Cytology For Cervical Cancer Screening Research Articles

Enhancing Cervical Cancer Screening: Review of p16/Ki-67 Dual Staining as a Promising Triage Strategy.

Cervical cancer, primarily caused by high-risk human papillomavirus (HR-HPV) types 16 and 18, is a major global health concern. Persistent HR-HPV infection can progress from reversible precancerous lesions to invasive cervical cancer, which is driven by the oncogenic activity of human papillomavirus (HPV) genes, particularly E6 and E7. Traditional screening methods, including cytology and HPV testing, have limited sensitivity and specificity. This review explores the application of p16/Ki-67 dual-staining cytology for cervical cancer screening. This advanced immunocytochemical method allows for simultaneously detecting p16 and Ki-67 proteins within cervical epithelial cells, offering a more specific approach for triaging HPV-positive women. Dual staining and traditional methods are compared, demonstrating their high sensitivity and negative predictive value but low specificity. The increased sensitivity of dual staining results in higher detection rates of CIN2+ lesions, which is crucial for preventing cervical cancer progression. However, its low specificity may lead to increased false-positive results and unnecessary biopsies. The implications of integrating dual staining into contemporary screening strategies, particularly considering the evolving landscape of HPV vaccination and changes in HPV genotype prevalence, are also discussed. New guidelines and further research are necessary to elucidate the long-term effects of integrating dual staining into screening protocols.

Comparative study of factors influencing cytological screening for cervical cancer attendance in Hungary among Roma and non-Roma population, in relation to Slovak and Romanian results

To the present day, the prevalence and incidence of cervical cancer remains very significant. For disadvantaged groups such as the Roma, screening for the disease should be given increased attention, as members of this minority have lower access to health care and lower average health literacy. The aim of our study was to assess the prevalence of cytological screening for cervical cancer among Hungarian-speaking Roma and non-Roma populations in Hungary, Romania and Slovakia, in relation to the possible influencing factors. We also investigated respondents' perceptions of the importance of cervical cancer screening and HPV vaccination. In this paper, we focus on presenting the data from Hungary in relation to the results from the other two countries. The study sample size was 1366. Data were presented as mean ± SD and proportion. To compare Roma and non-Roma samples, the independent samples t-test was used. Cross tabulation with Pearson's chi-square test with calculating phi/Cramér's V effect size (p<0.05) was used to reveal association between ethnicity and studied variables. In Hungary, a higher proportion of Roma women (p = 0.004) did not attend cytological screening for cervical cancer compared to non-Roma women, a difference confirmed in the other two countries. Non-Roma women attached greater importance to attendance at cervical cancer screening (p = 0.022). The Roma population aged 18-65 years had lower rates of annual cytological screening for cervical cancer compared to non-Roma in all age groups, while the annual screening rate decreased with age, regardless of ethnicity. Further health promotion to prevent cervical cancer in the Roma and non-Roma population would be necessary, regardless of national borders, specifically to address risk factors in all age groups, with a focus on young people, who are less aware of the risk, and older age groups, who mostly believe that the disease does not affect them due to their age. Orv Hetil. 2023; 164(36): 1416-1425.

A Comparison of Conventional Pap Smear and Liquid-Based Cytology for Cervical Cancer Screening.

Early diagnosis and treatment of preinvasive lesions have made cervical cytology one of the most effective methods of cancer screening in industrialized nations, which have seen a sharp decline in the incidence and death of invasive cancer. The aim of this study is to compare liquid-based cytology (LBC) and conventional Pap on cervical smears. From July 2018 to June 2022, 600 patients were included in this cross-sectional study, which was done at the Pathology Department of a Tertiary Care Facility in Western Maharashtra. Of the 600 patients, 570 (95%) had good conventional Pap smear (CPS), whereas 30 (5%) had poor ones. Five hundred and ninety-two (98.6%) LBC smears were satisfactory, whereas 8 (1.4%) were unsatisfactory. Endocervical cells were seen in 294 (49%) CPS, whereas 360 (60%) LBC smears showed endocervical cells. The morphology of inflammatory cells was similar in both techniques. Hemorrhagic background was seen in 212 (35%) CPS and 76 (12.6%) LBC smears. Only two samples showed diathetic background, which was seen on both CPS and smear. Out of the satisfactory smears in the case of CPS, 512 (85%) cases were reported as negative for intraepithelial lesion or malignancy (NILM), whereas 58 (9.7%) cases were reported as epithelial cell abnormality. In LBC smears, 526 (87.3%) were reported as NILM, whereas 66 (11%) were reported as epithelial cell abnormality. Organisms were detected in 208 (34%) CPS and 162 (27%) LBC smears. Screening time was 5 ± 1 min for CPS, whereas it was 3 ± 1 min for LBC smear. Mortality will be decreased using LBC on a bigger scale in nations where many smears can be made and screened in a short amount of time, with the provision of doing human papillomavirus-based testing on the remaining sample.

