Cervical Dysplasia
Reversing the Road to Cervical Cancer
Updated: 01/20/2006

Cervical dysplasia is characterized by abnormal (dysplastic) cells in the cervix. Extending into the vagina, the cervix is the lowest part of the uterus. Although cervical dysplasia does not produce symptoms itself, it is potentially dangerous because it can progress to cervical cancer, the second-most-common type of cancer in women, especially among younger women (Nicol AF et al 2005; Marshall K 2003; Rock CL et al 2000).

Since the introduction of the Pap smear in 1941, the death rate from cervical cancer has dropped significantly because of early detection of cervical dysplasia. In developing countries, where Pap smears are not as common as in industrialized countries, cervical cancer is reported to be the leading cause of cancer in women (Potischman N et al 1996). Worldwide, cervical cancer accounts for 11.6 percent of cancers in women (Giuliano AR et al 1998; Rock CL et al 2000).

In more than 99 percent of cases, cervical cancer and cervical dysplasia are caused by the human papillomavirus (HPV), the virus that causes genital warts (Yeo AS et al 2000). HPV is very common: the lifetime risk of a woman contracting genital HPV is estimated to be 80 percent (Bekkers RL et al 2004). It is transmitted through sexual intercourse. The virus may be present without symptoms, making it possible for carriers to transmit it unknowingly.

The vast majority of women with HPV will not develop cervical dysplasia or cancer (Marshall K 2003; Giuliano AR et al 1998). There are many variations of the virus, and some forms carry a higher risk for the development of cancer than others, especially HPV16 and HPV18 (Liu T et al 1993). HPV is often difficult to detect because it only rarely causes symptoms. Only about 1 percent of women with HPV have visible genital warts (Wright TC et al 2004), which adds to the importance of regular Pap smears.

The goal of cervical dysplasia treatment is reducing the risk of its progression to cervical cancer. This risk reduction may be accomplished through dietary modification and supplementation and possibly by chemoprevention through the use of medical or chemical modifiers (Rock CL et al 2000; Pereira DB et al 2004; Maissi E et al 2004). Fortunately, there is hope on the horizon: because of lifestyle changes, the prevalence of Pap smears, and exciting research into HPV vaccines, cervical cancer rates are expected to continue dropping in the industrialized world.

Classification and Screening for Cervical Dysplasia

Cervical dysplasia is commonly referred to as cervical intraepithelial neoplasia (CIN). It is often classified by the degree of penetration of abnormal cells into the tissue lining (epithelium):

• CIN I describes the involvement of the basal third of the epithelium.
• CIN II involves the basal two thirds of the epithelium.
• CIN III involves more than two thirds of the epithelium.

A diagnosis of cervical dysplasia does not necessarily mean that cervical cancer will develop. In fact, up to 74 percent of women with mild CIN will naturally regress to normal within five years (Holowaty P et al 1999). Of those cases that do progress, only a minority of women will actually develop cancer.

• Only 1 percent of women with CIN I who experience progression will progress to severe dysplasia or worse (Holowaty P et al 1999).
• Among patients with CIN II, 16 percent will advance to severe dysplasia within two years and 25 percent within five years.
• An overall progression rate of severe dysplasia (CIN III) to cervical cancer has been observed in 12 percent to 32 percent of patients (Arends MJ et al 1998; McIndoe WA et al 1984).

Pap smears are the standard tool used to screen women for cervical dysplasia or cancer. During a Pap smear, cells are scraped from the cervix, then evaluated microscopically. About 5 percent to 7 percent of Pap smears yield abnormal findings (Jones BA et al 2000).

One major problem with screening is poor follow-up testing among women with abnormal Pap smears. In most cases, an abnormal Pap smear requires a follow-up test in a few months. However, an estimated 10 percent to 61 percent of women with abnormal Pap smears do not undergo follow-up testing (Shinn E et al 2004). Factors associated with noncompliance include only an elementary education, prior surgery, additional diseases, consumption of medications for chronic conditions, and family illness (Bornstein J et al 2004).

In general, according to the American Cancer Society’s 2002 screening guidelines:

• Women should begin cervical cancer screening no later than three years after beginning vaginal intercourse but no later than 21 years of age.
• Cervical cancer screening should be performed annually with regular Pap tests or every two years with liquid-based Pap tests.
• A woman 30 years of age or older with three consecutive normal Pap smears may elect to be screened every two to three years.
• Women who have undergone hysterectomy can elect to discontinue Pap smears if the surgery was not performed to treat cervical cancer or precancer. Women with an intact cervix posthysterectomy should undergo screening until at least age 70.
• A woman older than age 70 may choose to discontinue Pap smear screening after three prior normal Pap smears and no abnormal results in the preceding 10 years.

Risk Factors for Progression

While it may take years for cervical dysplasia to progress to cancer, the cancer can quickly spread throughout the body once established. If left untreated, cervical cancer has a relatively high mortality rate, although the survival rate for properly treated early-stage cervical dysplasia and cervical cancer is high.

