Journal

Journal of the American Society of Cytopathology

Papers (35)

Assessment of reprocessed ThinPrep cytology cases after glacial acetic acid wash procedure using the Hologic Genius Digital Diagnostics System

This study focuses on ThinPrep Pap tests with a low to borderline number of cells and the performance of AI-assisted digital systems in cases that have undergone the acetic acid wash procedure (AAW). Four hundred sixty-two cases initially interpreted as unsatisfactory and finally interpreted as satisfactory after AAW procedure were included in the study. These ThinPrep Pap slides were scanned using the Genius Digital Diagnostic System (GDDS). Overall agreement between GDDS and Original ThinPrep Interpretation (OTPI) was 63.2% for diagnostic match (Negative for Intraepithelial Lesion, ASCUS, Low Grade Squamous Intraepithelial Lesion, Atypical Squamous Cells, High Grade, Atypical Glandular Cells, or unsatisfactory), and 66.0% when ASCUS + diagnoses are grouped. Out of the 462 cases, 364 (78.8%) were called Negative for Intraepithelial Lesion based upon the manual OTPI, as opposed to 310 (67.1%) reviewed using the GDDS. There were 17.5%, 1.3%, 0.9% and 1.5% cases called Atypical Squamous Cells of Undetermined Significance, Low Grade Squamous Intraepithelial Lesion, Atypical Squamous Cells, High Grade Cannot be Excluded, and Atypical Glandular Cells respectively on OTPI, as opposed to 24.7%, 3.0%, 0.6% and 1.5% respectively by the GDDS. Only 3.0% of the cases were deemed unsatisfactory by GDDS. All the cases with high grade results in the subsequent cervical biopsy were diagnosed as at least Atypical Squamous Cells of Undetermined Significance and above by the GDDS. The diagnostic agreement between GDDS and biopsy was 65.2% compared to 58.7% for OTPI, although this is not statistically significantly different, (χ Our results demonstrate that the GDDS can be successfully used to screen ThinPrep Pap Tests that have undergone the AAW procedure.

Primary tumor types and origins in positive abdominopelvic washing cytology, a single institution experience

Abdominopelvic washing cytology is a common specimen evaluated for ovarian, fallopian tubal, and peritoneal cancer staging or other nongynecologic malignancies presented as metastases. We reviewed our experience in diagnosing abdominopelvic washing specimens and assessing the primary tumor types and origins of the positive abdominopelvic washings. A pathology archive database search was performed for abdominopelvic washing specimens from 2007 to 2018. The corresponding cytologic diagnoses, results of ancillary studies, clinical histories, and surgical follow-up were reviewed. The primary sites were determined based on the synoptic reports, when available. A total of 5.8% (350 of 6023) of cases were positive for malignancy or neoplasm. Additionally, 1.3% (78 of 6023) were diagnosed as atypical cells. Of the 350 positive cases, 93.4% were müllerian tumors. The frequency of primary sites for müllerian tumors in descending order were: ovary, uterus, fallopian tube, peritoneum, and uncertain müllerian sites. The common ovarian tumors identified in pelvic washing in descending order were: high-grade serous carcinoma, serous borderline tumor, clear cell carcinoma, low-grade serous carcinoma, and endometrioid carcinoma. Gastrointestinal, breast, bladder, and lymphoma primaries were the 23 nongynecologic tumors identified in pelvic washings. Positive findings in abdominopelvic washing cytology is rare. The majority of the positive cases were from müllerian origins, with ovary and uterus as the most common sites. Endometrial adenocarcinoma, endometrioid type and ovarian high-grade serous carcinoma were the most common tumor types. Knowing prior history of malignancy, morphologic comparison with concurrent surgical cases, and performing ancillary studies are keys to improve diagnostic accuracy of abdominopelvic washings.

Significance of atypical endometrial cells in women younger than 40 years of age

The presence of atypical endometrial cells in the Papanicolaou (Pap) test has been associated with an increased rate of endometrial malignancy, with reported rates ranging from 14% to 47%. However, most reported studies have focused on patients who were aged >40 years. The purpose of the present study was to investigate the clinical significance of identifying atypical endometrial cells in Pap test samples in women aged <40 years of age. A search of the cytology Pap test database was performed from 2000 to 2014 using the keywords "atypical endometrial cells" or "atypical glandular cells favor endometrial origin" in women aged <40 years. The available ThinPrep slides were reviewed. The patients' clinical presentation, follow-up endometrial biopsy findings, treatment, and clinical follow-up data were recorded. Endometrial carcinoma tissue sections were screened for Lynch syndrome. The database search yielded 63 study cases. Of these 63 patients, 52 had subsequently undergone endometrial biopsy. Of the 52 patients with follow-up biopsy findings available, 9 (17.3%) had premalignant (5 with atypical hyperplasia) or malignant (4 with endometrioid adenocarcinoma) lesions. In addition, 16 patients (30.8%) had other endometrial pathologic features. The 9 patients with premalignant or malignant endometrial lesions (8 white, 1 black) were overweight or obese; 3 of the patients did not have any clinical symptoms. All 4 patients with endometrioid adenocarcinoma had negative Lynch syndrome screening findings. Our results suggest that it is important to recognize the presence of atypical endometrial cells in the Pap tests from young patients, given its association with the finding of premalignant and malignant pathologic features in subsequent endometrial biopsies.

Cytomorphologic alterations, histologic correlates, and clinical importance of pap test evaluation in intrauterine device users

Cytomorphologic changes in intrauterine device (IUD) users are well described on conventional smear preparations, but studies regarding liquid-based cytology and by IUD type are limited. Therefore, this study aimed to characterize inflammatory, infectious, and epithelial alterations associated with IUDs with attention to specimen preparation method and device type. The pathology information system of a large academic hospital was queried for Papanicolaou (Pap) tests from women with IUDs. Clinical, cytologic, and histologic features were reviewed and analyzed. A total of 342 cases were identified. Squamous cell abnormalities were diagnosed in 36.8% of cases and glandular cell abnormalities in 1.8%. One adenocarcinoma presented diagnostic challenge due to IUD-related background changes. Characteristic epithelial alterations were common, including small dark cells (50.2%) and large vacuolated cells (48.9%). Background findings were dominated by acute inflammation (68%), whereas organisms were less common (Actinomyces species 15%, Candida species 9%). Pseudoactinomycotic radiate granules were common overall and differed significantly by liquid-based cytology preparation method (SurePath 57% versus ThinPrep 27%; P = 0.002). The only significant association with IUD type was a higher prevalence of bland endometrial cells observed in copper IUD users. Small dark cells and vacuolated cells were consistently observed across specimen types, highlighting their importance as characteristic IUD-related changes. Differences between preparation techniques and device types were minimal but diagnostically important. Recognition of these IUD-associated alterations and subtle variations in preparation and IUD types is essential for accurate cytologic evaluation and appropriate patient management.

