高危型人乳头状瘤病毒检测在不除外高度鳞状上皮内病变的不典型鳞状上皮细胞中的意义

目的 探讨高危型人乳头状瘤病毒(HR-HPV)的检测在宫颈细胞学不除外高度鳞状上皮内病变的不典型鳞状上皮细胞(ASC-H)中的意义.方法 对45例诊断为ASC-H的患者用杂交捕获二代(HC-Ⅱ)方法检测HR-HPV DNA含量,并进行阴道镜检查及活检,分析其结果之间的关系.结果 45例ASC-H的活检结果为宫颈鳞状上皮内病变(SIL)33例(73.3%);45例ASC-H中36例HR-HPV阳性,其中高度鳞状上皮内病变(HSIL)及以上病变者19例(52.8%);9例HR-HPV阴性病例中,没有HSIL及以上病变;HR-HPV对ASC-H患者HSIL的敏感性及阴性预测值均为100%.结论 ASC-H高度提示宫颈病变的存在;HR-HPV可以作为ASC-H患者是否需要立即阴道镜检查的一个预测指标,HR-HPV阳性者应立即阴道镜检查及活检,HR-HPV阴性是HSIL阴性的一个预测指标.     

HPV检测在“不典型鳞状细胞-不除外宫颈高度上皮内病变”中的意义

目的探讨高危型人乳头状瘤病毒(HR-HPV)检测对细胞病理学诊断为不典型鳞状细胞-不除外宫颈高度上皮内病变的(ASC-H)患者的临床处理价值。方法 2004年6月～2007年4月于中日友好医院妇产科门诊进行宫颈细胞学检查的患者17 125例,选择其中细胞学诊断结果为不典型鳞状细胞的患者,应用第二代杂交捕获方法检测HR-HPV,观察HR-HPV检测对细胞学诊断结果为ASC-H进行分流的意义。结果 HR-HPV阳性的ASC-H患者中宫颈高度病变的检出率(48.1%)显著高于ASC-US(25.2%),(P<0.01)。13例HR-HPV阴性的ASC-H患者中1例宫颈活组织检查结果为CIN2(5.9%),与ASC-US(5.7%)相比无差异。在ASC-US和ASC-H患者中,HR-HPV检测对于宫颈高度病变的敏感性分别为82.8%、96.2%,阴性预告值分别为94.3%,92.3%。结论对于HR-HPV阴性的ASC-H患者可以考虑定期随诊细胞学和高危型HPV,减少阴道镜检查,HR-HPV检测可能对于ASC-H患者同样具有分流作用。     

Clinical significance of atypical squamous cells cannot exclude high grade squamous intraepithelial lesion with histologic correlation—: A 9‐Year experience

Atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion (ASC‐H) is a recognized category in the 2001 Bethesda Nomenclature System for cervical cytology. Although current ASCCP guidelines recommend colposcopic follow‐up, more recent studies are suggesting prior triage for HPV‐DNA analysis. We report on our experience at the University of Wisconsin Hospital and Clinics. From January 1, 2003 through December 31, 2011 (9‐y), the cytopathology laboratory processed 109,424 Pap Tests, of which 281 (0.26%) were diagnosed as ASC‐H. Tissue follow‐up was available in 181 (64%) of these cases, of which 45 (25%) were negative/cervicitis, 41 (23%) were CIN 1, 36 (20%) were CIN 2 and 59 (32%) were CIN 3. Stratification by age groups showed a higher percentage of high grade (CIN 2+) lesions (65%) in the premenopausal age group as compared with high grade lesion (35%) in the postmenopausal age group, whereas negative/CIN1 biopsies were more common in postmenopausal (65%) as compared to premenopausal (44%) women. Our data support the use of colposcopy in the management of women with ASC‐H on Pap Tests. However, in the older age group, prior HPV‐DNA testing may be of benefit to better identify those women at risk for high grade lesions. Diagn. Cytopathol. 2013;41:943–946. © 2013 Wiley Periodicals, Inc.     

