Cervical cancer screening pathways in France in 2015-2021, a nationwide study based on medico-administrative data.

To better document cervical cancer screening (CCS) pathways, the purpose of our study was to examine CCS pathways among women who had undergone a screening test (opportunistic or organised programme), based on real-life data over a 7-year period. This study used data from the French national health care database (SNDS), which covers almost 100 % of the French population of around 66 million inhabitants. Data from 2015 to 2021 were extracted. More than one quarter (27 %) of women who were at least 25 years old in 2015 and up to 65 years old in 2021 were not screened over the 2015-2021 period. Compared to women who had undergone screening at least once, women who were not screened were older (36 % vs. 23 % in the 50-59 years age group in 2015) and lived in the most deprived urban areas (21 % vs 16 % for less and most deprived respectively). 57 % of women underwent screening within recommended intervals, 13 % of women were under-screened, and 30 % were overscreened. Overall, our study identified that, in 2021, women who participated in the French organised screening programme were less likely to be screened within the recommended interval over the 7-year period. These analyses need to be continued over time in order to assess whether the programme helps reintegrate women into the screening process.

Cost-effectiveness analysis of alternative colorectal cancer screening strategies in high-risk individuals.

BACKGROUND AND AIMS: Current guidelines recommend colonoscopy every 3-5 years for colorectal cancer (CRC) screening of individuals with a familial history of CRC. The objective of this study was to compare the cost effectiveness of screening alternatives in this population. METHODS: Eight screening strategies were compared with no screening: fecal immunochemical test (FIT), Stool DNA and blood-based screening every 2 years, colonoscopy, computed tomography colonography, colon capsules, and sigmoidoscopy every 5 years, and colonoscopy at 45 years followed, if negative, by FIT every 2 years. Screening test and procedures performance were obtained from the literature. A microsimulation model reproducing the natural history of CRC was used to estimate the cost (€2018) and effectiveness [quality-adjusted life-years (QALYs)] of each strategy. A lifetime horizon was used. Costs and effectiveness were discounted at 3.5% annually. RESULTS: Compared with no screening, colonoscopy and sigmoidoscopy at a 30% uptake were the most effective strategy (46.3 and 43.9 QALY/1000). FIT at a 30 µg/g threshold with 30% uptake was only half as effective (25.7 QALY). Colonoscopy was associated with a cost of €484,000 per 1000 individuals whereas sigmoidoscopy and FIT were associated with much lower costs (€123,610 and €66,860). Incremental cost-effectiveness rate for FIT and sigmoidoscopy were €2600/QALY (versus no screening) and €3100/QALY (versus FIT), respectively, whereas it was €150,000/QALY for colonoscopy (versus sigmoidoscopy). With a lower threshold (10 µg/g) and a higher uptake of 45%, FIT was more effective and less costly than colonoscopy at a 30% uptake and was associated with an incremental cost-effectiveness ratio (ICER) of €4240/QALY versus no screening. CONCLUSION: At 30% uptake, current screening is the most effective screening strategy for high-risk individuals but is associated with a high ICER. Sigmoidoscopy and FIT at lower thresholds (10 µg/g) and a higher uptake should be given consideration as cost-effective alternatives. PLAIN LANGUAGE SUMMARY: Cost-effectiveness analysis of colorectal cancer screening strategies in high-risk individuals Fecal occult blood testing with an immunochemical test (FIT) is generally considered as the most cost-effective alternative in colorectal cancer screening programs for average risk individuals without family history.Current screening guidelines for high-risk individuals with familial history recommend colonoscopy every 3-5 years.Colonoscopy every 3-5 years for individuals with familial history is the most effective strategy but is associated with a high incremental cost-effectiveness ratio.Compared with colonoscopy, if screening based on FIT is associated with a higher participation rate, it can achieve a similar effectiveness at a lower cost.

Cost-effectiveness analysis of alternative colon cancer screening strategies in the context of the French national screening program.

