CANCER OF

HEAD & NECK

Contents

• Introduction• Definition• Nomenclature• Classification • Epidemiology• Etiology• Molecular biology • Tumor metastasis• Clinical features

Introduction

• Cancer is the common term for all malignant tumors.

• Cancer (Latin word) : crab (Ancient Greek word)

• Presumably because, a cancer cell adheres to any part that it seize upon in an obstinate manner like a crab.

• The study of cancer is – “Oncology’’

onco = Greek onkos, meaning bulk, mass, or tumor, 

logy = study

Definition

• Common terminologies : cancer or tumor

• Literature terminology : neoplasia or neoplasm

• It is a disorder of cell growth, characterized by uncontrolled, uncoordinated & undesirable cell division.

• There is no exact definition for cancer.

• British oncologist – Dr. Willis tried to define it as –

“A neoplasm is an abnormal mass of tissues,

the growth of which exceeds & is

uncoordinated with that of the normal tissues and

persists in the same excessive manner after

cessation of stimuli, which evoked the response ”

Kumar V. , Abbas A.K. , Fausto N. 2007. Robbins & Corton Pathologic Basis Of Disease.7th ed.  Saunders. ISBN 10: 0721601871

Nomenclature

Condition Tissue involved Suffix

Benign Mesenchymal tissue Oma

Benign Epithelial tissue

• adenoma• Papilloma• Cystadenoma• Papillary cystadenoma• polyp

Malignant Mesenchymal tissue Sarcoma

Malignant Epithelial tissue

Carcinoma

Classification

• More than 90% of head and neck malignancies are squamous cell carcinomas.

L. Licitra, E. Felip. Squamous cell carcinoma of the head and neck: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Ann Oncol . 2009; 20 (4):iv121-iv122. doi: 10.1093/annonc/mdp149.

• According to Stell & Maran’s Textbook Of Head & Neck Surgery & Oncology

CANCERS OF HEAD & NECKSquamous cell carcinoma Non - Squamous cell carcinoma

1. Cancer of oral cavity & oropharynx

2. Cancer of larynx & hypophaynx3. Cancer of nasopharynx4. Cancer of nasal cavity & paranasal

sinuses

1. Cancer of thyroid2. Cancer of salivary glands3. Sarcomas - soft tissue - hard tissue

Epidemiology

• Cancer is a leading cause of death worldwide, accounting for 7.6 million deaths (around 13% of all deaths) in 2008

• Head and Neck Cancer: Worldwide – 640,000 cases /year 356,000 deaths per annum (55% mortality) 5% incidence of all cancers (excl. skin) 5% mortality of all cancers

GLOBOCAN 2008 (IARC) Section of Cancer Information (8/12/2013).

Geographical distribution

- wide variations

France (supraglottic, oral cancers) Hong Kong (nasopharyngeal cancers) India (oral cancers)

Age & gender predilection

Region of cancer

Contribution

Oral cavity 41- 43%

Oropharynx 3rd most common

Larynx 30 %

Hypophaynx 10%

Nasopharynx 1-2%

Nasal cavity Rare

Paranasal sinuses

Rare (60-70% in

maxillary sinus)

Etiology

1. Tobacco

2. Alcohol

3. Dental factors

4. Occupational exposures

5. Infections

6. Nutritional factors

7. Inflammatory cause

8. Genetic factors

9. Immunologic factors

10. Endocrinal disturbances

11. Radiation

Tobacco

Smoking :• 90% cases • Contains 30 known carcinogens : polycyclic aromatic hydrocarbons

: nitrosamines• Alcohol adds up in pathology

Black / darkAir cured

Blend & blondFlute cured

More carcinogenic

The areas of oral cavity which is bathed with saliva, are most common sites to be involved.

Eg. – oropharynx, crypts of tonsil, glossotonsillar sulcus, tongue, soft palate &

posterior pharyngeal wall.

