Discovery and technical validation of high-performance methylated DNA markers for the detection of cervical lesions at risk of malignant progression in low- and middle-income countries.

BACKGROUND: Cervical cancer remains a leading cause of death, particularly in developing countries. WHO screening guidelines recommend human papilloma virus (HPV) detection as a means to identify women at risk of developing cervical cancer. While HPV testing identifies those at risk, it does not specifically distinguish individuals with neoplasia. We investigated whether a quantitative molecular test that measures methylated DNA markers could identify high-risk lesions in the cervix with accuracy. RESULTS: Marker discovery was performed in TCGA-CESC Infinium Methylation 450 K Array database and verified in three other public datasets. The panel was technically validated using Quantitative Multiplex-Methylation-Specific PCR in tissue sections (N = 252) and cervical smears (N = 244) from the USA, South Africa, and Vietnam. The gene panel consisted of FMN2, EDNRB, ZNF671, TBXT, and MOS. Cervical tissue samples from all three countries showed highly significant differential methylation in squamous cell carcinoma (SCC) with a sensitivity of 100% [95% CI 74.12-100.00], and specificity of 91% [95% CI 62.26-99.53] to 96% [95% CI 79.01-99.78], and receiver operating characteristic area under the curve (ROC AUC) = 1.000 [95% CI 1.00-1.00] compared to benign cervical tissue, and cervical intraepithelial neoplasia 2/3 with sensitivity of 55% [95% CI 37.77-70.84] to 89% [95% CI 67.20-98.03], specificity of 93% [95% CI 84.07-97.38] to 96% [95% CI 79.01-99.78], and a ROC AUC ranging from 0.793 [95% CI 0.68-0.89] to 0.99 [95% CI 0.97-1.00] compared to CIN1. In cervical smears, the marker panel detected SCC with a sensitivity of 87% [95% CI 77.45-92.69], specificity 95% [95% CI 88.64-98.18], and ROC AUC = 0.925 [95% CI 0.878-0.974] compared to normal, and high-grade squamous intraepithelial lesion (HSIL) at a sensitivity of 70% (95% CI 58.11-80.44), specificity of 94% (95% CI 88.30-97.40), and ROC AUC = 0.884 (95% CI 0.822-0.945) compared to low-grade intraepithelial lesion (LSIL)/normal in an analysis of pooled data from the three countries. Similar to HPV-positive, HPV-negative cervical carcinomas were frequently hypermethylated for these markers. CONCLUSIONS: This 5-marker panel detected SCC and HSIL in cervical smears with a high level of sensitivity and specificity. Molecular tests with the ability to rapidly detect high-risk HSIL will lead to timely treatment for those in need and prevent unnecessary procedures in women with low-risk lesions throughout the world. Validation of these markers in prospectively collected cervical smear cells followed by the development of a hypermethylated marker-based cervical cancer detection test is warranted.

Detection rates and factors affecting thereof in endometrial hyperplasia, endometrial carcinoma, and cervical glandular lesions on cervical smear.

INTRODUCTION: Endometrial lesions are morphologically diverse and uncommon on cervical smears, with its detection rate and associated diagnostic categories uncharacterized. In this study, cervical smears matched to histologically proven endometrial hyperplasias and carcinomas were reviewed and compared with cervical in-situ-carcinomas/carcinomas, aiming to detail the diagnostic performance of cervical smears for upper tract and glandular lesions. METHODS: Pathology reports of cervical smears, hysterectomies, endometrial and cervical biopsies from 1995 to 2021 were retrieved. Diagnoses of cervical smears were matched to endometrial hyperplasias and carcinomas, or cervical carcinomas and reviewed. RESULTS: Totally 832 cervical smears (272 cervical carcinomas, 312 endometrial carcinomas, and 248 hyperplasias) were included. Considering all cytologic glandular diagnosis as positive, the detection rate of cervical adenocarcinoma-in-situ was the highest (64.3%), followed by cervical adenocarcinoma (63.8%), endometrial carcinoma (31.7%), and hyperplasia (with atypia-8.5%; without atypia-2.3%) (p < 0.001). Endometrial hyperplasia was most often diagnosed as atypical squamous cells of undetermined significance (ASCUS) (5.0%) or atypical glandular cells, not otherwise specified (3.6%) without indication of endometrial origin. For endometrial carcinomas, higher FIGO grading and endocervical involvement were associated with higher detection rates across all diagnostic categories (p = 0.002-0.028). High FIGO grade was associated with suspicious/favor neoplastic (C4) (31.1%vs10.3%, p < 0.001) and carcinoma (C5) (17.8% vs. 5.6%, p = 0.005) categories, but not for all glandular diagnoses combined (33.3% vs. 31.0%, p = 0.761). CONCLUSION: Detection rates for endometrial lesions are lower than cervical lesions but not insignificant. Endometrial hyperplasia should be recognized as a differential of human papilloma virus-negative ASCUS and prompt consideration of investigation of the upper genital tract.

