Cervical
The Facts and Statistics
The cervix is the lower part of the uterus (womb). The upper part, or body, of the uterus, is where a fetus grows. The cervix connects the body of the uterus to the vagina (birth canal). The part of the cervix closest to the body of the uterus is called the endocervix. The part next to the vagina is the ectocervix. Most cervical cancers start where these 2 parts meet.
Cancer of the cervix (also known as cervical cancer) begins in the lining of the cervix. Cervical cancers do not form suddenly. Normal cervical cells gradually develop pre-cancerous changes that turn into cancer. Doctors use several terms to describe these pre-cancerous changes, including cervical intraepithelial neoplasia (CIN), squamous intraepithelial lesion (SIL), and dysplasia.
Pre-cancerous changes of the cervix can go away in some women. However, dysplasia may need to be treated to keep from developing into cancer. Cervical cancer develops when abnormal cells in the lining of the cervix begin to grow out of control, and when these abnormal cells later invade other parts of the body, it is called metastasis.
There are 2 main types of cervical cancers: squamous cell carcinoma and adenocarcinoma. Cervical cancers and cervical precancers are classified by how they look under a microscope. About 80% to 90% of cervical cancers are squamous cell carcinomas, which are composed of cells that resemble the flat, thin cells called squamous cells that cover the surface of the endocervix. Squamous cell carcinomas most often begin where the ectocervix joins the endocervix.
The remaining 10% to 20% of cervical cancers are adenocarcinomas. Adenocarcinomas are becoming more common in women born in the last 20 to 30 years. Cervical adenocarcinoma develops from the mucus-producing gland cells of the endocervix. Some cervical cancers have features of both squamous cell carcinomas and adenocarcinomas. These types of cervical cancers are called adenosquamous carcinomas or mixed carcinomas.
According to the American Cancer Society, it is estimated that in 2007, 11,150 women will be diagnosed with cervical cancer and 3,670 women will die from the disease.
Between 1955 and 1992 the cervical cancer death rate declined by 74%. The main reason for this change is the increased use of the Pap test. This screening procedure can find changes in the cervix before cancer develops. It can also find early cancer in its most curable stage. The death rate from cervical cancer continues to decline by nearly 4% a year.
Cervical cancer tends to occur in midlife. Half of women diagnosed with this cancer are between the ages of 35 and 55. It rarely occurs in women younger than 20. Although cervical cancer does affect young women, many older women do not realize that the risk of developing cervical cancer is still present as they age. Slightly over 20% of women with cervical cancer are diagnosed when they are over 65. It is important for older women to continue having regular Pap tests at least until age 70, and possibly longer.
The 5-year relative survival rate for the earliest stage of invasive cervical cancer is 92%. The overall (all stages combined) 5-year survival rate for cervical cancer is about 72%.
Signs & Symptoms of Cervical Cancer
Cervical precancers and early cancers usually show no symptoms or signs. A woman usually develops symptoms when the cancer has become invasive and invades nearby tissue. When this happens, the most common symptom is abnormal vaginal bleeding.
An unusual discharge from the vagina (separate from your normal monthly menstrual period) can be a sign of cervical cancer. Such discharge may include blood spots or light bleeding and may occur between your periods. Also, menstrual bleeding may last longer and be heavier than usual. Bleeding after menopause or increased vaginal discharge also may be symptoms.
Bleeding following intercourse, douching, or after a pelvic exam is a common symptom of cervical cancer but not pre-cancer.
Pain during intercourse may also indicate cervical cancer.
However, all of these signs and symptoms can be caused by conditions other than cervical cancer. For example, an infection can cause pain or, rarely, bleeding. If you have any of these signs or other suspicious symptoms, you should see your health care professional right away. Ignoring symptoms may allow the cancer to progress to a more advanced stage and lower your chance for effective treatment.
Even better, don’t wait for symptoms to appear. Have a regular Pap test and pelvic examination.
Your primary doctor can often treat pre-cancers. However, if your biopsy result indicates that you have cervical cancer, you may need to consult with a surgeon who specializes in treating this type of cancer. If there is a question of invasive cancer, your doctor will refer you to a gynecologic oncologist, a doctor who specializes in women’s reproductive system cancers. Some patients will be referred to a radiation oncologist, a doctor who specializes in treating cancers with radiation.
A risk factor is anything that increases your chance of getting a disease such as cancer. Different cancers have different risk factors. For example, exposing skin to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for cancers of the lung, mouth, larynx, bladder, kidney, and several other organs. But having a risk factor, or even several, does not mean that you will get the disease.
