Effects of Environmental Enrichment on the Behavior of Octopus vulgaris in a Recirculating Aquaculture System.

Octopus vulgaris is a commercially valuable species. It is overexploited in the natural environment and is considered to be an innovative species for aquaculture. However, large-scale farming is generally designed only based on economic requirements, disregarding any form of enrichment that induces the natural behavior of aquatic species. Although many studies have shown the influence of environmental enrichment on terrestrial vertebrates, fish, and cephalopod mollusks, information on the effect of environmental enrichment on the body patterns of O. vulgaris is limited. Therefore, in this study, we assessed how different environmental conditions (Basic vs. Enriched) affect sub-adults of O. vulgaris kept in recirculation systems, through qualitative-quantitative studies of the main body patterns and their potential application in the commercial production of this species. The results indicated that octopuses kept in the enriched environment showed several body patterns and gained a significantly higher weight than those kept in the basic environment. The body patterns displayed by the individuals kept in the basic environment were similar to those exhibited under situations of hostility and inter/intra-specific conflict. Hence, the environment of octopuses needs to be enriched, especially for the large-scale production of this species.

Bifidobacterium affects antitumor efficacy of oncolytic adenovirus in a mouse model of melanoma.

Gut microbiota plays a key role in modulating responses to cancer immunotherapy in melanoma patients. Oncolytic viruses (OVs) represent emerging tools in cancer therapy, inducing a potent immunogenic cancer cell death (ICD) and recruiting immune cells in tumors, poorly infiltrated by T cells. We investigated whether the antitumoral activity of oncolytic adenovirus Ad5D24-CpG (Ad-CpG) was gut microbiota-mediated in a syngeneic mouse model of melanoma and observed that ICD was weakened by vancomycin-mediated perturbation of gut microbiota. Ad-CpG efficacy was increased by oral supplementation with Bifidobacterium, reducing melanoma progression and tumor-infiltrating regulatory T cells. Fecal microbiota was enriched in bacterial species belonging to the Firmicutes phylum in mice treated with both Bifidobacterium and Ad-CpG; furthermore, our data suggest that molecular mimicry between melanoma and Bifidobacterium-derived epitopes may favor activation of cross-reactive T cells and constitutes one of the mechanisms by which gut microbiota modulates OVs response.

The Immune Response to SARS-CoV-2 Vaccine in a Cohort of Family Pediatricians from Southern Italy.

In Italy, from January 2021, the Ministry of Health indicated a vaccination plan against COVID for frail patients and physicians based on a three-dose scheme. However, conflicting results have been reported on which biomarkers permit immunization assessment. We used several laboratory approaches (i.e., antibodies serum levels, flow cytometry analysis, and cytokines release by stimulated cells) to investigate the immune response in a cohort of 53 family pediatricians (FPs) at different times after the vaccine. We observed that the BNT162b2-mRNA vaccine induced a significant increase of specific antibodies after the third (booster) dose; however, the antibody titer was not predictive of the risk of developing the infection in the six months following the booster dose. The antigen stimulation of PBMC cells from subjects vaccinated with the third booster jab induced the increase of the activated T cells (i.e., CD4+ CD154+); the frequency of CD4+ CD154+ TNF-α+ cells, as well as the TNF-α secretion, was not modified, while we observed a trend of increase of IFN-γ secretion. Interestingly, the level of CD8+ IFN-γ+ (independently from antibody titer) was significantly increased after the third dose and predicts the risk of developing the infection in the six months following the booster jab. Such results may impact also other virus vaccinations.

Oncolytic Adenoviral Vector-Mediated Expression of an Anti-PD-L1-scFv Improves Anti-Tumoral Efficacy in a Melanoma Mouse Model.

