The impact on clinical outcomes and healthcare resources from discontinuing colonoscopy surveillance subsequent to low-risk adenoma removal: A simulation study using the OncoSim-Colorectal model.

OBJECTIVE: To estimate the impact on clinical outcomes and healthcare resource use from recommending that patients with 1-2 low-risk adenomas (LRAs) return to routine fecal immunochemical test (FIT) screening instead of surveillance colonoscopy, from a Canadian provincial healthcare system perspective. METHODS: The OncoSim-Colorectal microsimulation model simulated average-risk individuals eligible for FIT-based colorectal cancer (CRC) screening in Alberta, Canada. We simulated two surveillance strategies that applied to individuals with 1-2 LRAs (<10 mm) removed as part of the average risk CRC screening program: (a) Surveillance colonoscopy (status quo) and (b) return to FIT screening (new strategy); both at 5 years after polypectomy. A 75 ng/mL FIT positivity threshold was used in the base case. The simulations projected average annual CRC outcomes and healthcare resource use from 2023 to 2042. We conducted alternative scenarios and sensitivity analyses on key variables. RESULTS: Returning to FIT screening (versus surveillance colonoscopy) after polypectomy was projected to have minimal impact on long-term CRC incidence and deaths (not statistically significant). There was a projected decrease of one (4%) major bleeding event and seven (5%) perforation events per year. There was a projected increase of 4800 (1.5%) FIT screens, decrease of 3900 (5.1%) colonoscopies, and a decrease of $3.4 million (1.2%) in total healthcare costs per year, on average. The annual colonoscopies averted and healthcare cost savings increased over time. Results were similar in the alternative scenarios and sensitivity analyses. CONCLUSIONS: Returning to FIT screening would have similar clinical outcomes as surveillance colonoscopy but could reduce colonoscopy demand and healthcare costs.

The OncoSim-Breast Cancer Microsimulation Model.

BACKGROUND: OncoSim-Breast is a Canadian breast cancer simulation model to evaluate breast cancer interventions. This paper aims to describe the OncoSim-Breast model and how well it reproduces observed breast cancer trends. METHODS: The OncoSim-Breast model simulates the onset, growth, and spread of invasive and ductal carcinoma in situ tumours. It combines Canadian cancer incidence, mortality, screening program, and cost data to project population-level outcomes. Users can change the model input to answer specific questions. Here, we compared its projections with observed data. First, we compared the model's projected breast cancer trends with the observed data in the Canadian Cancer Registry and from Vital Statistics. Next, we replicated a screening trial to compare the model's projections with the trial's observed screening effects. RESULTS: OncoSim-Breast's projected incidence, mortality, and stage distribution of breast cancer were close to the observed data in the Canadian Cancer Registry and from Vital Statistics. OncoSim-Breast also reproduced the breast cancer screening effects observed in the UK Age trial. CONCLUSIONS: OncoSim-Breast's ability to reproduce the observed population-level breast cancer trends and the screening effects in a randomized trial increases the confidence of using its results to inform policy decisions related to early detection of breast cancer.

Women's acceptability of and experience with primary human papillomavirus testing for cervix screening: HPV FOCAL trial cross-sectional online survey results.

