Factors associated with loss to follow up after abnormal cervical cancer screening in pregnancy.

OBJECTIVE: To assess risk factors associated with loss to follow up in patients referred for colposcopy after abnormal cervical cytology during pregnancy in a Southern safety net hospital population. METHODS: An urban colposcopy center was queried for patients referred for follow up of abnormal cervical cytology during pregnancy and the postpartum period. Patients were identified through a standardized referral code in the electronic medical record. Multivariable logistic regression was used to compare patient characteristics between those who followed up for colposcopy and those lost to follow up. Independent risk factors assessed included age, parity, race, insurance, HIV status, history of mental illness, BMI, gestational age and trimester at screening, cytology at colposcopy referral, interval days until colposcopy, and biopsy histology. RESULTS: 1063 patients were identified, with 40.8% of patients who completed referred colposcopy. Patient characteristics predictive for colposcopy follow up included: maternal age at referral cervical cytology >30 years (1.67; 1.27-2.20; < 0.003), gestational age < 18 weeks at abnormal cervical cytology (1.57; 1.23-2.01; <0.0002), maternal race non-African American (2.20; 1.32-3.65; <0.0024) and with high grade cervical cytology (2.42; 1.81-3.24; <0.0001). CONCLUSION: In this population, inadequate follow up for abnormal cervical cytology during pregnancy is prominent, especially among those with younger maternal age, African American (AA) race, cervical cytology completed at later gestational ages of pregnancy, and low-grade initial cytology. Higher no-show rate among AA patients supports well-documented health disparities and need for further investigation and protocols to identify those at risk for loss to follow up.

Criminal Justice Involvement and Abnormal Cervical Cancer Screening Results Among Women in an Urban Safety Net Hospital.

OBJECTIVE: The aim of the study was to elucidate the risk factors underlying abnormal cytology-based cervical cancer screening (Pap testing) in justice-involved women (JIW) compared with non-JIW in an urban safety net hospital. METHODS: Retrospective chart review of women with a history of correctional involvement who received care at Grady Health System between 2010 and 2018 and had a Pap test was performed (n = 191). An age-matched cohort of women with no correctional involvement and had a Pap test at Grady served as the control (n = 394). Variables of interest were age, HIV, smoking, race, mental health history, and history of incarceration. Outcomes of interests were rate of abnormal Pap tests and follow-up. χ2 and logistic regression models evaluated associations between the variables of interest and outcomes. RESULTS: Rates of abnormal Pap tests were significantly higher in JIW (35.6%) than controls (18.5%, p < .0001). Compared with controls, JIW were significantly more likely to have high-grade cervical cytology (odds ratio [OR] = 3.89, p < .0005) and be lost to gynecologic follow-up (OR = 8.75, p < .0001) and a history of severe mental illness (29.5% vs 4.3%, p < .0001). Those with abnormal Pap tests were likely to be HIV-positive (OR = 20.7, p < .001) and have a history of incarceration (OR = 2.33, p < .001). Predictors of high-grade Pap test were smoking history (OR = 0.16, p = .014), HIV-positive (OR = 3.66, p = .025), and history of incarceration (OR = 3.96, p < .0005). CONCLUSIONS: Justice-involved women represent a high-risk subpopulation with significantly increased rates of high-grade cytology and lost to follow-up. This underscores the need for attention to screening programs and follow-up interventions for JIW.

Do High Rates of Atypical Glandular Cells Correlate With Higher Incidence of Disease in a Large Safety Net Hospital.

