Explanation of your PAP smear

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1 Explanation of your PAP smear Approximately 5-10% of PAP smears in the United States are judged to be abnormal. Too often, the woman who receives this news worries that she already has, or will develop, cancer. Such a conclusion is not warranted, but at the same time, the interpretation of an abnormal PAP smear should be accompanied by further investigation to see what exactly is the problem. First, I should emphasize that the PAP smear is a screening test, and as such, it does not establish a diagnosis. Rather, the interpretation should be regarded as a prediction of what might be the problem. Second, the terminology that is recommended for reporting PAP smears has gone through several evolutions since Dr. Papanicolaou created the test 60 years ago. The most recent of these is termed the Bethesda System 2001; however, not all laboratories have adopted this system yet. Two or three previous systems remain in use, and can thus cause some confusion as to exactly what a report means. Medical Laboratory Associates has adopted the Bethesda System 2001, so your report conforms to this system. Following is a synopsis of the system, along with recommendations that our laboratory makes regarding further investigation or therapy. Please know that you and your physician are not bound by these recommendations, as the details about your own clinical situation (age, any history of previous abnormal gynecologic studies, the appearance of your cervix when examined by your physician, sexual activity, etc.), some of which are not (and should not be) available to the laboratory. The recommendations are made in the spirit of informing you of options that are available, as you educate yourself about the potential condition that you have. They conform to guidelines put forth by the American Society of Cytopathology and the American College of Obstetricians and Gynecologists. Bethesda System 2001: Negative for intraepithelial lesion or malignancy. This is the term used when there is no evidence of a malignancy or a pre-malignant condition. (Epithelium is the layer of cells on the surface of the cervix, and is the type of cell that can most often become malignant.) There are two types of epithelial cells in the cervix: a) squamous cells that coat the portion of the cervix that protrudes into the vagina, and b) glandular cells that coat the portion of the cervix that leads up to the uterine cavity, and that line the glands that are present in the wall of this passageway. Even though a negative report suggests the absence of an epithelial lesion, there may be minor abnormalities that are included in a negative report. Such abnormalities include: the presence of organisms, inflammatory or reactive changes, presence of changes suggestive of prior irradiation (such as might have been administered for previous cancer), presence of glandular cells in a patient who has previously had a hysterectomy, or presence of endometrial glandular cells.

2 If pathologic organisms are reported, the recommendation is usually made to treat the infection, and then to repeat the PAP smear after resolution of the infection, just to be sure that nothing was missed on the original PAP smear. Sometimes, PAP smears taken in the presence of infections can be very cellular, hiding pre-malignant changes in the epithelial cells. The presence of endometrial glandular cells in a post-menopausal woman can signal the presence of a malignancy in the endometrial cavity, although this is not often the case. Atypical Squamous Cells of Uncertain Significance (ASCUS). This term is the most commonly used term of all the abnormalities, and comprises about 90% of all abnormal interpretations (about 4% of all PAP smears). As the term implies, we cannot be sure what the true abnormality will be, except that something is wrong with the squamous cells that line the portion of the cervix that protrudes into the vagina. See below for a discussion of options to consider if you have a report of ASCUS. The vast majority of patients with ASCUS turn out to have nothing to worry about. Low-Grade Squamous Intraepithelial Lesion (LSIL). This condition has also been called mild dysplasia and Cervical Intraepithelial Neoplasia grade 1 (CIN 1). According to modern theory, this condition is the earliest recognizable lesion that is on the road to becoming cancer. On the other hand, only about 5% of people who have mild dysplasia ever develop true cancer; the other 95% revert to normal or are cured by a therapeutic intervention, such as freezing of the cervix, or other local, limited forms of therapy. And, with close monitoring, almost all of the 5% are cured before they progress to invasive cancer. You see, this is the beauty of the PAP smear; it allows lesions to be discovered well before they become malignant, and to be treated with virtually 100% success. 4. High-Grade Squamous Intraepithelial Lesion (HSIL). This condition has also been called moderate to severe dysplasia, Cervical Intraepithelial Neoplasia grade 2 or 3 (CIN 2 or 3), or carcinoma-in-situ (CIS). If left untreated, this condition is more likely to become invasive cervical cancer. (No one knows exactly how likely, since we cannot do the experiment to see how often progression to cancer occurs.) Thus, if your report reflects this terminology, you can expect a recommendation for some sort of therapeutic intervention. Depending on your own specific situation, this therapy might range from a conservative form, such as freezing or a superficial excision (called LEEP, or Laser Electro-Excision Procedure), to more extensive therapy, such as hysterectomy. Squamous Cell Carcinoma. This term is used when the PAP smear has certain findings that suggest that a malignant condition has become invasive into the underlying connective tissue of the cervix. Fortunately, in our culture, this interpretation is quite rare, because extensive use of the PAP smear has discovered the abnormalities before they get to this stage. This is the condition that we hope to eliminate by liberal use of the PAP smear. As an aside, the United States has among the lowest rate of invasive cervical cancer in the world, while those countries (an example is Mexico) where the PAP smear has not been integrated into routine use have rates of invasive cervical cancer that are several times higher than the U.S. Atypical Glandular Cells. This term is used when we find glandular cells of either endocervical or endometrial (uterine) origin, and the cells do not appear normal. The report will qualify as to what type of cells we are worried about, and give some estimate as to whether or not they represent a malignant or pre-malignant process. Guidelines as to what to do about such a finding are less well developed, and are highly dependent upon the patient s personal situation. They are beyond the scope of this brief summary. In summary, I hope that you can see that an abnormal PAP smear report, short of outright malignancy, is something to take action about, but not to worry about in terms of an invasive cancer. It will cause you some inconvenience, but if acted upon, will not be a harbinger of serious disease, because it is just doing what it was designed for to serve as an early warning, and to allow for the removal of a pre-malignant lesion. Recommendations for followup of a report of ASCUS:

