What is a Pap smear?
A Pap smear (also known as the Pap test) is a medical procedure in which a sample of cells from a woman's cervix (the end of the uterus that extends into the vagina) is collected and spread (smeared) on a microscope slide. The cells are examined under a microscope in order to look for pre-malignant (before-cancer) or;malignant (cancer) changes.
A Pap smear is a simple, quick, and relatively painless screening test. Its specificity;- which means its ability to avoid classifying a normal smear as abnormal (a "false positive" result) - while very good, is not perfect. The sensitivity of a Pap smear - which means its ability to detect every single abnormality -- while good, is also not perfect, and some "false negative" results (in which abnormalities are present but not detected by the test) will occur. Thus, a few women develop;cervical cancer despite having regular Pap screening.
In the vast majority of cases, a Pap test does identify minor cellular abnormalities before they have had a chance to become malignant and at a point when the condition is most easily treatable. The Pap smear is not intended to detect other forms of cancer such as those of the ovary, vagina, or uterus. Cancer of these organs may be discovered during the course of the gynecologic (pelvic) exam, which usually is done at the same time as the Pap smear.
Who should have a Pap smear?
Pregnancy does not prevent a woman from having a Pap smear. Pap smears can be safely done during pregnancy.
Pap smear testing is not indicated for women who have had a hysterectomy (with removal of the cervix) for benign conditions. Women who have had a hysterectomy in which the cervix is not removed, calledsubtotal hysterectomy, should continue screening following the same guidelines as women who have not had a hysterectomy.
The screening guidelines of several key medical organizations are summarized in the table below.
|Organization||When to start Pap smear testing||Frequency of Pap smeaer testing||
At what age to stop having Pap smears
American Cancer Society2004
|3 years after vaginal intercourse, no later than age 21||Yearly with exceptions
United States Preventative Services Task Force 2003
|Within 3 years of onset of sexual activity or age 21, whichever comes first||At least every 3 years (no evidence that every year is better than every 3 years)||
American College of Obstetrics and Gynecology
|3 years after first sexual intercourse or age 21, whichever comes first.||Yearly until age 30 years. Beginning at age 30, if three normal annual Pap results, can do a Pap alone every 2-3 years||Difficult to set an upper age limit-postmenopausal women screened within the prior 2-3 years have a very low risk of developing abnormal Pap smears.|
Which women are at increased risk for having an abnormal Pap smear?
- A number of risk factors have been identified for the development of cervical cancer and precancerouschanges in the cervix.
- HPV:The principal risk factor is infection with the genital wart virus, also called the human papillomavirus (HPV), although most women with HPV infection do not get cervical cancer. (See below for details). About 95%-100% of cervical cancers are related to HPV infection. Some women are more likely to have abnormal Pap smears than other women.
- Smoking: One common risk factor for premalignant and malignant changes in the cervix issmoking. Although smoking is associated with many different cancers, many women do not realize that smoking is strongly linked to cervical cancer. Smoking increased the risk of cervical cancer about two to four fold.
- Weakened immune system:Women whose immune systems are weakened or have become weakened by medications (for example, those taken after an organ transplant) also have a higher risk of precancerous changes in the cervix.
- Medications: Women whose mothers took the drug diethylstilbestrol (DES) during pregnancy also are at increased risk.
- Other risk factors:Other risk factors for precancerous changes in the cervix and an abnormal Pap testing include having multiple sexual partners and becoming sexually active at a young age.
How is a Pap smear done?
A woman should have a Pap smear when she is not menstruating. The best time for screening is between 10 and 20 days after the first day of her menstrual period. For about two days before testing, a woman should avoid douching or using spermicidal foams, creams, or jellies or vaginal medicines (except as directed by a physician). These agents may wash away or hide any abnormal cervical cells.
A Pap smear can be done in a doctor's office a clinic or a hospital by either a physician or other specially trained health care professional, such as a physician assistant, a nurse practitioner, or a nursemidwife.
- With the woman positioned on her back, the clinician will often first examine the outside of the patient's genital and rectal areas, including the urethra (the opening where urine leaves the body), to assure that they look normal.
