Improving breast cancer screening in Australia: a public health perspective.

There are currently no single disruptors to breast cancer screening akin to the impact of human papillomavirus testing and vaccination on cervical cancer screening. However, there is a groundswell of interest to review the BreastScreen Australia program to consider more risk-based screening protocols and to establish whether to routinely inform women about their breast density. We propose a framework for a considered, evidence-based review. Population-level effectiveness of breast cancer screening is ultimately measured through its impact on breast cancer mortality, and this has been realised in Australia. Effectiveness can also be measured through treatment intensity, estimated overdiagnosis, false-positive screens and health economics measures. Key levers to improve such population-level outcomes include screening participation, screening test sensitivity and specificity, risk assessment and screening protocols. We propose that the review of the program should fall under an evidence-based, consensus-guided framework comprising four complementary elements: improved evidence on current program performance for population risk subgroups; regularly updated evidence on key levers for change; clinical trials and population simulation modelling working in tandem; and consensus-based decision making about the degree of improvement required to justify change. Informing women about their breast density is feasible and would be valued by some BreastScreen clients to help understand the accuracy of their screening test. However, without agreed protocols for screening women with dense breasts, increases in supplemental screening as observed in other settings would, in Australia, shift screening costs to clients and Medicare. This would reduce equity of access to population screening, and maintaining BreastScreen’s usual standard of monitoring and quality management (such as screen-detected and interval cancer diagnoses, and imaging and biopsy rates) would require data linkage between BreastScreen and other services. The proposed framework assesses screening effectiveness in the era of personalised medicine, allows review of multiple factors that may together warrant change, and gives full, evidence-based consideration of the benefits, harms and costs of various approaches to breast cancer screening. To be effective, the framework requires a coordinated approach to generating the evidence required for policy makers, with time to prepare appropriate health services

HPV-FRAME: A consensus statement and quality framework for modelled evaluations of HPV-related cancer control.

Intense research activity in HPV modelling over this decade has prompted the development of additional guidelines to those for general modelling. A specific framework is required to address different policy questions and unique complexities of HPV modelling. HPV-FRAME is an initiative to develop a consensus statement and quality-based framework for epidemiologic and economic HPV models. Its development involved an established process. Reporting standards have been structured according to seven domains reflecting distinct policy questions in HPV and cancer prevention and categorised by relevance to a population or evaluation. Population-relevant domains are: 1) HPV vaccination in pre-adolescent and young adolescent individuals; 2) HPV vaccination in older individuals; 3) targeted vaccination in men who have sex with men; 4) considerations for individuals living with HIV and 5) considerations for low- and middle-income countries. Additional considerations applicable to specific evaluations are: 6) cervical screening or integrated cervical screening and HPV vaccination approaches and 7) alternative vaccine types and alternative dosing schedules. HPV-FRAME aims to promote the development of models in accordance with an explicit framework, to better enable target audiences to understand a model's strength and weaknesses in relation to a specific policy question and ultimately improve the model's contribution to informed decision-making

A Large Linked Study to Evaluate the Future Burden of Cancer in Australia Attributable to Current Modifiable Behaviours

Introduction The cancer burden preventable through modifications to risk factors can be quantified by calculating their population attributable fractions (PAFs). PAF estimates require large, prospective data to inform risk estimates and contemporary population-based prevalence data to inform the current exposure distributions, including among population subgroups. Objectives and Approach We provide estimates of the preventable future cancer burden in Australia using large linked datasets. We pooled data from seven Australian cohort studies (N=367,058) and linked them to national registries to identify cancers and deaths. We estimated the strength of the associations between behaviours and cancer risk using a proportional hazards model, adjusting for age, sex, study and other behaviours. Exposure prevalence was estimated from contemporary National Health Surveys. We harmonised risk factor data across the data sources, and calculated PAFs and their 95% confidence intervals using a novel method accounting for competing risk of death and risk factor interdependence. Results During the first 10-years follow-up, there were 3,471 incident colorectal cancers, 640 premenopausal and 2,632 postmenopausal breast cancers, 2,025 lung cancers and 22,078 deaths. The leading preventable causes were current smoking (53.7% of lung cancers), body fatness or BMI ≥ 25kg/m2 (11.1% of colorectal cancers, 10.9% of postmenopausal breast cancers), and regular alcohol consumption (12.2% of premenopausal breast cancers). Three in five lung cancers, but only one in four colorectal cancers and one in five breast cancers, were attributable to modifiable factors, when we also considered physical inactivity, dietary and hormonal factors. The burden attributable to modifiable factors was markedly higher in certain population subgroups, including men (colorectal, lung), people with risk factor clustering (colorectal, breast, lung), and individuals with low educational attainment (breast, lung). Conclusion/Implications Estimating PAFs for modifiable risk factors across cancers using contemporary exposure prevalence data can inform timely public health action to improve health and health equity. Testing PAF effect modification may identify population subgroups with the most to gain from programs that support behaviour change and early detection

