High-grade squamous intraepithelial lesion of the cervix

What is high-grade squamous intraepithelial lesion?

High-grade squamous intraepithelial lesion (HSIL) is a pre-cancerous disease that develops in the cervix. HSIL is called a pre-cancerous disease because over time it can turn into a type of cancer called squamous cell carcinoma. Because HSIL is a non-cancerous disease, the abnormal cells are unable to spread into the tissues outside of the cervix or to other parts of the body such as lymph nodes.

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 outer part of 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 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).​ The most common types of high-risk HPV to cause HSIL are HPV-16 and HPV-18.

How do pathologists make this diagnosis?

The diagnosis of HSIL is usually made after a small tissue sample is removed during a Pap test or a biopsy. The diagnosis can also be made when part or all of the cervix is removed for another reason.

When examined under the microscope, the abnormal squamous cells in HSIL are darker and larger than normal squamous cells. The chromatin (genetic material) which is found inside the nucleus of the cell may be described as coarse or vesicular which means it is divided into small groups. In a Pap smear, the abnormal squamous cells often form small groups but individual abnormal cells may also be seen.

When a larger tissue sample is removed in a biopsy or excision, the abnormal squamous cells will only be seen in the epithelium at the surface of the tissue. Unlike normal, healthy squamous cells, the abnormal cells do not become smaller and flatter as they move from the bottom of the epithelium to the top.

high grade squamous intraepithelial lesion cervix


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 your pathologist saw the p16 protein in the abnormal cells.

What happens after high-grade squamous intraepithelial lesion is diagnosed on a Pap test?

After being diagnosed with HSIL your doctor should refer you to a specialist who will perform a colposcopy. A colposcopy allows your doctor to see the entire outer surface of the cervix.​ During the colposcopy, the doctor will be looking for any areas that look abnormal on the surface of the cervix. If an abnormality is found, the doctor may decide to take a small biopsy, to confirm the diagnosis of HSIL and to look for squamous cell carcinoma. Your doctor may also take a small sample of tissue from the endocervical canal and endometrium.​

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

There are several treatment options available:​

  • Laser ablation – A laser is used to remove the abnormal squamous on the surface of the cervix.
  • Loop electrosurgical excision procedure (LEEP) – A special type of knife is used to remove the tissue from the surface of the cervix.
  • Large loop excision of the transformation zone (LLETZ) – Similar to LEEP (above).
  • Cold knife cone biopsy – Similar to LEEP (above).
  • Hysterectomy – In this procedure, the entire uterus and cervix are removed. This procedure is usually only performed when squamous cell carcinoma is found and for large tumours.​

There are many factors to consider when deciding which treatment option is best for you. Talk to your doctor about the options available.

​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. 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. Finding HSIL at the margin increases the risk that the tumour will grow back in that location.

by Jason Wasserman, MD PhD FRCPC (updated July 20, 2021)
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