- A speculum is then inserted into the vaginal area (the birth canal). (A speculum is an instrument that allows the vagina and the cervix to be viewed and examined.)
- A cotton swab is sometimes used to clear away mucus that might interfere with an optimal sample.
- A small brush called a cervical brush is then inserted into the opening of the cervix (the cervical os) and twirled around to collect a sample of cells. Because this sample comes from inside the cervix, is called the endocervical sample ("endo" meaning inside).
- A second sample is also collected as part of the Pap smear and is called the ectocervical sample ("ecto" meaning outside).
- These cells are collected from a scraping of the area surrounding, but not entering, the cervical os.
- Both the endocervical and the ectocervical samples are gently smeared on a glass slide and afixative (a preservative) is used to prepare the cells on the slide for laboratory evaluation.
A bimanual (both hands) pelvic exam usually follows the collection of the two samples for the Pap smear. The bimanual examination involves the physician or health care practitioner inserting two fingers of one hand inside the vaginal canal while feeling the ovaries and uterus with the other hand on top of the abdomen (belly).
The results of the Pap smear are usually available within two to three weeks. At the end of Pap smear testing, each woman should ask how she should expect to be informed about the results of her Pap smear. If a woman has not learned of her results after a month, she should contact her health care practitioner's office.
What are the risks of having a Pap smear?
There are absolutely no known medical risks associated with Pap smear screening. (However, there are medical risks from not having a Pap smear.)
How is a Pap smear read (analyzed)?
Pap smear analysis and reports are all based on a medical terminology system called The Bethesda System. The system was developed (at the National Institutes of Health (NIH) in Bethesda, Maryland) to encourage all medical professionals analyzing Pap smears to use the same reporting system. Standardization reduces the possibility that different laboratories might report different results for the same smear. Standardization and uniform terminology also make Pap smear reports less confusing for the clinicians who request the tests and for their women patients.
The Bethesda System was the outcome of a National Cancer Institute workshop that was held in 1988 in an effort to standardize Pap reports. The guidelines address many aspects of Pap smear testing and its results. In 2001 the guidelines were revised and improved. Acceptance of the Bethesda reporting system in the United States is virtually universal.
The major categories for abnormal Pap smears reported in the Bethesda Systems are as follows:
- ASC-US: This abbreviation stands for atypical squamous cells of undetermined significance. Under the old system of classification, this category was called atypical squamous cells just ASC. The new system requires the reader to pick one of two choices to add at the end of ASC: ASC-US, which means undetermined significance or ASC-H, which means cannot exclude HSIL-see below.
- LSIL: This abbreviation stands for low-grade squamous intraepithelial lesion. Under the old system of classification, this category was called CIN grade I.
- HSIL: This abbreviation stands for high-grade squamous intraepithelial lesion. Under the old system of classification, this category was called CIN grade II, CIN grade III, or CIS.
The word "squamous" describes the thin, flat cells that lie on the surface of the cervix. "Intraepithelial" indicates that the surface layer of cells is affected. A "lesion" means that abnormal tissue is present. These important terms - LSIL and HSIL - are described in greater detail below.
What information is included on a Pap smear report?
The first items on a Pap smear report are for purposes of identification. The report is expected to have the name of the woman the name of the pathologist and/or the cytotechnologist who read the smear, the source of the specimen (in this case, the cervix) and the date of the last menstrual period of the woman.
The Pap smear report should also include the following:
- A description of the woman's menstrual status (for example, "menopausal" (no longer menstruating) or "regular menstrual periods")
- The woman's relevant medical history (example, "history of genital warts")
- The number of slides (either one or two, depending on the health care practitioner's routine practice)
- A description of the specimen adequacy (whether the sample is satisfactory for interpretation)
- The final diagnosis (for example, "within normal limits")
- The recommendation for follow-up (for example, "recommend routine follow-up" or "recommend repeat smear")
Why is a woman's menstrual status important for the Pap smear?
