Centro de Endoscopía Avanzada - Láser Ginecológico

Management of Women with Cervical Cytologic Results Interpreted as Low-Grade Squamous Intraepithelial Lesion: The Foundation of the ASCCP Guidelines.

Mark Spitzer, MD, Edward J. Wilkinson, MD, Daron Ferris, MD, Alan G. Waxman, MD, Kenneth D. Hatch, MD, Claudia Werner, MD, Marluce Bibbo, MD, Terence J. Colgan, MD, Terri Cornelison, MD, and Edward E. Partridge, MDNorth Shore University Hospital, Manhasset, NY; University of Florida College of Medicine, Gainesville, FL; Medical College of Georgia, Augusta, GA; University of New Mexico, Albuquerque, NM; Arizona Cancer Center, Tucson, AZ; University of Texas Southwestern, Dallas, TX; Thomas Jefferson University Hospital, Philadelphia, PA; Mount Sinai Hospital, Toronto, Ontario, Canada; National Cancer Institute, Bethesda, MD; and University of Alabama at Birmingham, Birmingham, AL

Each year, of the 50 million Pap tests performed in the United States, 3.5 million (7%) are interpreted as having a cytologic abnormality that requires further evaluation [1]. During the same time period, there are approximately 12,800 new cases of cervical cancer, resulting in approximately 4,600 deaths [2]. Clinicians are challenged by the difficult task of identifying and evaluating the 750,000 women with cervical cancer precursors among the 3.5 million women with a cytologic abnormality.

In May 2001, the National Cancer Institute held a consensus workshop to reassess and revise The Bethesda System [3] terminology used to classify cervical cytologic abnormalities. Significant changes were made to the manner of reporting minor degrees of cytologic abnormalities compared with the older 1991 Bethesda System. The interpretation of atypical squamous cells (ASC) must now use only two subcategories of ASC: atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells-favor high-grade lesion. The term benign cellular changes has been discontinued as a separate interpretative category, and such cellular changes are now incorporated within the new category of negative for intraepithelial lesion or malignancy. A possible consequence of these changes may be an increase in the number of cytologic smears interpreted as low-grade squamous intraepithelial lesions (LSIL) because some cytologic interpretative categories for minor degrees of abnormality are no longer available for use.

At about the same time, the National Cancer Institute’s Atypical Squamous Cells of Undetermined Significance/Low-grade Squamous Intraepithelial Lesion Study (ALTS) clinical trial began reporting new information about the natural history, detection, and management of human papillomavirus (HPV) and cervical cancer precursors [4]. This new information, in conjunction with the recent availability of liquid-based cytologic analysis and sensitive molecular methods for the detection of oncogenic HPV types, suggested that the existing guidelines [5] were inadequate. This conclusion provided motivation for the American Society for Colposcopy and Cervical Pathology (ASCCP) to sponsor a National Consensus Conference to develop comprehensive management strategies for women with cytologic abnormalities and cervical cancer precursors. The evidence supporting the guidelines and the guidelines themselves have been published previously [6]. This article discusses the current evidence regarding the management of LSIL cytologic results and the rationale for the ASCCP guidelines [6].

To understand the guidelines for managing women with cervical cytologic abnormalities, one should understand the possible types of histologic findings associated with each cytologic abnormality. Cervical abnormalities can be divided into four categories: (1) benign and inflammatory cervical abnormalities; (2) productive viral infections with limited malignant potential (this includes cervical intraepithelial neoplasia [CIN] 1 and cervical condyloma acuminatum); (3) true premalignant disease (CIN 2 and CIN 3); and (4) invasive cancer. Cervical cytologic screening is intended to identify premalignant disease before it progresses to cancer. However, just like colposcopic impressions, cytologic diagnoses are some-what subjective. In fact, cytologic diagnoses may represent various histologic diagnoses. To better understand the new management guidelines, the range of histologic findings associated with each cytologic diagnosis should be known. Management also must be tailored to the individual and population being treated. The following examines the evidence supporting the new LSIL guidelines.