BACKGROUND: A nationwide colorectal cancer (CRC) screening program was set up in France from 2009 for average-risk, asymptomatic people aged 50-74 years based on an immunochemical fecal occult blood test [faecal immunochemical test (FIT)] every 2 years, followed by colonoscopy if positive. The European standard recommends a participation rate of 45% for the program to be cost-effective, yet the latest published rate in France was 34%. The objective of this study was to compare the cost effectiveness of screening alternatives taking real-world participation rates into account. METHODS: Eight screening strategies were compared, based either on a screening test (Guaiac or FIT testing, blood-based, stool DNA, computed tomography colonography, colon capsules, and sigmoidoscopy) followed by full colonoscopy if positive or direct colonoscopy. A microsimulation model was used to estimate the cost effectiveness associated with each strategy. RESULTS: Compared with no screening, FIT was associated with a 14.0 quality-adjusted life year (QALY) increase of €50,520 per 1000 individuals, giving an incremental cost-effectiveness ratio (ICER) of €3600/QALY. Only stool DNA and blood-based testing were associated with a QALY increase compared with FIT, with stool DNA weakly dominated by blood-based testing, and the latter associated with an ICER of €154,600/QALY compared with FIT. All other strategies were dominated by FIT. CONCLUSION: FIT every 2 years appears to be the most cost-effective CRC screening strategy when taking into account a real-world participation rate of 34%.

Breast cancer screening: Impact on care pathways.

BACKGROUND: Controversy persists concerning screening programs (SPs), related to a potential risk of overdiagnosis or the impact on survival. One of the main questions to be addressed concerns the aggressiveness of the related treatments. METHODS: Using the "Cancer Cohort," a national-based cohort (medico-administrative database), all women between the ages of 50 and 74 years and treated in 2014 for incident breast cancer were compared, according to whether their diagnosis was made following a mammogram performed within the framework of the SP (SP group) or outside it (NSP group). RESULTS: A total of 23 788 women were identified: 13 530 (57%) in the SP group and 10 258 (43%) in the NSP group. The women in the SP group had a higher rate of in situ or localized invasive breast cancer. They had a higher rate of breast-conserving surgery (82% vs 70%), and a lower rate of chemotherapy (34% vs 53%). These findings were observed irrespective of the stage. They had a higher rate of pathways involving breast-conserving surgery followed by radiotherapy. Among women with metastatic cancer, those in the SP group had a lower proportion of liver, lung, brain, and bone metastases, and a higher proportion of lymph node metastases (other than axillary), irrespective of the time to onset of the metastases. CONCLUSION: The women in whom cancer was diagnosed following a mammogram performed in the context of the SP had less advanced cancer and less aggressive treatments. This observational study helps illustrate the benefit of the SP in France using a different approach.

[Cancer screening: for who? Why? How? What organizational evolution?] / Dépistage des cancers : pour qui ? pourquoi ? comment ? quelle évolution organisationnelle ?

Cancer screening: for who? Why? How? What organizational evolution? Screening aims to anticipate the occurrence of symptoms to get an early detection of cancerous or pre-cancerous lesions in order to favorably influence the prognosis. However, the deployment of a screening program is not always justified and it must be based on a rigorous evaluation of its benefits, risks and limitations, especially for people apparently "in good health". Exposure of healthy people to unjustified or unassessed risks could result in loss of opportunity and be considered as unethical. The evaluation is generally carried out on the basis of Wilson and Jungner's criteria (WHO, 1968) which relate in particular to the acceptability of screening and the documentation of its efficacy, safety and efficiency. Once these prerequisites are verified, the strategy must be refined (Who to invite? How ?, Etc.) and the underlying organization determined so as to allow the program to be rolled out and to ensure its continuous operation and monitoring (Which centers? What information? What data collection and which indicators, etc.). In particular, it must not generate inequalities in access to screening and loss of opportunity. In France, territorial coordination of programs is generally devolved to local non-profitorganizations relying on health professionals who perform screening; a major reorganization is currently being rolled out to achieve a regional network. This reform will be accompanied by a quality approach to ensure the harmonized implementation of the missions.

