Pap smear test


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The Papanicolaou test (also called Pap smear, Pap test, cervical smear, or smear test) is a screening test used in gynecology to detect premalignant and malignant (cancerous) processes in the ectocervix.

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Pap smear test

  1. 1. Pap smear test Given by:
  2. 2. Introduction <ul><li>The Papanicolaou test (also called Pap smear, Pap test, cervical smear, or smear test) is a screening test used in gynecology to detect premalignant and malignant (cancerous) processes in the ectocervix. Significant changes can be treated, thus preventing cervical cancer. The test was invented by and named after the prominent Greek doctor Georgios Papanikolaou. An anal Pap smear is an adaptation of the procedure to screen and detect anal cancers. </li></ul><ul><li>In taking a Pap smear, a speculum is used to gather cells from the outer opening of the cervix of the uterus and the endocervix. The cells are examined under a microscope to look for abnormalities. The test aims to detect potentially pre-cancerous changes (called cervical intraepithelial neoplasia (CIN) or cervical dysplasia), which are usually caused by sexually transmitted human papillomaviruses (HPVs). </li></ul><ul><li>Continue… </li></ul>
  3. 3. Continue… <ul><li>The test remains an effective, widely used method for early detection of pre-cancer and cervical cancer. The test may also detect infections and abnormalities in the endocervix and endometrium. </li></ul><ul><li>In general, in countries where Pap smear screening is routine, it is recommended that females, aged 18 to 65, who have had sex, seek regular Pap smear testing. Guidelines on frequency vary from annually to every five years. If results are abnormal, and depending on the nature of the abnormality, the test may need to be repeated in six to twelve months. If the abnormality requires closer scrutiny, the patient may be referred for detailed inspection of the cervix by colposcopy. The patient may also be referred for HPV DNA testing, which can serve as an adjunct to Pap testing. Additional biomarkers which may be applied as ancillary test with Pap test are evolving </li></ul>
  4. 4. Indications <ul><li>Screening guidelines vary from country to country. In general, screening starts about the age of 20 or 25 and continues until about the age of 50 or 60. </li></ul><ul><li>Women should wait a few years after they first have intercourse before they start screening. For example, United States Preventive Services Task Force (USPSTF) recommends waiting three years. American Congress of Obstetricians and Gynecologists (ACOG) recommends starting screening at age 21 (since that is a few years after initial sex for most American women). Many other countries wait until age 25 or later to start screening. For instance, Great Britain starts screening at age 25. </li></ul><ul><li>Most women contract HPV soon after becoming sexually active. It takes an average of a year, but can take up to four years, for a woman's immune system to control the initial infection. Screening during this period may show this immune reaction and repair as mild abnormalities, which are usually not associated with cervical cancer, but could cause the woman stress and result in further tests and possible treatment. </li></ul><ul><li>Continue… </li></ul>
  5. 5. Continue…. <ul><li>Cervical cancer usually takes time to develop, so delaying the start of screening a few years poses little risk of missing a potentially precancerous lesion. For instance, screening women under age 25 does not decrease cancer rates under age 30. </li></ul><ul><li>There is little or no benefit to screening women who have not had sexual contact. HPV can be transmitted in sex between women, so women who have only had sex with other women should be screened, although they are at somewhat lower risk for cervical cancer. </li></ul><ul><li>Guidelines on frequency of screening vary - typically every three to five years for those who have not had previous abnormal smears. Some older recommendations suggested screening as frequently as every one to two years, but acknowledge that most women can be screened less often. Some guidelines recommend more frequent screening for younger women; for instance in Great Britain, screening is recommended every 3 years for women under 50, and every 5 years for those over. </li></ul>
  6. 6. Continue…. <ul><li>Guidelines vary on when to stop screening. There is probably no benefit screening women aged 60 or over whose previous tests have been negative. If a woman's last three Pap results were normal, she can stop at age 65, according to the USPSTF; ACS says 70, ACOG says 65 or 70, England's NHS says 64. There is no need to continue screening after a complete hysterectomy for benign disease. </li></ul><ul><li>Pap smear screening is still recommended for those who have been vaccinated against HPV, since the vaccines do not cover all of the HPV types that can cause cervical cancer. Also, the vaccine does not protect against HPV exposure before vaccination. </li></ul><ul><li>More frequent Pap smears may be needed to follow-up after an abnormal Pap smear, or after treatment for abnormal Pap or biopsy results, or after treatment for cancer. </li></ul>
  7. 7. QuickStats: Percentage of Women Aged >25 Years Who Had a Papanicolaou (Pap) Smear Test* During the Preceding 3 Years, by Age Group and Education Level -National Health Interview Survey, United States, 2005* The likelihood of having a Pap smear test during the preceding 3 years increased with education level in each of the age groups. Overall, older women were less likely to be tested; the lowest rate (46.1%) was among women aged >65 years who had not completed high school. Nine out of 10 women aged 25 - 44 years with some college or more reported having a Pap smear test during the preceding 3 years, the highest rate of any group.