OBJECTIVE: To study participant's acceptability of and attitudes towards human papillomavirus (HPV) testing compared with cytology for cervical cancer screening and what impact having an HPV positive result may have in future acceptability of screening. DESIGN: Cross-sectional online survey of clinical trial participants. SETTING: Primary care, population-based Cervix Screening Program, British Columbia, Canada. PARTICIPANTS: A total of 5532 participants from the HPV FOCAL trial, in which women received HPV and cytology testing at study exit, were included in the analysis. Median age was 54 years. The median time of survey completion was 3 years after trial exit. OUTCOME MEASURES: Acceptability of HPV testing for primary cervical cancer screening (primary); attitudes and patient perceptions towards HPV testing and receipt of HPV positive screen results (secondary). RESULTS: Most respondents (63%) were accepting of HPV testing, with the majority (69%) accepting screening to begin at age 30 years with HPV testing. Only half of participants (54%) were accepting of an extended screening interval of 4-5 years. In multivariable logistic regression, women who received an HPV positive screen test result during the trial (OR=1.41 95% CI 1.11 to 1.80) or were older (OR=1.01, 95% CI 1.00 to 1.02) were more likely to report HPV testing as acceptable. CONCLUSIONS: In this evaluation of acceptability and attitudes regarding HPV testing for cervix screening, most are accepting of HPV testing for screening; however, findings indicate heterogeneity in concerns and experiences surrounding HPV testing and receipt of HPV positive results. These findings provide insights for the development of education, information and communication strategies during implementation of HPV-based cervical cancer screening. TRIAL REGISTRATION NUMBERS: ISRCTN79347302 and NCT00461760.

Cost-effectiveness analysis of primary human papillomavirus testing in cervical cancer screening: Results from the HPV FOCAL Trial.

The Human Papillomavirus FOr CervicAL cancer (HPV FOCAL) trial is a large randomized controlled trial comparing the efficacy of primary HPV testing to cytology among women in the population-based Cervix Screening Program in British Columbia, Canada. We conducted a cost-effectiveness analysis based on the HPV FOCAL trial to estimate the incremental cost per detected high-grade cervical intraepithelial neoplasia of grade 2 or worse lesions (CIN2+). A total of 19,009 women aged 25 to 65 were randomized to one of two study groups. Women in the intervention group received primary HPV testing with reflex liquid-based cytology (LBC) upon a positive finding with a screening interval of 48 months. Women in the control group received primary LBC testing, and those negative returned at 24 months for LBC and again at 48 months for exit screening. Both groups received HPV and LBC co-testing at the 48-month exit. Incremental costs during the course of the trial were comparable between the intervention and control groups. The intervention group had lower overall costs and detected a larger number of CIN2+ lesions, resulting in a lower mean cost per CIN2+ detected ($7551) than the control group ($8325), a difference of -$773 [all costs in 2018 USD]. Cost per detected lesion was sensitive to the costs of sample collection, HPV testing, and LBC testing. The HPV FOCAL Trial results suggest that primary HPV testing every 4 years produces similar outcomes to LBC-based testing every 2 years for cervical cancer screening at a lower cost.

Assessing 10-Year Safety of a Single Negative HPV Test for Cervical Cancer Screening: Evidence from FOCAL-DECADE Cohort.

BACKGROUND: Long-term safety of a single negative human papillomavirus (HPV) test for cervical cancer screening is unclear. The HPV FOr cerviCAL Cancer Trial (FOCAL) was a randomized trial comparing HPV testing with cytology. The FOCAL-DECADE cohort tracked women who received one HPV test during FOCAL, and were HPV negative, for up to 10 years to identify cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) detected through a provincial screening program. METHODS: FOCAL participants who received one HPV test, were negative, and had at least one post-FOCAL cervix screen were included (N = 5,537). We constructed cumulative incidence curves of CIN2+/CIN3+ detection, analyzed cumulative risk of detection at intervals post-HPV test, calculated average incidence rates for detection, and compared hazard across ages. RESULTS: Ten years after one negative HPV test, the probability of CIN2+ detection was lower than 1%, with most lesions detected 7 years or later. Average incidence rates of CIN2+/CIN3+ lesions over follow-up were 0.50 [95% confidence interval (CI), 0.31-0.78] and 0.18 (95% CI, 0.07-0.36) per 1,000 person-years, respectively. Hazards were higher for younger ages (nonsignificant trend). CONCLUSIONS: Among women with a single negative HPV test, long-term risk of CIN2+ detection was low, particularly through 7 years of follow-up; thus, one negative HPV test appears to confer long-term protection from precancerous lesions. Even 10-year risk is sufficiently low to support extended testing intervals in average-risk populations. IMPACT: Our findings support the safety of screening policies using HPV testing alone at 5-year or longer intervals.

