Cervical cancer is cancer that originates in the cervix—the lower narrow part of the uterus that connects to the vagina.
Cervical cancer is usually a slow-growing cancer that originates from abnormal cells in the cervix. This
cervical dysplasia often develops in women in their 20s and 30s. However, cervical cancer more often develops in women over 40. Once cancer cells begin to grow they spread further into the cervix and surrounding tissue. Cervical cancer may not have symptoms. It is detected by screening with a Pap test or smear, in which cells are scraped from the cervix and examined under a microscope. Cervical cancer is both preventable and curable if detected early. Between 1974 and 2004 the incidence of cervical cancer declined about 50% due to widespread screening with the Pap test. Deaths from cervical cancer have declined an estimated 70% since the Pap test was first introduced in the mid-twentieth century.
It is projected that in the United States in 2008 there would be 11,070 new cases of cervical cancer and 3,870 deaths from cervical cancer. Although the overall age-adjusted incidence of cervical cancer between 2000 and 2004 was 8.7 per 100,000 women, the incidence among black American women was 11.4 per 100,000 and among Hispanic Americans it was 13.8 per 100,000.
It is estimated that one out of every 142 women will be diagnosed with cervical cancer at some point during her lifetime. Although the median age for diagnosis of cervical cancer in the United States between 2000 and 2004 was 48, almost half of all new cases of serious cervical cancer and deaths from cervical cancer were in women aged 65 and older. The risk of death from cervical cancer increases with age. African American women are more than twice as likely to die of cervical cancer as white Americans. White women are more likely to die from cervical cancer between the ages of 45 and 70, and black women are more likely to die from cervical cancer in their 70s. Hispanic Americans are also more likely to die of cervical cancer than white women.
In the developing world cervical cancer is the second most common cancer in women and the third most common cause of cancer death, with nearly 300,000 women dying annually.
Almost all cervical cancers are caused by persistent infection with the human papillomavirus (HPV), which is spread through sexual contact. Women who become sexually active at a young age and have many sexual partners are at increased risk of HPV infection and cervical cancer. Women infected with the human immunodeficiency virus (HIV) are also at increased risk for HPV infection and cervical-cell abnormalities.
Diethylstilbestrol (DES), which was given to pregnant women in the United States between 1940 and 1971, may increase the risk of a rare type of cervical cancer in women who were exposed to the drug before birth.
Causes and symptoms
Although most women with cervical cancer are infected with HPV, most women with HPV do not develop cervical cancer. HPV infection is very common (there are about 6 million new cases annually in the United States) and only a very small number of women with untreated HPV develop cervical cancer. HPV infections are much more common among younger women, especially those in their late teens and twenties. Fewer than 20% of women in their 50s are infected with HPV and primarily with strains that are not associated with cervical cancer. There are more than 100 strains of HPV, including those that cause common warts on the hands and feet. More than 30 strains are sexually transmitted, including those that cause genital warts. About 15 of these sexually transmitted strains can cause cell abnormalities or lesions that may develop into cervical cancer. Therefore, women who are infected with more than one HPV strain have a far greater risk of developing the lesions that can lead to cervical cancer. Often HPV infections go away without treatment; however, sometimes the virus remains detectable for years after infection. Thus women who do not have regular Pap tests are at far greater risk of developing cervical cancer.
Although cervical cancer often has no symptoms, possible symptoms include:
- menstrual bleeding that is unusually long or heavy
- vaginal bleeding between periods or after sexual intercourse, douching, or a pelvic exam
- bleeding after menopause
- painful sexual intercourse
- pelvic pain
Cervical cancer and precancerous conditions are usually first detected with a Pap test. However, various factors other than HPV can cause cervical cells to undergo changes that result in an abnormal Pap test but do not lead to cancer. These include:
- bacterial, viral, or yeast infections
- hormone changes during pregnancy or menopause
- growths such as benign polyps or cysts
A Pap test is usually accompanied by a pelvic exam, which sometimes diagnoses cervical cancer.
Most U.S. laboratories use the Bethesda System for reporting Pap-test results:
- “Negative for intraepithelial lesion or malignancy” is a normal result, meaning that no atypical cells were found on the surface of the cervix.