Successful Preventive Treatment of Oncogenic Transforming HPV Infections in Low-Grade Cytology (ASC-US/LSIL) Patients with an Adsorptive and Antioxidant Vaginal Gel.

OBJECTIVE: This study aimed to investigate the preventive effect of a vaginal gel on p16/Ki-67-positive abnormal cytological cervical findings (ASC-US, LSIL) and hr-HPV in women. METHODS: The study included 134 women with p16/Ki-67-positive ASC-US or LSIL. Participants were selected from a randomized controlled trial that focused on women with histological diagnoses of p16-positive CIN1 lesions or CIN2. In the treatment group (TG), 57 patients applied the vaginal gel daily for three months, while 77 patients in the "watchful wait" control group (CG) received no treatment. The study's endpoints were cytological development, p16/Ki-67 and hr-HPV clearances. RESULTS: At three months, cytopathological results improved in 74% (42/57) of patients in the TG, compared with 18% (14/77) in the CG. Progression occurred in 7% (4/57) of TG patients compared with 18% (14/77) of CG patients. The p16/Ki-67 status changed statistically significantly in favor of the TG (p < 0.001), with 83% (47/57) becoming negative, compared with 18% (14/77) in the CG. The prevalence of hr-HPV decreased significantly in the TG by 51%, and by 9% in the CG (p < 0.001). CONCLUSIONS: Topical application of the gel resulted in statistically significant clearance of hr-HPV and p16/Ki-67 concomitant with amelioration of cytological findings, thus providing effective prevention and protection against oncogenic development. TRIAL REGISTRATION: ISRCTN11009040, on 10 December 2019.

Feasibility of implementing cytology-based cervical cancer screening national program in Lebanon: A pilot study.

OBJECTIVE: To review our national cervical cancer screening program using existing Ministry of Public Health primary healthcare centers (PHCs) and report the impact of women's knowledge, attitude, behavior, and practices on screening uptake and outcome. METHODS: A cross-sectional study on cervical cancer screening offered to sexually active Lebanese women aged 21 years and above visiting PHCs. Exclusions were history of complete hysterectomy, gynecologic cancers, and current pregnancy. Data were collected through a questionnaire and conventional cervical smear performed by trained healthcare providers and sent to one centralized cytopathology laboratory. RESULTS: Of 12 273 eligible women, 1.7% had an abnormal cervical smear test including 161 atypical squamous cells (ASC) of undetermined significance, 6 atypical glandular cells of undetermined significance, 16 low-grade squamous intraepithelial lesion (SIL), 17 ASC-cannot rule out high-grade SIL, 11 high-grade SIL, and one invasive carcinoma. Knowledge and attitudes significantly affected participation in screening; women lacking awareness had rarely undergone a cervical smear. CONCLUSION: In Lebanon, cytology-based cervical cancer screening is feasible within the PHCs. Positive screen incidence was low. Despite previous campaigns, a low level of knowledge persists, and affects women's com with the screening guidelines. Advocacy and awareness activities by key healthcare providers may help to improve participation.

The role of micronucleus scoring in cervical papanicolaou smears: A 1-year study.

