Pap Smear test for cervical cancer under the Microscope

The Pap smear is a screening procedure that tests for cervical cancer. This test checks for the presence of precancerous or cancer cells on the cervix, the opening of the uterus. Women typically are advised to start getting Pap tests around age 21. During a Pap smear cells from the cervix are examined for abnormal growth.

There are a couple different methods for Pap smear testing.

In a traditional Pap test, cell samples are obtained from the vagina, cervix, and cervical canal and spread on a glass microscope slide.  The microscope slide is then sent to a lab for examination under the lab microscope.

The ThinPrep Pap test was designed to reduce some of the technical problems inherent in the tradition Pap smear method. In the ThinPrep Pap test, cell samples are collected using a special brush that is immediately washed in a special fluid. The ThinPrep machine then filters out the cells from the solution and deposits them in a thin uniform single layer of cells on a glass slide for microscope examination. The ThinPrep Pap test is used to screen for cervical disease, HPV and some common sexually transmitted infections.

This is an image of a ThinPrep Pap smear captured under a lab microscope at 100x magnification.

A few advantages to the ThinPrep Pap method include removing contaminants such as blood and mucus which can obscure cells in the traditional Pap smear. The single layer of cells is easier to examine under the microscope. This results in an increased rate of detection of abnormal cells. The disadvantage of the ThinPrep Pap smear method is that there is an increased cost incurred by the collection fluid and cost of continued operation of the ThinPrep machine.

This is an image of a ThinPrep Pap smear captured under the lab microscope at 400x.

To learn more about what you can expect during a Pap smear visit Mayo Clinic’s website. If you have questions regarding lab microscopes or digital microscopy Contact Microscope World.

Screening for Cervical Cancer Using Automated Analysis of PAP-Smears

Cervical cancer is one of the most deadly and common forms of cancer among women if no action is taken to prevent it, yet it is preventable through a simple screening test, the so-called PAP-smear. This is the most effective cancer prevention measure developed so far. But the visual examination of the smears is time consuming and expensive and there have been numerous attempts at automating the analysis ever since the test was introduced more than 60 years ago. The first commercial systems for automated analysis of the cell samples appeared around the turn of the millennium but they have had limited impact on the screening costs. In this paper we examine the key issues that need to be addressed when an automated analysis system is developed and discuss how these challenges have been met over the years. The lessons learned may be useful in the efforts to create a cost-effective screening system that could make affordable screening for cervical cancer available for all women globally, thus preventing most of the quarter million annual unnecessary deaths still caused by this disease.

1. Cervical Cancer Screening

Cancer of the cervix uteri is the second most common cancer among women worldwide, with more than half a million new cases each year and about half as many deaths. The variation in incidence rate between countries is striking. In many countries it is the most common cancer among women while in some countries it is down at 10th place. About 86% of the cases occur in developing countries. In Africa the age-standardized incidence rate is 25 per 100,000 per year; in some countries on that continent it is more than double that rate. In India the rate is 27 while it is 5.7 in USA and 3.7 in Finland [1]. We thus see more than a factor of ten variations in cervical cancer incidence rates between the lowest and highest countries.

While a part of this variation may be attributed to general variations in living conditions and the spread of the Human Papillomavirus, HPV, in the population the major part is attributed to the success of screening using the Papanicolaou test (PAP-test). If detected early, cervical cancer is curable and the 5-year survival rate is as high as 92% [2]. The idea behind the PAP-test is that cellular changes that may develop into cancer are detected at such an early stage that they can be removed through a simple operation, thus preventing the cancer. Evidence for the importance of the PAP-test can be found in statistics from many countries where the PAP-test is used in systematic, comprehensive screening programs. In Sweden, for example, the overall incidence of cervical cancer declined by 67% over a 40-year period, from 20 cases per 100 000 in 1965 to 6.6 cases per 100 000 women in 2005. Detailed studies of the cancer statistics confirm this [3, 4].

1.1. The PAP-Smear

The original PAP-smear is produced in a very simple and straightforward way; a brush or spatula is used to gently scrape cellular material from the squamocolumnar junction in the cervix and this is smeared onto a glass slide of about 25 × 50 mm. The cells are stained, fixated, and then visually examined under a microscope. The test was first suggested by Papanicolaou in 1928 but it took almost 15 years before it was generally accepted by the medical community [5, 6]. A monograph in 1943 [7] gave a detailed account of how the screening should be conducted and this procedure has since been widely adopted, leading to the remarkable reduction in cervical cancer incidence mentioned in the previous paragraphs.

The screening is conducted by cytotechnologists, cytotechs for short, who through a light microscope examine the cell sample for signs of malignancy. Through this procedure they can not only find proof of invasive cancer but also detect certain cancer precursors, allowing for early and effective treatment. The cytotechs are laboratory technologists who go through a specialized training, typically of about one year. When they find something that looks suspicious for malignancy on a specimen it is reported. In many labs the finding is then confirmed by a cytopathologist, a medical doctor specializing in cellular pathology, who makes the final decision whether it is a (pre-)malignant lesion or not and thus takes the medical responsibility for the diagnosis. A detected high grade premalignant lesion typically leads to the woman being offered a colposcopy and, if a lesion is confirmed, an operation to remove it. The detection of a low grade lesion may lead to a follow-up smear being taken after a shorter time interval than the normal 2-3 years.

In principle, the screening task is straightforward. The morphological changes that a cell undergoes when it is being transformed into a malignant cell are quite apparent and easy to describe. The nucleus becomes larger and more irregularly shaped, the cytoplasm becomes smaller so that the nuclear/cytoplasm size ratio changes, and the chromatin distribution in the nucleus changes to become more coarse and irregularly distributed (see Figure 2).

To visually detect these changes we need to see details close to the optical resolution limit. A nucleus is around 10 microns in diameter and the chromatin structures and shape variations are at the micron or submicron level. Therefore a high power lens is used, typically 40x. The precancerous lesion may be quite small and local and the number of diagnostic (pre-)malignant cells on a specimen may be low. It is desirable to detect a precancerous lesion even if there are only a few diagnostic cells present on the specimen. This creates a demanding search problem. A smear covers about 25 50 mm and typically contains a few hundred thousand cells, sometimes even more. The screening is initially done at low resolution using a 10x lens, and when something suspicious is seen the screener switches to 40x. At 10x around 1,000 fields of view need to be scrutinized to cover the whole sample. The time required for this varies depending on how difficult the sample is, but on average it only takes 5–10 minutes. There are recommendations saying that, due to the hazards of fatigue, a cytotech should not work more than 7 hours a day and analyse no more than 70 samples [8]. Even when following this recommendation, the cytotech has to inspect three image fields per second on the average. Furthermore, since the visible precancerous changes may be quite local, the cytotech needs to maintain full concentration all the time in order not to risk missing some diagnostic cells.

2. Historical Development of Automated Screening Systems

Based on the fact that the changes in cell morphology are quite obvious and the fact that the visual screening is very demanding, tedious, and expensive in terms of labour requirements, there were very early, only a decade after the PAP-test became generally accepted, proposals for automating the screening through some kind of scanning and image analysis mechanism [9]. The hope was that an automated system would be able to do the screening both at a lower cost and with higher accuracy.

Since then a large number of projects have attempted to develop screening systems. The problem turned out to be a lot harder than anticipated. It took more than 40 years before the first successful commercial systems appeared. And still automated screening is not sufficiently cost-effective to completely replace the visual screening judging from the relatively limited penetration of automated screening systems in the screening operations worldwide. In this section, we briefly outline this development and try to see for each new generation of systems in what ways they improved on earlier systems, what were the main problems, and what was learned. We also discuss the underlying technical aspects and try to understand what makes the problem so hard and how one can go about solving it.

2.1. First Generation Systems

The Cytoanalyzer project in the US was the first attempt at building an automated screening device for PAP-smears [10]. The system was based on the concept that cancer cells could be distinguished from normal cells on the basis of nuclear size and optical density. The system included automatic slide feed and autofocus circuits. The image analysis was based on hard-wired analogue video processing circuits that generated two-dimensional histograms of nuclear size versus nuclear optical density. The spatial resolution was 5 micrometers. Preliminary experiments had shown that it was possible to detect the difference in size between normal and malignant cells at this resolution. This was the first fully automated microscope and as such a quite expensive project. Unfortunately, tests with the Cytoanalyzer revealed that the special purpose fixed logic pattern recognition produced too many false alarms on the cell level [11]. There were numerous objects of a size similar to malignant cells present also on normal specimens, for example, clumps of blood cells, strands of tissue and mucus, overlapping epithelial cells, and so forth. Every sample, including the normal ones, was thus found to be suspicious for abnormality. The project failed in the early sixties, mainly because of this artefact rejection problem.

Due to the bad reputation for cytology automation caused by this early and expensive failure in the US, the attempts at automation over the next couple of decades were shifted to Europe and Japan. In Britain a one-parameter (nuclear size) automatic screener was developed in the late sixties [12]. It failed for the same reason as the Cytoanalyzer.

In Japan, Watanabe and coworkers at Toshiba developed CYBEST [13]. Their first version used special-purpose electronic circuits while later versions were based on general purpose digital computers, thus bridging the gap between old analogue and new digital technology. The pixel size was around one micron. They extracted four different features from the cell images: nuclear area, nuclear density, cytoplasmic area, and nuclear/cytoplasmic ratio. They also realized that nuclear shape and chromatin pattern were useful parameters but were not able to reliably measure these features automatically mainly because the automatic focusing was unable to reliably produce images with all the cell nuclei in sufficiently good focus. The chromatin pattern measure that was proposed by this group was the number of blobs within the nuclear region. Four generations of prototype systems were developed over a 15-year period. The last one used strobed illumination and nonstop scanning motion to reach high scanning speeds. The prototypes were used in large field trials in the Japanese screening program and showed promising results but none of them became a product [14].

