Participation in the national cervical screening programme among women from New South Wales, Australia, by place of birth and time since immigration: A data linkage analysis using the 45 and up study.

OBJECTIVE: Equitable elimination of cervical cancer in Australia within the next decade will require high National Cervical Screening Program (NCSP) participation by all subgroups of women. The aim of this study was to examine the participation of immigrants compared to Australian-born women. METHODS: Participation in the NCSP (≥1cytology test) over a 3-year (2010-2012) and 5-year (2008-2012) period, by place of birth and time since immigration was examined using individually linked data of 67,350 New South Wales (NSW) women aged ≥45 enrolled in the 45 and Up Study. RESULTS: Three-year cervical screening participation was 77.0% overall. Compared to Australian-born women (77.8%), 3-year participation was lower for women born in New Zealand (adjusted odds ratio 0.77, 95% confidence interval 0.69-0.87), Oceania (0.67, 0.51-0.89), Middle East/North Africa (0.76, 0.60-0.97), South-East Asia (0.72, 0.60-0.87), Chinese Asia (0.82, 0.69-0.97), Japan/South Korea (0.68, 0.50-0.94), and Southern/Central Asia (0.54, 0.43-0.67), but higher for women from Malta (2.85, 1.77-4.58) and South America (1.33, 1.01-1.75). Non-English-speaking-at-home women were less likely to be screened than English-speaking-at-home women (0.85, 0.78-0.93). Participation increased with years lived in Australia but remained lower in immigrant groups compared to Australian-born women, even after ≥20 years living in Australia. Similar results were observed for 5-year participation. CONCLUSIONS: Women born in New Zealand, Oceania, and parts of Asia and the Middle East had lower NCSP participation, which persisted for ≥20 years post-immigration. The NCSP transition to primary HPV screening, and the introduction of the universal self-collection option in 2022, will offer new opportunities for increasing screening participation for these groups.

A modelled analysis of the impact of COVID-19-related disruptions to HPV vaccination.

COVID-19 disrupted school attendance in many countries, delaying routine adolescent vaccination against human papillomavirus (HPV) in some settings. We used Policy1-Cervix, a dynamic model simulating HPV transmission, natural history, vaccination, cervical screening, and diagnosis of HPV-related cancers, to estimate the impact on HPV-related cancers from disruptions to HPV vaccination in a high-income setting. A baseline scenario of no disruption to HPV vaccination was modelled, which assumed uptake of the nonavalent vaccine at the age of 12 by 82.4% of females and 75.5% of males, as is the coverage in Australia. Additional lifetime HPV-related cancer cases were calculated for three disruption scenarios affecting one birth cohort (2008; aged 12 in 2020) compared to the baseline scenario: (1) 1-year delay (no doses missed); (2) 1- to 7-year delay (slow catch-up); (3) no catch-up (herd effects only). A fourth scenario assumed no catch-up HPV vaccination for two birth cohorts, that is all individuals born in 2008 and in 2009 missed vaccination (worst-case scenario). Compared to 1532 HPV-related cancer cases estimated for the baseline no disruption scenario, we found a 1-year delay could result in ≤0.3% more HPV-related cancers (n = 4) but the increase would be greater if catch-up was slower (5%; n = 70), and especially if there was no catch-up (49%; n = 750). Additional cancers for a single missed cohort were most commonly cervical (23% of the additional cases) and anal cancers (16%) in females and oropharyngeal cancers in males (20%). In the worst-case scenario of two birth cohorts missing vaccination, ≤62% more HPV-related cancers would be diagnosed (n = 1892). In conclusion, providing catch-up of missed HPV vaccines is conducted, short-term delays in vaccinating adolescents are unlikely to have substantial long-term effects on cancer.

A modelled evaluation of the impact of COVID-19 on breast, bowel, and cervical cancer screening programmes in Australia.