The diagnostic accuracy and prognostic implication of pelvic and peritoneal fluid cytology specimens in ovarian clear cell carcinoma

Ovarian clear cell carcinoma (OCCC) is a rare subtype of ovarian epithelial carcinoma. Patients with low-stage disease have an excellent prognosis, while the prognosis for those with high-stage disease is poor. Neoplastic cells in abdominopelvic washings upstages the patient to at least FIGO 1C3. Positive cytology confers a worse prognosis when compared to similar stage patients with negative cytology. This study aims to investigate the diagnostic performance of abdominopelvic fluid cytology specimens in cases with pure OCCC and reaffirm the importance of accurate cytologic detection and its impact on patient prognosis. The laboratory information system was queried to identify all patients treated for ovarian clear cell carcinoma at our institution over a period of 20 years with a companion abdominopelvic fluid cytology specimen at the time of surgical resection. Cases were sorted by the FIGO stage of the corresponding oophorectomy specimen. Cytology results, patient demographics, fluid volume, immunohistochemical results, and follow-up data were recorded. A total of 143 cases were identified. The overall detection rate was 38%, with 54 of 143 cases positive for malignancy. Cytologic detection rates increased as FIGO stages increased. Fifty percent of stage 1C cases were upstaged on cytology alone. Ascites fluids performed better among stage 1 cases compared to pelvic wash specimens (77% detection rate versus 23%). Stage 1 patients with positive cytology trended towards a worse prognosis compared to those with negative cytology. Positive cytology in low stage cases of OCCC has significant prognostic and therapeutic implications. Our large cohort further underscores the importance of accurate cytologic detection and subsequent staging in this setting.

Human papillomavirus genotype distribution and its correlation with intraepithelial neoplasia, vaccination, and ethnicity

Cervical cancer is primarily attributed to high-risk human papillomavirus (HPV), specifically genotypes 16 and 18. The introduction of HPV vaccines aimed to reduce the incidence of cervical cancer. This study reviewed cases of High-Grade Squamous Intraepithelial Lesion (HSIL) and Atypical Squamous Cells Cannot Exclude HSIL (ASC-H) with positive high-risk HPV and HPV genotyping data. The prevalence of HPV genotypes 16/18 and non-16/18 was compared in cases with high-grade intraepithelial neoplasia (IN2+), across different ethnicities and with HPV vaccination status. A total of 274 patients (94 HSIL and 180 ASC-H) were evaluated. HPV non-16/18 was significantly more prevalent in ASC-H (68%) than in HSIL patients (50%); (P = 0.003). HPV non-16/18 was more common in cases without -IN2+ (69%), but a significant proportion of IN2+ cases were also positive for non-16/18 HPV genotypes (56%); (P = 0.04). Overall, HPV non-16/18 was more prevalent in all ethnic groups. There was a trend to a higher prevalence in non-white and vaccinated compared with white and nonvaccinated women respectively, but the difference was not significant. HPV non-16/18 genotypes are more prevalent than HPV 16/18, even in women with high-grade lesions with a greater shift towards non-16/18 genotypes in non-white and in vaccinated women. The study suggests the need for extended HPV genotyping and vaccines targeting a broader range of HPV types to include HPV non-16/18 to improve prevention, particularly in certain ethnic groups.

Acidic alterations: impact of glacial acetic acid treatment on interpretations of atypical endocervical and atypical glandular cells, not otherwise specified in Pap tests

Glacial acetic acid (GAA) is used in ThinPrep Pap tests to clear excess blood, but it may alter glandular cell appearance, particularly that of endocervical cells, potentially increasing false-positive interpretations. This may be countered by increased awareness of these cytologic alterations. We retrospectively analyzed all cervical and vaginal Pap tests from 2018 to 2022, comparing rates of "Atypical Endocervical Cells" (AEC) and "Atypical Glandular Cells, Not Otherwise Specified" (AGC) interpretations in GAA-treated and untreated Pap tests. Human papillomavirus status and histologic follow-up within 1 year were recorded for GAA-treated Pap tests. Histologic follow-up for a GAA-untreated control group was recorded. AGC and AEC interpretations were significantly more frequent in GAA-treated Pap tests compared to untreated tests (AGC, 39/7004 versus 85/258,185, respectively; AEC, 34/7004 GAA-treated Pap tests versus 417/258,185 untreated Pap tests; P < 0.0001 for both). For GAA-treated tests with AGC interpretations, age was significantly associated with a malignant histologic outcome (P < 0.001), while no such association was observed for those with AEC interpretations (P = 0.19). Malignant histologic follow-up was significantly lower in GAA-treated group with AEC interpretation compared to control group (P < 0.001), and no significant difference was seen in malignant histologic follow-up for GAA-treated and control group with AGC interpretation (P = 0.61). GAA-treated Pap tests showed significantly higher rates of AGC and AEC interpretations compared to untreated tests. Additional follow-up may be warranted for patients with GAA-treated Pap tests and AGC interpretations, particularly in older patients.

Cervical cytology in endometrial cancer patients with Lynch syndrome: opportunities for early detection and limitations

Timely detection of endometrial carcinoma in Lynch syndrome patients ensures prompt treatment and appropriate cancer screening for the patient and impacted family members. While cervical cytology is utilized primarily in cervical cancer screening, endometrial glandular abnormalities can be identified as part of routine cervical cancer screening or during work-up for abnormal uterine bleeding. We retrospectively evaluated cervical cytology samples from Lynch syndrome patients with endometrial carcinoma to determine how often atypical/malignant glandular cells were identified on prior/concurrent cytology. We identified 14 Lynch syndrome patients with cervical cytology available within a year of endometrial carcinoma diagnosis. The average patient age was 55 years (36-73). Cervical cytology preceded diagnostic biopsy in 57% and was concurrent in 43%. A glandular abnormality was identified on original diagnosis in 43% and ranged from atypical glandular cells (AGC), not otherwise specified to adenocarcinoma consistent with endometrial primary. In 4 cases, abnormal cervical cytology triggered the subsequent biopsy. Evaluation of 8 cases with accessible cytology slides revealed 2 previously unrecognized glandular abnormalities, leading to an abnormal rate of 63% among cases reviewed retrospectively and a final glandular abnormality detection rate of 57% based on either original or review diagnosis. In summary, abnormal glandular cells were commonly identified in endometrial cancer patients with Lynch syndrome and led to endometrial cancer work-up and diagnosis in a subset. These results suggest that cervical cytology may have utility in endometrial cancer screening in this population and indicate that awareness of the patient's familial cancer risk is important for maximizing sensitivity of this test. They also caution against primary human papillomavirus screening in the Lynch syndrome population, as this may result in missed opportunities for early endometrial carcinoma detection among these high-risk individuals.

