ALL ABOUT PAP TESTS

WHAT IS IT AND WHO GETS TESTED
PAP TEST REPORT CLASSIFICATION
WHAT IT MEANS
EVALUATION OF AN ABNORMAL PAP TEST
TREATMENT OF PREMALIGNANT CONDITIONS
THE CAUSE OF CERVICAL DYSPLASIA
PAP TEST MISTAKES

WHAT IS IT AND WHO GETS TESTED

The Pap test is a screening test for malignant and premalignant changes of the cervix. A positive result indicates that there may be a problem and that further diagnostic procedures must be done. The Pap test is not a diagnostic test. It cannot be used to exclude a cancer of the cervix for a person who has symptoms that could be due to a cervical cancer.

Pap tests are done on women who have no symptoms of cancer and have no findings suggesting a cancer. Thus, Pap tests are done only on women who are normal. If the woman has symptoms or findings suggestive of cancer of the cervix then a diagnostic test must be done to exclude a cancer or to diagnose a cancer. Diagnostic tests are usually biopsies. This is the single most important lesson to learn: if you have a symptom or a finding that could be due to a cancer of the cervix, a normal Pap test never excludes the possibility of cancer.

In the vast majority of instances, an abnormal Pap test results in the diagnosis of a minor change on the cervix. Some of these changes will be premalignant, but most will be of minor significance. They will all have to be evaluated, diagnosed and treated, but most will be easily and effectively treated. Occasionally, a real cancer will be present which is why this is such an important test. Most cancers are visible on examination and can be biopsied as soon as they are seen. Sometimes the cancers are inside the cervix beyond view and the only indication that it is there is the abnormal Pap test.

Pap test screening is recommended for all women beginning at age 18 years or at the onset of sexual activity, if earlier. The screening interval is usually every year, although, if there have been no previous abnormal tests, the interval may be extended. The Pap test is performed by gently scraping cells from the cervix, smearing them onto a microscope slide and sending it to a pathology laboratory for evaluation. There are two reporting systems in current use. The older system which reported the result in one of five classes is being replaced by the newer Bethesda System.

CLASSIFICATION OF PAP TEST RESULTS

Class INormal
Class IIAtypical, inflammation or uterine cells seen
Class IIIDysplastic, mild, moderate or severe
Class IVCarcinoma-in-situ
Class VSuspicious for an invasive cancer

			BETHESDA SYSTEM

	Adequacy	
		Satisfactory
		Limited
		Unsatisfactory

	Descriptive
		Normal
		Benign
		Epithelial cell abnormality
			Atypical squamous cells of unknown significance
			Low grade squamous intraepithelial lesion
			High grade squamous intraepithelial lesion
		Glandular cell abnormality
			Atypical glandular cells
			Adenocarcinoma

WHAT IT MEANS

The cells obtained during the Pap test are removed from the outermost layer of cells from the surface of the cervix. The cervix is covered by an epithelial layer of cells that is 12-24 cells thick. This surface covering, called the epithelium, rests on a basement membrane beneath which are the deeper tissues that make up the substance of the cervix. The cells of this surface epithelium progress from large round cells at the basement membrane to flat cells at the surface.

Squamous (squay-mus) means flat and refers to the flat cells at the surface. This covering is called a squamous epithelium. In addition to the progression of the shape of the cells from the lowermost large round cells to the outermost flat cells, the nuclei of the cells also change. Those cells lowermost along the basement membrane have a large nucleus that becomes progressively more compact and smaller as the cells approach the surface. On exposed squamous epithelium such as skin the outermost cells have lost their nuclei completely and the cells are filled with keratin to produce a protective keratin layer. On the cervix there is normally no keratin layer and the outermost cells have a very small dense nucleus.

When there is a disorder of the normal progression of cells from the lower to outermost layer then that is called a dysplasia. If this disorder of maturation is limited to the inner third of the epithelium then that is a mild dysplasia; if two-thirds of the thickness then a moderate dysplasia; if almost the full thickness then a severe dysplasia. If the outermost cells look the same as those along the basement membrane then that is a full thickness disorder and is called a carcinoma-in-situ.

A carcinoma-in-situ is a premalignant change and can become a cancer if not treated. It is thought that there is a progression from mild to moderate to severe dysplasia before developing carcinoma-in-situ. It may take years for this progression to develop into a cancer. Often the early changes will resolve spontaneously. If these dysplastic cells penetrate the basement membrane and invade into the deeper tissues then that is a cancer.