Smokeless :• Most common in Indian suncontinent

Bidi Chutta

khaini paan

Alcohol• Synergistic action with tobacco.• Mostly associated with cancer of - lateral border of tongue

- glossotonsillar sulci

- pharyngoepiglotic fold

7 possible mechanisms –

1. Acts as an solvent

2. Some contents of alcoholic beverages

3. Metabolites like – acetaldehyde

4. Up regulation of enzyme – cyt p450

5. Decreased activity of DNA repair enzymes

6. Impairment of immunity

7. Decrease resistance to cancer

• Different alcoholic beverages have different carcinogenic contentes :

- Beer – Nitrosomethylamine

- Dark liquor – ester,

acetaldehyde

- Wine – tannin

- Light liquor – ester,

acetaldehyde

Dental factors• Sharp tooth

• Oral hygiene

• Patients with ill fitting dentures

• Alcohol containing mouth washes

(to mask the smell of tobacco/alcohol)

Occupational exposuresCancer Associated factors

Cancer of oral cavity & oropharynx

Wood dust, chemicals, coals

Cancer of larynx & hypophaynx

Wood dust, Ni & mustard gas and

asbestos exposure, H2so4 & HCl

exposure in battery plants

Cancer of nasopharynx

Cancer of nasal cavity &

paranasal sinuses

Wood dust, textile & lather dust, flour, formaldehyde, solvents, Ni &

Cr dust, mustard gas, radium, isopropyl alcohol.

Cancer of salivary glands Ni alloy dust & si

Sarcomas Urethane, ethylene derivatives, polycyclic hydrocarbons

Infections

30-100% verrucous carcinoma50% cases of NPC have HPV

5% cases of H&E cancers have HIV inhections (kaposi sarcoma)

Mostly associated with nasopharyngeal cacinoma

42 % oral cancer & all smokers with & without cancer,have higher HSV antibody titre.

Nutritional factors Anti-oxydantsVit A , C, E

Carcinogenic nitrosamine in high salted fish (NPC)

Diet low in iodine : carcinoma of thyroid gland

Inflammatory cause

1. GERD : Risk factor in 36-54 % cases of laryngeal / pharyngeal cancer.

2. PRECANCEROUS CONDITIONS OR LESIONS : leukoplakia, erythroplakia

OSMF – in anterior palatoglossal arch

Genetic factors

• Li- Fraumeni syndrome : autosomal dominant condition

mutation of p53 gene

• Fanconi’s anemia• Bloom syndrome• Ataxia• Telegiactasis

• 4-6% of cancer of larynx & hypophaynx have history of

- plummer vinson syndrome

or

- Patterson Brown – Kelly syndrome

Autosomal recessive disorder with increased chromosomal fragility are associated with

oral cavity & pharyngeal carcinoma.

• Cancer of nasopharynx has strong predilection for interaction between genetic & environmental factors.

• Gardener syndrome• Multiple polyposis• Cowden disease• Multiple endocrine neoplasia (autosomal dominant)

• Li- Fraumeni syndrome• Children with ratinoblastoma• Gardener syndrome• Nevoid basal cell

carcinoma syndrome

Increased incidence of thyroid cancer.25 % cases associated with hereditary form

osteosarcoma

sarcoma

Immunologic factors

• Patient suffering from HIV infection.

• Patient on long term immunosupressive medication for organ transplantations (risk of cancer of skin & oral cavity).

• Compromised general condition

Endocrinal disturbances

• Early menarchy • Nulliparity

• Older age at full term pregnancy• Log term Oral contraceptive

Increased risk for salivary gland carcinomas

Decreased risk for salivary gland carcinomas

Radiation

• NPC : Previous history of radiation therapy for cricoid carcinoma or carcinoma of posterior wall of pharynx.

• Thyroid & salivary gland cancer : history of radiation therapy, exposure to radiation fallot from nuclear power plant or nuclear weapon in childhood .

Biology of tumor growth

• 4 stages of tumor growth

1. Malignant changes in 1 cell (transformation)

2. Growth of transformed cell

3. Local invasion

4. Distant metastasis

Molecular basis of cancerAlteration in 4 normal regulatory genes

I. Growth promoting oncogenes

II. Growth inhibiting tumor suppressor genes

III. Genes that regulate apoptosis

IV. Genes involved in DNA repair

Growth promoting oncogenes

• A proto-oncogene is a normal gene that can become an oncogene due to mutations or increased expression.

• Proto-oncogenes code for proteins that help to regulate cell growth and differentiation.

• An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels

Growth inhibiting tumor suppressor genes

• A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from the path to cancer. 

• Tumor-suppressor genes, or more precisely, the proteins for which they code, either have a dampening or repressive effect on the regulation of the cell cycle or promote apoptosis, and sometimes do both.

