Condyloma and Anal Dysplasia.

Anal intraepithelial neoplasia (AIN) are precancerous lesions and are sequela of human papilloma virus (HPV) infection. AIN is classified as low-grade squamous intraepithelial lesion or high-grade squamous intraepithelial lesion. Screening with anal cytology and anoscopy should be considered for high-risk populations. Diagnosis is made through high resolution anaoscopy and biopsy. Options for treatment include ablation and several topical therapies; however, recurrence rates are high for all treatment options, and an ongoing surveillance is necessary to prevent progression to anal squamous cell carcinoma. HPV vaccination is recommended to prevent disease.

Deep Learning in High-Resolution Anoscopy: Assessing the Impact of Staining and Therapeutic Manipulation on Automated Detection of Anal Cancer Precursors.

INTRODUCTION: High-resolution anoscopy (HRA) is the gold standard for detecting anal squamous cell carcinoma (ASCC) precursors. Preliminary studies on the application of artificial intelligence (AI) models to this modality have revealed promising results. However, the impact of staining techniques and anal manipulation on the effectiveness of these algorithms has not been evaluated. We aimed to develop a deep learning system for automatic differentiation of high-grade squamous intraepithelial lesion vs low-grade squamous intraepithelial lesion in HRA images in different subsets of patients (nonstained, acetic acid, lugol, and after manipulation). METHODS: A convolutional neural network was developed to detect and differentiate high-grade and low-grade anal squamous intraepithelial lesions based on 27,770 images from 103 HRA examinations performed in 88 patients. Subanalyses were performed to evaluate the algorithm's performance in subsets of images without staining, acetic acid, lugol, and after manipulation of the anal canal. The sensitivity, specificity, accuracy, positive and negative predictive values, and area under the curve were calculated. RESULTS: The convolutional neural network achieved an overall accuracy of 98.3%. The algorithm had a sensitivity and specificity of 97.4% and 99.2%, respectively. The accuracy of the algorithm for differentiating high-grade squamous intraepithelial lesion vs low-grade squamous intraepithelial lesion varied between 91.5% (postmanipulation) and 100% (lugol) for the categories at subanalysis. The area under the curve ranged between 0.95 and 1.00. DISCUSSION: The introduction of AI to HRA may provide an accurate detection and differentiation of ASCC precursors. Our algorithm showed excellent performance at different staining settings. This is extremely important because real-time AI models during HRA examinations can help guide local treatment or detect relapsing disease.

Assessing the diagnostic value of CAIX and ProEx-C in cervical squamous intraepithelial lesions.

Cervical squamous intraepithelial lesions (SILs) may present a diagnostic challenge due to their morphological similarity to benign conditions and variability in interpretation, necessitating the exploration of objective biomarkers to aid in their identification and grading. This study evaluates the immunohistochemical markers Carbonic Anhydrase IX (CAIX) and ProEx-C to assess their diagnostic potential in cervical SILs. We retrospectively identified 56 SIL cases, including 20 low-grade SILs (LSIL) and 36 high-grade SILs (HSIL), alongside a control group of nine chronic cervicitis cases. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue blocks, and the sensitivity and specificity of CAIX and ProEx-C were evaluated for detecting and grading SILs. CAIX exhibited a sensitivity of 64.3 % and a specificity of 100 % for detecting SILs. ProEx-C staining displayed a sensitivity of 66.1 % and a specificity of 100 % for detecting SILs. The combination of CAIX and ProEx-C staining increased the sensitivity for detecting SILs to 80.4 % without compromising the specificity. These markers alone or in combination were not found to be significant in distinguishing LSIL from HSIL. Both markers showed positivity in benign endocervical and squamous epithelium in high rates. In conclusion, CAIX and ProEx-C are valuable immunohistochemical markers for detecting SILs in cervical specimens, with high sensitivity and specificity. Further research is needed to elucidate their roles in cervical carcinogenesis and their relationship with HPV infection.

Effectiveness of TruScreen for detecting CIN2+ in women with ThinPrep cytologic test results indicating atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions.