Aims and Objectives: To compare the micronucleus (MN) score in all the major diagnostic categories as per "The Bethesda System for Reporting Cervical Cytology" 2014 including negative for intraepithelial lesions and malignancy (NILM), inflammatory, abnormal squamous cells of undetermined significance (ASC-US), abnormal squamous cells cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H), low-grade squamous intraepithelial lesion (LSIL), HSIL, and invasive carcinoma (IC) and to assess the role of MN scoring as a biomarker for predicting risk of carcinoma. Materials and Methods: A total of 1000 conventional cervical smears stained with Papanicolaou (Pap) stain, comprising unsatisfactory for evaluation (86), NILM (140), inflammatory (696), ASC-US (23), ASC-H (16), LSIL (18), HSIL (15), and IC (6) were studied independently by two pathologists, and the number of MN cells per 1000 epithelial cells in high-power (×400) and oil immersion (×1000) was counted and expressed as MN score per 1000 cells. Results: The mean MN score ± standard deviation was found to be 0.99 ± 0.744 in NILM cases, 0.67 ± 0.782 in inflammatory cases, 1.57 ± 0.507 in ASC-US cases, 1.63 ± 0.50 in ASC-H cases, 1.56 ± 0.511 in LSIL cases, 2.47 ± 0.516 in HSIL cases, and 3.0 ± 0.00 in IC cases. A step-wise increase was observed in MN score from inflammatory to IC categories. Conclusions: MN score is a reliable and easy test that can be used in conjunction with routine cervical PAP to assess the risk of malignant transformation in the uterine cervix as a biomarker for predicting the risk of carcinoma.

Résumé Objectifs et objectifs: comparer le score du micronucléus (MN) dans toutes les principales catégories de diagnostic selon "le système Bethesda pour signaler la cytologie cervicale" 2014, y compris négatif pour les lésions intraépithéliales et la malignité (Nilm), inflammatoire et anormal des cellules squameuses de signification indéterminées (Nilm), inflammatoire et anormale des cellules squameuses de signification indéterminées (Nilm), inflammatoire et anormale des cellules pure ASC - US), les cellules squameuses anormales ne peuvent pas exclure la lésion intraépithéliale épidermoïde de haute qualité (HSIL) (ASC - H), la lésion intraépithéliale squameuse à faible teneur (LSIL), le carcinome invasif (IC) et pour évaluer le rôle de MN La notation en tant que biomarqueur pour prédire le risque de carcinome. Matériaux et méthodes: un total de 1000 frottis cervicaux conventionnels colorés avec une tache de papanicolaou (PAP), comprenant insatisfaisant l'évaluation (86), nilm (140), inflammatoire (696), ASC - US (23), ASC - H (16), LSIL (18), HSIL (15) et IC (6) ont été étudiés indépendamment par deux pathologistes, et le nombre de cellules Mn pour 1000 cellules épithéliales dans la puissance (× 400) et l'immersion à l'huile (× 1000) ont été comptées et exprimé en score MN par 1000 cellules. Résultats: Le score MN moyen ± l'écart type s'est révélé être de 0,99 ± 0,744 dans des cas nilms, 0,67 ± 0,782 dans des cas inflammatoires, 1,57 ± 0,507 dans les cas ASC - US, 1,63 ± 0,50 dans les cas ASC - H, 1,56 ± 0,511 dans LSIL cas, 2,47 ± 0,516 dans les cas HSIL et 3,0 ± 0,00 dans les cas IC. Une augmentation de pas de pas a été observée dans le score MN des catégories inflammatoires vers IC. Conclusions: Le score MN est un test fiable et facile qui peut être utilisé en conjonction avec le PAP cervical de routine pour évaluer le risque de transformation maligne dans le col utérine en tant que biomarqueur pour prédire le risque de carcinome. Mots-clés: Frottis cervical, micronucleus, dépistage.

The impact of offering multiple cervical screening options to women whose screening was overdue in Dumfries and Galloway, Scotland.

Most women who develop cancer have not been screened regularly. One in four women in Scotland, is overdue for cervical screening. Aim was to assess the impact of offering multiple cervical screening options to women whose screening is overdue. A prospective cohort study including all women whose screening was overdue, aged 30-60 years in Dumfries and Galloway in 2012. Potentially eligible women (n = 4146) were identified split into six groups. Women aged 30-55 years were allocated to three different groups. Group 1 (letter, n = 1246), Group 2 (letter and kit, n = 221), Group 3 (letter, n = 2031). Women aged 56-60 years were allocated to: Group 4 (letter, n = 292), Group 5 (letter and kit, n = 292) and Group 6 (control, n = 64). Women who self-collected a vaginal sample were requested to complete a questionnaire. The percentages of women responding were 24 % (21-26), 32 % (25-38), 16 % (14-18), 15 % (11-20) and 12 % (9-17) in groups 1 to 5 respectively, compared with 3 % (0-11) among controls. A significantly higher number of women (n = 383, 10 % of 3815) opted for self-sampling in comparison with undergoing a cervical screening test (CST) at the GP practice (n = 197, 5 %, x2 = 59.0, p < 0.0001). The Evalyn® Brush was well accepted (218/313 = 70 %) by those who requested self-sampling. Almost all (265/272 = 97 %) women who self-collected a vaginal sample said that if they had the option of self-sampling, they would regularly participate in future cervical screening. Offering more flexible screening options, self-sampling in particular, appears to increase cervical screening participation.