Australia introduced COVID-19 infection prevention and control measures in early 2020. To help prepare health services, the Australian Government Department of Health commissioned a modelled evaluation of the impact of disruptions to population breast, bowel, and cervical cancer screening programmes on cancer outcomes and cancer services. We used the Policy1 modelling platforms to predict outcomes for potential disruptions to cancer screening participation, covering periods of 3, 6, 9, and 12 mo. We estimated missed screens, clinical outcomes (cancer incidence, tumour staging), and various diagnostic service impacts. We found that a 12-mo screening disruption would reduce breast cancer diagnoses (9.3% population-level reduction over 2020-2021) and colorectal cancer (up to 12.1% reduction over 2020-21), and increase cervical cancer diagnoses (up to 3.6% over 2020-2022), with upstaging expected for these cancer types (2, 1.4, and 6.8% for breast, cervical, and colorectal cancers, respectively). Findings for 6-12-mo disruption scenarios illustrate that maintaining screening participation is critical to preventing an increase in the burden of cancer at a population level. We provide programme-specific insights into which outcomes are expected to change, when changes are likely to become apparent, and likely downstream impacts. This evaluation provided evidence to guide decision-making for screening programmes and emphasises the ongoing benefits of maintaining screening in the face of potential future disruptions.

Incidence profile of four major cancers among migrants in Australia, 2005-2014.

PURPOSE: To compare the incidence profile of four major cancers in Australia by place of birth. METHODS: In this retrospective population-based cohort study, the analysis included 548,851 residents diagnosed with primary colorectum, lung, female breast, or prostate cancer during 2005-2014. Incidence rate ratio (IRR) and 95% confidence intervals (CI) were calculated for migrant groups relative to Australian-born. RESULTS: Compared with Australian-born residents, most migrant groups had significantly lower incidence rates for cancers of the colorectum, breast and prostate. The lowest rates of colorectal cancer were among males born in Central America (IRR = 0.46, 95% CI 0.29-0.74) and females born in Central Asia (IRR = 0.38, 95% CI 0.23-0.64). Males born in North-East Asia had the lowest rates of prostate cancer (IRR = 0.40, 95% CI 0.38-0.43) and females born in Central Asia had the lowest rates of breast cancer (IRR = 0.55, 95% CI 0.43-0.70). For lung cancer, several migrant groups had higher rates than Australian-born residents, with the highest rates among those from Melanesia (males IRR = 1.39, 95% CI 1.10-1.76; females IRR = 1.40, 95% CI 1.10-1.78). CONCLUSIONS: This study describes cancer patterns among Australian migrants, which are potentially helpful in understanding the etiology of these cancers and guiding the implementation of culturally sensitive and safe prevention measures. The lower incidence rates observed for most migrant groups may be maintained with continued emphasis on supporting communities to minimize modifiable risk factors such as smoking and alcohol consumption and participation in organized cancer screening programmes. Additionally, culturally sensitive tobacco control measures should be targeted to migrant communities with high lung cancer incidence rates.

Female reproductive and hormonal factors and lung cancer mortality among never-smokers: A prospective cohort study of 287 408 Chinese women.

There is growing, but inconsistent evidence suggesting oestrogen may play a key role in lung cancer development, especially among never-smoking women for whom lung cancer risk factors remain largely elusive. Using the China Kadoorie Biobank, a large-scale prospective cohort with 302 510 women aged 30 to 79 years recruited from 10 regions in China during 2004 to 2008, we assessed the risk of lung cancer death among self-reported never-smoking women who were cancer-free at baseline, in relation to age at menarche, age at menopause, time since menopause, prior use of oral contraceptives (OCP), number of livebirths, breastfeeding and age at first livebirth. Women were followed up to December 31, 2016 with linkage to mortality data. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression, adjusting for key confounders including several socio-demographic, environmental and lifestyle factors. Among 287 408 never-smoking women, 814 died from lung cancer with a median follow-up of 10.3 years. Women who had used OCP within 15 years prior to baseline had a significantly higher hazard of lung cancer death compared with never-users: HR = 1.85 (95% CI: 1.14-3.00) and risk increased by 6% with each additional year of use: HR = 1.06 (1.01-1.10). Among parous women, the hazard of lung cancer death increased by 13% with each single livebirth: HR = 1.13 (1.05-1.23); and among post-menopausal women, the risk increased by 2% with each year since menopause: HR = 1.02 (1.01-1.04). These results suggest that reproductive factors which were proxies for lower endogenous oestrogen level, for example, longer duration of OCP use, could play a role in lung cancer development.

