight.
Irritation: Long-term irritation to the lining of
the mouth caused by poorly fitting dentures

Risk Factors Cont…
Poor nutrition: A diet low in fruits and vegetables is
associated with an increased risk
Mouthwash: Some studies have suggested that
mouthwash with a high alcohol content
Human papillomavirus (HPV) infection:
Immune system suppression:
Age: The likelihood of developing oral and oropharyngeal
cancer increases with age, especially after age 35.
Gender: Oral and oropharyngeal cancer is twice as
common in men as in women

How tobacco affects
Tobacco smoke contains >4000 chemicals, at least 60
shown to be carcinogens.
Smoke less tobacco:
main form: chewing, snuff
at least 28 carcinogens found in smokeless form

Relative Risk factors for Oral
Cancers
Habit Relative Risk %None
Betel nut Chewing
Smoking only
Betel chewing + Tobacco
chewing
Betel chewing + Smoking
Betel+Tobacco+smoking
1%
4%
3-6%
8-15%
4-25%
20%

How Alcohol affects
Chronic alcohol exposure results in increased
cancer incidence in animal model.
Acetaldehyde , reactive oxygen species- main
mutagen
Acetaldehyde: directly binds to DNA, alters
methyl transfer leading to hypomethylation
leading to alerted gene products
Alcohol promotes cytochrome P450- which
increases activation of procarcinogens( tobacco,
alcohol).
Alcohol can act as solvent facilitating entry of
carcinogens into cells

Role of HPV in Oral SCC
Role of human papilloma virus in the oral carcinogenesis: an
Indian perspective (Chocolatewala NM, et.al. J Cancer R Ther. 2009
Apr-Jun;5(2):7-17).
Association strongest for Oropharynx, specially cancer of tonsils
followed by base of tongue.
High risk HPV-16 predominate type.
Commonly affects younger age groups , male, non smokers.
Better outcomes, more responsive to RT, higher survival rate.

INHERITED RISK FACTORS
Defective DNA repair mechanism: xeroderma
pigmentosa, ataxia telangiectasia, bloom syndrome,
fanconi syndrome
Tumor suppressor gene(p53) defect: Li Fraumeni
syndrome.

Relationship between ABO blood groups and oral
cancer (Jaleel BF, et. al. Indian J Dental Research 2012
Jan;23(1):7-10:
found that people with blood group A had 1.46 times
higher risk of developing oral cancer as compared
with other blood group.

Allergies and risk of head and neck cancer
(Michaud DS, et.al. Cancer Causes Control. 2012
Aug;23(8):1317-22. Epub 2012 Jun 19).
Case control study
Allergies have heightened Th2 immunity
Had a 19% lower risk of HNSCC.
Statistically significant for oropharyngeal cancer.
HPV status does not confound or modify
associations with allergies.

MOLECULAR BIOLOGY
Cytogenetic : chromosomes 3,5,8,11,17,18.
Tumor suppressor genes inactivation: p16,p21,p53,RB
gene.
Proto-oncogene activation: cyclinD1/PRADD1.
Growth factors /receptors overexpression: EGF,EGF-
R,TGF- ,HER-2/neu,FGF,FGF-R,PDGF).ɑ

MOLECULAR BIOLOGY
RAS family oncogene.
Telomeres, telomerase, cell senescence
Tumor immunology(role of TIL, CTL, IL-2/4/6)
Tumor invasion and metastasis:(endothelial
proliferation:PGE2,TGFβ,FGF,VEGF),MMP

MOLECULAR PROGRESSION MODEL OF HNSCC CARCINOGENESIS
Normal squamous mucosa
EGF, EGFR
Overexpression
Squamous hyperplasia
Telomerase activation p16 inactivation
Dysplasia
PRAD-1 amplification 3p deletion
p53 inactivation
Carcinoma in-situ
4q, 5q, 8p, 13q
deletion
Invasive carcinoma
Matrix metalloproteinase
Over-expression
Metastasis

DNA changes
P53, p16, Ki67 immunoexpression in oral scc
( Dragomir LP, et.al, Rom jo morph embry 2012;
53(1)89-93:
positivity index- increased for p16
tumor invasion- identified with p53, Ki67.
Study highlights value of immunostain for p16 in
identifying dysplastic lesion
Predictive importance of p53, Ki16 markers in
identifying aggressive form of tumour.