Objective: To evaluate the effectiveness of TruScreen (TS) for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with abnormal ThinPrep cytologic test (TCT) results. Methods: 466 women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) were enrolled and underwent TS, colposcopy and biopsy examination. Results: Compared with the high-risk human papillomavirus (hrHPV) test for CIN2+, significantly higher specificity of TS, combined TS and hrHPV (69.6 and 75.0 vs 36.8% in ASCUS; 59.0 and 69.9 vs 30.1% in LSIL), significantly higher positive predictive value of combined TS and hrHPV were observed (32.7 vs 24.6% in ASCUS; 47.9 vs 35.6% in LSIL). Conclusion: TS combined with hrHPV showed better performance in diagnosing CIN2+ in ASCUS/LSIL.

Does the New National Cervical Screening Programme Guideline Detect Cases of High-Grade Squamous Intraepithelial Lesions That Previously Would Have Been Missed?

OBJECTIVE: The aim of this study was to determine the number of patients undergoing large loop excision of the transformation zone (LLETZ), for biopsy-confirmed high-grade squamous intraepithelial lesions (HSIL), where the original cervical screening test (CST) reported oncogenic human papillomavirus (HPV) and negative liquid-based cytology (LBC). This reflects the number of patients where a LLETZ procedure would not have occurred under the previous guideline. METHODS: Retrospective observational chart review of all patients (n = 477) who underwent LLETZ procedure in a single tertiary unit over a 36-month period. Prevalence of negative histopathology, positive margins, incidental cervical cancer, and accuracy of HSIL identification at colposcopy were measured. Diagnostic accuracy of HSIL diagnosis from initial colposcopic impression was calculated; factors influencing accuracy were evaluated using multivariable logistic regression analysis. There were no comparators. RESULTS: Of 477 LLETZs, 5.9% (n = 28) were for oncogenic HPV and normal LBC on referral CST. Demographics between the "study" (oncogenic HPV and normal LBC on referral CST) and the "standard" group were similar, except the study group was less likely to be using contraception (25% vs 47%, p = .023). In the study group, initial colposcopic cervical biopsy confirmed HSIL in 91.6% (n = 27) and low-grade squamous intraepithelial lesions in 3.6% (n = 1). Histopathological analysis of LLETZ specimens confirmed HSIL in 20 patients (71.4%) and low-grade squamous intraepithelial lesions in 2 (7.1%). No microinvasion was detected. CONCLUSIONS: The renewed National Cervical Screening Programme (NCSP), is detecting more "at risk" patients, predicted to lead to a further reduction in incidence of cervical cancer in adequately screened patients.

Construct validity and responsiveness of a health-related symptom index for persons either treated or monitored for anal high-grade squamous intraepithelial lesions (HSIL): AMC-A01/-A03.

PURPOSE: To determine whether treatment of anal high-grade squamous intraepithelial lesions (HSIL), vs active monitoring, is effective in reducing incidence of anal cancer in persons living with HIV, the US National Cancer Institute funded the Phase III ANal Cancer/HSIL Outcomes Research (ANCHOR) clinical trial. As no established patient-reported outcomes (PRO) tool exists for persons with anal HSIL, we sought to estimate the construct validity and responsiveness of the ANCHOR Health-Related Symptom Index (A-HRSI). METHODS: The construct validity phase enrolled ANCHOR participants who were within two weeks of randomization to complete A-HRSI and legacy PRO questionnaires at a single time point. The responsiveness phase enrolled a separate cohort of ANCHOR participants who were not yet randomized to complete A-HRSI at three time points: prior to randomization (T1), 14-70 (T2), and 71-112 (T3) days following randomization. RESULTS: Confirmatory factor analysis techniques established a three-factor model (i.e., physical symptoms, impact on physical functioning, impact on psychological functioning), with moderate evidence of convergent validity and strong evidence of discriminant validity in the construct validity phase (n = 303). We observed a significant moderate effect for changes in A-HRSI impact on physical functioning (standardized response mean = 0.52) and psychological symptoms (standardized response mean = 0.60) from T2 (n = 86) to T3 (n = 92), providing evidence of responsiveness. CONCLUSION: A-HRSI is a brief PRO index that captures health-related symptoms and impacts related to anal HSIL. This instrument may have broad applicability in other contexts assessing individuals with anal HSIL, which may ultimately help improve clinical care and assist providers and patients with medical decision-making.