Breast Cancer Risk Assessment Tools for Stratifying Women into Risk Groups: A Systematic Review.

BACKGROUND: The benefits and harms of breast screening may be better balanced through a risk-stratified approach. We conducted a systematic review assessing the accuracy of questionnaire-based risk assessment tools for this purpose. METHODS: Population: asymptomatic women aged ≥40 years; Intervention: questionnaire-based risk assessment tool (incorporating breast density and polygenic risk where available); Comparison: different tool applied to the same population; Primary outcome: breast cancer incidence; Scope: external validation studies identified from databases including Medline and Embase (period 1 January 2008-20 July 2021). We assessed calibration (goodness-of-fit) between expected and observed cancers and compared observed cancer rates by risk group. Risk of bias was assessed with PROBAST. RESULTS: Of 5124 records, 13 were included examining 11 tools across 15 cohorts. The Gail tool was most represented (n = 11), followed by Tyrer-Cuzick (n = 5), BRCAPRO and iCARE-Lit (n = 3). No tool was consistently well-calibrated across multiple studies and breast density or polygenic risk scores did not improve calibration. Most tools identified a risk group with higher rates of observed cancers, but few tools identified lower-risk groups across different settings. All tools demonstrated a high risk of bias. CONCLUSION: Some risk tools can identify groups of women at higher or lower breast cancer risk, but this is highly dependent on the setting and population.

Exploring monitoring strategies for population surveillance of HPV vaccine impact using primary HPV screening.

Australia's cervical screening program transitioned from cytology to HPV-testing with genotyping for HPV16/18 in Dec'2017. We investigated whether program data could be used to monitor HPV vaccination program impact (commenced in 2007) on HPV16/18 prevalence and compared estimates with pre-vaccination benchmark prevalence. Pre-vaccination samples (2005-2008) (n = 1933; WHINURS), from 25 to 64-year-old women had been previously analysed with Linear Array (LA). Post-vaccination samples (2013-2014) (n = 2989; Compass pilot), from 25 to 64-year-old women, were analysed by cobas 4800 (cobas), and by LA for historical comparability. Age standardised pre-vaccination HPV16/18 prevalence was 4.85% (95%CI:3.81-5.89) by LA; post-vaccination estimates were 1.67% (95%CI:1.21-2.13%) by LA, 1.49% (95%CI:1.05-1.93%) by cobas, and 1.63% (95%CI:1.17-2.08%) for cobas and LA testing of non-16/18 cobas positives (cobas/LA). Age-standardised pre-vaccination oncogenic HPV prevalence was 15.70% (95%CI:13.79-17.60%) by LA; post-vaccination estimates were 9.06% (95%CI:8.02-10.09%) by LA, 8.47% (95%CI:7.47-9.47%) by cobas and cobas/LA. Standardised rate ratios between post-vs. pre-vaccination rates were significantly different for HPV16/18, non-16/18 HPV and oncogenic HPV: 0.34 (95%CI:0.23-0.50), 0.68 (95%CI:0.55-0.84) and 0.58 (95%CI:0.48-0.69), respectively. Additional strategies (LA for all cobas positives; combined cobas and LA results on all samples) had similar results. If a single method is applied consistently, it will provide important data on relative changes in HPV prevalence following vaccination.

Accurate categorisation of menopausal status for research studies: a step-by-step guide and detailed algorithm considering age, self-reported menopause and factors potentially masking the occurrence of menopause.