  8. 8. QuickStats: Percentage of Women Aged ≥18 Years Who had a Papanicolaou (Pap) Smear Test* During the Preceding 3 Years, by Age Group and Poverty Status -National Health Interview Survey, United States, 2008 <ul><li>* Estimates are based on household interviews of a sample of the civilian, noninstitutionalized U.S. population. Responses are based on a series of questions in the cancer screening supplement of the 2008 National Health Interview Survey, including &quot;Have you ever had a Pap smear or Pap test?&quot; and &quot;When did you have your most recent Pap smear or Pap test?&quot; All women were included, regardless of whether they had had a hysterectomy. </li></ul><ul><li>Poverty status is family income as a percentage of the federal poverty level and takes into account family size and composition. </li></ul>
  9. 9. Continue…. <ul><li>95% confidence interval. </li></ul><ul><li>In all age groups, women with a family income of ≥200% of the poverty level were more likely to have had a Pap test in the preceding 3 years than those who were poor (income <100% of poverty) or near poor (income 100% to <200% of poverty). Women who were poor or near poor were equally likely to have had a Pap test in the preceding 3 years, in all age groups. Women aged ≥65 years were less likely to have had a Pap test in the preceding 3 years than were younger women, regardless of poverty status. </li></ul>
  10. 10. Types of screening <ul><li>Conventional cytology </li></ul><ul><li>Liquid-based monolayer cytology </li></ul><ul><li>Human papillomavirus testing </li></ul><ul><li>Testing in resource-poor areas </li></ul><ul><li>Other options </li></ul><ul><li>Visual inspection to detect pre-cancer or cancer </li></ul>
  11. 11. Conventional cytology <ul><li>In the conventional Pap smear, the physician collecting the cells smears them on a microscope slide and applies a fixative. In general, the slide is sent to a laboratory for evaluation. </li></ul><ul><li>Studies of the accuracy of conventional cytology report </li></ul><ul><ul><ul><ul><ul><li>sensitivity 72% </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>specificity 94% </li></ul></ul></ul></ul></ul>
  12. 12. Liquid-based monolayer cytology <ul><li>Since the mid-1990s, techniques based on placing the sample into a vial containing a liquid medium that preserves the cells have been increasingly used. Two of the types are Sure-Path (TriPath Imaging) and Thin-Prep (Cytyc Corp). The media are primarily ethanol-based for Sure-Path and methanol for ThinPrep. </li></ul><ul><li>Once placed into the vial, the sample is processed at the laboratory into a cell thin-layer, stained, and examined by light microscopy. The liquid sample has the advantage of being suitable for high-risk HPV testing and may reduce unsatisfactory specimens from 4.1% to 2.6%. Proper sample acquisition is crucial to the accuracy of the test, as a cell that is not in the sample cannot be evaluated. </li></ul><ul><li>Studies of the accuracy of liquid based monolayer cytology report: </li></ul><ul><ul><ul><ul><ul><li>sensitivity 61% to 66%, (although some studies report increased sensitivity from liquid-based smears) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>specificity 82% to 91% </li></ul></ul></ul></ul></ul>
  13. 13. Human papillomavirus testing <ul><li>Human papillomavirus (HPV) infection is a cause of nearly all cases of cervical cancer. Most women will successfully clear HPV infections within 18 months. Those that have a prolonged infection with a high-risk type (e.g. types 16, 18, 31, 45) are more likely to develop Cervical Intraepithelial Neoplasia, due to the effects that HPV has on DNA. </li></ul><ul><li>Studies of the accuracy of HPV testing report: </li></ul><ul><ul><ul><ul><li>sensitivity 88% to 91% (for detecting CIN 3 or higher) to 97% (for detecting CIN2+) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>specificity 73% to 79% (for detecting CIN 3 or higher) to 93% (for detecting CIN2+) </li></ul></ul></ul></ul><ul><li>By adding the more sensitive HPV Test, the specificity may decline. However, the drop in specificity is not definite. If the specificity does decline, the result is increased numbers of false positive tests and, for many women that did not have disease, an increased risk for colposcopy and treatment. A worthwhile screening test requires a balance between the sensitivity and specificity to ensure that those having a disease are correctly identified as having it and those without the disease are not identified as having it. </li></ul>