High-risk HPV testing vs liquid-based cytology for cervical cancer screening among 25- to 30-year-old women: A historical cohort study.

High-risk human papilloma virus (hrHPV) DNA testing is more sensitive than cytology screening, achieving greater protection against cervical cancer. Controversy exists regarding the preferred screening method for women 25-30 years of age. At this age, infection with HPV is common and usually transient. Consequently, hrHPV screening in this age group is fraught with high false-positive screening results, leading to more colposcopies and unnecessary treatments with the potential for harm. In the present study, we aimed to compare the results of two screening methods in relation to high-grade cervical intraepithelial lesion detection rate in the young age group of 25-30 years. Retrospective information on cervical cytology, hrHPV testing, colposcopy referrals and histologic results, from one screening round, were retrieved from the Maccabi HealthCare Health Maintenance Organization centralized database during the study period from March 1, 2017 to April 1, 2019 for 25- to 30-year-old women. Screening with hrHPV testing for types 16, 18 and 12 other hrHPV types was compared with the conventional PAP liquid-based cytology (LBC) test. Odds ratio (OR) of detection with 95% confidence interval (CI) was calculated for cervical intraepithelial neoplasia (CIN) grade 3 or higher (CIN 3+). During the study period, 42 244 women 25-30 years old underwent cervical cancer screening; of them, 20 997 were screened with LBC between March 1, 2017 and March 1, 2018 and compared with 21 247 who were screened with hrHPV between April 1, 2018 and April 1, 2019. Testing for hrHPV resulted in a higher colposcopy referral rate compared with primary LBC screening: 9.8% vs 7.8%, respectively; (OR 1.28; 95% CI 1.2-1.37; p< 0.001). Screening with hrHPV led to significantly higher detection of CIN 3+ lesions (OR 1.4; 95% CI 1.2-1.6; p< 0.001) compared with LBC. HPV infections with non-16/18 hrHPV (other hrHPV) were the most prevalent (84.8%). In women 25-30 years old, primary hrHPV screening was associated with a higher detection rate of CIN 3+ compared with cytology screening and should be considered for primary screening in this age group.

A comparison of high-grade cervical abnormality risks in women living with and without human immunodeficiency virus undergoing routine cervical-cancer screening

As the US moves increasingly towards using human papillomavirus (HPV) testing with or without concurrent cytology for cervical cancer screening, it is unknown what the corresponding risks are following a screening result for women living with HIV (WLWH), which will dictate the optimal clinical follow-up. Therefore, using medical records data from Kaiser Permanente Northern California, which introduced triennial HPV and cytology co-testing in women aged 30–64 years in 2003, we compared risks of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe diagnoses (CIN2+) in women not known to have HIV (HIV[−] women) (n = 67,488) frequency matched 111:1 on age and year of the first co-test to the 608 WLWH (n = 608). WLWH were more likely to test HPV positive (20.2% vs. 6.5%, p < 0.001) and have non-normal cytology (14.1% vs. 4.1%, p < 0.001) than HIV[−] women. Five-year CIN2+ risks for all WLWH and HIV[−] women were 3.5% (95%CI = 2.0–5.0%) and 1.6% (95%CI = 1.5–1.8%) (p = 0.01), respectively. Five-year CIN2+ risks for WLWH with positive HPV and non-normal cytology, positive HPV and normal cytology, negative HPV and non-normal cytology, and negative HPV and normal cytology were 24.9% (95%CI = 13.4–36.4%), 3.0% (95%CI = 0.0–7.4%), 3.6 (95%CI = 0.0–9.8%) and 0.3% (95%CI = 0.0–0.8%), respectively. Corresponding 5-year CIN2+ risks for HIV[−] women were 26.6% (95%CI = 24.6–28.7%), 8.5% (95%CI = 7.2–9.9%), 1.9% (95%CI = 1.0–2.8%), and 0.5% (95%CI = 0.4–0.6%), respectively. Thus, in this healthcare setting, the main cause in overall CIN2+ risk differences between WLWH and HIV[−] women was the former was more likely to screen positive and once the screening result is known, it may be reasonable to manage both populations similarly.