Genes that regulate apoptosis

• The tumor-suppressor protein p53 accumulates when DNA is damaged due to a chain of biochemical factors.

• Part of this pathway includes alpha-interferon and beta-interferon, which induce transcription of the p53 gene - p53 protein level and enhancement of cancer cell-apoptosis.

• P53 - stopping the cell cycle at G1/interphase, to give the cell time to repair, however it will induce apoptosis if damage is extensive and repair efforts fail.

• Any disruption to the regulation of the p53 or interferon genes will result in impaired apoptosis and the possible formation of tumors.

Essential alterations for malignant transformation

• Self sufficiency in growth signals

• Insensitivity to growth inhibiting signals

• Evasion of apoptosis

• Defects in DNA repair

• Limitless replicative potential

• Sustained angiogenesis

• Ability to invade & metastasize

Acquired / environmental• DNA damaging agents• chemicals• radiations• virus Inherited mutations in

• gene affecting DNA repairning• cell growth & apoptosis

Normal cells

DNA damage

Successful DNA repair

Failure of DNA repair

Mutation in the genome of somatic cells

Activation of growth promoting oncogenes

Alteration in genes regulating the apoptosis

Inactivation of tumor supressor genes

Unregulated cell proliferation

Decreased apoptosisClonal expansion

Malignant neoplasm

Tumor progression

Angiogenesis & Escape from immunity Additional mutations

Tumor metastasis• Pathway of metastasis

1. Haematogenous spread

2. Lymphatic spread

3. Other routes

- Trancelomic spread

- Spread through the epithelial surface

- Spread through CSF

- Implantation

Mechanism & molecular basis for metastasis

CLINICAL FEATURES

• Unfortunately patients are most often identified only after development of symptoms at advanced stages of disease.

• Discomfort is the most common symptom that leads a patient to seek care & may be present at the time of diagnosis in up to 85 % of cases.

• As the high risk sites of oral carcinoma are lower lip, anterior floor of mouth & the lateral border of tongue, the examination of oral cavity should not be neglected.

• Careful assessment of cervical & submandibular lymph nodes should be done & followed by examination of oral cavity.

General features

Common signs and symptoms of head and neck cancers include:

• A chronic sore throat • Hoarseness of voice • Difficulty in swallowing • Earache • Headaches • Unusual bleeding in the mouth • A discolouration on the gums, tongue, or lining of the mouth • Nasal obstruction • Numbness of the face • Trouble when breathing or speaking • Undefined weight loss

Local features

1. Red , white or red & white lesions (flat / elevated)

2. Change in surface texture (smooth, granular, rough, crusted)

3. Chronic ulcer , not responding to conservative management

4. Ulcer with irregular edge & induration of underlying soft tissues.

5. Varying degree of pain

6. Occasional episodes of bleeding

7. Exophytic growth may present as a cauliflower like irregular growth / flat

8. Submucosal growth with surrounding indurations (pain in advanced

stages )

9. Bleeding & fixity to surrounding structures

Local features

10. Buccal mucosa cancers involving the infratemporal fossa may lead to

trismus (D/D OSMF)

11. Hypoglossal palsy & restriction of tongue mobility, progressive difficulty

in mastication & speech, pooling of saliva, friability & surface bleeding.

12. Trismus affects the nutritional status, functional impairment (obstruction

from large mass) – decrease tolerance to CT, RT & surgery.

13. Unexplained loosening of the involved tooth/teeth.

14. Tumor closer to midline & posterior in position in oral cavity/ orophaynx

may involve bilateral lymph nodes.

15. Involved lymph nodes are –

Initially – soft, mobile, non-tender, enlarged

firm to hard in texture, usually non tender,

tender (due to inflammatory response )

Advanced stage (aggressive disease) – fixation of nodes to adjacent tissue

due to invasion of cells through the capsule

16. Fixation of primary tumor to adjacent tissue overlying bone suggests

involvement of periosteum & possible spread to bone.

CLINICAL FEATURESof

SPECIFIC LESIONS

• Clinical Examination:

– Tumours, when first seen, are almost always confined to the head and neck with no distant metastasis

– Head and neck tumours are rarely irremovable, all structures can be removed with the tumour in continuity and repaired later • The majority of cases are potentially treatable

• Whether to treat or not depend on:

– the age– the health status of the patient – advance stage– local disease

• Full assessment will lead to one of the following conclusions:– Patient is potentially curable– Primary tumour is curable but patient develop another

illness– Patient is incurable but should be treated– Patient is incurable and should not be treated

• History:– Age:

• Patient are generally over 45 years.