2.2. New Generations of Systems

When the first generation systems were developed there were no interactive computers and no display units capable of showing digital images available. This, of course, made development much harder. However, during the seventies it became possible to develop interactive image analysis systems, albeit with very limited capacity, typically with a memory size of a few hundred kB and a monochrome or binary display. These systems were used to explore new image segmentation, feature extraction, and classification designs which led to a new generation of systems in the early 1980-ies such as BioPEPR [15], FAZYTAN [16], Cerviscan [17], LEYTAS [18], and at the authors’ laboratory the Diascanner [19].

Typical cellular features used in these systems were similar to those used by CYBEST, although there were many variations in exactly how the features were extracted. The most important factor was found to be that the cells were digitized at sufficiently high resolution and in better focus. In order to be able to scan a whole specimen sufficiently rapidly while still being able to do the crucial analysis at high resolution, some of these designs, for example, the Diascanner, used a dual resolution approach, an initial low resolution search scan followed by high resolution scans of fields of interest. Most of these systems reached an operational prototype stage in the mideighties. Some of the systems reported classification accuracies that were well within the range of what is achieved by the conventional visual screening. But none reached the market, and an important reason for this was lack of cost effectiveness; automated microscopes and computers with sufficient processing power were still too expensive.

The progress in computer display technology, that had been important in making it possible to create interactive systems that could be used for developing new automated screenings systems, eventually also led to the possibility of developing interactive screening systems. For the early systems the only option was full automation, or possibly stopping the automated microscope to physically show an operator the cell that was suspected as being abnormal. The concept was to create a “prescreening” system; that is, a system that for a reasonably large fraction of specimens would be able to say that they are perfectly normal and could be classified as such without any human inspection. All other specimens, on which the system found something that indicated that they might not be normal, would have to be screened in the conventional fully manual way. In the late eighties, computer displays and memories had reached sufficient capacity to make it feasible to save images of suspicious cells that were good enough for a human to judge whether the object could be a malignant cell or something else. The PAPNET system from Neuromedical Systems was the first to introduce interaction into automated screening [20]. After an initial low resolution object search, high resolution fields were processed, first by an algorithmic classifier and then by a neural network classifier. The output of the classifiers was a ranking of the abnormality of the detected “cells,” so that images of the 64 most abnormal ones could be stored on a magnetic tape and later shown to the cytotech at a review station. There the decision whether the specimen should be classified as normal or suspicious was taken. For the suspicious cases a cytopathologist would do the final analysis and make the decision whether the woman should be called for follow-up or not.

In the late eighties there was a great increase in interest in cytology automation in the US for economic/legal reasons and many new projects were started [21]. One new aspect that appeared at this time was new ways of preparing the samples. The Cytyc Corporation had developed their own automated specimen preparation technique, ThinPrep, which based on liquid cytology made much cleaner specimens than the conventional smears, at the expense of significantly more complex preparation technique [22]. Another similar preparation method was developed by AutoCyte [23].

The AutoPap 300 from NeoPath was similar to PAPNET in that it used conventional Pap-smears and neural network classifiers [24]. It increased the image acquisition rate by utilizing strobed illumination similar to the CYBEST system. This was used at two resolution levels, an initial low resolution mapping of the specimen, followed by a high resolution field by field analysis of the most “interesting looking” parts of the specimen in a way similar to the earlier generation Diascanner. The image processing was carried out in custom designed processing boards. Most of the processing was based on mathematical morphology operations resulting in as many as 68 different features being sent to the classifiers. The final result was a “normal” versus “requires visual inspection” decision on the specimen level; that is, no interactive confirmation was used of the machine decision for the negative cases.

2.

3. The First Commercially Available Systems

During the nineties there was strong competition between the American companies developing screening technology as well as struggles to get the various solutions approved by the powerful Food and Drug Administration, FDA. Screening systems were classified in a category of medical devices requiring premarket approval, meaning that no system can be sold in the US without FDA approval. Hundreds of millions were spent on developments and field trials and there was a shake-out; the companies merged and were acquired by larger companies. The first company with a screening product to finally receive FDA approval was Tripath in 1998. It was the merger of NeoPath, Neuromedical, and AutoCyte. The Tripath Company was in turn acquired by BD in 2006 and the system renamed BDFocalPoint Slide Profiler [25]. It is to a large extent based on the AutoPap 300 system. A new liquid based specimen preparation technique called SurePath has been added to further improve the system performance although it can also analyse conventional smears. According to the FDA approval, the system can be used to recognize about 25% of the slides as normal for no further review; the other 75% are ranked into five categories at risk for abnormality. There is also a possibility of visually reviewing fields of particular interest at a special review station. The system can also be used for quality control and claims increased sensitivity in detecting abnormalities [26].

Cytyc was quite successful with their improved liquid based preparation technique and could demonstrate better performance for that technique as compared to conventional smears. They also developed an interactive system with a computer prescreen that selected the most abnormal looking objects on each specimen for human inspection. In 2003 they received FDA approval for their ThinPrep Imaging System [27], and in 2007 they became part of the Hologic Company. The system is marketed for increasing detection of abnormalities by improved specimen preparation and screening both visually and by machine [28].

3. The Technical Challenges

In the quick review of the historical development above we have briefly mentioned some of the key features of the different generations of systems. We will now return to the different crucial aspects of the technologies behind a screening system and discuss what needs to be achieved in order to screen a sample in a time comparable to that of a human screener that is less than 10 minutes.

3.1. Specimen Preparation

In the original PAP-smear the cellular material is manually spread over the glass slide. It is important that both the endocervical and ectocervical regions (see Figure 3) are represented in the sample and through the smearing there may actually be a mapping between the source region and the location on the slide. [29]. The samples are fixed and stained in a rather straightforward procedure, which can be done fully manually or in staining machines with varying degrees of sophistication. The material cost for the whole preparation is quite low, on the order of 1-2 US dollars. In Figure 1, an image of a high resolution field from a PAP-smear is shown.

The manual smearing and staining do unfortunately lead to big variations in specimen quality. Sometimes the cellular material may be unevenly distributed leading to dense clumps which light cannot penetrate while other parts of the slide may be empty. Even when the smear is done well there will still be regions which are too dense and have too many overlapping cells for reliable interpretation. An experienced cytotech can cope with great variations in specimen quality and still make a rather reliable assessment of the specimen, but the smears are very challenging to analyse automatically.

To make specimens that are better, both for visual and machine analysis, various liquid based cytology (LBC) preparation techniques have been developed. The common strategy here is to submerge the brush or spatula with all the cellular materials collected from the cervix in a liquid, which then is treated in various ways before it is deposited onto a glass slide, fixed, and stained. The result is ideally a cellular sample that is spread in a monolayer with optimal density over a well-defined part of the glass slide. The goal of this procedure is that the resulting samples should be easier to interpret reliably visually and in particular by machines. Several different techniques for liquid based preparations have been developed over the years, the two leading techniques are Surepath [25] and Thinprep [27] mentioned above. There have been numerous studies comparing the liquid based preparations to the conventional smears and most of them come to the conclusion that they are at least as good or better when it comes to reliability of detecting abnormalities [28, 30–32]. All currently marketed machine screening systems work with liquid based preparations.

The great disadvantage of the liquid based preparations is the associated operational costs. They require significantly more materials to be used for preparing a specimen, for example, vials, liquids, filters, and also more complex equipment, for example, centrifuges. The procedures are proprietary and the necessary equipment is sold as kits which increases the cost of preparing a slide to at least 10 US dollars. This causes significant economic problems in regions with limited resources. Still there are studies indicating that liquid based preparations are more effective [33, 34] while a large metastudy concluded that they could see no significant differences [35]. There are also alternative liquid based preparations that have been developed and are competing with lower costs [36, 37] although those have so far not been tested as extensively as the leading techniques.

3.2. Scanning

In order to analyse a cell sample in a computer, it should be scanned at sufficiently high resolution to reliably extract the features that can determine whether it is normal or indicating a precancerous change. This is very challenging. At a pixel size of 0.2 microns, a smear of 25 50 mm will give 31 billion pixels. Just transferring this amount of data from the camera to the computer will take minutes, even with the latest high-speed transfer techniques. Since there are no lenses that can resolve the whole specimen area at once and no image sensors with 31 gigapixels, we have the problem of repositioning the lens over a large number of image fields that together cover the specimen. A high resolution microscope lens gives a field of view with a diameter of around 0,5 mm and with a matching 6 megapixel sensor we will get 5000 image fields. Repositioning and capturing an image at each of these will take at least 10 minutes. This can be reduced by using nonstop motion and flash illumination to freeze the images. The CYBEST4 system was the first screening system to use this idea [14] and later it was used in the AutoPap [24]. An alternative is to use a 1D sensor with a length of, for example, 2000 pixels and smoothly move the microscope stage in the orthogonal direction. The Cerviscan [17] and Diascanner [19] systems used this idea. It is also used in the currently popular slide scanners by Aperio [38] although at a lower resolution.

Another serious issue is focusing. In order to reliably extract the texture information from the cell image they must be in very good focus which requires high quality autofocus, which also is time consuming. An alternative is to scan the specimen at several focus levels and choose the best for each cell, which reduces the need for autofocus but increases the amount of data even more. So in summary it is quite demanding to scan a whole smear in a sufficiently short time at sufficiently high image quality. In Figure 4, an illustration of the two different scanning approaches mentioned above is seen.

One way to decrease the demands is to use a smaller part of the slide surface for the specimen. With a smear this cannot be done without decreasing specimen sampling quality. With liquid based preparation the area of the sample is around 1/10 of that of a smear, a great advantage when it comes to scanning. For smears we can instead use a dual resolution approach mimicking the way cytotechs switch between 10x and 40x lenses. If we scan with 1 micron pixel size we can cover the smear in 200 fields which can be done in about 20 seconds. This will produce a map of where cellular material with a suitable density is distributed, which can then be used to control where a number of scans at high resolution are acquired. A variant of this approach is to not only look for areas with suitable density of cells but also for areas with cells that look suspicious for abnormality. This dual resolution screening approach was first proposed by Poulsen [39] and used in some of the early systems, for example, the Diascanner [19]. A potential risk with this design approach is that, if the low resolution scan systematically misses some type of abnormalities, those abnormalities never become subject to the high resolution analysis.

