What is cervical cancer?

The cervix is the lower part of the uterus (womb). It is sometimes called the uterine cervix. The body (upper part) 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 exocervix (or ectocervix). The place where these 2 parts meet is called the transformation zone. Most cervical cancers start in the transformation zone.

Cancer of the cervix (also known as cervical cancer) begins in the cells lining the cervix. The 2 main types of cells lining the cervix are squamous cells and glandular cells. Most cervical cancers begin in those cells. These cells do not suddenly change into cancer. Instead, the normal cells of the cervix 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.

Cervical cancers and cervical pre-cancers are classified by how they look under a microscope. There are 2 main types of cervical cancer: squamous cell carcinoma and adenocarcinoma. About 80% to 90% of cervical cancers are squamous cell carcinomas. These cancers start in the squamous cells that cover the surface of the exocervix. Under the microscope, this type of cancer is made up of cells that are like squamous cells. Squamous cell carcinomas most often begin where the exocervix 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. Less commonly, cervical cancers have features of both squamous cell carcinomas and adenocarcinomas. These are called adenosquamous carcinomas or mixed carcinomas.

Although cervical cancers start from cells with pre-cancerous changes (pre-cancers), only some of the women with pre-cancers of the cervix will develop cancer. The change from pre-cancer to cancer usually takes several years - but it can happen in less than a year. For most women, pre-cancerous cells will remain unchanged and go away without any treatment. Still, in some cases pre-cancers turn into true (invasive) cancers. Treating all precancers can prevent almost all true cancers. Pre-cancerous changes and specific types of treatment for precancers are discussed in the section, "Can Cervical Cancer Be Prevented?"

Importance of cervical cancer screening

The goal of screening for cervical cancer is to find cervix cell changes and early cervical cancers before they cause symptoms. Screening refers to the use of tests and exams to find a disease, such as cancer, in people who do not have any symptoms. Early detection means applying a strategy that results in an earlier diagnosis of cervical cancer than otherwise might have occurred. Screening tests offer the best opportunity to detect cervical cancer at an early stage when successful treatment is likely. Screening can also actually prevent most cervical cancers by finding abnormal cervix cell changes (pre-cancers) so that they can be treated before they have a chance to turn into a cervical cancer.

Cancer of the cervix may be prevented or detected early by regular Pap tests. If it is detected early, cervical cancer is one of the most successfully treatable cancers. In the United States, the cervical cancer death rate declined by 74% between 1955 and 1992, in large part due to the effectiveness of Pap smear screening. The death rate continues to decline each year.

Despite the recognized benefits of Pap test screening, not all American women take advantage of it. As of the year 2000, slightly over 80% of women had had a Pap test in the previous 3 years. Asian-American women, recent immigrants, women without health insurance, and women with fewer years of education were less likely to have had regular Pap tests.

Between 60% and 80% of American women with newly diagnosed invasive cervical cancer have not had a Pap smear in the past 5 years. Many of these women have never had a Pap test.

Cervical cancer deaths are higher in populations around the world where women do not have routine Pap tests. In fact, cervical cancer is the major cause of cancer deaths in women in many developing countries. These cases are usually diagnosed at an invasive late stage, rather than as pre-cancers or early cancers.

What are the risk factors for cervical cancer?

A risk factor is anything that changes 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 many cancers. But having a risk factor, or even several, does not mean that you will get the disease.

Several risk factors increase your chance of getting cervical cancer. Women without any of these risk factors rarely develop cervical cancer. Although these factors increase the odds of getting cervical cancer, many women with these risk factors do not develop this disease. When a woman develops cervical cancer or pre-cancerous changes of the cervix, 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 (like smoking or human papillomavirus infection), rather than those that you cannot (such as your age and family history). It is still important, though, to know about risk factors that cannot be changed, because it's even more important for women who have these factors to get regular Pap tests to detect cervical cancer early.

Cervical cancer risk factors include:

Human papilloma virus infection

The most important risk factor for cervical cancer is infection by the human papilloma virus (HPV). HPV is a group of more than 100 related viruses. They are called papilloma viruses because some of them can cause a type of growth called a papilloma. Papillomas, more commonly called warts, are benign tumors - they are not cancers. HPV is passed from one person to another during skin-to-skin contact. HPV can be spread during sex - including vaginal intercourse, anal intercourse, and even during oral sex.

Doctors believe that women must have been infected by HPV before they will develop cervical cancer. Certain types of HPV are called "high-risk" or “carcinogenic” types of HPV because they are often the cause of cancer of the cervix. These types include HPV 16, HPV 18, HPV 31, HPV 33, and HPV 45, as well as some others. About 70% of all cervical cancers are caused by HPV 16 and 18.

Different types of HPV cause warts on different parts of the body. Some types cause common warts on the hands and feet. Other types tend to cause warts on the lips or tongue.

Still other types of HPV may cause warts to appear on or around the female and male genital organs and in the anal area. These warts may barely be visible or they may be several inches across. The medical term for genital warts is condyloma acuminatum. Two types of HPV, HPV 6 and HPV 11, cause most cases of genital warts. These 2 types are seldom linked to cervical cancer; and so are called "low-risk" types of HPV. Other sexually transmitted HPVs have been linked with genital and anal cancers in both men and women.

Many women become infected with HPV, but very few will ever develop cervical cancer. In most cases the body's immune system fights off the virus, and the infection goes away without any treatment. In some cases, for reasons that we don't understand, the infection persists, which can cause cervical cancer. Although there is currently no cure for infection with HPV, there are ways to treat the warts and abnormal cell growth that HPV causes.

The Pap test looks for changes in cervical cells caused by HPV infection. Newer tests look for HPV infections by finding genes (DNA) from HPV in the cells. Some doctors use the test for HPV to help decide what to do when a woman has a mildly abnormal Pap test result. If the test finds a high-risk type of HPV, it may mean she will need a full evaluation with a colposcopy procedure.