The effect of carbomer versus noncarbomer lubricant on the adequacy of cervical cytology specimens

Cervical cytology remains a critical screening tool for cervical cancer. While various factors can influence cytology quality, the effect of lubricant type used during specimen collection has been previously studied with inconclusive results. This study aimed to evaluate the impact of surgical lubricant on cervical cytology results and elucidate risk factors associated with unsatisfactory results. We hypothesized that switching from a carbomer-containing lubricant to a noncarbomer, water-soluble lubricant would improve specimen adequacy in cervical cytology. A retrospective chart review was performed examining patient cytologic results from January to December 2017 at a single academic institution. After historical rates of unsatisfactory cytology were higher than acceptable standards, the practice changed lubricant formulation from a carbomer containing lubricant to a noncarbomer, water soluble lubricant. Demographic data and treatment characteristics were collected for eligible patients. Matched analysis was performed to examine factors associated with an unsatisfactory cytology result. After the change in lubricant, there was a significant decline in the rates of unsatisfactory cytology from 9.6% to 5.7%, P = 0.01. This decline was also observed when patients were matched based on menopausal status, personal history of gynecologic malignancy, pregnancy status, and cytology specimen type (10.0% to 4.8%, P = 0.001). Change in lubricant from a carbomer containing to noncarbomer, water soluble product was associated with a statistically significant decline in the rates of unsatisfactory cytology. Although prior data have had mixed results as to the etiology of unsatisfactory cytology, we feel that this directly contributed to the high rates observed at our institution.

Atypical glandular cells in Pap tests: cytology-histology correlation and risk assessment with human papillopmavirus (HPV) testing

Atypical glandular cells (AGC) represent less than 1% of Pap test cases and include a variety of lesions in both the cervix and endometrium. The study aimed to investigate the cytology-histology correlation in AGC patients and to evaluate the clinical utility of hrHPV testing in this diagnostic context. We identified 491 atypical glandular cells (AGC) cases in our quality analysis (QA) database of 336,064 Pap tests interpreted between March 1, 2013 and July 12, 2016. Of these, 251 cases had follow-up biopsies with hrHPV tests in 148 cases. The most common histologic diagnosis associated with AGC was normal/benign or low-grade lesions, comprising 55% of cervical biopsies and 24% of endometrial biopsies. High-grade lesions were identified in 21% of follow-up biopsies. In patients with AGC cytology, a positive hrHPV test significantly increased the likelihood of cervical HSIL or above lesions on biopsy by 26.4 times (OR = 26.4, 95% CI: 5.8-119.4, P < 0.0001). A positive genotyping result for HPV 16 dramatically increased the likelihood of cervical HSIL or above lesions on biopsy (OR = 84, 95% CI: 12.0-590.5, P < 0.0001). The HPV test had a negative predictive value of 97% (CI: 85%-100%). Our study confirms that AGC is a significant diagnosis with an overall risk for high-grade cervical or endometrial lesions as high as 21%. hrHPV testing with genotyping is an effective tool for identifying high-risk individuals within the AGC population, with excellent positive and negative predictive values. This approach is valuable for clinical risk stratification and differential diagnosis in patients with AGC cytology.

Colposcopic endocervical brushing cytology appears to be more sensitive than histologic endocervical curettage for detecting endocervical adenocarcinoma

Colposcopic endocervical brushing cytology (CEB) is more sensitive than endocervical curettage (ECC) for detecting squamous intraepithelial lesions. There are no data on performance of CEB for detecting endocervical adenocarcinoma. A total of 151 patients were identified in a word search for "endocervical adenocarcinoma" in surgical pathology reports from January 2007 to June 2019. To measure sensitivity, reports of CEB or ECC samples within 1 year preceding the first surgical pathology diagnosis of at least endocervical adenocarcinoma in situ (AIS+) were examined. Specificity was measured in a cohort in which at least atypical glandular cells (AGC+) was reported in CEB or ECC. Seven CEB preceding diagnosis of AIS were identified: 6 of 7 were positive or suspicious for AIS+. One of 7 was negative and it was negative on re-review. Three of 6 positive CEB cases used cell blocks with immunohistochemistry. Seventy ECC samples preceding diagnosis of AIS were identified: 40 of 70 were diagnosed as AGC+. The sensitivities of CEB and ECC for detecting AIS+ at a threshold of AGC+ are 86% and 57% (too few patients for statistics), respectively. For specificity, 12 of 18 CEB and 9 of 25 ECC reports with AGC+ were false positive by follow-up surgical pathology. The specificities of CEB and ECC are 99.4% and 99.9%, respectively. Sensitivity of CEB for detecting AIS+ (86%) is at least as high as ECC (57%). Specificity of CEB is similar to ECC. Addition of a cell block to CEB may be useful. CEB appears to be an appropriate test for follow-up of atypical glandular cells reported on Papanicolaou tests.

Negative Roche cobas HPV testing in cases of biopsy-proven invasive cervical carcinoma, compared with Hybrid Capture 2 and liquid-based cytology

The objective of this study was to conduct a retrospective analysis of results of cytology and Roche cobas (RC) and Hybrid Capture 2 (HC2) human papillomavirus (HPV) screening tests in cases of biopsy-proven invasive cervical carcinoma. The clinical data were obtained at a university hospital in New York, NY, between 2004 and 2017. Results of cytology, reported per Bethesda classification system, and HPV screening in 177 identified cases with cytology and biopsy-proven diagnosis of cervical carcinoma were included in the analysis. Two cohorts were analyzed. Of the 177 identified cases, cotesting was performed for 100 patients. Among these 100, cotesting screening results would not trigger immediate colposcopy in 6%; HPV screening results were reported as negative in 16% (16% of all RC, 16% of all HC2, 16% total) and, if HPV was the only screening modality, would not trigger a colposcopy. Of the 177 total cases, 128 patients underwent cytology screening prior to biopsy, with a cytology diagnosis that, alone, would not trigger immediate colposcopy in 14%. The HPV DNA screening and cytology screening alone were negative for 16% and 14%, respectively, of patients with biopsy-proven diagnoses of invasive carcinoma of cervical origin, without a significant difference in failure rates between cytology, HC2, and RC. The cotesting approach had a significantly lower failure rate (6%) compared with the 2 other screening modalities alone.

