Impact of the more restrictive definition of atypical squamous cells introduced by the 2001 Bethesda System on the sensitivity and specificity of the Papanicolaou test: a 5-year follow-up study of Papanicolaou tests originally interpreted as ASCUS, reclassified according to Bethesda 2001 criteria

BACKGROUND: The Bethesda 2001 (B2001) classification system raised the threshold for reporting atypical squamous cells. The category of Atypical Squamous Cells of Undetermined Significance (ASCUS)-favor reactive has been eliminated with a recommendation for cytologists to judiciously downgrade those Papanicolaou (Pap) tests that would formerly have been in this category to Negative for Intraepithelial Lesion or Malignancy (NILM). The effect of this change on sensitivity and specificity of the Pap test is not yet known. METHODS: A total of 535 consecutive SurePath Pap tests interpreted as ASCUS during a period from March 1 through December 31, 2001, with follow-up polymerase chain reaction(PCR)-based human papilloma virus (HPV) testing, were independently reviewed by 3 pathologists and 1 cytotechnologist who reinterpreted these tests according to Bethesda 2001 criteria. Follow-up HPV and biopsy results were compiled for a 5-year period. RESULTS: By consensus of the 4 observers, 169 (32%) of the ASCUS cases were downgraded to NILM. These cases showed a lower rate of underlying high-risk HPV infection (11% vs 30%) and cervical intraepithelial neoplasia of grades 2 to 3 (CIN 2/3) (5% vs 10%) on follow-up than those tests that were reinterpreted as ASCUS or higher. Nine women with follow-up CIN 2/3 would have had the Pap test interpreted as NILM instead of ASCUS under Bethesda 2001 (20% of all CIN 2/3 found). Individual reviewers downgraded 29% to 42% Pap tests to NILM including those of 5 to 10 women with follow-up CIN 2/3. CONCLUSIONS: The ASCUS threshold established by B2001 prevents a sizeable subset of women from having follow-up for ASC. However, as a consequence, a few women with CIN 2/3 are downgraded to NILM. The cost savings thus achieved must be weighed against the lost opportunities to detect CIN 2/3.     

Papanicolaou test interpretations of “atypical squamous cells,cannot exclude high‐grade squamous intraepithelial lesion”

BACKGROUND.

Management guidelines for women with Papanicolaou (Pap) test interpretations of ASC‐H (atypical squamous cells, cannot exclude high‐grade squamous intraepithelial lesion) reflect substantial risk, which ranges from 10% to 68%, of a cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in their follow‐up histologic samples. The present study was initiated to determine the number of colposcopic procedures and the time frame that are typically required for a definitive diagnosis of a CIN2+ lesion after a Papanicolaou (Pap) test interpretation of ASC‐H in routine practice.

METHODS.

Clinicopathologic data on consecutive ASC‐H interpretations, 97% of which were on liquid‐based preparations, were reviewed. The number of biopsies (which was used in this context as a surrogate indicator for the number of colposcopic procedures) as well as the average duration required for a follow‐up histologic diagnosis of CIN2+ were determined.

RESULTS.

Of 500 ASC‐H interpretations, 75 were excluded for a variety of reasons and 165 lacked follow‐up in our records. The average age and follow‐up duration for the remaining 260 patients was 35.6 years and 18.5 months, respectively. CIN2+ was diagnosed in 49 (40%) of the 122 patients with at least 1 histologic follow‐up. Of these 49 patients, 72% (35 of 49) were diagnosed on the first follow‐up cervical biopsy, 14% (7 of 49) and 8% (4 of 49) were diagnosed on the second and third follow‐up biopsies, respectively; in only 6% (3 of 49) was a fourth follow‐up biopsy required. Overall, an average of 1.53 biopsies (range, 1–4) was required to attain a definitive diagnosis of CIN2+, and 28% of patients required more than 1 follow‐up biopsy. The average period between the index ASC‐H interpretations and CIN2+ diagnoses was 5.5 months. The average time to CIN2+ diagnoses by the first follow‐up biopsy was 3 months; for diagnoses made on subsequent biopsies, the average additional follow‐up duration was 8 months. Of the eventual CIN2+ diagnoses, 84% were rendered within 12 months of their associated index ASC‐H interpretations.

