Michael Caruana's research while affiliated with The University of Sydney and other places

Genetic and genomic testing can provide valuable information on individuals’ risk of chronic diseases, presenting an opportunity for risk-tailored disease screening to improve early detection and health outcomes. The acceptability, uptake and effectiveness of such programmes is dependent on public preferences for the programme features. This study aims to conduct a systematic review of discrete choice experiments assessing preferences for genetic/genomic risk-tailored chronic disease screening. PubMed, Embase, EconLit and Cochrane Library were searched in October 2023 for discrete choice experiment studies assessing preferences for genetic or genomic risk-tailored chronic disease screening. Eligible studies were double screened, extracted and synthesised through descriptive statistics and content analysis of themes. Bias was assessed using an existing quality checklist. Twelve studies were included. Most studies focused on cancer screening (n = 10) and explored preferences for testing of rare, high-risk variants (n = 10), largely within a targeted population (e.g. subgroups with family history of disease). Two studies explored preferences for the use of polygenic risk scores (PRS) at a population level. Twenty-six programme attributes were identified, with most significantly impacting preferences. Survival, test accuracy and screening impact were most frequently reported as most important. Depending on the clinical context and programme attributes and levels, estimated uptake of hypothetical programmes varied from no participation to almost full participation (97%). The uptake of potential programmes would strongly depend on specific programme features and the disease context. In particular, careful communication of potential survival benefits and likely genetic/genomic test accuracy might encourage uptake of genetic and genomic risk-tailored disease screening programmes. As the majority of the literature focused on high-risk variants and cancer screening, further research is required to understand preferences specific to PRS testing at a population level and targeted genomic testing for different disease contexts.

COVID-19 disrupted cancer control worldwide, impacting preventative screening, diagnoses, and treatment services. This modelling study estimates the impact of disruptions on colorectal cancer cases and deaths in Canada and Australia, informed by data on screening, diagnosis, and treatment procedures. Modelling was used to estimate short- and long-term effects on colorectal cancer incidence and mortality, including ongoing impact of patient backlogs. A hypothetical mitigation strategy was simulated, with diagnostic and treatment capacities increased by 5% from 2022 to address backlogs. Colorectal cancer screening dropped by 40% in Canada and 6.3% in Australia in 2020. Significant decreases to diagnostic and treatment procedures were also observed in Australia and Canada, which were estimated to lead to additional patient wait times. These changes would lead to an estimated increase of 255 colorectal cancer cases and 1,820 colorectal cancer deaths in Canada and 234 cases and 1,186 deaths in Australia over 2020–2030; a 1.9% and 2.4% increase in mortality, respectively, vs a scenario with no screening disruption or diagnostic/treatment delays. Diagnostic and treatment capacity mitigation would avert 789 and 350 deaths in Canada and Australia, respectively. COVID-related disruptions had a significant impact on colorectal cancer screening, diagnostic, and treatment procedures in Canada and Australia. Modelling demonstrates that downstream effects on disease burden could be substantial. However, backlogs can be managed and deaths averted with even small increases to diagnostic and treatment capacity. Careful management of resources can improve patient outcomes after any temporary disruption, and these results can inform targeted approaches early detection of cancers.

Background Long-term projections of premature mortality (defined as deaths age <75 years) help to inform decisions about public health priorities. This study aimed to project premature mortality rates in Australia to 2044, and to estimate numbers of deaths and potential years of life lost (PYLL) due to premature mortality overall and for 59 causes. Methods We examined the past trends in premature mortality rates using Australian mortality data by sex, 5-year age group and 5-year calendar period up to 2019. Cigarette smoking exposure data (1945–2019) were included to project lung cancer mortality. Age-period-cohort or generalised linear models were developed and validated for each cause to project premature mortality rates to 2044. Findings Over the 25-year period from 1990–1994 to 2015–2019, there was a 44.4% decrease in the overall age-standardised premature mortality rate. This decline is expected to continue, from 162.4 deaths/100,000 population in 2015–2019 to 141.7/100,000 in 2040–2044 (12.7% decrease). Despite declining rates, total numbers of premature deaths are projected to increase by 22.8%, rising from 272,815 deaths in 2015–2019 to 334,894 deaths in 2040–2044. This is expected to result in 1.58 million premature deaths over the 25-year period 2020–2044, accounting for 24.5 million PYLL. Of the high-level cause categories, cancer is projected to remain the most common cause of premature death in Australia by 2044, followed by cardiovascular disease, external causes (including injury, poisoning, and suicide), and respiratory diseases. Interpretation Despite continuously declining overall premature mortality rates, the total number of premature deaths in Australia is projected to remain substantial, and cancer will continue to be the leading cause. These projections can inform the targeting of public health efforts and can serve as benchmarks against which to measure the impact of future interventions. They emphasise the ongoing importance of accelerating the prevention, early detection, and treatment of key health conditions. Funding No funding was provided for this study.

In 2020, the World Health Organization (WHO) launched a strategy to eliminate cervical cancer as a public health problem. To support the strategy, the WHO published updated cervical screening guidelines in 2021. To inform this update, we used an established modeling platform, Policy1-Cervix, to evaluate the impact of seven primary screening scenarios across 78 low- and lower-middle-income countries (LMICs) for the general population of women. Assuming 70% coverage, we found that primary human papillomavirus (HPV) screening approaches were the most effective and cost-effective, reducing cervical cancer age-standardized mortality rates by 63–67% when offered every 5 years. Strategies involving triaging women before treatment (with 16/18 genotyping, cytology, visual inspection with acetic acid (VIA) or colposcopy) had close-to-similar effectiveness to HPV screening without triage and fewer pre-cancer treatments. Screening with VIA or cytology every 3 years was less effective and less cost-effective than HPV screening every 5 years. Furthermore, VIA generated more than double the number of pre-cancer treatments compared to HPV. In conclusion, primary HPV screening is the most effective, cost-effective and efficient cervical screening option in LMICs. These findings have directly informed WHO’s updated cervical screening guidelines for the general population of women, which recommend primary HPV screening in a screen-and-treat or screen-triage-and-treat approach, starting from age 30 years with screening every 5 years or 10 years.