OBJECTIVE: Menopausal status impacts risk for many health outcomes. However, factors including hysterectomy without oophorectomy and Menopausal Hormone Therapy (MHT) can mask menopause, affecting reliability of self-reported menopausal status in surveys. We describe a step-by-step algorithm for classifying menopausal status using: directly self-reported menopausal status; MHT use; hysterectomy; oophorectomy; intervention timing; and attained age. We illustrate this approach using the Australian 45 and Up Study cohort (142,973 women aged ≥ 45 years). RESULTS: We derived a detailed seven-category menopausal status, able to be further consolidated into four categories ("pre-menopause"/"peri-menopause"/"post-menopause"/"unknown") accounting for participants' ages. 48.3% of women had potentially menopause-masking interventions. Overall, 93,107 (65.1%), 9076 (6.4%), 17,930 (12.5%) and 22,860 (16.0%) women had a directly self-reported "post-menopause", "peri-menopause", "pre-menopause" and "not sure"/missing status, respectively. 61,464 women with directly self-reported "post-menopause" status were assigned a "natural menopause" detailed derived status (menopause without MHT use/hysterectomy/oophorectomy). By accounting for participants' ages, 105,817 (74.0%) women were assigned a "post-menopause" consolidated derived status, including 15,009 of 22,860 women with "not sure"/missing directly self-reported status. Conversely, 3178 of women with directly self-reported "post-menopause" status were assigned "unknown" consolidated derived status. This algorithm is likely to improve the accuracy and reliability of studies examining outcomes impacted by menopausal status.

BreastScreen Australia national data by factors of interest for risk-based screening: routinely reported data and opportunities for enhancement.

OBJECTIVE: There is growing interest in more risk-based approaches to breast cancer screening in Australia. This would require more detailed reporting of BreastScreen data for factors of interest in the assessment and monitoring of risk-based screening. This review assesses the current and potential availability and reporting of BreastScreen data for this purpose. METHODS: We systematically searched governmental BreastScreen reports and peer-reviewed literature to assess current and potential availability of outcomes for predetermined factors including breast cancer risk factors and factors important for implementing, monitoring or evaluating risk-based screening. Outcomes evaluated were BreastScreen Performance Indicators routinely included in BreastScreen Australia monitoring reports, and key tumour characteristics. RESULTS: All outcomes were reported annually by age group, except for tumour hormone receptor status, nodal involvement and grade. Screening participation was reported nationally for many factors important for risk-based screening; other reporting was ad hoc or unavailable. CONCLUSIONS: There is potential to build on BreastScreen's existing high-quality national data collection and reporting systems to inform and support risk-based breast screening. IMPLICATIONS FOR PUBLIC HEALTH: Enhanced BreastScreen data collection and reporting would improve the evidence base and support evaluation of risk-based screening and improve the detail available for benchmarking any future changes to the program.

The impact of HPV vaccination beyond cancer prevention: effect on pregnancy outcomes.

While the benefits of human papillomavirus (HPV) vaccination relating to cervical cancer prevention have been widely documented, recent published evidence is suggestive of an impact on adverse pregnancy outcomes (APOs) in vaccinated mothers and their infants, including a reduction in rates of preterm births and small for gestational age infants. In this review, we examine this evidence and the possible mechanisms by which HPV vaccination may prevent these APOs. Large-scale studies linking HPV vaccination status with birth registries are needed to confirm these results. Potential confounding factors to consider in future analyses include other risk factors for APOs, and historical changes in both the management of cervical precancerous lesions and prevention of APOs. If confirmed, these additional benefits of HPV vaccination in reducing APO rates will be of global significance, due to the substantial health, social and economic costs associated with APOs, strengthening the case for worldwide HPV immunization.

Menopausal hormone therapy: Characterising users in an Australian national cross-sectional study.

Menopausal hormone therapy (MHT) is effective for menopausal symptoms, however, its use is also associated with risks of serious health conditions including breast, ovarian and endometrial cancer, stroke and venous thromboembolism. MHT-related health risks increase with longer durations of use. In Australia, while overall MHT use fell when risk-related findings were published in 2002, a significant number of women continue using MHT long-term. We aimed to examine socio-demographic, health-related and lifestyle characteristics in relation to post-2002 MHT use, and to compare use for <5 and ≥5 years. Data from 1,561 participants from an Australian, national, cross-sectional survey of women aged 50-69 in 2013 were analysed. Odds ratios (ORs) were calculated using logistic regression for characteristics related to overall MHT use post-2002 and multinomial logistic regression for associations between MHT duration of use [never/<5 years/≥5 years] and personal characteristics, adjusting for sociodemographic, reproductive, health and lifestyle factors. Post-2002 MHT use was associated with increasing age (p-trend<0.001), hysterectomy versus no hysterectomy (OR:2.55, 95%CI = 1.85-3.51), bilateral oophorectomy vs no oophorectomy (OR:1.66, 95%CI = 1.09-2.53), and ever- versus never-use of therapies other than MHT for menopausal symptoms (OR:1.93, 95%CI = 1.48-2.57). Women with prior breast cancer (OR:0.35, 95%CI = 0.17-0.74) and with more children (p-trend = 0.034) were less likely than other women to use MHT. Prior hysterectomy was more strongly associated with MHT use for ≥5 years than for <5 years (p = 0.004). Ever-use of non-MHT menopausal therapies was associated with MHT use for <5 years but not with longer-term use (p = 0.004). This study reinforces the need for MHT users and their clinicians to re-evaluate continued MHT use on an ongoing basis.

