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Tumor Biology


Key Points

  • 1.

    Cancer development requires an accumulation of genetic and cellular alterations.

  • 2.

    The most common risk factors associated with head and neck squamous cell cancer in the United States are tobacco use, alcohol use, and the HPV virus (type 16).

  • 3.

    HPV-positive and HPV-negative HNSCC have different drivers of carcinogenesis.

  • 4.

    There are recurring DNA translocations and receptor overexpression patterns in different salivary gland cancers.

  • 5.

    The key molecular drivers in differentiated thyroid cancer are BRAF mutations and RET translocations.

  • 6.

    Dysregulation of cell cycle progression, angiogenesis, and immune tolerance are hallmarks of tumorigenesis.

  • 7.

    Therapies targeting EGFR and immune checkpoint inhibitors are approved in HNSCC, with many more novel targeted therapies under investigation.

Questions

1

What is the multi-hit theory of carcinogenesis?

This theory postulates that cells must acquire multiple mutations or aberrations in order to develop into cancer. Different types of tumors may result from different cellular changes.

2

What biological processes contribute to cancer development, growth, and persistence?

  • Aberrant cell signaling controlling mitosis and cell differentiation

  • Decreased apoptosis (programmed cell death)

  • Angiogenesis (the growth of new blood vessels)

  • Immune system dysregulation and evasion

3

What are some molecular techniques used to analyze causes of head and neck cancer development?

  • Immunohistochemistry (IHC): stains for proteins in tumor specimens

  • Fluorescence in situ hybridization (FISH): uses fluorescent probes to analyze for DNA translocations

  • Next-generation sequencing: several methods that allow a wide number of genes to be analyzed for mutations and/or fusions simultaneously

4

What are oncogenes, proto-oncogenes, and tumor suppressor genes?

An oncogene is a gene that confers the potential to cause cancer, and a proto-oncogene is a normal gene that can contribute to cancer formation when mutated. A tumor suppressor gene is one that protects a cell from transitioning to cancer. Mutations in tumor suppressor genes that cause loss of function may allow the cell to progress to cancer, especially when combined with overexpression of oncogenes and mutations in proto-oncogenes.

Squamous Cell Carcinomas of the Head and Neck

5

What are the most common risk factors for head and neck squamous cell cancer (HNSCC) worldwide?

  • Tobacco use

  • Alcohol consumption

  • Human papillomavirus (HPV) infection, especially in oropharyngeal cancer

  • Betel nut chewing

  • Epstein-Barr virus (EBV) in nasopharyngeal cancer

  • Viral infections with hepatitis C (HCV) and human immunodeficiency virus (HIV)

  • Immunosuppression

6

What is the concept of field cancerization?

Field cancerization refers to epithelium changes adjacent to an invasive cancer showing precancerous alterations such as dysplasia or carcinoma in situ. This is more common in smoking-related cancers, implying that such risk factors may be more broadly impacting the tissues.

7

Which “high-risk” HPV virus type is most implicated in HNSCC?

HPV type 16. Less commonly found are HPV types 18, 31, and 33.

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