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Management of the Abnormal Pap Smear and Colposcopy

Pap smears are associated with a declining mortality from cervical cancer. Contrast this with women in third-world countries, in Africa and South America, where cervical cancer is not only the leading cause of death from cancer in these women, but itís even the leading cause in some of these areas of death, period, for women overall. So we are very fortunate in the United States, due to the widespread use of the Pap smear and other factors, that cervical cancer, Pap smear, colposcopy, cervix biopsy, culposcopy, culposcope, colposcopy, ASCUS

Letís not underestimate the value of simply looking at the cervix. Iíll probably mention this a few times today, but certainly the Pap smear is designed to pick up microscopic problems. Itís truly a screening test. Itís not a diagnostic test. If a person sees a problem on the cervix, if thereís a visible lesion, itís okay to go ahead and do a Pap smear but even if the Pap smear is normal, you canít say the patient is okay. If

Each test that we use for screening has to be a practical test, and the Pap smear is no exception. Itís a simple test, a quick test, painless - maybe because Iím a male and saying itís painless, but itís probably not painless anymore - inexpensive, without complications and

An awful lot of Pap smears are done in the United States per year. Probably 55 million done in the United States per year. A cytotechnologist screens about 60 slides per day. The 55 Pap smears that are done in the United States probably only comprise half of the Pap smears that should be done. So clearly not all women are receiving their Pap smears as advised, but thatís still a lot of Pap smears. These cytotechnologists are pretty amazing in how they screen slides. They, of course, have been specially trained and if you ever go to visit

Cervical cancer is not an endemic disease in the United States. So we are talking about a small percentage of a small percentage, and most Pap smears are wholly accurate and so I think we do a disservice to women in the sense that some might decide not to come in for a Pap smear thinking, I they are always wrong why should I bother. Itís an uncomfortable exam anyhow. When weíve gone back and looked - as

Those of you that do a lot of Pap smears like I do, probably view the false positive as a bigger problem. Itís not a big problem just because women are unduly alarmed or because women have to come in for unnecessary testing and spend a lot of money, but the biggest problem with the false positive rate is that the denominator in the false positive rate is the normal women. Itís everybody. Itís all women. So even

Iíd like to explain to you how to do a Pap smear briefly, simply because if sampling error is the major reason why we have false negative rates, then sometimes lawyers will try to blame physicians for a patient getting cancer or a precancerous condition, stating, "Well, you just did not do the Pap smear properly." Do not lubricate the speculum with oil-based lubricants or even K-Y jelly, if you can avoid it. The lubricant

Perhaps by using the cytobrush weíll see an earlier diagnosis of these glandular cancers than we have in the past. The problem with the cytobrushes is, it hurts. It used to be you could do a Pap smear and it would be relatively painless but you use those cytobrush - and Iím sure most of you have seen it - itís uncomfortable and the patient bleeds. So the sequence, I think, is really important. Start with the ectocervical scraping if you are going to use a cytobrush because if you use a cytobrush first and you get all this blood that comes back on

Then have your slides processed by a quality laboratory. What do I mean by that? Well, Iím not one of these guys like in Montana that wants to overthrow the government or anything, but lets face it. The government has really stepped wholesale into laboratory medicine and

This slide is a little bit for historical interest. Obviously we are still using speculums and still using large swabs to remove excessive mucus from the vagina. Most of us are using a wooden stick for Pap smears and using this end, although some people use a plastic stick for the ectocervical scraping. This is the cotton tipped applicator that we used to use for the endocervical scraping but now we use a cytobrush. Most of us are just using one slide instead of three. We used to do a cervix, endocervix and vaginal pool specimen. Now we combine the

One thing I want to mention just briefly, without going into too much detail, is this issue of doing Pap smears after hysterectomy to try to detect vaginal cancer. Vaginal cancer is very rare and so itís very uncommon that women will get vaginal cancer with the exception of

Most of the national organizations have signed onto the suggested screening guidelines for cervical cancer, including the American Cancer Society and the American College of Gynecology. All women who are, or who have been, sexually active or who have reached age 18 should undergo an annual Pap test and pelvic examination. After a woman has had three or more consecutive satisfactory annual

When you get a Pap smear report, how do you know whether you have done a good Pap smear or not? Well, letís just briefly touch on this because if you are interpreting results that are inadequate to interpret then you could make a mistake. Of course, having proper fixation, no drying artifact is important. Whether endocervical cells are present or not is considered to be important. The reason for this is - we will

