Squamous cell carcinoma of the cervix

What is squamous cell carcinoma?

Squamous cell carcinoma is a type of cervical cancer. The tumour starts from the squamous cells on the surface of the cervix. Most tumours arise from a pre-cancerous disease called high grade squamous intraepithelial lesion (HSIL).

The cervix

The cervix is part of the female genital tract. It is found at the bottom of the uterus where it forms an opening into the endometrial cavity. The cervix is lined by specialized cells called squamous cells that form a barrier on the surface of the cervix called an epithelium.  The tissue below the epithelium is called the stroma.

What causes squamous cell carcinoma?

Almost all cases of squamous cell carcinoma and HSIL in the cervix are a result of the normal squamous cells in the cervix becoming infected with a high-risk type of virus called human papillomavirus (HPV). Pathologists often indirectly look for HPV by performing a test called immunohistochemistry for a protein called p16. Cells infected with HPV will be positive for p16.

How do pathologists make this diagnosis?

The diagnosis of squamous cell carcinoma is usually made after a small sample of tissue is removed from the cervix during a Pap test. The diagnosis can also be made after a larger sample of tissue is removed in a biopsy or resection.​

What to look for in your report after the tumour has been removed

Tumour size

This is the size of the tumour, measured in three dimensions. The tumour size is used to determine the tumour stage (see Pathologic stage below). The tumour size can only be determined after the entire tumour has been removed. It cannot be measured on tissue from a Pap smear.​

1. Length – The tumour is measured from top to bottom.
2. Width – The tumour is measured from side to side.
3. Depth of invasion – The tumour is measured from the epithelium on the surface of the cervix to the cancer cells at the very deepest point of invasion.​

Extent of disease

Larger samples of tissue are usually sent for pathological examination as a single piece of tissue and the tissue is then divided into multiple sections before being examined under the microscope. Your pathologist will describe the number of pieces (or ‘blocks’ as they are often called) that show squamous cell carcinoma or HSIL in your report. For example, your report may say “3 out of 14 blocks are positive for squamous cell carcinoma” which means that 3 out of the 14 pieces of tissue examined contain cancer.

Tumour extension

Tumour extension describes the distance the cancer cells have travelled from their starting point in the cervix. All tumours start in the cervix however larger tumours can grow to involve the endometrium, vagina, bladder, or rectum. The soft tissue that surrounds and support the cervix is called the parametrium. This tissue will be carefully examined for cancer cells.

Your pathologist can only determine the tumour extension after the entire tumour has been removed. It will not be described in your report after a pap smear or a biopsy. Tumour extension into the parametrium or other organs around the cervix is associated with a worse prognosis and is used to determine the tumour stage (see Pathologic stage below).

Stromal invasion

The squamous cells at the surface of the cervix form a barrier called the epithelium. The tissue below the epithelium is called the stroma. When cancer cells enter the stroma it is called stromal invasion.

After examining your tissue sample, your pathologist will measure the amount of stromal invasion in two directions:​

1. Depth of invasion – This is the amount of invasion measured from the surface of the tumour to the deepest point of invasion.
2. Horizontal extent of invasion – This is the amount of invasion measured from one side of the tumour to the other.​

The size of stromal invasion is not the same as the tumour size because the tumour size also includes any HSIL that may be above the area of invasion. For that reason, the size of the tumour may be larger than the size of the stromal invasion.

The amount of stromal invasion is used to determine the tumour stage (see Pathologic stage below). In general, less stromal invasion is associated with a better prognosis while more invasion is associated with a worse prognosis.

Lymphovascular invasion

Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph which contains waste and immune cells moves around the body through lymphatic channels.

Cancer cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of cancer cells from the tumour to another part of the body is called metastasis.

Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion. Lymphovascular invasion increases the risk that cancer cells will be found in a lymph node or a distant part of the body such as the lungs.

Lymph nodes

Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of cancer cells from the tumour to a lymph node is called metastasis.

Your pathologist will carefully examine all lymph nodes for cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative. Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells.

Lymph nodes on the same side as the tumour are called ipsilateral while those on the opposite side of the tumour are called contralateral.

Lymph nodes examined are usually divided into those found in the pelvis and those found around a large blood vessel in the abdomen called the aorta. The lymph nodes found around the aorta are called para-aortic.

If cancer cells are found in a lymph node, the size of the area involved by cancer will be measured and described in your report.

• Isolated tumour cells – The area inside the lymph node with cancer cells is less than 0.2 millimetres in size.
• Micrometastases – The area inside the lymph node with cancer cells is more than 0.2 millimetres but less than 2 millimetres in size.
• Macrometastases – The area inside the lymph node with cancer cells is more than 2 millimetres in size.

Cancer cells found in a lymph node is associated with a higher risk that the cancer cells will be found in other lymph nodes or in a distant organ such as the lungs. The number of lymph nodes with cancer cells is also used to determine the nodal stage (see Pathologic stage below).

Margins

A margin is any tissue that has to be cut by the surgeon in order to remove the tumour from your body. Pap smears do not have margins.

If you underwent a surgical procedure to remove the entire tumour from your body, your pathologist will examine the margin closely to make sure there are no cancer cells at the cut edge of the tissue.

The number and type of margins will depend on the type of procedure performed to remove the tumour from your body.

• Endocervical margin – This is where the cervix meets the inside of the uterus.
• Ectocervical margin – This is the bottom of the cervix, closest to the vagina.
• Deep margin – This is the tissue inside the wall of the cervix.
• Radial margin – This is the soft tissue that surrounds the cervix. The radial margin will only be described in your report if you had your entire cervix and uterus removed at the same time.

A margin is considered positive when the cancer cells are seen at the edge of the cut tissue. If HSIL is seen at the margin that will also be described in your report.​ Finding cancer cells at the margin increases the risk that the tumour will grow back in that location.

Pathologic stage (pTNM)

​The pathologic stage for squamous cell carcinoma of the cervix is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer.

This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M)  to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means more advanced disease and a worse prognosis.

Tumour stage (pT) for squamous cell carcinoma

• T1a – Tumours in this category were found only after the tissue was examined under the microscope. These tumours also have a depth of invasion that is 5 millimetres or less AND and a horizontal spread that is 7 millimetres or less (see Stromal invasion above).
• T1b – The tumour was seen by your doctor during your physical examination OR the depth of invasion is greater than 5 millimetres OR the horizontal spread greater than 7 millimetres.
• T2a – The tumour extends outside of the uterus but not into the parametrium (see Tumour extension above).
• T2b – The tumour extends into the parametrium.
• T3a – The tumour extends to the lower part of the vagina.
• T3b – The tumour extends into the wall of the pelvis OR the tumour has caused injury to the kidney.
• T4 – The tumour extends into the bladder or rectum OR the tumour extends outside of the pelvis into the abdomen.

Nodal stage (pN) for squamous cell carcinoma

• NX – No lymph nodes were sent to pathology for examination.
• N0 – No cancer cells were found in any of the lymph nodes examined.
• N0(i+) – Only isolated cancer cells were found in a lymph node.
• N1 – A group of cancer cells larger than 0.2 millimetres was found in at least one lymph node.

Metastatic stage (pM) for squamous cell carcinoma

Squamous cell carcinoma is given a metastatic stage 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 determined 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.

by Jason Wasserman, MD PhD FRCPC (updated July 22, 2021)