3.3. Segmenting Cells and Nuclei

In order to extract the features describing the cells we must find and delineate each cell and/or cell nucleus in the specimen image. This is called image segmentation and is a crucial step in almost all image analysis based systems. Segmenting nuclei in PAP-smears is made very difficult by the same complications that make the smears hard for humans to analyse, that is, variable smear thickness and staining intensity, obscuring elements, and so forth. The earliest systems used thresholding based on greyscale for the segmentation in the very first systems using a fixed threshold value but later on with a value determined by histogram analysis as originally suggested by Prewitt and Mendelsohn [40]. More recent projects have used more complicated approaches. Bergmeir et al. [41] use mean shift and morphological filtering and later try Canny edge detection followed by the randomized Hough transform [42]. Bamford and Lovell [43] use a dual active contour algorithm. Malm and Brun [44] use Canny edge detection followed by anisotropic curve closing. In a recent review [45], five different classes of approaches to cell segmentation are identified and it is demonstrated how they have appeared and gained popularity over the years. There is still a need of developing new methods, since none of the existing ones are as flexible and robust as the human visual system in really identifying where the nuclear or cytoplasmic border is located in difficult cases.

The main requirement for a good cell nucleus segmentation method is that it accurately can detect and delineate the cell nucleus under different staining conditions and in the presence of disturbing object in the direct vicinity. A second important requirement is that this segmentation can be done quickly. We cannot spend more than a few milliseconds per cell if we are to accomplish the analysis in an acceptable time. The increasing computer power has made it possible to do this even with somewhat complex algorithms. It does, however, require the algorithms to be implemented in an efficient way, for instance, taking advantage of the possibilities of parallelism possible in modern computers.

3.4. Artefact Rejection

The goal for the segmentation algorithms is to find and accurately delineate cell nuclei (and sometimes cytoplasms) that are sufficiently well preserved and imaged to allow accurate extraction of features for the subsequent classification. But it will fail sometimes either because the image of the nucleus is corrupted by overlaying objects or other artefacts or when the cell is so poorly preserved or presented in the image that the extracted outline of the object will be wrong. It is then very important that we can detect this failure and discard the data from the object. Otherwise it will lead to unreliable classification performance on the specimen level. The process of analysing the segmentation results in order to remove erroneous results is called artefact rejection.

Artefact rejection is a difficult topic because there are an infinite variety of ways in which blood cells, inflammatory cells, folded and distorted cells, overlapping objects, mucus, staining mistakes, and so forth, influence the image of a cell (see Figure 5). But it is an absolutely essential step in a screening system. The motivation for this can be found in the statistics we have to deal with. A standard PAP-smear may typically contain 100,000–200,000 cells of the relevant cell types and we should be able to call it positive if we find 10–20 diagnostic, premalignant, or malignant cells (ideally a single clearly malignant cell should be enough). A classifier that only makes one percent false positive error will call at least 1000 cells positive even on a healthy sample, making every sample called positive and the system thus useless. One approach to deal with this problem is to make the classifier highly asymmetrical between false positive and false negative, that is, allowing it to miss-classify a large fraction of the actually malignant cells as normal. This may seem to defeat the purpose of the system which is to detect (pre-)malignancy. But the highly unbalanced numbers work that way. If the system has a false negative rate of 80% it will still detect 2–4 of the diagnostic malignant cells if we have 10–20 available. This is acceptable as long as the false positive rate is virtually zero, less than 0.001%. Creating such a classifier is hard but possible if we can work with perfectly imaged cells with accurate segmentation and carefully extracted features. To make sure this is the case we need very effective artefact rejection.

There is very little explicit research done on artefact rejection for cervical screening. Some research papers ignore the problem by working on visually selected or verified images of nuclei thus relying on manual artefact rejection, which of course cannot be done for a real screening system. Other papers include the artefact rejection in the segmentation or classification steps. Still, analysing the artefact rejection problem on its own makes it easier to see what performance can be achieved and to relate that to what is needed. Malm et al. recently presented such a study where they demonstrated a specificity of 99.38% on smears and 99.83% on LBC specimens, while maintaining a sensitivity of around 98% based on a material of around 12,000 automatically detected and segmented images of objects visually classified into cell nuclei and artefacts [46]. With that kind of performance we would still have a few hundred artefacts corrupting the data if we analyse 100,000 objects, so it may be hard to achieve the sensitivity of detecting a few abnormal cells without getting too many false positive samples. Still it points in the direction of what is necessary to achieve for a useful system.

3.5. Feature Extraction

When we have an accurate segmentation of cell nuclei, we can extract features describing the size, shape, and texture of the object. The most obvious features are those representing the greater size and more irregular overall shape of the malignant nuclei. Those features can be extracted at relatively low resolution and even without having the cell in perfect focus. Assuming perfect artefact rejection those features may be useful in detecting a large proportion of the clearly malignant cells and specimens. They were used in the first generation systems, which failed because of the lack of adequate artefact rejection. Over the years, many more features have been invented and tested. In [47] the different kinds of features that have been proposed were reviewed and systematically categorized.

The most important information about whether the nucleus is normal or (pre-)malignant is found in the chromatin pattern or texture of the nucleus. The DNA in the nucleus is distributed in a different way when the cell is influenced by a malignant process. This effect can be seen and measured even with PAP-stain which is not stoichiometric for DNA. Measuring the chromatin distribution is, however, difficult. The most common approaches are based on a statistical description of neighbouring grey levels typically measured through so-called transition probability matrices as originally proposed in [48]. Another approach is to see the individual chromatin granules as objects that are segmented, and then the spatial relations between these objects are described, for example, through graph analysis methods [49]. Different ways of measuring chromatin features are discussed in [50] and also in [47]. A very important aspect of the chromatin analysis is that you need perfect focus and very high quality images to reliably represent this pattern which is at or beyond the optical resolution limit.

4. Classification Strategies

The ultimate goal of the PAP-smear screening process is to find women with precancerous lesions, so that they can be treated before the malignancy develops into potentially lethal invasive cancer. When running the conventional visual screening process, the cytotechs can classify most specimens as clearly normal and needing no further review. It is important to realize that we typically are screening a general population so that the great majority of samples, perhaps 96%, are normal. Still some specimens look more suspicious and are referred to a cytopathologist for review; in some cases the malignancy may be so obvious that the cytotech can be sure about it; still the confirmation by a pathologist is required. A positive sample will then lead to the women being called in for additional investigation, possibly involving colposcopy and a biopsy, and if the lesion is confirmed, a simple operation with a loop electrosurgical excision procedure or similar to remove it. There are different levels of changes in cell appearance that can be detected and there is a consensus standard for how to classify these called the Bethesda system [51]. According to the Bethesda system there is also a range of abnormalities from the perfectly normal slide via slight abnormalities ASC-US, low grade lesions, LSIL, high grade lesions, HSIL, and finally cancer. It is of course particularly important to pick up the higher grades and not clear whether it really is necessary to detect the slight changes. Not all low grade lesions will progress to cancer even when left untreated and when they do it may take a decade or even more. With a regular recurring screening program taking a new sample with a few years interval, the probability of detecting a lesion before it progresses to cancer is therefore high even if the risk of missing it at a single screening occasion is rather high, perhaps 20–30%.

When adding an automated screening device to the overall screening setup, it can be used in various ways. The original concept was to do an automated prescreening, which would be able to say that a substantial fraction of the specimens were normal while having very few false negatives, that is, not missing any, or very few true positive specimens. To reach a low false negative rate a relatively high false positive rate could be accepted since those specimens were screened visually. Even if only 50% of the specimens could be dismissed as clearly normal the system would remove half the visual screening workload and could be cost-effective if it did not add too much to the overall screening cost. The SurePath system is typically used in this mode and set to only remove 25% of the specimens, while also ranking the positives into different categories of likelihood of being truly positive.

Another way of using an automated system is to run it in parallel to visual screening. Since humans and machine most likely will make different errors, the combined system will increase the sensitivity of the overall screening process, that is, reduce the false negative rate. But the downside is that the overall workload and cost are increased rather than decreased. The Thinprep system is mainly marketed to be used in this mode.

4.1. The Rare Event Approach

An image analysis based automated screening system analyzes cells one by one and can, based on the features extracted from the cell image, classify it as being normal or abnormal. The simplest way of using the information from the cell classifier is to simply count how many abnormal cells we have found on the specimen and if it is over a low threshold we call the specimen suspicious. The problem is to set the threshold so that we do not miss true positives in particular not high grade ones, while avoiding too many false positives [52].

This approach disregards the information about how certain the cell classifier is about its decision. It may be that one cell is found to be clearly malignant while another one is very close to the threshold for being normal. If we retain this information, we can make a specimen level decision about whether we have found too much abnormality to call the specimen normal, either based on just a few clearly malignant cells, or a larger number of cells slightly over the threshold [53].

If we can do the image analysis and feature extraction online as we scan the specimen, we may stop the analysis as soon as we have found sufficient evidence that the specimen is not clearly normal. This may save time by making it unnecessary to scan and process the rest of the specimen. This strategy is not controversial since it does not increase the risk of false negatives. But since the great majority of specimens are normal in a typical screening situation we would need to be able to stop early also when we have found sufficient evidence that a specimen is normal in order to really save time. And this is controversial; it is generally required that a cytotech looks at the entire specimen before calling it normal. Still only a small part of the cells scraped from the cervix really makes it onto the glass so we are not analysing all possible cells even when we look at the whole slide. However, with a conventional PAP-smear there is a kind of mapping between areas in the cervix onto the slide so we may systematically miss some important region by stopping early. For a liquid based preparation, much fewer cells are available for analysis on the specimen, but there is a mixing step involved so we can assume that we have a random sample and can stop as soon as we have sufficiently many cells for a required statistical significance in the decision function.