Cervical Cancer Screening among Female Refugees in Jordan: A Cross-Sectional Study.

BACKGROUND: Cervical cancer (CC) is mainly linked to infection with a high-risk oncogenic human papillomavirus (HPV), with 85% of deaths occurring in developing countries. Refugees are less likely to be aware of screening methods and to have routine gynecological examinations. METHODS: This is a cross-sectional study involving a total of 359 women aged 19-64 living in the Jerash camp in Jordan. Data were collected using a carefully developed and validated questionnaire. RESULTS: A total of 359 participants were included in the study, with a mean age of 38.99 ± 10.53. Participants demonstrated fair knowledge of CC risk factors (4.77 ± 2.85 out of 11). Among the participants, 73.5% had heard of the cervical smear test; however, only 12.8% had actually undergone the test, with a mean total number of smear tests performed of 1.48 ± 0.79 and the mean age at the time of the first test was 32.5 ± 7.89. CONCLUSIONS: Refugee women have a fair level of knowledge of CC risk factors but are unmotivated to have a Pap smear test to screen for CC. Efforts should be made to raise awareness about the issue and promote testing for underrepresented women in refugee camps.

Cervical cytology: Radiation and other therapy effects.

The different treatment options for carcinoma cervix include radiation, chemotherapy, and surgical treatments. Cytological analysis of smears is crucial for patient follow-up to determine response to therapy and to diagnose the persistence or recurrence of malignancy. Anatomical alterations and changes in cell morphology following radiation or chemotherapy make collecting and interpreting cervical cytology samples difficult. These issues can be mitigated by liquid-based cytology. Ionizing radiation is used in radiotherapy (RT) to kill cells. It is important that cytologists are aware of alterations in morphology of the cells. Radiation can cause cytoplasmic and nuclear changes. Cellular enlargement, vacuolation, granularity loss, and other changes linked with cell death are examples of cytoplasmic alterations. Nuclear enlargement and multinucleation are the most frequent nuclear alterations. These changes are determined by the amount of time that has passed since radiation. It should be emphasized that no one characteristic is pathognomonic. Post-irradiation dysplasia is a condition described as abnormal cellular changes in non-neoplastic epithelial cells after RT. Chemotherapy causes comparable alterations as radiation but impacts fewer cells. Busulfan and other chemotherapeutic treatments may produce morphological alterations, which cytologists must be aware of and able to identify. Immunosuppressive treatments, hormonal therapy, and tamoxifen are some of the other drugs that might cause changes in cervical morphology. Surgical methods used in the detection and treatment of cervical cancer may potentially cause alterations as a result of thermal damage and healing. For the treatment of cervical lesions, electrocautery and the loop electrosurgical excisional procedure are available. These procedures employ electric current ablation leading to ischemic changes in the cervical smear. Cytological analysis of smears following treatment with these modalities necessitates a comprehensive history, kind of therapy, and duration of treatment.

Gender-neutral HPV elimination, cervical cancer screening, and treatment: Experience from Bhutan.

Cervical cancer is preventable and also curable when detected early and treated adequately, yet it remains a leading cause of morbidity and mortality among women. In Bhutan, cervical cancer is the most common cancer among women. Bhutan was the first country among the low- and middle-income economies to have instituted a national HPV vaccination program, in 2010, and has achieved >90% coverage. In 2019, Bhutan launched a cervical cancer elimination flagship program well ahead of WHO's launch of the global strategy for accelerated elimination of cervical cancer. Bhutan initiated vaccination of adolescent boys and adopted a gender-neutral vaccination program beginning September 2020 through its well-established network of primary healthcare centres. The flagship program aims to screen women aged 30-69 years with HPV testing using liquid-based cytology (LBC) as triaging for screen positive women. For women aged 25-29 years, LBC will be continued as per American Society of Colposcopy and Cervical Pathology guidelines. Colposcopy and treatment will be performed in camps to decrease loss of follow up of screen positive women. This program is also expected to improve early diagnosis of cervical cancer and provide timely and adequate cancer treatment and palliative care services. This article reviews the progress made and the challenges facing the 2030 cervical cancer elimination targets in Bhutan.