The value of duplicate slides on atypical squamous cells, cannot exclude high-grade intraepithelial lesion

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) category was added to the 2001 Bethesda System. ASC-H accounts for a small percentage (0.2-0.6%) of abnormal Pap smears and includes heterogenous group of lesions. There are more high-grade cervical lesions (30-50%) in ASC-H than ASC-US (10-15%). An accurate Pap diagnosis is crucial for appropriate patient follow-up and treatment. A total of 43 consecutive ASC-H cases were collected from October 2007 to March 2008, and all duplicate and the original slides were reviewed blindly at the end of the study. On review of the duplicate Pap slides, 18 cases had diagnostic SIL cells (15 HSIL, 2 LSIL with ASC-H, and 1 LSIL). The duplicate slides could have potentially changed 18 (41.9%) ASC-H diagnoses to a more definitive SIL diagnosis. On review of the original Pap slides, 8 of these 18 cases also had HSIL cells. Twenty-one follow-up cervical biopsies (21/43, 48.8%) showed 12 CIN 2/3, 4 CIN 1, 1 VAIN 1, 2 cervical polyps, 1 negative for dysplasia, and 1 insufficient for diagnosis. The CIN 2/3 rate was 57.1% (12/21) based on the original ASC-H Pap diagnosis. The CIN 2/3 rates were 80% (8/10) with SIL cells on duplicate slides and 36.4% (4/11) without SIL cases on duplicate slides. Our study suggested that duplicate slides were very useful for further classification of ASC-H, but other ancillary tests might be necessary for some cases. We propose a systematic approach using combined duplicate slides and reflex HPV testing to further classify ASC-H.     

Reflex high-risk human papilloma virus DNA test is useful in the triage of women with atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion

This study is aimed to investigate the role of reflex high-risk human papilloma virus (HPV) DNA testing as an alternative triage method to colposcopy for women with atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) on Papanicolaou (Pap) tests. Reflex HPV DNA testing using Hybrid Capture II method was carried out on 88 women with ASC-H diagnosed by Thin Prep Pap test. Correlation with follow-up biopsies was available on 42 of these patients. The reflex HPV DNA test showed an overall positive rate of 67% and negative rate of 33% in 88 patients with ASC-H. Using age 30 as the cut off point, the positive rate had increased to 83.3% (35/42) in patients 30 yr or younger, while the positive rate for patients older than 30 yr had decreased to 52.2% (24/46). Follow-up colposcopic biopsy results were available in 35 of 59 HPV-positive women, which revealed 15 (43%) high-grade squamous intraepithelial lesions (HSIL), 12 low-grade squamous intraepithelial lesions (LSIL), and 8 negative for dysplasia. In 7 HPV-negative patients, the follow-up biopsies showed no evidence of HSIL or LSIL. Correlation between clinical risk factors and the HPV results demonstrated no significant differences in HPV positivity between the high-risk and low-risk patients. The high sensitivity (100%) and negative predictive rate (100%) in detecting HSIL in our study provide strong evidence that, instead of automatic referral to colposcopy, reflex HPV DNA testing may be used as an alternative triage method for women diagnosed with ASC-H on Thin Prep Pap test, especially for women older than 30 yr of age.     

Atypical squamous cells,cannot exclude high‐grade squamous intraepithelial lesion: Diagnostic features in surepath™ cervical samples

