Mammographic screening is a proven method for the early detection of breast cancer. The authors analyzed the impact of service mammographic screening on breast cancer mortality among British Columbia women who volunteered to be screened by the Screening Mammography Program of British Columbia. A cohort of women having at least one mammographic screen by Screening Mammography Program of British Columbia between the ages of 40 and 79 in the period 1988–2003 was identified. All cases and deaths from breast cancer occurring in British Columbia were identified from the British Columbia Cancer Registry and linked to the screening cohort. Expected deaths from breast cancer in the cohort were calculated using incidence and survival rates for British Columbia women not in the cohort. Adjustment was made for age and socioeconomic status of their area of residence at time of diagnosis. The breast cancer mortality ratio was calculated by dividing observed by expected breast cancer deaths. The mortality ratio (95% confidence interval) was 0.60 (0.55, 0.65) for all ages combined (p < 0.0001). The mortality ratio in women aged 40–49 at first screening was 0.61 (0.52, 0.71), similar to that in women over 50 (p = 0.90). Exclusion of mortality associated with breast cancers diagnosed after age 50 in women starting screening in their 40s increased the mortality ratio to 0.63 (0.52, 0.77), but it remained statistically significant. Correction for self‐selection bias using estimates from the literature increased the mortality ratio for all ages to 0.76. Mammographic screening at all ages between 40 and 79 reduced subsequent mortality rates from breast cancer.

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 <CIN2); Group 2: 103 HPV+, normal cytology with HPV persistence at 12 mo. (53 CIN2/3; 50 <CIN2); Group 3: 50 HPV+, normal cytology with HPV clearance at 12 mo. (assumed <CIN2), total n=257. For the combined groups, S5 risk score CIN2/3 relative sensitivity, specificity and positive predictive value (PPV) were compared with other triage approaches. Methylation showed a highly significant increasing trend with disease severity. For CIN3, S5 relative sensitivity and specificity were: 93.2% (95%CI: 81.4–98.0) and 41.8% (35.2–48.8), compared to 86.4% (75.0–95.7) and 49.8% (43.1–56.6) respectively for combined abnormal cytology/HPV16/18 positivity (differences not statistically significant at 5% level); adjusted PPVs were 18.2% (16.2–20.4) and 19.3% (16.6–22.2) respectively. S5 was also positive in baseline specimens from eight cancers detected during or after trial participation. The S5 methylation score had high sensitivity and PPV for CIN3, compatible with US and European thresholds for colposcopy referral. Methylation signatures can identify most HPV positive women at increased risk of cervical cancer from their baseline screening specimens.

In the HPV FOCAL trial, we will establish the efficacy of hr-HPV DNA testing as a stand-alone screening test followed by liquid based cytology (LBC) triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with ≥ CIN3 as the outcome. HPV-FOCAL is a randomized, controlled, three-armed study over a four year period conducted in British Columbia. It will recruit 33,000 women aged 25-65 through the province's population based cervical cancer screening program. Control arm: LBC at entry and two years, and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases; Two Year Safety Check arm: hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives; Four Year Intervention Arm: hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases To date, 6150 participants have a completed sample and epidemiologic questionnaire. Of the 2019 women enrolled in the control arm, 1908 (94.5%) were cytology negative. Women aged 25-29 had the highest rates of HSIL (1.4%). In the safety arm 92.2% of women were hr-HPV negative, with the highest rate of hr-HPV positivity found in 25-29 year old women (23.5%). Similar results were obtained in the intervention arm HPV FOCAL is the first randomized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population-based cervical cancer screening program. International Standard Randomised Controlled Trial Number Register, ISRCTN79347302