The role of cytomorphological studies in screening cervical cancer in the Republic of Tajikistan

Introduction. Currently, in developed countries, virological screening is used as the main screening tool, and the Papanicolaou cytological control service is used as an auxiliary one. For countries with limited financial resources, WHO has recommended various options for an imaging screening strategy called «screening, diagnosis and treatment». Aim. The choice of the optimal model for the use of cytological studies, economically justified for our country, against the background of the expanding population-based visual screening of cervical cancer. Material and methods. The data of official statistics and the results of the pilot design of the WHO screening and treatment strategy in the Kushoniyon district of the Khatlon region and B. Gafurov district of the Sughd region were used. Results. As this study has shown, over the past decades in the Republic of Tajikistan, cytological screening for cervical cancer has fallen into complete decline and in recent years provides only 4.73% of women of reproductive age. Cytological examinations of cervical smears in the country are performed only as an additional test in cases of suspected cervical intraepithelial neoplasia. Due to the existing economic problems in the country, since 2016, the visual screening recommended by WHO for countries with limited resources has been introduced in a pilot way. The first results of the pilot implementation of visual screening have shown its high efficiency at a low economic cost. However, the question of the role of cytological studies against the background of coverage of the population with visual screening remains unclear. The economic feasibility and scale of the reorganization of cytomorphological support for cervical cancer screening in the Republic of Tajikistan was confirmed. Conclusions. In the conditions of the Republic of Tajikistan, as a result of the widespread coverage of the population with visual screening, Papanicolaou cytological studies will serve as an auxiliary tool and can be reorganized on the basis of the Republican Cancer Research Center and its regional and interdistrict divisions.

P16/Ki-67 Dual Staining Is a Reliable Biomarker for Risk Stratification for Patients With Borderline/Mild Cytology in Cervical Cancer Screening.

To evaluate p16/Ki-67 dual-staining performance for detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in the management of women with minor cervical abnormalities. All 759 enrolled patients were tested for cytology, high-risk human papillomavirus (HR-HPV) and dual p16/Ki-67 staining. Positivity rates for HR-HPV and dual staining increased as dysplasia was worsened from non-CIN (37.6% and 0%) to CIN1 (62.5% and 1.6%) and CIN2+ (98.7% and 97.3%), respectively. HPV18 and HPV16 exhibited the highest odds ratios (53.16 and 11.31) in the CIN2+ group. Both p16/Ki-67 dual staining and HR-HPV presented similar sensitivities (97.3% and 98.7%, respectively) for CIN2+ detection. Dual staining specificity, however, was 99.3%, significantly higher compared to HR-HPV testing (52.2%). The utility of dual staining was evaluated in different screening strategies and appeared to reduce the number of colposcopies required for the detection of CIN2+ cases. p16/Ki-67 dual-staining cytology is a surrogate triage biomarker in cytology-based screening programs, with high performance for efficient risk stratification of women with mild cervical abnormalities.

Introducing Liquid-based Cytology for Cervical Cancer Screening during the COVID-19 Pandemic

Introducing Liquid-based Cytology for Cervical Cancer Screening during the COVID-19 Pandemic

Organizational issues in cytological screening for cervical cancer (literature review)

В данной статье рассматриваются вопросы повышения эффективности цитологического скрининга рака шейки матки, включая использование жидкостной цитологии, тестирование на вирус папилломы человека высокого риска, трансформацию оппортунистического скрининга в популяционный цитологический скрининг и обучение персонала.&#x0D; Ключевые слова: рак шейки матки, цитологический скрининг, популяционная организация скрининга.