Oncolytic virotherapy is an emerging therapeutic approach based on replication-competent viruses able to selectively infect and destroy cancer cells, inducing the release of tumor-associated antigens and thereby recruiting immune cells with a subsequent increase in antitumoral immune response. To increase the anticancer activity, we engineered a specific oncolytic adenovirus expressing a single-chain variable fragment of an antibody against PD-L1 to combine blockage of PD-1/PD-L1 interaction with the antitumoral activity of Onc.Ad5. To assess its efficacy, we infected B16.OVA cells, a murine model of melanoma, with Ad5Δ24 -anti-PD-L1-scFv and then co-cultured them with C57BL/6J naïve splenocytes. We observed that the combinatorial treatments were significantly more effective in inducing cancer cell death. Furthermore, we assessed the efficacy of intratumoral administrations of Ad5Δ24-anti-PD-L1-scFv in C57BL/6J mice engrafted with B16.OVA and compared this treatment to that of the parental Ad5Δ24 or placebo. Treatment with the scFv-expressing Onc.Ad induced a marked reduction of tumor growth concerning the parental Onc.Ad. Additionally, the evaluation of the lymphocytic population infiltrating the treated tumor reveals a favorable immune profile with an enhancement of the CD8+ population. These data suggest that Onc.Ad-mediated expression of immune checkpoint inhibitors increases oncolytic virotherapy efficacy and could be an effective and promising tool for cancer treatments, opening a new way into cancer therapy.

Serrated Lesion Detection in a Population-based Colon Screening Program.

BACKGROUND: Serrated lesions give rise to 15% to 30% of all colorectal cancers, driven predominantly by the sessile serrated polyp (SSP). Fecal immunochemical test (FIT), has low sensitivity for SSPs. SSP detection rate (SSPDR) is influenced by performance of both endoscopists and pathologists, as diagnosis can be subtle both on endoscopy and histology. GOALS: To evaluate the SSPDR in a population-based screening program, and the influence of subspecialty trained pathologists on provincial reporting practices. STUDY: The colon screening program database was used to identify all FIT-positive patients that received colonoscopy between January 2014 and June 2017. Patient demographics, colonoscopy quality indicators, pathologic diagnoses, and FIT values were collected. This study received IRB approval. RESULTS: A total of 74,605 colonoscopies were included and 26.6% had at least 1 serrated polyp removed. The SSPDR was 7.0%, with 59% of the SSPs detected having a concurrent conventional adenoma. The mean FIT value for colonoscopies with only serrated lesions was less than that for colonoscopies with a conventional adenoma or colorectal cancer (P<0.0001). Centers with a gastrointestinal subspecialty pathologist diagnosed proportionally more SSPs (P<0.0001), and right-sided SSPs than centers without subspecialists. CONCLUSIONS: Serrated lesions often occur in conjunction with conventional adenomas and are associated with lower FIT values. Knowledge of the characteristics of SSPs is essential for pathologists to ensure accurate diagnosis of SSPs.

Risks associated with colonoscopy in a population-based colon screening program: an observational cohort study.

BACKGROUND: The risks associated with colonoscopy performed through the British Columbia Colon Screening Program (BCCSP) are not known. We aimed to determine the rate of colonoscopy-related serious adverse events within this program. METHODS: For this prospective observational study, we used the BCCSP database to identify participants 50 to 74 years of age who had a positive result on fecal immunochemical testing (FIT) between Nov. 15, 2013, and Dec. 31, 2017, followed by colonoscopy. Unplanned medical events were recorded at the time of colonoscopy and 14 days later. We reviewed the unplanned events and defined them as serious adverse events if they resulted in death, hospital admission or intervention; we also classified them as probably, possibly or unlikely related to the colonoscopy. The primary outcome was the overall rate of serious adverse events; the secondary outcomes were 14-day post-colonoscopy rates of perforation, bleeding and death. RESULTS: During the study period, a total of 96 192 colonoscopies were performed by 308 physicians at 50 sites. The median age of patients was 62 (10th-90th percentile 52-71) years, and 56% were male. Of these, 78 831 patients were contacted after the colonoscopy. Serious adverse events were deemed to have occurred in 350 colonoscopies (44 per 10 000, 95% confidence interval [CI] 39-50 per 10 000), with a number needed to harm of 225. Of the 332 (94.9%) serious adverse events that were probably or possibly related to colonoscopy, perforation occurred in 6 (95% CI 5-8) per 10 000 colonoscopies, bleeding in 26 (95% CI 22-30) per 10 000 colonoscopies and death in 3 (95% CI 1-10) per 100 000 colonoscopies. INTERPRETATION: The rate of serious adverse events associated with colonoscopy in the BCCSP was in keeping with previous publications and met accepted benchmarks. The findings of this study inform stakeholders of the risks associated with colonoscopy in an FIT-based colon screening program.