CONCLUSIONS.

1) A substantial subset—28%—of patients with biopsy‐proven CIN2+ after ASC‐H interpretations required more than 1 colposcopy for a definitive diagnosis of a high‐grade dysplastic lesion. 2) If a CIN2+ lesion is present, the vast majority can be diagnosed in a biopsy performed within 1 year of the ASC‐H interpretation. Cancer (Cancer Cytopathol) 2007. © Published 2007 by the American Cancer Society.     

BD focalpoint slide profiler performance with atypical glandular cells on SurePath Papanicolaou smears

BACKGROUND:

The FocalPoint Slide Profiler is an automated cervical cytology screening system that is approved for primary screening. It identifies up to 25% of slides as requiring No Further Review. However, few studies have evaluated FocalPoint performance with glandular abnormalities.

METHODS:

Sixty‐six SurePath Papanicolaou (Pap) tests with a diagnosis of atypical glandular cells were identified. A total of 172 Pap tests with a diagnosis of “endometrial cells present” were included as controls. Follow‐up histology was abnormal if diagnosed as high‐grade squamous intraepithelial lesions, adenocarcinoma in situ, carcinoma, or complex endometrial hyperplasia. The FocalPoint software ranked each case into 1 of 7 categories: quintiles 1 (high risk) through 5 (low risk), No Further Review, and Process Review.

RESULTS:

A total of 215 slides were qualified for review; 38 (57.6%) atypical glandular cells cases were abnormal on follow‐up biopsy, and 27 (71.1%) atypical glandular cells with abnormal follow‐up qualified for review; no cases were classified No Further Review, and 9 (33%) were ranked in quintile 1. Twenty‐three (82.1%) atypical glandular cells with benign follow‐up were qualified for review; 3 (11%) cases were classified No Further Review, and 4 (17%) were ranked in quintile 1. There was a statistically significant difference between the ranking of benign atypical glandular cells cases, abnormal atypical glandular cells cases, and control cases (P = .03). However, when collapsed into No Further Review versus all other quintiles, the differences were not significant (P = .20).

CONCLUSIONS:

The FocalPoint Slide Profiler did not classify glandular lesions with abnormal follow‐up in the No Further Review category. However, these cases were not preferentially ranked in quintile 1. FocalPoint‐screened slides need to be carefully reviewed for glandular abnormalities, regardless of the quintile ranking. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.     

Cytologic diagnosis of atypical squamous cells of undetermined significance in perimenopausal and postmenopausal women

BACKGROUND.

The authors have noted that in cervical cytology specimens from perimenopausal and postmenopausal women, the diagnosis of atypical squamous cells of undetermined significance (ASC‐US), as defined in the Bethesda system, is often not associated with a clinically evident lesion on follow‐up. Reflex human papillomavirus (HPV) testing provides an opportunity to distinguish cytologic features of significance from those within the spectrum of benign cellular change in this age group.

METHODS.

Liquid‐based preparations that were diagnosed as ASC‐US between January 2003 and July 2005 at Emory University Hospital were identified from the computer files. The results of HPV‐DNA testing were recorded. Two hundred four Papanicolaou tests from perimenopausal women (n = 81, 40–49 years) and postmenopausal women (n = 123, >50 years) were reviewed in a blinded fashion.

RESULTS.

