Quantification of intracellular HPV E6/E7 mRNA expression increases the specificity and positive predictive value of cervical cancer screening compared to HPV DNA

e17025 Background:The estimated age-standardized incidence rate for cervical cancer is higher in Japan than in North America and the UK. It is important to improve cancer screening. The introduction of HPV testing with cytology for triage of those that test positive for cervical cancer screening has been challenging. The Fukui Cervical Cancer Screening (FCCS) study was designed to determine the best cervical cancer screening method in the Japanese population. We performed a subanalysis using baseline data of FCCS study to determine the performance of cytology, the human papillomavirus (HPV) testing and cotesting with cytology and HPV testing, and to evaluate whether the stratification of HPV16, HPV18, and 12 other hrHPV types appropriately balances risks and harms in the Japanese cancer screening population. Methods:The study enrolled 7,584 women aged 25 years or older undergoing routine screening. All women underwent liquid-based cytology (LBC) and cobas HPV testing. Women with abnormal cytology regardless of the HPV status, women with positive hrHPV results regardless of cytology results, and women randomly selected from among those with normal cytology and negative hrHPV results were referred for colposcopy. Results:The prevalence of hrHPV, HPV16, and HPV18 was 6.8%, 1.2%, and 0.5%, respectively. The estimated sensitivities for cervical intraepithelial neoplasia (CIN) 2 or worse for cytology, HPV testing, and cotesting with cytology and HPV testing were 71%, 92%, and 100%, respectively. The estimated positive predictive values for cytology, HPV testing, and cotesting with cytology and HPV testing were 33%, 21% and 21%, respectively. Using a strategy whereby those with abnormal cytology or positive HPV16 genotype undergo colposcopy and biopsy results in a sensitivity of 85% and a positive predictive value of 33%. This strategy results in improved sensitivity while at the same time maintains the positive predictive value compared to screening with cytology alone. Conclusions:Baseline data from the FCCS study suggests that strategy of using colposcopy for women with abnormal cytology and/or HPV16 positivity appropriately balances risks and harms for Japanese women. Clinical trial information: UMIN000025977.

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HPV E6/E7 mRNA versus HPV DNA biomarker in cervical cancer screening of a group of Macedonian women

Journal of Medical Virology ◽

10.1002/jmv.24199 ◽

2015 ◽

Vol 87 (9) ◽

pp. 1578-1586 ◽

Cited By ~ 14

Author(s):

Sotirija Duvlis ◽

Katerina Popovska-Jankovic ◽

Zorica Sarafinovska Arsova ◽

Shaban Memeti ◽

Zaneta Popeska ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Hpv Dna ◽

Hpv E6

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Evaluation of Liquid Based Cytology (LBC) and Conventional Pap’s Smear Test as Methods of Cervical Cancer Screening

International Journal of Human and Health Sciences (IJHHS) ◽

10.31344/ijhhs.v6i1.374 ◽

2022 ◽

Vol 6 (1) ◽

pp. 36

Author(s):

Mehdi Ashik Chowdhury ◽

Asim Ranjan Barua ◽

- Asaduzzaman ◽

Mohammad Mahabubul Hoque ◽

DM Arifur Rahman

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Positive Predictive Value ◽

Negative Predictive Value ◽

Cervical Cancer Screening ◽

Predictive Value ◽

Pap Smear ◽

Molecular Techniques ◽

Smear Preparation ◽

Liquid Based Cytology

Background: Cervical cancer screening can actually prevent most cervical cancers and also facilitates early detection which allows fruitful treatment.Objective: To evaluate and compare the efficacy of Liquid-based cytology (LBC) with conventional Pap smear test.Methods: This crosssectional study was conducted between March 2015 and June 2017. A total of 72 women participated in this study attending the Out-Patient Department (OPD) of Gynaecology (Colposcopy Clinic) of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, for VIA test. The smears prepared by the conventional Pap smear method and Liquid-based cytology method were observed by two independent observers in Department of Pathology of the same institution.Results: The mean age of the patients was 40.22±12.29 years. Considering histopathology as gold standard, in conventional Pap smear preparation our data suggested its sensitivity 87.5%, specificity 92.2%, accuracy 91.7%, positive predictive value 58.3% and negative predictive value 98.3%. In contrast, in Liquid-based cytology, we found its sensitivity 75.0%, specificity 90.6%, accuracy 88.9%, positive predictive value 50.0% and negative predictive value 96.7%.Conclusion: LBC has practical advantages over conventional preparation by producing monolayer of cells, smaller area to screen, reproducibility and availability of doing adjunct molecular techniques from residual sample. However, conventional preparation shows better sensitivity and positive predictive value and almost similar specificity, negative predictive value and accuracy with LBC.International Journal of Human and Health Sciences Vol. 06 No. 01 January’22 Page: 36-40

