Cervical Dysplasia

What is cervical dysplasia?

Cervical dysplasia refers to the presence of precancerous changes of the cells that make up the inner lining of the cervix, the opening to the womb (uterus). The term dysplasia refers to the abnormal appearance of the cells when viewed under the microscope. The degree and extent of abnormality seen on a tissue sample (such as a Pap smear) was formerly referred to as mild, moderate, or severe dysplasia. In recent years, this nomenclature has been replaced by two newer systems. These systems are based upon changes in the appearance of cells visualized when smears of individual cells (cytological changes) or tissue biopsies (histological changes) are reviewed under a microscope.

1. Squamous intraepithelial lesion is the pathology terminology for cervical dysplasia observed in smears of cells taken from the cervix. Squamous refers to the type of cell that lines the cervix. intraepithelial refers to the fact that these cells are present in the lining tissue of the cervix.
2. Cervical intraepithelial neoplasia iscervical dysplasia that is observed on a cervical biopsy or surgically removed cervix.

These classification systems will be further discussed below.

What causes cervical dysplasia?

Cervical dysplasia is caused by infection of the cervix with the human papillomavirus (HPV). Although there are over 100 HPV types, a subgroup of HPVs have been found to infect the lining cells of the genital and reproductive tract in women. HPV is a very common infection and is transmitted through sexual contact; over 75% of sexually active women are thought to acquire the virus at one point or another. It is believed that over 6 million people become infected with HPV every year in the US, and approximately 50% of those infected are between the ages of 15 and 25. Most infections occur in young women, do not produce symptoms, and resolve spontaneously without any long-term consequences. The average length of new HPV infections in young women is 8-13 months. However, it is possible to become re-infected with a different HPV type.

Some HPV infections persist over time rather than resolve, and the reason why the infection persists in these women is not fully understood. Factors that may influence persistence of the infection include:

• advancing age,
• duration of the infection, and
• being infected with a "high-risk" HPV type (see below).

Persistent HPV infection has been shown to play a causal role in the development of genital warts and precancerous changes (dysplasia) of the uterine cervix as well as cervical cancer. Even though HPV infection appears to be necessary for the development of cervical dysplasia and cancer, since not all women who have HPV infection develop dysplasia or cancer of the cervix. Additional, yet uncharacterized factors must also be important in causing cervical dysplasia and cancer. Since HPV infections are transmitted primarily by sexual intimacy, the risk of infection increases as the number of sexual partners increases.

Among the HPVs that infect the genital tract, certain types typically cause warts or mild dysplasia ("low-risk" types; HPV-6, HPV-11), while other types (known as "high-risk" HPV types) are more strongly associated with severe dysplasia and cervical cancer (HPV-16, HPV-18). Cigarette smoking and suppression of the immune system (such as with concurrent HIV infection) have been shown to increase the risk for HPV-induced dysplasia and cancer of the cervix.

The HPV types that cause cervical cancer also have been linked with both anal and penile cancer in men as well as a subgroup of head and neck cancers in both women and men.
Are there symptoms or signs of cervical dysplasia?

Typically, cervical dysplasia does not produce any signs or symptoms. So regular screening is important for early diagnosis and treatment.

How is cervical dysplasia diagnosed?

Screening for cervical dysplasia

Cervical dysplasia and cervical cancer generally only develop over a period of years, so regular screening is essential to detect and treat early precancerous changes and prevent cervical cancer. Traditionally, the Papanicolaou test (Pap test or Pap smear) has been the screening method of choice. To perform the Pap smear, the health care practitioner removes a swab or brush sample of cells from the outside of the cervix during a pelvic examination using a speculum in the vagina for visualization. The cells are smeared onto a glass slide, stained, and observed under the microscope for any evidence of dysplasia or cancer.

Newer, liquid-based systems to screen samples of cervical cells are also available and are effective screening tools for detection of dysplasia. The samples for this test are removed as for the conventional Pap smear, but the sample is collected in a vial of liquid that is later used to prepare a microscope slide for examination as with the Pap smear.