HPV‐DNA results were available for 903 of 1044 patients diagnosed as ASC‐US. Overall, 323 results (35.8%) were positive, 510 results (56.6%) were negative, and 70 results (7.8%) were indeterminate. In addition, 73% of ASC‐US specimens in patients aged ≥40 years were negative for HPV DNA. The HPV‐DNA detection rate dropped from 60% in the group ages 10 to 19 years to approximately 18% in the group aged >50 years. A review of HPV‐negative cases in the group aged >40 years showed squamous cells with random nuclear enlargement and slight hyperchromasia that likely were interpreted as ASC‐US (based on the cells that were dotted by the original reviewer). Nuclear grooves were frequent in these nuclei; and cytoplasmic halos, when present, usually were perinuclear.

CONCLUSIONS.

HPV‐DNA detection in cervical cytology specimens has an inverse relation to patient age. A diagnosis of ASC‐US in perimenopausal and postmenopausal women is likely to result in a negative HPV‐DNA test in a significant proportion of patients. Enlarged nuclei with nuclear grooves and slight hyperchromasia are possibly the cause of ASC‐US overdiagnosis in this age group. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.     

Invader human papillomavirus (HPV) type 16 and 18 assays as adjuncts to HPV screening of cervical papanicolaou smears with atypical squamous cells of undetermined significance

BACKGROUND:

High‐risk (HR) human papillomavirus (HPV) testing is standard practice for triaging women who have Papanicolaou (Pap) smears with atypical squamous cells of undetermined significance (ASC‐US), however, only 5% to 17% of these women have underlying cervical intraepithelial neoplasia 2 (CIN‐2)/CIN‐3. Recent reports have demonstrated that the presence of either HPV type 16 (HPV‐16) or HPV‐18 confers an elevated risk for CIN‐2/CIN‐3. The current study was designed to determine the prevalence of HPV‐16 and HPV‐18 in ASC‐US Pap smears and to determine whether further typing would enhance the risk stratification of patients for CIN‐2/CIN‐3.

METHODS:

One hundred seventy‐eight Pap smears with ASC‐US were screened retrospectively for HR HPV by using the proprietary Invader screening assay followed by typing for HPV‐16 and HPV‐18 by using Invader type‐specific probes on 100 of the samples. Clinical follow‐up results were correlated with HPV types.

RESULTS:

Fifty‐one percent of the ASC‐US samples were positive for HR HPV, the majority of which (70%) harbored non‐HPV‐16/HPV‐18 HR HPV types; 27% were associated with HPV‐16, whereas only 3% contained HPV‐18. The screening assay indicated that 46% of women who had Pap smears with ASC‐US were in need of further HPV‐16/HPV‐18 typing. Testing for HPV‐16 stratified women with ASC‐US into 3 groups: 1) 14% of women were positive for HPV‐16 and had a high risk (54%) of CIN‐2/CIN‐3 on follow‐up biopsy, 2) 35% of women were positive for non‐HPV‐16 HPV types and had an intermediate risk (9%), and 3) 51% of women were negative for HPV and had a negligible risk for CIN‐2/CIN‐3.

CONCLUSIONS:

The combined application of a proprietary screening assay and a type‐specific HPV‐16 assay demonstrated global potential for the development of tailored management protocols for women who have Pap smears with ASC‐US. Cancer 2009. © 2009 American Cancer Society.     

Visual estimates of nucleus‐to‐nucleus ratios

BACKGROUND

Apart from several subjective criteria, ASCUS and LSIL are defined by nuclear enlargement of 2.5× to 3× and ≥3× the area of a normal intermediate squamous cell nucleus, respectively. The aim of this study was to assess the ability of observers with various degrees of experience to estimate nuclear area ratios.

METHODS.

Forty‐five participants (5 anatomic pathologists, 5 cytopathologists, 2 cytopathology fellows, 16 pathology residents, 8 cytotechnologists, 6 medical students, and 3 cytopreparatory staff members) judged the area ratios of pairs of squamous cell nuclei imaged at ×100 objective magnification. For Test 1 (T1), participants chose between 5 preset area ratios (1.0× to 1.4×, 1.5× to 1.9×, 2.0× to 2.4×, 2.5× to 2.9×, 3.0× to 3.4×) for 15 pairs of cells with ratios falling in the middle of these intervals. One week after T1, an instructional tutorial was given and T1 was repeated in different order of cell pairs as Test 2 (T2).

