HNSCC Tumor Biology

Question 1

How many genetic mutations are seen in HNSCC pts’ genome

Answer 1

6,000-90,000

Most are ‘passenger mutations’ and are meaningless

Question 2

2 major carcinogens a/w HNSCC

Answer 2

• Tobacco smoke (4,000 toxic compounds including 81 carcinogens)
• Betel quid

Question 3

What is the most freq mutated gene in HNSCC

Answer 3

p53

Question 4

How does risk for HNSCC change based on tobacco and etoh use?

Answer 4

• Heavy tob –> Inc risk 5.8x
• Heavy etoh –> Inc risk 7.4x
• Both (male) –> Inc risk by 38x
• Both (female) –> Inc risk by 100x

Question 5

Characteristics of p16 + HNSCC in nonsmokers

Answer 5

• Better prognosis
• Fewer mutations than HNSCC in smokers
• Recent entity
• More prominent in USA

Question 6

What is leukoplakia

Answer 6

• Patch of white mucosa that doesn’t disappear by rubbing

- Exclusion Dx

Question 7

What is the rate that leukoplakia will turn to CA?

Answer 7

1-2% per year

Question 8

What percentage of leukoplakia and erythroplakia have dysplasia, premalignancy?

Answer 8

• Leukoplakia: 20%

- Erythroplakia: 90%

Question 9

What is the concept of field cancerization?

Answer 9

• The mucosa is diffusely diseased and at higher risk of developing tumor
• Even nl appearing mucosa next to cancer may have premalignancy and be a source of recurrence

Question 10

What is the 2 step process of chemical tumorgenesis?

Answer 10

1. Tumor induction - mutagen is applied to epithelium and damages the DNA leading to mutation
2. Tumor promotion - proliferation, then clonal growth

Question 11

Name 2 factors upstream of the cell cycle that impact tumorgenesis in HNSCC

Answer 11

1. EGFR (inc proliferation)

2. TGF-B (dec proliferation)