Evaluation and Management of Abnormal Pap Smear
Evaluation and Management of Abnormal Pap Smear
Author: Jim Nuovo, MD, Associate Professor, Department of Family & Community Medicine, University of California—Davis, Sacramento, Calif.
Editor’s Note—For more than 60 years, the Papanicolaou (Pap) smear has been a simple and effective method for reducing the incidence of invasive cervical cancer. As an indicator of its success, in countries that offer regular screening, invasive cervical cancer is a relatively infrequent cause of morbidity and mortality. In the United States, the majority of women who get cervical cancer have never had a Pap smear or have not had one in the past 5 years.1 While the detection of cervical cancer during routine screening is unusual, it is common to have a Pap smear result that suggests the presence of a cervical cancer precursor. These precursors have been labeled squamous intraepithelial lesions (SILs). While there is a wide spectrum of and severity of SILs, the overwhelming majority of these lesions encountered by primary care providers will be low-grade. An important characteristic of these low-grade lesions is their potential to regress spontaneously. It has been challenging to develop methods that can predict which lesions will resolve and which require intervention. In response to the need for useful prediction tools, ancillary tests (eg, human papillomavirus [HPV] testing) have been developed. The usefulness of this test, as well as other technologies, is currently under investigation.
In addition to the need to improve our understanding of the behavior of low-grade lesions, there has been concern about the false-negative rate of the screening Pap smear. The causes of false-negative Pap smears include failure of the clinician to obtain an adequate specimen, and failure of the cytopathology laboratory to detect the presence of abnormal cells. Methods implemented and under consideration to decrease errors include new devices to collect the Pap smear, new methods to prepare the slide, new methods to assist the cytopathologist in reading the slide, and new methods of reporting.
There has been an ongoing debate about the optimal approach method of management of a patient who has an abnormal Pap smear. Some clinicians, due to concerns for the possibility of an underlying high-grade lesion, recommend immediate colposcopy. Other clinicians, cognizant of the likelihood of spontaneous resolution of a low-grade lesion, recommend watchful waiting with repeat Pap smears. This approach uses colposcopy only for women with evidence of persistence or progression of their cytologic abnormality. There are ongoing efforts to differentiate those patients who are more likely to have a clinically meaningful lesion from those in whom watchful waiting is more appropriate.
The purpose of this article is to provide an update on the evaluation and management of patients who have an abnormal Pap smear—particularly those who have low-grade abnormalities. The focus is on the latest developments in cervical cancer screening and the application of these technologies and guidelines into practice.
One of the problems encountered by clinicians who obtain Pap smears is understanding the terminology used to describe cytologic and histologic abnormalities. In this paper, the term SIL will be used to denote all of the intraepithelial, neoplastic changes of the cervix. These lesions are called low grade or high grade by cytopathologists and dysplasia (mild, moderate, or severe), HPV, CIN (grades I, II, or III), or carcinoma in situ by histologists. Regardless of the name, they all represent a change in the epithelium that may have some potential to progress. The term cervical cancer refers only to invasive disease and does not include carcinoma in situ.
Definition of the Problem
SIL is a symptomless disease. It is a disease process characterized by a long period from the earliest cytologic and histologic abnormalities to the development of invasive cervical cancer. In most patients, the disease process spontaneously regresses. There are no currently available methods that can accurately predict which patients will experience spontaneous regression, and which will develop progression to a more severe lesion. However, given the natural history of this disease process, most women who have properly collected and reviewed Pap smears at regular intervals will have their cytologic abnormality detected at a point when a complete cure is likely. The challenge has involved the following issues: 1) reducing the chance of a false-negative Pap smear; 2) determining which patients with atypical squamous cells (ASC) or a low-grade squamous intraepithelial lesion (LSIL), are likely to experience spontaneous regression and which ones are likely to experience lesion persistence or progression; 3) identifying those whose index Pap smear does not reflect the severity of the underlying dysplasia, namely, high-grade dysplasia on biopsy when the Pap smear is read as ASC or LSIL; 4) identifying which patients would benefit from immediate colposcopy and which would benefit from watchful waiting with repeat Pap smears; 5) determining the usefulness of new tests for Pap smear screening, eg, HPV testing, liquid-based thin-layer preparations, and computer-assisted screening; 6) determining the most cost-effective method of screening for cervical cancer and its precursors; 7) determining a means to improve access to Pap smear screening for medically underserved groups of women; and 8) determining a means to ensure timely follow-up and evaluation for patients who have had an abnormal Pap smear.