• Tumours affecting younger age group are usually

sinister, defective immunological make-up

• Most tumours are of epithelial origin and they require

years of abuse by smoking and tobacco

• Tumours in younger patients, who do not smoke, is

usually very sinister

• Tumours developing in an immuno-compromised

patients do not respond to any treatment modality

• Complaint:

– Vary widely and is often unreliable

– Painless lump which persisted for a varying period of time

– Persistent ulceration

– Difficulty of wearing denture

– Later Symptoms:

• Pain locally or referred to the jaw or ear

• Difficulty with chewing food and swallowing

• Altered speech and respiratory difficulty

– Asymptomatic and noticed during routine dental examination

• Examination:

– Think in term of T Staging, delineate its border by

inspection and palpation

– Record and draw the lesion from different angles using

normal anatomical landmarks

– The status of teeth should be assessed as causative and if

radiotherapy is to considered

CARCINOMA OF ORAL CAVITY

CARCINOMA OF LIP

• Age and sex:– The sixth decade and Male : female ratio is 80:1

• 93% affect the lower lip with squamous cell carcinoma, exophytic type

• 5% in the upper lip and commonly basal cell carcinoma, commoner in females– Solar exposure, more radiation on the lower lip– Commoner in fair complexion– Smoker - cigarette, cigar, pipe stem – In the upper lip, SCC metastasizes earlier than lower lip

– Covered with non-keratinized stratified squamous epithelium which is

transparent, appear red, and contain no hair, sebaceous gland or pigments

– Crusted oozing, non-tender, indurated ulceration of <1 cm

– On the vermilion border it closely cover the orbicularis oris muscle but on

the lingual side mucous gland is present within the muscle and mucosa

– Perineural invasion through mental nerve

– Lymphatic drainage:• Mucosal and cutaneous systems.• Lower lip:

– One medial trunk which drain the inner third of the lip into the submental group

– Two lateral trunk which drain the outer two-third into the submandibular lymph nodes

– Anastomosis account for bilateral metastases• Upper lip:

– Drain into the periauricular, parotid, submandibular and submental lymph nodes

CARCINOMA OF LABIAL MUCOSA

• Lower labial mucosa > upper

• Tobacco pouching

• Exophytic growth , swelling, ulceration

• Unilateral or bilateral lymph nodes may be involved

CARCINOMA OF BUCCAL MUCOSA

Site : along or inferior to a line opposite to occlusion line

(distal to third molars)

Sign : painful lesion

Appearance

Metastasis : The submandibular lymph nodes to the lower deep

cervical chain

CARCINOMA OF TONGUE

• A disease of the middle age and elderly with equal

sex incidence, youngers

• 85% occurs in the lateral border of the anterior 2/3

while tip, dorsum and ventral surface are rarely

involved

• Appearance : painless indurated mass or ulcer

• The lesion may be infiltrative (small on the outside

but palpation shows deep invasion) or exophytic

and usually of the well-differentiated type

– Specialized keratinized epithelium with collection of

minor salivary gland and muscle fibres

– The interlacing muscle fibres form an easy pathway for

cancer spread and the constant movement of the tongue

disseminates the disease widely

• Excision should be wide with 2 cm

safe margin

• Lymph drainage:

– Tip of the tongue:• To the submental lymph nodes – to the lower

deep cervical chains

– The anterior 2/3:• the lower deep cervical chains – jugulo-

omohyoid nodes

– The posterior 1/3:• drain to the upper deep cervical chains

The tip and middle part of the tongue have rich bilateral capillary network

but less in the lateral margins

– Anterior medial part:

• Commoner than the lateral part

• Felame > male

• Spread medially into the ventral

surface of the tongue and laterally

• Deep spread to the base of the

tongue and the hyoglossus and

genioglossus muscles

• Shows bilateral lymphatic spread to

the submandibular and the

submental nodes

CARCINOMA OF FLOOR OF THE MOUTH

– Lateral part:

• Spread medially to the side of the tongue

• May involve sublingual &/or submandibular

glands

• Lateral spread to the alveolar ridge where

presence or absence of the teeth govern the

outcome:

– Teeth act as a barrier against buccal

spread

– In edentulous patient, the alveolar

process has resorbed and cortex is

incomplete, tumour reaches the

cancellous spaces and the canal and

spread through the nerve.