This study was undertaken to identify the situations in which a diagnosis of “Atypical squamous cells, cannot exclude a high‐grade squamous intraepithelial lesion (ASC‐H)” is offered in SurePath? cervical samples and to identify cytological criteria helpful in predicting high‐grade disease. 2,335 (3.4%) SurePath samples reported as atypical squamous cells (ASC) over a period of 2 years, including 1,112 cases with known hrHPV status were retrieved. 105/1,112 cases were categorized into ASC‐H, and slides were available for review in 88/105 cases. These 88 samples were divided into two categories based on follow‐up histological outcome and hrHPV status–category A: cases with CIN2+ lesions on follow‐up (n = 48) and category B: cases with ≤CIN1 lesions or hrHPV negative status (n = 40). 78% (82/105) cases of ASC‐H tested positive for hrHPV. Overall CIN2+ lesions were found in 50.3% (53/105) cases. Of 88 cases reviewed, HCGs were noted in 56.3% (27/48) cases in category A and 75% (30/40) cases in category B. Dispersed metaplastic cells and scattered small atypical cells were seen in 37.5% (18/48) cases in category A and 12.5%(5/40) in category B. The majority of cases with dispersed atypical cells had <20 cells/sample and cases with HCGs had <10 HCGs per sample. The majority of the cases reported as ASC‐H contained HCGs. Of these groups with nuclear crowding, disorganization and those with steep edges (“blocks”) are likely to predict high‐grade disease. The samples with only dispersed atypical cells had <20 cells/sample in majority of cases. In these, a disproportionate andespecially high nuclear: cytoplasmic ratio and irregular chromatin were the most useful features in predicting high‐grade disease. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.     

"Low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion" is a distinct cytologic category: histologic outcomes and HPV prevalence

We examined the histologic outcomes and prevalence of high-risk human papillomavirus (HR-HPV) in women with liquid-based Papanicolaou (Pap) tests interpreted as "low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion" (LSIL-H) compared with the 2001 Bethesda System (TBS 2001) cytologic categories of LSIL, high-grade SIL (HSIL), and atypical squamous cells, cannot exclude HSIL (ASC-H). A computer search identified 426 LSIL, 86 ASC-H, 81 LSIL-H, and 110 HSIL cytologic interpretations during a 1-year period, each with up to 2 years of histologic follow-up. The risk of histologic cervical intraepithelial neoplasia (CIN) 2 or worse (CIN 2+) associated with LSIL-H (32/81 [40%]) was intermediate between LSIL (46/426 [10.8%]) and HSIL (72/110 [65.5%]), but not significantly different from ASC-H (23/86 [27%]). However, LSIL-H was more frequently associated with a definitive histologic diagnosis of any CIN (CIN 1+) than ASC-H (53/81 [65%] vs 35/86 [41%]). Moreover, the prevalence of HR-HPV was significantly greater in patients with LSIL-H than in patients with ASC-H (15/15 [100%] vs 43/73 [59%]). The histologic outcomes and HR-HPV prevalence associated with LSIL-H differ significantly from the established categories of TBS 2001 and provide evidence to support the recognition of LSIL-H as a distinct cytologic category.     

Patients with negative cervical biopsies after papanicolaou test interpretations of "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion": comparative longitudinal follow-up

Approximately half of women with a Papanicolaou (pap) test interpretation of “atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion” (ASC-H) will have less than a high-grade dysplasia diagnosed on their follow-up cervical biopsy sample. Herein, we compared the follow-up findings in a group of women with a negative cervical biopsy after a pap test interpretation of ASC-H (study group) with those of a randomly selected control group of women whose pap tests were interpreted as “negative for intraepithelial lesion or malignancy” during the same period. The diagnoses in every follow-up sample in the control and study groups were tabulated. Patients with previous ASC-H or high-grade squamous intraepithelial lesion interpretations, and/or high-grade cervical intraepithelial neoplasia (CIN) diagnoses, were excluded. Both groups were then statistically compared regarding the diagnostic frequencies of each of the Bethesda 2001 categories and CIN grades. Of the 122 patients with ASC-H interpretations and documented histologic follow-up, the first follow-up biopsy was negative for dysplasia in 20 (16.4%). Seventy-six follow-up samples (70 pap tests, 6 biopsies) were obtained from these 20 patients. In the control group of 262 women with pap tests interpreted as “negative for intraepithelial lesion or malignancy,” 641 follow-up samples (629 pap tests, 12 biopsies) were obtained. Patients in the study group were significantly more likely than their control group counterparts to have a follow-up (1) cytologic and/or histologic abnormality (23/76 vs 76/641, respectively; P = .00006), (2) “atypical squamous cells of undetermined significance” (ASC-US) interpretation (13/76 vs 43/641; P = .005), and (3) CIN grade 1 diagnosis (4/76 vs 10/641; P = .05). Approaching statistical significance was the comparatively increased frequency of CIN grade 2 to 3 diagnoses in the study group (2/76 vs 2/641; P = .058). If the analysis is restricted to 1 follow-up sample (the most severe) per patient, patients in the study group were still more likely than those in the control group to have a follow-up cytologic and/or histologic abnormality (12/20 vs 40/262; P = .0002), ASC-US interpretation (6/20 vs 22/262; P = .008), and follow-up CIN grade 2 to 3 diagnosis (2/20 vs 2/262; P = .03). It is concluded that patients whose cervical biopsies are devoid of dysplasia after an ASC-H interpretation still require close surveillance and follow-up because their risk of being diagnosed with follow-up cervical abnormalities is significantly above baseline.     