Artificial intelligence assisted cytological detection for early esophageal squamous epithelial lesions by using low-grade squamous intraepithelial lesion as diagnostic threshold.

BACKGROUND: Manual cytological diagnosis for early esophageal squamous cell carcinoma (early ESCC) and high-grade intraepithelial neoplasia (HGIN) is unsatisfactory. Herein, we have introduced an artificial intelligence (AI)-assisted cytological diagnosis for such lesions. METHODS: Low-grade squamous intraepithelial lesion or worse was set as the diagnostic threshold for AI-assisted diagnosis. The performance of AI-assisted diagnosis was evaluated and compared to that of manual diagnosis. Feasibility in large-scale screening was also assessed. RESULTS: AI-assisted diagnosis for abnormal cells was superior to manual reading by presenting a higher efficiency for each slide (50.9 ± 0.8 s vs 236.8 ± 3.9 s, p = 1.52 × 10-76 ) and a better interobserver agreement (93.27% [95% CI, 92.76%-93.74%] vs 65.29% [95% CI, 64.35%-66.22%], p = 1.03 × 10-84 ). AI-assisted detection showed a higher diagnostic accuracy (96.89% [92.38%-98.57%] vs 72.54% [65.85%-78.35%], p = 1.42 × 10-14 ), sensitivity (99.35% [95.92%-99.97%] vs 68.39% [60.36%-75.48%], p = 7.11 × 10-15 ), and negative predictive value (NPV) (97.06% [82.95%-99.85%] vs 40.96% [30.46%-52.31%], p = 1.42 × 10-14 ). Specificity and positive predictive value (PPV) were not significantly differed. AI-assisted diagnosis demonstrated a smaller proportion of participants of interest (3.73%, [79/2117] vs.12.84% [272/2117], p = 1.59 × 10-58 ), a higher consistence between cytology and endoscopy (40.51% [32/79] vs. 12.13% [33/272], p = 1.54 × 10- 8), specificity (97.74% [96.98%-98.32%] vs 88.52% [87.05%-89.84%], p = 3.19 × 10-58 ), and PPV (40.51% [29.79%-52.15%] vs 12.13% [8.61%-16.75%], p = 1.54 × 10-8 ) in community-based screening. Sensitivity and NPV were not significantly differed. AI-assisted diagnosis as primary screening significantly reduced average cost for detecting positive cases. CONCLUSION: Our study provides a novel cytological method for detecting and screening early ESCC and HGIN.

Shared Decision-Making Concerning Anal Cancer Screening in Persons With Human Immunodeficiency Virus.

BACKGROUND: Anal high-grade squamous intraepithelial lesion (aHSIL) is the immediate precursor of anal cancer. Anal cytology is a recommended screening test to identify aHSIL among people with human immunodeficiency virus (HIV; PWH). Heterogeneity of risk for invasive anal cancer among PWH suggests the value of a shared decision-making framework regarding screening. METHODS: Using a longitudinal HIV cohort with a comprehensive anal cancer screening program, we estimated the adjusted probabilities of having aHSIL on the first anal cytology. We used logistic regression models with inverse probability weighting to account for differential screening in the cohort and to construct a predicted probability nomogram for aHSIL. Sensitivity analysis was performed to estimate aHSIL prevalence corrected for misclassification bias. RESULTS: Of 8139 PWH under care between 2007 and 2020, 4105 (49.8%) underwent at least 1 anal cytology test. First-time cytology aHSIL was present in 502 (12.2%) PWH. The adjusted probability of having aHSIL varied from 5% to 18% depending on patient characteristics. Prespecified factors in the aHSIL prediction model included nadir CD4 cell count, ethnicity, race, age, sex, gender identity, and HIV risk factors. The ability of the model to discriminate cytological aHSIL was modest, with an area under the curve of 0.63 (95% confidence interval, .60-.65). CONCLUSIONS: PWH are at increased risk for aHSIL and invasive anal cancer. Risk, however, varies by patient characteristics. Individual risk factor profiles predictive of aHSIL can be modeled and operationalized as nomograms to facilitate shared decision-making conversations concerning anal cancer screening.