Several risk factors increase your chance of developing cervical cancer. Women without any of these risk factors rarely develop cervical cancer. Although these risk factors increase the odds of developing cervical cancer, many women with these risks do not develop this disease. When a woman develops cervical cancer or precancerous changes, it is not possible to say with certainty that a particular risk factor was the cause.
In thinking about the following risk factors, it helps to focus on those that you can change or avoid (smoking, for example, or sexual behaviors that can lead to human papillomavirus infection), rather than those that you cannot (such as your age and family history). However, it is still important to know about risk factors that cannot be changed, because it’s even more important for women with these factors to get regular Pap tests to detect cervical cancer early.
Cervical cancer risk factors include:
Human papillomavirus infection: The most important risk factor for cervical cancer is infection by the human papillomavirus (HPV). Doctors believe that women must have been infected by this virus before they will develop cervical cancer. HPVs are a group of more than 100 types of viruses called papillomaviruses because some of them can also cause warts, or papillomas, which are non-cancerous (benign) tumors. Certain types, however, cause cancer of the cervix. These are called “high-risk” types of HPV and include HPV 16, HPV 18, HPV 31, HPV 33, and HPV 45, as well as some others. About two thirds of all cervical cancers are caused by HPV 16 and 18.
Other types of HPVs cause different types of warts in different parts of your body. Some types cause common warts on the hands and feet. Other types tend to cause warts on the lips or tongue. Genital HPVs may cause warts to appear on or around the female and male genital organs and the anal area. These HPV types are passed from one person to another during skin-to-skin sexual contact, including vaginal and anal intercourse, and possibly during oral sex.
When HPV occurs on the skin of the external (outer) genital organs and anal area, it often causes raised bumpy warts. These may be barely visible or they may be several inches across. The medical term for genital warts is condyloma acuminatum. Most genital warts are caused by 2 HPV types: HPV 6 and HPV 11. These seldom are linked to cervical cancer and are called “low-risk” types. Other sexually transmitted HPVs have been linked with genital or anal cancers in both men and women.
There is currently no cure or treatment for HPV infection. Many women will have HPV but very few will ever develop cervical cancer. Usually the infection disappears without any treatment, because the woman’s immune system has been successful in fighting the virus. In the future, however this problem may disappear, because vaccines have been developed that will prevent infection with HPV. Right now, one vaccine ha been approved for use by FDA and it protects against HPV types 16, 18, 6, and 11, but others are in development.
HPV infection usually causes no symptoms. However, the warts and abnormal cell growth caused by HPV can be treated effectively.
Precancerous changes in the cervix are diagnosed when abnormal cells are found with a Pap test or biopsy (these are discussed further in the section, “Can Cervical Cancer Be Prevented?” ). HPV infection causes changes in cells of the cervix that can be found by the Pap test. New tests can identify HPVs by finding their DNA in the cells. Many doctors are now testing for HPV if the Pap test result is mildly abnormal (doctors refer to these findings as atypical squamous cells, or ASC). If a high-risk type of HPV is present, they will do a colposcopy and consider further treatment.
Certain types of sexual behavior increase a woman’s risk of getting HPV infection:
• having sex at an early age
• having many sexual partners
• having a partner who has had many sex partners
• having sex with uncircumcised males
HPV infection occurs mainly in young women and is less common in women over 30. The reason for this is not known. Uncircumcised men are thought to be more likely to harbor the virus. HPV can be present for years with no symptoms, and HPV infection does not always cause warts or other symptoms; so you can be infected with HPV and pass it on without knowing it. Recent studies show that condoms (“rubbers”), while they do provide some protection, do not completely protect against HPV. This is because HPV can be passed from person to person by skin-to-skin contact with any HPV-infected area of the body, such as skin of the genital or anal area not covered by the condom. The absence of visible warts cannot be used to decide whether caution is needed, because HPV can be passed to another person even when there are no visible warts or other symptoms.
Although condoms do not completely protect against HPV, it is still important to use condoms to protect against AIDS and other sexually transmitted illnesses that are passed on through some body fluids.
Although it is necessary to have had HPV for cervical cancer to develop, most women with this virus do not develop cancer. Doctors feel that other factors must come into play for cancer to develop. Some of the known factors are listed below.
Smoking: Women who smoke are about twice as likely as non-smokers to get cervical cancer. Smoking exposes the body to many cancer-causing chemicals that affect more than the lungs. These harmful substances are absorbed by the lungs and carried in the bloodstream throughout the body. Tobacco by-products have been found in the cervical mucus of women who smoke. Researchers believe that these substances damage the DNA of cells in the cervix and may contribute to the development of cervical cancer.