Higher adenoma detection, sessile serrated lesion detection and proximal sessile serrated lesion detection are associated with physician specialty and performance on Direct Observation of Procedural Skills.

OBJECTIVE: Adenoma detection rate (ADR) and sessile serrated lesion detection rate (SSLDR) vary among physicians. We sought to determine physician characteristics associated with ADR and SSLDR in a population-based colon screening programme. DESIGN: Retrospective study of 50-74 year olds with positive faecal immunochemical test and colonoscopy from 15/11/2013 to 31/12/2018. Physician characteristics included: gender, specialty, year and country of medical school graduation, colonoscopy volume and Direct Observation of Procedural Skills (DOPS) performance. Multivariable regression was performed on the following dependent variables: ADR, advanced ADR, proximal and distal ADR, SSLDR, proximal and distal SSLDR. RESULTS: 104 326 colonoscopies were performed by 261 physicians. A higher ADR was associated with gastroenterology (OR for general surgery 0.87, 95% CI 0.80 to 0.95; OR for general/family/internal medicine 0.70, 95% CI 0.55 to 0.88), fewer years since graduation (OR for graduation >2000 10.48, 95% CI 1.30 to 1.69 compared with <1980) and DOPS performance (OR for lowest DOPS performance 0.64, 95% CI 0.50 to 0.82 compared with highest DOPS performance). SSLDR was associated with gastroenterology (OR for general surgery 0.89, 95%, CI 0.81 to 0.97; OR for general/family/internal medicine 0.67, 95% CI 0.49 to 0.92) and DOPS performance (OR for lowest DOPS performance 0.71, 95% CI 0.51 to 0.99 compared with highest DOPS performance). Proximal SSLDR was associated with gastroenterology (OR for general surgery 0.90, 95% CI 0.82 to 0.99; OR for general/family/internal medicine 0.69, 95% CI 0.50 to 0.97) and DOPS performance (OR for lowest DOPS performance 0.68, 95% CI 0.47 to 0.99). CONCLUSION: Higher ADR, SSLDR and proximal SSLDR was associated with gastroenterology specialty and improved performance on DOPS.

Colorectal adenocarcinomas diagnosed following a negative faecal immunochemical test show high-risk pathological features in a colon screening programme.

AIMS: The faecal immunochemical test (FIT) is used every 2 years to screen average-risk British Columbians aged 50-74 years, with follow-up colonoscopy for positive results. Non-screen-detected colorectal adenocarcinomas are defined as those detected within 25 months following a negative FIT. We aimed to more clearly characterise these malignancies. METHODS AND RESULTS: A medical chart and focused pathology review of colorectal malignancies from 926 individuals who completed FIT in the British Columbia Colon Screening Program in 2014, and whose pathology reports were available for review, was conducted. This cohort was divided into two groups: individuals with colorectal adenocarcinomas diagnosed following a positive FIT (screen-detected) and individuals with colorectal adenocarcinoma diagnosed within 25 months of a negative FIT (FIT-interval cancers). Rates of clinically relevant pathological parameters, as outlined in the American Joint Committee on Cancer (AJCC), 8th edition, were compared between the screen-detected and FIT-interval cancer groups. A total of 876 screen-detected and 50 FIT-interval cancers were identified. FIT-interval cancers exhibited higher rates of high-grade differentiation (including poorly differentiated and undifferentiated cases; P < 0.01) and aggressive histotype (signet ring cell and mucinous carcinomas; P < 0.01) than did screen-detected cancers after Bonferroni correction. Colorectal adenocarcinoma diagnosed after a negative FIT may therefore be associated with worse prognostic determinants than screen-detected cancers. CONCLUSION: FIT-interval cancers are associated with high-risk pathological features; the possibility that more aggressive, fast-growing lesions which arise in the interval after truly negative FITs cannot be ruled out. Further study of a larger cohort of FIT-interval cancers controlling for interaction among the different pathologic parameters will be undertaken.