Moving beyond the stage: how characteristics at diagnosis dictate treatment and treatment-related quality of life year losses for women with early stage invasive breast cancer.

Background:Although evaluations of breast cancer screening programs frequently estimate quality-adjusted life-year (QALY) losses by stage, other breast cancer characteristics influence treatment and vary by mode of detection - i.e. whether the cancer is detected through screening (screen-detected), between screening rounds (interval-detected) or outside screening (community-detected). Here, we estimate the association between early-stage invasive breast cancer (ESIBC) characteristics and treatment-related QALY losses.Methods:Using clinicopathological and treatment information from 675 women managed for ESIBC, we estimated the average five-year treatment-related QALY loss by detection group. We then used regression analysis to estimate the extent to which known cancer characteristics and the detection mode, are associated with treatment and treatment-related QALY losses.Results:Community-detected cancers had the largest QALY loss (0.76 QALYs [95% CI 0.73;0.80]), followed by interval-detected cancers (0.75 QALYs [95% CI 0.68;0.82]) and screen-detected cancers (0.69 QALYs [95%CI 0.67;0.71]). Adverse prognostic factors more common in community-detected and interval-detected breast cancers (large tumours, lymph node involvement, high grade) were largely associated with QALY losses from mastectomies and chemotherapy. Receptor-positive subtypes, more common in screen-detected cancers, were associated with QALY losses related to endocrine therapy.Conclusions:The associations between ESIBC characteristics and treatment-related QALY losses should be considered when evaluating breast cancer screening and treatment strategies.

Has Human Papillomavirus (HPV) Vaccination Prevented Adverse Pregnancy Outcomes? Population-Level Analysis After 8 Years of a National HPV Vaccination Program in Australia.

BACKGROUND: Human papillomavirus (HPV) infection, and its sequelae of precancerous cervical lesions and their subsequent treatment, have been linked with an increased risk of adverse pregnancy outcomes. Publicly funded HPV vaccination of female adolescents began in Australia in 2007 with initial catch-up to age 26 years. METHODS: Using data from the National Perinatal Data Collection we compared rates of preterm births and small-for-gestational-age infants born in Australia 2000-2015. We used generalized linear models, assuming a Poisson distribution and log link function, with single-year categories of infant birth year, maternal age, and age-specific HPV vaccination coverage as independent variables. RESULTS: In maternal cohorts with 60%-80% HPV vaccination coverage as achieved in Australia, there was a relative rate reduction of 3.2% (95% confidence interval, 1.1%-5.3%) in preterm births and 9.8% (8.2% to 11.4%) in small-for-gestational-age infants, after adjustment for infant's birth year and maternal age. CONCLUSION: This analysis provides provisional population-level evidence of a reduction in adverse pregnancy outcomes in cohorts of women offered HPV vaccination. Confounding by smoking or other variables and/or ecological analysis limitations, however, cannot be excluded. These findings indicate potential broader benefits of HPV vaccination than have been documented to date.

The financial impact of a breast cancer detected within and outside of screening: lessons from the Australian Lifepool cohort.