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.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Neoplasia intraepitelial escamosa cervical de alto grau: abordagem ambulatorial / High-grade cervical intraepithelial neoplasia: outpatient approach

As neoplasias intraepiteliais cervicais correspondem a alterações identificadas por rastreamento citológico cervical e estudo histológico, pós-biópsia incisional guiada por colposcopia ou procedimento diagnóstico excisional. Podem ser tratadas com abordagens conservadoras e procedimentos excisionais. A vacinação anti-HPV e o tratamento excisional oportuno constituem, respectivamente, prevenção primária e secundária contra o câncer do colo uterino.(AU)

Cervical intraephitelial neoplasms correspond to changes identified by cervical citological screening and histological study, post-incisional biopsy guided by colposcopy or excisional diagnostic procedure. They can be treated with conservative approaches and excision procedures. Anti-HPV vaccination and timely excional treatment are primary and secondary prevention against cervical cancer, respectively.(AU)

Concordância Interobservador no Diagnóstico Citológico de Atipia Escamosa de Significado Indeterminado Favorecendo Lesão de Alto Grau e de Lesão / Intraepitelial Escamosa de Alto Grau nas Lesões do Colo Uterino Interobserver Agreement in Cytological Diagnosis of Atypical Squamous Cell, Cannot Exclude a High-Grade Lesion and High-Grade Squamous Intraepithelial Lesion in Cervical Lesions / Concordancia Interobservador en el Diagnóstico Citológico de Atipia Escamosa de Significado Indeterminado Favoreciendo Lesión de Alto Grado y Lesión Intraepitelial Escamosa de Alto Grado en Lesiones del Cuello Uterino

Introdução: O exame de Papanicolau é uma importante ferramenta na triagem do carcinoma do colo uterino. O diagnóstico citológico de atipias celulares escamosas de significado indeterminado favorecendo lesão de alto grau (ASC-H) é a categoria de menor concordância interobservador. Objetivo: Avaliar o grau de concordância interobservador para os diagnósticos de ASC-H e de lesões intraepiteliais escamosas de alto grau (LIEAG) em um hospital terciário e avaliar a capacidade do diagnóstico de ASC-H para predizer lesões de maior grau. Método: Foram coletadas lâminas de pacientes atendidas entre 2007 e 2015 no Serviço de Anatomia Patológica do hospital, com diagnósticos originais de ASC-H ou LIEAG realizados pelo mesmo patologista, colposcopia e biópsia, quando indicadas, pelo mesmo ginecologista. Essas citologias foram posteriormente revisadas por outros dois patologistas separadamente e às cegas. Ambos tiveram acesso a dados sobre idade no momento do diagnóstico para reproduzir o diagnóstico da prática clínica. Resultados: Houve 65,1% de lâminas listadas com ASC-H e 34,9% com LIEAG. As duas revisões concordaram concomitantemente com o diagnóstico original em 54,7%. Os índices kappa para os dois diagnósticos e somente para ASC-H foram, respectivamente, 0,46 e 0,49 (concordâncias moderadas). Das lâminas originalmente interpretadas como ASC-H, 68,3% resultaram em lesões de maior grau na histologia. Conclusão: Os dados mostraram uma concordância moderada entre os patologistas para o diagnóstico de ASC-H. É importante destacar que o diagnóstico de ASC-H correspondeu à lesão de maior grau de malignidade na histologia, demonstrando que essas lesões devem ser seguidas clinicamente como LIEAG