The impact of episodic screening interruption: COVID-19 and population-based cancer screening in Canada.

BACKGROUND: Population-based cancer screening can reduce cancer burden but was interrupted temporarily due to the COVID-19 pandemic. We estimated the long-term clinical impact of breast and colorectal cancer screening interruptions in Canada using a validated mathematical model. METHODS: We used the OncoSim breast and colorectal cancers microsimulation models to explore scenarios of primary screening stops for 3, 6, and 12 months followed by 6-24-month transition periods of reduced screening volumes. For breast cancer, we estimated changes in cancer incidence over time, additional advanced-stage cases diagnosed, and excess cancer deaths in 2020-2029. For colorectal cancer, we estimated changes in cancer incidence over time, undiagnosed advanced adenomas and colorectal cancers in 2020, and lifetime excess cancer incidence and deaths. RESULTS: Our simulations projected a surge of cancer cases when screening resumes. For breast cancer screening, a three-month interruption could increase cases diagnosed at advanced stages (310 more) and cancer deaths (110 more) in 2020-2029. A six-month interruption could lead to 670 extra advanced cancers and 250 additional cancer deaths. For colorectal cancers, a six-month suspension of primary screening could increase cancer incidence by 2200 cases with 960 more cancer deaths over the lifetime. Longer interruptions, and reduced volumes when screening resumes, would further increase excess cancer deaths. CONCLUSIONS: Interruptions in cancer screening will lead to additional cancer deaths, additional advanced cancers diagnosed, and a surge in demand for downstream resources when screening resumes. An effective strategy is needed to minimize potential harm to people who missed their screening.

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.

Novel Microbial-Based Immunotherapy Approach for Crohn's Disease.

Background: Current Crohn's disease (CD) therapies focus on suppressing immune function and come with consequent risk, such as infection and cancer. Notwithstanding, most CD patients still experience disease progression. There is a need for new CD treatment strategies that offer better health outcomes for patients. Aims: To assess safety, efficacy, and tolerability of a novel microbial-derived immunotherapy, QBECO, that aims to restore rather than suppress immune function in CD. Methods: A randomized, double-blind, placebo-controlled trial was conducted in 68 patients with moderate-to-severe CD. Primary endpoints: safety and Week 8 clinical improvement. Secondary endpoints: Week 8 clinical response and remission. Week 8 responders continued blinded treatment through Week 16; non-responders received open-label QBECO from Weeks 9-16. Exploratory analyses included immune biomarker and genotype assessments. Results: QBECO was well-tolerated. Mean reduction in Crohn's Disease Activity Index (CDAI) score was -68 for QBECO vs. -31 for placebo at Week 8. Improvement with QBECO continued through Week 16 (-130 CDAI reduction). Week 8 QBECO clinical response, improvement and remission rates were 41.2%, 32.4%, 29.4% vs. 26.5%, 23.5%, 23.5% for placebo. TNFα inhibitor-naïve subjects achieved higher response rates at Week 8 with QBECO (64%) vs. placebo (26%). Specific immune biomarkers were identified that linked to QBECO response. Conclusion: This proof-of-concept study supports further investigation for the use of QBECO as a novel immunotherapy approach for CD. Biomarker analyses suggests it may be feasible to personalize CD treatment with QBECO. Larger trials are now needed to confirm clinical improvement and the unique biological findings. Clinical Trial Number: NCT01809275 (https://clinicaltrials.gov/ct2/show/NCT01809275).

Evaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial.