HPV infections occur mainly in young women and are less common in women over 30. The reason for this is not clear. Uncircumcised men are thought to be more likely to have the virus and be able to pass it on to someone else. HPV infection can be present for years without any symptoms. Even when someone doesn't have visible warts (or any other symptom), he (or she) can still be infected with HPV and pass the virus to somebody else.

Condoms ("rubbers") do offer some protection against HPV, but they cannot completely protect against infection. This is because condoms don't cover every possible HPV-infected area of the body, such as skin of the genital or anal area. HPV can still be passed from one person to another by skin-to-skin contact with an HPV-infected area of the body that is not covered by the condom. Still, it is important to use condoms to protect against AIDS and other sexually transmitted illnesses that are passed on through some body fluids.

Vaccines have been developed that may protect against infection with some types of HPV. By preventing HPV infection, these vaccines may reduce cervical cancer rates in the future. Right now, there is an HPV vaccine that has been approved for use in the United .States. by the Food and Drug Administration (FDA). This vaccine is called Gardasil^®, and it protects against HPV types 6, 11, 16, and 18. More HPV vaccines are being developed and tested. Giardasil is described in more detail in the section, “Can Cervical Cancer Be Prevented?” Other vaccines are also in development.

Although scientists believe that it is necessary to have had HPV for cervical cancer to develop, most women with this virus do not develop cancer. Doctors believe that other factors must come into play for cancer to develop. Some of these 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 cervix cells and may contribute to the development of cervical cancer.

Immunosuppression

Human immunodeficiency virus (HIV) is the virus that causes acquired immunodeficiency syndrome (AIDS). HIV damages the body's immune system and seems to make women more likely to become infected with HPV. This may be what increases the risk of cervical cancer in women with AIDS. 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 pre-cancer 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 reproductive system. It is spread by sexual contact. Some studies have seen a higher risk of cervical cancer in women whose blood test results show past or current chlamydia infection (compared with women with normal test results). Infection with chlamydia often causes no symptoms in women. A woman may not know that she is infected at all unless she is tested for chlamydia when she gets her pelvic exam. Long-term chlamydia infection can cause pelvic inflammation, leading 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 taking oral contraceptives (OCs) for a long time increases the risk of cancer of the cervix. Research suggests that the risk of cervical cancer goes up the longer a woman takes OCs, but the risk goes back down again after the OCs are stopped. In a recent study, the risk of cervical cancer was doubled in women who took birth control pills longer than 5 years, but the risk returned to normal 10 years after they were stopped.

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 infections 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 true. One theory is this may be because some of the women may have been exposed more to HPV through un-protected sexual contact. 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

Poverty 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 screened or treated for pre-cancerous cervical disease.

Diethylstilbestrol (DES)

DES is a hormonal drug that was given to some women to prevent miscarriage during the years between 1940 and 1971. Women whose mothers took DES when pregnant with them are often called "DES daughters." These women develop clear cell adenocarcinoma of the vagina or cervix more often than would normally be expected. There is about 1 case of this type of cancer in every 1,000 women whose mother took DES during their pregnancy. This means that about 99.9% of "DES daughters" do not develop these cancers.

DES-related clear cell adenocarcinoma is more common in the vagina than the cervix. The risk appears to be greatest in women whose mothers took the drug during their first 16 weeks of pregnancy. The average age of women when they are diagnosed with DES-related clear-cell adenocarcinoma is 19 years. Since the use of DES during pregnancy was stopped by the FDA in 1971, even the youngest DES daughters are older than 35 - past the age of highest risk. Still, there is no age cut-off when these women are safe from DES-related cancer - doctors do not know exactly how long women will remain at risk.

DES daughters may also be at increased risk of developing pre-cancerous changes of cervical squamous cells and squamous cell cancer of the cervix. These pre-cancers and cancers seem to be linked to HPV.

Although DES daughters have an increased risk of developing clear cell carcinomas women don’t have to be exposed to DES for clear cell carcinoma to develop. In fact, women were diagnosed with the disease before DES was invented.

Family history of cervical cancer

Cervical cancer may run in some families. If a woman’s mother or sister had cervical cancer, her chances of developing the disease are 2 to 3 times higher than normal. Some researchers suspect this familial tendency is caused by an inherited condition that makes some women less able to fight off HPV infection than others.

Signs and symptoms of cervical cancer

Women with early cervical cancers and pre-cancers usually have no symptoms. Symptoms often do not begin until a pre-cancer becomes a "true" invasive cancer and grows into nearby tissue. When this happens, the most common symptoms are:

• Abnormal vaginal bleeding, such as bleeding after sex (vaginal intercourse), bleeding after menopause, bleeding and spotting between periods, and having (menstrual) periods that are longer or heavier than usual. Bleeding after douching, or after a pelvic exam is a common symptom of cervical cancer but not pre-cancer.

• An unusual discharge from the vagina - the discharge may contain some blood and may occur between your periods or after menopause.

• Pain during sex (vaginal intercourse).

These signs and symptoms can also be caused by conditions other than cervical cancer. For example, an infection can cause pain or, rarely, bleeding. Still, if you have any of these problems, you should see your health care professional right away - even if you have been getting regular Pap tests. If it is an infection, it will need to be treated. If it is cancer, ignoring symptoms may allow it 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 exam.

Can cervical cancer be prevented?

Since the most common form of cervical cancer starts with pre-cancerous changes, there are 2 ways to stop this disease from developing. The first way is to prevent the pre-cancers, and the second is to find and treat pre-cancers before they become true cancers.