Menopausal hormone therapy: a systematic review of cost-effectiveness evaluations

Abstract Background Several evaluations of the cost-effectiveness (CE) of menopausal hormone therapy (MHT) have been reported. The aim of this study was to systematically and critically review economic evaluations of MHT since 2002, after the Women’s Health Initiative (WHI) trial results on MHT were published. Methods The inclusion criteria for the review were: CE analyses of MHT versus no treatment, published from 2002-2016, in healthy women, which included both symptom relief outcomes and a range of longer term health outcomes (breast cancer, coronary heart disease, stroke, fractures and colorectal cancer). Included economic models had outcomes expressed in cost per quality-adjusted life year or cost per life year saved. MEDLINE, EMBASE, Evidence-Based Medicine Reviews databases and the Cost-Effectiveness Analysis Registry were searched. CE evaluations were assessed in regard to (i) reporting standards using the CHEERS checklist and Drummond checklist; (ii) data sources for the utility of MHT with respect to menopausal symptom relief; (iii) cost derivation; (iv) outcomes considered in the models; and (v) the comprehensiveness of the models with respect to factors related to MHT use that impact long term outcomes, using breast cancer as an example outcome. Results Five studies satisfying the inclusion criteria were identified which modelled cohorts of women aged 50 and older who used combination or estrogen-only MHT for 5-15 years. For women 50-60 years of age, all evaluations found MHT to be cost-effective and below the willingness-to-pay threshold of the country for which the analysis was conducted. However, 3 analyses based the quality of life (QOL) benefit for symptom relief on one small primary study. Examination of costing methods identified a need for further clarity in the methodology used to aggregate costs from sources. Using breast cancer as an example outcome, risks as measured in the WHI were used in the majority of evaluations. Apart from the type and duration of MHT use, other effect modifiers for breast cancer outcomes (for example body mass index) were not considered. Conclusions This systematic review identified issues which could impact the outcome of MHT CE analyses and the generalisability of their results. The estimated CE of MHT is driven largely by estimates of QOL improvements associated with symptom relief but data sources on these utility weights are limited. Future analyses should carefully consider data sources and the evidence on the long term risks of MHT use in terms of chronic disease. This review highlights the considerable difficulties in conducting cost-effectiveness analyses in situations where short term benefits of an intervention must be evaluated in the context of long term health outcomes

Use of menopausal hormone therapy and bioidentical hormone therapy in Australian women 50 to 69 years of age: Results from a national, cross-sectional study

Menopausal Hormone Therapy (MHT) use in Australia fell by 55% from 2001 to 2005, following the release of large-scale findings on its risks and benefits. Comprehensive national data, including information on overall prevalence of MHT use as well as information on duration of use in Australia have not been reported since the 2004–5 National Health Survey, when 11% of women aged 45+ years were estimated to be current MHT users. No national data are available on prevalence of use of “bioidentical” hormone therapy (BHT). The objective of this study was to determine recent prevalence of MHT and BHT use. A cross-sectional, national, age-stratified, population survey was conducted in 2013. Eligible women, aged 50–69 years, resident in Australia were randomly sampled in 5-year age groups from the Medicare enrolment database (Australia’s universal health scheme). The response rate was 22% based on return of completed questionnaires, and analyses were restricted to 4,389 women within the specified age range. The estimated population-weighted prevalence of current use of MHT was 13% (95%CI 12–14), which was broadly similar to the previously reported national figures in 2004–5, suggesting that the use of MHT in Australia has largely stabilised over the past decade. A total of 39% and 20% of current-users with an intact uterus reported use of oestrogen-progestagen MHT and oestrogen-only MHT, respectively, whereas 77% of hysterectomised current-users used oestrogen-only MHT. Almost three-quarters of current-users [population-weighted prevalence 9% (95%CI 8–10)] had used MHT for ≥5 years. In regard to BHT, estimated population-weighted prevalence of ever use was 6% (95%CI 6–7) and 2% (95%CI 2–3) for current use. The population-weighted prevalence of MHT and BHT combined, in current users in their fifties and sixties was 15% (95%CI 14–16). These data provide a recent national “snapshot” of Australian women’s use of both conventional MHT and of BHT

Abstract P2-10-05: The estimated impact of COVID-19 on population breast cancer screening outcomes, and options for risk-based recovery