4.2. Malignancy Associated Changes (MAC)

In the approach to the screening problem described so far the systems have been mimicking the way humans do it, that is, searching for potentially rare (pre-)malignant cells. Achieving a low false negative rate even for specimens with a low number of diagnostic cells is challenging and requires analysing very many cells. There is, however, an alternative approach based on so-called malignancy associated changes (MAC). It was discovered already in 1967 that cells in the vicinity of a malignancy are influenced so that they undergo small, often subvisual changes in the chromatin texture [54]. These discoveries were confirmed in the early research on automated cervical screening [55, 56]. Even though these shifts were not strong enough to be useful on the individual cell level, it made it possible to detect abnormal specimens through a statistical analysis of the feature distributions of a small population, a few hundred cells, provided that these features were extracted very accurately. Since these changes are present in all cells in a large neighbourhood of a malignant process we can have a different approach to the screening. We need to be able to reliably detect these subtle changes in cell populations from a specimen. But we will not need to search through the whole specimen; only data from sufficiently many cells to characterize the chromatin distribution of the cell population is needed, typically around 500 cells. The group that has been pursuing this idea most systematically is the one at the British Colombia Cancer Research Centre [57, 58]. Also in this case we need very accurate artefact removal; we do not want to extract texture data from artefacts. And we need perfect focus for each cell. Even a small deviation from perfect focus causes significant changes in the chromatin image. It has not yet been convincingly demonstrated that MAC alone can detect early premalignant changes with sufficient sensitivity.

4.3. The DNA Ploidy Approach

The malignant process not only modifies the distribution of DNA in the nucleus, it also increases the amount of DNA. With a stoichiometric stain, a histogram over the integrated optical density of all the nuclei will show a diploid distribution for normal cells and a different aneuploid distribution for malignant cells. Therefore modified, stoichiometric PAP-like stains have been developed and used for automated screening studies [59–61], showing quite promising results. This method is currently being used in China in a study involving several hundred thousand women [62]. Since this approach is based on densitometric measurements, there are rather strong requirements of consistent staining and control of the illumination and calibration of the imaging. The artefact rejection is also very important; we must be sure that the DNA measurements are only from single, free-lying, well-preserved nuclei. A significant problem with these modified stains is to get them accepted by the wider community, since new appearance of the samples may require expensive retraining. This concept can also be used with the conventional PAP-stain, but due to the lack of stoichiometric staining the ploidy measurements will be less reliable.

4.4. Field Test Statistics and Performance Requirements: Technical and Ethical Issues

The statistics needed for developing a successful screening system is difficult on several levels as described in the previous paragraphs. But we also have difficult statistics on the highest population screening level. A screening machine that systematically misses a significant proportion of the positive samples will decrease the confidence in the screening programs and put the women at risk of developing invasive cancer before the problem is detected. Since a screening system is typically used mainly to analyse normal specimens, at most a few percent of the samples are truly positive. To prove the detection capabilities of the system with high confidence we need it to analyse hundreds of positive cases. In a development phase we can achieve high numbers of positive cases by selectively running positive cases in the machine. But for the final evaluation we should run it on the typical mix of routine specimens. We thus need a volume of tens of thousands of specimens to properly test the system. And the situation is made even more complicated by the fact that there are various kinds of rare abnormalities that are detected by the visual screening. We need to verify that the machine does an acceptable job also for those. During this testing phase the machine will have to be used in parallel to visual screening, causing double operational costs plus extra work for doing the comparisons and statistical evaluations. The final system verification stages are thus a difficult and expensive threshold to get over before a new system is ready for widespread use.

What performance requirements a screening machine must meet is an issue that has caused controversy over the years. The perfect machine should have zero percent false negatives and zero percent false positives. In practice this is impossible so we have to consider what the realistic requirements are.

The false negative rate is primarily an ethical issue. If we miss to detect high grade lesions, it may lead to the women getting cancer. The requirement should then be that the machine is at least as good as the current visual screening process. But there are two aspects also of this requirement. It should on average not miss more specimens than what is missed by a good cytotech. Additionally it should not systematically miss any relevant kind of lesion.

The false positive rate of the initial automated specimen inspection on the other hand is an economic issue. False positives from the whole screening setup, after inspection by a cytologist are expensive and cause anxiety for the woman who is called for a new investigation which may be interpreted as a message that she may have a cancer. But no screening system is set up so that the machine positive samples lead to a call for the woman to come to a new examination. The samples classified as potentially positive by the machine are screened visually by a cytotech and, if still found to be positive, by a cytologist. This rescreening costs money and reduces the gain of having the machine screening. Still very high levels of “machine false positives” can be accepted, for example, 75% for one of the commercial systems. The machine is then set up so that only clearly normal specimens are classified as normal, and everything else should be inspected also by a human.

4.5. Performance Requirements: Legal Issues

The deployment of an automated screening process is made significantly more complicated by the legal aspects. There are in most countries, for good reasons, strong regulations for how to test a screening machine before it is approved for routine use. In the USA a screening machine needs premarket approval by FDA before it can be sold for clinical screening use. Obtaining such approval involves detailed documentation of all aspects of the machine as well as extensive testing of its performance in large, well-documented studies. But the legal aspect is not limited to obtaining approval from the appropriate authorities. If a machine misses to detect a high grade lesion present in a sample and this leads to a woman getting cancer, the manufacturer of that machine can be sued for the damages caused. This can be extremely expensive and is a risk no manufacturer can take. Therefore the procedures for how to use the screening machines are designed to minimize this risk. One way of doing this is to require a human screener to visually inspect some data from every specimen, for example, a set of images of objects the machine determined to be the most “malignant looking” on the specimen or a number of selected image fields optically through the eye-piece of the microscope. Thus the responsibility of calling the specimen “normal” is transferred from the manufacturer to the user. Another approach has been to run the machine screening in parallel to conventional visual screening with the rationale that the errors done by machine and by the human are different and thus the overall sensitivity for detecting malignancy is increased. By setting the threshold for when to call a specimen “normal” without further human inspection very conservatively some manufacturers have decreased the risk of missing a positive specimen to the point where it has been deemed acceptable. In the USA that threshold currently seems to be at the 25% level; that is, 75% of all specimens will have to be screened both by machine and humans. No fixed such thresholds are set in other parts of the world.

All these legal precautions are meant to protect the women from unnecessary risks of obtaining cancer in spite of having been screened, which of course is a good thing. But they have also significantly contributed to the fact that automated screening so far has failed to have a real impact on the screening costs. Still the majority of women in the world are not offered regular screening because of the high associated costs. An automated screening system that is almost as good as the best visual screening systems at a significantly lower cost could save millions of women from dying in cervical cancer. But will such a device ever be accepted by the legal systems? It will not probably be accepted in the USA but perhaps in some other parts of the world.

5. Conclusion

We have in this paper outlined the 60-year history of efforts to automate the screening for cervical cancer and pointed out how the different generations of systems have tried to meet the challenges of this difficult task. We have also discussed the different aspects of these challenges and how they can be met. Now in conclusion let us discuss where we stand today.

The purpose of an automated inspection system is to decrease the cost and/or false negative rate of a screening program. To achieve the first goal it is necessary that the cost of operating the system including capital and maintenance costs in addition to the direct operational costs is less than what it costs to do the same work as the system does with conventional manual methods. It is doubtful if the present generation commercial systems meet these goals. They have been more focused on the second goal. By running machine screening in parallel to visual screening it is likely that the machine misses other abnormalities than the human screener, thus reducing the overall false negative rate. The overall operational cost will however be higher. The currently available commercial systems may thus marginally increase the quality of the screening but they will not significantly decrease the cost.

It is today known that cervical cancer is caused by human papillomavirus infection. An alternative or supplementary screening method is to test for such infections. There are studies showing that combining both kinds of analysis adds sensitivity of detecting precancerous lesions [63]. Still there seems to be limited advantage of replacing the PAP-test by only a virus test. The knowledge that the cancer is caused by a virus infection has also opened up the possibility of vaccination against the HPV virus. If such vaccination programs became globally comprehensive, the prevalence of the cancer could be decreased to the level where screening would be no longer necessary. But unfortunately it is not likely that that will happen any time soon and it will take decades even after everyone is offered vaccination before the effects reach all age groups.

The historical developments of the screening field have taken place in parallel to the fantastic development of computer technology. We now have millions of times more computer power available per dollar than we had when the first digital screening systems were built. Similarly the image sensor technology has developed dramatically. Even since the time the first version of the current commercial systems was developed some 15 years ago there has been significant progress in the underlying technologies. There have also been significant developments on the algorithmic side, although perhaps not as dramatic as for the hardware. All this sets the stage for a good opportunity today to develop a really cost-effective screening system. It is most likely that a fully automated screening system today can be built at a cost of at least an order of magnitude lower than the cost of the currently available commercial systems. Such a system could make it economically feasible to implement comprehensive screening systems also in the poorer parts of the world and eventually have an impact on the high incidence of cervical cancer there. There are of course major challenges in organizing an effective screening program in such countries, but a compact, robust automated screening system could make a big difference.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Pap Smear (Pap Test) | Lab Tests Online

Receiving test results

The results of a Pap smear are most often available within one to three weeks. Results may be sent to the patient electronically or by mail. A doctor’s office may also contact the patient to discuss Pap smear results or to arrange a follow-up appointment.

Interpreting test results

Pap smear results are reported as normal, abnormal, or unsatisfactory for evaluation. A normal, also called negative, Pap smear result indicates that no evidence of abnormal cells were found in the sample. An abnormal, or positive, result on a Pap smear indicates that abnormal cells were detected in the sample and additional treatment or testing may be necessary. Treatment of abnormal cervical cells prevents the development of cervical cancer.