Epidemiology
In underdeveloped countries, cervical cancer is common; it represents the third most common cancer worldwide, with at least 400,000 new cases identified each year.2 However, in the United States, death from cervical cancer is rare. Each year, approximately 13,000 US women develop cervical cancer, and 4500 will die of the disease. However, SILs are far more common. Of the more than 50 million Pap tests that are performed annually in the United States, approximately 5% are abnormal. More than 95% of these are categorized as ASC or LSIL.4 Therefore, most primary care providers will face the challenge of evaluating a low-grade cytologic abnormalities far more frequently than one showing high-grade changes.
Squamous cell carcinoma accounts for 80% of invasive cervical cancers; adenocarcinoma accounts for 15%, and the remainders are sarcomas, lymphomas, and other rare neoplasms.
Etiology
The evidence linking HPV with cervical cancer and its precursors is strong. More than 80 different genetic strains of HPV have been identified. However, not all subtypes of HPV are oncogenic. High-risk, genital, oncogenic strains include HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58. Types 16 and 18 are present in more than 80% of cervical cancers.5 The incidence of infection with HPV is directly related to sexual activity; the greater the number of partners, the greater the risk of HPV. Prevalence rates of HPV infection in sexually active young women have been reported to range from 19% to 46%.6 Several studies have attempted to clarify the natural history of a genital HPV infection. Most women who are infected with HPV clear it within 12-24 months.7 It is important to recognize that infection with an oncogenic strain does not mean that a women will develop a SIL. Moscicki and associates prospectively studied a cohort of young women who were HPV-positive. Among 496 HPV-positive women, 106 developed LSILs over a 5-year time period.8 The exact mechanism by which some women develop dysplasia and some go on to spontaneous resolution is unclear. There are other cofactors that play a role in the development of cervical neoplasia. There is strong evidence linking smoking with cervical cancer and its precursors; studies have suggested an increased risk of 1.5-14 times above baseline for the development of any SIL.8 Smoking-related carcinogens have been detected in cervical mucus and are the likely explanation for the increased rate of SILs. Sexual behavior (ie, early onset of sexual activity and multiple sexual partners) as well as exposure to sexually transmitted infections, such as chlamydia, have been associated with the development of cervical neoplasia.9 In addition, the immunological status of the patient plays a role in the development and progression of cervical cancer and its precursors. Women infected with HIV are at increased risk of developing preinvasive disease.10 Other factors with a less clear relationship to cervical dysplasia include nutritional status and the use of oral contraceptives. Previous work suggests a link between low red blood cell folate levels and the development of dysplasia. An understanding of the relationship between the use of oral contraceptives and cervical dysplasia has been problematic. It has been difficult to perform a study that is able to control for common confounding variables.
Pathophysiology
Most pathologists agree that SIL is a cellular response to HPV proteins that interact with the host DNA to induce cell proliferation.11 SIL (dysplasia, CIN, CIS) has a characteristic histologic appearance. The cytologic changes in epithelial cells include changes in nuclear-to-cytoplasmic ratio, chromatin clumping, perinuclear halos, multinucleated cells, and atypical mitotic figures. Details of the specific criteria used for diagnosis were developed at the Bethesda 2001 conference.12 Despite the availability of these criteria, it is important to recognize the subjective nature of a cytologic diagnosis.13 Grenko and associates sought to determine the variability of interpretation of biopsy reports for ASC. One hundred twenty-four biopsy specimens were reviewed by 5 independent pathologists. The rate of dysplasia ranged from 23% to 51%. All of the pathologists agreed in only 28% of the cases. In 52% of cases, diagnoses ranged from normal to dysplasia. The overall interobserver agreement was poor. Intraobserver reproducibility ranged from poor to excellent.