Introduction: The Papanicolaou test is an important screening exam for cervical carcinoma. The cytological diagnosis of undetermined atypical squamous cells favoring high-grade lesion (ASC-H) is the category with the least interobserver concurrence. Objective: Evaluate the interobserver concurrence for the ASC-H and high-grade squamous intraepithelial lesions (HSIL) categories at a teaching hospital and to estimate ASC-H's capacity to predict higher grade lesions. Method: Smears from patients admitted from 2007 to 2015 whose original diagnosis was made by one pathologist, in addition to colposcopy and biopsy, when indicated, made by one gynecologist were collected in the Pathologic Anatomy Service of the hospital. The cytology was reviewed by two other pathologists separately and blindly. Both reviewers had access to data about age at the moment of the diagnosis in order to reproduce the clinical diagnosis. Results: There were 65.1% smears considered as ASC-H and 34.9%, as HSIL. The reviews concurred simultaneously with the original diagnosis in 54.7% of the cases. The kappa indexes for both categories and only for ASC-H were, respectively, 0.46 and 0.49 (moderate concurrence). 68.3% of the smears primarily described as ASC-H resulted in higher grade lesions in histology. Conclusion: The data showed a moderate concurrence between the pathologists for the ASC-H's diagnosis. It is important to highlight that ASC-H matched with higher grade lesions at the histology, needing follow-up as HSIL

Introducción: La prueba de Papanicolaou es un importante examen de detección del carcinoma del cuello uterino. El diagnostico citológico de las células escamosas atípicas, no se descarta una lesión de grado alto (ASC-H) es la categoría de menor acuerdo interobservador. Objetivo: Los objetivos de este estudio fueron evaluar el grado de concordancia interobservador para los diagnósticos de atipias escamosas de significado indeterminado favoreciendo lesión de alto grado (ASC-H) y de lesiones intraepiteliales escamosas de alto grado (LIEAG) en un hospital terciario de Curitiba (PR) y evaluar la capacidad del diagnóstico de ASC-H de predecir las lesiones de mayor grado. Método: Se recogieron del Servicio de Anatomía Patológica del hospital las láminas de pacientes atendidas entre 2007 y 2015, con diagnósticos originales de ASC-H o LIEAG realizados por el mismo patólogo y colposcopia y biopsia, cuando indicadas, por el mismo ginecólogo. Esas citologías fueron revisadas después por otros dos patólogos separadamente y a ciegas. Ambos tuvieron acceso a datos sobre edad en el momento del diagnóstico para reproducir el diagnóstico de la práctica clínica. Resultados: Hubo el 65,1% de las láminas señaladas con ASC-H y el 34,9%, con LIEAG. Las revisiones concordaron concomitantemente con el diagnóstico original en el 54,7%. Los índices kappa para los dos diagnósticos y solamente para ASC-H fueron, respectivamente, 0,46 y 0,49 (concordancias moderadas). De las láminas originalmente interpretadas como ASC-H, 68,3% resultaron en lesiones de mayor grado en la histología. Conclusión: Hubo una concordancia moderada entre los patólogos para la categoría ASC-H. Se destaca también la correspondencia de ASC-H con lesiones de mayor grado en la histología, lo que dirige su seguimiento clínico como LIEAG

Artificial intelligence-assisted fast screening cervical high grade squamous intraepithelial lesion and squamous cell carcinoma diagnosis and treatment planning.

Every year cervical cancer affects more than 300,000 people, and on average one woman is diagnosed with cervical cancer every minute. Early diagnosis and classification of cervical lesions greatly boosts up the chance of successful treatments of patients, and automated diagnosis and classification of cervical lesions from Papanicolaou (Pap) smear images have become highly demanded. To the authors' best knowledge, this is the first study of fully automated cervical lesions analysis on whole slide images (WSIs) of conventional Pap smear samples. The presented deep learning-based cervical lesions diagnosis system is demonstrated to be able to detect high grade squamous intraepithelial lesions (HSILs) or higher (squamous cell carcinoma; SQCC), which usually immediately indicate patients must be referred to colposcopy, but also to rapidly process WSIs in seconds for practical clinical usage. We evaluate this framework at scale on a dataset of 143 whole slide images, and the proposed method achieves a high precision 0.93, recall 0.90, F-measure 0.88, and Jaccard index 0.84, showing that the proposed system is capable of segmenting HSILs or higher (SQCC) with high precision and reaches sensitivity comparable to the referenced standard produced by pathologists. Based on Fisher's Least Significant Difference (LSD) test (P < 0.0001), the proposed method performs significantly better than the two state-of-the-art benchmark methods (U-Net and SegNet) in precision, F-Measure, Jaccard index. For the run time analysis, the proposed method takes only 210 seconds to process a WSI and is 20 times faster than U-Net and 19 times faster than SegNet, respectively. In summary, the proposed method is demonstrated to be able to both detect HSILs or higher (SQCC), which indicate patients for further treatments, including colposcopy and surgery to remove the lesion, and rapidly processing WSIs in seconds for practical clinical usages.