DNA CHANGES
Immunohistochemical p53, Ki16, hTERT in oral
scc( Abraho AC et.al.Brazil oral research 2011 Jan-
Feb;25(1):34-41:
p53 positivity in 93.3% of PMD, 43.3% of OSCC, 80%
OEH.

Site of oral cavity
Tongue : 35%
Floor of mouth: 30%
Lower alveolus: 15%
Buccal mucosa: 10%
Upper alveolus/hard palate: 8%
RMT: 2%
Lips: lower-93%, upper-5%, commissure- 2%

Symptoms
a sore in the mouth that does not heal (most
common symptom)
pain in the mouth that doesn't go away (also
very common)
a persistent lump or thickening in the cheek
a persistent white or red patch on the gums,
tongue, tonsil, or lining of the mouth
a sore throat or a feeling that something is
caught in the throat that doesn't go away
Increased salivation

More Symptoms
difficulty chewing or swallowing
difficulty moving the jaw or tongue
swelling of the jaw that causes dentures to fit
poorly or become uncomfortable
loosening of the teeth or pain around the teeth or
jaw
voice changes
a lump or mass in the neck
weight loss
persistent bad breath

Patient Workup
History
Clinical examination
Investigations

Patient Workup
Investigations :
Primary: photographs
incisional biopsy
FNAC
Orthopantogram
CXR
ECG
Routine blood investigations

Patient Workup
Investigations: for staging
- CT face + neck ± CT chest
- MRI
- USG of neck or primary ± USG guided
FNAC of suspicious lymphadenopathy
- PET

INVESTIGATIONS FOR RECONSTRUCTION
Allen’s test of vascular supply to hand if a radial forearm
flap anticipated.
MRA of leg vessels if composite fibula reconstruction
anticipated.
Colour Doppler of chest , abdomen if DCIA(deep
circumflex iliac artery) free flap anticipated
Dental impression for all maxillary tumours

STAGING OF THE DISEASE
American joint committee on cancer:
T , N , M
Tx- primary tumour cannot be assessed
T0- No evidence of primary tumour
T1- ≤ 2cm in greatest dimension
T2- 4cm < 2cm> in greatest dimension
T3- > 4cm in greatest dimension

T4a- Oral cavity: tumour invades through cortical
bone, into deep(extrinsic) muscle of tongue, maxillary
sinus or skin.
Lips: cortical bone, inferior alveolar nerve, floor of
mouth, skin i.e. chin or nose.
T4b- involves masticator space, pterygoid plates, skull
base and/or encases internal carotid artery

N stage:
Nx- regional lymph nodes can not be assessed.
N0- no regional lymph node metastasis.
N1- metastasis in a single ipsilateral lymph node ≤
3cm in greatest dimension.
N2a- metastasis in a single ipsilateral LN > 3cm but <
6cm in greatest dimension.

N2b- metastasis in multiple ipsilateral LNs, none > 6cm
in greatest dimension.
N2c- metastasis in B/L or C/L LNs, none > 6 cm.
N3- metastasis in a LN > 6 cm in greatest dimension
M stage: Mx- cannot be assessed, M0- no distant
metastasis, M1- distant metastasisi.

Stage Grouping
Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage III T1, T2 N1 M0
T3 N0, N1M0
Stage IV A T1, T2, T3 N2 M0
T4a N0, N1, N2 M0
Stage IV B Any T N3 M0
T4b Any N M0
Stage IV C Any T Any N M1

TREATMENT
Treatment goals: to eradicate primary tumor and LN
metastasis, to maintain function, cosmetic
reconstruction
Factors affecting choice of treatment:
tumor factor
patient factor
resource factor

Treatment Goals for
Cancer of the Oral Cavity
• Cure of cancer
• Preservation or restoration of form and
function
• Avoid or minimize sequelae of treatment
• Prevent second primary cancers
Palliation
Restore cosmesis
Minimise morbidity and mortality

TUMOR FACTORS AFFECTING TREATMENT
• Site
• Size (T stage)
• Location
• Multiplicity
• Proximity to bone
• Pathological features
• Histology, grade, depth of invasion, tumor
type
• Status of cervical lymph nodes
• Previous treatment

TREATMENT
Patient factors:
 age,
 general medical condition,
 performance status,
occupation,
 lifestyle(smoking/drinking)
 socioeconomic considerations
 previous treatment

