Diagnosis
Because cervical cancer develops so slowly, it is usually preventable if discovered in its early stages using screening tests taken during regular gynecologic examinations.
Pap Smear
Every year about 50 million women undergo the Papanicolaou test (the Pap smear) and 7% have an abnormal result. Use of the Pap smear test has reduced the annual death rate from cervical cancer from 26,000 in 1941 to 4,600 in 2000. In spite of this, 40% of women with an abnormal Pap smear fail to follow-up for retesting and treatment.
The Procedure. The most accurate results seem to be obtained 12 to 14 days after menstruation begins. Women should not douche or have intercourse within 48 hours of the test. Douches and spermicidal creams may clean out abnormal cells and interfere with the results of a Pap smear. (In general, douching is not recommended at all.) A Pap smear is painless.
- Living cells are collected by gently scraping the surface of the cervix, and sometimes the upper vagina, with a plastic spatula.
- A brush (cytobrush), spatula, or both are then used to obtain cells from inside the cervical canal. Such cells include squamous and glandular cells and those that lie higher up in the cervical canal (known as the endocervix). The combination of the brush and spatula are optimal in obtaining sufficient samples to detect cancer when it is present.
- These cells are preserved with a fixative, stained for microscopic viewing, and then analyzed under a microscope by a specialist known as a cytopathologist.
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| A Pap test is a simple, relatively inexpensive procedure that can easily detect cancerous or precancerous conditions. |
Reliability and Accuracy. Over the course of a lifetime of regular screening, a woman faces a 40% chance of being told her Pap smear is abnormal. The Pap smear is not, however, a perfectly reliable measure of a woman's risk for cervical cancer.
In general, about 10% of Pap smears have abnormal results, but only about 0.1% of the women who have these results actually have cancer. In most cases, abnormal cells are low grade and not likely to progress to cancer or are due to benign conditions, including natural cell changes after menopause.
No test is 100% accurate, and it is possible for the Pap smear to miss the presence of cancer. However, it should be noted that if abnormal cells are missed on one test they are likely to be spotted during the next one without a significant danger.
Current Pap Smear Screening Recommendations
Recommendations for Most Adult Women. The 2003 guidelines from the US Preventive Service Task Force (USPST) recommends that all women should have annual Pap tests within three years of onset of sexual activity or at age 21 (which ever comes first).
Note: Women with no history of sexual activity should still have Pap smears. They are at low risk for squamous cell carcinoma, but adenocarcinoma (cancer that occurs in cervical glands) can occur, although this is very uncommon.
Elderly Women. In its 2003 guidelines, US Preventive Service Task Force recommends against routine screening in women over age 65 with low or no risk factors. (The ACS recommends stopping at age 70.) Such women have had at least three previous normal screenings and have had no abnormal results for at least 10 years. Older women should be screened if they have not been screened before or if there is a possibility that they have not been screened (e.g., coming from countries without routine screening.)
After a Hysterectomy. The 2003 guidelines recommend against routine screening for women who have undergone a total hysterectomy for benign causes. Women who have had a hysterectomy that preserves the cervix (called a supracervical hysterectomy) should continue with Pap screening.
Follow-up After Normal Results
If Pap smear results are normal for three consecutive years, most expert groups recommend a Pap test every three years thereafter in most women. (The ACS suggests that such women wait until they are 30 before extending the interval to three years.)
Both the ACS and the American College of Obstetricians and Gynecologists (ACOG) recommend that annual screening should continue in women in high-risk categories. High risk categories may include the following, depending on the medical group:
- Women who have had multiple sexual partners or whose male sexual partners have had multiple partners.
- Women who engaged in sexual activity at a young age.
- Women whose male sexual partners have had other sexual partners with cervical cancer.
- Women with current or prior HPV infection.
- Women who are HIV-positive or who are immunosuppressed.
- Women with a history of sexually transmitted diseases.
- Smokers and substance or drug abusers.
- Women who have a history of cervical dysplasia or cervical cancer or endometrial, vaginal, or vulvar cancer.
- Women in lower socioeconomic groups, particularly if they have not been able to obtain regular gynecologic screening and care.
Follow-up After Abnormal Results
Any abnormal result, even a mild abnormality, requires follow-up visits and additional tests. The extent of these tests depends on the degree of abnormalities.
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Tests for Improving the Accuracy of the Pap Smear
New tests and methods have been developed to improve the accuracy of the Pap smear in detecting actual cancer cells:
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Thin-Layer (Liquid Based) Testing. Thin-layer liquid based tests (ThinPrep, Hybrid Capture) use the original cervical sample, which is rinsed in a special solution to thin the mucus (rather then dried). The result is a clear, clean sample that may be able to accurately reveal abnormal cell. The fluid can also be examined for evidence of HPV and other early abnormalities. Some--but not all--studies have found this test to be more accurate than the standard Pap smear. More research is needed to confirm any advantages.
