HSIL (high grade squamous intraepithelial lesion) of the cervix

by Jason Wasserman MD PhD FRCPC
December 23, 2022

What is high-grade squamous intraepithelial lesion of the cervix?

High-grade squamous intraepithelial lesion (HSIL) is a pre-cancerous condition that starts from cells on the outside surface of the cervix. If not treated it can lead to a type of cervical cancer called squamous cell carcinoma.

What causes high-grade squamous intraepithelial lesion of the cervix?

HSIL is a sexually transmitted disease caused by infection with human papillomavirus (HPV). The virus infects specialized squamous cells on the outside surface of the surface. Over time the infected cells develop genetic changes which lead to HSIL. There are many types of HPV but most cases of HSIL are caused by the high-risk types 16 and 18.

Normal cervix

Is high-grade squamous intraepithelial lesion of the cervix a type of cancer?

No. HSIL is not cancer although patients with HSIL are at increased risk for developing a type of cervical cancer called squamous cell carcinoma. For this reason, most patients with HSIL are offered treatment to remove the area of abnormal tissue.

How is this diagnosis made?

The diagnosis of HSIL is usually made after some cells are removed from the cervix 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. The tissue sample is then sent to a pathologist who examines it under the microscope.

What does high-grade intraepithelial lesion look like under the microscope?

When examined under the microscope, the abnormal squamous cells in HSIL are darker and larger than the squamous cells normally found in the cervix. 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
In this image of the cervix, normal squamous cells can be seen on the left side of the image. HSIL can be seen on the right side of the image. The squamous cells in this area are darker and the nuclei are larger.

What is p16 and why is it important?

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. ​Talk to your doctor about the options available.

What is a margin?

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 such as an excision or resection, your pathologist will examine the margin closely to ensure there are no abnormal cells at the cut edge of the tissue. 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.

The number and type of margins described in your report will depend on the type of procedure performed to remove the tumour from your body. Your report will not describe margins after a Pap test or biopsy.

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.



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