  14. 14. Continue… <ul><li>Regarding the role of HPV testing, randomized controlled trials have compared HPV to colposcopy. HPV testing appears as sensitive as immediate colposcopy while reducing the number of colposcopies needed. Randomized controlled trial have suggested that HPV testing could follow abnormal cytology or could precede cervical cytology examination. </li></ul><ul><li>A study published in April 2007 suggested that the act of performing a Pap smear produces an inflammatory cytokine response, which may initiate immunologic clearance of HPV, therefore reducing the risk of cervical cancer. Women that had even a single Pap smear in their history had a lower incidence of cancer. &quot;A statistically significant decline in the HPV positivity rate correlated with the lifetime number of Pap smears received.“ </li></ul><ul><li>HPV testing can reduce the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cervical cancer detected by subsequent screening tests among women 32–38 years old according to a randomized controlled trial. The relative risk reduction was 41.3%. For patients at similar risk to those in this study (63.0% had CIN 2-3 or cancer), this leads to an absolute risk reduction of 26%. 3.8 patients must be treated for one to benefit (number needed to treat = 3.8). Click here to adjust these results for patients at higher or lower risk of CIN 2-3. </li></ul>
  15. 15. Testing in resource-poor areas <ul><li>Many resource-poor areas cannot provide regular screening, and must rely on infrequent screening. A study of cervical cancer screening of 131,746 women in rural India found that a single DNA test reduced the number of advanced cervical cancers and deaths over 8 years, while a single acetic acid examination or a single Pap screening did not. However, the DNA test cost US $30–40, which was unaffordable in many regions, it is time-consuming, and requires a sophisticated laboratory infrastructure. A simple, affordable, and accurate test is being evaluated in China and other countries. The new test may become available on the market in 2010 at significantly lower cost than current tests. </li></ul><ul><li>With HPV testing, there was a 50 percent reduction in the number of deaths from cervical cancer compared to unscreened women. Compared to other methods, the research showed the HPV testing reported the fewest false negatives. </li></ul>
  16. 16. Other options <ul><li>The Bill and Melinda Gates Foundation has funded an eight-year study of a DNA test for the virus that causes cervical cancer. The test manufactured by Qiagen for a low cost per test with results available in only a few hours may allow reduction in use of annual Pap smears. The test has been shown to work &quot;acceptably well&quot; on women who take the swabs themselves rather than allowing a physician to test. This may improve the chances of early diagnosis for women who are unwilling to be screened due to discomfort or modesty. </li></ul>
  17. 17. Visual inspection to detect pre-cancer or cancer <ul><li>In areas where Pap smear screening is not available or affordable, other methods of testing have been evaluated. </li></ul><ul><li>Visual inspection of the cervix, using acetic acid (VIA) or Lugol’s iodine (VILI) to highlight precancerous lesions so they can be viewed with the &quot;naked eye&quot;, shifts the identification of precancer from the laboratory to the clinic. Such procedures eliminate the need for laboratories and transport of specimens, require very little equipment and provide women with immediate test results. A range of medical professionals - doctors, nurses, or professional midwives - can effectively perform the procedure, provided they receive adequate training and supervision. </li></ul><ul><li>As a screening test, VIA may perform as well as or better than cervical cytology in accurately identifying pre-cancerous lesions. This has been demonstrated in various studies where trained physicians and mid-level providers correctly identified between 45% and 79% of women at high risk of developing cervical cancer. By comparison, the sensitivity of cytology has been shown to be between 47 and 62%. </li></ul>
  18. 18. Continue.. <ul><li>Cytology provides higher specificity (fewer false positives) than VIA. Like cytology, one of the limitations of VIA is that results are highly dependent on the accuracy of an individual's interpretation. This means that initial training and on-going quality control are of paramount importance. Increased false positives are particularly important in a screen-and-treat setting, since over-treatment and resulting impairment of fertility is more likely. </li></ul><ul><li>VIA can offer significant advantages over Pap in low-resource settings, particularly in terms of increased screening coverage, improved follow-up care and overall program quality. Due to the need for fewer specialized personnel and less infrastructure, training, and equipment, with VIA public health systems can offer cervical cancer screening in more remote (and less equipped) health care settings and can achieve higher coverage. Furthermore, providers can share the results of VIA with patients immediately, making it possible to screen and treat women during the same visit. </li></ul><ul><li>This helps ensure that follow-up care can be provided on the spot and reduces the number of women who may miss out on treatment because they are not able to return to the clinic at another time. In a &quot;screen and treat&quot; project in Peru, for example, only 9% of women who screened positive failed to receive treatment in the single-visit approach, compared with 44% of women who were lost to treatment using a multi-visit model. </li></ul>