Dépistage des cancers : pour qui ? Pourquoi ? Comment ? Quelle évolution organisationnelle ? Le dépistage vise à anticiper la survenue de symptômes pour favoriser une détection précoce de lésions cancéreuses ou pré-cancéreuses de sorte à influencer favorablement le pronostic par la mise en route précoce d'un traitement. Pour autant, le déploiement d'un programme de dépistage n'est pas toujours justifié aussi doit-il doit se fonder sur une évaluation rigoureuse de ses bénéfices, risques et limites, en particulier pour des personnes apparemment « en bonne santé ¼. L'exposition de personnes bien portantes à des risques injustifiés ou non évalués pourrait entrainer des pertes de chance et être considérée comme non éthique. L'évaluation du bien-fondé est généralement réalisée à partir des critères de Wilson et Jungner (OMS, 1968) lesquels portent en particulier sur l'acceptabilité du dépistage et sur la documentation de l'efficacité, de la sécurité et de l'efficience d'un programme. Dès lors que ces critères et prérequis sont vérifiés, la stratégie doit être affinée (qui inviter ? comment ?, etc.) et l'organisation sous-jacente déterminée de sorte à permettre le déploiement du programme, d'assurer son fonctionnement en continu et son suivi (quels centres ? quel retentissement sur l'offre de soins ? quelle information ? quel recueil de données et quels indicateurs ? etc .). Il s'agit en particulier de ne pas générer d'inégalités d'accès et de pertes de chances. En France, la déclinaison territoriale des programmes repose en arrière-plan sur des organisations le plus souvent départementales lesquelles s'appuient sur les professionnels de santé proposant ou réalisant les dépistages ; celles-ci se sont engagées en 2018 dans une profonde réorganisation en vue d'adopter un maillage régional. Cette réforme s'accompagnera d'une démarche qualité pour garantir la mise en oeuvre harmonisée des missions.

[French national cancer screening programs: What does the future hold?] / Quelle évolution pour les programmes de dépistage des cancers ?

French national cancer screening programs : what does the future hold? Three organized screening programs are in place or being rolled out in France for breast, colorectal and cervical cancers. Short or medium-term developments aim at facilitating the integration of technological or organizational innovations and at meeting the quality and safety requirements of the screening procedure. However, the stakes differ between the different programs. It is for the screening of breast cancer, the oldest program, the integration of technological innovations, such as breast tomosynthesis -3D- and dematerialization of mammograms, and the renovation of the program in order to propose a personalized follow-up, better coordinated and with an increased involvement of general practitioners. For colorectal cancer, given that a highly effective screening program using a fecal immunological test has been rolled out in 2015, the challenge is now to increase participation, which is too low -35%-, in order to improve the impact of the program. The cervical cancer screening program, whose opportunistic practice is already widespread, is currently being deployed ; it aims to reduce inequalities in access to screening by sending invitations to women who have not been tested in the last 3 years; the sampling will be performed in liquid phase which allows to anticipate a future migration to the HPV test.

Quelle évolution pour les programmes de dépistage des cancers ? Trois programmes de dépistage organisé sont en place ou en cours de déploiement en France pour les cancers du sein, colorectal et du col de l'utérus. Les perspectives d'évolution à court ou moyen termes visent à faciliter l'intégration des innovations technologiques ou organisationnelles dans ces programmes et à satisfaire aux exigences de qualité et de sécurité de la procédure de dépistage. Les enjeux diffèrent cependant entre les différents programmes. Il s'agit pour le dépistage des cancers du sein, le programme le plus ancien, de l'intégration d'innovations technologiques, notamment la tomosynthèse et la dématérialisation des mammographies pour la seconde lecture, et de la rénovation du programme de sorte à proposer aux femmes un suivi personnalisé, mieux coordonné et impliquant davantage le médecin traitant. Pour le cancer colorectal, dans la mesure où un programme performant de dépistage par test immunologique est en place, l'enjeu est d'augmenter la participation, par trop insuffisante, ce qui permettra d'améliorer l'impact du programme. Le programme de dépistage du cancer du col de l'utérus, dont la pratique est déjà bien répandue, est quant à lui en phase de déploiement ; il vise à réduire les inégalités d'accès par l'envoi d'invitations en direction des femmes n'ayant pas réalisé de dépistage dans les 3 dernières années ; le prélèvement sera réalisé en phase liquide ce qui permet d'anticiper un passage au test HPV le cas échéant.