OBJECTIVE: The aim of the study was to describe the incidence and correlates of atypical glandular cell (AGC) Pap tests in a low socioeconomic status, underserved population. MATERIALS AND METHODS: Medical records of patients with AGC Pap tests at a single institution were reviewed from January 2013 to August 2019. Baseline characteristics were extracted including age, body mass index, birth control, abnormal uterine bleeding, and human papillomavirus (HPV). All colposcopy and endometrial biopsies were classified into negative/low-risk (polyps, tubular metaplasia, microglandular hyperplasia, cervical intraepithelial neoplasia 1) and high-risk (HR) lesions (cervical intraepithelial neoplasia 2/3, adenocarcinoma in situ, endometrial hyperplasia, cervical cancer, endometrial cancer). Logistic regression identified significant associations. Sixty-eight randomly selected AGC cytology slides from the cohort and 32 non-AGC slides outside the cohort were blindly reviewed by 6 pathologists. Fleiss κ interrater agreement was assessed. RESULTS: Seven hundred forty patients with AGC Pap tests were identified (0.8% of all Pap tests performed during this time). After excluding for incomplete data, 478 patients were included. Sixty-three patients had HR lesions (13.3%). Patients with HR lesions had increased odds of abnormal uterine bleeding (odds ratio = 4.32, p < .001) and HPV positivity (odds ratio = 10.89, p < .001) when compared with patients with low-risk lesions. The κ agreement was 0.21 for all cases and 0.18 for AGC alone. CONCLUSIONS: This population falls within the national averages for AGC Pap tests. There was an increased risk of HR lesions in patients with abnormal uterine bleeding and HPV positivity. The rate of HR lesions among AGC Pap tests was at the lower end of values in the literature. After blinded pathologist review, interobserver κ agreement was low for AGC Pap tests.

Determining the impact of US mammography screening guidelines on patient survival in a predominantly African American population treated in a public hospital during 2008.

BACKGROUND: In November 2009, the US Preventive Service Task Force (USPSTF) published updated breast cancer screening guidelines. This marked a change from the 2002 recommendations and a significant divergence from the American Cancer Society (ACS) guidelines. In the current study, the potential effect of using the revised 2009 USPSTF guidelines on patient disease stage and survival were evaluated and compared with those actually observed and to predicted under ACS recommendations. METHODS: A retrospective chart review was performed for 84 patients who were diagnosed with stage I through III breast cancer at Grady Memorial Hospital during 2008. Previously published tumor volume doubling times were used to model an equation that would estimate tumor sizes. For each patient, a disease stage at diagnosis was predicted, and outcomes were modeled as though the patient had been screened according to the recommended versions of the ACS and USPSTF guidelines. Patient survival rates were then estimated based on prognostic data according to disease stage. RESULTS: The average age of patients in the study was 55 years, and 85% were African American. The USPSTF guidelines predicted later stages at diagnosis (14% stage I, 73% stage II), whereas the ACS guidelines predicted earlier stages (47% stage I, 53% stage II). CONCLUSIONS: A large stage migration was predicted, indicating significantly earlier diagnosis, when the ACS-recommended screening guidelines were followed. The authors concluded that practitioners should understand how race and/or socioeconomic factors increase the risk of breast cancer and should be encouraged to prioritize discussions regarding the benefits and risks of annual mammographic screening, especially among women who have a potentially greater risk of developing breast cancer at a younger age.

Human papillomavirus 16/18/45 are not the most frequent genotypes in African American women: analysis in cervical Papanicolaou smears of women in an inner-city hospital.

INTRODUCTION: Cervical cancer is considered the most common human papillomavirus (HPV)-associated disease in women. Primary and secondary prevention methods have been established through Pap tests, HPV molecular testing, and vaccines. Although the most common high-risk HPV (HR-HPV) genotypes in the United States are 16, 18, and 45, there is reported ethnic disparity in the distribution of these genotypes. MATERIALS AND METHODS: Data analysis of HPV genotype results on cervical pap tests in our institution between late 2018 and early 2020 was performed. The distribution of HPV genotypes in each Bethesda category was evaluated. RESULTS: A total of 13,160 smears were evaluated; 75.5% were from African American women. Of those tested for HR-HPV (10,060), 1412 (14%) were HR-HPV positive. In all diagnostic categories of the Bethesda classification system, non-16/18/45 HR-HPV genotypes were more prevalent, ranging from 60.8% even in high-grade squamous intraepithelial lesion to 90.4% in negative for intraepithelial lesion or malignancy. CONCLUSIONS: In this study with a predominantly African American population, non-16/18/45 HR-HPV genotypes were prevalent in the majority (60.8%) of high-grade squamous intraepithelial lesion cases. Ethnic variability should be considered when deciding which HPV genotypes to integrate into the HPV vaccine.

