High grade squamous intraepithelial lesion of the anal canal

What is a high-grade squamous intraepithelial lesion of the anal canal? 

A high-grade squamous intraepithelial lesion (HSIL) is a pre-cancerous disease that starts from the squamous cells in the mucosa of the anal canal. HSIL is called a pre-cancerous disease because over time it can turn into a type of cancer called squamous cell carcinoma.

Unlike squamous cell carcinoma, the abnormal cells in HSIL are unable to spread to tissues outside of the anal canal or to other parts of the body such as lymph nodes. The abnormal cells in HSIL are found only in the squamous mucosa.

The anal canal

The anal canal is the last part of the gastrointestinal tract. It connects the rectum to the anus. The anus is the external opening where fecal matter is released from the body. The anal canal is made up of 3 layers of tissue:

  1. Mucosa – The mucosa is the tissue that lines the inside of the anal canal. Within the mucosa of the anal canal, there are three zones: 1) colorectal zone, 2) transition zone and 3) squamous zone. The first is called the colorectal zone. It is made of epithelial cells that form glands. The second is the transition zone. In this zone, the epithelium changes from glands to specialized squamous cells. The transition point is called the dentate line. The third is the squamous zone. This zone is made entirely of squamous cells. The squamous zone connects with the skin at the very end of the anal canal.
  2. Submucosa – The submucosa contains many thick blood vessels that carry blood and lymphatic channels that carry waste and excess fluids away from the tissue.
  3. Muscle layer – This part of the anal canal is made up of different types of muscles which give the anal canal strength to store fecal matter and control defecation.

What causes a high-grade squamous intraepithelial lesion (HSIL) of the anal canal? 

Almost all cases of HSIL and squamous cell carcinoma in the anal canal arise from an infection of the normal squamous cells by a human papillomavirus (HPV). There are many different types of HPV and each type is given a number. HSIL of the anal canal is most likely to be caused by HPV types 6, 11, 16,18, and 51. These types are called “high risk” because of their association with both HSIL and cancer of the anal canal.

How do pathologists make this diagnosis? 

If your doctor is concerned that you may have an abnormality of your anal canal, they will perform a procedure called anoscopy. During anoscopy, your doctor will insert an instrument called an anoscope into your anal canal. An anoscope has a light source that allows your doctor to see the entire inner surface of the anal canal. If there is an area of abnormal tissue, your doctor may take a small sample of tissue called a biopsy.

In some hospitals, doctors may insert a special swab into the anal canal instead of performing a biopsy. The swab collects tissue cells from the surface of the anal canal. The specimen that is collected is called a cytology specimen.

After tissue samples from the anal canal have been collected, they are examined under a microscope by a pathologist. Unlike normal, healthy squamous cells, the nuclei of HSIL do not become smaller and flatter as they move from the bottom of the epithelium to the surface. Instead, the nuclei of HSIL are larger and darker and are found equally in all of the epithelial layers. The chromatin (genetic material) which is found inside the nuclei of the HSIL cells may be described as “coarse” or “vesicular”. Many dividing cells called mitotic figures may also be seen.  This indicates that the tissue is growing rapidly.

What is p16? 

Cells infected with high-risk types of human papillomavirus (HPV) produce large amounts of a protein called p16. Your pathologist may perform a test called immunohistochemistry to look for p16 inside the abnormal cells. This will confirm the diagnosis of HSIL and rule out other conditions that can look like HSIL under the microscope. Almost all cases of HSIL are positive or reactive for p16 which means that your pathologist saw the p16 protein in the abnormal cells.

What happens after HSIL is diagnosed?

All patients with HSIL should be followed closely or offered treatment to remove the disease.

There are several treatment options available for HSIL:

  • Local ablative therapy – Radiofrequency ablation or electrocautery can be used to remove the atypical tissue from the anal canal.
  • Topical therapy – A medication (e.g. trichloroacetic acid, imiquimod, 5-fluorouracil) can be applied to specific lesions or to the entire anal canal.
  • Surgery – Removal of the abnormal tissue through surgery may be recommended by your doctor if there is concern that there may also be squamous cell carcinoma. 

Please talk to your doctor about which of the options is best suited to you.

by Catherine Forse MD FRCPC (updated July 19, 2021)
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