It is important for clinicians to recognize that SILs originate in the transformation zone of the cervix. The transformation zone is the area of metaplasia between normal squamous epithelium and columnar epithelium. It is an active area of cell division that is prone to the oncogenic effects of HPV and other cofactors. SIL is typically a focal disease process that is confined to a limited area of the transformation zone occasionally entirely within the endocervical canal. It is for these two reasons that it is important to sample the entire transformation zone when performing a Pap smear.
It is well known that cervical neoplasia may regress, persist, or progress. Melnikow and associates performed a meta-analysis of papers designed to study the natural history of SILs. The most important results were as follows: Seven percent of patients with ASC and 21% of patients with LSIL demonstrated progression to HGSIL over a 24-month period. Sixty-eight percent of patients with ASC, 47% of patients with LGSIL, and 35% of patients with HGSIL demonstrated spontaneous regression to normal over this same time period. The following rates of invasive cancer were determined: ASC 0.25%, LGSIL 0.15%, and HGSIL 1.44%.14 This tendency for slow progression to high-grade lesions, high rates of spontaneous regression, and a low probability of invasive cervical cancer has formed the basis for the clinical opinion that watchful waiting is an appropriate management choice for patients with low-grade lesions.
Clinical Features
SIL is characteristically a symptomless disease. While invasive cervical cancer can present with vaginal bleeding, there are no symptoms that can be used as indicators for the presence of SIL. Further, there are no reliable visible signs on direct visual inspection of the cervix. Enhancement of visual inspection of the cervix with acetic acid has been described, but this technique has a high false-positive rate. Evaluation for the presence and extent of SIL requires use of colposcopy and biopsy. During colposcopic examination, the clinician looks for those features that are consistent with SIL. There are a number of resources available to clinicians to assist in obtaining skills in colposcopy.15,16
Diagnostic Tests
Pap Smear Nomenclature. For almost 60 years, the Pap smear has remained the most useful diagnostic test for screening for SIL. Over the years, there have been several different systems used to report Pap smear findings. In 1988, The Bethesda System (TBS) was introduced as a means to help standardize terminology for both clinicians and laboratories with more precise reports and to improve quality control. Most clinicians in the United States are now familiar with TBS. This terminology has undergone a recent revision. The Bethesda 2001 workshop was convened to review issues regarding terminology and reporting of cervical cytology results. More than 400 cytopathologists, cytotechnologists, clinicians, and patient advocates participated. Nine forum group sessions covered many topics including specimen adequacy, non-neoplastic changes, ASCUS, AGUS, ancillary testing, endometrial cells, SIL, automated computer review, and recommendations.12 (See Table 1.) The most notable change from the Bethesda 2001 report is that the category ASCUS will be replaced by 2 categories, ASC-US (atypical squamous cells of undetermined significance) and ASC-H (atypical squamous cells, cannot exclude HSIL). ASC-US has the same connotations as the original and should account for 90-95% of readings in this category. ASC-H carries the connotation that there are cytologic changes that are suggestive of HSIL but lack criteria for definitive interpretation.12
| Table 1. Bethesda 2001 Summary Report |
| Specimen Type |
| Indicate conventional smear (Pap smear) vs. liquid based vs. other |
| Specimen Adequacy |
| Satisfactory for evaluation (describe presence or absence of endocervical/transformation zone component and any other quality indicators, eg, partially obscuring blood, inflammation, etc) |
| Unsatisfactory for evaluation (specify reason) |
| Specimen rejected/not processed (specify reason) |
| Specimen processed and examined, but unsatisfactory for evaluation of epithelial abnormality because of (specify reason) |
| General Categorization (optional) |
| Negative for intraepithelial lesion or malignancy |
| Epithelial cell abnormality: See Interpretation/Result (specify "squamous" or "glandular" as appropriate) |
| Other: See Interpretation/Result (eg, endometrial cells in a woman > 40 years of age) |
| Automated Review |
| If case examined by automated device, specify device and result. |