Time to treatment for patients receiving BCS in a public and a private university hospital in Atlanta.

Delays in treatment for breast cancer can lead to poorer patient outcome. We analyzed time to treatment among female patients receiving breast-conserving surgery in two different hospital settings, public versus private. Retrospective chart review revealed 270 patients diagnosed during 2004-2008. Three consecutive time intervals were defined (Initial abnormal imaging [I] to core biopsy [II] to surgery /pathology staging [III] to oncology evaluation for adjuvant treatment). Multivariate analyses investigated hospital type and demographic factors. Overall median treatment time was 83 days, Interval II accounting for the longest (43 days). Only 55% of patients received the entire spectrum of care within 90 days; for each consecutive 30-day interval, percentages varied dramatically: 80.7%, 31.1%, and 68.9%.Public hospital patients experienced longer overall time to treatment than private patients (94 versus 77 days, p < 0.001); these differences persisted throughout the intervals. Longer wait times were experienced by African Americans versus Caucasians (89 versus 64 days, p = 0.003), unmarried versus married patients (93 versus 70 days, p < 0.001), and Medicaid-insured patients, p < 0.001. In multivariate analyses, hospital type, race, marital status, and insurance predicted timely treatment within one or more intervals. For patients undergoing breast-conserving therapy, time to treatment differs between private and public settings. However, barriers to timely treatment arise from both system-based issues and patient socio-demographic factors. Studies are needed to evaluate and intervene on this intricate connection.

Advancing Research on Medical Image Perception by Strengthening Multidisciplinary Collaboration.

Medical image interpretation is central to detecting, diagnosing, and staging cancer and many other disorders. At a time when medical imaging is being transformed by digital technologies and artificial intelligence, understanding the basic perceptual and cognitive processes underlying medical image interpretation is vital for increasing diagnosticians' accuracy and performance, improving patient outcomes, and reducing diagnostician burnout. Medical image perception remains substantially understudied. In September 2019, the National Cancer Institute convened a multidisciplinary panel of radiologists and pathologists together with researchers working in medical image perception and adjacent fields of cognition and perception for the "Cognition and Medical Image Perception Think Tank." The Think Tank's key objectives were to identify critical unsolved problems related to visual perception in pathology and radiology from the perspective of diagnosticians, discuss how these clinically relevant questions could be addressed through cognitive and perception research, identify barriers and solutions for transdisciplinary collaborations, define ways to elevate the profile of cognition and perception research within the medical image community, determine the greatest needs to advance medical image perception, and outline future goals and strategies to evaluate progress. The Think Tank emphasized diagnosticians' perspectives as the crucial starting point for medical image perception research, with diagnosticians describing their interpretation process and identifying perceptual and cognitive problems that arise. This article reports the deliberations of the Think Tank participants to address these objectives and highlight opportunities to expand research on medical image perception.

College of American Pathologists Cancer Protocols: From Optimizing Cancer Patient Care to Facilitating Interoperable Reporting and Downstream Data Use.

The College of American Pathologists Cancer Protocols have offered guidance to pathologists for standard cancer pathology reporting for more than 35 years. The adoption of computer readable versions of these protocols by electronic health record and laboratory information system (LIS) vendors has provided a mechanism for pathologists to report within their LIS workflow, in addition to enabling standardized structured data capture and reporting to downstream consumers of these data such as the cancer surveillance community. This paper reviews the history of the Cancer Protocols and electronic Cancer Checklists, outlines the current use of these critically important cancer case reporting tools, and examines future directions, including plans to help improve the integration of the Cancer Protocols into clinical, public health, research, and other workflows.