Evaluation of PathTezt™, a Liquid-Based Cytology System.

Liquid-based preparation (LBP) cytology is commonly used in most laboratories these days due to its convenience and reliable results for the cervical cancer screening program. The PathTezt™ Liquid-based Pap smear is a second-generation LBP, which uses a filter-based concentration technique in processing the sample. OBJECTIVE: This study was done to evaluate the cellular fixation, morphology, quality of smear in gynae cytology, and diagnostic interpretation of cervical cytological smears produced by the PathTezt liquid-based processor. MATERIALS AND METHODS: A total of 400 pap smear samples were taken and processed using the PathTezt 2000 processor. The slides were evaluated in terms of sample adequacy, percentage of the circle covered by epithelial cells, cellular distribution, obscuring factors, and cell fixation. RESULTS: About 95.25% (381) of the samples were satisfactory for the evaluation. In 19 (4.75%) of the samples, epithelial cells covered less than 50% of the circle. A sample with good cellular distribution was seen in 92% of the cases, while 354 (88.5%) samples showed minimal inflammatory background. Almost all the smears (95.75%) had no erythrocytes in the background. All smears showed good quality fixation features toward nuclear, cytoplasm, and microorganisms. The total performance rate was 99%. CONCLUSION: Although the PathTezt liquid-based processor is still new compared to other first-generation LBP, the smears produced by this method were of high quality and it was cost-effective.

Detection of Treponema pallidum by immunocytochemistry of cervical smear: A case report.

Syphilis is an infectious disease caused by Treponema pallidum (T. pallidum). A cervical smear is useful when screening for sexually transmitted diseases; however, T. pallidum is not detected in the usual Papanicolaou smear. We report the detection of T. pallidum by immunocytological examination of a cervical smear. A 22-year-old woman presented with nephrotic syndrome. On admission, we performed screening tests for infections, and her serology was positive for syphilis. A Papanicolaou cervical smear (Thin-Prep) showed slight nuclear enlargement, nuclear irregularity, and mild hyperchromasia in the superficial cells, but no organism was detected. T. pallidum was detected in the remaining specimen using immunocytochemistry. We also detected the T. pallidum DNA in a cervical biopsy specimen by polymerase chain reaction (PCR). Our findings suggest that immunocytological examination and PCR assay examination are useful tests for syphilis diagnosis.

An Adsorptive and Antioxidant Vaginal Gel Clears High-Risk HPV- and p16/Ki-67-Associated Abnormal Cytological Cervical Findings: A post-hoc Subgroup Analysis of a Prospective Randomized Controlled Trial on CIN2 and p16 Positive CIN1.

Objective: To analyze the course of p16/Ki-67-positive abnormal cytological cervical findings and high risk (hr)-HPV- and p16/Ki-67-clearances in women treated with a vaginal gel. Methods: 172 women with a histological diagnosis of CIN2 or p16-positive CIN1 lesions were selected based on a positive cytological p16/Ki-67 test. For 3 months, 75 patients in the active arm (AA) daily administered 5 ml of a vaginal gel. Ninety seven patients in the control arm (CA) underwent no treatment ("watchful waiting"). Endpoints were cytological evolution, p16/Ki-67- and hr-HPV-clearances. Results: At 3 months, cytological regression was observed in 76% (57/75) of patients in the AA compared with 25% (24/97) in the CA. Progression occurred in 5% (4/75) of the AA compared with 15% (15/97) of the CA. The p16/Ki-67 status change was statistically significantly (p < 0.001) in favor of the AA: 77% (58/75) became negative compared to 21% (20/97) in the CA. hr-HPV prevalence decreased significantly (p < 0.001) in the AA from 87 to 44%, while increasing in the CA from 78 to 84%. Cytological regression and p16/Ki-67 changes persisted in the AA at 6 months. Conclusions: The vaginal gel significantly cleared hr-HPV and p16/Ki-67 and was associated with improved cytological findings, thereby potentially offering an effective option against oncogenic risk. Clinical Trial Registration: Identifier: [ISRCTN11009040].