Things to do to prevent pre-cancers

Avoid being exposed to HPV

You can prevent most pre-cancers of the cervix by avoiding exposure to HPV. Certain types of sexual behavior increase a woman's risk of getting HPV infection, such as:

• having sex at an early age
• having many sexual partners
• having a partner who has had many sex partners
• having sex with uncircumcised males

Delay sex

Waiting to have sex until you are older can help you avoid HPV. It also helps to limit your number of sexual partners and to avoid having sex with someone who has had many other sexual partners. Remember that someone can have HPV for years yet have no symptoms - it does not always cause warts or any other symptoms. Someone can have the virus and pass it on without knowing it.

Use condoms

Condoms provide some protection against HPV. One study found that when condoms are used correctly they can lower the HPV infection rate by about 70% - if they are used every time sex occurs. Condoms cannot protect completely because they don't cover every possible HPV-infected area of the body, such as skin of the genital or anal area. Still, condoms provide some protection against HPV, and they also protect against HIV and some other sexually transmitted diseases.

Don’t smoke

Not smoking is another important way to reduce the risk of cervical pre-cancer and cancer.

Get vaccinated

Vaccines have been developed that can protect women from HPV infections. So far, a vaccine that protects against HPV types 6, 11, 16 and 18 (Gardasil^®) and one that protects against types 16 and 18 (Cervarix^®) have been studied.

Gardasil has been approved for use in this country by the FDA. It requires a series of 3 injections over a 6-month period. The second injection is given 2 months after the first one, and the third is given 4 months after the second. Side effects are said to be mild. The most common one is short-term redness, swelling, and soreness at the injection site. In clinical trials, Gardasil prevented genital warts caused by HPV types 6 and 11 and prevented pre-cancers and cancers of the cervix caused by HPV types 16 and 18. This vaccine only works to prevent HPV infection -- it will not treat an infection that is already there.

To be most effective, the HPV vaccine should be given before a person starts having sex. The Federal Advisory Committee on Immunization Practices (ACIP) has recommended that the vaccine be given routinely to females aged 11 to 12. It can be given to younger females (as young as age 9) at the discretion of doctors. ACIP also recommended women ages 13 to 26 who have not yet been vaccinated get "catch-up" vaccinations.

The American Cancer Society also recommends that the vaccine be routinely given to females aged 11 to 12 and as early as age 9 years at the discretion of doctors. The Society also agrees that “catch-up” vaccinations should be given to females aged 13 to 18. The independent panel making the Society recommendations found that there was not enough proof of benefit to recommend catch-up vaccination for every woman aged 19 to 26 years. As a result, the American Cancer Society recommends that women aged 19 to 26 talk with their health care provider about the risk of previous HPV exposure and potential benefit from vaccination before deciding to get vaccinated. Research is now being done on using Gardasil in older women and in males. The American Cancer Society guideline focuses on Gardasil at this time. As new information on Cervarix, Gardasil, and other new products becomes available, these guidelines will be updated.

Gardasil is expensive - the vaccine series costs around $360 (not including any doctor’s fee or the cost of giving the injections). It should be covered by most medical insurance plans (if given according to ACIP guidelines). It should also be covered by government programs that pay for vaccinations in children under 18. Because this vaccine costs so much, you may want to check your coverage with your insurance company first.

It is important to realize that the vaccine doesn’t protect against all cancer-causing types of HPV, so routine Pap tests are still necessary. One other benefit of the vaccine is that it protects against the 2 viruses that cause 90% of genital warts.

For more information on the vaccine and HPV, please see our document, Human Papilloma Virus: Questions and Answers.

Finding pre-cancerous changes

One way to prevent cervix cancer is to have testing (screening) to find pre-cancers before they can turn into invasive cancer. The Pap test (or Pap smear) is the most common way to do this. If a pre-cancer is found, it can be treated, stopping cervical cancer before it really starts. Since the HPV vaccine doesn't protect against all of the HPV types that can cause cancer of the cervix, it cannot prevent all cases of cervical cancer. This is why it is very important that women continue to have Pap tests, even after they’ve been vaccinated. Most invasive cervical cancers are found in women who have not had regular Pap tests.

The American Cancer Society recommends the following guidelines for early detection:

• All women should begin cervical cancer testing (screening) about 3 years after they start having sex (vaginal intercourse). A woman who waits until she is over 18 to have sex should start screening no later than age 21. A regular Pap test should be done every year. If the newer liquid-based Pap test is used, testing can be done every 2 years.

• Beginning at age 30, women who have had 3 normal Pap test results in a row may be tested less often - every 2 to 3 years. Either the conventional (regular) Pap test or the liquid-based Pap test can be used.

• Another reasonable option for women over 30 is to get tested every 3 years (but not more frequently) with either the regular Pap test or liquid-based Pap test, plus the HPV DNA test (see below for more information on this test).

• Women who have certain risk factors should continue getting tested yearly. This includes women exposed to diethylstilbestrol (DES) before birth and those with a weakened immune system (from HIV infection, organ transplant, chemotherapy, or chronic steroid use).

• Women who have had a total hysterectomy (removal of the uterus and cervix) may choose to stop having cervical cancer testing, unless the surgery was done as a treatment for cervical cancer or pre-cancer. Women who have had a hysterectomy without removal of the cervix (simple hysterectomy) need to continue cervical cancer screening, and should continue to follow the guidelines above.

• Women 70 years of age or older who have had 3 or more normal Pap tests in a row and no abnormal Pap test results in the last 10 years may choose to stop having cervical cancer testing. Women with a history of cervical cancer, DES exposure before birth, HIV infection, or a weakened immune system should continue to have testing as long as they are in good health.

Some women believe that they can stop having Pap tests once they have stopped having children. This is not correct. They should continue to follow American Cancer Society guidelines.