Prevalence and correlates of cervical squamous intraepithelial lesions among HIV-infected and uninfected women in Central Kenya.

INTRODUCTION: cervical intraepithelial neoplasia the precursor of cervical cancer occurs with increased frequency in women infected with human immunodeficiency virus (HIV). This study aimed at determining the prevalence and correlates of abnormal cervical cytology among HIV-infected women and compare to the uninfected women. METHODS: a cross-sectional study conducted among HIV-infected and uninfected women enrolled in a HIV study in Central Kenya. All women had baseline Pap smear examination assessed using Bethesda system. Bivariate and multivariate logistic regression methods were employed to assess the correlates of cervical squamous epithelial lesions (CSIL). RESULTS: a total 480 women had an acceptable baseline smear, 373 (78%) were HIV-infected. Median age was 30.2 years [IQR 25.4-35.5]. Overall prevalence of CSIL was 37% (176/480) with the prevalence of low grade squamous intraepithelial lesion (LSIL), atypical squamous cells undetermined significance (ASCUS), high grade squamous intraepithelial lesions (HSIL) and atypical glandular cells (AGC) were 17%, 14%, 4% and 2% respectively. HIV-infected women had a higher prevalence of CSIL at 42% as compared to HIV-uninfected women at 19%. HIV infection was the predictor associated with development of CSIL at multivariate analysis and specifically, HIV-infected women were 3 times (AOR 3.1, 95% CI: 1.8 - 5.4, p<0.005) more likely to have CSIL than HIV-uninfected women. The age 35 - 44 years was protective to developing CSIL (AOR 0.45, 95% CI: 0.24 - 0.87, p=0.018). CONCLUSION: cervical squamous epithelial lesions is a major problem among Kenyan women. HIV infection confers a higher risk to development of CSIL. Cervical cancer screening should be an established practice in HIV programs.

Xpert HPV as a Screening Tool for Anal Histologic High-Grade Squamous Intraepithelial Lesions in Women Living With HIV.

BACKGROUND: Women living with HIV (WLWH) experience high rates of anal cancer. Screening using anal cytology, high-resolution anoscopy (HRA) with biopsies, can histologically diagnose anal cancer precursors called high-grade squamous intraepithelial lesions (HSIL). The low specificity of screening using anal cytology results in HRA referral for many WLWH without HSIL. Screening using high-risk human papillomavirus (HR-HPV) may improve specificity. METHODS: Two hundred seven WLWH (63% non-Hispanic black) were screened for anal histologic HSIL (hHSIL) using cytology, HRA-guided biopsies, and Xpert HPV. Xpert performance for predicting anal hHSIL was compared with that of cytology. Usng Xpert 5 HPV genotypic results and accompanying cycle thresholds, receiver operator characteristic curve and recursive partitioning analyses were used to create predictive models for hHSIL. RESULTS: The performance of Xpert to predict hHSIL was not different from that of cytology with a sensitivity (Sn) of 89% and specificity (Sp) of 49%. Interpretation of Xpert was modified using genotypic results and receiver operator characteristic curve analysis, which produced a screen with an Sn and Sp of 75% and 84% for hHSIL, respectively. Another reinterpretation of Xpert was created using recursive partitioning and cycle thresholds, which predicted hHSIL with an Sn and Sp of 75% and 86%, respectively. The detection of HPV-16 was highly predictive of hHSIL in all analyses. These modified screening tests would reduce HRA referral in this population by almost half compared with anal cytology. CONCLUSIONS: Xpert HPV is an alternative to anal cytology to screen for anal HSIL and can be optimized to reduce the number of unnecessary HRAs performed in WLWH.

Comparison of two sample collection devices for anal cytology in HIV-positive men who have sex with men: Cytology brush and Dacron swab.

