HPV-associated squamous cell carcinoma of the oropharynx

by Jason Wasserman MD PhD FRCPC
August 25, 2022

What is HPV-associated squamous cell carcinoma of the oropharynx?

HPV-associated squamous cell carcinoma (SCC) is a type of oropharyngeal cancer. The oropharynx is an area of the throat that includes the tonsils, base of the tongue, uvula, and soft palate. This type of cancer quickly spreads to lymph nodes especially those in the neck. For many patients, the first sign of the disease is a noticeable lump in the neck.

What causes HPV-associated squamous cell carcinoma of the oropharynx?

As the name suggests, HPV-associated SCC is caused by human papillomavirus (HPV). The virus infects cells normally found in the oropharynx which over time causes these cells to become cancerous.

What are the symptoms of HPV-associated squamous cell carcinoma of the oropharynx?

Symptoms of HPV-associated SCC of the oropharynx include throat pain, a sensation of fullness in the back of the throat, and difficulty swallowing. However, many patients with HPV-associated SCC of the oropharynx do not experience any throat-related symptoms and only come to medical attention as a result of enlarged lymph nodes in the neck.

How is the diagnosis of HPV-associated squamous cell carcinoma in the oropharynx made?

The diagnosis of HPV-associated SCC is usually made after a small tissue sample is removed in a procedure called a biopsy. The biopsy may be taken from a part of the oropharynx such as the tonsil or base of tongue or it may be taken from an enlarged lymph node in the neck. The diagnosis can also be made after the entire tumour is removed although this is much less common.

What does it mean if the tumour is positive for p16?

p16 is a protein that is produced by both normal cells and cancer cells. Pathologists perform a special test called immunohistochemistry in order to be able to see p16 protein inside cells. Tumours caused by human papillomavirus (HPV) produce extra p16 which builds up inside the cancer cells. For this reason, most HPV-associated SCCs are described as positive for p16.

What does metastatic HPV-associated squamous cell carcinoma mean?

Metastatic is a term doctors use to describe cancer cells that have spread to another part of the body such as a lymph node. If lymph nodes or other types of tissues outside of the oropharynx were examined and any contained cancer cells, this will be described in your report as metastatic HPV-associated SCC. The number of lymph nodes that contain cancer cells is used to determine the pathologic nodal stage.

What does it mean if the tumour is described as non-keratinizing?

Most HPV-associated SCCs are described as “non-keratinizing” because the cancer cells are not producing significant amounts of a specialized protein called keratin. Cells that produce large amounts of keratin tend to look pink when examined under the microscope. In contrast, the cancer cells in a non-keratinizing tumour look blue.

What does it mean if the tumour is described as keratinizing?

HPV-associated SCC is described as “keratinizing” if the cancer cells are producing large amounts of a specialized protein called keratin. When examined under the microscope, cancer cells that produce large amounts of keratin appear pink. In contrast, the cancer cells in a non-keratinizing tumour look blue.

What is a margin?

A margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. The types of margins described in your report will depend on the organ involved and the type of surgery performed. Margins will only be described in your report after the entire tumour has been removed.

A negative margin means that no tumour cells were seen at any of the cut edges of tissue. A margin is called positive when there are tumour cells at the very edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will recur in the same site after treatment.

What is the pathologic stage (pTNM) for HPV-associated squamous cell carcinoma of the oropharynx?

​The pathologic stage for HPV-associated SCC of the oropharynx can only be determined after the entire tumour has been removed and sent to a pathologist for examination under the microscope. Your doctors will use the information in the pathologic stage to determine the final clinical stage.

Tumour stage (pT) for HPV-associated squamous cell carcinoma

HPV-associated SCC of the oropharynx is given a tumour stage between 1 and 4. The tumour stage is based on the size of the tumour and whether the tumour has grown to include parts of the mouth or throat outside of the oropharynx.

• T1 – The tumour is 2 cm or smaller.
• T2 – The tumour is greater than 2 cm but not larger than 4 cm.
• T3 – The tumour is larger than 4 cm but is still only located within the oropharynx.
• T4 – The tumour has spread into tissues outside of the oropharynx such as the deep muscles of the tongue, the larynx, or the bone of the lower jaw (the mandible).

Nodal stage (pN) for HPV-associated squamous cell carcinoma

HPV-associated SCC is given a nodal stage between 0 and 2 based on the number of lymph nodes that contain cancer cells.

• ​N0 – No cancer cells are found in any of the lymph nodes examined.
• N1 – Cancer cells are found in 1 to 4 lymph nodes examined.
• N2 – Cancer cells are found in more than 4 lymph nodes examined.

Metastatic stage (pM) for HPV-associated squamous cell carcinoma

These tumours are given a metastatic stage (pM) of 0 or 1 based on the presence of cancer cells at a distant site in the body (for example the lungs). The metastatic stage can only be assigned if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as pMX.