Performance of the Fecal Immunochemical Test in Patients With a Family History of Colorectal Cancer.

OBJECTIVE: To assess the performance of a fecal immunochemical test (FIT) among participants of a population-based colorectal cancer (CRC) screening program with one or more first-degree relatives (FDR) with CRC. METHODS: Asymptomatic 50 to 74 years olds with a FDR diagnosed with CRC, enrolled in a colon screening program completed FIT (two samples, cut-off 20 µg Hemoglobin/gram feces) and underwent colonoscopy. FIT-interval CRCs were identified from the British Columbia cancer registry. Logistic regression analysis was used to identify variables associated with the detection of CRC and high-risk polyps (nonmalignant findings that required a 3-year surveillance colonoscopy) in those patients undergoing FIT and colonoscopy. RESULTS: Of the 1387 participants with a FDR with CRC, 1244 completed FIT with a positivity rate of 10.8%, 52 declined FIT but underwent colonoscopy and 90 declined screening. Seven CRCs were identified: six in patients with a positive FIT, one in a patient who only had colonoscopy. No CRCs were found in patients with a negative FIT. The positive and negative predictive values of FIT in the detection of CRC were 4.8% and 100%, respectively. On multivariate logistic regression, positive FIT, and not type of family history, was the only variable associated with detection of CRC or high-risk polyps. At 2-year follow-up, there was no FIT interval cancer detected in the study cohort. CONCLUSION: FIT is more strongly associated with high-risk findings on colonoscopy than type of family history. FIT may be an alternative screening strategy to colonoscopy in individuals with a single FDR with CRC.

Re-examining the 1-mm margin and submucosal depth of invasion: a review of 216 malignant colorectal polyps.

Malignant colorectal polyps have a risk of lymph node metastases between 9 and 24%, but patients who are negative for certain histologic poor prognostic factors have the potential to be treated with polypectomy alone. Retrospective cohort of 216 malignant polyps from 213 patients identified through the British Columbia Colon Screening Program. Complete pathologic reporting (reporting of tumor grade, lymphovascular invasion, margin status, and tumor budding) was present in only 43% of patients. Sixty-one patients had no poor prognostic factors on polypectomy, and 23 (37%) of those underwent surgery. A positive margin cutoff of tumor at cautery showed significantly increased rates of lymph node metastases (p = 0.04) compared to a margin of greater than 0 mm, and polyps with a margin of greater than 0 mm had no risk of residual carcinoma. A submucosal depth of ≥ 2000 µm had an increased rate of lymph node metastases compared to < 2000 µm (p = 0.01). Malignant polyps with either tumor at cautery or a submucosal depth of ≥ 2000 µm, compared to polyps without these risk factors, had a relative risk for lymph node metastases of 16.3. Adoption of submucosal depth and refinement of the cutoffs for positive margin and submucosal depth have the potential to identify high-risk patients and reduce the number of surgeries required in patients with malignant polyps, a group that continues to grow significantly in part due to the introduction of colon screening programs.

Disease detection at the 48-month exit round of the HPV FOCAL cervical cancer screening trial in women per-protocol eligible for routine screening.