Organised screening for cervical cancer in France: a cost-effectiveness assessment.

OBJECTIVE: According to the third cancer plan, organised screening (OS) of cervical cancer (CC) among women aged 25-65 years should be implemented in France in the forthcoming years. The most efficient way to implement OS in the French healthcare system is yet to be determined. METHODS: A microsimulation model was developed adopting a collective 'all payers' perspective. A closed cohort of women eligible for CC screening and representative in terms of age and participation in individual screening (IndScr) by annual Papanicolaou (Pap) testing every 3 years was modelled on a lifetime horizon. Different OS strategies, additive to IndScr with a 61.9% participation rate based on mailed invitations to non-participant women to perform OS were assessed. Similar modalities were applied to OS and IndScr participants. Strategies implied different screening tests (Papanicolaou (Pap) test, human papillomavirus (HPV) test and p16/Ki67 double staining) and OS periodicity. RESULTS: Compared with IndScr only, all OS strategies were associated with decreased cancer incidence/mortality (from 14.2%/13.5% to 22.9%/25.8%). Most strategies generated extra costs ranging from €37.9 to €1607 per eligible woman. HPV testing every 10 and 5 years were cost saving. HPV tests every 10 and 5 years were the most efficient strategies, generating more survival at lower costs than Pap-based strategies. Compared to IndScr only, an HPV test every 10 years was cost saving. The most effective strategies were p16/Ki67 as primary or HPV positive confirmation tests, with respective incremental cost-effectiveness ratios of €6 541 250 and €101 391 per life year. Pap-based strategies generated intermediary results. CONCLUSION: OS strategies based on the HPV test appear highly efficient. However, our results rely on the assumption that women and practitioners comply with the recommended OS periodicities (3, 5, 10 years). Implementing these OS modalities will require major adaptations to the current CC screening organisation. Pap test-based strategies might be simpler to setup while preparing an appropriate implementation of more efficient OS screening modalities.

Study on polychlorobiphenyl serum levels in French consumers of freshwater fish.

INTRODUCTION: Polychlorobiphenyls (PCBs) are persistent pollutants that are widespread in the environment and in foodstuffs, particularly in freshwater fish, which frequently exceed the maximum levels set by European regulations. OBJECTIVES: First, we describe the consumption of freshwater fish and serum PCB levels in French anglers, a population expected to have the highest level of dietary PCB exposure. Second, we investigated whether there is a statistical relationship between serum PCB levels and the angler consumption of freshwater fish with high PCB bioaccumulation potential (PCB-BP(+) freshwater fish) in order to make recommendations with regard to safe consumption of freshwater fish. METHODS: We conducted a survey of anglers from six sites with contrasting PCB contamination levels. The survey included a food consumption frequency questionnaire and blood samples were taken to assess serum PCB levels. We used a regression model to determine the main factors contributing to serum PCB levels. RESULTS: Consumption of PCB-BP(+) freshwater fish was relatively infrequent. Serum PCB levels of the study population and of women of childbearing age were in the same range as those observed in the French population and in neighbouring European countries, but higher than in the North American population. The two factors with the highest positive association with serum PCB levels were age (R(2)=61%) and the consumption of PCB-BP(+) freshwater fish (R(2)=2%). Using the regression model, we calculated, for several scenarios depending on the age and gender of the population, the maximum annual frequencies for PCB-BP(+) freshwater fish consumption that do not exceed the critical body burden threshold. CONCLUSION: Following the results of this study, the French agency for food, environmental and occupational health and safety (ANSES) issued an opinion and recommended some specific maximum freshwater fish consumption frequencies to protect the French general population.

[Management of hemochromatosis linked to HFE gene]. / Prise en charge de l'hémochromatose liée au gène HFE.