A woman who is menstruating sheds cells from the lining of her uterus called endometrial cells. If these cells are seen on the Pap smear of a menstruating woman, the report may note "endometrial cells, cytologically benign, in a menstruating woman. The comment that cells are "cytologically benign" means that they do appear not to be malignant (cancerous) cells. A comment of this nature is absolutely not worrisome since a menstruating woman may be expected to shed such cells.
However, if a woman is menopausal (no longer menstruating) she would not be expected to be shedding cells from the uterine lining. Therefore, endometrial cells on a Pap report might be indicative of an abnormal thickening of the endometrium the lining of the uterus. The Pap smear is not specifically designed to detect such an abnormality. Nonetheless if these cells are noted in a non-menstruating woman, her physician should attempt to determine the cause of the shedding of the endometrial cells.
Sometimes, the cause is endometrial hyperplasia, a precancerous condition of the uterine lining, which can be detected by a relatively simple office procedure called an endometrial biopsy. Sometimes, menopausal hormone therapy can cause shedding of endometrial cells that appear on a Pap smear. The pattern of bleeding, the exact type of hormone therapy, and the individual woman's health history are the three components that guide the physician to know whether and what type of further evaluation is necessary.
Why is a woman's past Pap smear history pertinent?
If a woman has had a history of a cellular abnormality on a previous Pap smear, it is important for her to inform the health care practitioner performing the current Pap smear. The patient should provide the details of any previous problems and treatments so that this information can be noted on the lab form. The past history of the woman helps the person who is reading (interpreting) the current Pap smear, because a particular abnormality on previous screening alerts the health care practitioner to look more carefully for specific findings on the current Pap smear.
When might a Pap smear not be adequate for interpretation?
It is a requirement that the report comment on the adequacy of the smear sample for Pap analysis. If the sample is inadequate, the report details the reason. Examples of problems that might be listed under "sample adequacy" include "drying artifact" or "excessive blood." These comments refer to factors that the person analyzing the smear feels may have interfered with his or her ability to interpret the sample.
Sometimes, a Pap smear report will read "unsatisfactory due to excessive inflammation." Inflammation that is present in the woman's cervical area may make it difficult to interpret the Pap smear. Examples of causes of inflammation might include infections or irritation. Inflammation is a common finding on pap smears. If it is severe your doctor may want to try to determine the cause of the inflammation. In many cases a repeat pap smear is recommended to determine if the inflammation has resolved and to obtain a sample that is adequate for interpretation.
How is the final Pap smear diagnosis made?
The final Pap smear diagnosis is based on three determining factors:
- The patient's history: The reader (the person reading the smear) takes into account the woman's history as noted on the lab request by the clinician performing the smear.
- Sample adequacy: The reader then decides whether the sample was adequate for interpretation.
- The presence or absence of cellular abnormalities: The reader then notes whether cellular abnormalities were seen on the slides. If the appearance of the Pap smear does not seem to coincide with the woman's clinical history, a comment may also be made to that effect.
The final diagnosis is a short statement that summarizes what the reader has found. Examples of final diagnoses include:
- Within normal limits;
- Absence of endocervical cells on the Pap smear;
- Unreliable Pap smear due to inflammation;
- Atypical squamous cells of undetermined significance (ASCUS);
- Low-grade squamous intraepithelial lesion (LSIL); or
- High-grade squamous intraepithelial lesion (HSIL).
There may also be additional comments such as "low-grade squamous intraepithelial lesion (LSIL) with human papilloma virus."
What are the possible recommendations for follow-up after a Pap smear?
Once the final diagnosis has been made, the follow-up recommendation informs you what the appropriate next step(s) might be. For example, if the final diagnosis states that the smear was "within normal limits," the appropriate follow-up might be "recommend routine follow-up."
An abnormal Pap smear is one in which the laboratory interprets the cellular changes to be different from those normally seen on a healthy cervix. There are a number of possible follow-up scenarios for an abnormal Pap smear.