The interpretation of high-grade squamous intraepithelial lesion on anal cytology: a comparative analysis with the cervical Papanicolaou test

Prior studies have shown that high-grade squamous intraepithelial lesion (HSIL) tends to be underdiagnosed on anal cytology. Our study aims to decipher the interpretative challenges of HSIL that are more specific to anal cytology specimens by comparing them to cervical Papanicolaou tests. One hundred cases each of anal and cervical cytology specimens with HSIL interpretation and concordant histologic follow-up were retrieved and diagnostically confirmed. Patient demographic data were obtained from the electronic medical record. The cytologic specimens were reviewed and statistically compared in terms of proportion of HSIL cells, HSIL patterns and types, and cytoplasmic area of HSIL cells (with digital image analysis). A P value of <0.05 was considered statistically significant. Of the patients with anal HSIL, 97% were human immunodeficiency virus-positive and 60% were men who have sex with men. The anal cytology specimens significantly differed from the cervical ones in several respects: proportion of HSIL cells, cytoplasmic area of HSIL cells, cases with HSIL cells in syncytial groups (10 versus 57) and cases with keratinizing HSIL (45 versus 10). The P value was <0.0001 for all comparisons except for the proportion of HSIL cells (P = 0.001). Anal cytologic HSIL, in contrast to its cervical counterpart, exhibits fewer abnormal cells and smaller size of the diagnostic cells with a higher percentage of keratinizing lesions. A careful scrutiny of the sample with an enhanced understanding of the morphology and better sampling may help improve the detection of anal HSIL on cytology.

HPV detection rates and histopathologic follow-up of patients with HSIL cytology in a large academic women’s hospital laboratory

High risk (hr) human papillomavirus (HPV) testing has been proposed as a possible replacement for Papanicolaou (Pap) cytology for cervical screening. The aim of the present study was to assess the hrHPV detection rates using 3 available Food and Drug Administration-approved HPV assays in patients with high-grade squamous intraepithelial lesion (HSIL) cytology results and to correlate the cervical screening test results with the immediate histopathologic findings. Cases with positive HSIL ThinPrep cytology findings, concurrent hrHPV testing results, and histopathologic follow-up results obtained within 6 months of the Pap/HPV co-testing were identified from July 2010 to April 2018. A total of 943 HSIL Pap tests were identified with adjunctive hrHPV co-testing, and hrHPV was detected in 883 (93.6%) of these 943 cases. Cervical intraepithelial neoplasia ≥2 (CIN2+) lesions were diagnosed in 71.5% of patients, including 3.2% with invasive squamous cell carcinoma (SCC). In all hrHPV testing platforms, the detection rate for CIN2+ was significantly greater for the patients with positive HPV testing (72.7%) than for those with negative HPV testing (53.4%). However, CIN2+ lesions, including 3 cases of SCC, were found in 24 of 45 women (53.4%) with HSIL Pap and negative HPV testing results. The risk of CIN2+ histopathologic findings was significantly greater for patients with hrHPV-positive HSIL results. However, a subset of patients with HPV-negative HSIL results were found to have CIN2+ lesions, including SCC. The long-term effects of primary HPV screening on cervical cancer incidence, stage, and prognosis remain uncertain.

Prevalence and carcinogenic risk of high-risk human papillomavirus subtypes in different cervical cytology: a study of 124,251 cases from the largest academic center in China

We investigated the prevalence and carcinogenic risks of individual high-risk human papillomavirus (HR-HPV) in all types of cervical cytology specimens in the Shanghai population. A total of 124,251 cases with cotesting of cytology and HPV genotyping between October 2017 and February 2020 were included. The overall HPV positive rate was 24.3%, with 22.9% for HR-HPV and 6.1% for low-risk HPV. The top five most common HR-HPV subtypes were HPV 52/16/58/53/39 in the entire studied population, and HPV 16/53/56/51/39 in women with abnormal cytology. The most prevalent subtypes in negative/LSIL, HSIL, and glandular lesions were HPV 52, 16, and 18, respectively. HPV 16, 33, 26, 18, 58, and 82 were the most common subtypes significantly associated with an increased risk for HSIL + cytology. HPV 16/18 were present in 53.6% and 66.7%, and HPV 16/18/31/33/45/52/58 were identified in 90.3% and 80.1% of HSIL and squamous cell carcinoma cytology, respectively. HPV 16/18 and HPV 16/18/31/33/45/52/58 were detected in 37.0% and 44.4% of women with cytologic interpretation of in situ and invasive adenocarcinoma. This large-scale study identified the most common HPV subtypes in each cytology category, and the carcinogenic risks of individual HR-HPV in the studied Shanghai population. The results would provide valuable information for the development of next-generation HPV vaccines and cervical cancer screening programs for the Chinese population, and, more specifically, the Shanghai metropolitan population.

Utility of routine cytology in detecting asymptomatic cervical cancer recurrence

The objective of this study was to examine the utility of routine cervical cytology after cervical cancer treatment. We performed a retrospective study from 2004 to 2020, which identified 581 cervical cancer patients. Of the 581 patients, 233 were included in the analysis. The remaining 348 were excluded because of failure to enter the surveillance period, loss to follow-up, or treatment at an outside facility. The continuous data were summarized using the median and interquartile range for non-normally distributed data. The categorical data were summarized using frequencies and proportions. Comparisons between the categorical data were performed using the Fisher exact test. Of the 233 included patients, 78 (33.5%) had had ≥1 abnormal Papanicolaou (Pap) test during surveillance. Of these 78 patients, 22 (28.2%) underwent biopsy, with all biopsies negative for malignancy. Local recurrence was identified in 15 patients. Of these 15 patients, 14 (93.3%) were symptomatic at diagnosis, 7 (46.7%) had had visible disease on the physical examination, and 6 (40.0%) had normal cytology findings throughout surveillance. Only 1 case of local, asymptomatic cervical cancer recurrence was detected by Pap test alone. A subset analysis was performed to compare the rate of abnormal Pap tests between the radiation therapy and non-radiation therapy groups. Of the 233 patients, 154 (66.1%) underwent primary radiation therapy, 64 (41.6%) of whom had abnormal cytology during surveillance. Of 82 patients who did not undergo radiation therapy, only 14 (17.1%) had had abnormal cytology (P &lt; 0.01). None of the patients in either group had underlying recurrent disease at the time of abnormal cytology. The results of our study show that routine Pap tests have limited clinical utility in the surveillance of cervical cancer recurrence. Consideration should be given to removing routine cytology from the surveillance recommendations.