Long-term outcome and relative risk in women with atypical squamous cells of undetermined significance.

Few studies have compared long-term follow-up and risk for invasive cancer in women with atypical squamous cells of undetermined significance (ASCUS). We conducted a 6-year review of pathology files for 651 women in whom ASCUS had been diagnosed in 1992. Data collected included patient demographics, follow-up diagnoses, time between follow-up examinations, and procedures performed. At follow-up, high-grade squamous intraepithelial lesions (HSIL) had developed in 9.0% of the women, and invasive cancer in none. Previous cervical history did not affect risk for an HSIL. Although the average time to first follow-up was 6.18 months, in 20.9% of the women the diagnosis of HSIL was not established until after 2.0 years. For individual pathologists, the percentage of HSILs ranged from 0% to 18.8%. Thus women with ASCUS who are followed up regularly are at low risk for development of invasive cancer.     

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion. A follow-up study of conventional and liquid-based preparations in a high-risk population

We compared the histologic follow-up of 368 smears or slides with an interpretation of "atypical squamous cells, cannot rule out high-grade squamous intraepithelial lesion" (ASC-H) based on conventional and liquid-based preparations and age groups in a high-risk population. Patients with an ASC-H interpretation were 17 to 87 years old (mean, 36.8 years). The specimens were 52 liquid-based preparations and 316 conventional smears. For 218 cases (59.2%), including 28 liquid-based preparations (65%) and 190 conventional smears (58%), histologic follow-up was available. In 20 liquid-based preparations (71%) and 152 conventional smears (80.0%), cervical intraepithelial neoplasia (CIN) or higher was revealed on subsequent biopsy. Other results were as follows: liquid-based preparations, CIN1, 11 (55%); CIN2/3, 9 (45%); conventional smears, CIN1, 78 (51.3%); CIN2/3, 70 (46.1%); squamous cell carcinoma, 4 (2.6%). There was no statistically significant difference in the incidence of CIN or higher on subsequent biopsy after an interpretation of ASC-H based on preparation types. The incidences of CIN in patients 40 years old or older and patients younger than 40 years were 66% and 84%, respectively, a statistically significant difference. Because of the high incidence of clinically significant lesions noted on subsequent follow-up, patients with an interpretation of ASC-H should be observed closely and referred for colposcopic examination regardless of their age.     

Long-term follow-up of women with atypical squamous cells of undetermined significance (ASCUS)