Early symptoms of cervical cancer, such as altered vaginal discharge and abnormal vaginal bleeding, are rare. Advanced cervical cancer may present with pelvic, back, or leg pain, leaking of urine or feces from the vagina, loss of appetite, weight loss, and bone fracture.

Not all cases of cervical dysplasia progress into cancer (Marshall K 2003). Rather, it appears that certain factors may hasten the progression from cervical dysplasia to cervical cancer:

• Decreased methylation. DNA hypomethylation is significantly associated with grade of CIN (Fowler BM et al 1998; Goodman MT et al 2001).
• Multiple HPV types. One study showed a significantly increased risk of CIN in women with several HPV subtypes (Ho GY et al 1998).
• Viral load. A high level of the virus is a significant risk factor for CIN (Li SM et al 2004; Schlecht NF et al 2003; Dalstein V et al 2003; Ylitalo N et al 2000; Josefsson AM et al 2000; Ho GY et al 1998; Romney SL 1997; Flores R et al 2005).
• High-risk HPV variants. Certain virus strains are an independent risk factor for cervical dysplasia (Thomson et al 2000; Liu T et al 1995).
• Persistence of HPV infection. Persistent infection with HPV increases the risk of cervical cancer (Giuliano AR et al 1997; Romney SL et al 1997).
• Smoking. Smoking is a serious independent risk factor for advanced cervical dysplasia (Palan PR et al 1991). Passive cigarette smoking via a spouse also has been associated with a higher incidence of high-grade squamous intraepithelial lesions (Tay SK et al 2004). Women with abnormal Pap smears absolutely should avoid smoking.
• Obesity. In one large study, fewer overweight and obese women (78 percent in each group) underwent cervical cancer screening with Pap smears (Wee CC et al 2000). Because this group of women have a higher mortality rate for cervical cancer compared with women of normal weight, special attention should be paid to increasing screening among overweight and obese women.
• Number of sexual partners. The number of sexual partners increases the risk of cervical dysplasia (Thomson SW et al 2000), perhaps by increasing the chances of encounter with HPV strains.
• Multiple pregnancies. Multiple pregnancies have been cited as a possible risk factor for cervical dysplasia (Munoz N et al 2002; Liu T et al 1993; Thomson SW et al 2000).
• Lower socioeconomic status and lack of Pap smears. Women with a lower educational level may avoid follow-up Pap smears (Bornstein J et al 2004. Additionally, those with lower socioeconomic status may lack access to appropriate health care.
• Diethylstilbestrol (DES). DES was given to expectant mothers from the late 1930s until 1970 to prevent early delivery. However, many mothers were unaware that the drug was being administered to them; sometimes it was given with a vitamin supplement. Unfortunately, it resulted in increased cervical cancer in female offspring. Current research regarding the use of DES focuses on the effects of the drug in granddaughters and grandsons of those who received it (Centers for Disease Control 2005).
• Compromised immune function. Women with medical conditions that affect the immune system are at greater risk for cervical dysplasia. These conditions include HIV, systemic lupus erythematosus, and transplanted organs (Duerr A et al 2001; Robinson WR et al 2002; Bernatsky S et al 2004; Malouf MA et al 2004; Ozsaran AA et al 1999).
• Other sexually transmitted diseases. One study concluded that the presence of other sexually transmitted diseases, such as Herpes simplex virus and Chlamydia trachomatis, can cause dysplasia to progress to cervical cancer (Smith JS et al 2002a; Smith JS et al 2002b). However, other studies failed to show an association between these sexually transmitted diseases and cervical cancer progression (Castle PE et al 2003; Tran-Thanh D et al 2003).

Conventional Treatment of Cervical Dysplasia and Cancer

Cervical Dysplasia

The success rate of treating early-stage cervical dysplasia is extremely high. During treatment, a physician will attempt to remove the abnormal cells through a variety of methods, including cryotherapy, or freezing the cells to destroy them.

Alternatively, a procedure called loop electrosurgical excision may be performed. During this procedure, a thin wire loop with an electrical current is used to remove a cone-shaped piece of tissue. Women treated with loop excision are likely to convert to HPV-negative status, which eliminates the risk for HPV-related cervical dysplasia and cancer (Aschkenazi-Steinberg SO et al 2005). If a larger area of the cervix contains abnormal cells, a gynecologist may perform a surgical procedure called cervical conization to remove all the abnormal cells.

In case of high-grade CIN, or if previous surgeries left too little cervical tissue, a hysterectomy may be recommended (Das N et al 2005). In rare advanced cases, all the organs of the pelvis can be removed in a procedure called pelvic exenteration. Except for hysterectomy or pelvic exenteration, the surgical choices typically allow a woman to carry a child in future pregnancies.

Cervical Cancer

Sometimes radiation or chemotherapy is required in addition to surgery for cancers that are recurrent or have spread beyond the pelvis. Survival rates depend on the stage of the cancer. With treatment, five-year survival rates are 80 percent to 85 percent for cervical and uterine tumors, 60 percent to 80 percent for tumors involving the upper part of the vagina, 30 percent to 50 percent for tumors still retained in the pelvis, and 14 percent when cancer has invaded the bladder or rectum or metastasized outside the pelvis.