Performance of specific morphologic features in distinguishing low-grade squamous intraepithelial lesions from high-grade squamous intraepithelial lesions in borderline cases: a College of American Pathologists Cytopathology Committee multiobserver study

Distinguishing between low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) can be difficult on certain Papanicolaou (Pap) tests, hindering interobserver concordance. We investigated the variables influencing the interpretation of LSIL versus HSIL in Pap test slides rejected from the College of American Pathologists PAP education program. Eleven cytologists, who were unaware of the reference interpretation, examined 21 Pap slides (11 submitted as LSIL and 10 as HSIL) rejected from the PAP education program and recorded the number of LSIL cells, HSIL cells, keratinized dysplastic cells, LSIL clusters with mixed HSIL cells, atypical squamous metaplasia, atypical glandular cells, the presence of inflammation or infectious organisms, and the overall interpretation (LSIL or HSIL). We evaluated the significance of these 11 variables using a nonlinear mixed model analysis. LSIL had greater concordance (92 of 121 responses; 76.0% concordance) than HSIL (68 of 110 responses; 61.8% concordance; P < 0.001). The only predictors of misclassified cases were the number of atypical squamous metaplastic cells and the number of HSIL cells (P < 0.001). The more of these cells identified, the more likely the reviewers were to classify the slide as HSIL. The reproducibility of the diagnosis was fair (Gwet's agreement coefficient, 0.33). Interobserver reproducibility is a challenge for a subset of cases with features intermediate between LSIL and HSIL. Atypical squamous metaplasia and dysplastic nuclei with a nuclear/cytoplasmic ratio greater than one half of the cell volume (HSIL) present on a Pap test influenced the likelihood that a reviewer would interpret the case as HSIL rather than LSIL.

Endocervical adenocarcinoma in situ—from Papanicolaou test to hysterectomy: a series of 74 cases

Endocervical adenocarcinoma in situ (AIS) is not always identified on cervical Papanicolaou (Pap) test cytology because the Pap test has relatively low sensitivity for the diagnosis endocervical glandular lesions. We performed a retrospective study to determine the relative sensitivity of different diagnostic approaches, including Pap tests, cervical biopsy and/or endocervical curettage, loop electrosurgical excision procedure (LEEP), and hysterectomy specimens. Cases of endocervical AIS diagnosed from August 2005 to January 2019 were retrieved from our institution's pathology databases, and their clinicopathologic features were reviewed. A total of 74 patients with endocervical AIS with or without concurrent squamous intraepithelial lesions or cervical neoplasms were identified. Their mean age at diagnosis was 39.9 years. More than one half of the cases of AIS were not detected from screening Pap tests but were diagnosed during histologic examination of cervical biopsy or endocervical curettage, LEEP, or cone biopsy specimens (~66%). Only a few patients had had a definitive diagnosis of AIS from the Pap tests (10.8%). Other abnormal glandular cytology included atypical glandular cells, not otherwise specified (16.2%), atypical glandular cells favoring neoplasia (5.4%), and atypical glandular cells suspicious for malignancy (1.3%). Abnormal squamous cytology was common in the study population (54%), with high-grade squamous intraepithelial lesion the most common finding (30%). AIS was diagnosed in 31 of 42 cervical biopsies or curettages, with 16 cases an incidental finding and 15 cases confirming previous abnormal glandular cytology. In addition, AIS was identified in 51 of 53 LEEPs. Approximately 41.5% of those undergoing LEEP had a previous diagnosis of AIS, and 54.7% of the cases were incidental findings. More than one half of the AIS cases harbored significant concurrent cervical lesions, including 26.7% with high-grade squamous intraepithelial lesion, 5.7% with low-grade squamous intraepithelial lesion, 1.9% with invasive squamous cell carcinoma, 20.9% with invasive adenocarcinoma, and 6.7% with microinvasive adenocarcinoma. Our results have demonstrated that the ability to detect AIS with routine screening Pap testing or biopsy/curettage has variable efficacy depending on the screening methods. Given the relatively low combined sensitivity of Pap testing and biopsy/endocervical curettage in the diagnosis of AIS, all LEEPs and cervical cone biopsies performed for squamous cell abnormalities should be thoroughly evaluated for glandular lesions.

Cervical Papanicolaou tests in the female-to-male transgender population: should the adequacy criteria be revised in this population? An Institutional Experience

It is recommended that female-to-male (FTM) transgender patients with a cervix follow the same cervical cancer screening guidelines as cisgender women. This study analyzes Papanicolaou tests, HPV results, and follow-up histology in FTM patients, and compares those results to other atrophic populations at our institution. A cohort of FTM patients receiving androgen therapy was identified through our institution's translational research database. We collected data on Papanicolaou tests, human papillomavirus (HPV) results, follow-up surgical procedures, and duration of androgen therapy. ThinPrep slides were reviewed for cellularity and cytomorphology. The results of these tests were compared with those of an atrophic control group consisting of postpartum and postmenopausal cisgender women. We identified 71 FTM patients with 77 Papanicolaou tests collected over 6 years. Papanicolaou interpretations included: negative for intraepithelial lesion (69%), atypical cells of undermined significance (5%), low grade squamous intraepithelial lesion (1%), atypical glandular cells (1%), and unsatisfactory due to inadequate cellularity (23%). Five of 27 (18.5%) HPV tests were positive. Follow-up surgical specimens did not identify high-grade lesions. Unsatisfactory rates among FTM patients differed significantly from the atrophic group (P 0.05). Most FTM Papanicolaou tests reviewed showed features of atrophy. FTM patients receiving androgen have high Papanicolaou test unsatisfactory rates secondary to atrophy. Epithelial abnormality and HPV rates do not differ significantly from atrophic cisgender patients. Lowering the cellularity threshold for this population to 2000 like that of other atrophic groups should be considered.

High-risk HPV testing improves accuracy in detection of CIN2+ lesions in ASC-H postmenopausal women? An academic hospital experiences

Reflex human papilloma virus (HPV) testing with "atypical squamous cells, cannot exclude high-grade squamous lesion (ASC-H)" cytologic diagnosis is not recommended by American Society for Colposcopy and Cervical Pathology guidelines. Studies have shown human papillomavirus (HPV)-negative ASC-H patients of increased age are low risk for cervical intraepithelial neoplasia 2 or worse (CIN2+) lesions on colposcopic follow-up. We retrospectively assessed the efficacy of reflex HPV testing in postmenopausal women with ASC-H in the Los Angeles County hospitals and clinics in a 5-year period. Of a total 85 clinically postmenopausal women with ASC-H, 31 (36.5%) women were found to have CIN2+ lesions on follow-up biopsy and five of them were HPV-negative. Of the women with CIN2+ lesions and positive HPV, 13 (41.9%) were high-risk HPV (hrHPV) 16/18/45 positive and 13 (41.9%) were hrHPV-other subtype positive. Women with positive HPV had an over 3-fold increased risk of developing CIN2+ lesions (P = 0.008). Relative risk of hrHPV16/18/45 was 1.79-fold higher than that of hrHPV-other subtype. The positive predictive value and negative predictive value of hrHPV were 49.1% and 84.4%, respectively. CIN2+ detection rate in Hispanic women with positive hrHPV was higher than in non-Hispanic women (53.8% versus 35.7%). Overall, postmenopausal women with ASC-H cytology result and negative hrHPV were less likely to develop CIN2+ lesions, whereas about half of ASC-H postmenopausal women develop CIN2+ lesions if hrHPV positive, especially if hrHPV 16/18/45 positive. Therefore, triaging ASC-H postmenopausal women with cotesting or, ideally, hrHPV genotyping should be considered as optimal clinical practice to avoid overtreatment.