Then severe inflammation. If thereís severe inflammation then that can obscure the reading of the Pap smear and remember, a Pap smear is just a scraping of exfoliated cells and Pap smear diagnoses, as we will discuss, one of them is cancer, right? We all know that cancer is an

The original Pap smear definitions - most of us know - are class I through IV as defined by Papanicolaou and basically a class I was totally normal. A class II category was kind of a grab-bag category that they threw things in that didnít look like dysplasia, but werenít totally normal. In retrospect we figured out that the old class II category probably included about 20% Pap smears that actually were representative of dysplasia. Then clearly people with dysplasia - which simply means abnormal cells - in other words, precancerous conditions, that was the class III and class IV category and class V was cancer. Nobody argues over what to do with patients that have the word dysplasia on their Pap smear right now. Most of these people get colposcopy and biopsy at least at the first episode of dysplasia as part of the work-up for the abnormal Pap smear. But some of the confusion has arisen in what to do with people with the lower grade squamous lesions and

Now we are going to talk about the Bethesda system. This is a system that most labs use simply because thatís the system that Medicare requires. If you are going to use this for Medicare than you might as well use it for all patients. Why would you have two systems? So the government really has told us how to read Pap smears. And thatís a fact. A bunch of doctors got together in Bethesda Maryland, mainly pathologists, at the request of the NIH and they developed this system. The best thing about this system is this part that weíve already talked about and thatís that it tells you whether you can interpret the Pap smear or not. It really kind of takes it out of your hands. If it says, "Unsatisfactory for interpretation" you can read it but you really canít make a decision on it. Whereas if it says, "Satisfactory for interpretation" then you are basing your decisions on what the pathologist viewed as a smear that was adequate. So thatís really valuable. Iím really happy about that. The problem with the Bethesda system is the descriptive diagnoses have created some problems. Some difficulties in managing patients. What they tried to do - they had very good intentions - they tried to reduce the number of abnormal diagnoses. Whereas before we had signs of virus infection, human papilloma infection - which is considered an etiologic factor for getting cervical cancer and weíll discuss that in a second - and then they had mild dysplasia, moderate dysplasia, severe dysplasia, carcinoma in situ - which is really just a severe form of precancerous change - and then cancer.

We had all these abnormal diagnoses and we figured out that the pathologists couldnít agree about what these were. Two pathologists would disagree commonly on whether something was a moderate or severe dysplasia. So they said, "Weíll fix this inter-observer variability" - for that matter there was intra-observer too. A pathologist could be asked to come back and look at his or her same slides that they just read and theyíd give a different diagnosis. So they said, ĎWeíll create only two categories of abnormality that suggest precancerous change. LSIL: low grade squamous intraepithelial lesion and HSIL: high grade squamous intraepithelial lesion. By having only two categories, if you take three pathologists and lock them in a room with only two diagnoses, at least two of them gotta agree. So they said, "Voila, we have solved this problem" and the problem is that this low grade category they include the so-called HPV atypia in it. And this is really difficult because 50% of American women who are sexually active have been exposed to HPV. So if they truly could tell that theyíve been exposed to HPV on their Pap smear, 50% of Pap smears would have LSIL on it. But also it includes this mild dysplasia category, and remember that dysplasia word? I told you gee, youíve got to do something, at least at the initial time that they have been diagnosed with that. So this system causes sudden increases in the number of patients needing colposcopy and biopsies.

Remember the false positive issue, even though these are clearly not normal diagnoses, are these serious pathologic conditions? Well, thatís a whole other lecture. But the bottom line is that the NIH has embarked on a study at five or six sites around the United States where we will have the answer to this question in the year 2002 or something. Maybe later than that. What theyíve done is theyíve taken these people with LSIL and theyíve randomized them to "no treatment" versus "immediate colposcopy and biopsy" versus "virus testing" and if they have what they call a high-risk virus infection with HPV then they will go immediately to colposcopy and biopsies. Now where does that leave us? Those of us that are in the trenches? I think if you see LSIL on a Pap smear and then in parenthesis is says "suspect or favor mild dysplasia" I think that person is going to have to have colposcopy and biopsies. Whereas if they have HPV atypia, I think if itís a compliant patient -