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Computerized Analysis. One test, Papnet, is used to rescreen the original smear. A computer system selects over 100 abnormal images from the sample, which are then reexamined using high-resolution video. Papnet is useful for detecting cancers when there are few malignant cells in the sample and for identifying small-cell cancer. Autopap also uses a computerized process that selects out abnormal smears, but it is performed on the original sample, and the cells are viewed under standard microscope.
Studies using all of these tests have reported a higher accuracy rates in detecting cancer cells than the standard Pap smear. However, in one 2001 analysis, experts reported that the methods used in nearly all the studies did not allow true comparison. In any case, there is no data as yet to determine if these new tests actually save lives compared to the use of the standard Pap smear.
Of note, the new tests produce a high number of false-positive results. This means they can identify cells as suspicious that turn out to be normal, but which may lead to additional unnecessary and even invasive tests. These tests are also expensive. They are, then, most likely to be cost effective if they are used only as additional back up for women at high risk for cervical cancer and who are screened infrequently.
Tests for Human Papilloma Virus (HPV)
The human papilloma virus (HPV) is now a known cause of cervical cancer, and tests are now available for identifying it. Its presence is a strong predictor of high-grade aggressive abnormalities or cancer itself. Testing for HPV does not replace the Pap smear, except possibly in high-risk women who live in regions it is difficult to obtain regular Pap smear screening. HPV tests, however, are proving to be important in determining if high-grade aggressive or cancerous cells (CIN 3 or higher) are present in abnormal Pap smears.
There are two methods that allow detection of HPV:
- HPV DNA test. The human papilloma virus DNA (HPV DNA) test uses polymerase chain reaction (PCR), which looks for tiny pieces of the DNA of the virus, then replicates them millions of times until the virus is detectable. This is the preferred method.
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Thin-Layer (Liquid Based) Testing. Thin-layer tests (e.g., ThinPrep) are a variant of the Pap Smear and provide a clear liquid that can be used for evaluation and detection of the HPV virus.
A 2003 study suggested that the HPV DNA test was much more accurate (88.2%) in identifying women with aggressive pre-cancerous or cancerous cells compared to the ThinPrep (61.3%). The ThinPrep, however, was more accurate in ruling out women who did not have serious abnormalities, which means that more women would have to undergo unnecessary invasive tests. Both tests were less accurate in women over 30 years old than in younger women. The recent identification of the HPV genetic types occurring in 95% of cervical cancers will further improve the accuracy of these tests.
There is a danger in over-testing, particularly in younger women who are unlikely to develop any serious condition, even if they have the HPV infection. (HPV clears up within five years in 90% of cases.) If HPV testing achieves FDA approval, the American Cancer Society recommends HPV screening no more frequently than every three years in women over 30. At this time, major medical and government groups have found insufficient evidence on its benefits to recommend widespread use of this test.
Other Screening Tests
Other screening tests are being investigated for use in combination with the Pap smear for improving accuracy. For example, combinations with HPV DNA tests or cervicography may prove to be more effective for detecting CIN II and III dysplasia (potentially invasive cells) than Pap smears alone.
Cervicography. Cervicography uses a photograph of the cervical region (a cervigram), which is then highly magnified and examined. It may prove to be a useful companion to a Pap test, particularly in high-risk younger women. It is painless, easy to use, provides documentation of the area, and is highly sensitive to abnormal changes. (It also, however, picks up abnormalities that are not cancerous.)
Acid Test. A diluted solution of acetic acid (similar to vinegar) is applied to the cervix. When viewed through a special green lens, this solution makes abnormal cells look white, whereas normal cells appear pink. Skilled physicians may also be able to spot abnormal blood vessel patterns indicative of cancer areas on the cervix. This is an inexpensive and simple test and in one 2002 study identified 70% of aggressive cancers.
Fluorescence Spectroscopy. Small noninvasive probes that can be swept across the surface of the cervix to detect cancer are showing promise as an effective screening tool for cervical cancer. One probe emits a laser light. The head of the probe catches the return signals from the woman's cervical cells and compares them with a computer library of cancer cells. In one comparison test, fluorescent spectroscopy was more accurate than the Pap smear but not as effective as other screening methods.
Other Investigative Tests. Experts are working on an antibody-based method for improving the identification of true cancerous cells in a cervical smear, which could significantly reduce the need for expensive and distressing tests in women who do not actually have cancer. In addition, they are looking for biologic markers to improve diagnosis, such as specific proteins that indicate the presence of cancer cells.
