Vagina -

High grade squamous intraepithelial lesion (HSIL)

This article was last reviewed and updated on October 31, 2018
by Emily Goebel, MD  FRCPC

Quick facts:

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

  • HSIL is caused by a virus called human papillomavirus (HPV) that infects the cells in the vagina.

  • If not treated, patients with high grade squamous intraepithelial lesion are at high risk for developing a cancer called squamous carcinoma.


The normal vagina

​The vagina is part of the female genital tract.  It forms a canal that starts at the cervix and ends at the vulva on the outside of the body.  The vagina is lined by special cells called squamous cells that form a barrier on the inner lining of the vagina called the epithelium. The tissue beneath the epithelium is called the lamina propria and contains blood vessels and connective tissue. Together, the epithelium and lamina propria are called mucosa.

What is high grade squamous intraepithelial lesion (HSIL)?

High grade squamous intraepithelial lesion (HSIL) is  pre-cancerous disease that develops in the vagina when the squamous cells become infected with a virus called human papillomavirus (HPV).

HSIL is called a pre-cancerous disease because it can, over time, turn into a cancer (a malignant tumour) called squamous cell carcinoma. The cells in HSIL are abnormal and look almost identical to cancer cells, however, they are only seen in the epithelium and no abnormal cells are found in the lamina propria.

HSIL of the vagina was previously called to as vaginal intraepithelial neoplasia (VAIN2-3) and some reports may still use this terminology.

The diagnosis of HSIL is usually made after a small sample of tissue is removed in a procedure called a biopsy and a larger surgical procedure (for example, an excision or vaginectomy) is later performed to remove the disease and look for abnormal cells in the lamina propria.


A margin is any tissue that needs to be cut by the surgeon to remove the tumour from your body. A margin is considered positive when HSIL is seen at the cut edge of the tissue.
Margins will only be described in your report after all the diseased tissue is removed.

Why is this important? HSIL seen at the cut edge of the tissue (a positive margin) increases the risk that the disease will come back in the same location after surgery.

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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