- Atypical squamous cells of undetermined significance (ASC-US) indicates that the squamous cells (the flat thin cells that line the surface of the cervix) do not appear completely normal, perhaps due to an HPV infection, but the significance of the abnormality is unknown.
- Atypical squamous cells-H (ASC-H) indicates that the cells are atypical, and although the significance is unclear, a precancerous high-grade squamous intraepithelial lesion (SIL) cannot be excluded.
- Atypical glandular cells (AGC) indicates that the mucus-producing cells in the endocervical canal (the opening at the center of the cervix) or in the lining of the uterus do not appear normal, but the significance of the changes is unclear.
- Endocervical adenocarcinoma-in-situ (AIS) means that precancerous cells are found in the glandular or mucus-producing tissue.
- Low-grade squamous intraepithelial lesion (LSIL) indicates early changes in the size and shape of the squamous cells caused by HPV infection.
- High-grade squamous intraepithelial lesion (HSIL) indicates markedly abnormal or precancerous cells with a higher probability of progressing to invasive cervical cancer.
- Cancer cells are present.
Healthcare providers may use slightly different terms to describe abnormal Pap-test results:
- Dysplasia indicates the presence of abnormal cells that could develop into very early cervical cancer. It is categorized as mild, moderate, severe, or carcinoma-in-situ (CIS) (cancer cells confined to the surface of the cervix), depending on the degree of abnormality; mild dysplasia is a LSIL and moderate to severe dysplasia or CIS is an HSIL.
- Cervical intraepithelial neoplasia (CIN) indicates abnormal growth of cells on the surface of the cervix. It is categorized as CIN-1 to 3 depending on the severity; CIN-1 is equivalent to a LSIL or mild dysplasia; CIN-2 and -3 are HSIL, moderate to severe dysplasia, or CIS.
- Cervical cancer indicates that cancer cells have spread deeper into the cervix.
- Invasive cervical cancer means that cancer cells have spread to other tissues or organs.
Of about 55 million Pap tests performed annually in the United States, about 3.5 million or 6% are abnormal and require medical follow-up. The Pap test may be repeated, particularly if the results were ambiguous or indicated only a minor abnormality, since abnormal cervical cells often disappear without treatment. An ASC-US Pap in a woman who is approaching or past menopause may be due to low levels of the female hormone estrogen. Application of an estrogen cream to the surface of the cervix for a few weeks often leads to a normal test result.
ASC-US, ASC-H, LSIL, or HSIL Pap results are often followed by colposcopy, in which the cervix is coated with a dilute vinegar solution that turns abnormal cells white and a lighted magnifying instrument called a colposcope is used to examine the vagina and cervix.
An HPV DNA test may be performed to determine whether the abnormal cells are the result of infection with HPV that is linked to cervical cancer. A large clinical trial has indicated that testing a cervical sample for HPV is more efficient than colposcopy or a repeat Pap test for identifying ASC-US abnormalities that require treatment.
If colposcopy reveals abnormal cells, the cervix may be examined with a LUMA Cervical Imaging System, which shines a light on the cervix. Normal and abnormal cells respond differently to the light, and the system produces a colored map that distinguishes between them.