HPV FOCAL is a randomized control trial of cervical cancer screening. The intervention arm received baseline screening for high-risk human papillomavirus (HPV) and the control arm received liquid-based cytology (LBC) at baseline and 24 months. Both arms received 48-month exit HPV and LBC cotesting. Exit results are presented for per-protocol eligible (PPE) screened women. Participants were PPE at exit if they had completed all screening and recommended follow-up and had not been diagnosed with cervical intraepithelial neoplasia Grade 2 or worse (CIN2+) earlier in the trial. Subgroups were identified based upon results at earlier trial screening. There were 9,457 and 9,552 and women aged 25-65 randomized to control and intervention and 7,448 (77.8%) and 8,281 (86.7%), respectively, were PPE and screened. Exit cotest results were similar (p = 0.11) by arm for PPE and the relative rate (RR) of CIN2+ for intervention vs. control was RR = 0.83 (95% CI: 0.56-1.23). The RR for CIN2+ comparing intervention women baseline HPV negative to control women with negative cytology at baseline and at 24 months, was 0.68 (95% CI: 0.43-1.06). PPE women who had a negative or CIN1 colposcopy in earlier rounds had elevated rates (per 1,000) of CIN2+ at exit, control 31 (95% CI: 14-65) and intervention 43 (95% CI: 25-73). Among PPE women HPV negative at exit LBC cotesting identified little CIN2+, Rate = 0.3 (95% CI: 0.1-0.7). This per-protocol analysis found that screening with HPV using a 4-year interval is as safe as LBC with a 2-year screening interval. LBC screening in HPV negative women at exit identified few additional lesions.

Premature Fecal Immunochemical Testing in British Columbia Canada: a Retrospective Review of Physician and Screening Participant Characteristics.

BACKGROUND: Colorectal cancer (CRC) screening is an evidence-based strategy to reduce CRC-related mortality. OBJECTIVE: This study identifies physician and participant characteristics, as well as previous FIT values associated with premature FIT usage. DESIGN: This is a retrospective review of all FITs ordered from January 1, 2016, until June 30, 2017. For each ordered FIT, the participant's chart was reviewed to identify if a previous FIT had occurred in the prior 21 months. A premature FIT was defined as an ordered test with a negative FIT in the preceding 21 months. PARTICIPANTS: Screening participants were average risk for CRC, aged 50-74, and had a FIT ordered by their primary care provider in British Columbia, Canada. MAIN MEASURES: The BC College of Physicians and Surgeons' database was used to identify the location of referring physician, date of graduation from medical school, and gender. The participant's age, gender, and value of previous FIT were recorded. Physician and participant variables and previous FIT value were examined with logistic regression to identify associations with premature FIT ordering. KEY RESULTS: In total, 385,375 FITs were ordered during this period with 116,727 representing participants returning following a previous negative FIT. In total, 35,148 (30.1%) returned early for screening. Men were more likely to return early than women (OR 1.14; 95% CI 1.11-1.17; p < 0.0001). Male physicians were more likely to order premature FITs (OR 1.15; 95% CI 1.06-1.24; p < 0.0001). A higher quantitative FIT value (ng/mL) of the previous FIT was also associated with early screening (OR 1.11; 95% CI 1.09-1.14; < 0.0001). CONCLUSIONS: This study found that approximately 30% of FIT tests, ordered for CRC screening, were ordered before they were due. This may lead to wasted resources, unnecessary participant stress, and unwarranted patient risk.

[Organ donation and transplantation: the "friendly access initiative" in the Federico II Hospital (Naples), between nudging and narrative medicine]. / Donazione e trapianto d'organi: l'esperienza dello "sportello amico" dell'AOU Federico II (Napoli), tra nudging e medicina narrativa.

In Italy, to show the willingness to donate one's organs, there is the principle of the explicit consensus (or disagreement) (Law n. 91 of the 01.04.1999, Art. 23; Decree of the Italian Health Ministry of the 08.04.2000). According to data of the Italian Association for the donation of organs, tissues and cells (AIDO), in 2017 in Campania Region (Southern Italy) an average of 12.5 people x1,000,000 donated their organs vs. a national average of 23.7. This negative discrepancy between national and regional data highlights that it is imperative to promote awareness-raising measures to address to the population of Campania Region in order to improve the following of a practice which is still object of preconceptions and scarce knowledge. This paper describes a pilot project started in 2017 by the "Sportello amico trapianti" (friendly access to transplantation) to promote the donation of organs within the university-hospital "Federico II" (Naples, Campania Region). The first phase of this project was based on the nudge theory, that is the "little push" to direct decisional processes of groups and individuals. This phase took place during the "Atelier della salute" (a health workshop), organized by the Medicine and Surgery school of the university-hospital "Federico II": here, a questionnaire was administered to 60 people. The questionnaire consisted in 12 questions, answered by volunteers, which aim was to test the general knowledge about organ donation and transplantation. Analysing the answers, a panel of 7 experts (2 epidemiologists, 1 social worker, 2 experts in public and institutional communication, 1 biologist expert in donation of haematopoietic progenitor cell, 1 transplant surgeon), responsible for the coordination and monitoring of the activities, identified the critical elements to bring attention to in order to raise awareness in the population. The second phase consisted in a literary workshop which aim was to identify nudge cases. The text used was Never let me go by Kazuo Ishiguro, a novel focused on organ donation in a dystopic context where the protagonists are clones created to facilitate the donation of organs. Six students participated in this workshop: all six considered the dystopic scenario as a potential nudge to humanize the approach to organ donation and transplant. In conclusion, we believe that the nudge methodology may be used in order to improve awareness and adherence to donation of organs.