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Cervical cancer screening by conventional Pap smear versus liquid based cytology

Nepal Journal of Obstetrics and Gynaecology ◽

10.3126/njog.v14i2.28435 ◽

2019 ◽

Vol 14 (2) ◽

pp. 22-25

Author(s):

Subi Basnyat ◽

Gehanath Baral ◽

Karishma Malla

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Positive Predictive Value ◽

Cervical Cancer Screening ◽

Sensitivity And Specificity ◽

Predictive Value ◽

Pap Smear ◽

Premalignant Lesions ◽

Cross Sectional ◽

Liquid Based Cytology

Aims: To evaluate Liquid Based Cytology (LBC) diagnostic performance compared with Conventional Pap Smear (CPS) for cervical cancer screening and to compare the sensitivity and specificity of the two cytology methods with gold standard cervical biopsy. Methods: This is a hospital based cross-sectional study conducted from April 2017 to April 2018 in 110 sample randomly selected at gynecology OPD in Paropakar Maternity and Women’s Hospital. Paired samples (CPS and LBC) were taken from the same patient. Abnormal epithelial lesion detected in LBC and CPS was sent for biopsy. Bethedsa reporting system was followed and data analyzed in terms of diagnostic accuracy. Results: LBC vs CPS for satisfactory report was 96.4% vs 91.8% while unsatisfactory was 3.6% vs 1.8% (p=0.02). The detection of premalignant lesions was ASCUS 2.7%, HSIL 4.5%, ASCUS-H 1.8% and LSIL 0.9% by LBC while by CPS- ASC-US 0.9%, HSIL 3.6%, LSIL 1.8% and ASC-H 0.9% were detected. The sensitivity and specificity of LBC vs CPS was 100% vs 88% and 81.8% vs 99% respectively. The positive predictive and negative predictive value of LBC vs CPS was 81.8% vs 88% and 100% vs 99% respectively. Conclusions: Cell pick-up was satisfactory in both LBC and CPS. The sensitivity and positive predictive value of CPS is similar whereas the positive predictive value of LBC is less than its sensitivity. Cervical cancer screening with CPS is effective alternative over LBC by its cost and level of accuracy.

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Assessing the implementation of population based cervical cancer screening in Amadora, Portugal

European Journal of Public Health ◽

10.1093/eurpub/ckaa166.1291 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

A Leite ◽

S Pereira ◽

D Vaz ◽

T Smet ◽

C Portilheiro ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Positive Predictive Value ◽

Cervical Cancer Screening ◽

Predictive Value ◽

Intraepithelial Neoplasia ◽

Cost Effective ◽

Target Population ◽

Population Based ◽

Screening Tests

Abstract Background Population-based cervical cancer screening (CCS) are deemed to be more cost-effective than opportunistic screening and to reduce inequalities. Implementation in Portugal has been heterogeneous, at the regional level. In Amadora healthcare cluster (Lisbon area), implementation started in April 2018 in a pilot unit and was scaled-up. We aimed to assess population-based CCS implementation in Amadora. Methods Population-based CCS targets women aged 30-65, and utilises liquid-based cytology with partial HPV genotyping (HPV16/18 and other high-risk HPV - hrHPV). Samples positive for other hrHPV undergo a cytology. HPV16/18+ and other hrHPV+ with ≥ASCUS (atypical squamous cells of undetermined significance) are referred to colposcopy. We assessed implementation according to key indicators extracted from our information system: geographic coverage, number of tests, positive results, positive predictive value of referral (number of cervical intraepithelial neoplasia-CIN/number colposcopies). Results As of 30 August 2019, CCS were in place in 4 of the 9 units, potentially covering 20904 women (48.4% of the target population). 1797 womem performed screening within the programme. Invitation for screening is currently implemented in 1 of the 4 units. Screening results were available for 1702 women, 11,1% were HPV+. From these, 26,5% were HPV 16/18+ and 86.2% positive for other hrHPV. Among the latter, 63.2% were negative for intraepithelial lesion and 36.8% were ≥ASCUS. Overall, of these 189 women, 51.3% (n = 97) were referred for colposcopy. Colposcopy results were available for 37 women, of which 13 had a CIN. PPV of referral was 35.1% (95%confidence interval: 20.7;52.6). Conclusions Despite being a population-based screening most tests are still opportunistic. There is still a limited number of colposcopies results but the current PPV of referral is low and requires further investigation. Implementation towards a full population-based screening in Amadora should continue. Key messages Implementation of a population-based cervical cancer screening in Amadora, Portugal is underway but most screening tests are still applied in an opportunistic manner. A limited number of results is avaliable to estimate positive predictive value of referral to colposcopy. Results available indicate a value of 35.1%, which requires further investigation.