Absence of endocervical cells on the Pap smear: There is a particular area wherein the cells lining the vagina change to the endocervical cells that characterize the inside of the cervix. This is called the "transition zone" and is the target of the endocervical sample. However, it may be so far up inside the cervix that the Pap smear sampling instrument simply cannot reach that high. To further complicate the situation, the transition zone in a woman migrates (changes its position) at different times in her life and under different conditions. Sometimes, the transition zone may be less accessible to the Pap brush or the cervical os (opening to the cervix) cannot be seen well enough to obtain an adequate sample. Sometimes the reason for the absence of endocervical cells on the Pap smear is simply not evident.
Regardless, if the cause of the absent endocervical cells is known or unknown, the situation must be evaluated by the physician. In everyday practice, an appropriate response to the absence of endocervical cells is to redo the Pap smear, but also to take the woman's prior history into account in determining the timing. If the woman has had regular Pap smears has never had an abnormal one, and does not have an added risk factor for an abnormal Pap smear then the clinician will often wait a year before repeating the smear. If the woman does have risk factors the clinician will often elect to repeat the smear sooner.
Unreliable Pap smear due to inflammation: If severe inflammation is present, its cause(s) must be investigated. The physician's goals are to identify the cause of inflammation and to treat and resolve the condition, if possible. Untreated inflammation can have consequences for the woman as well as her sexual partner(s).
Sometimes, the woman's medical history will shed light on the cause of inflammation. For example, a woman may complain of irritation, dryness, or pain in her vaginal area. The inflammation can then be verified by the physician during a pelvic exam. The vaginal irritation may be caused by a lack ofestrogen, such as occurs after menopause when the ovaries stop producing this hormone. This lack of estrogen tends to make the vaginal walls irritated and red. If a woman has this condition and it is related to an estrogen deficiency (called "atrophic vaginitis" and usually described on the Pap smear report as "atrophic changes"), her physician may recommend a trial of topical (locally- applied) vaginal estrogen (cream, vaginal estrogen tablets vaginal estrogen ring) to hopefully heal the inflammation. The Pap smear is then repeated.
In summary, the physician will use clinical judgment in terms of the specific follow-up after a Pap smear that reports inflammation.
Atypical squamous cells of undetermined significance (ASCUS): Sometimes, atypical squamous cells of undetermined significance (also called "ASCUS"), is the determination written on the Pap report. This is the mildest form of cellular abnormality on the spectrum of cells ranging from normal to cancerous. ASCUS means that the cells appear abnormal but are not malignant.
"Of undetermined significance" means that the atypical-appearing cells may be the end result of a number of different types of injuries to the cervix. For example, the human papilloma virus (HPV) could be the cause of ASCUS. Most instances of ASCUS (80%-90%) resolve spontaneously (by themselves without specific medical intervention or treatment). This is the reason why many women with ASCUS readings will be asked to simply have a repeat Pap smear in 4 to 6 months. The expectation is that regardless of the original cause of the ASCUS, it will be resolved by the time the Pap smear is repeated. If not, the cause of the ASCUS can still be identified and treated if ASCUS is again observed on the repeat Pap smear 4 to 6 months later. This standard recommendation of serial Pap smears - repeating the Pap smear in 4 to 6 months - is made unless the physician has a concern that the woman is not willing or able to return for a repeat Pap smear. In these cases a colposcopy (see below) may be done without waiting to repeat the Pap smear.
The third approach to ASCUS (besides serial Pap testing and immediate colposcopy) is called reflex HPV testing. Reflex HPV testing refers to a process in which the HPV test is only performed if the Pap smear result is abnormal. If the Pap smear result is normal, it is not performed. For reflex testing to be possible, a liquid-based Pap testing kit is required which allows the lab to store the sample until the Pap smear result tells them whether the HPV test will be necessary or not. Not all facilities have access to liquid-based cytology kits. If repeat smears are to be done for monitoring, the testing needs to be done every 4 to 6 months for 2 years until there have been three consecutive normal smears, at which time routine screening can be resumed. The Pap smears however, must not only be negative, but also satisfactory for interpretation, according to National Cancer Institute Workshop Guidelines.