Effect of Screening With Primary Cervical HPV Testing vs Cytology Testing on High-grade Cervical Intraepithelial Neoplasia at 48 Months: The HPV FOCAL Randomized Clinical Trial.

Importance: There is limited information about the relative effectiveness of cervical cancer screening with primary human papillomavirus (HPV) testing alone compared with cytology in North American populations. Objective: To evaluate histologically confirmed cumulative incident cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) detected up to and including 48 months by primary HPV testing alone (intervention) or liquid-based cytology (control). Design, Setting, and Participants: Randomized clinical trial conducted in an organized Cervical Cancer Screening Program in Canada. Participants were recruited through 224 collaborating clinicians from January 2008 to May 2012, with follow-up through December 2016. Women aged 25 to 65 years with no history of CIN2+ in the past 5 years, no history of invasive cervical cancer, or no history of hysterectomy; who have not received a Papanicolaou test within the past 12 months; and who were not receiving immunosuppressive therapy were eligible. Interventions: A total of 19 009 women were randomized to the intervention (n = 9552) and control (n = 9457) groups. Women in the intervention group received HPV testing; those whose results were negative returned at 48 months. Women in the control group received liquid-based cytology (LBC) testing; those whose results were negative returned at 24 months for LBC. Women in the control group who were negative at 24 months returned at 48 months. At 48-month exit, both groups received HPV and LBC co-testing. Main Outcomes and Measures: The primary outcome was the cumulative incidence of CIN3+ 48 months following randomization. The cumulative incidence of CIN2+ was a secondary outcome. Results: Among 19 009 women who were randomized (mean age, 45 years [10th-90th percentile, 30-59]), 16 374 (8296 [86.9%] in the intervention group and 8078 [85.4%] in the control group) completed the study. At 48 months, significantly fewer CIN3+ and CIN2+ were detected in the intervention vs control group. The CIN3+ incidence rate was 2.3/1000 (95% CI, 1.5-3.5) in the intervention group and 5.5/1000 (95% CI, 4.2-7.2) in the control group. The CIN3+ risk ratio was 0.42 (95% CI, 0.25-0.69). The CIN2+ incidence rate at 48 months was 5.0/1000 (95% CI, 3.8-6.7) in the intervention group and 10.6/1000 (95% CI, 8.7-12.9) in the control group. The CIN2+ risk ratio was 0.47 (95% CI, 0.34-0.67). Baseline HPV-negative women had a significantly lower cumulative incidence of CIN3+ at 48 months than cytology-negative women (CIN3+ incidence rate, 1.4/1000 [95% CI, 0.8-2.4]; CIN3+ risk ratio, 0.25 [95% CI, 0.13-0.48]). Conclusions and Relevance: Among women undergoing cervical cancer screening, the use of primary HPV testing compared with cytology testing resulted in a significantly lower likelihood of CIN3+ at 48 months. Further research is needed to understand long-term clinical outcomes as well as cost-effectiveness. Trial Registration: isrctn.org Identifier: ISRCTN79347302.