Possible high-grade squamous intraepithelial lesion (pHSIL) in the new cervical screening paradigm: The outcomes and the role of clinicopathological review.

BACKGROUND: A renewed National Cervical Screening Program (NCSP) was introduced in Australia in December 2017. Under the renewed NCSP, there are limited data to guide the management of discordant colposcopy and biopsy results after a liquid-based cytology (LBC) finding of 'possible high-grade squamous intraepithelial lesion' (pHSIL). AIMS: This study aims to determine the proportion of women referred with pHSIL who are found to have HSIL, identify influencing factors of women most at risk, and examine the role that cytopathology review plays in management decisions. MATERIALS AND METHODS: Two-hundred and thirty-two women presenting to a tertiary women's hospital in Australia with pHSIL since December 2017 were identified. Women with HSIL following colposcopy directed biopsy were referred for treatment. When HSIL was not identified, these patients were referred for multidisciplinary clinicopathological review. Pathological outcomes and treatment recommendations are included. MAIN OUTCOME MEASURES: The primary outcome of the study was histological confirmation of HSIL. RESULTS: Primary outcome data were available for 182 women (78.5%); 62 (34.1%) had HSIL on histology, three (1.7%) had adenocarcinoma in situ (AIS) and one (1%) had cervical squamous cell carcinoma (SCC). There was no association between age and the presence of HSIL. The presence of human papillomavirus 16 and/or 18 increased the likelihood of HSIL on histology (relative risk 1.9; 95% CI 1.27-2.80, P = 0.002). Fifty-nine (25.4%) women were referred for observation who had low-grade squamous intraepithelial lesion/no dysplasia. CONCLUSIONS: Clinicopathological review optimises management and triage of patients with pHSIL on referral cytology. Understanding outcomes in these patients informs counselling and management.

Evaluation of the consistency ratios of cervical smear, cervical biopsy and conization results.

OBJECTIVES: Possible discrepancies between the cervical smear, biopsy histology and loop electrosurgical excision procedure (LEEP) results of the same patient is a matter of debate in the literature. In this study, we investigate the degree to which these results differ, and the clinical reasons for these differences. MATERIAL AND METHODS: With a retrospective design, cervical smear, cervical biopsy and LEEP results of patients were compared in terms of consistency. One hundred sixty-four patients who underwent till LEEP procedure due to pathologic initial smear and biopsy results between January 2015 and March 2020 were included in the study. RESULTS: Exact diagnosis discrepancy and high grade squamous intraepithelial lesion (HSIL) discrepancy were 78.9% and 50.0% between smear and cervical biopsy, 64.6% and 31.7% between cervical smear and LEEP and 43.8% and 28.1% between cervical biopsy and LEEP results, respectively. Age did not affect the consistency rates of pathologic results between smear-biopsy (p = 0.408) and biopsy-LEEP (p = 0.590). However, the probability of the consistency of smear and LEEP results exhibited a statistically significant linear relation with age (OR = 1.043, p = 0.015). HPV infections did not affect the discrepancy between smear-biopsy (p = 0.533), smear-LEEP (p = 1.000) and biopsy-LEEP (p = 0.529). CONCLUSIONS: Smear technique has a serious discrepancy and under-diagnosis problem when its results are compared with biopsy and LEEP. The consistency between smear and LEEP results appears to improve with age. When HSIL is evaluated in terms of detection, this discrepancy decreases. A smear test can detect HSIL and carcinoma with a higher accuracy than low-grade lesions.

The comparison of two methods in cervical smear screening - which method is better for smear adequacy rates?