Human papillomavirus (HPV)-based cervical cancer screening requires triage of HPV positive women to identify those at risk of cervical intraepithelial neoplasia grade 2 (CIN2) or worse. We conducted a blinded case-control study within the HPV FOCAL randomized cervical cancer screening trial of women aged 25-65 to examine whether baseline methylation testing using the S5 classifier provided triage performance similar to an algorithm relying on cytology and HPV genotyping. Groups were randomly selected from women with known HPV/cytology results and pathology outcomes. Group 1: 104 HPV positive (HPV+), abnormal cytology (54 CIN2/3; 50

Comparative performance of human papillomavirus messenger RNA versus DNA screening tests at baseline and 48 months in the HPV FOCAL trial.

BACKGROUND: HPV FOCAL is a randomized trial comparing high-risk HPV [Hybrid Capture 2 (HC2)] vs. liquid-based cytology (LBC) for primary cervical screening. OBJECTIVE: The present study objective was to compare Aptima HPV (AHPV) and HC2 assay performance at the intervention arm baseline and 48 mo. screens in relation to the rates of cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+). STUDY DESIGN: Women enrolled after December 2010 (n = 3475) were screened at baseline with both AHPV and HC2 (AHPV was blinded). Women with CIN2+ exited the trial; HC2 negative (-) women and those HC2 positive (+) with

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.

Cancer in First Nations people living in British Columbia, Canada: an analysis of incidence and survival from 1993 to 2010.

BACKGROUND: For First Nations (FN) peoples living in British Columbia (BC), little is known regarding cancer in the population. The aim of this study was to explore cancer incidence and survival in the FN population of BC and compare it to the non-FN population. METHODS: All new cancers diagnosed from 1993 to 2010 were linked to the First Nations Client File (FNCF). Age-standardized incidence rates (ASIR) and rate ratios, and 1- and 5-year cause-specific survival estimates and hazard ratios were calculated. Follow-up end date for survival was December 31, 2011 and follow-up time was censored at a maximum of 15 years. RESULTS: ASIR of colorectal cancer (male SRR = 1.42, 95% CI 1.25-1.61; female SRR = 1.21, 95% CI 1.06-1.38) and cervical cancer (SRR = 1.84, 95% CI 1.45-2.33) were higher overall in FN residents in BC, compared to non-FN residents. Incidence rates of almost all other cancers were generally similar or lower in FN populations overall and by sex, age, and period categories, compared to non-FN residents. Trends in ASIR over time were similar except for lung (increasing for FN, decreasing for non-FN) and colorectal cancers (increasing for FN, decreasing for non-FN). Conversely, survival rates were generally lower for FN, with differences evident for some cancer sites at 1 year following diagnosis. CONCLUSION: FN people living in BC face unique cancer issues compared to non-FN people. Higher incidence and lower survival associated with certain cancer types require further research to look into the likely multifaceted basis for these findings.

Post-Loop Electrosurgical Excision Procedure High-Risk Human Papillomavirus Testing as a Test of Cure: The British Columbia Experience.

OBJECTIVES: To determine whether Hybrid Capture 2 High-Risk HPV DNA Test (HC2) can be used as a test of cure in women treated for cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) and allow discharge from colposcopy follow-up with a return to a cytology-based screening program for HC2-negative women. MATERIALS AND METHODS: Data were analyzed for all women who underwent a loop electrosurgical excision procedure between August 1, 2008, and June 30, 2011, and had a valid HC2 result after loop electrosurgical excision procedure and follow-up histopathology result, to determine risk of persistent or recurrent CIN 2+ in HC2-positive and HC2-negative women. RESULTS: Two thousand three hundred forty women had adequate biopsies and valid HC2 results. Of 460 HC2-positive women, 118 (25.7%) were diagnosed with CIN 2+, whereas of 1,880 HC2-negative women, 35 (1.9%) had a subsequent diagnosis of CIN 2+ (p < .0002) yielding a HC2-negative predictive value of 98.1% (95% confidence interval = 97.4-98.7). Of 460 HC2-positive women, 306 initially had negative biopsies. In the subsequent 36 months, 38 of the 306 were diagnosed with CIN 2+. CONCLUSIONS: We conclude that women with a negative HC2 test can safely return to routine annual cytology screening by primary care providers while women who test HC2 positive are at higher risk and should continue to be followed by colposcopy, even if their initial biopsy is negative.