Human immunodeficiency virus (HIV) infection: HIV is the virus that causes acquired immunodeficiency syndrome (AIDS). Because this virus damages the body’s immune system, it makes women more at risk for HPV infections, which may increase the risk of cervical cancer. Scientists believe that the immune system is important in destroying cancer cells and slowing their growth and spread. In women infected with HIV, a cervical precancer might develop into an invasive cancer faster than it normally would.
Chlamydia infection: Chlamydia is a relatively common kind of bacteria that can infect the female reproductive system. It is spread by sexual contact. Although infection may cause symptoms, many women do not know they are infected unless samples taken at the time of their Pap test are analyzed for this type of bacteria.
Some recent studies suggest that women whose blood test results show past or current chlamydia infection are at greater risk for cervical cancer than are women with a negative blood test. Although further studies are needed to confirm this finding, there is already good reason to avoid this infection and to have it treated with antibiotics promptly after diagnosis. Long-term chlamydia infection is well known as a cause of pelvic inflammation that can lead to infertility.
Diet: Women with diets low in fruits and vegetables may be at increased risk for cervical cancer. Also overweight women are more likely to develop this cancer.
Oral contraceptives (birth control pills): There is evidence that long-term oral contraceptive (OC) use increases the risk of cancer of the cervix. Some research suggests a relationship between using OCs for 5 or more years and an increase in the risk of cervical cancer. In one study the risk was increased fourfold in women who used OCs longer than 10 years.
In the meantime, the American Cancer Society believes that a woman and her doctor should discuss whether the benefits of using OCs outweigh this very slight potential risk. A woman with multiple sexual partners should use condoms to lower her risk of sexually transmitted illnesses no matter what other form of contraception she uses.
Multiple pregnancies: Women who have had many full-term pregnancies have an increased risk of developing cervical cancer. No one really knows why this is, but it has been proven beyond doubt by large studies. One theory is this may be because some of the women may have had a higher exposure to HPV. Also, studies have pointed to hormonal changes during pregnancy as possibly making women more susceptible to HPV infection or cancer growth. Another thought is that the immune system of pregnant women might be weaker, allowing for HPV infection and cancer growth.
Low socioeconomic status: Low socioeconomic status is also a risk factor for cervical cancer. Many women with low incomes do not have ready access to adequate health care services, including Pap tests. This means they may not get treated for precancerous cervical disease.
Diethylstilbestrol (DES): DES is a hormonal drug that was prescribed between 1940 and 1971 for some women thought to be at increased risk for miscarriages. Of every 1,000 women whose mother took DES when pregnant with them, about 1 develops clear-cell adenocarcinoma of the vagina or cervix. Stated another way, about 99.9% of “DES daughters” do not develop these cancers.
Clear cell adenocarcinomas are more common in the vagina than the cervix. The risk appears to be greatest in those whose mothers took the drug during their first 16 weeks of pregnancy. The average age at diagnosis of DES-related clear-cell adenocarcinoma is 19 years. Most DES daughters are now between 35 and 65, so the number of new cases of DES-related cervical and vaginal clear-cell adenocarcinoma has been decreasing during the past 2 decades. However, this type of cancer has recently been found in a woman in her early 40s, and doctors still do not know exactly how long women remain at risk for DES-related cancers.
Although DES daughters have an increased risk of developing clear cell carcinomas, about 40% of women with this cancer have not been exposed to DES or related medications. Some of these patients’ mothers might have taken DES but did not recall the name of the drug. It is certain, however, that women don’t have to be exposed to DES for clear cell carcinoma to develop since some cases of the disease were diagnosed before DES was invented. Some studies suggest that DES daughters are also at somewhat increased risk of developing squamous cell cancer of the cervix and precancerous changes of cervical squamous cells.
Family history of cervical cancer: Cervical cancer may run in some families. If your mother or sister had cervical cancer, your chances of developing the disease are increased by 2 to 3 times. Some researchers suspect that some instances of this familial tendency are caused by an inherited condition that makes some women less able to fight off HPV infection than others. In other instances, women from the same family as a patient already diagnosed may be more likely to have one or more of the other non-genetic risk factors previously described in this section.
How is Cervical Cancer Diagnosed?
Many of the diagnostic tests described below are not necessary for every patient. Decisions about using these tests are based on the results of the physical exam and initial biopsy.
Medical History and Physical Exam
Getting your complete personal and family medical history is the first step your doctor will take in your consultation. This includes information related to risk factors and symptoms of cervical cancer. A complete physical exam will help evaluate your general state of health. In addition, special attention will be paid to your lymph nodes for evidence of metastasis (cancer spread).