OBJECTIVES: In the cervical smear screening test as a sample collection method for liquid-based thin layer cytology, classically the collecting device is placed into a liquid fixative solution and vigorously swirled or rotated ten times in the solution and the collection device is removed from the solution. In this study, a plastic smear brush was used as the collection device. After the cervical cell sample was obtained, the smear brush was detached from the stick and left in the solution and given to the laboratory. Our aim in the study is to examine whether smear inadequacy rates have decreased with the method used in the study compared to the classical method. MATERIAL AND METHODS: While the classical technique which the collecting device is placed into a solution and mixed and removed from the solution is defined as Method 1. The technique used in the study was defined as Method 2. The cervical smear screening test results obtained by two different methods in two consecutive time periods were analyzed. The two methods were compared using chi-square test in terms of smear inadequacy. RESULTS: A total of 2129 test results, including 1129 smears in Method 1 and 1000 smears in Method 2 were examined. The mean ages of the patients tested in both methods were similar (36 ± 6.1 and 37 ± 6.7). Abnormal test result rate was similar for Method 1 and Method 2 (5.8% vs 4.9%, respectively). The inadequate sample rate was higher in Method 1 than Method 2 (8.3% vs 2.1%, respectively). CONCLUSIONS: The study showed that leaving the smear brush in the solution is a better way to reduce the inadequacy sample rates. This result may guide clinicians about smear techniques.

Hierarchical pathology screening for cervical abnormality.

Cervical smear screening is an imaging-based cancer detection tool, which is of pivotal importance for the early-stage diagnosis. A computer-aided screening system can automatically find out if the scanned whole-slide images (WSI) with cervical cells are classified as "abnormal" or "normal", and then alert pathologists. It can significantly reduce the workload for human experts, and is therefore highly demanded in clinical practice. Most of the screening methods are based on automatic cervical cell detection and classification, but the accuracy is generally limited due to the high variation of cell appearance and lacking context information from the surroundings. Here we propose a novel and hierarchical framework for automatic cervical smear screening aiming at the robust performance of case-level diagnosis and finding suspected "abnormal" cells. Our framework consists of three stages. We commence by extracting a large number of pathology images from the scanned WSIs, and implementing abnormal cell detection to each pathology image. Then, we feed the detected "abnormal" cells with corresponding confidence into our novel classification model for a comprehensive analysis of the extracted pathology images. Finally, we summarize the classification outputs of all extracted images, and determine the overall screening result for the target case. Experiments show that our three-stage hierarchical method can effectively suppress the errors from cell-level detection, and provide an effective and robust way for cervical abnormality screening.

Implementation of pre-captured videos for remote diagnosis of cervical cytology specimens.

OBJECTIVE: The objective of this study was to investigate the feasibility of implementing short videos captured by static telecytological applications for remote evaluation of cervical smears prepared by means of liquid-based cytology. METHODS: The study was performed on representative short videos captured from a total of 404 cervical smears (benign, 135; atypical squamous cells of undetermined significance, 92; low-grade squamous intraepithelial lesion, 62; high-grade squamous intraepithelial lesion, 87; squamous cell carcinoma, 26; adenocarcinoma, 2) that were sent via file transfer protocol to password-protected accounts for remote review by three independent cytopathologists. In addition to diagnosis, reviewers commented on the overall digital video quality. Contributors' and reviewers' diagnoses were collected, recorded, and statistically evaluated. RESULTS: Statistical evaluation detected no significant difference in diagnostic accuracy between cytological diagnoses based on short videos versus conventional slides. The overall interobserver agreement ranged from substantial to almost perfect with κ values of 0.74-0.91. CONCLUSIONS: Short videos produced by static telecytology applications can be used as an alternative method for telecytological diagnosis of cervical smears, particularly for quality control purposes. It is a prompt and valid method for quality assessment and proficiency testing and can be integrated into the daily workflow. Short pre-captured videos of cervical smears can be used for rapid and accurate diagnosis, diminishing turnaround times and improving small cytology departments' quality indices. They can also be used for archiving, teleconsultation, and second opinion purposes, improving the performance of already existing static telecytology stations.

Women's attitudes and understanding of cervical cancer and the new National Cervical Screening Program.

ISSUES ADDRESSED: The new National Cervical Screening Program (NCSP) has recently been implemented. Little research is available on women's attitudes towards the program. This study aims to quantitatively assess Australian women's understanding and attitudes towards the new guidelines and their barriers to screening. METHOD: Authors designed a cross-sectional survey which was piloted and distributed as a waiting room survey to eligible women who attended a private general practice in North Queensland. RESULTS: Of the respondents, 53.8% had accurate knowledge of the new NCSP. Most participants (75.8%) believed they were not provided sufficient information about the NCSP and 60.2% wished to receive this information from their general practitioner. The screening test itself remains an issue, with embarrassment and discomfort listed as the most common barriers to screening. CONCLUSION: Many women do not have accurate knowledge of the new NCSP. Further health promotion in this area is warranted, where the general practitioner may play a key role. SO WHAT?: While the new NCSP will lead to further reduction in cervical cancer mortality, it appears from the data that women did not fully understand cervical cancer and its screening. This suggests the need for further health education to women about updated screening guidelines.