RESULTS.

The kappa values for all participants were 0.30 for T1 and 0.39 for T2. Accurate responses were given in 50.5% in T1 and 53.5% in T2. Both T1 and T2 responses failed to differentiate between area ratios corresponding to ASCUS and LSIL. There were no differences in accuracy according to sex, experience, or expertise in cytopathology.

CONCLUSIONS.

The overall accuracy of participants in estimating nuclear area ratios was low, especially for ratios in the range of ASCUS versus LSIL, with only minimal improvement after an instructional tutorial. Nuclear area ratio estimation may, therefore, contribute to the well‐known substantial variability in ASCUS rates and ASC/squamous intraepithelial lesion ratios. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.     

Clinical Relevance of Atypical Squamous Cells of Undetermined Significance by the 2001 Bethesda System: Experience from a Cervical Cancer High Incidence Region

The aim of this study was to evaluate the underlying lesions and factors predicting cervical intraepithelialneoplasia (CIN) 2+ in women who had “atypical squamous cells of undetermined significance” (ASC-US) oncervical cytology in the region with a high incidence of cervical cancer. This study was prospectively conductedat Chiang Mai University Hospital, Chiang Mai, Thailand. All women with ASC-US cytology undergoingcolposcopic evaluation between October 2004 and August 2008 were recruited. During the study period, 208women were enrolled. Mean age was 44.4 years. The histopathologic results at the initial evaluation were asfollows: CIN 2-3, 21 (10.1%); adenocarcinoma in situ, 3 (1.4%); cancer, 5 (2.4%); CIN 1, 26 (12.5%); and nolesions, 153 (73.6%). Multivariate analysis revealed that nulliparity (adjusted odds ratio [aOR] =4.09; 95%confidence interval [CI] = 1.04-16.10) and current oral contraceptive use (aOR=2.85; 95%CI= 1.14-7.15) wereindependent predictors for having CIN 2+ at the initial colposcopy. At the median follow-up time of 6.7 months,CIN 2-3 lesions were additionally detected in 2 women. In conclusion, ASC-US cytology in our population has arelatively high prevalence of underlying invasive carcinoma. Nulliparity and current oral contraceptive use areindependent predictors for harboring CIN 2+.     

Human papillomavirus mRNA and DNA testing in women with atypical squamous cells of undetermined significance: A prospective cohort study

In this prospective cohort study, we compared the performance of human papillomavirus (HPV) mRNA and DNA testing of women with atypical squamous cells of undetermined significance (ASC‐US) during cervical cancer screening. Using a nationwide Danish pathology register, we identified women aged 30–65 years with ASC‐US during 2005–2011 who were tested for HPV16/18/31/33/45 mRNA using PreTect HPV‐Proofer (n = 3,226) or for high‐risk HPV (hrHPV) DNA using Hybrid Capture 2 (HC2) (n = 9,405) or Linear Array HPV‐Genotyping test (LA) (n = 1,533). Women with ≥1 subsequent examination in the register (n = 13,729) were followed for up to 9.5 years for high‐grade cervical intraepithelial neoplasia (CIN) or cancer. After 3 years' follow‐up, mRNA testing had higher specificity for CIN3 or worse (CIN3+) than HC2 testing (88.1% [95% confidence interval (CI): 86.8–89.6%] versus 59.3% [95% CI: 58.1–60.4%]) and higher positive predictive value (PPV) (38.2% [95% CI: 33.8%–43.1%] versus 19.5% [95% CI: 17.8–20.9%]). However, the sensitivity of mRNA testing was lower than that of HC2 testing (66.7% [95% CI: 59.3–74.5%] versus 97.0% [95% CI: 95.5–98.4%]), and women testing mRNA negative had higher 3‐year risk for CIN3+ than those testing HC2 negative (3.2% [95% CI: 2.2–4.2%] versus 0.5% [95% CI: 0.3–0.7%]). Patterns were similar after 18 months and 5 years'; follow‐up; for CIN2+ and cancer as outcomes; across all age groups; and when comparing mRNA testing to hrHPV DNA testing using LA. In conclusion, the HPV16/18/31/33/45 mRNA test is not optimal for ASC‐US triage due to its low sensitivity and the substantial risk for precancer following a negative test.     