The effects of additional tumor cavity sampling at the time of breast-conserving surgery on final margin status, volume of resection, and pathologist workload.

INTRODUCTION: Margin status is an important prognostic factor for local recurrence after breast-conserving surgery (BCS) in patients with breast malignancy. It is unclear whether the removal of additional tumor cavity margins reduces the reoperation rate and is cosmetically acceptable. This study compares the reoperation rates, volume of breast excised in cm(3), and number of pathology slides examined in two groups of patients who underwent BCS with or without four or five additional margins (BCS + M). METHODS: We retrospectively analyzed 320 patients who underwent BCS or BCS + M for stage 0-I-II breast cancer from 2004 to 2007. We classified the margins as negative (>or=1 mm), close (<1 mm), or positive based on the distance from the tumor to the margin of resection. RESULTS: Of 320 cases analyzed, 199 (62.2%) underwent BCS and 121 (37.8%) had BCS + M. Overall, patients with BCS + M had a higher negative margins rate (85.1% vs. 57.2%, P < 0.05) and a lower reoperation rate. However, when ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) were analyzed separately, only patients with IDC showed a higher negative margin rate (91% vs. 62.1%, P < 0.001) and a lower volume of breast tissue excised (205.63 vs. 392.27, P = 0.03). There was no significant increase in pathology workload in both groups. CONCLUSIONS: Resection of four to five additional margins during BCS for early-stage invasive breast cancer results in a higher rate of negative microscopic margins, lower volume of breast excised, and subsequently, a lower reoperation rate. The advantages of this approach include improved patient satisfaction and decreased cost.

Freeing the data from cytology databases in order to improve the quality of cytology.

INTRODUCTION: To review how changes in data storage and analysis can impact quality and quality assessment in cytology. METHODS: Review of the literature. RESULTS: All quality assessment is dependent on the data available for review and the methods available for evaluation. Current laboratory information systems (LISs) incorporate both a relational or hierarchical database and built in methods to analyze current quality assessment standards. In contrast, most information systems outside of medicine are separating data storage from analysis, allowing increasingly more sophisticated forms of evaluation. CONCLUSION: There is an opportunity for improvement in cytology by improving the way data can be extracted and analyzed from the cytology LIS.

Preanalytics and Precision Pathology: Pathology Practices to Ensure Molecular Integrity of Cancer Patient Biospecimens for Precision Medicine.

Biospecimens acquired during routine medical practice are the primary sources of molecular information about patients and their diseases that underlies precision medicine and translational research. In cancer care, molecular analysis of biospecimens is especially common because it often determines treatment choices and may be used to monitor therapy in real time. However, patient specimens are collected, handled, and processed according to routine clinical procedures during which they are subjected to factors that may alter their molecular quality and composition. Such artefactual alteration may skew data from molecular analyses, render analysis data uninterpretable, or even preclude analysis altogether if the integrity of a specimen is severely compromised. As a result, patient care and safety may be affected, and medical research dependent on patient samples may be compromised. Despite these issues, there is currently no requirement to control or record preanalytical variables in clinical practice with the single exception of breast cancer tissue handled according to the guideline jointly developed by the American Society of Clinical Oncology and College of American Pathologists (CAP) and enforced through the CAP Laboratory Accreditation Program. Recognizing the importance of molecular data derived from patient specimens, the CAP Personalized Healthcare Committee established the Preanalytics for Precision Medicine Project Team to develop a basic set of evidence-based recommendations for key preanalytics for tissue and blood specimens. If used for biospecimens from patients, these preanalytical recommendations would ensure the fitness of those specimens for molecular analysis and help to assure the quality and reliability of the analysis data.

Cervical cytology specimen adequacy: patient management guidelines and optimizing specimen collection.