The Papanicolaou (Pap) test

The Pap test (Pap smear) is the main screening test for cervical cancer and pre-cancerous changes.

Although the Pap test has been more successful than any other screening test in preventing a cancer, it is not perfect. One of the limitations of the Pap test is that it needs to be examined by humans, so an accurate analysis of the hundreds of thousands of cells in each sample is not always possible. Engineers, scientists, and doctors are working together to improve this test. Because some abnormalities may be missed (even when samples are looked at in the best laboratories), it is not a good idea to have this test less often than American Cancer Society guidelines recommend.

Pelvic exam versus Pap test

Many people confuse pelvic exams with Pap tests. The pelvic exam is part of a woman's routine health care. During a pelvic exam, the doctor looks at and feels the reproductive organs, including the uterus and the ovaries and do tests for sexually transmitted disease. Pap tests are often done during pelvic exams, but you can have a pelvic exam without having a Pap test. A pelvic exam without a Pap test will not help find cervical cancer at an early stage or find abnormal cells of the cervix.

The Pap test is often done at the start of the pelvic exam, after the speculum is placed. To do a Pap test, the doctor must remove cells from the cervix by gently scraping or brushing with a special instrument. Pelvic exams may help find other types of cancers and reproductive problems, but only Pap tests give information on early cervical cancer or precancers.

How the Pap test is done

Cytology is the branch of science that deals with the structure and function of cells. It also refers to tests to diagnose cancer by looking at cells under the microscope. The Pap test (or Pap smear) is a procedure used to collect cells from the cervix for cervical cytology testing.

The health care professional first places a speculum inside the vagina. The speculum is a metal or plastic instrument that keeps the vagina open so that the cervix can be seen clearly. Next, using a small spatula, a sample of cells and mucus is lightly scraped from the exocervix (the surface of the cervix that is closest to the vagina). A small brush or a cotton-tipped swab is then used to take a sample from the endocervix (the inside part of the cervix that is closest to the body of the uterus). There are 2 main ways to prepare the cell samples so that they can be examined under a microscope in the laboratory.

1. Conventional cytology: The first way is to smear the sample directly onto a glass microscope slide, which is then sent to the laboratory. For about 50 years, all cervical cytology samples were handled this way. This method works quite well and is relatively inexpensive, but it does have some drawbacks. One problem with this method is that the cells smeared onto the slide are sometimes piled up on each other, making it hard to see the cells at the bottom of the pile. Also, white blood cells (pus), increased mucus, yeast cells, or bacteria from infection or inflammation can hide the cervical cells. Another problem with direct smears is that if the slides are not treated (with a preservative) right away, the cells can dry out. This can make it difficult to tell if there is something wrong with the cells. If the cervical cells cannot be seen well (because of any of these problems), the Pap smear may need to be done again.
   
   
2. Liquid based cytology: Another method is to put the sample of cells from the cervix into a special preservative liquid (instead of putting them on a slide directly). Technicians use special lab instruments that spread the cells in the liquid onto glass slides to look at under the microscope. This method is called liquid-based cytology, or a liquid-based Pap test. The liquid helps remove some of the mucus, bacteria, yeast, and pus cells in a sample. It also allows the cervical cells to be spread more evenly on the slide and keeps them from drying out and distorting. Cells kept in the liquid can also be tested for HPV. Using liquid-based testing reduces the chance that the Pap test will need to be repeated, but it does not seem to find more pre-cancers than a regular Pap test. This method, also known by brand names ThinPrep^® or AutoCyte^®, is more expensive than a usual Pap test.

Another way to improve the Pap test is by using computerized instruments that can spot abnormal cells in Pap tests. The AutoPap^® instrument has been approved by the FDA to read Pap tests first (instead of them being examined by a technologist). It is also approved by the FDA for rechecking Pap test results that were read as normal by technologists. Any smear identified as abnormal by the AutoPap^® would then be reviewed by a doctor or a technologist.

Computerized instruments can find abnormal cells that technologists sometimes miss. Most of the abnormal cells found in this way are in rather early stages, such as atypical squamous cells (ASCs), but sometimes high-grade abnormalities missed by human testing can be found. Scientists do not know yet whether the instrument can find enough high-grade abnormalities missed by human testing to have a real impact on preventing invasive cervical cancers. Automated testing also increases the cost of the cervical cytology testing.

For now, the best way to detect cervical cancer early is to make certain that all women are tested according to American Cancer Society guidelines. Unfortunately, many of the women most at risk for cervical cancer are not being tested often enough or at all.

Making your Pap tests more accurate

You can do several things to make your Pap test as accurate as possible:

• Try not to schedule an appointment for a time during your menstrual period. The best time is at least 5 days after your menstrual period stops.
• Don't use tampons, birth-control foams, jellies or other vaginal creams for 2 to 3 days before the test.
• Don't douche for 2 to 3 days before the test.
• Don't have sexual intercourse for 2 days before the test.

Is there a "home" Pap test?

Doctors have been trying to find ways to get more women involved in cervical cancer screening. Some have proposed methods that would allow women to obtain cervical cell samples at home. For this test, a woman would collect cervical cells herself by inserting a small plastic applicator into the vagina and moving it around on the cervix. This would be placed in a special container to preserve the cells. This type of approach has been used to check for sexually transmitted diseases in poorer countries, and it has also been useful to check for HPV infections. So far, however, no "home-based" Pap test has been approved for use in the U.S. Currently, the American Cancer Society does not recommend any "at home" Pap test.

How Pap test results are reported

The most widely used system for describing Pap test results is the Bethesda System (TBS). This system has been revised twice since it was developed in 1988 -- first in 1991 and, most recently, in 2001. The information that follows is based on the 2001 version. There are 3 main categories, some of which have sub-categories:

• negative for intraepithelial lesion or malignancy,
• epithelial cell abnormalities, and
• other malignant neoplasms.