  19. 19. Continue… <ul><li>VIA has successfully been paired with cryotherapy, a relatively simple and inexpensive method of treating cervical lesions that can be performed by primary care physicians and mid-level providers. </li></ul>
  20. 20. How to Prepare for Your Pap Test <ul><li>If you are going to have a Pap test in the next two days, you should not - </li></ul><ul><ul><ul><li>Douche, which means rinsing the vagina with water or another fluid. </li></ul></ul></ul><ul><ul><ul><li>Use a tampon. </li></ul></ul></ul><ul><ul><ul><li>Have sex. </li></ul></ul></ul><ul><ul><ul><li>Use a birth control foam, cream, or jelly. </li></ul></ul></ul><ul><ul><ul><li>Use a medicine or cream in your vagina. </li></ul></ul></ul><ul><ul><ul><li>Schedule your Pap test for a time when you are having your period. </li></ul></ul></ul>
  21. 21. Procedure <ul><li>For best results, a Pap test should not occur when a woman is menstruating. However, Pap smears can be performed during a woman's menstrual period, especially if the physician is using a liquid-based test; if bleeding is extremely heavy, endometrial cells can obscure cervical cells, and it is therefore inadvisable to have a Pap smear if bleeding is excessive. </li></ul><ul><li>Getting a pap smear should not cause pain, but it can if the patient has certain untreated vaginal problems such as cervical stenosis or vaginismus, or if the person performing it is too harsh, or uses the wrong size speculum. The patient should speak up if they are in pain. Many women experience spotting or mild diarrhea afterward. </li></ul><ul><li>The health care worker begins by inserting a speculum into the woman's vagina, which spreads the vagina open and allows access to the cervix. The health care provider then collects a sample of cells from the outer opening or os of the cervix by scraping it with an Aylesbury spatula. An endocervical brush is rotated in the central opening of the cervix. The cells are placed on a glass slide and taken to the laboratory to be checked for abnormalities. </li></ul>
  22. 22. Continue… <ul><li>A plastic-fronded broom is sometimes used in place of the spatula and brush. The broom is not as good a collection device, since it is much less effective at collecting endocervical material than the spatula and brush. The broom is used more frequently with the advent of liquid-based cytology, although either type of collection device may be used with either type of cytology. </li></ul><ul><li>The sample is stained using the Papanicolaou technique, in which tinctorial dyes and acids are selectively retained by cells. Unstained cells cannot be seen with a light microscope. Papanicolaou chose stains that highlighted cytoplasmic keratinization, which actually has almost nothing to do with the nuclear features used to make diagnoses now. </li></ul><ul><li>In some cases, a computer system may prescreen the slides, indicating those that do not need examination by a person or highlighting areas for special attention. The sample is then usually screened by a specially trained and qualified cytotechnologist using a light microscope. The terminology for who screens the sample varies according to the country; in the UK, the personnel are known as cytoscreeners, biomedical scientists (BMS), advanced practitioners and pathologists. The latter two take responsibility for reporting the abnormal sample which may require further investigation. </li></ul>
  23. 23. Results <ul><li>In screening a general or low-risk population, most Pap results </li></ul><ul><li>are normal. </li></ul><ul><li>In the United States, about 2-3 million abnormal Pap smear results are found each year. Most abnormal results are mildly abnormal (ASC-US (typically 2-5% of Pap results) or low-grade squamous intraepithelial lesion (LSIL) (about 2% of results)), indicating HPV infection.[citation needed] Although most low-grade cervical dysplasias spontaneously regress without ever leading to cervical cancer, dysplasia can serve as an indication that increased vigilance is needed. </li></ul>In a typical scenario, about 0.5% of Pap results are high-grade SIL (HSIL), and less than 0.5% of results indicate cancer; 0.2 to 0.8% of results indicate Atypical Glandular Cells of Undetermined Significance (AGC-NOS). As liquid based preparations (LBPs) become a common medium for testing, atypical result rates have increased. The median rate for all preparations with low-grade squamous intraepithelial lesions using LBPs was 2.9% compared with a 2003 median rate of 2.1%. Rates for high-grade squamous intraepithelial lesions (median, 0.5%) and atypical squamous cells have changed little.
