Diseases

With the woman positioned on her back, the health-care professional 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 small brush or swab is inserted into the opening of the cervix and twirled around to collect a sample of cells.
• A second sample is also collected on the surface of the cervix as part of the Pap smear
• The samples are placed in a solution from which cells are isolated and used to produce slides 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 professional 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).

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. The Bethesda System was the outcome of a National Cancer Institute workshop that was held in 1988 in an effort to standardize Pap smear reports. 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 (described in further detail in the "What are the possible recommendations for follow-up after a Pap smear?" section):

• ASC-US: This abbreviation stands for atypical squamous cells of undetermined significance.
• 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.
• ASC-H: This means atypical cells are present and HSIL cannot be excluded.

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. An abnormal or inadequate Pap smear report may contain the following diagnoses. Absence of endocervical cells on the Pap smear There is a particular area inside the opening of the cervix where the cells lining the vagina change to the cells that characterize the inside of the cervix (endocervical cells). This is called the "transition zone". The Pap smear sample from the cervical opening attempts to sample these cells. However, this area may be so far up inside the cervix that the Pap smear sampling instrument simply cannot reach that high. Sometimes, the transition zone may be less accessible to the Pap brush or the cervical opening cannot be seen well enough to obtain an adequate sample. Unreliable Pap smear due to inflammationIf severe inflammation is present, its cause(s) are 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). The vaginal irritation may be caused by a lack of estrogen, 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 heal the inflammation. The Pap smear is then repeated. Atypical squamous cells of undetermined significance (ASC-US)Sometimes, atypical squamous cells of undetermined significance (also called "ASC-US"), is the Pap report. This is the mildest form of cellular abnormality on the spectrum of cells ranging from normal to cancerous. ASC-US 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 ASC-US. Most instances of ASC-US (80%-90%) resolve spontaneously (by themselves without specific medical intervention or treatment). Low-grade squamous intraepithelial lesion (LSIL)A reading of LSIL is a reason for immediate further investigation because it is more abnormal than ASC-US. 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 (an examination of the cervix using a special visualizing scope, often accompanied by a cervical biopsy, see below). Even LSIL spontaneously returns to normal without therapy in many women within several months. 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 evaluation and treatment.

The final Pap smear diagnosis is based on three determining factors:

1. 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.
2. Sample adequacy: The reader then decides whether the sample was adequate for interpretation.
3. 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.

The results of the Pap smear are usually available within one to two 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 professional's office.

A number of risk factors have been identified for the development of cervical cancer and precancerous changes 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. Almost all 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 is smoking. Although smoking is associated with many different cancers, many women do not realize that smoking is strongly linked to cervical cancer. Smoking increases 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, having an abnormal Pap test, having multiple sexual partners, and becoming sexually active at a young age.

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.

There are absolutely no known medical risks associated with Pap smear screening. (However, there are medical risks from not having a Pap smear.) A woman may experience a small amount of spotting (light vaginal bleeding) immediately after a Pap smear, but heavy or excessive bleeding is not normal.

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 professional'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")

A Pap smear (Papanicolau smear; also known as the Pap test) is a screening test for cervical cancer. The test itself involves collection of a sample of cells from a woman's cervix (the end of the uterus that extends into the vagina) during a routine pelvic exam. The cells are placed on a glass slide and stained with a substance known as Papanicolau stain. The stained cells are then examined under a microscope 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, also is 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.

An abnormal Pap smear shows cancer or precancerous changes in the cells of the cervix. It is especially important to identify abnormal cells in the early stages, because treatment can be carried out to remove the abnormal cells. The section below entitled "How is a Pap smear read and analyzed" contains the specific terminology used in the report for an abnormal Pap smear.

HPV is a sexually transmitted virus that may be spread from one person to another even when the genital sores are not visible. Many sexually active people are carriers of HPV, very often without even knowing they are carriers. It is estimated that up to 60% of sexually active women harbor this virus on their cervix or in their vaginal area. It is not unusual for a woman to be unaware that she has HPV - only to find out that her Pap smear shows evidence of HPV. HPV is not curable, although the cellular damage it causes is generally treatable and vaccines against the most commonly found HPV types are available. The main use of HPV testing in screening for cervical cancer is for determination of treatment and follow-up recommendations for women with Pap smears interpreted as atypical squamous cells of undetermined significance (ASC-US).