Cell types commonly described in Pap smear results include squamous and glandular cells. Squamous cells are a type of cell that lines the outer portion of the cervix. Abnormal changes in squamous cells are divided into several categories:

• Atypical squamous cells (ASC): Atypical squamous cells are the most common abnormal finding on a Pap smear. Atypical squamous cells may be reported as atypical squamous cells of undetermined significance (ASC-US) or atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion (ASC-H). Both results indicate that cervical cells appear abnormal under the microscope, but the meaning of the cell changes is unclear. A result of ASC-H indicates that cells may be at a higher risk of becoming cancerous than a result of ASC-US.
• Low-grade squamous intraepithelial lesions (LSIL): Sometimes called mild dysplasia, a result of LSIL indicates that the Pap smear detected mild cell changes. A result of LSIL may not require treatment, as these changes are often resolved by the immune system, especially in younger people.
• High-grade squamous intraepithelial lesions (HSIL): Sometimes called moderate or severe dysplasia, an HSIL finding indicates that somewhat to very abnormal cell changes were detected. These changes are more likely than LSILs to progress into cancer if left untreated.
• Carcinoma in situ (CIS): A result of CIS indicates that more severe cell changes were found during the Pap smear. These changes appear similar to cervical cancer, but have not yet spread beyond the surface of the cervix. CIS is likely to progress into cancer if left untreated.
• Squamous cell carcinoma: Squamous cell carcinoma is a type of cervical cancer. Finding squamous cell carcinoma on a Pap smear is very rare for patients who receive regular cervical cancer screening. This result indicates that abnormal squamous cells have spread more deeply into the cervix or to other parts of the body.

Glandular cells are found in the tissue that lines the inner portion of the cervix. Abnormal cell changes in glandular cells are divided into the following categories:

• Atypical glandular cells (AGC): A result of AGC indicates that abnormal glandular cells were seen under the microscope, but the meaning of these cell changes is unclear. 
• Endocervical adenocarcinoma in situ (AIS): This result means that more severe cell changes were found but have not yet spread beyond the glandular tissue of the cervix. 
• Adenocarcinoma: Adenocarcinoma is a type of cervical cancer that begins in glandular cells. While very rarely found on Pap tests in people who are regularly screened for cervical cancer, a result of adenocarcinoma indicates that abnormal glandular cells have spread more deeply into the cervix or to other parts of the body.

In addition to detecting the presence of cell changes in squamous and glandular tissue, a Pap smear may also detect several other kinds of abnormalities:

• Endometrial cells: A Pap smear may detect endometrial cells, which are cells from the lining of the uterus. While these cells may be present in healthy individuals during menstruation, they should not be present in a cervical sample after menopause. Because this finding may be normal in young patients, endometrial cells are only reported in Pap smear results for patients 45 and older. 
• Other types of cancer: Although not the primary goal of a Pap smear, this test can sometimes detect cancerous cells not related to cervical cancer. A Pap smear may detect cancerous cells from the fallopian tubes, ovaries, endometrium, peritoneum, vulva, or vagina.
• Infection or inflammation: A Pap test may detect evidence of infections and inflammation of the cervix.

Unsatisfactory results on a Pap smear indicate that the sample of cervical cells obtained for the test either didn’t have enough cells on the slide to be examined or the quality of the slide wasn’t satisfactory. Unsatisfactory results may be followed up by a repeat Pap smear.

Are test results accurate?

A Pap smear is not 100% accurate. Abnormal cells may be missed in some individuals. Fortunately, cervical cancer typically develops slowly and it can take years, or even decades, for abnormal cells to develop into cervical cancer. Because cell changes progress slowly, regular Pap smears can usually detect cell changes before they progress into cervical cancer.

Do I need follow-up tests?

Follow-up testing after a Pap smear will depend on the test results and a patient’s reason for being tested. For individuals undergoing screening for cervical cancer who have a normal Pap smear result, it’s important to continue cancer screening at regular intervals. 

People who receive abnormal Pap smear results require follow-up tests and/or treatment in order to further assess the cervix for signs of disease. For minor abnormalities such as ASC-US, a doctor may recommend a human papillomavirus (HPV) test and/or having another Pap smear in a year to see if the abnormality resolves without treatment.

For a result of LSIL, a doctor may recommend additional testing to look for more serious abnormalities on another portion of the cervix.

If a patient has more severe abnormalities, including ASC-H or HSIL a doctor may recommend a colposcopy. A colposcopy is a procedure that involves the use of an instrument called a colposcope to more closely examine the cervix. Doctors may perform a biopsy during a colposcopy to remove additional tissue for examination.

Questions for your doctor about test results

Your doctor can address detailed and specific questions about your Pap smear results. Some questions that you might review with your doctor include: 

• Was any part of my Pap smear result abnormal? 
• If there was an abnormal Pap smear result, can you explain what was found and what it may mean? 
• If Pap smear results were normal, when should I have this testing again in the future? 
• Are there any follow-up tests that may be beneficial given my test result?

HPV and Pap Testing – National Cancer Institute

Cervical Cancer Tests | How to Test For Cervical Cancer

Finding cervical cancer often starts with an abnormal HPV (human papillomavirus) or Pap test result. This will lead to further tests which can diagnose cervical cancer or pre-cancer. The Pap test and HPV test are screening tests, not diagnostic tests. They cannot tell for certain if you have cervical cancer. An abnormal Pap test or HPV test result may mean more testing is needed to see if a cancer or a pre-cancer is present.

Cervical cancer may also be suspected if you have symptoms like abnormal vaginal bleeding or pain during sex. Your primary doctor or gynecologist often can do the tests needed to diagnose pre-cancers and cancers and may also be able to treat a pre-cancer.

If there is a diagnosis of invasive cancer, your doctor should refer you to a gynecologic oncologist, a doctor who specializes in cancers of women’s reproductive systems.

Understanding abnormal cervical screening test results

Your current screening test results along with your past test results, determine your risk of developing cervical cancer. Your doctor will use them to figure out your next test or treatment. It could be a follow-up screening test in a year, a colposcopy, or one of the other procedures discussed below to treat any pre-cancers that might be found.  

Because there are many different follow-up or treatment options depending on your specific risk of developing cervical cancer, it is best to talk to your healthcare provider about your screening results in more detail, to fully understand your risk of cervical cancer and what follow-up plan is best for you.

Tests for people with symptoms of cervical cancer or abnormal cervical screening test results

Medical history and physical exam

First, the doctor will ask you about your personal and family medical history. This includes information related to risk factors and symptoms of cervical cancer. A complete physical exam will help evaluate your general state of health. You will have a pelvic exam and maybe a Pap test if one has not already been done. In addition, your lymph nodes will be felt to see if the cancer has spread (metastasis). 

Colposcopy

If you have certain symptoms that could mean cancer, if your Pap test result shows abnormal cells, or if your HPV test is positive, you will most likely need to have a procedure called a colposcopy. You will lie on the exam table as you do with a pelvic exam. The doctor will put a speculum in the vagina to help keep it open while examining the cervix with a colposcope. The colposcope is an instrument that stays outside the body and has magnifying lenses. It lets the doctor clearly see the surface of the cervix up close. Colposcopy itself is usually no more uncomfortable than any other speculum exam. It can be done safely even if you are pregnant. Like the Pap test, it is better not to do it during your menstrual period.

The doctor will put a weak solution of acetic acid (similar to vinegar) on your cervix to make any abnormal areas easier to see. If an abnormal area is seen, a small piece of tissue will be removed (biopsy) and sent to a lab to be looked at carefully. A biopsy is the best way to tell for certain if an abnormal area is a pre-cancer, a true cancer, or neither.

Types of cervical biopsies

Several types of biopsies can be used to diagnose cervical pre-cancers and cancers. If the biopsy can completely remove all of the abnormal tissue, it might be the only treatment needed.

Colposcopic biopsy

For this type of biopsy, first the cervix is examined with a colposcope to find the abnormal areas. Using a biopsy forceps, a small (about 1/8-inch) section of the abnormal area on the surface of the cervix is removed. The biopsy procedure may cause mild cramping, brief pain, and some slight bleeding afterward.

Endocervical curettage (endocervical scraping)

If colposcopy does not show any abnormal areas or if the transformation zone (the area at risk for HPV infection and pre-cancer) cannot be seen with the colposcope, another method must be used to check that area for cancer.

A narrow instrument (either a curette or a brush) is inserted into the endocervical canal (the part of the cervix closest to the uterus). The curette or brush is used to scrape the inside of the canal to remove some of the tissue, which is then sent to the lab to be checked. After this procedure, patients may feel a cramping pain, and they may also have some light bleeding.

Cone biopsy

In this procedure, also known as conization, the doctor removes a cone-shaped piece of tissue from the cervix. The base of the cone is formed by the exocervix (outer part of the cervix), and the point or apex of the cone is from the endocervical canal. The tissue removed in the cone includes the transformation zone (the border between the exocervix and endocervix, where cervical pre-cancers and cancers are most likely to start). A cone biopsy can also be used as a treatment to completely remove many pre-cancers and some very early cancers.

The methods commonly used for cone biopsies are the loop electrosurgical excision procedure (LEEP), also called the large loop excision of the transformation zone (LLETZ), and the cold knife cone biopsy.

• Loop electrosurgical procedure (LEEP, LLETZ): In this method, the tissue is removed with a thin wire loop that is heated by electricity and acts as a small knife. For this procedure, a local anesthetic is used, and it can be done in your doctor’s office.
• Cold knife cone biopsy: This method is done in a hospital. A surgical scalpel or a laser is used to remove the tissue instead of a heated wire. You will receive anesthesia during the operation (either a general anesthesia, where you are asleep, or a spinal or epidural anesthesia, where an injection into the area around the spinal cord makes you numb below the waist).

Possible complications of cone biopsies include bleeding, infection and narrowing of the cervix. 

Having had any type of cone biopsy will not prevent most women from getting pregnant, but if a large amount of tissue has been removed, women may have a higher risk of giving birth prematurely.

For people with cervical cancer

If a biopsy shows that cancer is present, your doctor may order certain tests to see if and how far the cancer has spread. Many of the tests described below are not necessary for every patient. Decisions about using these tests are based on the results of the physical exam and biopsy.

Cystoscopy, proctoscopy, and examination under anesthesia

These are most often done in women who have large tumors. They are not necessary if the cancer is caught early.