OBJECTIVE: To provide updated management guidelines according to cervical cytology specimen adequacy and techniques to optimize adequacy based on literature review and expert opinion. MATERIALS AND METHODS: Selected members of the American Society for Colposcopy and Cervical Pathology committee and invited experts conducted a literature review and discussed appropriate management and areas for future research emphasis. RESULTS: The guidelines recommend a repeat Pap test in a short interval of 2 to 4 months for most women when the cytology result is unsatisfactory. The preferred follow-up for women with a negative cytology result lacking an endocervical/transformation zone component or showing other quality indicators is a repeat Pap test in 12 months. Indications for an early repeat Pap test in 6 months are provided, and the influence of human papillomavirus testing results on management is discussed. Techniques for optimizing specimen adequacy are provided in detail. CONCLUSION: The specimen adequacy management guidelines will help promote uniform and optimal follow-up of patients receiving cervical cytology screening. The topics for future research emphasis will be helpful in promoting studies in needed areas.

Preoperative cytologic interpretation of noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a 1-year multi-institutional experience.

INTRODUCTION: Encapsulated follicular variant of papillary thyroid carcinoma (PTC) has an indolent behavior; hence, a change in terminology to "noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)" has been proposed. Data are scant on the fine-needle aspiration (FNA) diagnosis of nodules proven to be NIFTP upon resection. The aim was to evaluate the FNA diagnosis of nodules diagnosed as NIFTP upon resection. MATERIALS AND METHODS: The archives of 8 participating institutions were searched for thyroid resection specimens obtained in a 1-year period, and pertinent demographic and pathology data were recorded. RESULTS: 2226 thyroid surgeries were performed over the indicated time period. NIFTP was diagnosed in 6.3% of cases; 118 patients (119 nodules) with NIFTP and available preoperative thyroid FNA were included. Preoperative cytologic diagnosis were: non-diagnostic: 0.8%; benign: 5.9%; atypia of undetermined significance/follicular lesion of undetermined significance: 42.9%; follicular neoplasm/suspicious for a follicular neoplasm: 31.0%; suspicious for malignancy: 15.9%; malignant: 3.4%. Molecular data was available for 49 cases, either by Afirma or ThyGenX/ThyroSeq. Of the Afirma cases, 11% were classified as "benign", 2% as "indeterminate", and 87% as "suspicious"; of the ThyGenX/ThyroSeq cases, 50% had NRAS mutations, 20% demonstrated KRAS mutations, 20% showed HRAS mutations, and 10% showed a BRAF mutation (K601E). CONCLUSIONS: NIFTP are tumors demonstrating nuclear features similar to those seen in PTC. Our series shows that a preoperative diagnosis of "suspicious for malignancy" or "malignant" is uncommon in NIFTP, suggesting that there are sufficient cytomorphologic differences between PTC and NIFTP to allow for the suspicion of NIFTP on FNA specimens.

The Clinical Course of Patients With Prostate-Specific Antigen ≥100 ng/ml: Insight Into a Potential Population for Targeted Prostate-Specific Antigen Screening.