| Ancillary Testing |
| Provide a brief description of the test methods and report the result so that it is easily understood by the clinician. |
| Interpretation Result |
| Negative for intraepithelial lesion or malignancy (when there is no cellular evidence of neoplasia, state this in the General Categorization above and/or in the Interpretation/Result section of the report, whether there are organisms or other non-neoplastic findings) |
| Organisms |
| Trichomonas vaginalis |
| Fungal organisms morphologically consistent with Candida spp. |
| Shift in flora suggestive of bacterial vaginosis |
| Bacteria morphologically consistent with Actinomyces spp. |
| Cellular changes consistent with Herpes simplex virus |
| Other Non-neoplastic Findings (Optional to report; list not inclusive): |
| Reactive cellular changes associated with inflammation (includes typical repair) radiation, intrauterine contraceptive device (IUD) |
| Glandular cells status post-hysterectomy |
| Atrophy |
| Other |
| Endometrial cells (in a woman > 40 years of age) |
| (Specify if "negative for squamous intraepithelial lesion") |
| Epithelial Cell Abnormalities |
| Squamous Cell |
| Atypical squamous cells of undetermined significance (ASC-US) cannot exclude HSIL (ASC-H) |
| Low-grade squamous intraepithelial lesion (LSIL) encompassing: HPV/mild dysplasia/CIN 1 |
| High-grade squamous intraepithelial lesion (HSIL) encompassing: moderate and severe dysplasia, |
| CIS/CIN 2 and CIN 3 with features suspicious for invasion (if invasion is suspected) |
| Squamous cell carcinoma |
| Glandular Cell |
| Atypical |
| Endocervical cells (NOS or specify in comments) |
| Endometrial cells (NOS or specify in comments) |
| Glandular cells (NOS or specify in comments) |
| Atypical |
| Endocervical cells, favor neoplastic |
| Glandular cells, favor neoplastic |
| Endocervical adenocarcinoma in situ |
| Adenocarcinoma |
| Endocervical |
| Endometrial |
| Extrauterine |
| Not otherwise specified (NOS) |
| Other Malignant Neoplasms (specify) |
| Educational Notes and Suggestions (optional) |
| Suggestions should be concise and consistent with clinical follow-up guidelines published by professional organizations (references to relevant publications may be included). |
|
|
Pap Smear Technique. It is important that the clinician obtains an adequate cell sample. Given the small size and focality of SIL, it is important for clinicians to sample the entire area of the cervix where the neoplastic process is most likely to occur. This includes the area of the transformation zone on the ectocervix and in the endocervical canal. Many cell collection devices have been investigated. In the United States, the most commonly used devices include the Ayre spatula (a plastic or wooden device with a broad head in the shape of the cervix), the cytobrush (a brush with perpendicular nylon fibers at the tip), and the cervix "broom" (a broom-shaped device with parallel plastic fibers at the tip of the handle). A recently performed Cochrane review of these and other sampling devices found that the Ayre spatula alone was shown to be less effective when compared to the use of a spatula and cytobrush.17
A marker that can be used by clinicians for the adequacy of the Pap smear is the presence of metaplastic or endocervical cells. These act as a surrogate to determine if the Pap smear was likely to sample the transformation zone. The Bethesda 2001 report has specific criteria to determine whether an adequate number of endocervical cells have been collected.12
| Table 2. Recommended Pap Smear Techniques | |
| 1. | Perform before digital examination |
| 2. | Lubricants other than warm water should be avoided. |
| 3. | Patients should not have an active infection. |
| 4. | The ectocervical area should be sampled first by using a spatula. |
| 5. | The endocervical area should then be sampled with a cytobrush. |
| 6. | A cervical "broom" device may be used in place of the spatula and cytobrush. Its performance is enhanced by multiple rotations on the cervix. |
| 7. | The samples should be smeared onto a glass side and fixed as quickly as possible to avoid air-drying artifact. |
| 8. | The fixative spray should be held approximately 12 in from the surface of the slide to avoid cellular damage. |
| 9. | In offices that use liquid-based systems, the collection device should be placed into the bottle of fixative solution and vigorously agitated. |
|
|
|