Now, if that wasnít difficult enough, this ASCUS category is another one. This pretty much corresponds to this old class II category. Some of these atypical squamous cells that arenít bad enough to call LSIL or HSIL will actually have LSIL or HSIL. Perhaps as many as 20 to 30%. So we are recommending repeat Pap smears for this group, at least after the first one. And if they continue to have Pap smears every six months or so that show ASCUS then we recommend colposcopy and biopsies to try to get a better handle on whatís going on. The real scary part about the ASCUS category is that besides the fact that the number of these cases being diagnoses as ASCUS is increasing, is also

Obviously anybody with HSIL or with squamous cell carcinoma on a Pap smear is going to need further evaluation. I didnít have time in todayís lecture to talk about the glandular lesions, but certainly the people that have the words "Glandular atypia" or "Adenocarcinoma in situ" or "Glandular hyperplasia. Suspect precancerous change", anything like that is also going to

Now, in order to be successful in screening you have to screen a disease that is appropriate for screening. I want to emphasize that because people sometimes wonder, "Why do we do Pap smears every year? How did we decide to do them every year versus every two years, versus every six months? Why donít we screen for all cancers? Why is cervical cancer a disease we can screen for, and others arenít?" Well, letís face it. We keep hearing about preventive care and how important it is and everything. I just wish it worked as good as the politicians think it should. But cervical cancer is a disease where prevention make sense because patients go from this mild dysplasia, this

The other thing I want to mention is a lot of people use this CIN 3, 2 and 1 terminology and the benefit of it is that when we were using terms like carcinoma in situ - and how many of you have had patients who have come in the office and said, "Iíve had cervical cancer and my doctor froze my cervix and I was cured." It doesnít work that way. You canít freeze cancer. Cancer goes to the oncologist. They either have radiation treatment or, for selected early cases, radical surgery, radical hysterectomy, pelvic lymphadenectomy. Itís not an office procedure for cervical cancer. So the problem was this term, carcinoma in situ, itís kind of a conflicting term because in situ doesnít really go along with carcinoma, does it? So they switched to this CIN terminology, Cervical Intraepithelial Neoplasia, but the problem is some of the etiologic factors for getting cervical cancer, the use of CIN 1, CIN 2, CIN 3 doesnít go over real well with patients. Something about sinning and

Obviously these precancerous conditions are a serious problem. This is from Canada but itís not much different than the United States. The thing I want to emphasize from this slide is that the average age for getting these precancerous conditions is in the reproductive age group. So

Letís talk about HPV a little bit. Iím sure itís a big problem in most of your practices. Condyloma or warts of the cervix - and actually most women wonít get visible warts, theyíll get warts that you can see with colposcopic magnification - it is in almost, not quite all, but almost all cases a sexually transmitted virus. It precedes other intraepithelial lesions, it can coexist with dysplasia or carcinoma in situ. And you can see

This is a slide, actually this is a slide of the condyloma. I will often Ö I show some of this lecture to my medical students. These big white lesions - this is a colposcopic view of the cervix - these are condylomas. It is very infrequent that you would ever see something this florid on a cervix, but the bottom line is, how do you know thatís condyloma? Are you going to do a Pap smear and just say, "Oh, maíam youíve got

What are the risk factors, then, for getting cervical cancer? How can we do a risk assessment and decide whether patients can go from every year Pap smears to Pap smears less frequently? Well, known human papilloma infection, weíve already beat that drum. But what are the

What about intercourse at an early age? This is a very very important risk factor. One of my students three or four years ago asked me, in a lecture, "what do you mean by an early age?" I had never really thought about it. I thought it was obvious. I said, "Well, you know, my daughter is ten now and I think 30 is looking pretty good." But what we mean is less than 16. I think that there are several reasons why this is

There are other factors you can get cervical cancer from. One of them is cigarette smoking. Sounds weird, doesnít it, but the bottom line is that the smoke gets these carcinogens in the blood stream that get deposited in the cervical mucus. I think if you do an evaluation of a normal Pap smear and you donít tell a patient that they should quit smoking because it could increase their risk of getting cancer you are going to be in trouble. Certain vitamin deficiencies - vitamins A, C and folic acid - now Iím not saying you need to run out to GNC and have your