Sign & symptoms :• Painful / painless lesion • Restricted tongue movement• Slurring of speech• Excessive salivation• loosening / exfoliation of teeth• Root resorption

Deeper spread, mylohyoid muscle act as a barrier anteriorly, posteriorly

the floor is close to the skin, appear as a palpable lump in the

submandibular area.

Lymphatic drainage – through submandibular lymph nodes to the upper

deep cervical chains

CARCINOMA OF GINGIVA & ALVEOLOUS

Least associated with tobacco chewing

The lesion is usually painless

Looks like inflammatory or reactive lesion

(eg. Pyogenic granuloma)

Warts around the denture flanges

– Carcinoma of the lower alveolus affects the antero-lateral part and spread to the floor of the mouth

– Tongue and floor of the mouth tumours reach the lower alveolus by marginal spread in the mucosa and submucosa overlying the sublingual, submandibular glands and the mylohyoid muscle. They act as barrier against deep infiltration.

• Edentulous jaws, mylohyoid line is on the occlusal ridge and the loss of the cortical bone barrier will allow tumour to spread downward into the medullary cavity

– The inferior alveolar nerve provide a pathway for perineural spread in

a predominately proximal direction with little involvement of the bone

• Nerve looks clinical normal till late

• Spread is not continuous, multiple pathological samples is required

– Lymphatic spread to the submandibular lymph nodes

CARCINOMA OF PALATE

• Disease of the elderly (60 – 70 years)• Associated with reverse smoking• Common location for carcinoma of the minor salivary

gland • Presented as smooth, rounded, bulging masses• Squamous cell carcinomas present as ulcerative or

exophytic lesion

• Invade the bone at an early stage

• Involve the tonsillar pillars, soft palate, nasal

cavity, nasopharynx and the antrum

• Metastases to submandibular and upper deep

cervical chains

CARCINOMA OF OROPHARYNX

• Site : soft palate & oropharyngeal mucosa• Appearance : like other lesions• Size : greater than that of other sites• Symptoms : dysphagia (most common)

: pain (dull, sharp, radiating to ear)

• Derived from lining epithelium

of lymphoid tissue.

• Older age & male predilection

• Initial lesion is small & difficult

to detect.

CARCINOMA OF NASOPHARYNX

SIGN :• First sign is firm to hard

(enlarged) cervical lymph nodes

• Neurological symptoms

SYMPTOMS :

• Serious otitis media

• Otalgia

• Obstruction of eustachian tube

• Hearing loss

• Nasal obstruction

• Pharyngeal pain

CARCINOMA OF MAXILLARY SINUS

• The sinus is related to the orbit, nose, alveolar process, infratemporal fossa

and nasopharynx.

• It has an outlet to the nose, ethmoid sinuses and the root of the teeth

• Old age & male predilection

SIGN :• Ulceration or mass on the hard palateSYMPTOMS :

• Pain• swelling• Nasal obstruction• Unilateral nasal stiffness• Pain / paresthesia of midface

(involvement of maxillary nerve)

• The inferior orbital fissure provide a route for entry of tumours into the orbit, the periostium offer an excellent resistant barrier to spread into the orbit.

• The roots of the upper premolars and molars and the alveolus are in intimate contact to the floor.

• The infratemporal fossa is the space behind the maxillary antrum and it connects to the para-pharyngyeal space, and the sphenoid bone superiorly with foramen spinosium and ovale with their emerging nerves.

Lymphatic drainage:• Drain posteriorly to the retropharyngeal nodes • Directly to the jugulo-digastric nodes• If it cross to the nose or the cheek it will drain to submandibular lymph

nodes

Premalignant lesions & conditions

Precancerous lesion (precancer/ premalignancy)

A benign, morphologically altered tissue that has a greater than normal risk of malignant transformation .