TREATMENT
Physician factors:
 surgery,
 radiotherapy,
chemotherapy
 nursing & rehabilitation services,
 dental,
 prosthetics,
support services

Treatment
Surgery
Radiotherapy
Chemotherapy
Immunotherapy
Targeted therapy
Gene therapy

Treatment of Choice
Stage I , II: single modality treatment is effective and
preferable.
Stage III , IV: multimodal therapy is essential

TREATMENT
SURGERY:
Early stage T1/2No tumor: Wide excision +/ - ND
High risk of locoregional recurrent (40%)
Management of No Neck:
High incidence of occult metastasis in the clinically No
Neck (15-43%)
Controversy : Observation or Surgery/Radiation
Depend on primary site.
Should be have minimal morbidity
ELND if risk of occult meta >20%. (SND/SOHND).
Locally advanced tumor: Combined modality treatment

Classification of ND
1991 Classification:
RND
Modified RND
Selective ND:
Supraomohyoid
Lateral
Posterolateral
Anterior
Extended ND
2001 Classification:
RND
Modified RND
Selective ND (SND):
SND (L.I-III/IV)
SND (L.II-IV)
SND (L.II-V)
SND (L.VI)
Extended ND
Proposed by American HN Society and AAOHNS

Selective neck dissection Modified RND type 1,2,3.

Standard treatment options for
management of lymph node:
Radiation therapy alone or neck dissection:
N1 (0–2 cm).
N2b or N3; all nodes smaller than 2
cm. (A combined surgical and
radiation therapy approach should also
be considered.)
Radiation therapy and neck dissection:
N1 (2–3 cm), N2a, N3.
Surgery followed by radiation therapy,
indications for which are as follows:
Multiple positive nodes.
Contralateral subclinical metastases.
Invasion of tumor through the capsule
of the lymph node.
N2b or N3 (one or more nodes in each
side of the neck, as appropriate, >2
cm).
Radiation therapy prior to surgery:
Large fixed nodes.

SURGICAL APPROACHES
 Trans-oral approach
 Lower cheek approach
 Upper cheek approach
 mandibulotomy
 Visor flap

Surgical approach depends on
• Tumor size
• Tumor site
• Tumor location
• Proximity to mandible or maxilla
• Need for neck dissection
• Need for reconstructive surgery

Factors predicting positive margin
Large tumour.
Perineural spread.
Vascular permeation.
Noncohesive invasive front
Cervical metastasis

Carcinoma tongue

Carcinoma tongue
Tongue functions
Taste
Mastication
swallowing
Speech
intimacy

Carcinoma tongue
Pathological types
1. nonhealing ulcer
2. proliferative growth with everted edge
3. indurated variety with frozen tongue
4. fissure variety

Carcinoma tongue - clinical
Bleeding ulcer
Pain
Ankyloglossia
Dysarticulation
Dysphagia
Fetor oris
Neck nodes

Carcinoma tongue- surgery
Wide local excision – CIS
Partial glossectomy
Hemiglossectomy
Total glossectomy
Neck dissection
Flap reconstruction- PMMC/DP/FREE ALT/FRFF

CARCINOMA LIP

Oral competence
Deglutition
Articulation
Expression of emotion
Symbol of beauty
Lip Function

EPIDEMIOLOGY
It is one of most common malignant tumor affecting
head & neck
Squamous cell Carcinoma is most common in India
Factors affecting are:
1. Solar radiation
2.Tobacco smoking
3. Viruses
LIP CANCER

Male:female ratio – 14:1
Lower lip > upper lip (solar radiation)
90% : lower lip
6%: oral commissure
4%: upper lip

1. Lip should have sensation, motion, prevent
drooling, permit speech & resonable cosmetic
appearance.
2. Full thickness skin flaps used whenever possible
3. It should provide sufficient mucosa contiguous to
commisure to avoid contracture
Principles of lip repair

FIGURE 2. Direct excision and repair of lower lip lesions. Lesions up to
one half of the lip can be excised and repair primarily.
Small lesions can be excised using the "V" excision, and can be angled to blend into the
chin-lip crease. Larger lesions can be
excised using a "W" pattern. The "W" avoids crossing the chin-lip crease and retains an
adequate margin of tissue around the
lesion inferiorly. The largest lesions can be excised as a rectangle and incisions made in
the chin-lip crease to allow advancement
of lateral lip tissue for closure.sumeryadav2004@gmail.com

FIGURE 6. Abbe cross lip flap. (A)
"V"-shaped incision diagramed around lower
lip lesion and proposed upper lip flap outlined.
(B) Lesion removed, flap rotated and sutured
into defect. Flap is designed with height 1 to 2
mm greater than defect to be reconstructed

FIGURE 6. Estlander cross lip flap. (A)
"V"-shaped incision diagramed around lower
lip lesion and proposed upper lip flap outlined.
(B) Lesion removed, flap rotated and sutured
into defect. Flap is designed with height 1 to 2
mm greater than defect to be reconstructed.