Aptima HPV Assay versus Hybrid Capture® 2 HPV test for primary cervical cancer screening in the HPV FOCAL trial.

BACKGROUND: Cervical cancer screening programs are switching from Pap screening to high-risk HPV testing. OBJECTIVES: To compare the Aptima HPV Assay (AHPV) with the Hybrid Capture® 2 High-Risk HPV DNA Test® (HC2) for primary cervical screening. STUDY DESIGN: HPV FOCAL is a randomized trial comparing HC2 to liquid-based cytology (LBC) for screening women aged 25-65. AHPV and HC2 were compared at the baseline screen (n=3473). Genotyping was by the Aptima HPV 16 18/45 Genotype Assay. We assessed HPV genotyping and reflex LBC for colposcopy triage. RESULTS: AHPV/HC2 agreement was 96.5% (kappa 0.76); positive agreement was 77.4%. The AHPV positive rate was 7.2% vs. 8.4% for HC2 (p=0.06). Based on HC2 screening, round 1 CIN2 and CIN3+ rates were 9.2/1000 and 5.2/1000 respectively. Using HC2 as the comparator test, AHPV CIN2+ and CIN3+ relative sensitivities were 0.96 and 1.00 (p=1.00) respectively. High-grade reflex LBC and HPV 16 infection were significantly associated with CIN3+. AHPV specificity was 0.94 vs. 0.93 (p=0.05) for HC2. Compared with triage of HC2+ with abnormal cytology or HPV persistence for 12 months, colposcopy referral would be significantly reduced (38.3/1000 vs. 60.8/1000; p<0.001) if AHPV+ women with abnormal LBC and HPV 16/18/45 were referred at baseline. CIN2+ and CIN3+ detection rates were not significantly different for the two strategies. CONCLUSIONS: AHPV vs. HC2 screening had equivalent CIN2+ and CIN3+ detection. Triage of AHPV+ by abnormal reflex LBC and the presence of HPV 16/18/45 would result in a significantly lower colposcopy referral rate with similar CIN2+ and CIN3+ detection rates as the overall HC2+ referral algorithm.

Cervical cancer incidence in British Columbia: Predicting effects of changes from Pap to human papillomavirus screening and of changes in screening participation.

Objectives To estimate the impact of increased participation in screening, and of the proposed change from Pap to human papillomavirus screening on the incidence of cervical cancer in British Columbia. Methods For invasive cervical cancer cases diagnosed in British Columbia between 2002 and 2011, data were extracted on age and cancer morphology from the British Columbia Cancer Registry, and Pap screening history was obtained from the British Columbia Cervical Cancer Screening Program database. Only screening performed two to seven years prior to diagnosis was assumed to reduce subsequent risk of cancer. Results from randomized trials of human papillomavirus versus cytology screening and population based estimates of cytology screening were used to estimate the effect of a change in screening test and increases in participation. Results Between 2002 and 2011, there were 1663 cases of cervical cancer reported; 660 (367 squamous and 293 non-squamous) were eligible and screened two to seven years prior to diagnosis. The predicted reduction by changing to human papillomavirus screening was 363 (95% confidence interval = 124-496) representing 22% of all cases. If 50% of subjects not screened two to seven years prior had undergone Pap screening, it is projected that a further 268 cases (16%) could have been prevented; if they had undergone human papillomavirus screening, a further 365 cases (22%) could have been prevented. Conclusions For many women who develop cervical cancer, primary human papillomavirus testing could have substantially reduced their cancer risk. Human papillomavirus rather than Pap testing would further increase the gains from any increases in population screening participation.

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.