Women’s acceptability of and experience with primary human papillomavirus testing for cervix screening: HPV FOCAL trial cross-sectional online survey results

ObjectiveTo study participant’s acceptability of and attitudes towards human papillomavirus (HPV) testing compared with cytology for cervical cancer screening and what impact having an HPV positive result may have in...

Real-world effectiveness of primary screening with high-risk human papillomavirus testing in the cervical cancer screening programme in China: a nationwide, population-based study

BackgroundRandomized controlled trials have shown a higher sensitivity and longer negative predictive value of high-risk human papillomavirus (HPV) testing than cytology for cervical cancer screening; however, little is known about the effectiveness of HPV testing in middle-income countries. Understanding the characteristics of HPV testing may increase the priority of HPV testing in health policies. The study aims to evaluate the effectiveness of HPV testing in the national cervical cancer screening programme in China.MethodsWe performed a nationwide, population-based study using individual data from the national cervical cancer screening programme in rural China between 2015 and 2017. The analyses included 1,160,981 women aged 35–64 years who underwent cytology alone or high-risk HPV testing with cytology or genotyping triage. The main outcome was cervical intraepithelial neoplasia 2 or worse (CIN2+). We used multivariate logistic regressions and performed sensitivity analyses with propensity score matching to compare the screening positive, colposcopy referral, detection rate, and positive predictive value (PPV).ResultsThe screening positive rates for HPV testing and cytology were 10.1% and 4.0%, respectively. The per protocol colposcopy referral rate of HPV testing was significantly lower than that of cytology (3.5% vs 4.0%), and this difference was mostly due to the low referral threshold of cytology (≥ASC-US). Overall, HPV testing detected more CIN2+ (5.5 vs. 4.4 per 1000, adjusted odds ratio [aOR]=1.18, 95% confidence interval 1.11–1.25) and had a higher PPV (13.8% vs 10.9%, aOR 1.29, 95% CI 1.21–1.37) than cytology. The colposcopy referrals of HPV testing in comparison to cytology differed by income status; it significantly increased in lower-middle-income areas (3.7% vs 3.1%, aOR 1.21, 95% CI 1.17–1.25) and significantly decreased in upper-middle-income areas (3.4% vs 4.9%, aOR 0.69, 95% CI 0.67–0.71). Sensitivity analyses demonstrated the reliability and robustness of the results.ConclusionsThe introduction of HPV testing could improve both the CIN2+ detection rate and efficiency of cervical cancer screening programme, supporting the introduction of primary screening with high-risk HPV testing in China. Further study is needed to investigate the long-term effect of this change.

The difficulty to diagnose cervical cancer developing in the perinatal period with the first-trimester cytology: A retrospective study.

Cytological cervical cancer screening for pregnant women is routinely performed and still plays an essential role in Japan because of the considerably low rate of human pappillomavirus (HPV) vaccination. Though almost all pregnant women undergo cytological screening at their first trimester, we experienced invasive cervical cancers (ICC) diagnosed during pregnancy or postpartum period. We investigated the characteristics of perinatally diagnosed ICCs to clarify the difficulty in diagnosis during the pregnancy. We retrospectively reviewed the clinical data on ICC diagnosed during pregnancy or within 1 year after delivery from 2010 to 2018 at Hokkaido University Hospital. We identified 18 ICC patients, and the median follow-up period was 46.5months. Among eight patients with negative for intraepithelial lesion or malignancy (NILM), the mean duration to reach ICC diagnosis was 10.7months, seven had stage IB1 or worse, and one was dead. On the other hand, among 10 women with abnormal cytology, the mean duration for diagnosis was 1.4months, and 6 had stage IB1 or worse, and 1was dead. In terms of the timing of the final diagnosis, 8 were during pregnancy and 10 in the postpartum periods. Among eight pregnant patients, three resulted in a preterm delivery (33, 34, and 35 gestational weeks), and four terminated their pregnancies. One decided to continue the pregnancy until the term period. We performed conization in one patient and hysterectomy in seven. A part of cytological examinations of pregnant women may result in presumed false-negative or underestimation, which keeps them away from the additional examination to find ICC.

Is the HPV-test more cost-effective than cytology in cervical cancer screening? An economic analysis from a middle-income country.

