European validation of an image-derived AI-based short-term risk model for individualized breast cancer screening-a nested case-control study.

Background: Image-derived artificial intelligence (AI)-based risk models for breast cancer have shown high discriminatory performances compared with clinical risk models based on family history and lifestyle factors. However, little is known about their generalizability across European screening settings. We therefore investigated the discriminatory performances of an AI-based risk model in European screening settings. Methods: Using four European screening populations in three countries (Italy, Spain, Germany) screened between 2009 and 2020 for women aged 45-69, we performed a nested case-control study to assess the predictive performance of an AI-based risk model. In total, 739 women with incident breast cancers were included together with 7812 controls matched on year of study-entry. Mammographic features (density, microcalcifications, masses, left-right breast asymmetries of these features) were extracted using AI from negative digital mammograms at study-entry. Two-year absolute risks of breast cancer were predicted and assessed after two years of follow-up. Adjusted risk stratification performance metrics were reported per clinical guidelines. Findings: The overall adjusted Area Under the receiver operating characteristic Curve (aAUC) of the AI risk model was 0.72 (95% CI 0.70-0.75) for breast cancers developed in four screening populations. In the 6.2% [529/8551] of women at high risk using the National Institute of Health and Care Excellence (NICE) guidelines thresholds, cancers were more likely diagnosed after 2 years follow-up, risk-ratio (RR) 6.7 (95% CI 5.6-8.0), compared with the 69% [5907/8551] of women classified at general risk by the model. Similar risk-ratios were observed across levels of mammographic density. Interpretation: The AI risk model showed generalizable discriminatory performances across European populations and, predicted ∼30% of clinically relevant stage 2 and higher breast cancers in ∼6% of high-risk women who were sent home with a negative mammogram. Similar results were seen in women with fatty and dense breasts. Funding: Swedish Research Council.

Benefits and harms of breast cancer mammography screening for women at average risk of breast cancer: A systematic review for the European Commission Initiative on Breast Cancer.

OBJECTIVES: Mammography screening is generally accepted in women aged 50-69, but the balance between benefits and harms remains controversial in other age groups. This study systematically reviews these effects to inform the European Breast Cancer Guidelines. METHODS: We searched PubMed, EMBASE and Cochrane Library for randomised clinical trials (RCTs) or systematic reviews of observational studies in the absence of RCTs comparing invitation to mammography screening to no invitation in women at average breast cancer (BC) risk. We extracted data for mortality, BC stage, mastectomy rate, chemotherapy provision, overdiagnosis and false-positive-related adverse effects. We performed a pooled analysis of relative risks, applying an inverse-variance random-effects model for three age groups (<50, 50-69 and 70-74). GRADE (Grading of Recommendations Assessment, Development and Evaluation) was used to assess the certainty of evidence. RESULTS: We identified 10 RCTs including 616,641 women aged 38-75. Mammography reduced BC mortality in women aged 50-69 (relative risk (RR) 0.77, 95%CI (confidence interval) 0.66-0.90, high certainty) and 70-74 (RR 0.77, 95%CI 0.54-1.09, high certainty), with smaller reductions in under 50s (RR 0.88, 95%CI 0.76-1.02, moderate certainty). Mammography reduced stage IIA+ in women 50-69 (RR 0.80, 95%CI 0.64-1.00, very low certainty) but resulted in an overdiagnosis probability of 23% (95%CI 18-27%) and 17% (95%CI 15-20%) in under 50s and 50-69, respectively (moderate certainty). Mammography was associated with 2.9% increased risk of invasive procedures with benign outcomes (low certainty). CONCLUSIONS: For women 50-69, high certainty evidence that mammography screening reduces BC mortality risk would support policymakers formulating strong recommendations. In other age groups, where the net balance of effects is less clear, conditional recommendations will be more likely, together with shared decision-making.

HPV screening performance indicators in women who previously tested HPV-negative: The second round of Vallecamonica screening programme, Northern Italy.

OBJECTIVE: To present performance indicators from the second round of the Vallecamonica-Sebino HPV screening programme in women who had tested negative about four years earlier (mean 45 months). METHODS: From 2010 to 2012, the target female population (aged 25-64) was invited to the first HPV screening round. In 2013-2017, women were rescreened for the second round. HPV-negative women at the first round were initially rescreened after three years. The interval was gradually increased to five years. HPV-positive women underwent cytology triage: positives were referred to colposcopy and negatives to repeat testing after one year. If HPV was persistently positive, women were referred to colposcopy, if negative, to normal interval rescreening. RESULTS: In the second round, of 13,824 previously HPV-negative women, 598 were HPV-positive (4.3%), of whom 297 were positive at cytology triage. Of those referred to one-year HPV test, 291 complied (98.0%), 133 (50.2%) of whom were persistently positive. Total referral was 3.1% compared with 6.6% in the first round (age-adjusted relative referral 0.59, 95% CI: 0.53-0.65). There were 24 cervical intraepithelial neoplasia 2+ (three cervical intraepithelial neoplasia 3+). Detection was 0.17%, compared with 0.9% in the first round. Age-adjusted relative detections were 0.25 (95% CI: 0.16-0.39) and 0.18 (95% CI: 0.05-0.61) for cervical intraepithelial neoplasia 2+ and cervical intraepithelial neoplasia 3+, respectively. Positive predictive value was 5.7%, compared with 14.6% in the first round. CONCLUSIONS: At second round, referral was half that at first round, while cervical intraepithelial neoplasia 2+ detection decreased nine-fold. Consequently, positive predictive value decreased dramatically. Rescreening four years after an HPV-negative test makes the process inefficient due to the low prevalence of lesions.