Cytology-histology correlation of atypical glandular cells on cervical Papanicolaou tests: A study of 628 cases

The finding of atypical glandular cells (AGC) on Papanicolaou test is becoming more important as the incidence of squamous intraepithelial lesions decreases in recent decades. Therefore, the interpretation and follow-up of patients with AGC are particularly important. The aim of our study was to assess the histologic findings and clinical correlations in patients with AGC identified on Papanicolaou test. A total of 714 patients with AGC identified on cervical Papanicolaou tests were studied for their clinicopathologic features, such as follow-up histology and patient age. We investigated the histologic follow-up results for each individual subcategories of AGC and their correlation with patients' age. Most of the glandular cell abnormalities (80.0%) in the study group were classified as "atypical glandular cells, not otherwise specified (NOS)". About 28.9% of patients' follow-up histology showed malignant or precancerous lesions. The mean age of patients with malignant or precancerous lesions was significantly higher than that of patients with benign or non-precancerous lesions. The malignant histologies included 52 cases of endometrial cancers and 31 cases of cervical carcinomas. The second most common subcategory was "atypical glandular cells, favor neoplastic" (5.0%), while "atypical endocervical cells, favor neoplastic" constituted about 2.7% of cases in our study. The average age of patients with "atypical glandular cells, favor neoplastic" was significantly higher than that of patients with "atypical endocervical cells, favor neoplastic". The follow-up histology of about 82.1% of "atypical glandular cells, favor neoplastic" showed endometrial (73.9%) or cervical malignancies (26.1%). The follow-up histology of about 70.6% of "atypical endocervical cells, favor neoplastic" showed endometrial (50.0%) or cervical cancers (50.0%). Other glandular abnormalities included 25 of 714 cases of "atypical endometrial cells" (3.5%) and 6 of 714 cases of "atypical endocervical cells" (0.8%). Based on our data, we have observed significantly more endometrial malignancies in both "atypical glandular cells, NOS" and "atypical glandular cells, favor neoplastic" subcategories and even some in "atypical endocervical cells, favor neoplastic" category. This predominance of endometrial malignancies is also associated with patients' age and tumor types.

Diagnostic performance of the hologic genius digital diagnostics system for low-grade squamous intraepithelial lesion (LSIL) ThinPrep papanicolaou tests

Advancements in digital imaging technology for Papanicolaou test slides, combined with artificial intelligence are driving the development and adoption of innovative computer-assisted screening methods for cervical cancer within the cytology community. Our study aimed to assess the performance of the Hologic Genius Digital Diagnostic System (HGDDS) in the interpretation of low-grade squamous intraepithelial lesions (LSIL) in ThinPrep Papanicolaou slides. As part of a validation study performed with 890 ThinPrep Papanicolaou slides using the HGDDS, a subset of 146 LSIL cases were included in this study. Performance characteristics for the detection of cervical intraepithelial neoplasia (CIN) and interobserver variability among 3 cytopathologists were assessed. On evaluation of the consensus results of the 3 cytopathologists, of the 146 LSIL Papanicolaou cases, 60.3% were interpreted as LSIL with the HGDDS. The remainder were interpreted as ASCUS (26%), ASC-H (10.3%), HSIL (2.7%), and NILM (0.7%). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting CIN1+ lesions in the ASCUS + category with the HGDDS were 100%, 25%, 97.9%, and 100%, respectively. The sensitivity, specificity, PPV, and NPV for the detection of CIN1+ lesions in the LSIL + category with the HGDDS were 74.7%, 75%, 99.1%, and 7.7%, respectively. Kendall's W coefficient was 0.792, indicating strong agreement among participating pathologists. Our study demonstrated that ThinPrep Papanicolaou tests with LSIL could be interpreted with strong agreement among pathologists and with good performance indicators when utilizing the HGDDS.

Long-term clinical significance of benign endometrial cells identified on routine cervical cytology in women aged more or equal to 45 years

Within the Bethesda System, the recommendation of describing benign-appearing endometrial cells (BECs) has changed over recent years. Since the 2014 revision, their presence in cervical cytology reports has been deemed essential, beginning with age 45. Recent studies have suggested rising the reporting age to 50 years. Does the presence of these cells necessitate further assessment? This retrospective cohort study included patients aged between 45 and 65 years in whom BECs were present on cervical cytology between January 2001 and December 2010, with a follow-up at 5 and 10 years. Women who had abnormal cervical cells or atypical endometrial cells on cervical cytology were excluded, as well as women with a history of cervical or endometrial cancer, or a history of hysterectomy and incomplete follow-up data. One hundred seventy-six women were included. Of these, 31% were postmenopausal of which 65% used hormonal substitution therapy. Twenty-eight percent presented with abnormal uterine bleeding at inclusion. During the follow-up period of 10 years, 87.5% had a normal gynecological follow-up and 11.4% underwent a hysterectomy for benign pathology. One percent (2 patients) had been diagnosed with endometrial malignancy, both presenting with postmenopausal bleeding and aged over 60 years. Our study confirmed that the presence of BECs is not a reason for concern when no additional clinical indicator is recognized, especially with normal ultrasonographic examination. Further invasive exploration may be controversial. If reporting BECs in cervical cytology continues, we strongly agree on rising the reporting age to 50 years or postmenopausal state.