PREVALENCE OF LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESIONS

The College of American Pathologists Q-probes survey [7] reported in 2000 that the median rate of LSIL reports among laboratories in the United States was 1.6% (10^th percentile, 0.7%; 90^th percentile, 4.3%). The prevalence of LSIL varied based on the population being screened. Laboratories serving high-risk populations have LSIL rates as high as 7.7% [1]. Young, sexually active populations have the highest rates of LSIL [8]. However, using social and sexual risk factors to identify women with LSIL who are most likely to have CIN 2,3 is not reliable. Data from the Q-probes study indicates approximately 13.5% of LSIL cytologic results are associated with biopsies showing benign cervical changes, 86% with biopsies showing CIN (86% CIN 1 and 18% CIN 2,3) and 0.2% with biopsies showing invasive cancer [7]. This means that the diagnosis of about a quarter of all CIN 2,3 is preceded by a LSIL cytologic interpretation. In women referred for colposcopic evaluation after LSIL cytologic results, case series show a variable rate of biopsy-confirmed CIN 2,3 typically between 15% and 30% [9-14]. Some series report rates as high as 40% to 70% [15-17]. Although the range in the rates of CIN 2,3 in these series is large, it may be explained in part by the high intraobserver and interobserver variability associated with the cytologic interpretation of LSIL. In ALTS, only 68% of the index cytologic cases interpreted as LSIL were confirmed as LSIL by the QC pathology group; 26% were changed to ASC-US or negative and 6% were changed to high-grade squamous intraepithelial lesion [18].

The variability in the prevalence of LSIL representing biopsy-proven CIN 2 and CIN 3 among series may also reflect differences in the patient populations studied. Studies reporting a high (30 % or higher) prevalence of CIN 2 and CIN 3 often are comprised of women undergoing excisional procedures for persistent LSIL or for CIN 1 [15,16]. The percentage of women with LSIL cytologic results found to have CIN at colposcopy is higher in younger women and decreases with age. Schiffman et al. [19] suggested that women more than 35 years of age with a cytologic diagnosis of LSIL were more likely to have LSIL mimics than true LSIL. These patients were more likely to have their initial cytologic interpretation downgraded to normal on expert review. Cytologic results reported as koilocytotic atypia in post-menopausal women were more likely to be caused by atrophy and test negative for HPV DNA.

MANAGEMENT OPTIONS FOR WOMEN WITH LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESIONS CYTOLOGIC RESULTS

There are of biopsy-proven CIN 2,3 in women with LSIL cytologic results underscores the importance of proper evaluation. A review of the literature suggests four possible evaluation options: immediate colposcopy, follow-up with cytologic analysis alone, an intermediate triage tool such as HPV DNA testing, or “see and treat” loop electrosurgical excision (LEEP). There are advantages and disadvantages to each of these LSIL management options.

Immediate Colposcopy

Immediate colposcopy, with biopsies as indicated, has been used for the last three decades to evaluate women with mild dysplasia or LSIL. Colposcopy allows rapid detection of CIN 2 or CIN 3, when present . It quickly confirms the presence, size, and extent of a low-grade CIN lesion, when present, or affirms normality. Immediate colposcopy reduces the risk that women with significant lesions will be lost to follow-up.

Women may be reassured when CIN 2,3 is excluded and only CIN 1 or no disease is identified [20]. However, the colposcopic impression of low-grade is less reproducible than the colposcopic impression of high-grade [21-23]. Spitzer et al. [24] identified 233 women with LSIL cytologic results who had no indication of CIN 2,3 by colposcopic impression, colposcopically directed biopsies, or repeat cytologic analysis. Of these, 49 (21%) had CIN 2,3 on cervical excision (LEEP or laser conization). Hopman et al. [21] reviewed eight studies that reported colposcopic impressions and histologic correlates in patients with satisfactory colposcopic examinations. They found that a colposcopic impression of CIN 1 accurately predicted the histologic diagnosis of CIN 1 only 42.8% of the time (range, 20.0 %-60%). This finding correlated with rates of 61.6%, 59.0%, and 78.3% for the prediction of no CIN, CIN 2, and CIN 3, respectively. The study showed an intraobserver agreement of 66.7% when 23 expert colposcopists reviewed colpophotographs of varying degrees of CIN during two study session 2 to 3 months apart. The interobserver agreement for the two readings was only 52.4% and 51.0%, respectively. The found both interobserver and intraobserver concordance to be worse with CIN 1 and CIN 2 than with the categories of no CIN and CIN 3 [23].