HPV for cervical cancer screening (HPV FOCAL): Complete Round 1 results of a randomized trial comparing HPV-based primary screening to liquid-based cytology for cervical cancer.

Complete Round 1 data (baseline and 12-month follow-up) for HPV FOCAL, a randomized trial establishing the efficacy of HPV DNA testing with cytology triage as a primary screen for cervical cancer are presented. Women were randomized to one of three arms: Control arm - Baseline liquid-based cytology (LBC) with ASCUS results triaged with HPV testing; Intervention and Safety arms - Baseline HPV with LBC triage for HPV positives. Results are presented for 15,744 women allocated to the HPV (intervention and safety combined) and 9,408 to the control arms. For all age cohorts, the CIN3+ detection rate was higher in the HPV (7.5/1,000; 95%CI: 6.2, 8.9) compared to the control arm (4.6/1,000; 95%CI: 3.4, 6.2). The CIN2+ detection rates were also significantly higher in the HPV (16.5/1,000; 95%CI: 14.6, 18.6) vs. the control arm (10.1/1,000; 95%CI: 8.3, 12.4). In women ≥35 years, the overall detection rates for CIN2+ and CIN3+ were higher in the HPV vs. the control arm (CIN2+:10.0/1,000 vs. 5.2/1,000; CIN3+: 4.2/1,000 vs. 2.2/1,000 respectively, with a statistically significant difference for CIN2+). HPV testing detected significantly more CIN2+ in women 25-29 compared to LBC (63.7/1,000; 95%CI: 51.9, 78.0 vs. 32.4/1,000; 95%CI: 22.3, 46.8). HPV testing resulted in significantly higher colposcopy referral rates for all age cohorts (HPV: 58.9/1,000; 95%CI: 55.4, 62.7 vs. CONTROL: 30.9/1,000; 95%CI: 27.6, 34.6). At completion of Round 1 HPV-based cervical cancer screening in a population-based program resulted in greater CIN2+ detection of across all age cohorts compared to LBC screening.

Performance of a quantitative fecal immunochemical test in a colorectal cancer screening pilot program: a prospective cohort study.

BACKGROUND: British Columbia undertook a colorectal cancer screening pilot program in 3 communities. Our objective was to assess the performance of 2-specimen fecal immunochemical testing in the detection of colorectal neoplasms in this population-based screening program. METHODS: A prospective cohort of asymptomatic, average-risk people aged 50 to 74 years completed 2 quantitative fecal immunochemical tests every 2 years, with follow-up colonoscopy if the result of either test was positive. Participant demographics, fecal immunochemical test results, colonoscopy quality indicators and pathology results were recorded. Non-screen-detected colorectal cancer that developed in program participants was identified through review of data from the BC Cancer Registry. RESULTS: A total of 16 234 people completed a first round of fecal immunochemical testing, with a positivity rate of 8.6%; 5378 (86.0% of eligible participants) completed a second round before the end of the pilot program, with a positivity rate of 6.7%. Of the 1756 who had a positive test result, 1555 (88.6%) underwent colonoscopy. The detection rate of colorectal cancer was 3.5 per 1000 participants. The positive predictive value of the fecal immunochemical test was 4.9% (95% confidence interval [CI] 3.8%-6.0%) for colorectal cancer, 35.0% (95% CI 32.5%-37.2%) for high-risk polyps and 62.0% (95% CI 59.6%-64.4%) for all neoplasms. The number needed to screen was 283 to detect 1 cancer, 40 to detect 1 high-risk polyp and 22 to detect any neoplasm. INTERPRETATION: Screening every 2 years with a 2-specimen fecal immunochemical test surpassed the current benchmark for colorectal cancer detection in population-based screening. This study has implications for other jurisdictions planning colorectal cancer screening programs.

Disease detection and resource use in the safety and control arms of the HPV FOCAL cervical cancer screening trial.