Eg : leukoplakia

erythroplakia

mucosal changes associated with smoking habits

carcinoma insitu

Bowen disease

Actinic keratosis, cheilitis & elastosis

Leukoplakia

Mild / thin leukoplakia

Homogenous / thick leukoplakia

Ulcerated leukoplakia

Nodular/ speckled leukoplakia

Verrucous leukoplakia

Erythroleukoplakia

Malignant potential : 0.3 – 10 %

Erythroplakia

Homogenous & smooth Erythroplakia Granular Erythroplakia

Erythroleokoplakia

Mucosal changes associated with smoking habits

Stomatitis nicotina Snuff dipper's lesion

Cigarette smoker’s lip lesion

Carcinoma insitu

-Mostly involve skin- but sometime also may involve mucosa- SCC in situ is termed as – Bowen Disease

Actinic keratosis

• A cutaneous premalignant lesion

• Gives – SAND PAPER APPEARANCE

• KERATIN HORN may present

Cheilitis

Precancerous condition

It is a disease or patient’s habit that doesn’t necessarily alter the clinical appearance of the local tissue but it is associated with a greater than normal risk of precancerous lesion / cancer development in the tissue.

Eg : OSMF

syphilis

sideropenic dysphagia

OLP

Diskeratosis congenita

Lupus Erythmatosis

OSMF oral submucous fibrosis

Malignant potential : 0.2 – 0.5 % in INDIA

OLP (Oral lichen planus)

Wickham’s striae are diagnostic

Malignant potential : 0.4 – 12.3 %

OLP

Erosive lichen planus

It presents a chronic multiple oral mucosal ulcers, which occurs when there is extreme degeneration of basal cell layer of epithelium.

Malignant potential : 1 – 15 %

Diskeratosis congenita(zinssner- engman-cole syndrome)

Lupus Erythmatosis

Staging of cancer

Staging is the process subdivision of cases of cancer into same groups in which behavior will be similar.

• Over the last decade the 2 principle staging classification system of head & neck cancer, those of AJCC & UICC have undergone a convergent evolution & are now to all interest & purposes identical.

• Classification by anatomical extent of disease is determined clinically & histopathologicalyl is the one that the TNM system primarily uses:

T : enlargement of & invasion by primary tumor

N : spread to regional lymph nodes

M : spread to different metastatic sites

4 classifications –1. Clinical classification / pretreatment Clinical classification (cTNM)

2. Pathological classification / postsurgical H/P classification (pTNM)

3. Retreatment classification (rTNM)

4. Autopsy classification (aTNM)

Other descriptors

i. “m” suffix (> 1 primary at single site)

ii. “y” prefix : ycTNM, ypTNM

Gx : Grade Of Differentiation Can Not Be Assessed

G1 : Well Differentiated

G2 : Moderately Differentiated

G3 : Poorly Differentiated

G4 : Undifferentiated

Rx : Grade Of Differentiation Can Not Be Assessed

R0 : No residual tumor is present

R1 : microscopic residual tumor

R2 : macroscopic residual tumor

T. Primary Tumor

TX. Primary tumor cannot be assessed 

T0. No evidence of primary tumor 

Tis. Carcinoma in situ 

T1, T2, T3, T4. Increasing size and/or local extent of the primary tumor

N. Regional Lymph Nodes

NX. Regional lymph nodes cannot be assessed 

N0. No regional lymph node metastasis 

N1, N2, N3. Increasing involvement of regional lymph nodes

Mx : Metastasis cannot be assessed

M0 : No evidence of metastasis

M1 : Presence of metastasis

1. Barnes L, Eveson JW, Reichart PA, Sidransky D. World Health Organization classification of tumours. Pathology and genetics. Head and neck tumours. World Health Organization; 2005.

2. Isaäc van der Waal. Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management. 2009; 45(4-5):317–323

Classification schemes that histologically categorize precursor and related lesions

Definition WHO 2005

Squamousintraepithelial

neoplasia(SIN)

Ljubljana classification

system

An increase in the number of cells, but with no cellular atypia

Squamous cell

hyperplasia

Squamous cell (simple)

hyperplasia

Changes are confined to the lower third of epithelium

Mild dysplasia

SIN 1 Basal/parabasal cell hyperplasia

Changes extend to the middle third of the epithelium. Cytological changes can

be more marked

Moderatedysplasia

SIN 2 Atypical hyperplasia

Changes involve at least 2/3rd of the epithelium & atypia is more marked.

SevereDysplasia

SIN 3 Atypical hyperplasia

Changes involve the full thickness of epithelium, but no invasion of basement

membrane

Carcinomain situ

SIN 4 Carcinoma in situ