OBJECTIVE: To determine the government and out-of-pocket community costs (out-of-hospital medical services and prescription medicines) associated with screen-detected and community-detected cancers (i.e. cancers detected outside of Australia's organised screening program [BreastScreen]). METHODS: We analyse administrative data on government-subsidised medical services and prescription medicines for 568 Victorian women diagnosed with breast cancer or ductal carcinoma in situ (DCIS). Using multivariable regression analysis, we estimate the government and out-of-pocket community costs incurred in the three years after diagnosis for screen-detected cancers and community-detected cancers. Additionally, we estimate the government costs associated with diagnosis within and outside of BreastScreen. RESULTS: Average government costs for breast cancer diagnosis were similar within and outside of BreastScreen [$808 (lower limit 676; upper limit 940) vs $837 (95%CI 671; 1,003) respectively]; however, women with community-detected cancers incurred an additional $254 (95%CI 175; 332) out-of-pocket. Controlling for differences in known cancer characteristics, compared to screen-detected cancers, community-detected breast cancers were associated with an additional $2,622 (95%CI 644; 4,776) in government expenditure in the three years following diagnosis. Adverse cancer characteristics that were more prevalent in community-detected cancers (high grade, lymph node involvement, HER2 positive receptor status) were associated with increased government and out-of-pocket costs. CONCLUSIONS: Community-detected breast cancers were associated with increased government and out-of-pocket costs. Implications for public health: These costs should be considered when evaluating current and alternative breast cancer screening strategies.

Trends in Prescribing Menopausal Hormone Therapy and Bisphosphonates in Australia and Manitoba, Canada and Adherence to Recommendations.

Background: Recommendations for using menopausal hormone therapy (MHT) and bisphosphonates for postmenopausal osteoporosis management have changed over time. After the release of the Women's Health Initiative (WHI) trial results in 2002, new evidence on risks and benefits of MHT became available, and newer guidelines generally specify that MHT should not be prescribed for prevention of chronic disease, including osteoporosis. This raises the question of whether bisphosphonate prescribing changed over time to compensate for the decrease in MHT use. Materials and Methods: We examined trends in dispensed prescriptions in Australia (national) and Canada (province of Manitoba) in relation to prescribing recommendations. Administrative data were used to describe dispensing patterns and changes for persons of all ages from 1996 to 2008, and for women aged 50 to ≥80 years from 2003 to 2008 in Australia and 1996 to 2008 in Canada. Results: In both geographic settings, MHT dispensing increased 1996-2001, peaked in 2001, and declined substantially thereafter (67% reduction in MHT prescriptions for Australia; 64% reduction for Manitoba, Canada to 2008). From 2003 to 2008, the number of MHT prescriptions declined among all age groups in both settings, with the highest declines among women in their 50s. Concurrently, bisphosphonate dispensing increased until 2005 (2001-2005: 260% increase in the number of prescriptions in Australia; 125% increase in Manitoba) and stabilized thereafter, in both settings. Annual bisphosphonate dispensing rates increased 4.1-10.9% for women in their 70s and 80s in Australia and Manitoba during the period studied. Conclusions: Based on dispensed prescriptions data, more recent guidelines for MHT and bisphosphonates use for postmenopausal osteoporosis, which were updated during the study period (and are still consistent with the current guidelines), appear to have been broadly adhered to in both settings.

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.

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.

The preventable burden of endometrial and ovarian cancers in Australia: A pooled cohort study.

OBJECTIVE: Evidence on the endometrial and ovarian cancer burden preventable through modifications to current causal behavioural and hormonal exposures is limited. Whether the burden differs by population subgroup is unknown. METHODS: We linked pooled data from six Australian cohort studies to national cancer and death registries, and quantified exposure-cancer associations using adjusted proportional hazards models. We estimated exposure prevalence from representative health surveys. We then calculated Population Attributable Fractions (PAFs) with 95% confidence intervals (CIs), accounting for competing risk of death, and compared PAFs for population subgroups. RESULTS: During a median 4.9 years follow-up, 510 incident endometrial and 303 ovarian cancers were diagnosed. Overweight and obesity explained 41.9% (95% CI 32.3-50.1) of the endometrial cancer burden and obesity alone 34.5% (95% CI 27.5-40.9). This translates to 12,800 and 10,500 endometrial cancers in Australia in the next 10 years, respectively. The body fatness-related endometrial cancer burden was highest (49-87%) among women with diabetes, living remotely, of older age, lower socio-economic status or educational attainment and born in Australia. Never use of oral contraceptives (OCs) explained 8.1% (95% CI 1.8-14.1) or 2500 endometrial cancers. A higher BMI and current long-term MHT use increased, and long-term OC use decreased, the risk of ovarian cancer, but the burden attributable to overweight, obesity or exogenous hormonal factors was not statistically significant. CONCLUSIONS: Excess body fatness, a trait that is of high and increasing prevalence globally, is responsible for a large proportion of the endometrial cancer burden, indicating the need for effective strategies to reduce adiposity.