A biopsy may be performed to remove cells or tissue for examination by a pathologist. Several types of biopsies are used to diagnose cervical cancer and precancerous conditions:
- endocervical curettage, in which a small spoonshaped curette or a thin soft brush is used to scrape cells from the inside of the endocervical canal
- punch biopsy, in which a sharp hollow instrument pinches off small pieces of cervical tissue
- conization or cervical cone biopsy, in which a cone-shaped piece of tissue is removed from higher up in the cervical canal; this may be performed in a hospital under general anesthesia and often requires stitches
- loop electrosurgical excision procedure (LEEP), in which an electrical current is passed through a thin looped wire to slice off a thin round piece of tissue
If invasive cancer cells are found, additional tests are performed to stage or determine the extent of the cancer:
- chest x rays to determine if the cancer has spread to the lungs
- computed tomography (CT) or computerized axial tomography (CAT) scans to x ray internal tissues that are visualized with a dye
- a lymphangiogram, in which dye is injected into lymph glands in the feet and travels up the lymphatic system while x rays check for blocked lymph nodes that may be cancerous
- ultrasound, in which high-energy sound waves are bounced off internal tissues to form a picture or sonogram
- magnetic resonance imaging (MRI) or nuclear magnetic resonance imaging (NMRI), which uses a magnet, radio waves, and a computer to obtain detailed images of internal tissues
- pretreatment surgical staging to determine whether the cancer has spread within the cervix or to other areas; sometimes the cancer is surgically removed in the process
Cervical cancer is staged as follows:
- stage O—CIS; abnormal cells that may become cancerous are found in the innermost lining of the cervix
- stage IA—cancer is microscopic and confined to the cervix
- stage IB—cancer is larger but confined to the cervix
- stage IIA—cancer has spread to the upper two-thirds of the vagina
- stage IIB—cancer has spread to the upper two-thirds of the vagina and to tissues around the uterus
- stage IIIA—cancer has spread to the lower third of the vagina
- stage IIIB—cancer has spread to the pelvic wall and/or the tumor is large enough to block the ureters (the tubes that connect the kidneys with the bladder), causing the kidneys to enlarge or fail; may have spread to lymph nodes in the pelvis
- stage IVA—cancer has spread to the bladder or wall of the rectum and possibly to lymph nodes in the pelvis
- stage IVB—cancer has spread to other parts of the body such as the abdomen, liver, intestinal tract, or lungs
- recurrent—cervical cancer that has returned to the cervix or elsewhere in the body after treatment
Abnormal cells that have a high potential for becoming cancerous may be destroyed by the following techniques:
- conization with a knife, laser, or LEEP
- laser therapy
- cryotherapy or freezing
HSIL sometimes requires a total hysterectomy (removal of the cervix and uterus).
Sometimes cervical cancer must be treated immediately, but more often there is time to get a second opinion. Treatment options depend on the following:
- the cancer stage
- the tumor size
- the woman's age and general health
The standard treatments for cervical cancer are surgery, radiation therapy, and chemotherapy . Studies have shown that a combination of radiation therapy and chemotherapy reduces the death rate by 30 to 50%. However, although women aged 65 and older are more likely to die from cervical cancer than younger women, they often receive less aggressive treatment regardless of the stage of their cancer.
Surgical treatments include:
- laser surgery for a surface lesion or tumor
- total vaginal hysterectomy (removal of the uterus and cervix through the vagina)
- total abdominal hysterectomy (removal of the uterus and cervix through a large abdominal incision)
- total laparoscopic hysterectomy (removal of the uterus and cervix with a laparoscope through a small abdominal incision)
- bilateral salpingo-oophorectomy (removal of the ovaries and fallopian tubes)
- radical hysterectomy (removal of the uterus, cervix, a portion of the vagina, and possibly the ovaries, fallopian tubes, and nearby lymph nodes)
- pelvic exenteration (removal of the uterus, cervix, ovaries, nearby lymph nodes, lower colon, rectum, and bladder, with construction of artificial openings for collecting feces and urine and possible plastic surgery to construct an artificial vagina)
External radiation therapy uses high-energy x rays to kill cancer cells. With internal radiation therapy thin tubes or implants containing a radioactive substance are placed in the vagina for a few hours or up to three days, two or more times over a period of several weeks.
Cisplatin is the most common chemotherapy drug for treating cervical cancer. It is usually injected into a vein.
Treatment options by stage are:
- O—conization; LEEP; laser surgery; cryosurgery; total hysterectomy for women who cannot or do not want to have children; internal radiation therapy for women who cannot have surgery
- IA—conization; total hysterectomy with or without bilateral salpingo-oophorectomy; radical hysterectomy with removal of lymph nodes; internal radiation therapy
- IB, IIA—combination internal and external radiation therapy; radical hysterectomy with removal of lymph nodes, possibly followed by radiation therapy and chemotherapy; radiation therapy plus chemotherapy
- IIB, III, IVA—internal and external radiation therapy and chemotherapy
- IVB—radiation therapy to relieve symptoms and improve quality of life; chemotherapy
- recurrent—pelvic exenteration followed by radiation therapy and chemotherapy; chemotherapy to relieve symptoms and improve quality of life
QUESTIONS TO ASK YOUR DOCTOR
- What tests will be performed to stage my cancer?
- Will they be performed in the hospital?
- Will I have anesthesia?
- Are there risks to these tests?
- How soon will I know the results?
- What stage is my cancer?
- What are my treatment options? What do you recommend?
- Should I get a second opinion?