  24. 24. Continue.. <ul><li>Abnormal results are reported according to the Bethesda system[16]. They include: </li></ul><ul><ul><li>Squamous cell abnormalities (SIL) </li></ul></ul><ul><ul><ul><li>Atypical squamous cells of undetermined significance (ASC-US) </li></ul></ul></ul><ul><ul><ul><li>Low-grade squamous intraepithelial lesion (LGSIL or LSIL) </li></ul></ul></ul><ul><ul><ul><li>Atypical squamous cells - cannot exclude HSIL (ASC-H) </li></ul></ul></ul><ul><ul><ul><li>High-grade squamous intraepithelial lesion (HGSIL or HSIL) </li></ul></ul></ul><ul><ul><ul><li>Squamous cell carcinoma </li></ul></ul></ul><ul><ul><li>Glandular epithelial cell abnormalities </li></ul></ul><ul><ul><ul><li>Atypical Glandular Cells not otherwise specified (AGC or AGC-NOS) </li></ul></ul></ul><ul><li>Endocervical and endometrial abnormalities can also be detected, as can a number of infectious processes, including yeast, herpes simplex virus and trichomoniasis. However it is not very sensitive at detecting these infections, so absence of detection on a Pap does not mean absence of the infection. </li></ul>
  25. 25. Effectiveness <ul><li>Prior to the introduction of the Pap test, carcinoma of the cervix was a leading cause of cancer death in women. Since the introduction of the Pap test, deaths caused by carcinoma of the cervix have been reduced by up to 99% in some populations wherein women are screened regularly. A regular program of pap smear screening, with appropriate follow-up, can reduce cervical cancer incidence by up to 80%. </li></ul><ul><li>Failure of prevention of cancer by the Pap test can occur for many reasons, including not getting regular screening, lack of appropriate follow up of abnormal results, and sampling and interpretation errors. In the US, over half of all invasive cancers occur in women that have never had a Pap smear; an additional 10 to 20% of cancers occur in women that have not had a Pap smear in the preceding five years. About one-quarter of US cervical cancers were in women that had an abnormal Pap smear, but did not get appropriate follow-up (woman did not return for care, or clinician did not perform recommended tests or treatment). </li></ul><ul><li>Adenocarcinoma of the cervix has not been shown to be prevented by Pap tests. In the UK, which has a Pap smear screening program, Adenocarcinoma accounts for about 15% of all cervical cancers. </li></ul>
  26. 26. Continue.. <ul><li>Estimates of the effectiveness of the United Kingdom's call and recall system vary widely, but it may prevent about 700 deaths per year in the UK. A medical practitioner performing 200 tests each year would prevent a death once in 38 years, while seeing 152 women with abnormal results, referring 79 for investigation, obtaining 53 abnormal biopsy results, and seeing 17 persisting abnormalities lasting longer than two years. At least one woman during the 38 years would die from cervical cancer despite being screened. </li></ul><ul><li>Since the population of the UK is about 61 million, the maximum number of women who could be receiving Pap smears in the UK is around 15 million to 20 million (eliminating the percentage of the population under 20 and over 65). This would indicate that the use of Pap smear screening in the UK saves the life of 1 person for every approximately 20,000 people tested (assuming 15,000,000 are being tested yearly). If only 10,000,000 are actually tested each year, then it would save the life of 1 person for every approximately 15,000 people tested. </li></ul>
  27. 27. Experimental techniques <ul><li>In the developed world result of cervical biopsy guided by colposcopy is the &quot;gold standard&quot; for diagnosing cervical abnormalities after an abnormal pap smear. The procedure requires a trained colposcopist and can be expensive to perform. However, Pap smears are very sensitive and some negative biopsy results may represent undersampling of the lesion in the biopsy, so negative biopsy with positive cytology requires careful follow up. </li></ul><ul><li>Experimental visualization techniques use broad-band light (e.g., direct visualization, speculoscopy, cervicography, visual inspection with acetic acid or with Lugol's, and colposcopy) and electronic detection methods (e.g., Polarprobe and in-vivo Spectroscopy). These techniques are less expensive and can be performed with significantly less training. They do not perform as well as Pap smear screening and colposcopy. At this point, these techniques have not been validated by large-scale trials and are not in general use. </li></ul>
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