Evaluation of P16/Ki67 (CINtecPlus) and L1-capsid compared with HPV-genotyping in cervical cytology in women ≥35 years old focusing on patients with atypical squamous cells of undetermined significance

Cervical cancer is the third most common cancer in women worldwide. Conventional cytological examination as a screening method with Papanicolaou has been established to reduce the incidence of dysplasia and cervical cancer for years. In addition to the conventional screening, the introduction of immunocytochemical examinations, including CINtecPlus and L1-capsid, has been demonstrated to have a positive impact on screening results. In addition to morphological screening methods, human papillomavirus (HPV)-testing has also been demonstrated to possess an enormous potential in the cervical screening process. Additionally, different screening models ranging from conventional cytological screening to primary HPV-testing do exist in different countries. At the beginning of the year 2020, a combination of cytological screening and HPV-testing was introduced in Germany for women ≥35 years. The aim of the present study was to evaluate the role of morphological screening, including immunocytochemistry, and to compare it with HPV-genotyping. Immunocytochemistry was added to confirm the diagnosis but needs established infrastructure and well-trained personnel. Furthermore, there was a need to establish the HPV-screening method. In the Institute for Pathology and Cytology (Schuettorf, Leer, Germany), 146,800 samples of women (>35 years old) were examined between January 2020 and January 2021. The present study retrospectively analyzed 146,800 samples. Each sample was examined using a conventional cytological technique and HPV-high risk-Test (HPV-HR-Test) with Viper-BD. Immunocytochemistry with CINtecPlus and L1-capsid was added in some cases. A total of 555 cases were cytological diagnosed as atypical squamous cells of undetermined significance (ASC-US; IIp). After performing immunocytochemistry, 79% of cases were suspected to be positive and 1.48% of cases were definitely positive. The HPV-HR-Test was positive in 26.4% of cases. Among cases of ASC-US and HPV-HR-negativity, 33.7% were suspicious of immunocytochemical positivity and 0.5% were definitely positive. Among patients with HPV-16-negativity, 13.6% were patients with highly squamous intraepithelial lesion (HSIL) and 22.7% were patients with low-grade squamous intraepithelial lesion (LSIL) and HSIL. Among patients with HPV-18-negativity, 14.3% were patients with HSIL and 19.5% were patients with LSIL and HSIL. There were 107 cases in this group of cases with negativity of both HPV-16 and HPV-18. After performing the colposcopy and biopsy, there were 6.5% with cervical intra-epithelial neoplasia (CIN) I, 8.4% with CIN II and 5.6% with CIN III. In conclusion, there is still a need for conventional cytological examination and maybe the addition of immunocytochemistry to confirm the diagnosis and to exclude dysplasia of cervical epithelium. The HPV-HR-Test is not enough as a screening method and may be misleading.     

Clinical significance of the diagnosis of low‐grade squamous intraepithelial lesion,cannot exclude high‐grade squamous intraepithelial lesion

BACKGROUND:

The diagnosis of low‐grade squamous intraepithelial lesion (LSIL), cannot exclude high‐grade squamous intraepithelial lesion (LSIL‐H) was not included in the 2001 Bethesda System. It is used in some institutions to diagnose cases that fulfill criteria for both the diagnosis of LSIL and atypical squamous cells, cannot exclude high‐grade squamous intraepithelial lesion (ASC‐H). In this study, the authors reviewed their experience with cases reported as LSIL‐H during a 4‐year interval.