There are other terms for these dysplastic changes. The more modern term is intraepithelial neoplasia, grade I, II and III. The term carcinoma-in-situ, CIS, has been dropped since the word carcinoma means cancer and this is not a cancer. CIN III, cervical intraepithelial neoplasia grade III, means a full thickness dysplasia and has replaced CIS.

These premalignant changes can only be diagnosed by a biopsy of the cervix. The pathologist has to have a piece of tissue to evaluate not just a collection of scraped off cells. The Pap test is just a collection of scraped off cells. If these are abnormal, i.e. large round cells with a large nucleus that should not be on the surface, the pathologist can recognize them and report the test as abnormal. But, he cannot diagnose the true condition without an adequate biopsy specimen. Obtaining an adequate tissue biopsy specimen is the result of a comprehensive evaluation of the cervix following the report of an abnormal Pap test.

EVALUATION OF AN ABNORMAL PAP TEST

If a Pap test report indicates a malignant or premalignant condition the patient is reexamined and the Pap test repeated. The cervix is viewed with a magnifying instrument called a colposcope. Acetic acid, ordinary table vinegar, is applied to the cervix. This causes the nucleus of the outermost cells to swell with water and not transmit light. The cervix is illuminated with light from the colposcope. The areas that do not transmit light reflect it back to the colposcopist. Reflected light is white, so white areas are sought. The outermost cells of the normal cervix have a very small nucleus and will transmit light. If they have a large round nucleus then they are dysplastic and will not transmit light. White areas are the dysplastic areas. The whiter the area the worse the dysplasia.

Abnormal blood vessels can also be seen. Neoplasia means new growth. New growth means new blood vessels. Often these new blood vessels are abnormal. These abnormal vessels can be seen through the colposcope. The worse the vessels appear, the worse is the dysplasia. Cancers have the worst vascular appearance of all the changes that can occur on the cervix.

During a colposcopic examination the first determination is if there are abnormal areas. If so, can the entire abnormal area be seen? If so, then the most abnormal areas are biopsied. If the entire abnormal area cannot be seen then that cervix cannot be evaluated colposcopically. Usually the abnormal area extends up into the endocervical canal beyond view. In this case the canal must be removed to evaluate the cervix adequately. There are several techniques for removing the canal. Sometimes a cone biopsy is done. This removes a circular portion of the cervix extending up the canal to an apex. The specimen is shaped like a cone. A more modern technique that can be done in the office is called a LEEP. This means Loop Electrosurgical Excision Procedure, and removes portions of the cervix with an electrified thin wire loop.

If the colposcopic evaluation is satisfactory, meaning all the abnormal areas can be seen, then the most abnormal areas are biopsied and sent to the pathologist. The pathology report will indicate the diagnosis. It will be either something minimal, some degree of dysplasia, or CIN, possibly even a cancer. But whatever it is, it is the diagnosis, and the abnormal Pap test has been evaluated. If the colposcopy is unsatisfactory, then either a cone biopsy or a LEEP needs to be done and the pathological report of that material will be the diagnosis. If a specimen is scraped from the endocervix ( endocervical curettage, ECC) and shows dysplasia then a cone or LEEP also is indicated. Only after a diagnosis has been established can treatment be recommended.

TREATMENT OF PREMALIGNANT CONDITIONS

Once a diagnosis has been established treatment can be performed. Treatment of dysplasia is usually simple and almost 100 percent effective. It is not even mandatory that it be treated. It is not treated during pregnancy. It need not even be specifically diagnosed during pregnancy. During pregnancy all that need be done is to be assured that there is no invasive cancer present. This can often be accomplished by careful repeat colposcopic examinations, without a biopsy. Mild dysplasia may go away by itself without treatment.

If a cone biopsy or LEEP were done that had removed the abnormal areas it would be therapeutic as well as diagnostic. Otherwise, the abnormal area can be destroyed by freezing (cryocautery), vaporization (laser), removal by biopsy, cone, LEEP, or even hysterectomy if necessary. Hysterectomy may be best in certain circumstances, but is seldom a medical necessity for dysplasia. If the biopsy shows an invasive cancer then staging procedures need to be done and appropriate treatment given. This is an entirely different problem and will usually require referral to an oncologic specialist.