OBJECTIVE: To characterize men presenting to a tertiary care safety-net hospital with prostate-specific antigen (PSA) values ≥100 ng/mL and to identify a potential population for targeted PSA screening. MATERIALS AND METHODS: Retrospective review of 100 randomly selected patients of a total of 204 who presented to Grady Memorial Hospital from 2004 to 2011 with initial PSA ≥100 ng/mL was performed. Demographics, disease characteristics, and survival status were obtained via the Tumor Registry and a combination of electronic medical records and older paper charts, with missing data from paper charts excluded on analyses. RESULTS: Sixty-five patients were newly diagnosed with prostate cancer on presentation and 35 were previously diagnosed. Median PSA at presentation was 405.5 ng/mL (minimum, 100 and maximum, 7805), 81% had metastatic disease, and 94% had Gleason ≥7. Median Cancer of the Prostate Risk Assessment score was 8. Median age at presentation was 67.4 years (minimum, 40.8 and maximum, 90.6). Eighty-nine percent of patients were African American, 24% lived alone, 12% were homeless or incarcerated, 51% were insured by Medicare or Medicaid, and 47% were uninsured. Only 1% had human immunodeficiency virus, 19% had diabetes, and 13% had chronic kidney disease. Of the 65 newly diagnosed patients, only 23% had ever been screened and 9% were previously biopsied. Median time from presentation to death was 17.8 months (minimum, 0.16 and maximum, 107.1). CONCLUSION: Among men presenting with PSA ≥100 ng/ml at a safety-net hospital, the majority were African American, of lower socioeconomic status, and had metastatic disease. Uniform absence of prostate cancer screening may expose greater numbers of at-risk men to similar outcomes. Discussion is needed regarding targeted PSA screening in higher risk, vulnerable patients.

Evaluation of RNA markers for early detection of cervical neoplasia in exfoliated cervical cells.

Numerous molecular biomarkers have been suggested for early detection of cervical cancer, but their usefulness in routinely collected exfoliated cells remains uncertain. We used quantitative reverse transcription-PCR to evaluate expression of 40 candidate genes as markers for high-grade cervical intraepithelial neoplasia (CIN) in exfoliated cervical cells collected at the time of colposcopy. Samples from the 93 women with CIN3 or cancer were compared with those from 186 women without disease matched (1:2) for age, race, and high-risk human papillomavirus status. Normalized threshold cycles (C(t)) for each gene were analyzed by receiver operating characteristics to determine their diagnostic performance in a split sample validation approach. Six markers were confirmed by an area under the curve >0.6 in both sample sets: claudin 1 (0.75), minichromosome maintenance deficient 5 (0.71) and 7 (0.64), cell division cycle 6 homologue (0.71), antigen identified by monoclonal antibody Ki-67 (0.66), and SHC SH2-domain binding protein 1 (0.61). The sensitivity for individual markers was relatively low and a combination of five genes to a panel resulted in 60% sensitivity with 76% specificity, not positively increasing this performance. Although the results did not indicate superiority of RNA markers for cervical cancer screening, their performance in detecting disease in women referred for colposcopy suggests that the genes and pathways they highlight could be useful in alternative detection formats or in combination with other screening indicators.

Recent Developments in Surgical Pathology of the Uterine Corpus.

There have been several updates recently on the classification of uterine tumors. Endometrial carcinomas have traditionally been divided into 2 types, but some are difficult to classify and do not fit readily into either of the currently recognized categories. The Cancer Genome Atlas Research Network has recently defined 4 new categories of endometrial cancer on the basis of mutational spectra, copy number alteration, and microsatellite instability, which might provide independent prognostic information beyond established risk factors. The Society of Gynecologic Oncology, moreover, now recommends systematic screening of every patient with endometrial cancer for Lynch syndrome. The new definition of high-grade endometrial stromal sarcoma disregards the number of mitotic figures as a primary diagnostic criterion and instead specifies moderate atypia still resembling stromal origin but lacking the pleomorphism of undifferentiated uterine sarcoma; these tumors also harbor a JAZF1-SUZ12 gene rearrangement. Mitotic count, atypia, and coagulative necrosis are the main histologic criteria that define leiomyosarcoma. Determining the type of necrosis can be very challenging in patients receiving various treatment modalities for symptomatic fibroids before myomectomy, since key histologic features of ischemic-type necrosis are often absent. Ancillary stains including p16, p53, MIB-1, trichrome, and reticulin may be helpful in tumors harboring necrosis that is difficult to classify. Minimally invasive gynecologic surgeries have introduced histologic artifacts that complicate the diagnosis. It is essential to recognize these as procedure-related artifacts to avoid upstaging tumors and triggering unnecessary adjuvant treatment.