METHODS:

Clinical information and histologic follow‐up data were retrieved for Papanicolaou (Pap) tests (PTs) that were diagnosed as LSIL‐H, LSIL, ASC‐H and high‐grade squamous intraepithelial lesion (HSIL) from January 1, 2004 to December 31, 2007.

RESULTS:

Of 235,645 PTs (97% SurePath) that were processed during the study period, the laboratory diagnosed 0.52% as ASC‐H, 2% as LSIL, 0.30% as LSIL‐H, and 0.39% as HSIL. Biopsy follow‐up was available for 47%, 49%, 56.7% and 74% of these cases, respectively. Cervical intraepithelial neoplasia 2 (CIN‐2) and CIN‐3 or more severe lesions (CIN‐3+) were identified on follow‐up cervical biopsy more often in women who had diagnoses of LSIL‐H and ASC‐H (33.14% and 26.33%, respectively) than in women who had a diagnosis of LSIL (16.11%).

CONCLUSIONS:

The similarity of histologic follow‐up results between LSIL‐H and ASC‐H suggested that the management of women who have a diagnosis of LSIL‐H should be similar to the management of women who have a diagnosis of ASC‐H. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Visual inspection with acetic acid for detection of high grade lesion in atypical squamous cells and low grade squamous intraepithelial lesions from cervical Pap smear

Objective

To evaluate the value of visual inspection with acetic acid (VIA) test to detect high grade lesion in women with atypical squamous cells or low grade squamous intraepithelial lesions cervical cytology.

Methods

Women with atypical squamous cells or low grade squamous intraepithelial lesions who were scheduled to undergo colposcopy at Vajira Hospital and met inclusion criteria were included. All participants underwent VIA test prior to usual steps of colposcopy. The VIA results were interpreted as positive or negative using the criteria by the International Agency for Cancer Research. The standard colposcopic examination and appropriate investigations for cervical pathology were then continued. The diagnostic values of VIA test including sensitivity, specificity, positive predictive value, and negative predictive value were determined using high grade lesion including cervical intraepithelial neoplasia 2-3 and squamous cell carcinoma as a threshold.

Results

Total of 106 women was included. The VIA test was positive in 33 women (31.1%) and negative in 73 women (68.9%). Among the women with VIA test positive, 14 had high grade lesion (42.4%) while 19 had no significant lesions. Only 2/73 (2.7%) cases with negative VIA test had high grade lesion (both had cervical intraepithelial neoplasia 2). The sensitivity, specificity, positive predictive value and negative predictive value with 95% confidence interval were 87.5% (81.2 to 93.8%), 78.8% (71.1 to 86.7%), 42.4% (33.0 to 51.8%), and 97.2% (94.2 to 1.0%) respectively.

Conclusion

VIA as the intermediate test in atypical squamous cells and low grade squamous intraepithelial lesions cytology may reduce the necessity to refer some women for colposcopy.     

Differential Impact of Education Level,Occupation and Marital Status on Performance of the Papanicolaou Test among Women from Various Regions in Brazil