Once a premalignant condition has been treated then the woman should be reexamined every three months for at least a year and have a Pap test done. If all goes well then she should be reexamined annually. If the woman was pregnant when the abnormal Pap test was found and examination at that time was not suggestive of cancer then her definitive examination and biopsy can be deferred until six weeks postpartum.

THE CAUSE OF CERVICAL DYSPLASIA

The cause of cervical dysplasia and cervical cancer is unknown. Current studies strongly implicate the Human Papilloma Virus (HPV), as at least a cofactor in its development. This is the same virus that causes genital warts. There are over sixty sub-types of HPV that have been isolated, only a few of which are associated with cervical cancer. HPV can be transmitted by direct physical contact. Once there is an infection with HPV it will probably always be in the tissue. Complete obliteration of the virus from the body is not currently feasible and probably not necessary. All of us probably have a multitude of viruses of which we are unaware and which cause us no discernible problem.

If you have been told that your Pap test indicates the presence of HPV, do not be alarmed. If a definite viral change can be seen with the colposcope then it can be obliterated with cryocautery, laser or left alone. Only dysplasias need to be treated. You are not at great risk for developing cervical cancer. Continue to have annual Pap tests and treat any dysplasia if it is diagnosed.

Where did the HPV come from? Who knows, it may have been there for years. The point is that it is unknowable; there is no way to find out. Since it is of no demonstrable detriment to your health it is not worth the time worrying about where it came from. Some studies have demonstrated that about one third of college students have evidence of past or present infection with HPV. It is not unusual to find it reported on Pap tests in women in their seventh decade.

PAP TEST MISTAKES

The major error with the Pap test is not so much with misinterpretation of the slide by the pathology laboratory, but by the misapplication of a screening test for a diagnostic test. It is well known that at least 10 percent of women with an obvious visible palpable cervical cancer have a non-suspicious Pap test. This is because there is such a large amount of inflammation and necrosis associated with the cancer that all that is on the slide is this debris. The pathologist cannot see the cancer cells in the midst of all the debris.

When a woman has a symptom such as bleeding after intercourse, bleeding between periods, a watery or foul watery discharge, then a cancer of the cervix must be excluded. Only a thorough examination and biopsies can rule out a cervical cancer. A Pap test cannot rule out a cancer. A cervical cancer is usually visible on examination. If the cervix looks abnormal it must be biopsied. A Pap test cannot rule out a cancer. If a woman has symptoms that could be caused by a cervical cancer and the cervix looks normal then a biopsy from inside the endocervical canal must be done. A biopsy from inside the uterus may also be necessary. A Pap test never rules out a cancer.

IF YOU HAVE ABNORMAL BLEEDING, A WATERY DISCHARGE, OR FOUL WATERY DISCHARGE, YOU MUST HAVE A DIAGNOSTIC TEST TO RULE OUT CANCER. NEVER, NEVER, NEVER, EVER ACCEPT A NORMAL PAP TEST AS PROOF OF THERE BEING NO CANCER.

Another error is to treat on the basis of the Pap test rather than on the basis of the diagnosis. An abnormal Pap test never leads to treatment. An abnormal Pap test is not a diagnosis. Treatment cannot be performed until a diagnosis is obtained. An abnormal Pap test leads to diagnosis by colposcopy and biopsy, then to treatment. If a simple hysterectomy is done because of an abnormal Pap test, most women will have had an unneeded hysterectomy. If a cancer is present, a simple hysterectomy may be fatal. Cancers cannot be treated by simple means.

Many women do not obtain annual Pap tests. Many who do think that a normal Pap test means that they are cancer free. The Pap test evaluates only the squamous epithelium covering the visible part of the cervix. The endocervical canal has a glandular epithelium that is not easily evaluated by Pap tests. This glandular epithelium can also become malignant and not be detected. Cancers of the uterus, ovaries and fallopian tubes are not usually detected by the Pap test.

The Pap test is an excellent screening test. It is easy to do, easy to interpret, easy to evaluate when abnormal and most importantly can find changes before they become malignant. These premalignant changes are easy to treat. Cancers are hard to treat.

William M. Rich, M.D.
Clinical Professor of Obstetrics and Gynecology
University of California, San Francisco
Director of Gynecologic Oncology
University Medical Center
Fresno, California