Negative for intraepithelial lesion or malignancy: This first category means that no signs of cancer, precancerous changes, or other significant abnormalities were found. Some specimens in this category appear entirely normal. Others may have findings that are unrelated to cervical cancer, such as signs of infection (with yeast, herpes, or trichomonas, for example). Some cases may also show "reactive cellular changes", which the way cervical cells respond to infection or other irritation.

Epithelial cell abnormalities: The second category, epithelial cell abnormalities, means that the cells of the lining layer of the cervix show changes that might be cancer or a pre-cancerous condition. This category is divided into several groups for squamous cells and glandular cells. The epithelial cell abnormalities for squamous cells are:

Atypical squamous cells (ASCs): This term is used when there are cells that look abnormal, but it is not possible to tell (by looking at the cells under a microscope) if this caused by infection, irritation, or precancer. This group is further divided into 2 groups, atypical squamous cells of uncertain significance (ASC-US) and atypical squamous cells where high-grade squamous intraepithelial lesion (SIL) can’t be excluded (ASC-H). Most of the time, cells labeled ASC-US are not pre-cancer.. Some doctors will recommend repeating the Pap test after several months. Some doctors use the HPV DNA test to help them decide on the best treatment plan. If a woman with ASC-US is infected with a high-risk type of HPV, doctors are more inclined to do a colposcopy. The term ASC-H is used if a SIL is suspected. Colposcopy is usually done in cases of ASC-H.

Squamous intraepithelial lesions (SILs): These abnormalities are subdivided into low-grade SIL and high-grade SIL. All patients with this Pap test result should have colposcopy. High-grade SILs are less likely than low-grade SILs to go away without treatment. They are also more likely to eventually develop into cancer if they are not treated. Treatment can cure all SILs and prevent true cancer from developing. A Pap test cannot tell for certain whether a woman has a high- or low-grade SIL. It merely flags the result as fitting into one of these abnormal categories. All patients with a Pap test result of SIL should have colposcopy. The need for treatment is based on the results of the colposcopy. Since most SILs are positive for HPV, HPV testing is not very helpful in deciding what to do for an SIL.

Squamous cell carcinoma: This result means that the woman is likely to have an invasive squamous cell cancer. Further testing will be done to be sure of the diagnosis beforetreatment can be planned.

The Bethesda System also describes epithelial cell abnormalities for glandular cells.

Adenocarcinoma: Cancers of the glandular cells are called adenocarcinomas. In some cases, the pathologist examining the cells can suggest whether the adenocarcinoma started in the endocervix, in the uterus (endometrium), or elsewhere in the body.

Atypical glandular cells: When the glandular cells do not look normal, but have features that do not permit a clear decision as to whether they are cancerous, the term used is atypical glandular cells (AGCs). The patient will usually have more testing if her cervical cytology result shows atypical glandular cells.

Other malignant neoplasms: This category refers to forms of cancer that rarely affect the cervix, such as malignant melanoma, sarcomas, and lymphoma.

Other methods of describing Pap test results have also been used in the past.

The HPV DNA Test

As mentioned earlier, the most important risk factor for developing cervical cancer is infection with HPV. Doctors can now test for the types of HPV that are most likely to cause cervical cancer ("high-risk" or "carcinogenic" types) by looking for pieces of their DNA in cervical cells. The test is done in a similar way to the Pap test in terms of how the sample is collected, and in some cases can even be done on the same sample.

The HPV DNA test can be used in 2 situations:

• The FDA recently approved the HPV gene test to be used combination with the Pap test to screen for cervical cancer in women over 30 years old (see American Cancer Society screening guidelines above). It does not replace the Pap test.. Women in their 20s who are sexually active are much more likely (than older women) to have an HPV infection that will go away on its own. For these younger women, results of this test are not as significant and may be more confusing. . For this reason, the HPV DNA test is not recommended as a screening test in women under 30. For more information, see the American Cancer Society documents, What Every Woman Should Know About Cervical Cancer and the Human Papilloma Virus and Thinking About Testing for HPV?

• The HPV DNA test is also used in women of any age who have slightly abnormal Pap test results to find out if they might need more testing or treatment. (see next section).

Other tests for women with abnormal cervical cytology results

The Pap test is a screening test, not a diagnostic test - it cannot tell for certain that cancer is present. An abnormal Pap test result means that you will likely need to have other tests to find out if a cancer or a pre-cancer is actually present. The tests that are used include colposcopy (with biopsy) and endocervical scraping. These tests are commonly used when the results of a Pap test are reported as SIL, atypical glandular cells, or cancer. If a biopsy shows a pre-cancer, doctors will take steps to keep an actual cancer from developing.

Doctors are less certain about what to do when the Pap test result shows atypical squamous cells. In deciding what to do, some doctors take into account your previous Pap test results, whether you have any cervical cancer risk factors, whether you have remembered to have Pap tests done in the past, and whether the test result is ASC-H or ASC-US. For ASC-H, many doctors will recommend colposcopy and biopsy. For ASC-US some doctors will recommend colposcopy and biopsy if a high-risk HPV DNA is detected, but others recommend repeating the Pap test after several months.

Colposcopy

If you have certain symptoms that suggest cancer or if your Pap test shows abnormal cells, you will need to have a test called colposcopy. In this procedure you will lie on the exam table as you do with a pelvic exam. A speculum will be placed in the vagina to help the doctor see the cervix. The doctor will use the colposcope to examine the cervix. The colposcope is an instrument with magnifying lenses (like binoculars), that lets the doctor see the surface of the cervix closely and clearly. The doctor may "treat" your cervix with a weak solution of acetic acid (similar to vinegar) to make any abnormal areas easier to see.