Background: Women with mutations in BRCA1 or BRCA2 are at high risk of developing breast cancer and, in British Columbia, Canada, are offered screening with both magnetic resonance imaging (MRI) and mammography to facilitate early detection. MRI is more sensitive than mammography but is more costly and produces more false positive results. The purpose of this study was to calculate the cost-effectiveness of MRI screening for breast cancer in BRCA1/2 mutation carriers in a Canadian setting.Methods: We constructed a Markov model of annual MRI and mammography screening for BRCA1/2 carriers, using local data and published values. We calculated cost-effectiveness as cost per quality-adjusted life-year gained (QALY), and conducted one-way and probabilistic sensitivity analysis.Results: The incremental cost-effectiveness ratio (ICER) of annual mammography plus MRI screening, compared to annual mammography alone, was $50,900/QALY. After incorporating parameter uncertainty, MRI screening is expected to be a cost-effective option 86% of the time at a willingness-to-pay of $100,000/QALY, and 53% of the time at a willingness-to-pay of $50,000/QALY. The model is highly sensitive to the cost of MRI; as the cost is increased from $200 to $700 per scan, the ICER ranges from $37,100/QALY to $133,000/QALY.Conclusions: The cost-effectiveness of using MRI and mammography in combination to screen for breast cancer in BRCA1/2 mutation carriers is finely balanced. The sensitivity of the results to the cost of the MRI screen itself warrants consideration: in jurisdictions with higher MRI costs, screening may not be a cost-effective use of resources, but improving the efficiency of MRI screening will also improve cost-effectiveness.

High-risk HPV DNA testing has been proposed as a primary tool for cervical cancer screening (HPV-CCS) as an alternative to the Papanicolaou cytology- method. This study describes factors associated with women’s intentions to attend cervical cancer screening if high-risk HPV DNA testing (HPV-CCS) was implemented as a primary screening tool, and if screening were conducted every 4 years starting after age 25. This online survey was designed using the Theory of Planned Behaviour to assess factors that impact women’s intentions to attend HPV-CCS among women aged 25–69 upon exit of the HPV FOCAL trial. Univariate and regression analyses were performed to compare the demographic, sexual history, and smoking characteristics between women willing and unwilling to screen, and scales for intention to attend HPV-CCS. A qualitative analysis was performed by compiling and coding the comments section of the survey. Of the 981 women who completed the survey in full, only 51.4 % responded that they intended to attend HPV-CCS with a delayed start age and extended screening interval. Women who intended to screen were more likely to have higher education (AOR 0.59, 95 % CI [0.37, 0.93]), while both positive attitudes (AOR 1.26, 95 % CI [1.23, 1.30]) and perceived behavior control (AOR 1.06, 95 % CI [1.02, 1.10]) were significant predictors of intention to screen. Among women who provided comments in the survey, a large number of women expressed fears about not being checked more than every 4 years, but 12 % stated that these fears may be alleviated by having more information. Acceptability of increased screening intervals and starting age could be improved through enhanced education of benefits. Program planners should consider measures to assess and improve women’s knowledge, attitudes and beliefs prior to the implementation of new screening programs to avoid unintended consequences.

The objective of this study is to evaluate the incidence of non-AIDS defining malignancies (NADMs) among people living with HIV/AIDS (PLWHA) in British Columbia, focusing on clinical correlates, highly active antiretroviral therapy (HAART) use, and survival, in order to elucidate mechanisms for NADM development. A retrospective population based analysis was carried out for individuals with HIV/AIDS that began their treatment between 1996 and 2008. There were 145 (2.95%) NADMs and 123 (2.50%) AIDS defining malignancies (ADMs) identified in 4918 PLWHA in the study population. NADMs were represented by a range of cancer types including, most commonly, lung cancer, followed by anal, breast, head/neck, prostate, liver, rectal, and renal cancers. PLWHA had a SIR of 2.05 (CI:1.73, 2.41) for the development of NADMs compared to individuals without an HIV/AIDS diagnosis in the general population. Independent factors significantly associated with a NADM were: male gender, older age, lower CD4 cell counts, previous NADM, absence of HAART (non-HAART versus HAART) and treatment during the early-HAART era (before 2000 versus after 2000). NADMs represent an important source of morbidity for PLWHA. Use of HAART with its associated improvement in immune-restoration, and tailored targeted cancer screening interventions, may be beneficial and improve outcomes in this unique patient population.