OBJECTIVE: HIV-positive men who have sex with men (MSM) are a vulnerable group for anal cancer (AC), a cancer with a well-described precursor lesion, which can be detected early in screening programs using anal liquid-based cytology (aLBC). We aim to compare two aLBC sample collection devices: cytology brush (CB) and Dacron swab (DS). METHODS: Retrospective analysis of two consecutive study periods, the first using CB and the second DS. Participants underwent an aLBC, a human papillomavirus (HPV) DNA test and a high-resolution anoscopy (HRA), and a biopsy was performed for suspicious lesions. The sensitivity and specificity of aLBC, area under the receiver operating characteristic (ROC) curve (AUC), and concordance between cytology and HRA were assessed using Cohen's kappa coefficient. RESULTS: A total of 239 participants were enrolled (CB group, 120; DS group, 119). aLBC was benign in 46% of samples, and high-grade squamous intraepithelial lesion (HSIL) was detected in 11.7%. Prevalence of biopsy-proven HSIL was 15.3%. No differences in cytological and histological results were observed between the groups. aLBC-HRA concordance was weak for benign results (CB group, k = 0.309; DS group, k = 0.350) as well as for HSIL (k = 0.321 and 0.387, respectively). Sensitivity and specificity were 100% and 51.4%, respectively, in the CB group and 88% and 54.3% in the DS group (AUC = 0.711 and 0.759, respectively, P-value = .514). Representation of the transformation zone (TZ) was adequate in 83.3% of samples in the CB group and 50.4% in the DS group (P-value <.001). CONCLUSION: Our data suggest that both devices had similar accuracy to detect anal HSIL, although samples collected with CB are more likely to have an adequate TZ representation, the presence of which could be an indicator of sample quality.

The reporting rates of high-grade squamous intraepithelial lesions and their human papillomavirus testing and histologic follow-up results: A comparison between ThinPrep and SurePath preparations.

BACKGROUND: Liquid-based cytology (LBC) tests SurePath (SP) and ThinPrep (TP) have largely replaced conventional Papanicolaou (Pap) tests for cervical cytology screening due to higher sensitivity. However, comparison between SP and TP test sensitivity and efficacy in detecting squamous abnormalities is lacking. Our study aims to compare high-grade squamous intraepithelial lesion (HSIL) reporting rates, human papillomavirus (HPV) positivity rates, and histologic outcome between these two LBC methods. MATERIALS AND METHODS: We performed a retrospective search of the period between January 2014 and June 2017, when both TP and SP were utilized at our institution, to identify HSIL cases and collect the HPV testing and histologic follow-up results for those cases. RESULTS: One hundred twenty-five HSILs were identified from the 15 382 TP specimens (0.81%) and 93 HSILs were identified from the 25 105 SP specimens (0.37%), a statistically significant difference (P < .0001). The corresponding HPV positivity rates were 95.6% and 89.7% in TP-HSILs and SP-HSILs, respectively, a statistically non-significant difference. Histologic follow-up showed HSILs or carcinomas were identified in 78% (49/63) of TP-HSILs and 79% (45/57) of SP-HSILs, with no statistically significant difference. CONCLUSION: TP demonstrated a higher HSIL detection rate than SP with no significant difference in follow-up HPV or histologic results.

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.

INTRODUCTION: 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. METHODS: A total of 124,251 cases with cotesting of cytology and HPV genotyping between October 2017 and February 2020 were included. RESULTS: 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. CONCLUSIONS: 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.

Anal cytology and high-risk human papilloma virus testing in atypical squamous categories: Value of concurrent testing in management of high-risk population.