3 Dysplasia Literally, this term means disordered form or differentiation, meaning that a tissue does not form properly. It has come to be used as a term meaning a lesion that has an increased probability of becoming malignant. Cervical Intraepithelial Neoplasia (CIN) This is a term that was introduced several years ago to be used in place of dysplasia, because the latter was not being used uniformly by pathologists and other physicians. CIN has, in turn, been replaced by: Squamous Intraepithelial Lesion (SIL) This distinguishes the process from a glandular process of preneoplastic change, and is graded as low (LSIL) or high (HSIL) grade. When patients with an interpretation of ASCUS are followed up carefully, one finds the following: about 75% are normal, 15% are low grade dysplasia (Cervical Intraepithelial Neoplasia grade 1, or CIN 1) and 10% have higher grade dysplasia. (See glossary for explanation of terms.) There are three options available to you for further investigation into the situation. Since most of the cases of ASCUS turn out to be normal, you could wait a few months and have a repeat PAP done. Historically, this has been the most common thing to do. Often, the second PAP will revert to normal; however, you will have spent several months waiting to find that out. And, what if it doesn t turn out normal, but instead is still ASCUS or worse? Alternatively, your physician could evaluate your cervix with a colposcope, an instrument that allows a magnified image of the cervix to be seen and evaluated. Any observed abnormalities can then be subjected to biopsy, and then microscopic evaluation by the pathologist. But this would turn out to have been unnecessary 75% of the time. A third alternative that is just becoming available is to have the PAP smear evaluated for the presence or absence of what is termed high risk HPV, or Human Papilloma Virus. There are approximately 70 strains of HPV currently known, and about 14 of them have been associated with cervical cancer. These 14 are collectively known as high risk HPV. Most of the rest of the strains of HPV do not infect the cervix, and are not of interest in this discussion. The remaining few strains that do infect the cervix, but which are not associated with cervical cancer, are termed low risk HPV. Since they rarely, if ever, cause cervical cancer, they are also not of interest in this discussion. Now, if one tests for high risk HPV in patients with ASCUS, we find that only about 30% harbor high risk HPV. This means that 70% of patients with ASCUS have changes that are not associated HPV infection, and thus, with progression to a dysplastic lesion or cancer, and can rest more easily that they do not have significant disease. There have been advances in the technology for PAP smears in the past few years, most notably in the way the specimens are processed onto the glass microscopic slides. A conventional PAP smear is made by the person taking the cells from your cervix. This is done by smearing the instrument (spatula, brush, broom, etc.) containing the cells onto the microscopic slide and then quickly spraying the slide with an alcohol fixative, thus preserving the cells from deterioration. This results in a preparation in which cells are piled upon one another, obscuring many of them, so that the technologist who is charged with the responsibility of screening the slide cannot see all of the cells clearly. We now have the ability to improve upon this process. The person obtaining the cells can now drop the end of the collecting device into a bottle of alcohol preservative and send the bottle to the laboratory. In the laboratory, we have automated equipment that shakes the cells off the collecting device, separates them from contaminating materials such as blood and mucous, and gently settles them onto the glass microscopic slide in a single layer of cells, so that every cell is clearly visible. This process has resulted in a significant improvement in recognition of abnormal changes (reduction in the rate of falsely negative smears), and a reduction in the number of unsatisfactory smears. Since a portion of the cells remain in the collection vial after making the PAP smear, there is material available to test for HPV infection without asking the patient to come back for an additional specimen. It thus allows us to refine the diagnosis of ASCUS much more quickly than if a conventional PAP smear had been done. Glossary

4 neoplastic change, and is graded as low (LSIL) or high (HSIL) grade. Neoplasm Literally this means new growth, and formally is divided into benign or malignant types of neoplasm. Benign neoplasms are those that generally do not result in the death of the patient, while malignant neoplasms may result in death, if not treated successfully. We at Medical Laboratory Associates are committed to providing quality cytology services to our physicians and patients, and would welcome your communications (by phone, , snail mail, etc.) if you have further questions that you think we could help with. Edward A. Barker, MD, PhD Medical Director Pathologist Medical Laboratory Associates Lake City Way, NE, Suite 300 Seattle, Washington, FAX

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