Prediction of high-grade cervical intraepithelial neoplasia in cytologically normal women by human papillomavirusesting

Human papillomavirus (HPV) testing has been suggested for primary screening of cervical cancer. Prediction of future high-grade cervical lesions is crucial for effectiveness and cost. We performed a case control study in a retrospective cohort of women with at least two cervical smears, all but the last one being negative, from the organized cervical screening programme in Florence, Italy. We searched for high-risk HPV in all previous, archival, smears from cases (new histologically confirmed cervical intraepithelial neoplasia (CIN) grade II or worse) and in one previous smear from each control (last smear cytologically normal, matched by age and interval (latency) from last smear). We applied polymerase chain reaction (PCR), and the b-globin gene was used as a DNA preservation marker. High-risk HPV was identified in 71/92 (77.17%) previous smears from 79 cases and 17/332 controls (5.12%). The odds ratio (OR) was 63.76 (95% CI 30.57–132.96). Among cases the proportion of HPV-positive smears declined slightly with increasing latency. Among cases, HPV was found in 81.24% (95% CI 69.93–88.96%) of smears with latency < 4 years and in 67.80% (95% CI 47.72–82.93%) of those taken at longer intervals, up to 6 years. These findings suggest that testing for high-risk HPV allows predicting 80% of CINII/III 3 years before the cytological diagnosis and two thirds 6 years before. They also suggest that testing women negative for high-risk HPV at longer interval and strictly following-up women who are HPV positive could be an effective strategy for cervical cancer screening. © 2000 Cancer Research Campaign http://www.bjcancer.co

Association of FOBT-assessed faecal Hb content with colonic lesions detected in the Florence screening programme

We assessed the correlation between quantitative results of immunological faecal occult blood testing (I-FOBT) and colonic lesions (191 colorectal cancers, 890 adenomas) detected at colonoscopy in 2597 FOBT+ (cutoff 100 ng ml−1 Hb) subjects. At univariate analysis, a higher average faecal Hb content was significantly associated with male gender (P=0.003), age (P=0.02), and colonoscopy findings (P=0.000). Among adenomas, higher faecal Hb content was significantly associated with size (P=0.0000), presence of severe dysplasia (P=0.0001), presence of villous component (P=0.0002), and location in the left colon (P=0.003). At multivariate analysis adjusting for potential confounders, age (P=0.03), size (P=0.0000), and location in the left colon (P=0.0005) were confirmed as having an independent association with higher faecal Hb content. Immunological FOBT is confirmed to be a specific screening test to detect cancer and adenoma, with a low positivity rate (3.7%) and a high positive predictive value (41.5%). Faecal Hb content is significantly higher for those lesions (cancer and high-risk adenomas) screening is aimed at detecting

Comparison of HPV-positive triage strategies combining extended genotyping with cytology or p16/ki67 dual staining in the Italian NTCC2 study

Background Each high-risk HPV genotype has different oncogenic potential, and the risk of CIN3+ varies according to genotype. We evaluated the performance of different strategies of HPV-positivity triage combining cytology, p16/ki67 dual staining (DS), and extended genotyping. Methods Samples from 3180 consecutive women from the NTCC2 study (NCT01837693) positive for HPV DNA at primary screening, were retrospectively analyzed by the BD Onclarity HPV Assay, which allows extended genotyping. Genotypes were divided into three groups based on the risk of CIN3+. HPV DNA-positive women were followed up for 24 months or to clearance. Findings Combining the three groups of genotypes with cytology or DS results we identify a group of women who need immediate colposcopy (PPV for CIN3+ from 7.8 to 20.1%), a group that can be referred to 1-year HPV retesting (PPV in those HPV-positive at retesting from 2.2 to 3.8), and a group with a very low 24-month CIN3+ risk, i.e. 0.4%, composed by women cytology or DS negative and positive for HPV 56/59/66 or 35/39/68 or negative with the Onclarity test, who can be referred to 3-year retesting. Interpretation Among the baseline HPV DNA positive/cytology or DS negative women, the extended genotyping allows to stratify for risk of CIN3+, and to identify a group of women with a risk of CIN3+ so low in the next 24 months that they could be referred to a new screening round after 3 years

Priority actions for Fusarium head blight resistance in durum wheat: Insights from the wheat initiative