Karapandzic flap, (A) Lower lip defect
after resection of carcinoma.
Proposed incisions outlined. (B)
Incisions made
through skin. Buccal branches of
facial nerve and labial artery branches
preserved to greatest extent possible.
(C) Tissue
advanced and defect closed.sumeryadav2004@gmail.com

RADIOTHERAPY
Applications:
- Radical : early tongue cancer
- palliative : advanced total control not possible: 20Gy
x5 daily fractions x 1 week.
-combined therapy.
-preoperative.
-postoperative.

POST-OP RT
Indications:
-presence of nodal disease with exptracapsular spread.
-presence of involved surgical margin
-excision margin less than 5mm.
-stage III/IV.
-perineural or vascular invasion.
-poor differentiation.
-oral cavity primary.
-multicentric primary.
->4 nodes positive.
-soft tissue invasion.
-dysplasia or carcinoma insitu at resection margin.

IMMUNOTHERAPY
HPV Vaccines
Estimated that 25% of HNSCC are HPV associated
 Tend to arise in younger patients
 Lingual and palatine tonsils
 Occur predominantly in non smoker/drinker
 Associated with a more favorable prognosis
HPV viral oncogenes E6 and E7 are consistently expressed in HPV
associated cancers
 Thought to integrate into the host DNA, and when expressed, bypass
the regulation of cell proliferation
Both protein and DNA vaccines targeting HPV DNA are currently
in phase I and phase II trials

TARGETED THERAPY
Targeted therapy in head and neck cancer: state
of the art 2007 and review of clinical
applications( Langer CJ. Cancer 2008 Jun
15;112(12):2635-45:
-anti-EGFR monoclonal antibody(MoAb)
cetuximab first targeted therapy to be developed
-single agent cetuximab confer clinical benefits in
patient with cisplatin refractory metastatic
disease.

TARGETED THERAPY
Molecular targeted therapies in head and neck cancer - An
update of recent developments(Martin Goerner, et.al,
Head & Neck Oncology 2010, 2:8):
-anti-EGFR MoAbs :cetuximab , pantimumab,
zalutumumab
-EGFR targeted tyrosine kinase inhibitors: gefitinib,
erlotinib
- EGFR & HER-2 combined tyrosine kinase inhibitors:
lapatinib, BIBW-2992.
- VEGFR inhibitor: bevacicumab, sorafenib, sunitinib.

GENE THERAPY
Gene therapy for oral squamous cell carcinoma: An
overview( TR Saraswathi, et.al, Indian J Dent Res.
2007 Jul-Sep;18(3):120-3)
STRATEGIES:
-genegene addition therapytherapy: reconstitution of wild type p-53 function
with p-53 expressing adenovirus-> led to inhibition of SCC cell
lines.
- antisense RNA therapy: introducing a remedial gene that
prevents expression of a specific defective gene: potential target
E6 & E7 genes of HPV.
- suicide gene therapy: introduction of a gene into a cell
inabling a prodrug to be activated into an active cytotoxic drug.

Recurrent lips & oral cavity cancer
Surgery is preferred, if radiation was used initially.
Surgery, radiation or combination if surgery used
initially.
Chemotherapy , but no increase in survival
demonstrated.
Other novel therapy method

PROGNOSIS
Location/thickness/depth of primary tumor
Staging
Type of histology
Grading
Presence of perineural spread
Mandibular invasion
Ln extension (Level, size, exptracapsular)
Molecular markers (?)

What happens after Treatment?
Speech and Swallowing Therapy
Follow-up tests
Chemoprevention
Watch for new symptoms
General health considerations

Summary
Risk factors
Premalignant lesions
Sign and symptoms
Investigations
TNM staging and diagnosis
Treatment plan
Surgery
Radiotherapy
Chemotherapy
Follow up

THANKS

Malignancies of Oral Cavity, Lip, Tongue

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