Pathways to a cancer-free future: A protocol for modelled evaluations to maximize the future impact of interventions on cervical cancer in Australia.

OBJECTIVE: Australia's HPV vaccination and HPV-based cervical screening programs are changing the landscape in cervical cancer prevention. We aim to identify areas which can make the biggest further impact on cervical cancer burden. This protocol describes the first stage of a program of work called Pathways-Cervix that aims to generate evidence from modelled evaluations of interventions across the cervical cancer spectrum. METHODS: Based on evidence from literature reviews and guidance from a multi-disciplinary Scientific Advisory Committee (SAC), the most relevant evaluations for prevention, diagnosis and treatment were identified. RESULTS: Priority evaluations agreed by the SAC included: increasing/decreasing and retaining vaccination uptake at the current level; vaccinating older women; increasing screening participation; methods for triaging HPV-positive women; improving the diagnosis of cervical intraepithelial neoplasia (CIN) and cancer; treating cervical abnormalities and cancer; and vaccinating women treated for CIN2/3 to prevent recurrence. Evaluations will be performed using a simulation model, Policy1-Cervix previously used to perform policy evaluations in Australia. Exploratory modelling of interventions using idealised scenarios will initially be conducted in single birth cohorts. If these have a significant impact on findings then evaluations with more realistic assumptions will be conducted. Promising strategies will be investigated further by multi-cohort simulations predicting health outcomes, resource use and cost outcomes. CONCLUSIONS: Pathways-Cervix will assess the relative benefits of strategies and treatment options in a systematic and health economic framework, producing a list of 'best buys' for future decision-making in cervical cancer control.

The preventable burden of breast cancers for premenopausal and postmenopausal women in Australia: A pooled cohort study.

Estimates of the future breast cancer burden preventable through modifications to current behaviours are lacking. We assessed the effect of individual and joint behaviour modifications on breast cancer burden for premenopausal and postmenopausal Australian women, and whether effects differed between population subgroups. We linked pooled data from six Australian cohort studies (n = 214,536) to national cancer and death registries, and estimated the strength of the associations between behaviours causally related to cancer incidence and death using adjusted proportional hazards models. We estimated exposure prevalence from representative health surveys. We combined these estimates to calculate Population Attributable Fractions (PAFs) with 95% confidence intervals (CIs), and compared PAFs for population subgroups. During the first 10 years follow-up, there were 640 incident breast cancers for premenopausal women, 2,632 for postmenopausal women, and 8,761 deaths from any cause. Of future breast cancers for premenopausal women, any regular alcohol consumption explains 12.6% (CI = 4.3-20.2%), current use of oral contraceptives for ≥5 years 7.1% (CI = 0.3-13.5%), and these factors combined 18.8% (CI = 9.1-27.4%). Of future breast cancers for postmenopausal women, overweight or obesity (BMI ≥25 kg/m2 ) explains 12.8% (CI = 7.8-17.5%), current use of menopausal hormone therapy (MHT) 6.9% (CI = 4.8-8.9%), any regular alcohol consumption 6.6% (CI = 1.5-11.4%), and these factors combined 24.2% (CI = 17.6-30.3%). The MHT-related postmenopausal breast cancer burden varied by body fatness, alcohol consumption and socio-economic status, the body fatness-related postmenopausal breast cancer burden by alcohol consumption and educational attainment, and the alcohol-related postmenopausal breast cancer burden by breast feeding history. Our results provide evidence to support targeted and population-level cancer control activities.