In ALTS, 1572 women were enrolled with LSIL cytologic results. Of the 673 who were triaged to the immediate colposcopy arm of the study, 100 (14.9%) had CIN 3 or invasive cancer (CIN 3+) by the conclusion of the study 24 months later. Sixty-one (61%) of these lesions were identified at the initial colposcopy. However, 18 (18%) were not identified colposcopically, rather only after LEEP was performed at the conclusion of the study. The same was true of CIN 2 lesions. Eighty-nine CIN 2 lesions (13.2%) were identified in the immediate colposcopy arm of the study. Of these , only 70 (79%) were identified at the initial colposcopy, and 14(16%) were not identified colposcopically, rather only after a LEEP was performed at the conclusion of the study (Solomon D, written communication, September 6-8, 2001). Although immediate colposcopy theoretically identifies all patients with CIN 2,3, this study suggests that a single colposcopy can miss approximately 20% of these high-grade lesions and that 16 % to 18% may not be identified by any colposcopy.

Follow-up by Repeat Cytologic Analysis

In some settings, women with LSIL cytologic results are followed up with cytologic analysis alone, and only selected high-risk patients are referred for colposcopy. Those who oppose immediate colposcopy for women with LSIL cytologic results note the relatively high regression rate of the CIN lesions identified in these women. Furthermore, the rate of cervical cancer in these women is very low. In 1993, Ostor [25] reviewed the literature and found that 57%, 43%, and 32% of CIN 1,2, and 3, respectively, regressed, whereas only 11% and 22% of CIN 1 and 2, respectively, progressed to CIN 3 and only 12% of CIN 3 progressed to cancer. Melkinow et al. [26], in a metaanalysis, found that only 21% of LSIL progressed to high-grade squamous intraepithelial lesion, whereas 47% regressed to normal. In both these studies [25,26], and others [27,28], the risk of invasive cancer was extremely small. Opponents of immediate colposcopy argue that identifying lesions immediately increases the likelihood that women will be treated; a treatment that is likely to have been unnecessary because many of these lesions regress on their own [20]. A comparison of the immediate colposcopy and the conservative management (i.e., cytologic follow-up) arms of ALTS highlighted this phenomenon. Despite randomization that would be expected to have equalized the number of CIN 2 lesions in each arm of ALTS, only 51 CIN 2 lesions (7.6%) were identified in the conservative management arm compared with 89 (13.2%) in the immediate colposcopy arm. The deficit in the number of identified CIN 2 lesions in the conservative management arm (compared with a number expected to be similar to those found in the immediate colposcopy arm) was interpreted as being the results of CIN 2 lesions that would have been identified had colposcopy been performed immediately but that subsequently regressed during observation. As expected, a much smaller deficit was noted in the conservative management arm for CIN 3 lesions. In the conservative management arm, CIN 3 was found in 13.6% of the patients, versus 14.9% in the immediate colposcopy arm. This is interpreted as the result of the lesser regression rate for CIN 3 (Solomon D, written communication, September 6-8, 2001).

Proponents of cytologic follow-up most women with LSIL cytologic results identify a subset of women who are at greater risk for high-grade disease and suggest that they may benefit from immediate colposcopy. Women considered to be at greatest risk for having CIN 2 or CIN 3 are those with a previous diagnosis of CIN 2, CIN 3, or cervical carcinoma [29]; a previous ASCUS or worse cervical cytologic results [30]; or those who are inmunosuppressed [31,32], are postmenopausal without atrophy, are smokers [33], or for whom the laboratory added a descriptive modifier to the cytologic interpretation suggesting the presence of a more severe lesion.

The experience of managing women with LSIL (i.e., mild dyskaryosis) with a program of repeat cervical cytologic analysis has been reported in several large prospective follow-up studies from the U.K. [34-36]. Robertson et al. [34] evaluated a cohort of 1,781 women with LSIL followed up with repeat cytologic analysis. By 24 months, 35% of the women had two consecutive negative cervical cytologic results, 11.5% had biopsy-confirmed CIN 3 or invasive cervical cancer, and 24% of the women were lost to follow-up. Flannelly et al. [36] followed up a group of 520 women with LSIL for up to 24 months. The final cervical cytologic results were interpreted as normal in 30%, as LSIL in 30%, and as high-grade squamous intraepithelial lesion in 40%. However, 23% of the women assigned to 24 months of cytologic follow-up were lost to follow-up before 24 months.