ASCUS is the most common epithelial abnormality diagnosed in cytology laboratories in the US. Recently, the clinical importance of this diagnosis has been seriously questioned, with some investigators advocating elimination of this diagnostic category. This might be inappropriate if the ASCUS designation does define a population that is at significant risk for the development of dysplasia. Cytology and surgical pathology reports for all patients diagnosed as ASCUS in our laboratory during 1990 were reviewed. Patients with previous dysplasia or carcinoma were excluded from analysis. The pathology reports for the subsequent 9.1 yr were obtained and follow-up data collected. In 1990, 15,860 cervical cytology cases were examined in our laboratory. A diagnosis of ASCUS was made in 1,117 cases (7.0%). After excluding 345 patients with previous dysplasia or human papillomavirus-related diagnoses and 129 patients with no follow-up specimens, 643 study patients remained. Among these, the mean number of subsequent cervical smears was 4.3 (range, 1-18). Subsequent histologic material was available for 134 (20.8%) patients and the mean number of surgical specimens was 1.5 (range, 1-10). Squamous intraepithelial lesion (SIL) or dysplasia was subsequently diagnosed in 197 patients (30.6%). High-grade squamous intraepithelial lesion (HSIL) or at least moderate dysplasia was diagnosed in 64 patients (10.0%). In 21 cases (3.3%) the high-grade dysplasia developed more than 2 yr after the first ASCUS diagnosis. Follow-up disclosed no cases of invasive carcinoma. Among ASCUS patients followed for up to 9 yr, 20% develop only low-grade SIL or mild dysplasia and 10% develop HSIL or moderate or severe dysplasia. ASCUS should be retained as a diagnostic category since it identifies a significant percentage of patients who are at an increased risk for the development of cervical dysplasia.     

Reflex high-risk human papillomavirus testing for women with atypical squamous cells of undetermined significance in cytologic smears: effects since implementation in a large clinical practice

Reflex high-risk human papillomavirus (HPV) testing often is used in the management of women with atypical squamous cells of undetermined significance identified in cervicovaginal screening. Following implementation of reflex testing, our laboratory processed 8,022 specimens during a 20-month period; sufficient material was available for testing in 7,334 specimens. High-risk HPV was detected in 34.10% of these specimens. Detection rates varied with age, with positive rates as high as 58.46% in women 20 years old or younger, decreasing to 14.58% in women older than 35 years. The detection rate, categorized in 5-year age increments, showed a significant decrease until after 35 years, when the rate remained fairly constant (P < .0001). The detection rate decreased over the time of the study. These results demonstrate that high-risk HPV detection might vary according to the age mix of the population tested and the interval after implementation of testing.     

Cervical screening behavior of women with atypical squamous cells of undetermined significance (ASCUS)

Expectant follow-up based on early repeat Papanicolaou (Pap) smear(s) is the most commonly recommended management of patients with atypical squamous cells of undetermined significance (ASCUS). In a cervical cytology laboratory in northern Italy, a retrospective study of 1,087 ASCUS patients aged 25-64 was conducted. The primary aim was to assess the actual probability of early repeat Pap smear and associated factors. Univariate comparisons were based on the actuarial method. Multivariate associations were evaluated by Cox regression analysis. The cumulative probability of early repeat Pap smear was 0.11 at 6 mo, 0.29 at 12 mo, and 0.41 at 24 mo, with a multivariate association with screening sector (relative hazard, 3.0 for public offices and 2.8 for private offices vs. organized screening) and previous Pap smear history. Laboratory recommendation, patient age, place of birth, place of residence, marital status, and occupation exerted no independent effect. In conclusion, the probability of early repeat Pap smear was poor and independent of demographic and social factors. The frequency of follow-up failures emerged as a major problem with ASCUS management.     

Evaluation of p16 immunostaining to predict high‐grade cervical intraepithelial neoplasia in women with Pap results of atypical squamous cells of undetermined significance