Abstract OBJECTIVES AND RATIONALE Estimating the impact of COVID-19 on cancer screening programs and related outcomes can help health services prepare for potential delays in diagnoses and different demands on treatment services and plan for best approaches to recovery. Simulation modelling enables estimation of outcomes for a range of scenarios. In this study, we estimate the impact of various disruptions and recovery strategies for the Australian biennial mammographic breast screening program (BreastScreen). METHOD Policy1-Breast is a continuous-time, multiple-cohort micro-simulation model that simulates the whole Australian female population, incorporating breast cancer risk and natural history, breast density, menopause, hormone therapy use and breast cancer screening. Firstly, in the early stages of the COVID pandemic we used Policy1-Breast to evaluate how 3, 6, 9 and 12-month pauses to BreastScreen would impact on population-level breast cancer diagnoses, tumour staging, and breast cancer survival, compared to business-as-usual (BAU) outcomes. Secondly, to explore options for recovery after an actual one-month screening pause in April 2020, we evaluated a range of assumed throughput levels following screening resumption (50% or 80% up to December, then 100% to 120% from Jan 2021), comparing various protocols where specific sub-groups of clients were prioritised for screening during the recovery period. Outcomes are reported for the target age range for the BreastScreen program (50-74 years). RESULTS For 3- to 12-month pauses, we estimated a slight reduction in 5-year survival following diagnosis for women directly affected by a pause, but no discernible changes to population-level breast cancer mortality rates up to 2023. We estimated marked fluctuations in population rates of invasive breast cancer diagnoses with a 10% increase in cancer diagnoses between 2020-2021 and 2022-2023. For a 12-month pause to screening we estimate that population-level breast cancers would increase in size (with an additional 4% >15mm at diagnosis) and be more likely to involve the nodes (increasing from 26% to 30% of all cancers). We estimate that median screening intervals during 2020-2021 would increase from 104 weeks under BAU up to 130 weeks with a 12-month pause, and BreastScreen recall rates and false positive recall rates would fluctuate markedly over time. For the second evaluation of a one-month pause followed by various throughput and prioritisation scenarios, we estimated that screen-detected cancer rates would vary markedly with throughput but interval cancer rates would not, leading to fluctuations in program sensitivity of up to 6%. Reflecting the periodic nature of screening participation, we estimated the extent to which longer-term future screening participation rates are expected echo the peaks and troughs in participation due to the impacts of the COVID pandemic in 2020. We estimate that for a given throughput assumption, client prioritisation could lead to different rescreening rates, screening intervals, and time required for prioritisation protocols, with little change to cancer outcomes. CONCLUSION These modelled evaluations estimate short and longer-term effects of COVID-19 on the impact of population breast cancer screening in Australia. The estimated changes in breast cancer rates and characteristics would be expected to have a flow-on effect on the demand for treatment services in terms of throughput and case-mix. Preparing for such outcomes is critical given that treatment services are also directly impacted by the pandemic. The modelled outcomes are likely to be relevant to other high-income settings with established population breast cancer screening programs. Citation Format: Pietro Procopio, Sabine Deij, Louiza S Velentzis, Amanda Tattam, Lara Petelin, Carolyn Nickson. The estimated impact of COVID-19 on population breast cancer screening outcomes, and options for risk-based recovery [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-10-05

Factors related to vaccine uptake by young adult women in the catch-up phase of the National HPV Vaccination Program in Australia: Results from an observational study

Background: Australia commenced a publically-funded, National Human Papillomavirus (HPV) Vaccination Program in 2007 with a two year catch-up phase for females aged 12-26 years. Objective: To identify the factors associated with the uptake of the HPV vaccine (which has a recommended 3-dose schedule in Australia) by young adult women vaccinated by general practitioners and community-based programs within the catch-up phase. Methods: 1139 women who were eligible to receive the free HPV vaccine during the catch-up period were recruited in 2008-2009 (age 20-29 years at recruitment), in New South Wales, after having a normal (negative) cervical smear result recorded on the NSW Pap Test Register. Participants completed a self-administered questionnaire providing information on vaccination status, and sociodemographic and other factors. Results: Overall, 880 (77%) women reported receiving ≥1 dose of the vaccine and 777 women (68%) reported receiving ≥2 doses. In multivariable analysis (adjusting for the period for which each woman was eligible for free HPV vaccination), uptake of ≥1 dose of the vaccine was significantly associated with being born in Australia (p<. 0.01), being single (p= 0.02), being nulliparous (p<. 0.01), living in a higher socioeconomic status area (p-trend. = 0.03), living in more remote areas (p= 0.03), drinking alcohol (p<. 0.01) and using hormonal contraceptives (p<. 0.01). Although vaccinated women were more likely to have fewer sexual partners than unvaccinated women (p-trend. = 0.02), they were also more likely to report a prior sexually transmitted infection (STI) (p= 0.03). Similar factors were associated with receiving ≥2 doses. Conclusions: In this group, women living in higher socioeconomic status areas were more likely to be vaccinated against HPV in the catch-up phase of the national program. Although vaccinated women tended to have fewer sexual partners, they also reported prior STIs, which may be a marker of increased risk of prior exposure to HPV. The findings of this study reinforce the continuing need to prioritise equitable delivery of vaccination to various population subgroups