Another study followed up 278 women with LSIL using a protocol in which referral to colposcopy occurred if either of two 6-monthly repeat cytologic analyses were interpreted as squamous intraepithelial lesion. Return to routine 3-year screening occurred only after two consecutive normal cytologic results [35]. After an average of 27 months of follow-up, 114 women who had not had repeat abnormal cytologic results and who were still under cytologic surveillance underwent colposcopy. Biopsy-confirmed CIN 2 or CIN 3 was identified in 18% and biopsy-confirmed CIN 1 in 44%. Only 38% of the women whose repeat cytologic analysis had been consistently normal had no evidence of CIN at colposcopy. A randomized controlled clinical trial of women younger than 35 years of age with LSIL randomized to undergo either immediate LEEP or cytologic follow-up for 24 months found little clinical usefulness associated with following up patients with LSIL without performing an initial colposcopic evaluation [37]. At the end of 24 months of follow-up, the prevalence of CIN 1 was 13% in 171 women in the cytologic follow-up arm compared with 25% in the treatment arm, indicating that approximately one half of the CIN 1 lesions spontaneously regressed. At 24 months, the prevalence of biopsy-confirmed CIN 2or CIN 3 in the cytologic follow-up arm was identical to the prevalence found in the immediate treatment arm, indicating that regression of CIN 2 or CIN 3 had not occurred. In addiction, two cases of CIN 3 and one case of invasive cervical cancer were identified in women in the cytologic follow-up arm who had repeatedly negative cervical cytologic results.

These studies document high-rates of noncompliance with program of repeat cervical cytologic analysis, a high cumulative prevalence of biopsy-confirmed CIN 2 or CIN 3, and in one study, a high prevalence of biopsy-confirmed CIN 2 or CIN 3 in women in whom repeat cervical cytologic specimens had been interpreted as normal[26,34-40].

In a records linkage study, Holowaty et al. [38] reported on more than 17,000 Pap smears. The cumulative actuarial rate of progression from mild dysplasia to invasive cervical carcinoma was 0.1 per 100 (95% CI, 0.0-0.1) in women followed up for 4 to 24 months and 0.4 per 100 (95% CI, 0.3-0.5) for women followed up for more than 120 months. In another retrospective study of 1,781 women with LSIL, Robertson et al. [34] subsequently identified 10 cases of invasive cervical cancer (0.56 cases per 100), three of which occurred in women lost to follow- up and who sought treatment an average of 6.6 years after the initial LSIL.

Although cytologic follow-up of women with LSIL may conserver resources by lessening the number of colposcopic examinations needed and may decrease over treatment of transient lesions that ordinarily would regress on their own, there are risks associated with this approach. These risks include that infrequently (fewer than 0.2%), patients will have cervical carcinoma, that a lesion may progress to invasive carcinoma during cytologic follow-up, or that a patient will be lost to follow-up and invasive cervical carcinoma will develop [20].

Intermediate Triage with Human Papillomavirus DNA Testing

The ALTS investigated the usefulness of HPV DNA testing as a triage tool to identify those women with LSIL cytologic results who had CIN 2,3 or invasive cancer on biopsy. Using a sensitive molecular DNA assay, the authors found oncogenic HPV DNA types in cervical samples from 532 of the 642 women (82.9%) [41]. Other clinical studies have reported somewhat lower rates of oncogenic HPV DNA among women with LSIL cytologic results. In the studies of both Bergeron et al. [42] and of Ferris et al. [43], 58% of women with LSIL were found to have oncogenic HPV DNA. Receiver operator curve analysis, comparing the performance of HPV DNA testing for intermediate triage in women with ASC and LSIL, found that HPV DNA testing had a lower specificity at a given level of sensitivity among women with LSIL that with women with ASC [44].

Because of the high prevalence of oncogenic HPV types among women with LSIL, it is unlikely that HPV DNA testing will prove to be a cost-effective tool for determining which women with LSIL should undergo colposcopy, although a cost-effectiveness study has not yet been performed. There is a possibility, however, that HPV DNA testing may prove beneficial in selected subpopulations of women with LSIL who have a lower prevalence HPV DNA. A subpopulation where further investigation of the usefulness of HPV triage is needed include postmenopausal women. They exhibit a lower prevalence of HPV and biopsy-confirmed CIN 3 associated with LSIL cytologic results than women in the general population [30,45,46]. The authors of ALTS concluded that the use of HPV DNA testing to triage women with LSIL into a group that should receive colposcopy and a group that can undergo cytologic follow-up was not useful because of the high prevalence of oncogenic HPV DNA types among women with LSIL, and so they discontinued that arm of the trial [41].

