Reducing overtreatment associated with overdiagnosis in cervical cancer screening—A model‐based benefit–harm analysis for Austria

Sroczynski, Gaby; Esteban, Eva; Widschwendter, Andreas; Oberaigner, Wilhelm; Borena, Wegene; Laer, Dorotheé von; Hackl, Monika; Endel, Gottfried; Siebert, Uwe

doi:10.1002/ijc.32849

Cited by 18 publications

(13 citation statements)

References 36 publications

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“…While this strategy has significantly reduced cancer incidence and mortality in screened populations, it is accompanied by overtreatment in the form of unnecessary procedures that have their own risks and complications, particularly among women of reproductive age. Thus, the ability to reduce the frequency of surveillance screening and the number of unnecessary treatments is expected to reduce this overtreatment burden on screened women (27)(28)(29)(30)(31). More importantly, the current source of cervical cancer resides primarily in unscreened or under-screened populations, and here an approach that triages samples based on the potential for future regression has the potential for even greater impact.…”

Section: Discussionmentioning

confidence: 99%

“…A consequence of this protocol is that women in under-resourced settings or hard-to-reach communities (e.g., immigrant or rural communities) are often under-screened and therefore at risk of undetected precancerous lesions and cancer (23)(24)(25)(26). In contrast, in adequately screened populations, there is a potential for overtreatment, with its associated risks and complications (27)(28)(29)(30)(31). Methods to improve risk assessment for cervical cancer, particularly assays that can predict regression of precursor lesions or clearance of HPV infection, would be expected to benefit both populations.…”

Section: Introductionmentioning

confidence: 99%

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T Cell Receptor Repertoires Acquired via Routine Pap Testing May Help Refine Cervical Cancer and Precancer Risk Estimates

et al. 2021

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Cervical cancer is the fourth most common cancer and fourth leading cause of cancer death among women worldwide. In low Human Development Index settings, it ranks second. Screening and surveillance involve the cytology-based Papanicolaou (Pap) test and testing for high-risk human papillomavirus (hrHPV). The Pap test has low sensitivity to detect precursor lesions, while a single hrHPV test cannot distinguish a persistent infection from one that the immune system will naturally clear. Furthermore, among women who are hrHPV-positive and progress to high-grade cervical lesions, testing cannot identify the ~20% who would progress to cancer if not treated. Thus, reliable detection and treatment of cancers and precancers requires routine screening followed by frequent surveillance among those with past abnormal or positive results. The consequence is overtreatment, with its associated risks and complications, in screened populations and an increased risk of cancer in under-screened populations. Methods to improve cervical cancer risk assessment, particularly assays to predict regression of precursor lesions or clearance of hrHPV infection, would benefit both populations. Here we show that women who have lower risk results on follow-up testing relative to index testing have evidence of enhanced T cell clonal expansion in the index cervical cytology sample compared to women who persist with higher risk results from index to follow-up. We further show that a machine learning classifier based on the index sample T cells predicts this transition to lower risk with 95% accuracy (19/20) by leave-one-out cross-validation. Using T cell receptor deep sequencing and machine learning, we identified a biophysicochemical motif in the complementarity-determining region 3 of T cell receptor β chains whose presence predicts this transition. While these results must still be tested on an independent cohort in a prospective study, they suggest that this approach could improve cervical cancer screening by helping distinguish women likely to spontaneously regress from those at elevated risk of progression to cancer. The advancement of such a strategy could reduce surveillance frequency and overtreatment in screened populations and improve the delivery of screening to under-screened populations.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

T Cell Receptor Repertoires Acquired via Routine Pap Testing May Help Refine Cervical Cancer and Precancer Risk Estimates

et al. 2021

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“… 2016 ; Sroczynski et al. 2020 ). To detect efficient strategies, so-called strongly dominated strategies are first excluded.…”

Section: Decision Analysismentioning

confidence: 99%

On the role of data, statistics and decisions in a pandemic

Jahn¹,

Friedrich

Behnke

et al. 2022

AStA Adv Stat Anal

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A pandemic poses particular challenges to decision-making because of the need to continuously adapt decisions to rapidly changing evidence and available data. For example, which countermeasures are appropriate at a particular stage of the pandemic? How can the severity of the pandemic be measured? What is the effect of vaccination in the population and which groups should be vaccinated first? The process of decision-making starts with data collection and modeling and continues to the dissemination of results and the subsequent decisions taken. The goal of this paper is to give an overview of this process and to provide recommendations for the different steps from a statistical perspective. In particular, we discuss a range of modeling techniques including mathematical, statistical and decision-analytic models along with their applications in the COVID-19 context. With this overview, we aim to foster the understanding of the goals of these modeling approaches and the specific data requirements that are essential for the interpretation of results and for successful interdisciplinary collaborations. A special focus is on the role played by data in these different models, and we incorporate into the discussion the importance of statistical literacy and of effective dissemination and communication of findings.

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“…MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions, or products referred to in the content. eliminated by the immune system during 1 to 2 years, resulting in a considerable risk of overdiagnosis and overtreatment of the HPV primary screening positives [7].…”

Section: Introductionmentioning

confidence: 99%

Performance of a 7-type HPV mRNA Test in Triage of HPV DNA Primary Screen Positive Women Compared to Liquid-based Cytology

Sørbye¹,

Falang²,

Antonsen³

2023

Preprint

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Background: A plethora of data supports HPV-based screening to be the preferred strategy for cervical cancer prevention. The shift to a more sensitive firstline test brings the need of effective triage up for discussion. Currently, most algorithms apply cytology as triage of HPV-DNA positive women. This study compared the performance of a 7-type HPV-mRNA test to cytology. Methods: From 2019-01-01, until 2021-12-31, cervical samples from 58,029 women were examined at the University Hospital of North Norway. 30.5% (17,684/58,029) fulfilled the criteria for HPV-DNA primary screening. All positive samples were triaged by cytology and followed-up according to national guidelines. Additionally, a 7-type HPV-mRNA test was applied. Study endpoint was histologically confirmed high grade lesion (CIN2+). Results: 5.6% (990/17,684) had positive HPV-DNA test, 97.2% (962/990) with valid HPV-mRNA results. 55.5% (534/962) had abnormal cytology (ASC-US+) and 35.1% (338/962) had positive HPV-mRNA test. 9.8% (94/962) had CIN2+. Sensitivity (CIN2+) of cytology versus the HPV-mRNA test was 83.0% (78/94) versus 76.6% (72/94), p=0.36. The specificity was 47.5% (412/868) versus 69.4% (602/868), p<0.001. PPV was 14.6% (78/534) and 21.3% (72/338), p=0.014 respectively. The number of colposcopies per CIN2+ detected by cytology and HPV-mRNA test was 6.8 and 4.7. Conclusion: The 7-type HPV mRNA test was more specific than cervical cytology in triage of HPV-DNA positive women. Using this biomarker as threshold for colposcopy may better balance the benefits and harms of screening.

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Reducing overtreatment associated with overdiagnosis in cervical cancer screening—A model‐based benefit–harm analysis for Austria

Cited by 18 publications

References 36 publications

T Cell Receptor Repertoires Acquired via Routine Pap Testing May Help Refine Cervical Cancer and Precancer Risk Estimates

T Cell Receptor Repertoires Acquired via Routine Pap Testing May Help Refine Cervical Cancer and Precancer Risk Estimates

On the role of data, statistics and decisions in a pandemic

Performance of a 7-type HPV mRNA Test in Triage of HPV DNA Primary Screen Positive Women Compared to Liquid-based Cytology

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