Fusarium head blight (FHB), mainly caused by Fusarium graminearum and Fusarium culmorum, is a major wheat disease. Significant efforts have been made to improve resistance to FHB in bread wheat (Triticum aestivum), but more work is needed for durum wheat (Triticum turgidum spp. durum). Bread wheat has ample genetic variation for resistance breeding, which can be readily exploited, while durum wheat is characterized by higher disease susceptibility and fewer valuable resistance sources. The Wheat Initiative - Expert Working Group on Durum Wheat Genomics and Breeding has promoted a scientific discussion to define the key actions that should be prioritized for achieving resistance in durum wheat comparable to that found in bread wheat. Here, a detailed state of the art and novel tools to improve FHB resistance in durum are presented, together with a perspective on the next steps forward. A meta-analysis grouping all quantitative trait loci (QTL) associated with FHB resistance in both bread and durum wheat has been conducted to identify hotspot regions that do not overlap with Rht alleles, which are known to negatively correlate with FHB resistance. A detailed list of QTL related to FHB resistance and deoxynivalenol contamination and durum lines carrying different sources of FHB resistance are provided as a strategic resource. QTL, closely linked markers and durum wheat lines carrying the useful alleles, can be selected to design an effective breeding program. Finally, we highlight the priority actions that should be implemented to achieve satisfactory resistance to FHB in durum wheat

Immunochemical faecal occult blood test: number of samples and positivity cutoff. What is the best strategy for colorectal cancer screening?

Immunochemical faecal occult blood tests have shown a greater sensitivity than guaiac test in colorectal cancer screening, but optimal number of samples and cutoff have still to be defined. The aim of this multicentric study was to evaluate the performance of immunochemical-based screening strategies according to different positivity thresholds (80, 100, 120 ng ml−1) and single vs double sampling (one, at least one, or both positive samples) using 1-day sample with cutoff at 100 ng ml−1 as the reference strategy. A total of 20 596 subjects aged 50–69 years were enrolled from Italian population-based screening programmes. Positivity rate was 4.5% for reference strategy and 8.0 and 2.0% for the most sensitive and the most specific strategy, respectively. Cancer detection rate of reference strategy was 2.8‰, and ranged between 2.1 and 3.4‰ in other strategies; reference strategy detected 15.6‰ advanced adenomas (range=10.0–22.5‰). The number needed to scope to find a cancer or an advanced adenoma was lower than 2 (1.5–1.7) for the most specific strategies, whereas it was 2.4–2.7, according to different thresholds, for the most sensitive ones. Different strategies seem to have a greater impact on adenomas rather than on cancer detection rate. The study provides information when deciding screening protocols and to adapt them to local resources

Extended HPV genotyping by the BD Onclarity assay: concordance with screening HPV-DNA assays, triage biomarkers, and histopathology in women from the NTCC2 study

The use of clinically validated human papillomavirus (HPV) assays is recommended in cervical cancer screening, and extended genotyping is getting attention as a triage biomarker because of the different oncogenic risk of the high-risk HPV genotypes. We compared the results of the Becton &amp; Dickinson (BD) Onclarity HPV assay, on the residual baseline cervico-vaginal specimens of the NTCC2 trial, to those of the screening HPV-DNA assay (Cobas 4800 or HC2) and to cytology, p16/ki67 and E6/E7 mRNA triage results. We genotyped virtually all HPV-positive women and a consecutive sample of HPV-negatives. Among the 3,129 baseline-positives, 75.5% (k = 0.368) were BD-positive, as were 5 of the 333 baseline-negatives (1.5%). The concordance between BD and HPV-DNA screening test was 87% for Cobas (1,250/1,436) and 65.9% for HC2 (1,115/1,693). A higher than the recommended positivity threshold for Onclarity would increase the agreement but would not improve concordance in the overall screening population. Among the baseline-positive cases, we observed an increasing trend of BD positivity with cytology severity (from 71.6% in negative for intraepithelial lesion of malignancy to 95.1% in ASC-H+ samples), with histologically confirmed CIN3 (96.9%), with p16/ki67 dual staining positivity (90.9% among the positive and 69.6% among the negative specimens), and with E6/E7 mRNA positivity (93.4% in the mRNA-positive cases vs 39.7% among the mRNA-negatives). Our findings confirm some disagreement among different HPV assays used for screening. Nevertheless, the agreement is substantial for women with high-grade cytology, histologically confirmed CIN3, and p16/ki67 or mRNA positivity at triage, thus confirming a good clinical performance of all the tests used

Measurement of the Positive Muon Anomalous Magnetic Moment to 127 ppb

A new measurement of the magnetic anomaly $a_{\mu}$ of the positive muon is presented based on data taken from 2020 to 2023 by the Muon $g-2$ Experiment at Fermi National Accelerator Laboratory (FNAL). This dataset contains over 2.5 times the total statistics of our previous results. From the ratio of the precession frequencies for muons and protons in our storage ring magnetic field, together with precisely known ratios of fundamental constants, we determine $a_{\mu} = 116\,592\,0710(162) \times 10^{-12}$ (139 ppb) for the new datasets, and $a_{\mu} = 116\,592\,0705(148) \times 10^{-12}$ (127 ppb) when combined with our previous results. The new experimental world average, dominated by the measurements at FNAL, is $a_{\mu}(\text{exp}) =116\,592\,0715(145) \times 10^{-12}$ (124 ppb). The measurements at FNAL have improved the precision on the world average by over a factor of four