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A post hoc analysis of the ATHENA study was performed to determine whether true HPV‐negative cervical lesions occur and whether they have clinical relevance. The ATHENA database was searched for all CIN2 or worse (CIN2+) cases with cobas HPV‐negative results and comparison was made with Linear Array (LA) and Amplicor to detect true false‐negative HPV results. Immunostaining with p16 was performed on these cases to identify false‐positive histology results. H&E slides were re‐reviewed by the study pathologists with knowledge of patient age, HPV test results and p16 immunostaining. Those with positive p16 immunostaining and/or a positive histopathology review underwent whole tissue section HPV PCR by the SPF10/LiPA/RHA system. Among 46,887 eligible women, 497 cases of CIN2+ were detected, 55 of which tested negative by the cobas® HPV Test (32 CIN2, 23 CIN3/ACIS). By LA and/or Amplicor, 32 CIN2+ (20 CIN2, 12 CIN3/ACIS) were HPV positive and categorized as false‐negatives by cobas HPV; nine of 12 false‐negative CIN3/ACIS cases were p16+. There were 23 cases (12 CIN2, 11 CIN3/ACIS) negative by all HPV tests; seven of 11 CIN3/ACIS cases were p16+. H&E slides were available for six cases for re‐review and all were confirmed as CIN3/ACIS. Tissue PCR was performed on the six confirmed CIN3/ACIS cases (and one without confirmation): four were positive for HPV types not considered oncogenic, two were positive for oncogenic genotypes and one was indeterminate. In summary, subanalysis of a large cervical cancer screening study did not identify any true CIN3/ACIS not attributable to HPV.

Background: Interval cancer rates can be used to evaluate whether screening with digital breast tomosynthesis (DBT) contributes to a screening benefit. Purpose:To compare interval cancer rates and tumor characteristics in DBT screening to those in a contemporary population screened with digital mammography (DM). Materials and Methods:The prospective population-based Malmö Breast Tomosynthesis Screening Trial (MBTST) was designed to compare one-view DBT to two-view DM in breast cancer detection. The interval cancer rates and cancer characteristics in the MBTST were compared with an age-matched contemporary control group, screened with two-view DM at the same center. Conditional logistic regression was used for data analysis.Results: There were 14 848 women who were screened with DBT and DM in the MBTST between January 2010 and February 2015. The trial women were matched with two women of the same age and screening occasion at DM screening during the same period. Matches for 13 369 trial women (mean age, 56 years  10 [standard deviation]) were found with 26 738 women in the control group (mean age, 56 years  10). The interval cancer rate in the MBTST was 1.6 per 1000 screened women (21 of 13 369; 95% CI: 1.0, 2.4) compared with 2.8 per 1000 screened women in the control group (76 of 26 738 [95% CI: 2.2, 3.6]; conditional odds ratio, 0.6 [95% CI: 0.3, 0.9]; P = .02). The invasive interval cancers in the MBTST and in the control group showed in general high and 75% [54 of 72]), and low proportions of luminal A-like subtype (26% [five of 19] and 17% [12 of 72]), respectively. Conclusion:The reduced interval cancer rate after screening with digital breast tomosynthesis compared with a contemporary agematched control group screened with digital mammography might translate into screening benefits. Interval cancers in the trial generally had nonfavorable characteristics.