Benefit and burden in the Dutch cytology-based vs high-risk human papillomavirus-based cervical cancer screening program.

BACKGROUND: In 2017, the Dutch cervical cancer screening program had replaced the primary cytology-based screening with primary high-risk human papillomavirus-based screening, including the opportunity to participate through self-sampling. Evaluation and balancing benefit (detection of high-grade cervical intraepithelial neoplasia) and burden of screening (unnecessary referrals, invasive diagnostics, and overtreatment) is needed. OBJECTIVE: This study aimed to compare the referral rates, detection of high-grade cervical intraepithelial neoplasia, overdiagnosis, and overtreatment in the new high-risk human papillomavirus-based screening program, including physician-sampled and self-sampled material, with the previous cytology-based screening program in the Netherlands. STUDY DESIGN: A retrospective cohort study was conducted within the Dutch population-based cervical cancer screening program. Screenees with referrals for colposcopy between 2014 and 2015 (cytology-based screening) and 2017 and 2018 (high-risk human papillomavirus-based screening) were included. Data were retrieved from the Dutch Pathology Registry (PALGA) and compared between the 2 screening programs. The main outcome measures were referral rate, detection of high-grade cervical intraepithelial neoplasia or worse, overdiagnosis (cervical intraepithelial neoplasia grade 1 or less in the histologic specimen), and overtreatment (cervical intraepithelial neoplasia grade 1 or less in the treatment specimen). RESULTS: Of the women included in the study, 19,109 received cytology-based screening, and 26,171 received high-risk human papillomavirus-based screening. Referral rates increased from 2.5% in cytology-based screening to 4.2% in high-risk human papillomavirus-based screening (+70.2%). Detection rates increased to 46.2% for cervical intraepithelial neoplasia grade 2 or worse, 32.2% for cervical intraepithelial neoplasia grade 3 or worse, and 31.0% for cervical cancer, and overdiagnosis increased to 143.4% with high-risk human papillomavirus-based screening. Overtreatment rates were similar in both screening periods. The positive predictive value of referral for detection of cervical intraepithelial neoplasia grade 2 or worse in high-risk human papillomavirus-based screening was 34.6% compared with 40.2% in cytology-based screening. Women screened through self-sampling were at higher risk of cervical intraepithelial neoplasia grade 2 or worse detection (odds ratio, 1.38; 95% confidence interval, 1.20-1.59) and receiving treatment (odds ratio, 1.31; 95% confidence interval, 1.16-1.48) than those screened through physician-sampling. CONCLUSION: Compared with cytology-based screening, high-risk human papillomavirus-based screening increases detection of high-grade cervical intraepithelial neoplasia, with 462 more cervical intraepithelial neoplasia grade 2 or worse cases per 100,000 women but at the expense of 850 more cases per 100,000 women with invasive diagnostics indicating cervical intraepithelial neoplasia grade 1 or less.

Screening for cervical cancer in Africa: A proposal of a different combination of VIA test and cervical smear in Uganda.

OBJECTIVE: To evaluate the efficacy of visual inspection with acetic acid (VIA) screening combined with a cervical smear in Uganda. METHODS: Nine screening campaigns were held in Uganda between January 2011 and October 2019. In the last three campaigns, a new approach was used: the cervical smear was performed before the VIA test and, in case of a positive VIA test, the slide was sent for examination. The data collected were divided into two groups: the first six campaigns and the last three campaigns. RESULTS: During the study period, 10 520 women were screened, of whom 911 had a positive VIA test. The VIA test showed 84.2% false positives. In the first group, the VIA test was positive in 516 women, of whom 93% were referred for further examinations. In the second group, the VIA test was positive in 395 women, but the cervical smear was positive in only 65 women. Thus, only 16.5% women were referred for further examinations. CONCLUSION: Combining cervical smear, VIA test, and slide analysis in positive VIA tests may allow women who need treatment to be selected more effectively, while waiting for other more expensive solutions to become more affordable for this setting.