The irritation of the genital area that accompanies menopause can trigger ASCUS by causing inflammation. If the physician suspects that this is the cause of ASCUS, he or she may prescribe intravaginal estrogen (local estrogen, such as a vaginal ring, vaginal cream, or vaginal estrogen tablets) and repeat the Pap smear in 4 to 6 months to confirm that the inflammation is resolved. If the inflammation persists, colposcopy will be necessary. Sometimes, the ASCUS reading is accompanied by a comment to the effect that the Pap smear reader thinks there may be a suggestion of dysplasia(abnormally dividing or abnormal appearing cells), often worded as "favor dysplasia." In this case, the ASCUS is generally not monitored over time but rather treated as if it is dysplasia (see discussion below). Similarly, a woman who has a suppressed immune system is not a good candidate for serial Pap smear tests because she is at higher risk of serious abnormalities. Therefore, she should undergo colposcopy instead of serial Pap smears. It is evident from this discussion that many factors go into a physician's decision regarding which of the three treatment options to recommend to an individual woman.
Low-grade squamous intraepithelial lesion (LSIL): A more serious cellular abnormality is low-grade squamous intraepithelial lesion (LSIL). A reading of LSIL is a reason for immediate further investigation because it is more abnormal than ASCUS. Fifteen to 30% of women who have this abnormality on Pap testing will have a more serious abnormality on biopsy of the cervix. Thus, all women with LSIL are recommended to undergo colposcopy. On the brighter side, even LSIL spontaneously returns to normal without therapy in many women within several months. For that reason, if the initial colposcopy and biopsy results are favorable serial Pap smears every 4 to 6 months may be recommended after which a return to normal screening is possible if there are three negative, consecutive, satisfactory Pap smears.
High-grade squamous intraepithelial lesion (HSIL): The most severe cellular abnormality that is not actually cancer is high-grade squamous intraepithelial lesion (HSIL). A finding of HSIL unquestionably requires prompt treatment.
Women with HSIL have a 70%-75% chance of having a more serious abnormality (CIN 2,3 see below) on biopsy of the cervix and a 1%-2% chance of having actual cervical cancer on biopsy of the cervix. Therefore, colposcopy is undoubtedly the routine recommendation for all women with HSIL.
Cervical intraepithelial neoplasia (CIN): This is the most severe form of high-grade squamous intraepithelial lesion (HSIL). A neoplasia is within the realm of cancer. Type 1 CIN is "low grade," or less serious than Type 2, 3 CIN (high-grade). The diagnosis of a cervical intraepithelial neoplasia (CIN) on a woman's Pap smear means that she needs to be evaluated and treated as soon as possible by a qualified physician.
Carcinoma in situ: This diagnosis is also a form of high-grade squamous intraepithelial lesion (HSIL). A reading of "carcinoma in situ" on a Pap smear report means there is cervical cancer present. However, the cancer is "in situ," which means that it appears to be limited to the cervix and not to have invaded other tissues.
What treatments are available if a Pap smear is abnormal?
If a Pap smear is interpreted as abnormal, there are a number of different management and treatment options including colposcopy conization, cryocauterization, laser therapy, and large-loop excision of the transformation zone.
All of these procedures have essentially the same overall cure rate of over 90%. However, the procedures do vary considerably in a number of other respects and so will be discussed separately.
Colposcopy: Colposcopy is a procedure that allows the physician to take a closer look at the cervix. The colposcope is essentially a magnifying glass for the cervix. For colposcopy to be adequate the whole cervical lesion, as well as the whole transformation zone (the transition between the vagina-like lining and the uterus-like lining) must be seen.
During colposcopy the cervix is cleaned and soaked with 3% acetic acid. This acid not only cleans the surface of the cervix but it also allows cellular abnormalities to show up as white areas (called acetowhite epithelium or acetowhite lesions).
If suspicious areas of cervical tissue are seen during colposcopy a biopsy (tissue sampling) is often done. The sample is sent to the laboratory for analysis by a pathologist and the biopsy results determine the next step in the treatment.
The procedure is essentially painless and quite simple, usually taking only several minutes to perform. Generally the woman is instructed not to have intercourse, douche, or use tampons for about a week afterwards if a biopsy is done. Pregnancy is not a contraindication to colposcopy. Colposcopy can adequately eval