Cystoscopy, Proctoscopy, and Examination Under Anesthesia
These are most often done in women who have large tumors. They are not necessary if the cancer is caught early. In cystoscopy a slender tube with a lens and a light is placed into the bladder through the urethra. If you have cervical cancer, this allows your doctor to check your bladder and urethra to see if your cancer is growing into these areas.
Small tissue samples can also be removed during cystoscopy for pathologic (microscopic) testing. This procedure can be done using a local anesthetic, but some patients may need general anesthesia. Your doctor will let you know what to expect before and after the procedure.
Proctoscopy is a visual inspection of the rectum through a lighted tube to check for spread of cervical cancer into your rectum. Your doctor will also do a pelvic exam while you are under anesthesia to find out whether the cancer has spread beyond the cervix.
Imaging Studies
If your doctor finds that you have cervical cancer, certain imaging studies may be done. These include magnetic resonance imaging (MRI) and computed tomography (CT) scans. These studies can show whether the cancer has spread beyond the cervix.
Chest x-ray: A plain x-ray of your chest will be done to see if your cancer has spread to your lungs. This is very unlikely unless your cancer is far advanced. This x-ray can be done in any outpatient setting. If the results are normal, you probably donÂ’t have cancer in your lungs.
Computed tomography (CT): The CT scan is an x-ray procedure that produces detailed cross-sectional images of your body. Instead of taking one picture, like a conventional x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these pictures into an image of a slice of your body (think of a loaf of sliced bread). The machine takes pictures of multiple slices of the part of your body that is being studied. Often after the first set of pictures is taken you may receive an intravenous injection of a contrast agent, or “dye,” that helps better outline structures in your body. A second set of pictures is then taken.
CT scans take longer than regular x-rays and you will need to lie still on a table while they are being done. But just like other computerized devices, they are getting faster and your stay might be pleasantly short. The newest CT scanners take only seconds to complete the study. Also, you might feel a bit confined by the ring-like equipment youÂ’re in when the pictures are being taken.
The contrast dye is injected through an IV (intravenous) line. Some people are allergic to the dye and get hives, a flushed feeling, or, rarely, more serious reactions like trouble breathing and low blood pressure can occur. Be sure to tell your doctor if you have ever had a reaction to any contrast material used for x-rays. If you have, you may need medicine before you can have such an injection during your test.
You may also be asked to drink a contrast solution. This helps outline your intestine if your doctor is looking at organs in your abdomen. The CT scan will provide precise information about the size, shape, and position of a tumor and can help find enlarged lymph nodes that might contain cancer.
Magnetic resonance imaging (MRI): MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of tissue and by certain diseases. A computer translates the pattern of radio waves given off by the tissues into a very detailed image of parts of the body. Not only does this produce cross sectional slices of the body like a CT scanner, it can also produce slices that are parallel with the length of your body.
MRI images are particularly useful in examining pelvic tumors. They are also helpful in detecting cancer that has spread to the brain or spinal cord.
A contrast material might be injected just as with CT scans, but is used less often. MRI scans take longer – often up to an hour. Also, you have to be placed inside a tube-like piece of equipment, which is confining and can upset people with claustrophobia (a fear of enclosed spaces). The machine makes a thumping noise that you may find annoying. Some places provide headphones with music to block this out.
Intravenous urography: Intravenous urography (also known as intravenous pyelogram, or IVP) is useful in finding abnormalities of the urinary tract, such as changes caused by spread of cervical cancer to the pelvic lymph nodes, which may compress or block a ureter. However, this test is rarely used in the initial evaluation of patients with cervical cancer. An IVP is an x-ray of the urinary system taken after injecting a special dye into a vein. This dye is removed from the bloodstream by the kidneys and passes into the ureters and bladder. You will not usually need an IVP if you have already had a CT or MRI.
Positron emission tomography: Positron emission tomography (PET) uses glucose (a form of sugar) that contains a radioactive atom. Cancer cells in the body absorb large amounts of the radioactive sugar and a special camera can detect the radioactivity. This test is useful to see if the cancer has spread to lymph nodes. PET scans are also useful when your doctor thinks the cancer has spread but doesn’t know where. PET scans can be used instead of several different x-rays because they scan your whole body. Newer devices combine a CT scan and a PET scan to even better pinpoint the tumor. However, this test is rarely used for patients with early cervical cancer.