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igital breast tomosynthesis (DBT) has the potential to become a widespread screening modality. Results from large prospective European population-based screening trials (1-3) have shown that DBT as a stand-alone modality or as an adjunct to digital mammography (DM; acquired or synthetic) improves the cancer detection rate by about 30% with acceptable recall rates compared with DM alone. Retrospective studies performed in the United States showed a more moderate improvement in cancer detection rates but a substantial reduction in recall rates (4). Before the broad implementation of DBT in screening, it is important to assess whether the detection of additional cancers leads to an actual screening benefit (ie, reduced breast cancer mortality) or whether mainly low-risk tumors are detected, potentially resulting in overdiagnosis. Because data from randomized DBT trials with breast cancer mortality as the outcome are likely to be limited, studies on cancer biology as a surrogate can elucidate this issue.Breast cancer is a heterogeneous disease in terms of its biologic profile and clinical manifestation. Histopathologic parameters, such as hormone receptor status and grade, and staging can be used for prognostic and predictive stratification. Classification of intrinsic subtypes on the basis of gene expression profiling can be used to further refine the stratification of invasive cancers (5). Because gene expression analysis is not always available, a practical approach was proposed by the St Gallen International Expert Consensus to use surrogate molecular subtyping on the basis of routine immunohistochemical and in situ hybridization analyses (6,7). The St Gallen classification consists of five

Mammographic tumour appearance may provide prognostic useful information. For example, spiculation indicates invasiveness, but also better survival compared to tumours with other appearances. We aimed to study the relationship between mammographic tumour appearance and established clinicopathological factors, including surrogate molecular breast cancer subtypes, in the large Malmö Diet and Cancer Study. A total of 1116 women with invasive breast cancer, diagnosed between 1991 and 2014, were included. Mammographic tumour appearance in relation to status for oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2, histological grade, Ki67 and molecular subtype was analysed using various regression models. All models were adjusted for relevant confounders, including breast density, which can affect mammographic appearance. The results consistently showed that spiculated tumours are indicative of favourable characteristics, as they are more likely to be ER and PR positive, and more often exhibit lower histological grade and lower Ki67 expression. Furthermore, spiculated tumours tend to be of luminal A-like subtype, which is associated with a good prognosis. The establishment of associations between mammographic tumour appearance and clinico­pathological factors may aid in characterizing breast cancer at an earlier stage. This could contribute to more individualized breast cancer treatment in the future.

Background: Digital breast tomosynthesis (DBT) improves breast cancer (BC) detection compared to mammography, however, it is unknown whether this reduces interval cancer rate (ICR) at follow-up. Methods: Using individual participant data (IPD) from DBT screening studies (identified via periodic literature searches July 2016 to November 2019) we performed an IPD meta-analysis. We estimated ICR for DBTscreened participants and the difference in pooled ICR for DBT and mammography-only screening, and compared interval BC characteristics. Two-stage meta-analysis (study-specific estimation, pooled synthesis) of ICR included random-effects, adjusting for study and age, and was estimated in age and density subgroups. Comparative screening sensitivity was calculated using screen-detected and interval BC data. Findings: Four prospective DBT studies, from European population-based programs, contributed IPD for 66,451 DBT-screened participants: age-adjusted pooled ICR was 13.17/10,000 (95%CI: 8.25À21.02). Pooled ICR was higher in the high-density (21.08/10,000; 95%CI: 6.71À66.27) than the low-density (8.63/10,000; 95%CI: 5.25À14.192) groups (P = 0.03) however estimates did not differ across age-groups (P = 0.32). Based on two studies that also provided data for 153,800 mammography screens (age-adjusted ICR 17.69/10,000; 95%CI: 13.22À23.66), DBT's pooled ICR was 16.83/10,000 (95%CI: 11.89À23.82). Comparative meta-analysis showed a non-significant difference in ICR (-0.44/10,000; 95%CI: -11.00À10.11) and non-significant difference in screening sensitivity (6.79%; 95%CI: -0.73À14.87%) between DBT and DM but a significant pooled difference in cancer detection rate of 33.49/10,000 (95%CI: 23.88À43.10). Distribution of interval BC prognostic characteristics did not differ between screening modalities except that those occurring in DBT-screened participants were significantly more likely to be negative for axillary-node metastases (P = 0.005). Interpretation: Although heterogeneity in ICR estimates and few datasets limit recommendations, there was no difference between DBT and mammography in pooled ICR despite DBT increasing cancer detection.

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