Adjunctive Tests. New technologies have been investigated to determine whether they can decrease the chance of a false-negative Pap smear and help in the triage of women with ASC and LSIL. These include liquid-based/thin-layer preparations (to improve the quality of the Pap smear), computer-assisted screening (to aid the cytotechnologist in providing an accurate reading), and HPV testing (to assist in determining the likelihood of a significant cervical lesion).18
Liquid-based/thin-layer preparations use a fluid medium to capture and preserve the cells collected from the Pap smear. The sample is collected with a cervical "broom" device or an Ayre spatula combined with a cytobrush. The clinician does not smear the sample on the glass slide. Instead, the sample is placed in a small bottle containing a fixative solution. This is sent to the cytopathology laboratory. The laboratory filters and centrifuges the sample in order to remove debris. The resulting sample is plated in a "thin-layer." This specimen affords the cytotechnologist with a high-quality smear. Sulik and associates performed a recent systematic review of papers reporting results of fluid-based cytologies. They found that for most women, there is no reason to replace the standard Pap smear with this technology. However, for women at high risk of cervical cancer or for those who are screened infrequently, the possible increase in sensitivity may outweigh the potential problems from additional false-positives.19
Computer-assisted screening provides the cytotechnologist with a means to preview the slide and to help determine whether an abnormality is present. A computer "reads" the slide and determines the likelihood of a SIL. This technique cannot entirely replace the cytotechnologist but can reduce the workload of a laboratory.20
HPV testing has been available for almost 15 years and has undergone multiple changes. The latest refinement, Hybrid Capture II, can detect 13 high-risk HPV types. The test can be performed directly from residual material collected for a liquid-based/thin-prep smear or from a swab of the cervix. The DNA from the sample is denatured and mixed with a nucleic acid probe that binds only to HPV DNA. This produces a chemoluminescent reaction, and the amount of light can be measured to determine the viral load.21 Whether HPV testing is of value in clinical decision-making is debatable. Triage based on HPV testing for women with ASCUS would result in referring approximately 31% to colposcopy.22 The ASCUS/LSIL Triage Study (ALTS) Group performed a large randomized trial including 3600 women diagnosed with ASC and 3600 women diagnosed with LSIL. For patients with LSIL, HPV testing was not valuable in decision-making as HPV DNA was detected in approximately 83% of the women.23 The entry data from the ALTS trial for patients with ASC were recently reported. The study reported a high sensitivity (96%) for HPV testing to identify patients with high-grade SIL. It was concluded that HPV testing is a viable option for managing ASC smears.24 In a review of the ALTS trial, Herbst and associates concluded that there were methodological flaws in the study and that HPV testing should be considered an investigational tool.25
Two additional tests, cervicography and direct visual inspection after application of acetic acid, have been investigated also. Cervicography involves a standardized photograph (cervigram) that is done after application of acetic acid to the cervix. The cervigram is submitted to a central laboratory for interpretation. The reviewer determines the likelihood that the findings on the cervigram represent underlying neoplasia. In a systematic review of cervicography, Nuovo and associates found that false-positive results were common. This rate ranged from 8-61% for any neoplasia to 10-63% for high-grade lesions. The usefulness of cervicography was found to be heavily dependent on the approach used by the clinician to evaluate an abnormal Pap smear. If the clinician typically offers colposcopy to all patients with low-grade findings, cervicography will decrease colposcopy use and allow for detection of high-grade dysplasia missed by the index Pap smear. If the provider typically uses watchful waiting, cervicography will substantially increase the use of colposcopy.26 Direct visual inspection after application of acetic acid has also been evaluated. Similar results were found. Both tests may have a role as cancer screening tests in countries with poor health care infrastructures where cytology is too expensive and complex.27 However, in the United States, these tests add little to the diagnosis of SIL. Newer tests under development include those that assay for proteins present in dysplastic cells obtained during a Pap smear.