Use of Loop Electrosurgical Excision for “See and Treat” in Women with Low-Grade Squamous Intraepithelial Lesions

“See and treat”, the performance of colposcopy and LEEP together in the initial postcytologic visit, avoids the performance of a confirming biopsy and the need for a return visit for a LEEP after the biopsy. The value of a “see and treat” approach for women with any cytologic abnormality depends on the likelihood of finding disease needing treatment. Data from the Q-probes study [7] indicated that approximately 13.5% of LSIL cytologic results are associated with benign cervical changes, 86% with CIN (68% CIN 1 and 18% CIN 2,3), and 0.2% with invasive cancer. “See and treat” LEEP in women with LSIL cytologic results has the advantages of identifying the 18% of women with CIN 2,3 missed at colposcopy. However 82% of women with LSIL cytologic results (13.5% with benign cervical changes and 68% with CIN 1) have disease that has minimal premalignant potential. “See and treat” LEEP unnecessarily treats these women.

Because “see and treat” LEEP in women with LSIL cytologic results is likely to identify so few women with CIN 2,3, LEEP should not be used routinely in women with an initial cervical cytologic results interpreted as LSIL in the absence of a biopsy-confirmed CIN.

RECOMMENDATIONS FOR MANAGING WOMEN WITH LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESIONS

Critical issues in planning the management of women with abnormal cytologic results are whether the lower genital tract has been completely evaluated and CIN 2,3 or invasive cancer has been excluded confidently. Evaluation of the lower genital tract includes adequate evaluation of the transformation zone (satisfactory colposcopy), evaluation of the endocervical canal (endocervical sampling), and evaluation of the vagina. When a non-pregnant woman has a satisfactory colposcopic examination (colposcopy is defined as satisfactory when the transformation zone is fully visualized), a lesion is seen in the transformation zone, and the likely cause of the LSIL cytologic results is identified, endocervical sampling is not required but is acceptable [6]. When no lesion is identified in the transformation zone or no the ectocervix, the vagina must be evaluated. Frequently, evidence of active HPV infection can be detected in the vaginal fornices. If the patient is not pregnant, endocervical sampling is recommended. In ALTS, 26% of the index cytologic results interpreted as LSIL were reinterpreted as ASC-US or negative by the quality control pathologic group [18], so failure to identify a lesion may be related to overinterpreting the index cytologic results.

Few studies address managing a patient with LSIL cytologic results, a satisfactory colposcopic examination, and no lesion identified on the cervix or in the vagina. The critical issue in such patients is whether they harbor occult CIN 2,3 or cancer lesions. In a subpopulation of a larger study, Spitzer et al. [24] reported on 25 patients with LSIL cytologic results and a satisfactory colposcopic examination, and no identifiable lesion. Of these patients, 16% had CIN 2 or CIN 3 in the cone biopsy specimens but none had invasive cancer. In another report of 64 women who underwent a cone biopsy after a negative or LSIL cytologic results and negative colposcopy, five (7.8%) had high-grade lesions (CIN 2,3) There were no invasive cancers [46]. In a follow-up study of 328 women with cytologic results classified as low-grade squamous intraepithelial lesion with negative colposcopic examinations, 52 (15.9%) subsequently were found to have CIN 2 or CIN 3. None had cervical carcinomas [47]. The average duration of follow-up was 10.6 years.

Because the risk of invasive cancer is so small, the ASCCP consensus guidelines recommend that women with LSIL cytologic results, a satisfactory colposcopic examination, and no lesion identified on the cervix or in the vagina be followed without treatment. Acceptable follow-up options include repeat cytologic analysis at 6 and 12 months, with referral to colposcopy when repeat cytologic analysis is reported as ASC-US or greater, or HPV DNA testing at 12 months, with referral to colposcopy of any woman testing positive for oncogenic HPV types [6].

The use of HPV testing as an alternative to follow-up by repeat cytologic analysis is based on studies that have demonstrated that only women with persistently positive HPV tests for oncogenic HPV DNA types progress to high-grade CIN. Lesions generally resolve in women who test negative for high-risk HPV DNA [48]. Data derived in part from the study of populations with ASC-US cytologic results shows that the sensitivity of a single HPV DNA test for oncogenic HPV types is comparable with two repeat cytologic examinations, provided sufficient time is give for possible regression of the HPV infection [49]. In addition, in ALTS, a single HPV test for oncogenic types identified nearly all women found to have a high-grade precancerous lesion during the 24 months of the study and was more effective than a single colposcopic examination or two cytologic examinations [50].