The treatment of cervical cancer varies with the stage of the disease. For early invasive cancer, surgery is the treatment of choice. In more advanced cases, radiation combined with chemotherapy is the current standard of care. In patients with disseminated disease, chemotherapy or radiation provides symptom palliation. The treatment of choice for stage IA disease is surgery.
Stage IB or IIA
For patients with stage IB or IIA disease, treatment options are either combined external beam radiation with brachytherapy or radical hysterectomy with bilateral pelvic lymphadenectomy.
Most retrospective studies have shown equivalent survival rates for both procedures, although such studies usually are flawed due to patient selection bias and other compounding factors. However, a recent randomized study showed identical overall and disease-free survival rates.
Quality-of-life data, particularly in the psychosexual area, is relatively scant.
Postoperative radiation to the pelvis decreases the risk of local recurrence in patients with high-risk factors.
A recent randomized trial showed that patients with parametrial involvement, positive pelvic nodes, or positive surgical margins benefit from a postoperative combination of cisplatin-containing chemotherapy and pelvic radiation.
Stage IIB-IVA
For locally advanced cervical carcinoma (stages IIB, III, and IVA), radiation therapy traditionally has been the treatment of choice. For treatment with radiation alone, 5-year survival rates reportedly are 65-75%, 35-50%, and 15-20% for stages IIB, III, and IVA, respectively. Treatment begins with a course of external beam radiation to reduce tumor mass to enable subsequent intracavitary application. Brachytherapy is delivered using afterloading applicators that are placed in the uterine cavity and vagina.
• Combined chemotherapy plus radiation therapy for cervical cancer
In the Radiation Therapy Oncology Group trial, 403 patients with bulky IB and IIB-IVA cancers were randomized to either radiotherapy to a pelvic and paraaortic field or pelvic radiation with concurrent cisplatin and fluorouracil. Rates of both disease-free survival and overall survival were significantly higher in the group that received combination treatment.
Rose and associates conducted a Gynecologic Oncology Group (GOG) trial for patients with stage IIB, III, or IVA cancer, comparing the combination of radiation with 3 different chemotherapy regimens (cisplatin alone, cisplatin/5-fluorouracil/hydroxyurea, and hydroxyurea alone). Overall survival rates were significantly higher in the 2 groups that received cisplatin-containing regimens.
In another GOG trial, patients with bulky stage IB disease were randomized to either radiation alone or a combination of weekly cisplatin and radiation. All patients had adjuvant hysterectomy. Both disease-free survival and overall survival rates were significantly higher in the combined-therapy group at 4 years of follow-up.
Based on the aforementioned study results, using cisplatin-based chemotherapy in combination with radiation for patients with locally advanced cervical cancer now is a reasonable option.
Surgical Care:
• Carcinoma in situ (stage 0) is treated with local ablative measures such as cryosurgery, laser ablation, and loop excision.
Hysterectomy should be reserved for patients with other gynecologic indications to justify the procedure.
After local treatment, these patients require lifelong surveillance.
• The treatment for disseminated cervical cancer primarily is palliative in nature because cure is not possible.
Chemotherapy with single agents such as cisplatin or ifosfamide results in response rates of approximately 20%. Combination regimens have higher response rates and can prolong disease-free survival. However, toxicity is increased and no survival advantage is gained. In addition, the duration of response usually is short.
Palliative radiation often is used individually to control bleeding, pelvic pain, or urinary or partial large bowel obstructions from pelvic disease.
Invasive procedures such as nephrostomy or diverting colostomy sometimes are performed in this group of patients to improve their quality of life.
Special effort should be made to ensure comprehensive palliative care, including adequate pain control for these patients.
• The standard treatment for microinvasive disease (stage IA) is total hysterectomy.
Lymph node dissection is not required if the depth of invasion is less than 3 mm and no lymphovascular invasion is noted.
Selected patients with stage IA1 disease but no lymphovascular space invasion who desire to maintain fertility may have a therapeutic conization with close follow-up, including cytology, colposcopy, and endocervical curettage.
Patients with medical comorbidities who are not surgical candidates can be successfully treated with radiation.
Why is it so important to be treated by a gynecologic oncologist?
The importance of being treated by a gynecologic oncologist cannot be stressed enough. According to numerous medical studies, there are significant survival advantages for those women who are treated, managed, and operated on by a gynecologic oncologist.
A gynecologic oncologist is a professional who specializes in treating women with reproductive tract cancers.
Gynecologic oncologists are initially trained as obstetrician/gynecologists and then undergo three-four years of specialized education in all of the effective forms of treatment for gynecologic cancers (surgery, radiation, chemotherapy and experimental treatments) as well as the biology and pathology of gynecologic cancers.