SQUAMOUS CELL CARCINOMA:

RISK FACTORS & PATHOGENESIS

EESHAH MARYIUM (ROLL # 37)
KINZA ANSARI (ROLL # 81)
INTRODUCTION

Squamous cell carcinoma, also known as Epidermoid

carcinoma, is a malignant neoplasm of stratified squamous
epithelium that is capable of locally destructive growth and
distant metastasis.
It is the most common malignant neoplasm of oral cavity.
SITES & EPIDEMIOLOGY
It occurs in various oral sites:
• Lower lip (most common)
• Lateral borders of tongue
• Floor of the mouth
The incidence varies between 2-10 per 100000 population per year. The incidence of
oral carcinoma in blacks is somewhat lower than whites. SCC usually occurs after the
fourth decade of life. They are responsible for 2% of annual deaths in males and 1%
in females. The incidrnce differs significantly, depending upon the tobacco habits.
ETIOLOGY

• Multifactorial
• No single causative agent or factor (carcinogen) has been clearly defined or
accepted.
• More than single factor is needed to produce such a malignancy
(carcinogenesis)
ETIOLOGY

INTRINSIC FACTOTS (SYSTEMIC OR

EXTRINSIC FACTORS GENERALIZED STATES)
• Tobacco smoke • Malnutrition
• Alcohol • Iron deficiency anemia
• Dyskeratosis congenita
• Sunlight
• Fanconi amemia
 RISK FACTORS: TOBACCO SMOKING
(CIGARETTES, CIGARS & PIPE)
• It contaions more than 70 known carcinogens. Its major components are:
Nitrosamine, Arsenic, Benzopyrene, benzene, etc.
• Smoked tobacco produces free radicals and oxidants that promote the
destruction and counteract the protective effects of endogenous oxidants.
• The pooled risk for oral cancer is approximately 3 times greater among
smokers than non-smokers.
• Its relative risk (RR) is dose dependent.
TOBACCO SMOKING

• Bidi smoking is associaged with an approximately threefold greater risk of

oral cancer compared to cigarette smoking.
• The highest_ practice of reverse smoking is popuar, especially among women.
SMOKELESS TOBACCO

• Increased risk associated with moist snuff and chewing tobacco.

• Comparitively less risk associated with dry snuff
• 50% of all oral cancers in smokeless tobacco users occurs at the site of whrre
the tobacco is habitually placed.
BETEL QUID (PAN)

• Combination of natural substances (i.e., areca palm nuts, betel leaf, slaked lime and
perhaps Tobacco leaf) are chewed foe their psychostulatory effects.
• The carcinogenicity of betel quid has been attributed to tobacco although Areca nut
alone also appears to be carcinogenic.
• It is also asdociated with the development of precancers such as leukoplakias.
• Chronic placement of pan in the mouth usually leads to OSF which is a premalignant
condition
ALCOHOL CONSUMPTION

• The evidence for a direct topical effect by orally ingested alcohol is lacking,
because most chronic alcohol drinkers are also smokers.
• Most investigators believe, it is related to liver damage (cirrhosis).
• The association between cirrhosis of liver and scc of the floor of the mouth and
tongue is especially high.
RADIATIONS
• Radiotherapy of head and
neck increases the risk
• Dose depemdent
realtionship exists.
INFECTIONS

• Human papilloma virus

• Epstein Barr virus
• Human immunodeficiency virus
• Candida albicans
• Treponema pallidum
IMMUNOSUPPRESSION

Aids predisposes relatively young individuals to various oral and non-oral

malignancies. Patients with HIV infection and those who are undergoing
immunosuppressive therapy for mailgnancy or organ transplantation are at
increased risk of oral SCC And other head nd neck malignancies especially
when Tobacco smoking and alcohol abuse are present.
DIETARY FACTORS

• High intake of fruits and vegetables decreases the risk of numerous cancer
tyes including the oral cancer.
• May be related to the protective effects of vitamin A, vitamin C, vitamin E,
fibers and folate present within plant food.
• Animal fats and processed or salted meats may increase the risk for oral
cancer.
• Patients with chronic iron deficiency anemia (Plummer Vinson Syndrome)
develop epithelial atrophy of GIT, including that or oral cavity, and have
increased susceptibility to esophageal and oral cacinomas.
PREEXISTING ORAL DISEASES

• Oral submucous fibrosis predisposes oral mucosa to develop squamous cell

carcinoma.
• Some evidence exists that chronic forms of oral lichen planus also predisposes
the oral mucosa to decelop SCC.
PATHOGENESIS

HPV:
• HPV has 4 genes E1 E2 E6 and E7.
• In early stages when HPV virus infect the cells,E1 and E2 genes become dormant.
• E6 genes bind with p53 and leads to its ubiquitin mediated lysis.
• E7 binds with Rb gene which leads to the removal of E2F factor ,thus promoting the
cell cycling as there is no p53 that prevents the phosphorylation of Rb genes.
PATHOGENESIS
PATHOGENESIS

Malfunctioning growth receptors

• Basal cells of oral epithelium have high mitotic activity.
• Under normal circumstances,growth factors bind with tyrosine kinase receptors with
leads to activation of of its intracellular domain and normal poliferation.
• But in case of mutated growth receptors,the receptor proteins deliver continuous
mitogenic signals even in the absence of autocrine or paracrine action.
PATHOGENESIS

Malfunctioning growth factors

• When abnormal grrowth factors bind with receptor,it evoke the activity of kinase within the
cytoplasm and leads to phosphorylation.
• By using singal transduction pathway the growth factors activate the transcription factors.
• There are 3 proteins that are involve in cell cycle.
• Cyclins
• Cyclin dependent kinase
• Cyclin dependent kinase inhibitors(p16,p53,p21)
PATHOGENESIS

• mRNA is now translated to cyclins and CDKs.

• But there will be no CDK inhibitors synthesis ,thus no inhibition of CDKs
• The cyclins and CDKs now causes the phosphorylation of Rb and release of
E2F transcription factor from its binding site and promote cell cycling.