In a cystoscopy, a slender tube with a lens and a light is placed into the bladder through the urethra. This lets the doctor check your bladder and urethra to see if cancer is growing into these areas. Biopsy samples can be removed during cystoscopy for testing in the lab. Cystoscopy can be done under a local anesthetic, but some patients may need general anesthesia. Your doctor will let you know what to expect before and after the procedure.

Proctoscopy is a visual inspection of the rectum through a lighted tube to look for spread of cervical cancer into your rectum.

Your doctor may also do a pelvic exam while you are under anesthesia to find out if the cancer has spread beyond the cervix.

Imaging studies

If your doctor finds that you have cervical cancer, certain imaging studies may be done to look inside the body. These tests can show if and where the cancer has spread, which will help you and your doctor decide on a treatment plan.

Chest x-ray

Your chest may be x-rayed to see if cancer has spread to your lungs.

Computed tomography (CT)

CT scans are usually done if the tumor is larger or if there is concern about cancer spread. For more information, see CT Scan for Cancer.

Magnetic resonance imaging (MRI)

MRI scans look at the soft tissue parts of the body sometimes better than other imaging tests, like a CT scan. Your doctor will decide which imaging test is best to use in your situation.

For more information, see MRI for Cancer. 

Positron emission tomography

(PET scan)

For a PET scan, a slightly radioactive form of sugar (known as FDG) is injected into the blood and collects mainly in cancer cells.

PET/CT scan: Often a PET scan is combined with a CT scan using a special machine that can do both at the same time. This lets the doctor compare areas of higher radioactivity on the PET scan with a more detailed picture on the CT scan. This is the type of PET scan most often used in patients with cervical cancer.

This test can help see if the cancer has spread to lymph nodes. PET scans can also be useful if your doctor thinks the cancer has spread but doesn’t know where.

Intravenous urography

Intravenous urography (also known as intravenous pyelogram, or IVP) is an x-ray of the urinary system taken after a special dye is injected into a vein. This test can find abnormal areas in the urinary tract, caused by the spread of cervical cancer. The most common finding is that the cancer has blocked the ureters (tubes that connect the kidneys to the bladder). IVP is rarely used for patients with cervical cancer because CT and MRI are also good at finding abnormal areas in the urinary tract, as well as others not seen with an IVP.

Best Pap Smear Rancho Cucamonga

Conveniently located to serve the areas of Rancho Cucamonga, CA

Pap smears are one of the most effective ways to screen the health of your cervix and detect any changes long before they turn into something more serious. As part of his routine gynecological exam, Dr. Daniel B. Channell, gynecologist at the Channell Wellness & Aesthetics in Rancho Cucamonga, California, will perform this simple test to determine whether further examination or intervention may be needed.

What is a Pap smear?

A Pap smear refers to a routine test to detect any abnormal cells on your cervix that may indicate the potential for, or presence of, cervical cancer. The test is painless and entails a simple swab of your cervix, which is usually performed during your annual gynecological or pelvic exam.

As a screening aid, the Pap test is an extremely valuable tool for catching issues before they become major problems.

If a test comes back showing the presence of abnormal cells, there is no immediate cause for alarm. It simply means that some cells on your cervix do not appear normal and may require additional testing or monitoring.

What does an abnormal result mean?

In an overwhelming majority of Pap tests, the cause for an abnormal result is the human papillomavirus (HPV), which is a sexually transmitted infection. Most sexually active women will have some form of HPV during their lives, and symptoms can range from non-existent to the appearance of genital warts. There are over 100 types of HPV and many women are not even aware they have the virus, which usually resolves itself on its own. In rare cases, HPV can lead to cervical cancer, which is what makes the Pap test such a valuable diagnostic tool in catching and treating the precancerous conditions.

Outside of HPV, there are other factors may contribute to your abnormal result, such as:

• Herpes
• An infection or inflammation caused by bacteria
• Trichomoniasis
• Menopause
• A yeast infection

What happens after an abnormal Pap smear?

If you have an abnormal Pap test result, Dr. Channell will determine an appropriate follow-up plan based on:

• Your medical history
• Whether the presence of HPV has already been confirmed
• Family history

If you’ve already had an abnormal Pap test result due to the presence of HPV, Dr. Channell may choose to simply wait and retest. Often, cell changes on the cervix caused by HPV resolve themselves.

If you are not sure whether you have HPV, a follow-up HPV test, which is much like the Pap test, will help in detecting the virus.

If you’ve had several abnormal tests in a row, you will most likely have a colposcopy, which allows the doctor to get a closer look at your cervix and take a tissue sample for further testing. The colposcopy is an in-office procedure and takes only minutes to perform.

Pathology Outlines – Trichomonas vaginalis

Cervix

Inflammatory / infectious

Trichomonas vaginalis

Topic Completed: 1 August 2015

Minor changes: 4 December 2020

Copyright: 2003-2021, PathologyOutlines.com, Inc.

PubMed Search: Trichomonas vaginalis [title] cervix

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Cite this page: Philip J, Salih Z. Trichomonas vaginalis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cervixtrichomonasvaginalis.html. Accessed May 31st, 2021.

Definition / general

• Trichomonas vaginalis is a parasitic protozoan that causes trichomoniasis, a sexually transmitted disease

Epidemiology

• Trichomoniasis is the most prevalent nonviral sexually transmitted infection in the United States, affecting an estimated 3.7 million persons (CDC – Trichomoniasis)
• Having multiple sexual partners is the primary risk factor
• Mainly affects women from ages 16 – 35 years, but can occur in postmenopausal women

Sites

• Female: vagina, cervix, urethra and occasionally Bartholin’s gland
• Male: urethra, epididymis and prostate

Diagrams / tables

Images hosted on other servers:

Diagram

Clinical features

• Most infected persons (70% – 85%) have minimal or no symptoms, and untreated infections might last for months to years (CDC – Trichomoniasis)
• Copious yellow, green or gray, white vaginal discharge with a strong odor
• Itching and irritation are frequent
• Discomfort during sexual intercourse or urination
• In pregnancy, can cause premature rupture of membranes and preterm delivery
• Largely asymptomatic in men, act as a carrier; may cause urethritis

Diagnosis

• Nucleic acid amplification test (NAAT)
• OSOM trichomonas rapid test: Immunochromatographic test that detects pathogen antigens from vaginal swab
• DNA hybridization probe test
• Direct microscopic examination of secretions – wet mount
• Culture: Was considered as a gold standard before the availability of molecular tests

Prognostic factors

• Treatment reduces the signs and symptoms of infection and might reduce transmission (CDC – Trichomoniasis)

Treatment

• Metronidazole or tinidazole
• Sexual partners must also be treated

Clinical images

Images hosted on other servers:

Strawberry cervix

Cytology description

• Pear shaped, oval or round cyanophilic organisms, 15 – 30 microns
• Eosinophilic cytoplasmic granules are often evident
• Nucleus is pale, vesicular and eccentrically located
• Flagella are sometimes observed
• Leptothrix may be seen in association with Trichomonas vaginalis
• Mature squamous cells with slightly enlarged, dark nuclei and small perinuclear halos (“trich change”) are common that may mimic a low grade squamous dysplasia
• 3 dimensional clusters of neutrophils (“polyballs”) may be seen in the background
• Numerous lymphocytes and many mast cells may be seen
• Organisms tend to be smaller and rounder with better visualized nuclei, cytoplasmic eosinophilic granules and flagella in liquid based preparations
• Neutrophils and “polyballs” are reduced in liquid based preparations compared to the conventional smears
• Occasional kite shaped forms may be seen, especially on SurePath preparations (Nayar: The Bethesda System for Reporting Cervical Cytology, 3rd Edition, 2015)

Cytology images

Contributed by Dr. Marilin Rosa

Trichomonas

Images hosted on other servers:

Trichomonas in wet mount

Trichomonas in conventional
pap smear

Trichomonas vaginalis with leptothrix

Trichomonas

Trophozite

Various images

Electron microscopy images

Images hosted on other servers:

T. vaginalis parasite

Differential diagnosis

• Cell fragments, cytoplasmic debris, bare epithelial nuclei, small mucus aggregates and leukocytes:
  • Identification of a definite elliptical nucleus helps avoid misinterpretation
  • Presence of eosinophilic cytoplasmic granules will be helpful
  • In most cases, trichomonad organisms are plentiful (“trich party”)
    • Therefore, a rare fragment of cyanophilic debris is not likely to be a true trichomonad

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90,000 Pap smear. Pap test

Research method

Cytological examination of smears taken from the cervix is ​​the basis of programs aimed at the early detection of precancerous conditions and cervical cancer. The study of cytological preparations obtained from the cervical canal and the vaginal part of the cervix includes an assessment of the quality of the material obtained, determination of the presence and nature of the lesion of the cervix in accordance with the generally accepted assessment system, including the Bethesda system.

Cervical cancer most often develops in the transformation zone, it is preceded by intraepithelial lesions (dysplasia). Due to the fact that dysplasias can be located in small, limited areas, it is very important that the material is obtained from the entire surface of the neck, especially from the transformation zone. The number of pathologically altered cells in a cytological preparation can be different, and if there are few of them, they can be missed during screening.

Various methods are used to stain smears.The Pap smear method is the most widely used smear staining technique in the world. In Russia, staining according to Romanovsky is also used in the modification of Leishman.

Indication for examination:

• screening studies for the detection of oncological pathology of the cervix;
• Monitoring the state of the cervix after therapy.

The result of a cytological study carried out in the CMD can only be formalized in accordance with the terminological system of Bethesda 2014.(with Leishman staining without a description of the cytogram – studies 120015, 120016) or additionally may include a descriptive part (with Leishman staining and Papanicolaou staining with a description of the cytogram – studies 120001, 120002, 120003, 120004).

The Terminology Bethesda System (TBS) was developed in 1988 in Bethesda (USA, Maryland) in connection with the emergence of new knowledge about the role of HPV in the genesis of cervical cancer and with the aim of more efficient transmission of information from laboratories to clinicians , increasing the reproducibility of the results of cytological diagnostics and ensuring the standardization of the treatment of the revealed disorders.TBS is most consistent with the biology of cervical carcinogenesis and is currently implemented in most countries of the world.