Anal squamous cell carcinoma is relatively rare, but its incidence and mortality have been increasing worldwide. While anal cytology is a sensitive cancer screening modality, its specificity is low, and data for concurrent high-risk human papilloma virus (HR-HPV) testing are limited. At our institution, anal cancer screening consists of combined anal cytology and high-risk human papilloma virus (HR-HPV) testing on all specimens. The aims of the study were to correlate results of atypical cytological diagnoses [atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells cannot exclude high grade squamous intraepithelial lesion (ASC-H)] with HR-HPV testing and determine if co-testing may potentially influence management. A retrospective search over 24-months was performed for anal cytology specimens with diagnoses of ASCUS and ASC-H. Corresponding HR-HPV (HPV 16/18 and Other-31/33/35/39/45/51/52/56/58/59/66/68) results were retrieved, and concordance/discordance was recorded. Cytology results were correlated with anal biopsy diagnoses, when available. A total of 139 patients, including 127 with ASCUS and 12 with ASC-H, were identified. Of the ASCUS cases, 90/127 (70.9%) had HR-HPV, and a squamous intraepithelial lesion (SIL) was evident in 20/39 (51.2%) of biopsies. All 12/12 (100%) ASC-H were associated with HR-HPV and 3/6 (50%) biopsies had a SIL. Our study supports use of concurrent cytology and HR-HPV for anal cancer screening cytology. Co-testing improves specificity of atypical cytology diagnoses and can identify patients requiring further intervention.

Five-year retrospective review in gynecologic cytopathology: is it time to amend?

INTRODUCTION: According to the Clinical Laboratory Improvement Amendments 1988 regulations, 5-year retrospective review (5YRR) of normal Papanicolaou tests in patients with a newly diagnosed high grade squamous intraepithelial lesion or above (HSIL+) is mandatory. Since this mandate has been in place, a multitude of changes have taken place in the screening and management guidelines of cervical cancer. The aim of this study is to assess the role of this mandate in our laboratory and to investigate the lessons learned. MATERIAL AND METHODS: The cytopathology electronic database and institutional quality assurance records at Loyola University Medical Center were searched from January 2009 to December 2019 to identify all Papanicolaou tests diagnosed as new "HSIL and above" (HSIL+). Major discrepancy (2+) was defined as initial negative diagnosis changed to HSIL+. RESULTS: A total of 153,083 Papanicolaou tests were performed during this period; out of these, 1452 (0.94%) were diagnosed as HSIL+. A total of 695 HSIL+ Papanicolaou tests had a negative prior Papanicolaou and in 615 of 695 there was agreement with the initial negative diagnosis. In 61 Papanicolaou tests, the initial diagnosis was changed from negative and they were reclassified on review as 3 HSIL, 9 ASC-H, 7 AGC, and 42 ASCUS or LSIL. Major discrepancy rate was calculated as 3 of 695 (0.43%). None required an amended report. CONCLUSIONS: It is important to revisit the 5YRR as a method of implementing the quality indicators in gynecologic cytology so that the process retains its value without overburdening cytology laboratories and personnel.

Comparing Anal Cancer Screening Algorithms Using Cytology and Human Papillomavirus DNA Testing in 3 High-Risk Populations.

BACKGROUND: Screening strategies for high-risk human papillomavirus (hrHPV)-associated anal cancer are evolving. Herein, we compare anal cytology to hrHPV DNA testing and 2 novel cytology/hrHPV cotesting algorithms among 3 high-risk populations. METHODS: Anal cytology, hrHPV DNA testing, and high-resolution anoscopy (HRA)-guided biopsy results were analyzed from 1837 participants (1504 HIV-infected men who have sex with men (MSM), 155 HIV-uninfected MSM, and 178 HIV-infected women). Performance to detect histological high-grade squamous intraepithelial lesions (HSIL)/cancer was compared between 4 strategies with distinct HRA referral thresholds: cytology (atypical squamous cells of undetermined significance, ASCUS); hrHPV testing (any hrHPV positive); algorithm A (benign cytology/HPV16/18 positive or ASCUS/hrHPV positive); and algorithm B (benign or ASCUS/hrHPV positive). RESULTS: Histological HSIL/cancer was detected in 756 (41%) participants. Cytology had the lowest sensitivity (0.76-0.89) but highest specificity (0.33-0.36) overall and for each subgroup. Algorithm B was the most sensitive strategy overall (0.97) and for MSM (HIV-infected 0.97; HIV-uninfected 1.00). For women, hrHPV testing and both algorithms yielded higher sensitivity than cytology (0.96, 0.98, and 0.96). Specificity was low for all strategies/subgroups (range, 0.16-0.36). CONCLUSIONS: Screening algorithms that incorporate cytology and hrHPV testing significantly increased sensitivity but decreased specificity to detect anal precancer/cancer among high-risk populations.