Endocervical sampling is also preferred for women with LSIL and an unsatisfactory colposcopy. In a subpopulation of larger study, Spitzer et al. [24] reported on 14 patients with LSIL cytologic results and an unsatisfactory colposcopy, two (14%) had CIN 2 or CIN 3 on cervical cone biopsy; there were no invasive cancers.

Although there is very limited evidence, because the risk for cancer is so small, the ASCCP consensus conference recommended that a diagnostic cervical excisional procedure is not necessary under these circumstances. If biopsy-confirmed CIN is not identified and the colposcopy is unsatisfactory, acceptable management options include follow-up with repeat cytologic analysis at 6 and 12 months, or HPV testing at 12 months [6].

LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESIONS IN SPECIAL CIRCUMSTANCES

Postmenopausal Women

Postmenopausal women, as well as other women with low estrogen levels, may have atrophic changes of their cervical-vaginal epithelium. Atrophic epithelium can produce a wide range of cytologic changes, including some that resemble the cellular changes of LSIL [51]. Postmenopausal women with LSIL also are less likely to test positive for HPV [3], indicating that the effects of declining estrogen may results in cellular changes that are misclassified as LSIL. No studies adequately have compared the specificity and positive predictive value of LSIL cytologic results in postmenopausal women as compared with younger women. Also, the colposcopic appearance of CIN lesions becomes less prominent when the epithelium is atrophic, marking them more difficult to identify. Clinical experience and expert opinion have suggest that a short course of vaginal estrogen cream may be helpful in causing the regression of non-HPV/CIN-related LSIL cytologic results that typically represent only atrophic change and in improving the colposcopic detection of those lesions that are related to HPV/CIN. There are no clinical trials specifically and adequately addressing the use of vaginal estrogen cream in postmenopausal women with LSIL. Nevertheless, the ASCCP consensus conference suggested that providing a course of intravaginal estrogen followed by repeat cytologic analysis, obtained approximately 1 week after completing the regimen, is an acceptable option for women with LSIL who have clinical or cytologic evidence of atrophy and no contraindications to the use of vaginal estrogen [6]. If the repeat cytologic analysis is “negative for intraepithelial lesion or malignancy”, the patient should have a second repeat cytologic analysis in 4 to 6 months. If both are normal, she can return to routine cytologic screening. If the repeat cytologic analysis is reported as ASC or worse, the patient should be referred for colposcopy.

According to clinical opinion, some postmenopausal women not having signs of atrophy may be managed without initial colposcopy by either repeating the cytologic analysis at 6 and 12 months or by testing for the presence of oncogenic HPV in 12 months. Women with any repeat cytologic results of worse than ASC should be referred to colposcopy, as should any woman testing positive for oncogenic HPV types. Women whose repeat cytologic results are negative or who test negative for HPV DNA can return to repeat cytologic analysis testing in 12 months.

Adolescents

Many young women in the United States are exposed to HPV within the first few years after becoming sexually active. Concurrent and sequential infections with different HPV types may occur. Although these infections may cause cytologic changes (ASC-US, atypical squamous cells-favor high-grade lesion, or LSIL cytologic results), most of these infections are transient. However, approximately 10% remain infected 5 years later. These women have an increase risk for a premalignant lesion (CIN 2,3). If cervical cancer develops, in most cases it occurs only after many years or decades from the time of the initial HPV infection. Eve though adolescents have a very high incidence of LSIL cytologic results, they have very low risk for developing rapidonset invasive cancer. For selected adolescents, acceptable options for follow-up consist of repeat cervical cytologic analysis at 6 and 12 months, with referral to colposcopy when any repeat abnormal cytologic results are ASC or worse, or HPV testing at 12 months, with referral to colposcopy of HPV-positive adolescents [6].

Pregnant Women

Colposcopy in pregnant women is more technically challenging that in nonpregnant women. The interpretation of colposcopic findings in pregnant women is also more difficult. Vascular changes are more prominent. Acetowhite epithelium is less prominent. As pregnancy progresses, the vascularity of the cervix increases the risk of bleeding associated with a colposcopically directed biopsy. Although biopsy of lesions suspicious for high-grade CIN or invasive cancer is preferred, most experts prefer to defer biopsy when they confidently can exclude a high-grade lesion by colposcopic appearance. Endocervical curettage is unacceptable in pregnant women because of the risk that it may cause ruptured membranes. For these reasons, it is preferred that a clinician who is experienced in the colposcopic evaluation during pregnancy conduct colposcopy in pregnant women [6].

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