Background: In Brazil, little is known regarding the underlying causes of differences among populations regardingsocio-economic variables that affect women’s cervical cancer screening behavior. The present study focused onsocio-economic variables that affect women’s performance of the Papanicolaou test, comparing two distinct Brazilianpopulations. Methods: We collected data regarding performance of the Papanicolaou test and socio-economic variablesfrom 559 women in Mato Grosso do Sul (MS), in the Central East region, and 338 women in Paraíba (PB), in theNortheast region of Brazil. Nominal logistic regression modeling was performed to identify independent variables forboth groups of data. Results: Of the women interviewed from MS and PB, 116 out of 599 (19.37%) and 94 out of 338(27.81%), respectively, had not performed the Papanicolaou test within the last three years (p = 0.025). Low educationallevel characterized 570 (95.16%) and 203 (60.06%) of women from MS and PB, respectively (p = 0.000). Women inPB who had a low educational level and were unemployed had a 2.96-fold (OR = 0.338; 95% CI: 0.121 - 0.939) and2.40-fold (OR = 0.416; 95% CI: 0.199 - 0.869) lower chance, respectively, to have performed the Papanicolaou test ≥three times, or once within the last three years (p = 0.029; p = 0.014). The chance of women in MS who did not live ina stable relationship to have performed the test ≥ three times was 1.79-fold (OR = 0.560; 95% CI: 0.348 – 0.901) lowercompared to women who reported a stable relationship (p = 0.039). Conclusions: High educational level, employment,and having a stable interpersonal relationship positively associated with performance of the Papanicolaou test amongwomen in PB and MS. Despite having predominantly a low educational level, women in MS performed the Papanicolaoutest more frequently than those in PB.     

Implementation of the Thinprep imaging system in a tertiary military medical center

BACKGROUND:

The ThinPrep Imaging System (TIS) was implemented at Brooke Army Medical Center (BAMC) in February 2006 and has been a crucial part of the ability of the Department of Pathology and Laboratory Services ability to improve efficiency and turnaround times for Papanicolaou (Pap) test reporting. The increased detection rate of squamous abnormalities, specifically high‐grade squamous intraepithelial lesions (HSIL), has been well documented by many studies. In addition, the TIS has increased productivity for many laboratories. The objective of this study was to evaluate the effects of implementing the TIS at BAMC, a tertiary military medical center. Specifically, the following were assessed: 1) whether the detection of squamous abnormalities was increased with the TIS, 2) how the rate of high‐risk human papillomavirus (HR‐HPV) detection in atypical squamous cells (ASC) of undetermined significance (ASC‐US) cases changed (or did not change) before and after implementation of the TIS, and 3) how the TIS influenced productivity.

METHODS:

All gynecologic cytology at BAMC has been collected and processed using the ThinPrep system since 2002. Before February 2006 and before implementation of the TIS, Pap tests were screened manually by the cytotechnologists. Detection rates of squamous abnormalities were compared between the period from February 2005 to December 2005 (manual screening) and the period from February 2006 to December 2006 (image‐assisted screening). Squamous abnormalities included ASC‐US; ASC, cannot rule out HSIL (ASC‐H); low‐grade squamous intraepithelial lesion (LSIL); HSIL; glandular abnormalities; and malignancies (squamous or glandular). In addition, the rates of HR‐HPV‐positive, HR‐HPV‐negative, and HR‐HPV‐quantity not sufficient were compared for the same periods. During both periods, testing for HR‐HPV was performed only on ASC‐US Pap tests. HR‐HPV was tested with Digene Hybrid Capture 2 methodology. Productivity was calculated as the change in average slides screened per hour before and after imager implementation.

RESULTS:

In total, 107,647 Pap tests were analyzed in the 2005 (54,438 Pap tests) and 2006 (53,209 Pap tests) timeframes. Increases in the detection of ASC‐H, atypical glandular cells (AGC), LSIL, and HSIL were statistically significant. The proportion of negative for intraepithelial lesion or malignancy (NILM) and unsatisfactory cases decreased significantly with implementation of the TIS. The ASC to squamous intraepithelial lesion (ASC:SIL) ratio decreased from 1.5 to 1.0 after TIS implementation. Decreases in the ASC‐US HR‐HPV‐positive proportion and increases in the ASC‐US HR‐HPV‐negative proportion after implementation of the TIS were statistically significant. In our laboratory, a 60% increase in productivity was noted with use of the TIS.