p16 immunostaining has been examined to detect high‐grade cervical intraepithelial neoplasia grade (CIN2+) in Pap cytology specimens. However, the utility of p16 in predicting CIN2+ in Pap specimens with atypical squamous cells of undetermined significance (ASC‐US) or atypical squamous cells, cannot exclude high‐grade squamous intraepithelial neoplasm (ASC‐H), is controversial. In this study, we evaluated the utility of p16 immunostaining for predicting CIN2+ in 78 Pap specimens with ASC‐US/ASC‐H and compared the results in high‐risk HPV DNA and the follow‐up biopsies. p16 immunostaining was positive in 47% (37/78) of the Pap specimens. Of the 13 Pap specimens with follow‐up biopsy results of CIN2+, 7 (54%) were positive for p16. p16 positivity in the Pap specimens was not significantly associated with a CIN2+ biopsy result (P = 0.76). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of p16 immunostaining for predicting CIN2+ were 54%, 52%, 19%, and 85%, respectively. High‐risk HPV DNA was detected in 40% (31/78) of the Pap specimens. The sensitivity, specificity, PPV, and NPV of HPV DNA for predicting CIN2+ were 100%, 72%, 42%, and 100%, respectively. High‐risk HPV genotypes were detected in six p16‐negative specimens with follow‐up biopsy results of CIN2+. Our findings suggest that the utility of p16 immunostaining for predicting CIN2+ in Pap specimens with ASC‐US/ASC‐H is limited. Scant abnormal cells in Pap specimens with ASC‐US/ASC‐H may have contributed to the low p16 sensitivity. Diagn. Cytopathol., 2011. © 2010 Wiley‐Liss, Inc.     

Effect of Bethesda 2001 on reporting of atypical squamous cells (ASC) with special emphasis on atypical squamous cells-cannot rule out high grade (ASC-H)

We compared the overall ASC rate and the outcomes for women with different categories of ASC before and after TBS 2001 to evaluate the impact of TBS 2001. Our laboratory reported ASC in four subcategories before TBS 2001; ASC, favor reactive (ASC-R), favor low-grade squamous intraepithelial lesion (SIL) (ASC-L), undetermined significance (ASC-US), and ASC-H. Since the implementation of TBS 2001, we have been reporting ASC as ASC-US and ASC-H. After TBS 2001, our ASC rate decreased from 6.2% to 4% (P < 0.0001). Before TBS 2001, ASC-R carried the same risk as ASC-US for underlying condyloma/CIN 1. Moreover, ASC-R was rarely associated with CIN 2 or 3. Before TBS 2001, ASC-H captured more low-grade (condyloma/CIN 1) and less high-grade (CIN 2, 3, and SCC) lesions compared to after TBS 2001. More women with ASC-H after TBS 2001 underwent colposcopy (80% vs. 71%, P < 0.05). Twenty-two percent of women with ASC-H required 2-4 colposcopies to identify the high-grade lesion. Our results confirm that consistent application of TBS 2001 terminology for ASC reduces the ASC rate, and better identifies women at high risk for CIN 2, 3, and SCC. In addition, ASC-H requires very close clinical follow-up as a significant percentage of women require more than one colposcopy to identify the high-grade lesion.     

Prevalence and epidemiologic correlates of atypical squamous cells of undetermined significance in women at low risk for cervical cancer

Our aim was to determine the prevalence and epidemiologic correlates of atypical squamous cells of undetermined significance (ASCUS) in a population at low risk for cervical cancer in Porto Alegre, Brazil. Sociodemographic data and gynecological and obstetrical history from 977 women screened at an outpatient clinic were recorded. Specimens were collected for Papanicolaou cervical cytology, colposcopy, and biopsy (if indicated). Sixty-two (6.3%) patients presented ASCUS, 21 (2.1%) presented low-grade squamous intraepithelial lesions, and 6 (0.6%) presented high-grade lesions. Presence of human papillomavirus (HPV) DNA in cervical cells (odds ratio (OR) = 1.57; confidence interval (CI) 95% = 1.11-2.23), history of HPV infection (OR = 3.12; CI 95% = 1.22-7.96), and becoming sexually active at 18 yr or younger (OR = 1.70; CI 95% = 1.15-2.51) were independently associated with ASCUS. ASCUS patients reported HPV infections and presented HPV DNA in cervical cells more often than did patients with normal cytology; therefore, they should be carefully monitored to ensure early detection of cancer precursor lesions and prevention of cervical cancer.     