- What are the risks and possible side effects of treatment?
- Are there any clinical trials that might be appropriate?
- What is my prognosis?
The overall five-year survival rate for women diagnosed with cervical cancer is almost 75%. However, African American women are more likely to be diagnosed at an advanced stage, and their survival rate is only 63%.
Risk factors for cervical cancer include:
- sexual intercourse at an early age
- numerous sexual partners
- sexual partners who have had numerous sexual partners
- giving birth to seven or more children
- smoking cigarettes
- using oral contraceptives for at least five years
- a weakened immune system
AGC —Atypical glandular cells; a Pap-test result indicating that mucus-producing cells in the cervix or the lining of the uterus appear abnormal.
AIS —Endocervical adenocarcinoma-in-situ; a Pap test result indicating precancerous cells in the glandular or mucus-producing tissue of the cervix.
ASC-H —Atypical squamous cells; a Pap-test finding of atypical cells of unknown significance with the possibility of a precancerous high-grade squamous intraepithelial lesion.
ASC-US —Atypical squamous cells of undetermined significance; a Pap-test result.
Carcinoma-in-situ (CIS) —Cancer cells confined to the surface of the cervix.
Cervical intraepithelial neoplasia (CIN) —Abnormal growth of cells on the surface of the cervix.
Cervix —The lower narrow part of the uterus that opens to the vagina.
Colposcopy —The use of a magnifying instrument to examine the vagina and cervix.
Conization —Excision of a cone-shaped tissue from the cervix.
Cryosurgery —Surgery that removes or destroys tissue by freezing.
Curettage —Surgical scraping using a spoon-shaped tool called a curette.
Dysplasia —Growth of abnormal cells.
Endocervical canal —The opening at the center of the cervix.
HSIL —High-grade squamous intraepithelial lesion; moderate to severe dysplasia; a Pap-test finding of abnormal or precancerous cells with a higher probability of progressing to invasive cervical cancer.
Human papillomavirus (HPV) —Some strains of this virus cause warts and others cause cervical cancer.
Hysterectomy —Surgical removal of the uterus and cervix through the vagina or abdomen.
Intraepithelial —On the surface of the cervix.
Lesion —Abnormal cells.
Loop electrosurgical excision procedure (LEEP) —A procedure in which an electrical current is passed through a thin looped wire to slice off or destroy a piece of tissue.
LSIL —Low-grade squamous intraepithelial lesion; mild dysplasia; a Pap-test finding of early changes in the size and shape of squamous cells.
Neoplasia —Tumor formation.
Pap test —Pap smear; examination of cervical cells for the early detection of cancer.
Pelvic exenteration —Surgical removal of the uterus, cervix, ovaries, nearby lymph nodes, lower colon, rectum, and bladder.
Punch biopsy —The use of a sharp hollow instrument to pinch off small pieces of cervical tissue.
SIL —Squamous intraepithelial lesion; abnormal squamous cells on the surface of the cervix.
Squamous —Small scale-like cells on the surface of the cervix.
Some methods of preventing sexually transmitted disease reduce the risk of cervical cancer. Barrier methods of birth control and/or spermicides (gels that kill sperm) provide incomplete protection from HPV.
The most reliable early detection method for cervical cancer is a regular Pap test. Among American women diagnosed with cervical cancer, 60% had not had a Pap test in the previous five years. However, screening tests for HPV may eventually replace Pap tests.
A vaccine introduced in 2006 protects against the two HPV strains that cause 70% of cervical cancers and the two strains that cause 90% of genital warts. The vaccine is known to protect against HPV infection for at least five years; however, it does not protect or treat women who are already infected with HPV. According to some authorities, it is recommended that females aged 9 through 26 be vaccinated.
Following treatment for cervical cancer regular monitoring for possible recurrence is very important and may include physical exams, Pap tests, and chest x rays.
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Gynecologic Cancer Foundation, 230 W. Monroe, Suite 2528, Chicago, IL, 60606, (312) 578-1439, (800) 444-4441, (312) 578-9769, [email protected], http://www.wcn.org/gcf.
National Cancer Institute, NCI Public Inquiries Office, 6116 Executive Blvd., Room 3036A, Bethesda, MD, 20892-8322, (800) 4-CANCER, http://www.cancer.gov.
Margaret Alic Ph.D.