Cervix -

High grade squamous intraepithelial lesion (HSIL)

This article was last reviewed and updated on July 16, 2019
by Jason Wasserman, MD PhD FRCPC

Quick facts:

  • High grade squamous intraepithelial lesion (HSIL) is a pre-cancerous disease that develops in the cervix.

  • HSIL is caused by a virus called human papillomavirus (HPV).

  • If left untreated, patients with HSIL are at high risk for developing a cancer of the cervix called squamous carcinoma.


The normal cervix

The cervix is part of the female genital tract. It is found at the bottom of the uterus where it forms an opening and a canal into the endometrial cavity of the uterus.


The outer surface of the cervix is lined by two types of cells that form a barrier called the epithelium. The first part of the cervix is called the exocervix and it is lined by squamous cells. The second part of the cervix is called the endocervical canal and it is lined by rectangular shaped cells which connect together to make small structures called glands.


The tissue below the epithelium is called the stroma and is made up of connective tissue and blood vessels. 

What is high grade squamous intraepithelial lesion (HSIL)?

High grade squamous intraepithelial lesion (HSIL) is a pre-cancerous condition. The disease starts from the squamous cells in the exocervix. HSIL is considered a pre-cancerous disease because over time it can turn into an invasive cancer called squamous cell carcinoma.


The diagnosis of HSIL means that abnormal cells were seen only in the epithelium. No abnormal cells were found in the stroma below the epithelium. In contrast, squamous cell carcinoma develops when the abnormal cells move from the epithelium into the stroma. The movement of cancer cells into the stroma is called invasion.

Why is this important? The abnormal cells in HSIL are unable to spread to tissues outside of the cervix or to other parts of the body such as lymph nodes.

What causes high grade squamous intraepithelial lesion?

Almost all cases of HSIL and squamous cell carcinoma in the cervix are a result of the normal squamous cells becoming infected with a high risk type of human papillomavirus (HPV).

How do pathologists make this diagnosis?

The diagnosis of HSIL is usually made on a pap smear and a larger surgical procedure is later performed to remove the disease and to look for abnormal cells in the stroma.​

​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 HSIL in your report.

For example, your report may say "3 out of 14 blocks are positive for high grade squamous intraepithelial lesion (HSIL)" which means that 3 out of the 14 pieces of tissue examined show the disease.


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. Typical margins include:


  • 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.

  • Stromal margin - This is the tissue inside the wall of the cervix.

A margin is considered positive when HSIL is seen at the edge of the cut tissue.

Why is this important? Finding HSIL at the margin increases the risk that the tumour will grow back in that location.

p16 status

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. 


Why is this important? Almost all cases of HSIL are positive or reactive for p16 which means your pathologist saw the p16 protein in the abnormal cells.

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