Interobserver variability in human papillomavirus test results in cervicovaginal cytologic specimens interpreted as atypical squamous cells

We studied interobserver variability in the proportions of human papillomavirus (HPV)-positive results for atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) diagnoses among 5 pathologists from the me laboratory during a 2-year period. These proportions were compared with individual pathologist's ASCUS/squamous intraepithelial lesion (SIL) ratios. Of 1,299 ASCUS diagnoses, 32.3% had HPV testing; 49.4% were HPV+. Positive findings by individual pathologists ranged from 38% to 67% (P = .057). There was a difference in the proportions of high risk HPV results for individual pathologists (P < .001). For the pathologist who diagnosed 38% (23/61) of samples as HPV+, the ASCUS/SIL was 0.58; the pathologist who diagnosed 67% (28/42) as HPV+ had a ratio of 1.02. Of the ASC-H diagnoses, 32.9% were tested for HPV; 63% (46/73) were positive. Although the HPV+ proportion by pathologist ranged from 54% to 83%, no significant differences were identified. Within the me laboratory, interobserver variability exists in the proportions of HPV positivity for ASCUS and ASC-H interpretations.     

The clinical significance of "squamous intraepithelial lesion of indeterminate grade" as a distinct cytologic category

The histologic and/or cytologic follow-up of 127 cases of cervical lesions termed "squamous intraepithelial lesion of indeterminate grade" (SIL) on Papanicolaou (Pap) smears by the 2001 Bethesda System was compared with 150 control cases of low-grade SIL (LSIL), high-grade SIL (HSIL), and atypical squamous cells, cannot exclude HSIL (ASC-H). A follow-up diagnosis of cervical intraepithelial neoplasia (CIN) 2 or higher was identified in 22.8% of SIL cases, which was 2.6 times higher than LSIL, 3 times lower than HSIL, and 1.5 times lower than ASC-H. A follow-up diagnosis of CIN 1 was identified in 31.5% of SIL cases, which was 2 times lower than the LSIL group, 1.5 times higher than the ASC-H cases, and 1.8 times higher than the HSIL group. We found that 22.0% of cases diagnosed as SIL were followed up by Pap smears rather than colposcopy and biopsy, compared with about 1% of LSIL and HSIL cases. Because SIL cases have a significant risk of harboring CIN 2 or greater, we recommend follow-up by colposcopy and biopsy.     

Clinical relevance of benign endometrial cells in postmenopausal women

Our objective was to determine if the finding of benign endometrial cells on a Papanicolaou (Pap) smear of a postmenopausal woman is associated with endometrial/uterine pathology, independent of symptomatology and hormone replacement therapy (HRT) status. The medical records of 146 postmenopausal patients who had a Pap smear showing normal-appearing endometrial cells between January 9, 1997 and January 12, 2000 were reviewed. Uterine pathology for each patient was determined by reviewing the results of endometrial sampling (endometrial biopsy or dilatation and curettage), hysterectomy, or pelvic sonogram, which were performed within 24 mo of the cytologic smear. The results were then correlated with clinical symptomatology and HRT status of each patient at the time the cytologic smear was obtained. Of the 146 Pap smears coded with "endometrial cells in a postmenopausal woman," 50 were excluded due to prior hysterectomy, perimenopausal status, and absence of further follow-up. Of the remaining 96 women, 27 (28%) had benign pathologic findings including polyps, leiomyomata, and simple hyperplasia without atypia, whereas 11 (12%) had significant pathologic findings including hyperplasia with atypia, adenocarcinoma, mixed Mullerian tumor, and leiomyosarcoma. Of the 11 patients with significant pathology, only one patient did not have abnormal vaginal bleeding but instead had a 30-wk-size irregular uterus on examination, and only 2 patients received hormone replacement therapy. In conclusion, Reporting endometrial cells on Pap smears in postmenopausal women did not lead to the diagnosis of any cases of significant pathology that would have gone unsuspected clinically. Moreover, HRT status did not affect the incidence of normal endometrial cells on Pap smears in postmenopausal women, nor did it aid in distinguishing which postmenopausal women had endometrial/uterine pathology. This calls into question the usefulness of the current Bethesda guideline to report "benign endometrial cells in a postmenopausal woman."