Okay, what are we going to do about that abnormal Pap smear? Well, first of all we want to rule out cancer because if theyíve got cancer, go to the oncologist. It they donít have cancer, we want to know the lesionís distribution - where is it on the cervix? - and then we want to

Let me also say that the colposcope is just a telescopic instrument with a magnifying lenses somewhere between 4 and 16 x and a really bright light. As I get older Iím starting to get an appreciation for light. It really makes a huge difference in what you can see by projecting that light into the vagina and looking at the cervix. This is a stratified squamous epithelium - this is supposed to be a drawing of a normal cervix. This is the normal process of squamous metaplasia and this is the glandular cells and these grape-like fronds of the glands release mucus that we see on the cervix at the os. This is just a normal colposcopic picture of the cervix. This is the external os. You can see the squamocolumnar junction there and thereís no lesions. Nice and pink, perfectly normal. Hereís a picture of squamous metaplasia. You can see through squamous metaplasia. Itís opalescent, itís not opaque. It does have this kind of diffuse border on it. When the squamous metaplasia covers over a gland opening instead of just replacing the gland by squamous epithelium, you get something known as nabothian cysts. Thatís how they form. Nabothian cysts are normal. Thereís nothing wrong having nabothian cysts. They are not a pathologic condition. And they are useful because they tell you that squamous metaplasia has occurred here. Obviously you donít see patients every month and you are not watching their squamous metaplasia going on. You see them once a year on a good year, and when they come in you have to guess where the squamocolumnar junction used to be if you are going to do a colposcopy. So you look for nabothian cysts and

This is this issue of squamous metaplasia. Here is perhaps a younger woman or a woman who has never been pregnant and her squamocolumnar junction is on the outer portion of the cervix. Hereís maybe somebody who has had a few children. Maybe she is in her 30ís or 40ís and squamocolumnar junction has moved up inwards. So you can see the process that has occurred. This drawing here is one that a lot of us do when we do colposcopy for the abnormal Pap smear. This is our estimation of where the squamocolumnar junction used to be and this is where it currently resides. The distance between where we think it used to and where we can see it at this time is known as the - that area of the cervix is known as the transformation zone. This is a really important concept in colposcopy because if the transformation zone is located on the outside of the cervix entirely where you can see it, then that is known as satisfactory colposcopy. Whereas if the transformation zone extends into the canal of the cervix where you canít see it - even if thereís no problem up there - you still have to call it unsatisfactory colposcopy because you canít see in there. So satisfactory colposcopy is something that usually indicates that

So weíve seen normal. Whatís abnormal? Letís focus on this aceto-white epithelium and some of these vascular changes. Well, remember that picture I showed you of squamous metaplasia, well hereís a photograph of white epithelium. This the so-called aceto-white epithelium. It turns bright white when you apply the vinegar. Notice how itís different. It has got really sharp margins, you canít really see through it, itís a little bit raised. This is just classic. Perfect dysplastic epithelium. Itís all on the outside of the cervix so itís satisfactory. Anytime you have a

So what should we do for treatment? How do we treat people with dysplasia? Well, I mentioned to you that observation - thatís a pretty gutsy treatment. I usually reserve observation for my patients that have failed treatment once and have those mild dysplasia or really HPV atypia lesions where Iím not wondering if they wonít get better on their own, more than what I can do for them. But most of the time we are fairly interventionists, because we don't want people to get cancer and they want you to do something. Sometimes youíll read, "Well, the

The LEEP procedure weíll talk about briefly. Primarily reserved for external lesions. Perhaps those that extend just slightly into the canal of the cervix, and then the more traditional conization of the cervix which is a cutting procedure that includes at least half of the cervical canal in an effort to detect and treat disease that is extended up inside the

Letís go through a few flow diagrams. Basically if you do a biopsy and an endocervical curettage and the patient doesnít have cancer but they do have dysplasia and they donít have any disease in their canal, these are your classic - the most common scenario of all the patients we treat fall in this mainline here - laser or cryosurgery. Sometimes you will get fooled and the patient will have something in the canal and

That LEEP procedure is where we hook it up to an electric current - and you can use a combined cautery and cutting current or just cutting alone - you numb the cervix, it has to be numb or it really hurts, and itís like a hot knife going through butter. This is drawing of it. You just remove the external disease. It goes very quickly. Less than 15 seconds, most of the time for one swipe. Thereís all different sizes of loops.