Cervical intraepithelial neoplasia (CIN)

by Jason Wasserman MD PhD FRCPC
December 13, 2023

Cervical intraepithelial neoplasia (CIN) is a pre-cancerous disease caused by human papillomavirus (HPV). It is composed of abnormal squamous cells that have been infected and transformed by the virus. The squamous cells are found in a part of the cervix called the transformation zone.

CIN is called a pre-cancerous disease because over time it can change into a type of cervical cancer called squamous cell carcinoma. CIN is divided into three levels – CIN1, CIN2, and CIN3 – and the risk of developing cancer is lowest with CIN1 and highest with CIN3.

How is this diagnosis made?

The diagnosis of CIN starts with the microscopic examination of cells or tissue from the cervix. The cells or tissue can come from a Pap test, biopsy, or excision.

How do pathologists grade cervical intraepithelial neoplasia?

When examined under the microscope, the squamous cells in the epithelium on the surface of the cervix look abnormal. Pathologists divide cervical intraepithelial neoplasia (CIN) into three levels – CIN1, CIN2, and CIN3 – based on the amount of epithelium that has been replaced by the abnormal squamous cells. Your pathology report should include the type of CIN seen (for example CIN1) and for larger tissue samples, whether CIN was seen at the margin of the tissue (see below for more information about margins).

Cervical intraepithelial neoplasia 1 (CIN1)

In CIN1, abnormal cells are found mostly in the lower one-third of the epithelium and abnormal cells called koilocytes are often seen. Koilocytes are larger than normal squamous cells and the nucleus of the cell (the part that holds the genetic material) is often hyperchromatic (darker) and irregular in shape. A clear space may be seen around the nucleus. Pathologists describe this space as a ‘halo’ because it looks like a ring surrounding the nucleus. Some koilocytes may have more than one nucleus. These cells are called binucleated or multinucleated. Koilocytes look abnormal because they have been infected by HPV. An increased number of mitotic figures (dividing cells) may also be seen. Another name for CIN1 is low grade squamous intraepithelial lesion (LSIL). The risk of developing cancer with CIN1 is low and for most women, the condition will resolve over time without treatment.

Cervical intraepithelial neoplasia 2 (CIN2)

In CIN2, abnormal cells are found mostly in the lower two-thirds of the epithelium. The abnormal cells are hyperchromatic (darker) and they lack the maturation that is normally seen as the squamous cells move towards the surface of the epithelium. As a result, the cytoplasm (body of the cell) is small compared to the nucleus (the part that holds the genetic material) and it looks less pink. An increased number of mitotic figures (dividing cells) are typically seen and some of these mitotic figures may be dividing in an abnormal way that results in an unequal distribution of genetic material between the two new cells. Pathologists call this cell an atypical mitotic figure. Another name for CIN2 is high grade squamous intraepithelial lesion (HSIL). The risk of developing cancer with CIN2 is higher than with CIN1 but lower than with CIN3.

Cervical intraepithelial neoplasia 3 (CIN3)

In CIN3, abnormal cells are found throughout the entire epithelium (from the top to the bottom). The abnormal cells are hyperchromatic (darker) and they lack the maturation that is normally seen as the squamous cells move towards the surface of the epithelium. As a result, the cytoplasm (body of the cell) is small compared to the nucleus (the part that holds the genetic material) and it looks less pink. An increased number of mitotic figures (dividing cells) are typically seen and some of these mitotic figures may be dividing in an abnormal way that results in an unequal distribution of genetic material between the two new cells. Pathologists call this cell an atypical mitotic figure. Another name for CIN3 is high grade squamous intraepithelial lesion (HSIL). The risk of developing cancer with CIN3 is high and most women are offered treatment to remove the abnormal tissue.

What is p16?

Cells infected with high-risk types of human papillomavirus (HPV) produce large amounts of a protein called p16 and increased p16 is commonly seen in CIN2 and CIN3. For this reason, pathologists perform a test called immunohistochemistry that allows them to see p16 inside cells. Pathologists use the term positive or reactive to describe cells that show increased amounts of p16. A positive result supports the diagnosis of CIN2 or CIN3 and helps exclude other conditions that can look like CIN2 and CIN3 under the microscope.

What is a margin and why are margins important?​

A margin is any tissue that has to be cut by the surgeon to remove the area of CIN from your cervix. If you underwent a surgical procedure such as a LEEP, your pathologist will examine the margin closely to ensure there are no abnormal cells at the cut edge of the tissue. Pap smears and small biopsies do not have margins.

A margin is considered positive when CIN is seen at the edge of the cut tissue. Finding CIN at the margin increases the risk that the disease 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 abnormal tissue from your body.

Typical cervical 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.

About this article

This article was written by doctors to help you read and understand your pathology report. Contact us if you have questions about this article or your pathology report. For a complete introduction to your pathology report, read this article.

Related articles on MyPathologyReport

Low grade squamous intraepithelial lesion of the cervix (LSIL)

High grade squamous intraepithelial lesion of the cervix (HSIL)

Squamous cell carcinoma of the cervix

Human papillomavirus (HPV)

Other helpful resources

American College of Obstetricians and Gynecologists

Atlas of pathology