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      Risk factors of cervical cancer after a negative cytological diagnosis in Polish cervical cancer screening programme

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          Abstract

          Risk factors of cervical cancer (CC) development are well investigated, however, those influencing the risk of a potential false negative cytology preceding diagnosis of an invasive CC are not. We have aimed to explore these factors according to the data from Organised Cervical Cancer Screening Programme (OCCSP) in Poland. A total of 2.36 million of Pap tests sampled in 2010–2012 within OCCSP were merged with the Polish National Cancer Registry to identify CC cases after abnormal cytology and after normal cytology within 3 years of screening. Of 1460 invasive CCs, 1025 were preceded by abnormal and 399 by normal cytology result. Multivariate logistic analysis indicated that the presence of microorganisms in the Pap (OR = 2.18, 95% CI 1.65–2.87), evaluation by smaller (below 9000 slides processed per year) laboratories (OR = 1.60, 95% CI 1.22–2.09) and non‐squamous histology of cancer increased the odds for a potential false negative result (OR = 3.39, 95% CI 2.37–4.85 for adenocarcinoma, OR = 1.99, 95% CI 1.11–3.55 for other types of carcinoma), whereas cervical ectropion, other macroscopic changes on the cervix and smoking decrease the odds for a potential false negative Pap test result preceding CC (OR = 0.61, 95% CI 0.45–0.82, OR = 0.41, 95% CI 0.25–0.67, OR = 0.60, 95% CI 0.46–0.78, respectively). Proper triage of women with microscopic signs of microorganisms in the Pap smear should be reconsidered and cytology should be assessed in laboratories processing over 9000 slides annually to decrease the odds for negative Pap test result in 2 years before CC diagnosis. Information on macroscopic changes on the cervix provided to cytomorphologist may reduce the risk of a potential false negative cytology result.

          Abstract

          Although aetiology of cervical cancer is well established, risk factors for missing advanced cervical neoplasia in screening vary. In our study, on over 2.36 million of Pap tests higher risk of a potential false negative smear was associated with a low laboratory workload, and thus, we propose a minimum benchmark. Additional risk factors of a negative cytology result before cervical cancer diagnosis were presence of microorganisms in the smear and non‐squamous histology of cancer. Ectropion, other macroscopic changes of the cervix and smoking decreased the risk.

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          The 2001 Bethesda System: terminology for reporting results of cervical cytology.

          The Bethesda 2001 Workshop was convened to evaluate and update the 1991 Bethesda System terminology for reporting the results of cervical cytology. A primary objective was to develop a new approach to broaden participation in the consensus process. Forum groups composed of 6 to 10 individuals were responsible for developing recommendations for discussion at the workshop. Each forum group included at least 1 cytopathologist, cytotechnologist, clinician, and international representative to ensure a broad range of views and interests. More than 400 cytopathologists, cytotechnologists, histopathologists, family practitioners, gynecologists, public health physicians, epidemiologists, patient advocates, and attorneys participated in the workshop, which was convened by the National Cancer Institute and cosponsored by 44 professional societies. More than 20 countries were represented. Literature review, expert opinion, and input from an Internet bulletin board were all considered in developing recommendations. The strength of evidence of the scientific data was considered of paramount importance. Bethesda 2001 was a year-long iterative review process. An Internet bulletin board was used for discussion of issues and drafts of recommendations. More than 1000 comments were posted to the bulletin board over the course of 6 months. The Bethesda Workshop, held April 30-May 2, 2001, was open to the public. Postworkshop recommendations were posted on the bulletin board for a last round of critical review prior to finalizing the terminology. Bethesda 2001 was developed with broad participation in the consensus process. The 2001 Bethesda System terminology reflects important advances in biological understanding of cervical neoplasia and cervical screening technology.
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            Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review.