Bethesda terminology system, 2014 basic terminological characteristics and abbreviations

description of the procedure, the method of recognizing cancer

Currently, cervical cancer is the second most common cancer among women.

A significant decrease in mortality from cervical cancer in the middle of the 20th century was associated with the discovery of George Papanicolaou – he argued that the study of vaginal secretions could lead to the detection of atypical cells from the cervix. After a couple of decades, the dads test received recognition from doctors and began to spread throughout the world.

What is the advantage of the Pap test, or Pap smear from the cervix? During testing, material is taken from all areas of the cervix (endo- and exocervix) with a special spatula or brush.After taking the material, a special smear-imprint is prepared, its staining according to the Papanicolaou method.

The advantage of Papanicolaou staining – allows you to assess the degree of maturity of the cytoplasm of cells, the nuclei of atypical cells are stained better. Conducting a pap test allows you to detect atypical cells even in cases where no manifestations of cancer are still visible. Cervical cancer is detected in the early stages, which makes it possible to achieve almost 100% cure of this terrible disease.

Despite the fact that the Pap test technique was developed many decades ago, scientists are constantly developing to improve it. Despite its importance, the dad test is not very informative – according to various sources, from 40% to 60%. This is due to the need to prepare a smear by hand, which often leads to poor quality samples. In addition, all elements of secretions get into the smear: not only cells of the mucous membrane, but also blood elements, mucus, pathogens (if any), which can complicate its study and lead to an incorrect assessment of the results.

Atypical cells may not get into the cytological smear during the traditional pap test, or they will be masked by layered cellular elements. All these shortcomings are responsible for the not very high information content of the traditional test.

To eliminate errors in the preparation of smears and their examination of the test, modern medical equipment was developed for conducting liquid cytology. Liquid cytology is the same pap test, but more advanced, with almost 100% reliability.

The first advantage of liquid cytology is the improved automated smear preparation. The sampling of material for the test is carried out with a cytobrush of a special design – it allows you to obtain material from absolutely all areas of the cervix.

For further work, an innovative cytological processor is required – such as NOVAPREP®NPS25, NPS50. To obtain smears, the operator only needs to load the material into the processor.

The processor automatically processes the material with the removal of excess elements (mucus, blood cells) in a cytocentrifuge (for example, a Cyto-Tek® centrifuge), the subsequent application of the cellular material in one layer on special glasses, drying and staining of smears.

Test quality

Modern processors, when carrying out a pap test, allow not only to prepare high-quality smears for research, but also conduct a preliminary assessment of smears – for this, an extensive database of normal and altered cells is loaded into the processor’s memory.

If a cytologist detects cells suspicious for atypia in a smear, he can perform additional studies of the pap test without re-sampling of the material: after all, all the material is stored in a special test tube with a stabilizer for a long time.A study can be made for the presence of papillomavirus or P16ink4a protein – their detection will indicate the presence of an oncological process in the cervix.

In the coming years, the traditional pap test will remain the main method for diagnosing cervical cancer – after all, modern medical equipment for liquid cytology is quite expensive, and not all women can afford the study itself. The traditional test method has drawbacks that will soon supplant liquid cytology:

• When carrying out the Pap test, all the work on the preparation of smears is done manually, which reduces the quality of the preparations, takes a long time
• Study duration (usually at least two weeks) and workload of laboratory personnel
• False results are received quite often

Pap smear (PAP test) or smear for oncocytology

The founder of Russian gynecology, Professor Vladimir Fedorovich Snegirev often used to say:

“What have I seen the most? Cancer.What do I know least of all? Cancer. “

Many decades have passed, but oncological diseases of the uterus, ovaries and mammary glands still claim the lives of many Russian women. The fact is that the tissues subject to the greatest hormonal changes during the menstrual cycle are most prone to malignant degeneration.

• A special place among various types of cancer of the female genital organs is held by

cervical cancer . Among all female cancers, cervical cancer ranks second after breast cancer.Its specificity lies in the fact that it often develops against the background of benign processes. Refusal of preventive examinations, early onset of sexual activity, sexually transmitted diseases, abortions, bad habits are factors that contribute to the development of cervical diseases. Therefore, more and more experts are talking about the epidemic of cervical cancer that has swept the modern world.

Such simple and affordable diagnostic methods: Pap smear and colposcopy – allow you to catch the initial precancerous changes and carry out simple and effective treatment at an early stage.

That is why, if every woman finds the opportunity to undergo such an examination every year, deaths from cervical cancer will be prevented.

Pap smear = Oncocytology is a simple and effective test for detecting abnormalities in the cell structure of the cervix.

The test was developed in 1943, but even now, using this test, abnormalities in cells at the precancerous stage are detected. With the right plan of further action, all abnormalities can be successfully healed !!!.

Who needs a Pap smear?

Pap smear should be done for all women who are sexually active. It is recommended that the woman have this smear once a year. A Pap smear should not be done during menstruation or if there is an inflammatory process in the vagina. During the day before taking a smear, you should not live sexually, use spermicidal creams, vaginal douches, douches or tampons, because all this can interfere with the correctness of the study.

How is Pap smear done?

A Pap smear is part of a routine pelvic exam and is quick and painless. During the examination, the doctor obtains a certain amount of cells from the cervix. To collect cells, a small brush is used with which a smear is made on a glass plate. After that, the slides are sent to the laboratory, where specially trained cytologists examine them under a microscope.

How and where to get a Pap smear?

You can take the analysis in our clinic at a time convenient for you, including at a consultation.For the convenience of our patients, we work seven days a week from morning to evening. The analysis is not given on the days of menstruation.

What are the Pap smear results?

A Pap smear is normal (negative) when all cells are of normal size and shape. An abnormal (positive) smear occurs when cells with abnormalities in shape and size are found. To describe the degree of abnormality, special terminology is used: inflammatory process, intraepithelial damage of low or high degree.An abnormal Pap smear does not always mean a woman has cancer.

What are the causes of abnormal Pap smear results?

In the presence of an infection such as thrush, Trichomonas, chlamydia, or gonococcus, the cells in the cervix show signs of inflammation and appear abnormal. After the infection is treated, the Pap smear usually returns to normal.

Human papillomavirus is a common cause of abnormalities in Pap smears. The virus can be present in the cervix and also cause genital warts.There are many types of human papillomavirus, some of which are associated with an increased risk of cervical cancer. Therefore, women who have found human papillomavirus are at risk of developing cervical cancer.

Cancer cells are the most abnormal cells found on a Pap smear. In pre-invasive cancer, only the superficial cells are affected. Invasive cervical cancer means that the disease has expanded beyond the surface layer of cells.

What do you do if your Pap smear is abnormal?

The plan of action depends on the degree of cellular changes described by the cytologist. If the changes are associated with inflammation, then the smear is usually repeated after a few months. Appropriate treatment can be prescribed if necessary. Smears in which low-grade abnormalities are found can be repeated after a few months with a control colposcopy. A high degree of deviation is always an indication for colposcopy.Patients with smear abnormalities are advised to use condoms or abstain from intercourse until the examination is completed.

What is colposcopy?

The colposcope is a microscope-like instrument that allows the physician to magnify the vulva, vagina and cervix so that areas with changes can be more easily identified. The patient is placed on a gynecological chair and a gynecological speculum is inserted into the vagina.The doctor lubricates the cervix with special solutions that make it easier to see cellular abnormalities. The colposcope itself does not touch the patient. Colposcopy is not done during menstruation. 24 hours before colposcopy, the patient should not do douching, use vaginal gels, ointments or tampons, because this can affect the accuracy of the study.

Analysis of a smear for oncocytology has a greater diagnostic quality when conducting a colposcopic targeted examination of the cervical tissue.

What is done if cellular changes are detected during colposcopy?

In case of detection of cellular abnormalities, the doctor may take a biopsy. A biopsy is the removal of a small piece of tissue from an altered area. The woman may feel a sharp prick or discomfort (some women may not feel anything at all). For several days after the biopsy, there may be slight bloody or spotting discharge from the genital tract. The tissue sample is sent to the histological laboratory, where it is examined by a specialist under a microscope in all sections.

What if the biopsy shows abnormalities?

Medical advice will depend on the histological report. At the Za Rozhdeniye clinic, experienced doctors-experts in cervical pathology will prescribe the appropriate treatment and follow-up plan with a repeat Pap smear at regular intervals. It is possible that procedures with the use of electric wave therapy or laser therapy will be prescribed to remove altered cells.

Dear women, remember to undergo an examination of the cervix once a year
COLPOSCOPY WITH ONCOCYTOLOGY
will save you from fears of cervical cancer !!!

Related articles 90,000 Pap smear or (Pap test)

Pap smear or (Pap test) is a minimally invasive examination method that is used to diagnose pathologies of the cervix.The pap test makes it possible to effectively detect precancerous changes in the epithelium – cervical intraepithelial neoplasias of varying severity.

This type of study is mandatory for women over 30 years of age, especially those who have previously or are currently found to have human papillomavirus (HPV) of high oncogenic risk, as well as for women who have zones of altered epithelium during colposcopic examination of the cervix.

The material is taken with the help of special cytobrushes, the procedure is painless and feels comparable to the usual taking of a gynecological smear on the flora.

Immediately after taking the biomaterial, a smear-imprint is prepared, touching all surfaces of the cytobrush to the surface of the slide. The finished swab is placed in individual packaging (plastic or paper bag), attached to the direction with a stapler and sent to the laboratory.

According to international standards , the first Pap test is performed 3 years after the onset of sexual activity or at the age of 21 (whichever comes first).Then – once a year. If for 3 consecutive years the results of the Pap test do not reveal changes in the structure of the cells of the cervix, the Pap test is performed once every 2-3 years until the age of 65. After age 65, the Pap test can be discontinued, provided all previous results have been negative.

How to prepare for delivery?