To report a modelling study using local health care costs and epidemiological inputs from a population-based program to access the cost-effectiveness of adopting hrHPV test. A cost-effectiveness analysis based on a microsimulation dynamic Markov model. Data and costs were based on data from the local setting and literature review. The setting was Indaiatuba, Brazil, that has adopted the hrHPV test in place of cytology since 2017. After calibrating the model, one million women were simulated in hypothetical cohorts. Three strategies were tested: cytology to women aged 25 to 64 every three years; hrHPV test to women 25-64 every five years; cytology to women 25-29 years every three years and hrHPV test to women 30-64 every five years (hybrid strategy). Outcomes were Quality-adjusted life-years (QALY) and Incremental Cost-Effectiveness Ratio (ICER). The hrHPV testing and the hybrid strategy were the dominant strategies. Costs were lower and provided a more effective option at a negative incremental ratio of US$ 37.87 for the hybrid strategy, and negative US$ 6.16 for the HPV strategy per QALY gained. Reduction on treatment costs would influence a decrease in ICER, and an increase in the costs of the hrHPV test would increase ICER. Using population-based data, the switch from cytology to hrHPV testing in the cervical cancer screening program of Indaiatuba is less costly and cost-effective than the old cytology program.

Comparison of Visual Inspection using Acetic Acid and Liquid Based Cytology for Cervical Cancer Screening in Rural Area: A Cross-Sectional Study

Introduction: Cervical cancer is the primary malignancy in Indian women. The most significant method for untimely diagnosis of cancer cervix is cytology screening, but it is not possible to launch nationwide cytology screening programme of cervical cancer. So, this has lead to the development of low cost technology e.g., visual inspection of the cervix after application of acetic acid. Aim: To compare Visual Inspection using Acetic Acid (VIA) and Liquid Based Cytology (LBC) in evaluation of abnormal cervical lesions. Materials and Methods: This was a cross-sectional study conducted on 1600 women who fulfill selection criteria. Patients attending Gynaecology Outpatient Department (OPD) with the following signs and symptoms like vaginal discharge, abnormal uterine bleeding, lowback pain, contact bleeding, and lower abdominal pain were included. After taking informed consent, the participant was subjected to detailed history, physical examination, LBC, VIA and Colposcopy followed by biopsy (if required). The sensitivity and specificity of each test are determined and compared. Data entry and analysis were done using SPSS Inc., version 11.0. Results: In present study, VIA was more sensitive (92.06%) than the LBC (68.25%) for the detection of dysplasia. However, the specificities of VIA (56.76%) and LBC (54.05%) had not much difference. Positive Pedictive Value (PPV) of VIA was 78.38% and Negative Predictive Value (NPV) of VIA was 80.77% while PPV of LBC was 71.67% and NPV of LBC was 50%. The accuracy of VIA (79%) is higher than LBC (63%). Conclusion: The VIA is more sensitive screening modality than LBC. The accuracy of VIA is higher than LBC in detecting premalignant lesion which makes it a suitable and valuable alternative screening method to cytology in poor resource setting.

Сontroversial issues in cytological screening for cervical cancer (literature review)

This article discusses the controversial issues of cytological screening for cervical cancer, including the use of liquid-based cytology and automated screening systems, high-risk human papillomavirus testing, and organizational issues of screening and staff training.

Evaluation of Visual Inspection of Cervix with Acetic Acid and Liquid Based in Cervical Cancer Screening with Cervical Biopsy.