Further testing

For women whose initial screening result is unclear or abnormal, other diagnostic tests are used:

• Colposcopy is a gynecological procedure that illuminates and magnifies the vulva, vaginal walls, and uterine cervix in order to detect and examine abnormalities of these structures. A colposcope is a microscope that resembles a pair of binoculars. The instrument has a range of magnification lenses. It also has color filters that allow the physician to detect tiny abnormal blood vessels on the cervix. The colposcope is used to examine the vaginal walls and cervix through the vaginal opening. Colposcopy is a safe procedure with no complications other than mild vaginal spotting of blood.
• Biopsies are tissue samples obtained for examination under the microscope A biopsy may be taken of suspicious areas seen during colposcopy.
• HPV testing to detect whether or not HPV infection with a "high-risk" HPV type is present may be recommended for some women. This may be particularly useful if the results from regular screening tests are ambiguous, such as results suggesting atypical squamous cells of uncertain significance or ASC-US (see below). Because of the number of women infected with HPV in general and because the infection can be temporary and short-lived, regular screening of all women for HPV infection is not thought to be useful and is not routinely performed in the U.S.

How is cervical dysplasia classified?

Cytologic analysis (screening tests)

Pap smear analysis and reports are all based on a medical terminology system called The Bethesda System that was developed at the National Institutes of Health (NIH) in Bethesda, Maryland in 1988 and modified in 2001. The major categories for abnormal Pap smears reported in the Bethesda Systems are as follows:

1. ASC-US: This abbreviation stands for atypical squamous cells of undetermined significance. The word "squamous" describes the thin, flat cells that lie on the surface of the cervix. One of two choices are added at the end of ASC: ASC-US, which means undetermined significance, or ASC-H, which means cannot exclude HSIL (see below).
2. LSIL: This abbreviation stands for low-grade squamous intraepithelial lesion. This means changes characteristic of mild dysplasia are observed in the cervical cells.
3. HSIL: This abbreviation stands for high-grade squamous intraepithelial lesion. And refers to the fact that cells with a severe degree of dysplasia are seen.

Histologic analysis (cervical biopsies)

When precancerous changes are seen in tissue biopsies of the cervix, the term cervical intraepithelial neoplasia (CIN) is used. "Intraepithelial" refers to the fact that the abnormal cells are present within the lining, or epithelial, tissue of the cervix. "Neoplasia" refers to the abnormal growth of cells.

CIN is classified according to the extent to which the abnormal, or dysplastic, cells are seen in the cervical lining tissue:

• CIN 1 refers to the presence of dysplasia confined to the basal third of the cervical lining, or epithelium (formerly called mild dysplasia). This is considered to be a low-grade lesion.
• CIN 2 is considered to be a high-grade lesion. It refers to dysplastic cellular changes confined to the basal two-thirds of the lining tissue (formerly called moderate dysplasia).
• CIN 3 is also a high grade lesion. It refers to precancerous changes in the cells encompassing greater than two-thirds of the cervical lining thickness, including full-thickness lesions that were formerly referred to as severe dysplasia and carcinoma in situ.

What are treatments for cervical dysplasia?

Most women with low grade (mild) dysplasia (LGSIL, CIN1) (when the diagnosis is confirmed and all abnormal areas have been visualized), will undergo spontaneous regression of the mild dysplasia without treatment. Therefore, monitoring without specific treatment is often indicated in this group. Treatment is appropriate for women with high-grade cervical dysplasia.

Treatments for cervical dysplasia fall into two general categories: destruction (ablation) of the abnormal area and removal (resection). Both types of treatment are equally effective. Generally, destruction (ablation) procedures are used for milder dysplasia and removal (resection) is recommended for more severe dysplasia or cancer.

The destruction (ablation) procedures are carbon dioxide laser photoablation and cryocautery. The removal (resection) procedures are loop electrosurgical excision procedure (LEEP), cold knife conization, and hysterectomy. Treatment for dysplasia or cancer is not usually done at the time of the initial colposcopy, since the treatment depends on the analysis of the biopsies done during colposcopy.