            To evaluate the accuracy of conventional and new methods of Papanicolaou (Pap) testing when used to detect cervical cancer and its precursors. Systematic search of English-language literature through October 1999 using MEDLINE, EMBASE, other computerized databases, and hand searching. All studies that compared Pap testing (conventional methods, computer screening or rescreening, or monolayer cytology) with a concurrent reference standard (histologic examination, colposcopy, or cytology). Two reviewers independently reviewed selection criteria and completed 2 x 2 tables for each study. 94 studies of the conventional Pap test and three studies of monolayer cytology met inclusion criteria. No studies of computerized screening were included. Data were organized by cytologic and histologic thresholds used to define disease. For conventional Pap tests, estimates of sensitivity and specificity varied greatly in individual studies. Methodologic quality and frequency of histologic abnormalities also varied greatly between studies. In the 12 studies with the least biased estimates, sensitivity ranged from 30% to 87% and specificity ranged from 86% to 100%. Insufficient high-quality data exist to estimate test operating characteristics of new cytologic methods for cervical screening. Future studies of these technologies should apply adequate reference standards. Most studies of the conventional Pap test are severely biased: The best estimates suggest that it is only moderately accurate and does not achieve concurrently high sensitivity and specificity. Cost-effectiveness models of cervical cancer screening should use more conservative estimates of Pap test sensitivity.
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              Screening-preventable cervical cancer risks: evidence from a nationwide audit in Sweden.

              The effectiveness of cervical cancer screening programs differs widely in different populations. The reasons for these differences are unclear. Routine and comprehensive audits have been proposed as an ethically required component of screening. We performed a nationwide audit of the effectiveness of the Swedish cervical cancer screening program. We identified all invasive cervical cancer cases that were diagnosed in Sweden from January 1, 1999, through December 31, 2001, and had been reported to the Swedish Cancer Registry (n = 1230 cases). We verified the diagnoses by histopathologic rereview and matched each case subject to five (population-based) age-matched control subjects who were identified from the National Population Register. The Pap smear screening histories for case and control subjects were reviewed for a 6-year period using the National Cervical Cancer Screening Register, which contains data on essentially all relevant cytological and histological diagnoses in Sweden. Odds ratios (ORs), and their 95% confidence intervals (CIs), of cervical cancer according to screening history were calculated in conditional logistic regression models. All statistical tests were two-sided. Women who had not had a Pap smear within the recommended screening interval had higher risk of cervical cancer than women who had been screened (OR = 2.52, 95% CI = 2.19 to 2.91). This risk was similarly increased for all age groups (P(homogeneity) = .96). The risk for non-squamous cell cervical cancers (OR = 1.59, 95% CI = 1.20 to 2.11) was also increased. Women who had not had a Pap smear within the recommended screening interval had a particularly high risk of advanced cancers (OR = 4.82, 95% CI = 3.61 to 6.44). Among women who had been screened within the recommended interval, those with abnormal Pap smears had a higher risk of cervical cancer than those with normal smears (OR = 7.55, 95% CI = 5.88 to 9.69) and constituted 11.5% of all women with cervical cancer. Nonadherence to screening intervals was the major reason for cervical cancer morbidity. The screening program was equally effective for women of all ages and was also effective against non-squamous cancers.
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                Author and article information

                Contributors
                macios.anna@gmail.com
                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                02 May 2021
                May 2021
                : 10
                : 10 ( doiID: 10.1002/cam4.v10.10 )
                : 3449-3460
                Affiliations
                [ 1 ] Department of Cancer Prevention Maria Sklodowska‐Curie National Research Institute of Oncology Warsaw Poland
                [ 2 ] Department of Gastroenterology, Hepatology and Clinical Oncology Centre of Postgraduate Medical Education Warsaw Poland
                [ 3 ] Polish National Cancer Registry Maria Sklodowska‐Curie National Research Institute of Oncology Warsaw Poland
                [ 4 ] Department of Oncological Gastroenterology Maria Sklodowska‐Curie National Research Institute of Oncology Warsaw Poland
                [ 5 ] Department of Health Management and Health Economics University of Oslo Oslo Norway
                Author notes
                [*] [* ] Correspondence

                Anna Macios, Department of Cancer Prevention; Maria Sklodowska‐Curie National Research Institute of Oncology, Roentgen Street 5, 02‐781 Warsaw, Poland.

                Email: macios.anna@ 123456gmail.com

                Author information
                https://orcid.org/0000-0002-4279-5441
                Article
                CAM43857
                10.1002/cam4.3857
                8124104
                33934537
                186b5384-a8b6-4790-974b-9b2a25d3acbf
                © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 01 March 2021
                : 10 September 2020
                : 03 March 2021
                Page count
                Figures: 4, Tables: 2, Pages: 12, Words: 8186
                Funding
                Funded by: Polish Ministry of Health
                Categories
                Original Research
                Cancer Prevention
                Original Research
                Custom metadata
                2.0
                May 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:16.05.2021

                Oncology & Radiotherapy
                cancer prevention,cancer risk factors,screening,women's cancer
                Oncology & Radiotherapy
                cancer prevention, cancer risk factors, screening, women's cancer

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