Psammoma bodies in Papanicolaou tests and associated factors to predict an underlying malignancy: a clinicopathological analysis of 10 cases

Psammoma bodies (PBs) are rarely encountered in Papanicolaou tests. They have been described in benign and malignant conditions of the gynecologic tract and peritoneum. The aim of our study was to reveal the associated factors with PBs in Papanicolaou tests to predict an underlying malignancy, particularly in the absence of atypical glandular cells (AGCs). From 1987 to 2018, all gynecologic cytology reports with PBs were identified from the computerized pathology database of Baystate Medical Center, Springfield, Massachusetts. Patients with previous history of gynecologic and/or peritoneal malignancy were excluded. Clinical information and follow-up data were obtained from chart review. PBs were found in 10 of the 1,497,540 Papanicolaou tests (0.0006%). Six patients with age ranging from 19 to 58 years (mean age, 37.6 years) had benign outcome (eg, endometritis, ovarian serous cystadenofibroma). Four patients with age ranging from 31 to 54 years (mean age, 41.7 years) had borderline/malignant outcome (eg, ovarian borderline serous tumor, peritoneal serous psammocarcinoma). All patients with borderline/malignant outcome had family history of cancer and/or gene mutation (eg, sister with breast cancer, father with BRCA-1 mutation). PBs were accompanied by AGCs in 2 of 4 borderline/malignant cases. PBs should not be ignored in Papanicolaou tests because of their possible association with an underlying malignancy. To our knowledge, this is the first study demonstrating that relevant family history of cancer and/or gene mutation may be a helpful clue regarding an underlying malignancy, especially in the absence of accompanied AGCs with PBs.

The clinical significance of atypical glandular cells in Papanicolaou tests: changes in diagnostic patterns over 15 years at a single institution

Detection of atypical glandular cells (AGCs) by Papanicolaou (Pap) test remains a significant challenge in gynecological cytology. We compared follow-up diagnoses, age groups, and human papillomavirus (HPV) results for AGC at our institution to that of our previous study (study period 2008-2013). AGC Paps diagnosed and HPV results between January 2020 and June 2024 were obtained from the database at UPMC Magee-Womens Hospital. Of the total 188,320 Paps performed during the study period, 1025 had AGC diagnoses comprising 0.54% of the total. A total of 92.2% of cases had a companion HPV test, with positive HPV results seen in 32.9% of cases. Overall, 33.3% (286/859) of AGC cases had subsequent significant histologic findings (cervical intraepithelial neoplasia 2 and 3, adenocarcinoma in-situ, endocervical adenocarcinoma, endometrial lesions, metastatic carcinoma). Detection of cervical lesions was highest in women <30 years (50%) and significantly decreased with increasing age (P < 0.0001). Identification of endometrial lesions was highest in the ≥50-year group (P < 0.0001). Nearly half of AGC/HPV-positive cases had significant cervical findings, while these were detected in only 2.1% of AGC/HPV-negative cases (P < 0.0001). Endometrial lesions were identified in 25.7% of AGC/HPV-negative cases, but only in <1% of AGC/HPV-positive cases (P < 0.0001). Significant differences were identified comparing the 2 study periods: increased HPV testing (P < 0.0001), increased HPV-positivity (P = 0.0029), decreased AGC rate (P < 0.0001), and increased endometrial lesions on follow-up (P < 0.0001). Our findings continue to support HPV results and patient age as valuable data in triaging AGC. AGC/HPV-positive results frequently suggest a cervical/HPV-related lesion, often in younger patients. Conversely, AGC/HPV-negative results, especially in patients ≥50 years, support noncervical lesional origins.

Benchmarking high-risk human papillomavirus testing against cytology and biopsy results in the detection of cervical dysplasia to inform clinical screening guidelines

The United States Preventive Services Task Force (USPSTF) recommendation for cervical cancer screening includes the option to screen with high-risk human papilloma virus (hrHPV) alone, but some studies have reported that hrHPV testing alone missed precancerous and cancerous lesions. In this study, we evaluated the test performance characteristics of hrHPV in detecting cervical dysplasia with cervical cytology and biopsy as comparators. We conducted a retrospective analysis of Papanicolaou smears between January and December 2019 performed at our institution with concurrent hrHPV and cytology testing. Cases were identified in the laboratory information system and abstracted data included patient age, hrHPV result, concurrent cytology result, and follow-up cervical biopsy result where available. A total of 3748 cases were identified with concurrent hrHPV and cytology testing and 79 cases with concurrent hrHPV and biopsy results. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) "hrHPV for detecting dysplasia on cytology was 70% (95% CI: 60.7%-77.8%), 98% (95% CI: 97.4%-98.4%), 53% (95% CI: 46.2%-58.8%), and 99% (95% 98.7%-99.2%), respectively (P value <0.00001). The sensitivity, specificity, PPV, and NPV of hrHPV for detecting dysplasia on biopsy was 76% (95% CI: 61.1%-86.7%), 30% (95% CI: 14.7%-49.4%), 64% (95% CI: 57.0%-70.5%), and 43% (95% CI: 46.6%-61.0%), respectively (P value <0.3). hrHPV testing alone would have missed 30% of dysplastic samples identified by cytology and 24% of dysplastic samples confirmed by cervical biopsy. These findings support a comprehensive strategy of dual cervical cancer screening with cytology and hrHPV testing.

Rescreening of high-risk HPV positive Papanicolaou tests initially screened as negative is a low yield procedure in the era of HPV genotyping

Many laboratories rescreen Papanicolaou test slides initially interpreted as negative, but positive for human papillomavirus (HPV) high-risk types, as a quality control measure. We have evaluated the utility of this practice in the era of HPV genotyping as a laboratory improvement project. Between August 2016 and October 2019, we identified 3618 rescreened Papanicolaou tests with follow-up biopsies. The biopsy results were put into 3 groups: 1) Negative; 2) LSIL: HPV changes or low-grade squamous intraepithelial lesion; and 3) HSIL: high-grade squamous intraepithelial lesion or carcinoma. HPV molecular testing results with subtyping for types 16 and 18 were available for 3117 of these cases. A total of 530 of 2812 Papanicolaou tests (18.8%) with positive HPV results were reinterpreted as cytologically abnormal after rescreening; 75 (14.2%) had a biopsy result of HSIL. The subset positive for HPV types 16/18 had 38 of 133 cytology positive cases diagnosed as HSIL on biopsy vs. 107 of 935 cytology negative cases diagnosed as HSIL on biopsy (28.6% vs. 11.4%, P < 0.0001). The subset positive for "other" (non-16/18) high-risk HPV types had 37 of 397 cytology positive follow-up HSIL vs. 84 of 1288 cytology negative follow-up HSIL (9.3% vs. 6.5%, P = 0.075). Rescreening has the highest yield in specimens positive for types 16/18. However, for this group colposcopy is recommended regardless of cytology findings, reducing the patient benefit. Routine rescreening of cytology negative/HPV positive Papanicolaou tests has reduced utility when HPV subtyping is performed and should be reconsidered.