Phenotypic expression of the homozygous C282Y/C282Y mutation of the HFE gene has been classified in five stages, and appropriate management recommended for each stage. Phlebotomy is indicated for stages>or=2, that is, with elevated transferrin saturation and serum ferritin levels >300 microg/L in men and >200 microg/L in women. Maximal volume per phlebotomy is 7 mL/kg and should not exceed 550 mL. The main goal of this iron-depletion therapy is to reach and maintain serum ferritin levels

Current approaches to the management of hemochromatosis.

The term hemochromatosis encompasses at least four types of genetic iron overload conditions, most of them recently distinguished from one another as a result of the identification of a series of genes related to iron metabolism. At least three of these entities (HFE hemochromatosis, juvenile hemochromatosis and transferrin receptor 2 hemochromatosis) involve systemic hepcidin deficiency as a key pathogenetic factor. Major advances in the management of hemochromatosis influence the diagnostic approach to the disease, with the development of an overall non invasive strategy, mainly based on clinical, biological (iron parameters and genetic testing), and imaging (especially magnetic resonance imaging) data. Therapeutic management remains, on the curative side, dominated by phlebotomy (venesection), practical aspects of which have been recently revisited by the Guidelines Department of the French "Haute Autorité de Santé." However, innovative treatment approaches, based on the improved pathophysiological understanding of these diseases and the progress in iron chelation therapy, are emerging. Preventive therapy, focused on family screening, remains a key part of the management of hemochromatosis.

[Practical management of HFE hemochromatosis]. / Prise en charge de l'hémochromatose HFE.

HFE-linked, or type 1, hemochromatosis is by far, in the causasians, the most frequent form of chronic iron overload of genetic origin. Its practical management has been recently defined by the French Agency "Haute Autorité de santé". It rests upon a new classification of phenotypic expression. This staging comprises 5 grades according to the combined results of plasma transferrin saturation, ferritinemia and clinical data. The extension of the initial work-up as well as the follow-up modalities is adapted to the staging. A liver biopsy remains indicated only in case of suspected cirrhosis. Venesection therapy is the reference treatment. It is indicated when grade is > or = 2 (i.e. when both transferrin saturation and ferritinemia are increased). The phlebotomy volume should be adapted to the patient's weight. The goal of depletion treatment is to obtain and maintain ferritinemia < or = 50 microg/L. Venesections, especially for maintenance therapy, can be performed at home, which requires a close coordination between the various medical and paramedical partners. Family screening, based upon HFE test, transferrin saturation and serum ferritin, is highly recommended.

Haemophilus influenzae carriage in children attending French day care centers: a molecular epidemiological study.

The nasopharyngeal Haemophilus influenzae flora of healthy children under the age of 3 years attending day care centers in three distinct French geographic areas was analyzed by sampling during two periods, spring 1999 (May and June) and fall 1999 (November and December). The average carrier rate among 1,683 children was 40.9%. The prevalence of capsulated H. influenzae carriers was 0.4% for type f and 0.6% for type e. No type b strains were found among these children, of whom 98.5% had received one or more doses of anti-Haemophilus b vaccine. Among the strains, 44.5% were TEM-type beta-lactamase producers and nine (1.3%) were beta-lactamase-negative ampicillin-resistant strains. Pulsed-field gel electrophoresis restriction patterns showed a large diversity with 366 SmaI patterns from 663 strains. Among the strains isolated during a given period, 33% were isolated simultaneously in more than one area. In each area, depending on the sampling period, 68 to 72% of the strains had new pulsotypes and persistence of 28 to 32% of the strains was noted. For the 297 beta-lactamase-producing strains, 194 patterns were found. The genomic diversity of these strains was comparable to that of the whole set of strains and does not suggest a clonal diffusion. Among the beta-lactamase-producing strains isolated in November and December, depending on the area, 66 to 73% had new pulsotypes with persistence of only 27 to 33% of the strains. In any given geographic area, colonization by H. influenzae appears to be a dynamic process involving a high degree of genomic heterogeneity among the noncapsulated colonizing strains.