Pap testing is performed by obstetrician-gynecologists (OB-GYNs) or by primary care physicians including family practitioners, internal medicine specialists, or pediatricians. Pap smears can also be performed by other specially trained health-care professionals including physician assistants, nurse practitioners, or nurse midwives.

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 doctor 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 (vinegar). This mild 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 evaluate 90% of women who have abnormal Pap smear results. ConizationConization allows the entire area of abnormal tissue to be removed and provides the maximum amount of cervical tissue for laboratory evaluation to rule out the presence of invasive cancer. After the cervical area is visualized, generally by colposcopy, a small cone-shaped specimen of tissue is taken from around the endocervical canal. Conization is usually done on an out-patient basis under anesthesia in a hospital or surgical facility. For three weeks after the procedure, the woman needs to avoid douching, and using tampons and refrain from sexual intercourse. Cure rates close to 100% are achieved with conization as long as the cells along the margins of treatment are normal. With conization, there are associated risks from anesthesia and postoperative hemorrhage (bleeding-in about 10% of cases) as well as possible future adverse effects on fertility. Conization is generally performed only on women who have had severe changes on biopsy, have adenocarcinoma in situ (a diagnosis of cancer in the inner portion of the cervix), or whose Pap smears suggest they may have some invasion of cancer into the nearby tissue. Large-loop excision (LEEP) of the transformation zoneLarge-loop excision of the transformation zone (LEEP) removes the cervical transformation zone (the area where the vaginal-type lining changes to the uterine-type lining) using a thin-wire loop to administer electrocautery. It allows samples to be collected for additional tissue analysis and can be performed in the office under local anesthesia. Specialized (more frequent) follow-up is necessary after LEEP. This follow-up includes Pap smears, colposcopy, and sometimes other techniques. This is now the most commonly used treatment for Pap smear abnormalities. HysterectomyA hysterectomy for the treatment of abnormal Pap smears is appropriate only for those women who are finished with childbearing and have severe pre-cancerous abnormalities that have persisted despite other treatments.

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.

Guidelines have been developed for cervical cancer screening that address the frequency with which women should have Pap smears. The US Preventive Services Task Force (USPSTF) and the American Cancer Society (ACS) both recommend that all women receive cervical cancer screening every 3 years between the ages of 21 and 65. A Pap smear is the typical screening procedure, but when a Pap smear is combined with a test for human papillomavirus (HPV, the known cause of cervical cancers), screening every 5 years is acceptable for women aged 30 and above. Pregnancy does not prevent a woman from having a Pap smear, therefore, 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, called subtotal hysterectomy, should continue screening following the same guidelines as women who have not had a hysterectomy.

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 that these cells are present. This is normal if the Pap test was done around the time of the woman's menstrual period. The comment that these cells are "cytologically benign" means that they do not appear to be malignant (cancerous) 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 doctor 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.

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 professional performing the current Pap smear. The woman 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 professional to look more carefully for specific findings on the current Pap smear.

It is critically important to recognize that the women who are at highest risk for abnormal Pap smear testing are those who are not getting regular Pap testing. Therefore, it follows that in order to improve overall cervical cancer screening, women who are not getting regular Pap smears should be educated about and offered Pap testing. These under-served women should be the most heavily targeted for Pap screening. Between 60% and 80% of American women who are newly diagnosed with invasive cervical cancer have not had a Pap smear in the past five years and may never have had one. Women who have not had Pap smear screening tend to be concentrated in certain population groups including:

• Older women;
• The uninsured;
• Ethnic minorities, especially Latino, African American, and Asian American women;
• Poor women; and
• Women in rural areas.

Many doctors feel that the emphasis should be on universal access to proper Pap screening as opposed to the comparatively small benefit that would come from utilizing the newer technologies in women already undergoing screening. Cervical cancer is one of the most common causes of cancer worldwide. It is also one of the most preventable and treatable cancers.