To support a strategy to eliminate cervical cancer as a public health problem, the World Health Organisation (WHO) reviewed its guidelines for screening and treatment of cervical pre-cancerous lesions in 2021. Women living with HIV have 6-times the risk of cervical cancer compared to women in the general population, and we harnessed a model platform (‘Policy1-Cervix-HIV’) to evaluate the benefits and harms of a range of screening strategies for women living with HIV in Tanzania, a country with endemic HIV. Assuming 70% coverage, we found that 3-yearly primary HPV screening without triage would reduce age-standardised cervical cancer mortality rates by 72%, with a number needed to treat (NNT) of 38.7, to prevent a cervical cancer death. Triaging HPV positive women before treatment resulted in minimal loss of effectiveness and had more favorable NNTs (19.7–33.0). Screening using visual inspection with acetic acid (VIA) or cytology was less effective than primary HPV and, in the case of VIA, generated a far higher NNT of 107.5. These findings support the WHO 2021 recommendation that women living with HIV are screened with primary HPV testing in a screen-triage-and-treat approach starting at 25 years, with regular screening every 3–5 years.

While previous reviews found a positive association between pre‐existing cancer diagnosis and COVID‐19‐related death, most early studies did not distinguish long‐term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher‐quality evidence on risk of COVID‐19‐related death for people with recent/active cancer (compared to people without) in the pre‐COVID‐19‐vaccination period. We searched the WHO COVID‐19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk‐of‐bias assessment was based on the Newcastle‐Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse‐variance random‐effects models. Random‐effects meta‐regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID‐19‐related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36‐1.61, I² = 0; people with COVID‐19: aOR = 1.58, 95% CI: 1.41‐1.77, I² = 0.58; inpatients with COVID‐19: aOR = 1.66, 95% CI: 1.34‐2.06, I² = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4‐4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68‐2.68, I² = 0.43), and for metastatic cancers. Meta‐regression suggested risk of COVID‐19‐related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37‐1.75) at 1 year and aOR = 0.98 (95% CI: 0.80‐1.20) at 5 years post‐cancer diagnosis/treatment. In conclusion, before COVID‐19‐vaccination, risk of COVID‐19‐related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment.

Guidelines for prostate specific antigen (PSA) testing in Australia recommend that men at average risk of prostate cancer who have been informed of the benefits and harms, and who decide to undergo regular testing, should be offered testing every 2 years from 50 to 69 years. This study aimed to estimate the benefits and harms of regular testing in this context. We constructed Policy1‐Prostate, a discrete event microsimulation platform of the natural history of prostate cancer and prostate cancer survival, and PSA testing patterns and subsequent management in Australia. The model was calibrated to pre‐PSA (before 1985) prostate cancer incidence and mortality and validated against incidence and mortality trends from 1985 to 2011 and international trials. The model predictions were concordant with trials and Australian observed incidence and mortality data from 1985 to 2011. Out of 1000 men who choose to test according to the guidelines, 36 [21‐41] men will die from prostate cancer and 126 [119‐133] men will be diagnosed with prostate cancer, compared with 50 [47‐54] and 94 [90‐98] men who do not test, respectively. During the 20 years of active PSA testing, 32.3% [25.6%‐38.8%] of all PSA‐test detected cancers are overdiagnosed cases that is, 30 [21‐42] out of 94 [83‐107] PSA‐test detected cancers. Australian men choosing to test with PSA every two years from 50 to 69 will reduce their risk of ever dying from prostate cancer and incur a risk of overdiagnosis: for every man who avoids dying from prostate cancer, two will be overdiagnosed with prostate cancer between 50 and 69 years of age. Australian men, with health professionals, can use these results to inform decision‐making about PSA testing.

Objective To compare 50-year forecasts of Australian tobacco smoking rates in relation to trends in smoking initiation and cessation and in relation to a national target of ≤5% adult daily prevalence by 2030. Methods A compartmental model of Australian population daily smoking, calibrated to the observed smoking status of 229 523 participants aged 20–99 years in 26 surveys (1962–2016) by age, sex and birth year (1910–1996), estimated smoking prevalence to 2066 using Australian Bureau of Statistics 50-year population predictions. Prevalence forecasts were compared across scenarios in which smoking initiation and cessation trends from 2017 were continued, kept constant or reversed. Results At the end of the observation period in 2016, model-estimated daily smoking prevalence was 13.7% (90% equal-tailed interval (EI) 13.4%–14.0%). When smoking initiation and cessation rates were held constant, daily smoking prevalence reached 5.2% (90% EI 4.9%–5.5%) after 50 years, in 2066. When initiation and cessation rates continued their trajectory downwards and upwards, respectively, daily smoking prevalence reached 5% by 2039 (90% EI 2037–2041). The greatest progress towards the 5% goal came from eliminating initiation among younger cohorts, with the target met by 2037 (90% EI 2036–2038) in the most optimistic scenario. Conversely, if initiation and cessation rates reversed to 2007 levels, estimated prevalence was 9.1% (90% EI 8.8%–9.4%) in 2066. Conclusion A 5% adult daily smoking prevalence target cannot be achieved by the year 2030 based on current trends. Urgent investment in concerted strategies that prevent smoking initiation and facilitate cessation is necessary to achieve 5% prevalence by 2030.