Hormonal contraceptive use and smoking as risk factors for high-grade cervical intraepithelial neoplasia in unvaccinated women aged 30-44 years: A case-control study in New South Wales, Australia

Background: Human papillomavirus (HPV) vaccines protect against HPV types 16/18, but do not eliminate the need to detect pre-cancerous lesions. Australian women vaccinated as teenage girls are now entering their mid-thirties. Since other oncogenic HPV types have been shown to be more prevalent in women ≥30 years old, understanding high grade cervical lesions in older women is still important. Hormonal contraceptives (HC) and smoking are recognised cofactors for the development of pre-malignant lesions. Methods: 886 cases with cervical intraepithelial neoplasia (CIN) 2/3 and 3636 controls with normal cytology were recruited from the Pap Test Register of NSW, Australia. All women were aged 30–44 years. Conditional logistic regression was used to quantify the relationship of HC and smoking to CIN 2/3 adjusted for various factors. Results: Current-users of HC were at higher risk for CIN 2/3 than never-users [odds ratio (OR) = 1.50, 95%CI = 1.03–2.17] and risk increased with increasing duration of use [ORs:1.13 (0.73–1.75), 1.51 (1.00–2.72), 1.82 (1.22–2.72) for <10, 10–14, ≥15 years of use; p-trend = 0.04]. Ex-users had risks similar to never-users (OR 1.08, 95%CI = 0.75–1.57) regardless of duration of use. Current smoking was significantly associated with CIN 2/3 (OR = 1.43, 95%CI = 1.14–1.80) and risk increased with increasing number of cigarettes/day (p-trend = 0.02). Among ex-smokers, the risk of CIN 2/3 decreased with increasing time since quitting (p-trend = 0.04). Conclusions: In this benchmark study, current, long term users of HC and current smokers of ≥5 cigarettes/day were each at increased risk of developing CIN 2/3. Findings support smoking cessation in relation to decreasing the risk of pre-cancerous lesions and reinforce the continuing need for cervical screening for cancer prevention in vaccinated and unvaccinated populations.Funding for the study was provided by the National Health and Medical Research Council (NHMRC) Grant no. 337600

Hormonal contraceptive use and smoking as risk factors for high-grade cervical intraepithelial neoplasia in unvaccinated women aged 30-44 years: A case-control study in New South Wales, Australia

Background: Human papillomavirus (HPV) vaccines protect against HPV types 16/18, but do not eliminate the need to detect pre-cancerous lesions. Australian women vaccinated as teenage girls are now entering their mid-thirties. Since other oncogenic HPV types have been shown to be more prevalent in women ≥30 years old, understanding high grade cervical lesions in older women is still important. Hormonal contraceptives (HC) and smoking are recognised cofactors for the development of pre-malignant lesions. Methods: 886 cases with cervical intraepithelial neoplasia (CIN) 2/3 and 3636 controls with normal cytology were recruited from the Pap Test Register of NSW, Australia. All women were aged 30–44 years. Conditional logistic regression was used to quantify the relationship of HC and smoking to CIN 2/3 adjusted for various factors. Results: Current-users of HC were at higher risk for CIN 2/3 than never-users [odds ratio (OR) = 1.50, 95%CI = 1.03–2.17] and risk increased with increasing duration of use [ORs:1.13 (0.73–1.75), 1.51 (1.00–2.72), 1.82 (1.22–2.72) for <10, 10–14, ≥15 years of use; p-trend = 0.04]. Ex-users had risks similar to never-users (OR 1.08, 95%CI = 0.75–1.57) regardless of duration of use. Current smoking was significantly associated with CIN 2/3 (OR = 1.43, 95%CI = 1.14–1.80) and risk increased with increasing number of cigarettes/day (p-trend = 0.02). Among ex-smokers, the risk of CIN 2/3 decreased with increasing time since quitting (p-trend = 0.04). Conclusions: In this benchmark study, current, long term users of HC and current smokers of ≥5 cigarettes/day were each at increased risk of developing CIN 2/3. Findings support smoking cessation in relation to decreasing the risk of pre-cancerous lesions and reinforce the continuing need for cervical screening for cancer prevention in vaccinated and unvaccinated populations.Funding for the study was provided by the National Health and Medical Research Council (NHMRC) Grant no. 337600