BACKGROUND: The HPV FOCAL Trial is a RCT comparing human papilloma virus (HPV) with Liquid Based Cytology (LBC) screening for cervical cancer. Results are presented for the comparison of the Safety and Control arms after two rounds. METHODS: HPV FOCAL included randomisation of women aged 25-65 into the Safety arm, where they were initially screened with HPV and the Control arm, where they received entry screening with LBC, with both arms screened again with LBC at 24 months. RESULTS: There are 6203 (Safety) and 6075 (Control) women included in this analysis. For the Safety vs Control arms, Round 1 screening resulted in increased detection of cervical intraepithelial neoplasia 2 or worse (CIN2+),15.3 vs 10.4 per 1000, RR=1.48 (95%CI=1.08-2.03) and higher colposcopy referral rates, 5.6% vs 3.2%. LBC screening at 24 months resulted in similar colposcopy referral rates, 1.5% vs 1.9%, and decreased CIN2+ detection, 2.0 vs 4.7 per 1000, RR=0.43 (95%CI=0.21-0.88) in the Safety vs Control arms. CIN2+ detection and colposcopy referral rates declined with increasing age in both arms. One round of HPV screening detected similar levels of CIN2+ as two rounds of LBC screening. INTERPRETATION: CIN2+ detection at 2 years was lower in those screened by HPV, indicating an improved 2-year negative predictive value of the HPV test.

Correlating Quantitative Fecal Immunochemical Test Results with Neoplastic Findings on Colonoscopy in a Population-Based Colorectal Cancer Screening Program: A Prospective Study.

Background and Aims. The Canadian Partnership Against Cancer (CPAC) recommends a fecal immunochemical test- (FIT-) positive predictive value (PPV) for all adenomas of ≥50%. We sought to assess FIT performance among average-risk participants of the British Columbia Colon Screening Program (BCCSP). Methods. From Nov-2013 to Dec-2014 consecutive participants of the BCCSP were assessed. Data was obtained from a prospectively collected database. A single quantitative FIT (NS-Plus, Alfresa Pharma Corporation, Japan) with a cut-off of ≥10 µg/g (≥50 ng/mL) was used. Results. 20,322 FIT-positive participants underwent CSPY. At a FIT cut-off of ≥10 µg/g (≥50 ng/mL) the PPV for all adenomas was 52.0%. Increasing the FIT cut-off to ≥20 µg/g (≥100 ng/mL) would increase the PPV for colorectal cancer (CRC) by 1.5% and for high-risk adenomas (HRAs) by 6.5% at a cost of missing 13.6% of CRCs and 32.4% of HRAs. Conclusions. As the NS-Plus FIT cut-off rises, the PPV for CRC and HRAs increases but at the cost of missed lesions. A cut-off of ≥10 µg/g (≥50 ng/mL) produces a PPV for all adenomas exceeding national recommendations. Health authorities need to take into consideration endoscopic resources when selecting a FIT positivity threshold.

Comparison of One versus Two Fecal Immunochemical Tests in the Detection of Colorectal Neoplasia in a Population-Based Colorectal Cancer Screening Program.

Objective. To determine the positive predictive value (PPV) of two versus one abnormal FIT in the detection of colorectal neoplasia in a Canadian population. Methods. Three communities enrolled in a colorectal cancer (CRC) screening pilot program from 01/2009 to 04/2013 using 2 FITs. Data collected included demographics, colonoscopy, pathology, and FIT results. Participants completed both FITs and had one positive FIT and colonoscopy. PPV of one versus two abnormal FITs was calculated using a weighted-generalized score statistic. A two-sided 5% significance level was used. Results. 1576 of 17,031 average-risk participants, 50-75 years old, had a positive FIT. Colonoscopy revealed 58 (3.7%) cancers, 419 (31.6%) high-risk polyps, and 374 (23.7%) low-risk polyps as the most significant lesion. PPV of one versus two positive FITs for cancer, high-risk polyps, and any neoplasia were 1% versus 8%, 20% versus 40%, and 48% versus 67%, respectively (p value < 0.0001). When the first FIT was negative, the second positive FIT detected 7 CRCs and 98 high-risk polyps. Conclusions. PPV of two positive FITs is superior to one positive FIT for CRC and high-risk polyps. The added value of the second FIT was 12% of total CRCs and 23% of total high-risk polyps.