Colposcopy is not painful, has no side effects, and can be done safely even if you are pregnant. If an abnormal area is seen on the cervix, a biopsy will be done. For a biopsy, small piece of tissue is removed from the area that looks abnormal. The sample is sent to a pathologist to look at under a microscope. A biopsy is the only way to tell for certain whether an abnormal area is a pre-cancer, a true cancer, or neither.

Cervical biopsies

Several types of biopsies are used to diagnose cervical precancers and cancers. If the biopsy can completely remove all of the abnormal tissue, it may be the only treatment needed. In some situations, additional treatment of precancers or cancers is needed.

Colposcopic biopsy: For this type of biopsy, a doctor or other health care professional first examines the cervix with a colposcope to find the abnormal areas. Using a biopsy forceps, the doctor will remove a small (about 1/8-inch) section of the abnormal area on the surface of the cervix. The biopsy procedure may cause mild cramping or brief pain, and you may have light bleeding afterward. A local anesthetic is sometimes used to numb the cervix before the biopsy.

Endocervical curettage (endocervical scraping): The colposcope does not help the doctor see into the endocervix. The endocervix will have to be scraped to see if it is affected by pre-cancer or cancer. This procedure is usually done at the same time as the colposcopic biopsy. A local anesthetic may be used to numb the cervix. Then, a narrow instrument (called a curette) is inserted into the endocervical canal (the passage between the outer part of the cervix and the inner part of the uterus). Some of the tissue that is lining the endocervical canal is removed by scraping with the curette. This tissue sample is sent to the lab for examination. After this procedure, patients may feel a cramping pain, and they may also have some light bleeding.

Cone biopsy: In this procedure, also known as conization, the doctor removes a cone-shaped piece of tissue from the cervix. The base of the cone is formed by the exocervix (outer part of the cervix), and the point or apex of the cone is from the endocervical canal. The transformation zone (the border between the exocervix and endocervix) is contained within the cone. This is the area of the cervix where pre-cancers and cancers are most likely to develop. The cone biopsy can be used as a treatment to completely remove many pre-cancers and some very early cancers. Having a cone biopsy will not keep most women from getting pregnant, but if the biopsy removes large amount of tissue these women may have a higher risk of giving birth prematurely.

There are 2 methods commonly used for cone biopsies: the loop electrosurgical excision procedure (LEEP; also called large loop excision of the transformation zone [LLETZ]) and the cold knife cone biopsy.

• LEEP (LLETZ): With this method, the tissue is removed with a thin wire loop that is heated by electrical current and acts as a scalpel. For this procedure, a local anesthetic is used, and it can be done in your doctor's office. It can take as little as 10 minutes. You may have mild cramping during and after the procedure, and mild to moderate bleeding may persist for several weeks.

• Cold knife cone biopsy: This method uses a surgical scalpel or a laser instead of a heated wire to remove tissue. It requires general anesthesia (you are asleep during the operation) and is done in a hospital, but no overnight stay is needed. After the procedure, cramping and some bleeding may persist for a few weeks.

How biopsy results are reported: The terms for reporting biopsy results are slightly different from the Bethesda System for reporting Pap test results. Pre-cancerous changes are called "cervical intraepithelial neoplasia" (CIN) or, rarely, "dysplasia," instead of "squamous intraepithelial lesion" (SIL). The terms for reporting cancers ("squamous cell carcinoma" and "adenocarcinoma") are the same.

How women with abnormal Pap test results are treated to prevent cervical cancers from developing

If an abnormal area is seen during the colposcopy, your doctor will be able to remove it with LEEP (LLETZ procedure). Other options include a cold knife cone biopsy and destroying the abnormal cells with cryosurgery or laser surgery.

During cryosurgery, the doctor uses a metal probe cooled with liquid nitrogen to kill the abnormal cells by freezing them.

In laser surgery, the doctor uses a focused beam of high-energy light to vaporize (burn off) the abnormal tissue. This is done through the vagina, with local anesthesia.

Both cryosurgery and laser surgery can be done in a doctor's office or clinic. After treatment, you may have alot of watery brown discharge for a few weeks.

These treatments are almost always effective in destroying pre-cancers and preventing them from developing into true cancers. You will need follow-up exams to make sure that the abnormality does not come back. If it does, the treatments can be repeated.

Cervical cancer prevention and screening: Financial issues

Financial issues can play an important role in whether or not women are screened for cervical cancer. Women with lower incomes and those without health insurance are less likely to be screened.

Many states ensure that private insurance companies, Medicaid, and public employee health plans provide coverage and reimbursement for Pap smear screening tests. The ACS supports such coverage assurances, because they remove financial barriers for women who have health insurance, but whose insurance plans previously did not cover Pap smears.

Other programs are also available to help provide financial assistance for women with lower incomes and those without insurance.

State efforts to ensure coverage of cervical cancer screening for private health insurance

Twenty-six states and the District of Columbia now require private health insurers to cover annual cervical cancer screening services (see table).