It must be noted that these new technologies, while decreasing the false-negative rate, are associated with an increase in the false-positive rate and cost of screening. The increase in false-positives is not without harm. Patients given false-positive results may experience detrimental side effects such as anxiety, unnecessary biopsies, and overtreatment. Further, no large population-based, prospective study has been completed to determine whether any of these techniques lowers the incidence of invasive cervical cancer or improves survival.28
Screening Frequency. Optimal screening frequency has been the subject of numerous papers. It has been estimated that screening every 3 years for women who are between 20-65 years decreases the incidence and mortality rates of invasive cervical cancer by approximately 90%.29 Guidelines on optimal screening frequency vary among organizations and among countries. In the United States, the annual Pap smear remains widely recommended by many clinicians partly because of concerns about false-negative results. Many other developed countries screen women at less frequent intervals such as every 3-5 years and have had equivalent or greater reductions in cervical cancer mortality than has been seen in the United States, presumably because a larger proportion of the population is sampled. Modeling studies have consistently shown that the benefits of screening decline rapidly as screening intervals decrease; marginal gains in life expectancy from annual screening compared with biennial screening are very small.30 There is also no consensus as to when Pap smear screening should end. However, in women who have had a hysterectomy for non-neoplastic reasons, there is no value to Pap smear screening for the detection of SIL.
It is important to remember that 70% of women who have cervical cancer have never had a Pap smear, have failed to have one in the previous 5 years, or failed to follow-up after having an abnormal result.1 Studies from many countries show consistent findings as to which women are more likely not to adhere to screening recommendations. Low adherence rates have been observed among women who are older, less well-educated, from lower socioeconomic groups, or who reside in rural locations.31 Certain ethnic groups also have been identified as having lower rates of adherence with Pap smear recommendations. In the United States, these include African-American, Hispanic, Native American, and Asian women.32 Improving adherence among these groups requires an understanding of the many factors that influence screening behavior. These include perceptions of vulnerability, cost, anxiety, embarrassment, fear of cancer, culture, and other personal circumstances.33 It remains important for clinicians to recognize these barriers and to consider the use of appropriate interventions.
Differential Diagnosis
On visual inspection, cervical conditions that might raise concern about possible neoplasia include a friable cervix and cervical polyps. While there are reports of cervical metastatic ovarian cancer, bladder cancer, and rectal cancer, as well as other conditions such as tuberculosis and syphilitic chancres, these are rarely seen. The decision to pursue the biopsy of a cervical lesion in the context of a negative, well-performed Pap smear must be left to the judgment of the clinician and patient. Patients with a friable cervix should have an examination for SILs and common vaginal pathogens.
There are non-neoplastic conditions that can cause cytologic abnormalities mimicking SIL. These occur mostly in patients identified with ASC. Normal reparative processes, infections, and hormonal effects are among the most common confounding problems. Concurrent infections of the cervix may produce atypical changes. Postmenopausal women who are not on hormone replacement therapy also may show evidence of atypical changes that do not represent underlying SIL.
