Human Papillomaviruses and Cancer, Part 2

by National Cancer Institute

(Page 2 of 2)

8. How are cervical cell abnormalities classified?

A Pap test is used to detect abnormal cells in the cervix. It involves the collection of cells from the cervix for examination under the microscope. Various terms have been used to describe the abnormal cells that may be seen in Pap tests.

The major system used to report the results of Pap tests in the United States is the Bethesda System. In this system, samples with cell abnormalities are divided into the following categories:

ASC — Atypical Squamous Cells. Squamous cells are the thin, flat cells that form the surface of the cervix. The Bethesda System divides this category into two groups:

1. ASC-US-Atypical Squamous Cells of Undetermined Significance. The squamous cells do not appear completely normal, but doctors are uncertain what the cell changes mean. Sometimes the changes are related to HPV infection. An HPV test may be done to clarify the findings.

2. ASC-H-Atypical Squamous Cells cannot exclude a High-grade squamous intraepithelial abnormality. Intraepithelial refers to the layer of cells that forms the surface of the cervix. The cells do not appear normal, but doctors are uncertain what the cell changes mean. ASC-H may indicate a higher risk of being precancerous compared with ASC-US.

AGC — Atypical Glandular Cells. Glandular cells are mucus-producing cells found in the endocervical canal (opening in the center of the cervix) or in the lining of the uterus. The glandular cells do not appear normal, but doctors are uncertain what the cell changes mean.

AIS — endocervical Adenocarcinoma In Situ. Precancerous cells are found in the glandular tissue.

LSIL — Low-grade Squamous Intraepithelial Lesion. Low-grade means there are early changes in the size and shape of the cells. The word lesion refers to an area of abnormal tissue. LSILs are considered mild abnormalities caused by HPV infection and are a common condition, especially among young women. The majority of LSILs return to normal over months to a few years.

HSIL — High-grade Squamous Intraepithelial Lesion. High-grade means that the cells look very different in size and shape from normal cells. HSILs are more severe abnormalities and may eventually lead to cancer if left untreated.

Pap test results may also be described using an older set of categories called the "dysplasia scale." Dysplasia is a term used to describe abnormal cells. Although dysplasia is not cancer, it may develop into very early cancer of the cervix. The cells look abnormal under the microscope, but they do not invade nearby healthy tissue.

There are four degrees of dysplasia: mild, moderate, severe, and carcinoma in situ. Carcinoma in situ is a precancerous condition that involves only the layer of cells on the surface of the cervix, and has not spread to nearby tissues. In the Bethesda System, mild dysplasia is classified as LSIL; moderate or severe dysplasia and carcinoma in situ are combined into HSIL.

Cervical intraepithelial neoplasia (CIN) is another term that is sometimes used to describe abnormal tissue findings. Neoplasia means an abnormal growth of cells. The term CIN along with a number describes how much of the thickness of the lining of the cervix contains abnormal cells. CIN-3 is considered to be a precancerous condition that includes carcinoma in situ.

9. What tests are used to screen for and diagnose precancerous cervical conditions?

A Pap test is the standard way to check for any cervical cell changes. A Pap test is usually done as part of a gynecologic exam. The U.S. Preventive Services Task Force guidelines recommend that women have a Pap test at least once every 3 years, beginning about 3 years after they begin to have sexual intercourse, but no later than age 21.

Because the HPV test can detect high-risk types of HPV in cervical cells, the FDA approved this test as a useful addition to the Pap test to help health care providers decide which women with ASC-US need further testing, such as colposcopy and biopsy of any abnormal areas. (Colposcopy is a procedure in which a lighted magnifying instrument called a colposcope is used to examine the vagina and cervix. Biopsy is the removal of a small piece of tissue for diagnosis.) In addition, the HPV test may be a helpful addition to the Pap test for general screening of women age 30 and over.

10. What are the treatment options for HPV infection?

Although there is currently no medical cure for papillomavirus infection, the lesions and warts these viruses cause can be treated. Methods commonly used to treat lesions include cryosurgery (freezing that destroys tissue), LEEP (loop electrosurgical excision procedure, the removal of tissue using a hot wire loop), and conventional surgery. Similar treatments may be used for external genital warts. In addition, some drugs may be used to treat external genital warts.

11. What research is being done on HPV-related cancers?

Researchers at the National Cancer Institute (NCI) and elsewhere are studying how HPVs cause precancerous changes in normal cells and how these changes can be prevented. For example, scientists are developing HPV vaccines that will be stable at room temperature. The goal is to develop a vaccine that does not require refrigeration for storage and distribution, which could allow for its use in many climates and locations.

Laboratory research has indicated that HPVs produce proteins known as E5, E6, and E7. These proteins interfere with the cell functions that normally prevent excessive growth. For example, HPV E6 interferes with the human protein p53. This protein is present in all people and acts to keep tumors from growing. This research is being used to develop ways to interrupt the process by which HPV infection can lead to the growth of abnormal cells.

Researchers at the NCI and elsewhere are also studying what people know and understand about HPV and cervical cancer, the best way to communicate to the public about the latest research results, and how doctors are talking with their patients about HPV. This research will help to ensure that the public receives accurate information about HPV that is easily understood, and will facilitate access to appropriate tests for those who need them.

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