To obtain the most accurate result, a number of conditions must be met before performing the Papanicolaou test:

1. it is not recommended to carry out the examination during menstruation;
2. it is not recommended to conduct an examination in the presence of any inflammatory process;
3. 48 hours before taking a PAP smear, refrain from sexual intercourse, the use of tampons, the use of any vaginal creams, suppositories and medications, douching and vaginal douches;
4. it is advisable to take a shower instead of a bath 2 days before the Pap test;

A

5. smear should be taken before a gynecological examination, colposcopy, or no earlier than 48 hours after these manipulations.

90,000 PAP test – consultations and diagnosis of diseases, high-quality treatment in Israeli clinics

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What is a PAP test?

Pap test is a gynecological examination at the cellular level, which is characterized by a high level of accuracy and information content. Today, dads take a smear for cytology without fail during the examination of the patient on the gynecological chair. It is the pap test that allows you to determine the smallest changes in the nature of the vagina at the cellular level, which can cause the subsequent development of cancerous tumors.Detection of pathological processes at an early stage will make it possible to make an adequate decision in the appointment of effective treatment.

To whom, when and why is the dad analysis performed?

• A Pap smear is performed annually for every woman, starting at the age of majority or in the event of sexual intercourse.
• If a woman is taking oral contraceptives or has genital herpes, then a pap smear test is done twice a year.
• At risk are women who are obese and change multiple sex partners in a short period of time. In these patients, a pap smear is taken more frequently.

With age, the risk of developing cervical cancer becomes higher, so you should take the dad test regularly. It is worth noting that the risk does not diminish with the onset of menopause.

How is PAP analysis taken?

A smear is taken from the surface layer of the cervix using a professional spatula.The material is applied to a special glass and sent to the laboratory for further study. There it is stained according to the Papanicolaou technique and examined for abnormalities in the structure and development of cells.

You can take a swab at any time, except during your period. Two days before going to the gynecologist, you should avoid sexual intercourse, the use of vaginal creams, suppositories, syringes.

PAP test analysis: evaluation of results

There are five stages of gynecological pathology.

1. First – there are no abnormal cells, the patient’s health is normal.
2. Second – there is an inflammatory process, the presence of infection.
3. Third – there are several abnormal cells that can cause oncology.
4. Fourth – clear pathological changes in the cells were found, a biopsy is prescribed without fail.
5. Fifth – cancer cells are clearly visible, and there can be no doubt about the diagnosis.

However, despite its greater accuracy, the liquid cytology pap test is not the only basis for diagnosis.In addition, other tests are always prescribed, which together help to confirm the result.

90,000 Cervical dysplasia. What will the PAP test show us?

I recently had a swab for a PAP test and my gynecologist said the results showed cervical dysplasia. What does it mean? Is it cancer?

Gynecologist Lyudmila Ivanovna Kernosenko answers:
No. Cervical dysplasia is not cancer. The test indicates that abnormal cells have been found on the surface of the cervix.

Cervical dysplasia can range from mild to severe, depending on the appearance of the abnormal cells. In rare cases, it can develop into cancer.

Tests to determine the degree of cervical dysplasia

After detecting abnormalities on the Pap smear, the doctor may recommend additional tests, including:

Human papillomaviruses are often the main cause of cervical cancer. An ordinary dad test calculates about 55% of oncological pathologies.The HPV test is more sensitive for cell changes that lead specifically to cervical cancer.

Colposcopy is an examination of the cervix, vagina and vulva using a magnifying device. During a colposcopy, your doctor can determine where the abnormal cells are growing and the extent of the abnormality. A cell sample (biopsy) can be taken for analysis. Biopsy results may indicate cervical intraepithelial neoplasia (another term for dysplasia), which is classified as CIN I, II, or III.

Treatment and monitoring of cervical dysplasia

Treatment is often unnecessary for mild dysplasia (CIN I). In most cases, mild dysplasia goes away on its own and does not become cancerous. The gynecologist may recommend retesting after a year to check for additional changes.

If you have severe dysplasia (II or III), your doctor may recommend treatment, such as surgery or other procedures to remove abnormal cells.

Chest pain appeared. Is it worth it to panic. Read more ……

What else can be found in the results of the PAP cervical test?

With the help of the PAP test, not only the presence of abnormal cells is determined, but also many different types of infections are often detected.

Papillomavirus . It is an infection that causes warts to appear on the cervix and in the vagina.

Chlamydia . This infection is the most common and is sexually transmitted.It is very difficult to diagnose, which significantly slows down the treatment process. And this, in turn, threatens to cause complications.

Gonorrhea . An infection that is often the cause of female infertility.

Fungus (yeast infection). The growth of fungus in the vagina ultimately leads to an inflammatory process. Symptoms: itching, white discharge with a pungent odor, irritation.

Trichomoniasis . A sexually transmitted disease that can be completely cured if detected in time.Symptoms: itching, pain during urination and sexual intercourse, greenish discharge.

Cytology The PAP test is an absolutely harmless analysis that is allowed to be done during pregnancy. It is done to all women who have reached the age of 18, as well as those who have begun to have sex life
. According to the WHO recommendations, the PAP test should be taken once a year.

See your doctor every 6 months. Watch your health!

Kernosenko Lyudmila Ivanovna, gynecologist of the International Innovation Clinic

Obstetrics-Gynecology

Women who do not suffer from gynecological diseases need to visit a gynecologist once a year, and with existing pathology – much more often.

Preventive appointments with a doctor are necessary to identify such diseases as: cervical erosion, fibroids, as well as cervical cysts at an early stage of their development, since these diseases are often asymptomatic.

An obstetrician-gynecologist should be consulted if the following symptoms appear:

• Menstrual disorders
• painful sensations during menstruation;
• profuse menstruation;
• Pain, burning or cramps when urinating; frequent urination.
• pain in the lower abdomen;
• discharge, burning and itching of the genitals;
• painful sensations during intercourse;

90,013 problems with conception;

• Suspected pregnancy
• hormonal problems of reproductive age and menopause.

How is a consultative appointment with an obstetrician-gynecologist:

The doctor conducts a visual and instrumental examination, takes a smear for analysis for oncocytology and exclusion of the inflammatory process.

In addition, if necessary, you may be referred for an ultrasound of the pelvic organs and mammary glands.

During the consultation appointment, the gynecologist can ask clarifying questions that relate to intimate life. Try not to be shy and answer in as much detail as possible. Any little thing that seems insignificant can actually be extremely important in the diagnosis.

It should be remembered that some tests must be taken on a specific day of the menstrual cycle.When writing out a referral, the specialist will tell you about it in detail.

If you have the results of analyzes, medical reports, they must be shown to the doctor. It is desirable to track many changes over time.

Also, do not forget to talk about existing chronic diseases, allergic reactions, drugs that you are currently taking.

At the Center for Respiratory Physiology and Pathology, you can undergo the following examinations and analyzes:

• PAP test (Pap smears) for cytology – to detect atypical cells;
• Ultrasound of the pelvic organs;
• Ultrasound of the mammary glands;
• Blood test for hormones;
• Blood test for tumor markers;
• Blood test for infections.

  Obstetrician-gynecologist

Consultative and diagnostic department

Price

Reception (examination, consultation) of a gynecologist

800

Ultrasound diagnostics

Price

Ultrasound examination of mammary glands

600

Ultrasound examination of mammary glands (complex) with CDC

650

Ultrasound examination of the mammary glands with the determination of microcalcifications in the nodes (and CDC)

700

Sighting puncture puncture of breast neoplasm under ultrasound control

700

Transvaginal ultrasound examination of the uterus and appendages

550

Transabdominal ultrasound examination of the uterus and appendages

550

Ultrasound examination of the uterus and appendages (complex) (with CDC)

600

Obstetrician-gynecologist

Price

Collection of urogenital smears (PCR, flora, atypia, tank.sowing)

100

Introduction of intrauterine contraceptive

500

Removing the intrauterine contraceptive

500

Tray (tray with a tampon)

150

Bath (bath with a tampon) with medicine)

170

Clinical diagnostic laboratory

Price

Clinical blood test: – Determination of the erythrocyte sedimentation rate according to Panchenko – Determination of the erythrocyte sedimentation rate according to Westergren

300

Study of blood reticulocytes

100

Bleeding Time Study

120

Platelet count according to Fonio

150

II.IMMUNOLOGY

Serological reactions to various infections, viruses

Antibodies to Candida Ig A

250

Antibodies to Candida Ig G

250

Antibodies to Cytomegalovirus Ig G

250

Antibodies to Cytomegalovirus Ig M

250

Autoantibodies to therioglobulin (TG)

370

Autoantibodies to thyroid peroxidase (AT to TPO)

370

Determination of antigen to fungi of the genus Aspergillus

300

ELISA: Syphilis sum.IgG + IgM

300

Joint detection of antigen and antibodies to HIV 1 + 2

400

Study of the level of hormones in blood serum

Study of the level of thyroid-stimulating hormone (TSH) in blood serum

350

Study of the level of free thyroxine in blood serum with T4 (automatic analyzer)

350

Study of the level of estradiol in blood serum by ELISA

350

Study of the level of cortisol in blood serum by ELISA

370

Study of prolactin level in blood serum by ELISA

350

Determination of the level of CA-125 in the blood, determined for women

200

III.PCR DIAGNOSTICS

Study of the biocenosis of the urogenital tract in women “Femoflor screen”

1800

Trichomonas vaginalis

370

IV. BACTERIOLOGY

Study of biomaterial for microflora and antibioticogram

Bacteriological examination of genitals for microflora and antibiotic sensitivity

350

Bacteriological examination of genitals for fungi of the genus Candida with determination of their sensitivity to antibiotics

290

Microbiological (cultural) study of the detached genital organs for mycoplasma (Mycoplasma)

330

Microbiological (cultural) study of genital discharge for ureaplasma (Ureaplasma urealyticum)

330

Bacteriological examination of genitals for ureaplasma (Ureaplasma urealyticum) + antibiotic sensitivity

350

Bacteriological examination of genitals for mycoplasma (Mycoplasma genitalium) + antibiotic sensitivity

350

.