Management
Squamous Cell Abnormalities. All patients with a Pap smear showing HGSIL should undergo immediate colposcopy. The management of the initial abnormal Pap smear in patients with ASC or LSIL is controversial. Some clinicians recommend immediate colposcopy, some recommend watchful waiting with repeat Pap smears, and others recommend the use of secondary triage in order to identify high-risk patients. Melnikow and associates performed a decision analysis on this subject. It was determined that there was no substantive difference in the detection of cervical cancer when immediate colposcopy was compared to watchful waiting over a period of 2 years.34 A number of organizations have produced clinical guidelines to assist clinicians with their recommendations. The Institute for Clinical Systems Improvement has prepared recommendations in the form of 6 algorithms.35 The American Society of Colposcopy and Cervical Pathology (ASCCP) recommends that clinicians choose from 1 of 4 management options. These 4 options include repeat Pap smear, immediate colposcopy, management on the basis of an adjunctive test, or management by subdividing ASC.15
These recommendations do not incorporate an extensive discussion of patient preference in the decision process. Ferris and associates assessed women’s preferences of the evaluation and management of ASC and LSIL. A convenience sample of 968 women was included in the study. They found that most women preferred a repeat Pap smear to further evaluate an initial finding of ASC, and immediate colposcopy to evaluate an initial finding of LSIL.36
Follow-Up. As many as 10% of women who develop invasive cervical cancer have had an abnormal Pap smear and have failed to obtain appropriate evaluations.1 The interaction of the differing practices of physicians and patient adherence to follow-up was studied by McKee and associates. They found that among their sample of 387 women, providers recommended repeat Pap smear in 67%, colposcopy in 12%, and there was no clear plan in 19%. Complete adherence was achieved for 27% of patients, moderate adherence for 28%, and low adherence for 45%.37 Studies have been done to assess the effectiveness of measures to improve the follow-up of patients with abnormal Pap smear results. Block and Branham described an intervention in an academic family practice center in which patients received follow-up care based on a protocol using educational input, logistic aids, and automated prompting. Their interventions increased follow-up adherence rates from 64% to 87%.38
Other Cytologic Abnormalities: Atypical Glandular Cells of Undetermined Significance (AGUS). AGUS is an uncommon finding on a screening Pap smear (approximately 0.3%). The Bethesda 2001 conference recommended that all women with AGUS should have colposcopy with endocervical curettage and endometrial sampling should be considered.12 Koonings and Price performed a retrospective study of 280 women with Pap smears showing AGUS. All patients underwent colposcopy, endocervical curettage, and endometrial biopsy. Significant abnormalities were found in 32% including 31 women with invasive cancer (11%). Patients older than 50 had a lower chance of high-grade cervical dysplasia but a 12 times greater risk of having endometrial cancer.39
Remaining Up-to-Date
Despite a 60-year history of cervical cancer screening, the understanding of the disease process, the recommendations for screening, and the recommendations for management of an abnormal Pap smear remain dynamic. Recommended web sites for ongoing developments in this area include www.bethesda2001.cancer.gov, www.asccp.com, www.icsi.org, and www.guidelines.gov.
Disposition
The decision to refer a patient to a gynecologist for evaluation of an abnormal Pap smear depends on the availability of colposcopy at the primary care provider’s site and the management approach used for ASC and LSIL. The challenge is to assure that all women have access to cervical cancer screening and that patients with an abnormal smear have appropriate and timely follow-up. These two approaches will have the greatest effect on reducing the burden of cervical cancer. Patient preferences should be incorporated into clinical decision-making. If patients choose watchful waiting, those with persistence or progression should be referred to colposcopy.
Summary
SIL is a common problem encountered by clinicians. Patients who have a well-performed Pap smear on a regular basis that do read in a laboratory with appropriate quality controls should not develop cervical cancer. Most women who develop cervical cancer do not have access to regular screening, fail to take advantage of available screening, or fail to follow-up after an abnormal test. New technologies have been and will continue to be developed in an effort to reduce the false-negative rate of the Pap smear. It remains controversial whether these new technologies will have an effect on long-term outcomes. In the primary care setting, the majority of women with abnormal results will have a Pap smear showing ASC or low-grade changes. Whether the decision to perform immediate colposcopy is appropriate is not clear. Clinicians should consider recommendations from published practice guidelines, patient preferences, and the circumstances of each case to determine which women should undergo immediate colposcopy and which should have watchful waiting.
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