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Performance of HPV16/18 in Triage of Cytological Atypical Squamous Cells of Undetermined Significance

Analytical Cellular Pathology ◽

10.1155/2019/4324710 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6

Author(s):

Xiaoqin Cao ◽

Shuzheng Liu ◽

Manman Jia ◽

Hongmin Chen ◽

Dongmei Zhao ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Predictive Value ◽

Statistical Tests ◽

Predictive Values ◽

Squamous Cells ◽

Link Type ◽

Hpv Test ◽

Undetermined Significance

Context. Human papillomavirus (HPV) testing is widely used in cervical cancer screening in women; however, its efficiency in triaging women with atypical squamous cells of undetermined significance (ASC-US) needs to be validated. Objective. To evaluate the performance of HPV16/18 in the triage of women with ASC-US. Methods. Women presenting for routine cervical cancer screening had cervical specimens collected, with which both liquid-based cytology (LBC) and hrHPVs were examined; those with ASC-US cytology underwent colposcopy. HPV16/18 and 12 other types were tested with domestic hybridization capture and chemiluminescence signal amplification (DH3). Performance characteristics of HPV test (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) for identification of cervical intraepithelium neoplasma (CIN) grade 2 or worse (CIN2+), and CIN grade 3 or worse (CIN3+)) were determined using standard statistical tests. Results. 317 women with ASC-US were eligible for the study. HrHPV prevalence was 15.77% (50/317); HPV16/18 prevalence was 3.61% (20/317). Sensitivity and specificity of HPV16/18 for detection of CIN 2+ were 64.71% and 97% and 64.29% and 96.37% for detection of CIN 3+, respectively. The positive predictive values (PPVs) and negative predictive values (NPVs) of HPV16/18 were 55.00% and 97.98% for CIN2+ and 45.00% and 98.32% for CIN3+, respectively. Conclusion. HPV16/18 can be considered as an effective method to triage women with ASC-US as its good clinical performance. Trial Registration. This trial is registered with Henan Cancer Hospital Medical Ethics Committee on July 5, 2016 (http://www.anti-cancer.com.cn), with registry no.: 2016037.

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Accuracy of Visual Tests for Primary Cervical Cancer Screening in Rural Nepal

Journal of Nepal Medical Association ◽

10.31729/jnma.3857 ◽

2018 ◽

Vol 56 (214) ◽

pp. 917-923

Author(s):

Niresh Thapa ◽

Muna Maharjan ◽

Girishma Shrestha ◽

Narayani Maharjan ◽

Deborah Lindell ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Negative Predictive Value ◽

Cervical Cancer Screening ◽

Predictive Value ◽

Odds Ratio ◽

Screening Program ◽

Diagnostic Odds Ratio ◽

Screening Tests ◽

Resource Setting

Introduction: In Nepal, cervical cancer is the most common female cancer. Unfortunately, there is no uniform effective screening system available all around the country. The objective of this study is to evaluate the cytology, Visual Inspection with Acetic Acid and with Lugol’s Iodine alone or in combination to detect a pre-cancerous lesion in rural Nepal.Methods: It is an analytical cross-sectional study. Convenience sampling technique was used to select participants who were apparently healthy, married, non- pregnant women of aged 20-65 years for cervical cancer screening program. Screening tests were performed on all eligible women (n=2143) after socio-demographic and reproductive health data collection. A biopsy was applied as a gold standard test. Cross-tabulations were used to describe the test sensitivity, specificity, positive predictive value, and negative predictive value at a 95% confidence interval. Diagnostic odds ratio was also calculated. Results: A majority, 2143 (94%), of women accepted and participated in this study. The sensitivity vs specificity of cytology, VIA, and VILI was 57.1% vs 98.3%, 71.4% vs 88.8% and 78.6% vs 85.1%, and of the co-testing of ‘Both positive VIA and VILI’ and ‘Either positive VIA or VILI’ was 64.3% vs 85.7% and 90.1% vs 83.7% respectively. Negative predictive value of all tests exceeded 99.7%. Cytology had the highest Diagnostic odds ratio (64.9), followed by the co-test ‘Either positive VIA or VILI’ (27.7).Conclusions: Cervical cancer screening by co-testing ‘Either positive VIA or VILI’ is more useful than cytology; VIA and or VILI are easy, safe, feasible and well-accepted tests in a low resource setting, Nepal.