Cervical cancer is the second most common cancer among women in developing countries. Cervical cancer generally develops slowly over a period of 10-15 years. Incidence and mortality related to cervical cancer both have declining in developed countries because of effective screening programs through Papanicolaou smear. Therefore, cervical cancer can be prevented through implementation of different methods of screening programs like visual inspection of cervix with application of acetic acid visual inspection with acetic acid, liquid based cytology and human papilloma virus deoxyribonucleic acid. The purpose of this study is to compare the efficacy of visual inspection with Acetic Acid with liquid based cytology in cervical cancer screening taking cervical biopsy as a gold standard. The study was conducted at Paropakar Maternity and Women's Hospital, Kathmandu. One hundred forty four patients underwent visual inspection with acetic acid and liquid based cytology test followed by biopsy for confirmation of the lesion, when required. Data were obtained and statistically analyzed. Out of 144 screened patients, 62 (43.05%) were positive in visual inspection with acetic acid test. Eighteen (12.5%) cases were positive in liquid based cytology. Thirteen women were positive with both tests. Thirty-nine cases underwent histopathological examination including 13 cases who were positive in both tests. The sensitivity, specificity, positive predictive value and negative predictive value for visual inspection with acetic acid was 81.25%, 65.22%, 61.90% and 83.33%, whereas for liquid based cytology it was 100%, 91.30%, 88.89% and 94.87% respectively. Liquid based cytology was more efficacious to diagnose atypical cells with higher sensitivity and specificity in comparison to that of visual Inspection with Acetic Acid test.

HrHPV testing vs liquid-based cytology in cervical cancer screening among women aged 50 and older: a prospective study

IntroductionEvidence supports high-risk human papilloma virus (HPV) testing as the primary cervical cancer screening tool. However, benefits and harms should be carefully considered before replacing liquid-based cytology. In women age...

Analysis of results of cytological screening of cervix in persons living in Perm territory

Objective. To analyze the results of cytological screening for cervical cancer in women, living in the Perm Territory.&#x0D; Materials and methods. The work is based on the results of a cytological study of 4670 women aged 29 to 70 years who underwent additional medical examinations in medical institutions of Perm and the Perm Territory for the period from 2017 to 2019.&#x0D; Results. It was established that regardless of the place of residence, normal cytograms prevail. Inflammatory changes were more often observed in the urban population than among women living in the village. As age increased, the number of neoplastic changes in the cervix increased with a peak incidence at the age of 50. Detection of cervical cancer in the Perm Territory was 0.03 % that corresponds to the average statistical indicators in Russia, although this apparently reflects the problems of hypodiagnosis in cytological screening, since in the country in recent years the incidence of cervical cancer and mortality from it has been increasing.&#x0D; Conclusions. The cytological method is a key step in cervical cancer screening, since it allows you to identify early pathological changes in case of adequate collection of material, correct staining of preparations, and a highly qualified cytologist.

Accuracy and Efficiency of Deep-Learning-Based Automation of Dual Stain Cytology in Cervical Cancer Screening.

BackgroundWith the advent of primary human papillomavirus testing followed by cytology for cervical cancer screening, visual interpretation of cytology slides remains the last subjective analysis step and suffers from low sensitivity and reproducibility.MethodsWe developed a cloud-based whole-slide imaging platform with a deep-learning classifier for p16/Ki-67 dual-stained (DS) slides trained on biopsy-based gold standards. We compared it with conventional Pap and manual DS in 3 epidemiological studies of cervical and anal precancers from Kaiser Permanente Northern California and the University of Oklahoma comprising 4253 patients. All statistical tests were 2-sided.ResultsIn independent validation at Kaiser Permanente Northern California, artificial intelligence (AI)-based DS had lower positivity than cytology (P < .001) and manual DS (P < .001) with equal sensitivity and substantially higher specificity compared with both Pap (P < .001) and manual DS (P < .001), respectively. Compared with Pap, AI-based DS reduced referral to colposcopy by one-third (41.9% vs 60.1%, P < .001). At a higher cutoff, AI-based DS had similar performance to high-grade squamous intraepithelial lesions cytology, indicating a risk high enough to allow for immediate treatment. The classifier was robust, showing comparable performance in 2 cytology systems and in anal cytology.ConclusionsAutomated DS evaluation removes the remaining subjective component from cervical cancer screening and delivers consistent quality for providers and patients. Moving from Pap to automated DS substantially reduces the number of colposcopies and also achieves excellent performance in a simulated fully vaccinated population. Through cloud-based implementation, this approach is globally accessible. Our results demonstrate that AI not only provides automation and objectivity but also delivers a substantial benefit for women by reduction of unnecessary colposcopies.

Deep-Learning-Based Evaluation of Dual Stain Cytology for Cervical Cancer Screening: A New Paradigm.

Deep-Learning-Based Evaluation of Dual Stain Cytology for Cervical Cancer Screening: A New Paradigm.