CONCLUSIONS:

Implementation of the TIS at BAMC significantly increased the detection of ASC‐H, AGC, LSIL, and HSIL but had no significant impact on the ASC‐US detection rate. Although the ASC‐US rate did not change, both the HR‐HPV‐positive rate and the ASC:SIL ratio decreased. The data from the current study suggested that, at least initially, the use of imager‐directed screening may increase the number of clinically insignificant ASC‐US Pap tests. Cancer (Cancer Cytopathol) 2009. Published 2009 by the American Cancer Society.     

Liquid-based Papanicolaou test (SurePath) interpretations before histologic diagnosis of endometrial hyperplasias and carcinomas: study of 272 cases classified by the 2001 Bethesda system

BACKGROUND: In addition to the reporting of atypical glandular cells (AGC) and adenocarcinoma (ADCA), the 2001 Bethesda System requires the reporting of benign-appearing endometrial cells in women aged >40 years (BAEMC). In this study, the authors evaluated the contribution of each of these reporting categories to the sensitivity and specificity of a liquid-based Papanicolaou test for endometrial carcinoma or hyperplasia. METHODS: Over the 3-year study period, in the setting of a large, multihospital health care system, the authors analyzed the results from liquid-based Papanicolaou tests that were performed within the 6 months that preceded a histologic diagnosis of endometrial carcinoma or hyperplasia and that were reported according to the 2001 Bethesda System. RESULTS: Two hundred seventy-two women had a histologic diagnosis of endometrial hyperplasia (n = 199) or malignancy (n = 73) within 6 months after a Papanicolaou test. In total, 188,594 Papanicolaou tests (91,385 from women aged >40 years) were interpreted during the study period and resulted in 3810 diagnoses of BAEMC, 326 diagnoses of AGC, and 30 diagnoses of ADCA. Only 28 of 73 women (38.4%) with endometrial carcinoma had cytologically AGC or ADCA reported on a previous Papanicolaou test. The reporting of BAEMC increased this sensitivity by only 5.5% (4 additional tests) but decreased the specificity of the Papanicolaou test for endometrial malignancy from 99.8% to 96%. For endometrial hyperplasias, the sensitivity of the Papanicolaou test was even lower (39 of 198 tests; 19.7%), but BAEMC represented the majority of endometrial-type cells reported (36 of 39 tests). CONCLUSIONS: The reporting of BAEMC led to an only marginal increase in sensitivity that had to be weighed against the significant loss in specificity of the Papanicolaou test for endometrial neoplasia.     

宫颈液基细胞学中非典型腺细胞的形态结构特征与临床意义

目的:探讨宫颈液基细胞学中非典型腺细胞诊断的临床意义,评估有临床意义的细胞学形态结构特征,研究细胞学中鉴别腺上皮细胞病变与鳞状细胞病变的形态线索。方法:对我院2011年至2019年液基细胞学筛查为非典型腺细胞(atypical glandular cell, AGC)的病例复阅,通过与组织学结果对照,评估相关的细胞学特征。结果:514例AGC患者中,组织学结果阳性232例(45.1%),包括腺细胞病变114例(22.2%),鳞状上皮细胞病变104例(20.2%),腺细胞病变合并鳞状上皮细胞病变11例(2.1%),其他恶性肿瘤3例(0.6%)。评估的11个细胞学特征中,有8个特征在良性变化和癌或癌前病变之间有显著的统计学差异(P<0.05),分别为失去极性、羽毛状结构、乳头样结构、核膜不规则、出现大核仁、粗糙的染色质、中性粒细胞口袋、细胞浆内大空泡。有6个与腺上皮病变相关,前3位依次是：中性粒细胞口袋、羽毛状结构、细胞浆内大空泡;有4个与鳞状上皮病变相关,前3位分别是：核膜不规则、核深染、粗糙的染色质;羽毛状结构对于区别腺上皮病变和鳞状上皮病变最有意义。结论:AGC随访恶性率高,细...