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Evaluating smartphone strategies for reliability, reproducibility, and quality of VIA for cervical cancer screening in the Shiselweni region of Eswatini: A cohort study

PLoS Medicine ◽

10.1371/journal.pmed.1003378 ◽

2020 ◽

Vol 17 (11) ◽

pp. e1003378

Author(s):

Ramin Asgary ◽

Nelly Staderini ◽

Simangele Mthethwa-Hleta ◽

Paola Andrea Lopez Saavedra ◽

Linda Garcia Abrego ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Predictive Value ◽

Kappa Statistic ◽

World Health ◽

Operating Characteristics ◽

Humanitarian Settings ◽

The Impact

Background Cervical cancer is among the most common preventable cancers with the highest morbidity and mortality. The World Health Organization (WHO) recommends visual inspection of the cervix with acetic acid (VIA) as cervical cancer screening strategy in resource-poor settings. However, there are barriers to the sustainability of VIA programs including declining providers’ VIA competence without mentorship and quality assurances and challenges of integration into primary healthcare. This study seeks to evaluate the impact of smartphone-based strategies in improving reliability, reproducibility, and quality of VIA in humanitarian settings. Methods and findings We implemented smartphone-based VIA that included standard VIA training, adapted refresher, and 6-month mHealth mentorship, sequentially, in the rural Shiselweni region of Eswatini. A remote expert reviewer provided diagnostic and management feedback on patients’ cervical images, which were reviewed weekly by nurses. Program’s outcomes, VIA image agreement rates, and Kappa statistic were compared before, during, and after training. From September 1, 2016 to December 31, 2018, 4,247 patients underwent screening; 247 were reviewed weekly by a VIA diagnostic expert. Of the 247, 128 (49%) were HIV–positive; mean age was 30.80 years (standard deviation [SD]: 7.74 years). Initial VIA positivity of 16% (436/2,637) after standard training gradually increased to 25.1% (293/1,168), dropped to an average of 9.7% (143/1,469) with a lowest of 7% (20/284) after refresher in 2017 (p = 0.001), increased again to an average of 9.6% (240/2,488) with a highest of 17% (17/100) before the start of mentorship, and dropped to an average of 8.3% (134/1,610) in 2018 with an average of 6.3% (37/591) after the start of mentorship (p = 0.019). Overall, 88% were eligible for and 68% received cryotherapy the same day: 10 cases were clinically suspicious for cancer; however, only 5 of those cases were confirmed using punch biopsy. Agreement rates with the expert reviewer for positive and negative cases were 100% (95% confidence interval [CI]: 79.4% to 100%) and 95.7% (95% CI: 92.2% to 97.9%), respectively, with negative predictive value (NPV) (100%), positive predictive value (PPV) (63.5%), and area under the curve of receiver operating characteristics (AUC ROC) (0.978). Kappa statistic was 0.74 (95% CI; 0.58 to 0.89); 0.64 and 0.79 at 3 and 6 months, respectively. In logistic regression, HIV and age were associated with VIA positivity (adjusted Odds Ratio [aOR]: 3.53, 95% CI: 1.10 to 11.29; p = 0.033 and aOR: 1.06, 95% CI: 1.0004 to 1.13; p = 0.048, respectively). We were unable to incorporate a control arm due to logistical constraints in routine humanitarian settings. Conclusions Our findings suggest that smartphone mentorship provided experiential learning to improve nurses’ competencies and VIA reliability and reproducibility, reduced false positive, and introduced peer-to-peer education and quality control services. Local collaboration; extending services to remote populations; decreasing unnecessary burden to screened women, providers, and tertiary centers; and capacity building through low-tech high-yield screening are promising strategies for scale-up of VIA programs.

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