Triage options for positive high-risk HPV results from HPV-based cervical cancer screening: a review of the potential alternatives to Papanicolaou test cytology

The American Cancer Society has recommended high-risk human papillomavirus (HPV) testing as the primary screening method for cervical cancer since 2020. Up to this point, the transition from Pap test cytology-based screening or co-testing with cytology and HPV testing has been slow and limited. However, more health systems in the United States are in the process of implementing this change. The transition to HPV-based screening requires a triage strategy for positive results. Genotyping to specifically detect HPV types 16 and 18 in conjunction with reflex cytology for the remaining high-risk HPV genotypes has been the recommended method. Testing options including Dual Stain for p16/Ki-67 and extended HPV genotyping are currently being incorporated into treatment algorithms as alternatives. Methylation testing is another promising method extensively investigated around the world. This review, performed by members of the Clinical Practice Committee of the American Society of Cytopathology, examines the rationale behind the switch away from reliance on Pap test cytology in the cervical cancer screening algorithm and the opportunities and problems associated with the most promising alternative approaches. Published studies that give insight into the performance characteristics of these newer tests are reviewed. At the present time, Pap test cytology remains a viable triage option for positive HPV screening results, but alternative tests have significant appeal and should be considered in tandem with the decision to offer primary HPV screening.

Low-grade squamous intraepithelial lesion on Papanicolaou test: follow-up rates and stratification of risk for high-grade squamous intraepithelial lesion

Low-grade squamous intraepithelial lesion (LSIL) Papanicolaou test is associated with moderate risk of high-grade squamous intraepithelial lesion (HSIL) at colposcopic biopsy. High-risk human papillomavirus (hrHPV) cotesting risk stratifies patients with LSIL Papanicolaou test, with higher rates of HSIL for those hrHPV+. hrHPV genotyping is not considered in current LSIL management algorithms. We performed a 2-year retrospective review of LSIL Papanicolaou tests in patients 25 to 65 years old to assess rates of follow-up and HSIL at biopsy. Patient age, hrHPV cotest and genotype results, prior screening results, and follow-up testing for 3 years were recorded. A total of 71.5% (376 of 526) of patients had at least 1 follow-up colposcopic biopsy; 18% had HSIL on follow-up, including 20% of hrHPV+ and 12% of hrHPV-. HSIL at biopsy was most common when HPV16/18 was present (32%) and when multiple subtypes were detected (46%) versus when non-16, non-18 hrHPV alone was present (16%) or hrHPV was negative (12%). Of those hrHPV-, 5 of 22 (23%) with a prior screening abnormality had HSIL versus 1 of 27 (4%) for those without prior abnormalities. Follow-up occurred more commonly for hrHPV+ cotests (82%) than hrHPV- cotests (54%). No differences in follow-up rate based on hrHPV genotyping was seen. The highest HSIL rates were seen when HPV16/18 was present (32%). HSIL rates were similar for those hrHPV- (12%) and non-16, non-18 hrHPV+ (16%). Follow-up was more common for those hrHPV+, but genotype results did not impact follow-up rates. Past screening results may impact risk of HSIL for hrHPV- cases.

Validation of cobas 4800 HPV assay in SurePath Papanicolaou specimens for cervical cancer screening

The cobas (Roche Diagnostics, Indianapolis, IN) HPV assay was approved by the US Food and Drug Administration for human papillomavirus (HPV) testing in SurePath (Becton Dickinson, Franklin Lakes, NJ) Papanicolaou specimens for cervical cancer prevention. To validate the cobas HPV assay in SurePath specimens in our institution, we compared its accuracy and clinical efficacy to that of the Cervista (Hologic, Marlborough, MA) HPV HR assay. This study used 138 Papanicolaou (Pap) cytology specimens collected in SurePath preservative fluid at our institution in 2018. After Pap cytology testing, the residual specimens were split for testing with the cobas and Cervista assays. Polymerase chain reaction (PCR)-based HPV testing (GP5+/GP6+) was performed on specimens with discrepant results. Clinical follow-up data were reviewed. The cobas HPV and Cervista HPV HR assays showed good concordance (89.1%), with a kappa value of 0.78 (95% CI: 0.675-0.885). Fifteen specimens showed discrepant results between the 2 assays. Of 7 cases with cobas+/Cervista- results, 5 (71%) were confirmed positive by PCR. Of 8 cases with cobas-/Cervista+ results, 4 (50%) were confirmed positive by PCR. cobas HPV and Cervista HPV HR showed the same HPV-positive rate in cases of pathologically diagnosed ASC-H, LSIL, or HSIL. The sensitivities and specificities for detecting high-risk HPV of cobas HPV (93.7%, 97.3%) and Cervista HPV HR (92.1%, 94.7%) were comparable. The cobas HPV assay had false-negative results in 4 cases (5.2%) including 1 false-negative case that failed to predict CIN3. The cobas HPV assay is valid in SurePath Pap cytology specimens for cervical cancer screening but has limitations of false-negative results with clinical implications.

False-negative Papanicolaou tests in women with biopsy-proven invasive endocervical adenocarcinoma/adenocarcinoma in situ: a retrospective analysis with assessment of interobserver agreement

The objectives of our study were to identify factors contributing to false-negative Papanicolaou (Pap) tests in patients with endocervical adenocarcinoma (EA) or adenocarcinoma in situ (AIS), and to analyze the impact of educational instruction on interobserver agreement in these cases. False-negative Pap tests from patients with EA/AIS were reviewed by a consensus group and by 12 individual reviewers in 2 rounds, with an educational session on glandular neoplasia in Pap tests conducted between the 2 rounds. Of 79 Pap tests from patients with EA/AIS, 57 (72.2%) were diagnosed as abnormal and 22 (27.8%) as negative. Of the 22 false-negative cases, 10 remained negative on consensus review, with false-negative diagnoses attributed to sampling variance. The other 12 cases were upgraded to epithelial abnormalities (including 8 to glandular lesions). The false-negative diagnoses were attributed to screening variance in 2 cases and interpretive variance in 10 cases. On individual review, abnormal cells were misinterpreted as reactive glandular cells or endometrial cells in 7 of 8 and 5 of 8 cases upgraded to glandular abnormalities, respectively. With education, the proportion of individual reviewers demonstrating at least moderate agreement with the consensus diagnosis (Cohen's kappa >0.4) increased from 33% (4 of 12) to 75% (9 of 12). Sampling and interpretive variance each accounted for nearly one-half of the false-negative Pap tests, with underclassification as reactive glandular or endometrial cells the main source of the interpretive variances. Educational instruction significantly decreased the interpretive variance and interobserver variability in the diagnosis of glandular abnormalities.

Publisher

Elsevier BV

ISSN

2213-2945