A few states have also enacted laws specifically requiring managed care organizations such as health maintenance organizations (HMOs) and preferred provider organizations (PPOs) to cover cervical cancer screening. Some states have ensured that public employee health benefit plans cover cervical cancer screening. While Maryland does not have a statewide benefit for cervical cancer screening, they do have a unique law requiring hospitals to offer a Pap test to adult female inpatients. Nebraska has a law that requires the Department of Health to contract with health clinics of American Indian tribes to cover cervical cancer detection services. Individual state laws vary widely. Ask your health care provider what coverage is mandatory in your state

States With Laws Assuring Coverage of Cervical Cancer Screening (as of December 2006)

State	Private Insurance	Other
Alaska	Annual Pap test for persons age 18 and over	Copay, deductibles, and/or co-insurance may apply
California	Annual Pap test, pelvic exam, and HPV testing Need referral for patient's health care provider	Copay, deductibles and/or co-insurance may apply
Delaware	Annual Pap test for persons age 18 and over	Copay, deductibles and/or co-insurance may apply
District of Columbia	Annual Pap test More frequent tests if recommended by a physician
Georgia	Annual Pap test Need referral of patient's health care provider More frequent tests if recommended by a physician	Copay, deductibles and/or co-insurance may apply
Illinois	Annual Pap test
Kansas	Annual Pap test Need referral of patient's health care provider	Copay, deductibles and/or co-insurance may apply
Louisiana	Annual Pap test
Maine	Annual Pap test and pelvic exam Need referral of patient's health care provider
Maryland	Covers HPV testing only, according to ACOG Guidelines (see below)	Copay, deductibles and/or co-insurance may apply
Massachusetts	Annual Pap test for persons age 18 and over
Minnesota	Cover Pap test when ordered by doctor, according to standard practice
Missouri	Cover Pap test and pelvic exam according to ACS guidelines (see below)	Copay, deductibles and/or co-insurance may apply
Nevada	Annual Pap test for persons age 18 and over
New Jersey	Cover Pap test every 2 years for persons 20 and over More frequent testing if recommended by a doctor Need referral of patient's health care provider	Certain specified HMOs must only offer and not provide coverage
New Mexico	Cover Pap test, pelvic exam, and HPV testing for persons age 18 and over Medical standards determine how often testing should be done Need referral of patient's health care provider	Copay, deductibles and/or co-insurance may apply
New York	Annual Pap test and pelvic exam for persons 18 and over	Copay, deductibles and/or co-insurance may apply
North Carolina	Cover Pap test and HPV testing  according to ACS guidelines (see below) or those established by the NC Advisory Committee on Cancer Coordination and Control	Copay, deductibles and/or co-insurance may apply
Ohio	Cover Pap test	Public employee plan: specified coverage
Oregon	Annual Pap test and HPV testing for persons age 18-64 More frequent testing if recommended by a doctor
Pennsylvania	Cover Pap test and pelvic exam according to ACOG Guidelines (see below)
Rhode Island	Cover Pap test according to ACS guidelines (below)
South Carolina	Annual Pap test More frequent testing if recommended by a doctor Need referral of pateint's health care provider	Copay, deductibles and/or co-insurance may apply
Texas	Annual Pap test and HPV test when done at the same time, for persons age 18 and over, according to ACOG (or similar national organization) Guidelines (see below)
Virginia	Annual Pap test
West Virginia	Annual Pap test and HPV testing for persons age 18 and over, according to ACOG Guidelines or USPSTF Recommendations (see below)	Copay, deductibles and/or co-insurance may apply
Wyoming	Cover Pap test and pelvic exam	Co-insurance may apply

ACOG (American College of Obstetricians and Gynecologists) Guidelines: Cervical cancer screening should begin within 3 years after first vaginal intercourse, or by age 21, whichever comes first. Guidelines for subsequent screening differ based on age, type of screening test, and prior test results.

ACS (American Cancer Society) Guidelines: Cervical cancer screening should begin about 3 years after a woman begins having vaginal intercourse, but no later than 21 years of age. Guidelines for subsequent screening differ based on age, type of screening test, and prior test results.

USPSTF (United States Preventative Services Task Force) Recommendations: The USPSTF strongly recommends screening for cervical cancer in women who have been sexually active and recommends against routinely screening women older than age 65 or women who have had a total hysterectomy for benign disease.

Source: National Cancer Institute: State Cancer Legislative Database Program, Bethesda, MD. 2006.

Self-Insured Plans

ERISA, or self-insured plans, are not regulated at the state level and therefore women in these plans do not necessarily get cervical cancer screening benefits, even if there are state laws ensuring coverage for such benefits. Self-insured plans are typically large employers. Women who have self-insured based health insurance should check with their health plans to see what cervical cancer screening services are offered.

Medicaid

By statute or agency policy, Medicaid or public assistance programs in all 50 states and the District of Columbia cover screening for cervical cancer either routinely or upon a doctor’s recommendation. This coverage may or may not conform to American Cancer Society guidelines. Please check with your state Medicaid office to learn more about what services are provided for cervical cancer screening.

Medicare

Medicare provides coverage for a screening Pap test, pelvic exam, and a clinical breast exam every 2 years for Medicare beneficiaries. And if a woman is of childbearing age and has had an abnormal Pap test in the previous 3 years, or is at high risk for cervical or vaginal cancer, she would be eligible under Medicare to be covered for screening every year. The deductible is waived for this screening.

National Breast and Cervical Cancer Early Detection Program

All states are making cervical cancer screening more available to medically underserved women through the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). This program provides breast and cervical cancer screening to women without health insurance for free or at very little cost. The NBCCEDP attempts to reach as many women in medically underserved communities as possible, including older women, women without health insurance and women who are members of racial and ethnic minorities.

Though the program is administered within each state, the Centers for Disease Control and Prevention (CDC) provides matching funds and support to each state program.

Since 1991, the program has provided over 4.5 million screening exams to underserved women, diagnosed over 17,000 breast cancers, over 61,000 pre-cancerous cervical lesions, and over 1,100 cervical cancers. These accomplishments demonstrate a truly nationwide effort. However, due to limited resources, only about 15% of all eligible women are served nationwide.

Each state's Department of Health will have information on how to contact the nearest program participant. For more information on this program, you can also contact the CDC at 1-800-CDC-INFO (1-800-232-4636) or on the Web at www.cdc.gov/cancer/nbccedp.

If cervical cancer is detected during screening in this program, most states can now extend Medicaid benefits to these women to cover the costs of treatment.