Classifying Cervical Cells and Determining Further Testing
The cells viewed in a cervical smear sample are classified on a scale representing the spectrum of cell changes from normal to cancerous. The smear is first characterized as either "normal" or "abnormal."
Once abnormal cells are identified, the physician must decide whether the patient needs only repeat Pap smears, a test for the HPV virus, or colposcopy (a procedure used to magnify the cervix and permit detection of lesions for biopsy). To help the physician make the decision, the abnormal cells are divided into categories, depending on the degree of abnormality.
Atypical Squamous Cells (ASC). Atypical squamous cells (ASC) are mildly abnormal cells on the surface of the cervix. They may simply represent inflammation. Over 80% of these cells normalize, but unfortunately, between 5% and 17% of these women have a chance for having CIN II and III dysplasia (potentially invasive cells). Experts then have now further categorized ASC as the following:
- ASCUS. This category identifies atypical squamous cells of undetermined significance. They are the lowest risk abnormal cells. Women with ASCUS should be tested for human papillomavirus infection (HPV). If results indicate they are infected with HPV, they should be given colposcopy, a more invasive diagnostic procedure to determine if the condition is actually at a more aggressive stage. If they do not have HPV they are simply monitored with repeat Pap smears.
- ASC-H. This category refers to the presence of atypical squamous cells, but a physician cannot exclude possible high-grade squamous intraepithelial lesions. Such women have a 24% to 94% chance of having CIN II and III. All are referred for colposcopy.
Among those with ASC, immunosuppressed women and those with high-risk human papillomavirus infections are at higher risk for CIN II and III and should always be given colposcopy. Postmenopausal women with normal immune systems have a lower risk than younger women. It should be strongly noted, however, that actual risk for cervical cancer in general in women with ASC is only 0.1% to 0.2%.
Low Grade Squamous Intraepithelial Lesions (LSIL). Low-grade squamous intraepithelial lesions (LSIL) are typically associated with human papillomavirus changes, with or without early dysplasia (CIN I). Between 15% and 30% of women with LGIL, however, may have CIN II or III on biopsy. Women with LSIL are either monitored with repeat Pap smears or given colposcopy. Experts recommending colposcopy argue that these are high-risk women and there is a risk for delaying a diagnosis of cancer using only repeat Pap smears.
High-Grade Squamous Intraepithelial Lesions (HSIL). High-grade squamous intraepithelial lesions (HSIL) are associated with moderate dysplasia and other CIN II or III. Such women are always referred to colposcopy for biopsy. Even if colposcopy results report only CIN I, over a third of these women are likely to have CIN II or III. Experts, therefore, recommend a careful review of the tests in such cases. Pregnancy poses a problem since it increases the chance in HSIL for both normal and abnormal results. In nonpregnant women, particularly when fertility is not an issue, immediate treatment with loop electrosurgical excision procedure (LEEP) may be appropriate.
Atypical Glandular Cells (AGS). Atypical glandular cells are uncommon, but pose a higher risk for cancerous changes than ASC or LSIL. Between 9% and 54% have some CIN, between 0% and 8% have carcinoma in situ, and between 1% and 9% have invasive cancer. Experts recommend that the next step should be a colposcopy (rather than a repeat Pap smear).
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Colposcopy and Biopsy
The Pap smear only shows the presence of abnormal cells and is useful simply as a screening test that identifies women who may have preinvasive or early cancerous changes. For a definitive diagnosis, the next step is usually colposcopy, during which the cervix is visualized under low power magnification. The surgeon takes samples of suspicious cells for biopsies. A biopsy will determine the stage of the precancerous growth or whether frankly invasive cancer is present.
The Procedure. Colposcopy can be performed in a doctor's office without anesthesia in 10 to 15 minutes. It causes about as much discomfort as mild menstrual cramps:
- First, using a speculum to keep the vagina open, the physician aims a light at the cervix.
- The physician then looks through the eyepiece of a special microscope, known as a colposcope, to view the cervix. (Some colposcopies include a TV attachment that transmits the picture to a nearby monitor for easier viewing.)
- A biopsy (a sampling of the tissue) is taken of suspicious areas, of the endocervical canal (the inner part of the cervix and uterus), and any abnormal-looking areas. This may cause cramping or pinching.
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Click the icon to see an image of a colposcopy-directed biopsy. |
After the colposcopy, the woman may have a brownish discharge from an iron solution, known as Monsel's solution, that the physician applies to prevent bleeding. The physician usually advises sexual abstinence for one or two weeks.
Follow-Up Procedures. Women with evidence of cervical intraepithelial neoplasia (CIN) or cervical cancer require treatment. Women with biopsies that show low-grade abnormal cells (LGSIL) but whose cervix is otherwise normal are generally given follow-up colposcopies.
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