Carbon dioxide laser photoablation

This procedure, which is also known as CO2 laser, uses an invisible beam of infrared light to essentially vaporize the abnormal area. A local anesthetic is given to numb the area prior to the laser treatment. A substantial amount of clear vaginal discharge and spotting of blood can occur for a few weeks after the procedure. The complication rate of this procedure is very low, about 1%. The most common complications are narrowing (stenosis) of the cervical opening and delayed bleeding. Disadvantages of this treatment include that this procedure does not allow sampling of the abnormal area and is not satisfactory for treating cervical cancer. It is useful, however, for milder dysplasia.
Cryocautery

Like the laser treatment, cryocautery is an ablation therapy. It uses nitrous oxide to freeze the abnormal area. This technique, however, is not optimal for large areas or areas where abnormalities are already advanced or severe. After the procedure, women may experience a significant watery vaginal discharge for several weeks. As with laser ablation, significant complications of this procedure are rare and occur in about 1% of patients. They include narrowing (stenosis) of the cervix and delayed bleeding. Cryocautery also does not allow sampling of the abnormal area and is generally felt to be inappropriate for women with advanced cervical disease. Thus, this procedure is not satisfactory for treating cervical cancer, but is useful for milder dysplasia.

Loop electrosurgical excision procedure

Loop electrosurgical excision procedure, also known as LEEP, is an inexpensive, simple technique that uses a radio-frequency current to remove abnormal areas. It has an advantage over the destructive techniques in that an intact tissue sample for analysis can be obtained. Vaginal discharge and spotting commonly occur after this procedure. Complications occur in about 1% to 2% of women undergoing LEEP, and include cervical narrowing (stenosis) and bleeding. This procedure is used most commonly for treating dysplasia, including severe dysplasia.

Cold knife cone biopsy (conization)

Cone biopsy (conization) was once the primary procedure used to treat cervical dysplasia, but the other methods have now replaced it for this purpose. However, when a physician cannot view the entire area that needs to be seen during colposcopy, a cone biopsy is typically recommended. It is also recommended if additional tissue sampling is needed to obtain more information regarding the diagnosis. This technique allows the size and shape of the sampling to be tailored. Cone biopsy has a slightly higher risk of cervical complications than the other treatments, and these can include postoperative bleeding in 5% of women and narrowing of the cervix.
Hysterectomy

Hysterectomy is the surgical removal of the uterus. This operation is used to treat virtually all cases of invasive cervical cancer. Sometimes, a hysterectomy is done to treat severe dysplasia. It may also be used if dysplasia recurs after any of the other treatment procedures.

What is the prognosis (outlook) for cervical dysplasia?

Low-grade cervical dysplasia (LGSIL and/or CIN1) often spontaneously resolves without treatment, but careful monitoring and follow-up testing is required. Both ablation and resection of areas of cervical dysplasia cure approximately 90% of women with dysplasia, meaning that 10% of women will have a recurrence of their abnormality after treatment, requiring additional treatment. When untreated, high grade cervical dysplasia may progress to cervical cancer over time. Resection and ablation therapies have been shown to reduce the risk of developing cervical cancer by 95% in the first eight years after treatment in women with high grade dysplasia.

Can cervical dysplasia be prevented?

A vaccine is available against four common HPV types associated with the development of dysplasia and cervical cancer. This vaccine (Gardasil) has received FDA approval for use in women between 9 and 26 years of age and confers immunity against HPV types 6, 11, 16 and 18.

Abstinence from sexual activity can prevent the spread of HPVs that are transmitted via sexual contact. However, some researchers believe that HPV infection might be transmitted from the mother to infant in the birth canal, since some studies have identified genital HPV infection in populations of young children and cloistered nuns. Hand-genital and oral-genital transmission of HPV has also been documented and is another means of transmission.

HPV is transmitted by direct genital contact. The virus is not found in or spread by bodily fluids, and HPV is not found in blood or organs harvested for transplantation. Condom use seems to decrease the risk of transmission of HPV during sexual activity but does not completely prevent HPV infection. Spermicides and hormonal birth control methods do not prevent the spread of HPV infection.
Cervical Dysplasia At A Glance

• Cervical dysplasia refers to the presence of precancerous changes in the lining cells of the cervix of the uterus.
• Cervical dysplasia is caused by infection with the human papillomavirus (HPV), but other factors also play a role.
• HPV infection is common in the general population. It is unclear why some women develop dysplasia and cervical cancer related to HPV infection while most do not.
• Cervical dysplasia is diagnosed by sampling cells or tissue from the cervix.
• Treatment, when necessary, involves ablation (destruction) or resection (removal) of the abnormal area.
• A vaccine is available against four common HPV types associated with the development of dysplasia and cervical cancer.