HPV vaccine costs

It is expected that insurance plans will cover the cost of the HPV vaccine in accordance with the Federal Advisory Committee on Immunization Practices (ACIP) recommendations. ACIP has also recommended that the HPV vaccine be included in the federal Vaccine for Children (VFC) entitlement program, which covers vaccine costs for children and teens who do not have insurance or who are underinsured.

Additional resources

More information from your American Cancer Society

The following information may also be helpful to you. These materials may be ordered from our toll-free number, 1-800-ACS-2345 (1-800-227-2345).

American Cancer Society Recommendations For Human Papillomavirus (HPV) Vaccine Use To Prevent Cervical Cancer And Pre-Cancers

Cervical Cancer (also available in Spanish)

Human Papilloma Virus (HPV) Vaccines -- Frequently Asked Questions (also available in Spanish)

Thinking About Testing for HPV? (also available in Spanish)

What Every Woman Should Know About Cervical Cancer and the Human Papilloma Virus (also available in Spanish)

National organizations and Web sites*

In addition to the American Cancer Society, other sources of patient information and support include:

Gynecologic Cancer Foundation
Toll free number: 1-800-444-4441 or 1-312-578-1439
Web site:www.thegcf.org/

Centers for Disease Control and Prevention (CDC)
National Breast and Cervical Cancer Early Detection Program
Toll free number: 1-800-CDC-INFO (1-800-232-4636)
Web site: www.cdc.gov/cancer/nbccedp

National Cervical Cancer Coalition
Toll free number: 1-800- 685-5531or 1-818-909-3849
Web site: www.nccc-online.org

*Inclusion on this list does not imply endorsement by the American Cancer Society.

No matter who you are, we can help. Contact us anytime, day or night, for information and support. Call us at 1-800-ACS-2345 or visit www.cancer.org.

References

American Cancer Society. Cancer Facts & Figures 2008. Atlanta, Ga: American Cancer Society; 2008.

American Cancer Society. Cancer Prevention & Early Detection Facts & Figures 2007. Atlanta, Ga: American Cancer Society; 2005.

American Cancer Society. Detailed Guide: Cervical Cancer. 2008. Available at: www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=8. Accessed 3/12/2008

Eifel PJ, Berek JS, Markman, M. Cancer of the cervix, vagina, and vulva. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2005:1295-1340.

International Collaboration of Epidemiological Studies of Cervical Cancer. Appleby P, Beral V, Berrington de González A, Colin D, Franceschi S, Goodhill A, Green J, Peto J, Plummer M, Sweetland S. Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies. Lancet. 2007 Nov 10;370(9599):1609-1621.

Jhingran A, Eifel PJ, Wharton JT, et al. Neoplasms of the cervix. In: Kufe DW, Pollock RE, Weichselbaum RR, Bast RC, Gansler TS, Holland JF, Frei E, eds. Cancer Medicine 6. Hamilton, Ontario: BC Decker; 2003. 1779-1808.

National Cancer Institute, State Cancer Legislative Database Program. Fact Sheet: Cervical Cancer. 2006. Available at:. www.scld-nci.net/factsheets/pdf/CervicalCancer_Fall06.pdf. Accessed April 10, 2007.

PDQ database. Cervical cancer: Prevention. Bethesda, Md: National Cancer Institute; 2005. Available at: www.cancer.gov/cancertopics/pdq/prevention/cervical/healthprofessional. Accessed March 28, 2006.

Russel AH, Seiden MV, Duska LR, et al. Cancers of the cervix, vagina and vulva. In: Abeloff MD, Armitage JO, Lichter AS, et al, eds. Clinical Oncology. 3rd ed. Philadelphia, Pa; Elsevier; 2004: 2217-2271.

Saslow D, Castle PE, Cox JT, et al. American Cancer Society guideline for human papillomavirus (HPV) vaccine use to prevent cervical cancer and its precursors. CA Cancer J Clin. 2007;57:7-28.

Solomon D, Davey D, Kurman R, et al; Bethesda 2001 Workshop. The 2001 Bethesda System: Terminology for reporting results of cervical cytology. JAMA. 2002;287:2114-2119.

Winer RL, Hughes JP, Feng Q, et al. Condom use and the risk of genital human papillomavirus infection in young women. N Engl J Med. 2006;354:2645-2654.

Ronco G, Cuzick J, Pierotti P, et al. Accuracy of liquid based versus conventional cytology: overall results of new technologies for cervical cancer screening: randomised controlled trial. BMJ. 2007 Jul 7;335(7609):28. Epub 2007 May 21.

Ault KA, Future II study group. Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials. Lancet. 2007 Jun 2;369(9576):1861-8.

Hatch EE, Herbst AL, Hoover RN, Noller KL, Adam E, Kaufman RH, Palmer JR, Titus-Ernstoff L, Hyer M, Hartge P, Robboy SJ. Incidence of squamous neoplasia of the cervix and vagina in women exposed prenatally to diethylstilbestrol (United States). Cancer Causes Control. 2001 Nov;12(9):837-45.

Troisi R, Hatch EE, Titus-Ernstoff L, Hyer M, Palmer JR, Robboy SJ, Strohsnitter WC, Kaufman R, Herbst AL, Hoover RN. Cancer risk in women prenatally exposed to diethylstilbestrol. Int J Cancer. 2007 Jul 15;121(2):356-60.

Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet. 2007 Sep 8;370(9590):890-907.

Adam E, Kaufman RH, Adler-Storthz K, Melnick JL, Dreesman GR. A prospective study of association of herpes simplex virus and human papillomavirus infection with cervical neoplasia in women exposed to diethylstilbestrol in utero. Int J Cancer. 1985 Jan 15;35(1):19-26.

Revised: 03/31/2008