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.

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.

Clinical Validation of the cobas HPV Test on the cobas 6800 System for the Purpose of Cervical Screening.

This study demonstrates that the clinical sensitivity, specificity, and reproducibility of the novel cobas human papillomavirus (HPV) test on the cobas 6800 system for high-risk HPV types fulfills the criteria for use in population-based cervical screening. The criteria were formulated by an international consortium, using the cobas 4800 HPV test as a validated reference assay. The cobas HPV test detected over 98% of histologically confirmed cervical intraepithelial neoplasia grade 2+ (CIN2+) lesions in women age 30 years or older, with a specificity of 98.9% compared with the reference cobas 4800 test. Both the intra- and interlaboratory agreement for the cobas HPV test were 98%. The clinical performance of the cobas HPV test is comparable to those of longitudinally validated HPV assays and fulfills the criteria for its use in primary cervical screening.

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.

Prospective validation of the NCI Breast Cancer Risk Assessment Tool (Gail Model) on 40,000 Australian women.

BACKGROUND: There is a growing interest in delivering more personalised, risk-based breast cancer screening protocols. This requires population-level validation of practical models that can stratify women into breast cancer risk groups. Few studies have evaluated the Gail model (NCI Breast Cancer Risk Assessment Tool) in a population screening setting; we validated this tool in a large, screened population. METHODS: We used data from 40,158 women aged 50-69 years (via the lifepool cohort) participating in Australia's BreastScreen programme. We investigated the association between Gail scores and future invasive breast cancer, comparing observed and expected outcomes by Gail score ranked groups. We also used machine learning to rank Gail model input variables by importance and then assessed the incremental benefit in risk prediction obtained by adding variables in order of diminishing importance. RESULTS: Over a median of 4.3 years, the Gail model predicted 612 invasive breast cancers compared with 564 observed cancers (expected/observed (E/O) = 1.09, 95% confidence interval (CI) 1.00-1.18). There was good agreement across decile groups of Gail scores (χ2 = 7.1, p = 0.6) although there was some overestimation of cancer risk in the top decile of our study group (E/O = 1.65, 95% CI 1.33-2.07). Women in the highest quintile (Q5) of Gail scores had a 2.28-fold increased risk of breast cancer (95% CI 1.73-3.02, p < 0.0001) compared with the lowest quintile (Q1). Compared with the median quintile, women in Q5 had a 34% increased risk (95% CI 1.06-1.70, p = 0.014) and those in Q1 had a 41% reduced risk (95% CI 0.44-0.79, p < 0.0001). Similar patterns were observed separately for women aged 50-59 and 60-69 years. The model's overall discrimination was modest (area under the curve (AUC) 0.59, 95% CI 0.56-0.61). A reduced Gail model excluding information on ethnicity and hyperplasia was comparable to the full Gail model in terms of correctly stratifying women into risk groups. CONCLUSIONS: This study confirms that the Gail model (or a reduced model excluding information on hyperplasia and ethnicity) can effectively stratify a screened population aged 50-69 years according to the risk of future invasive breast cancer. This information has the potential to enable more personalised, risk-based screening strategies that aim to improve the balance of the benefits and harms of screening.

How will transitioning from cytology to HPV testing change the balance between the benefits and harms of cervical cancer screening? Estimates of the impact on cervical cancer, treatment rates and adverse obstetric outcomes in Australia, a high vaccination coverage country.

Primary HPV screening enables earlier diagnosis of cervical lesions compared to cytology, however, its effect on the risk of treatment and adverse obstetric outcomes has not been extensively investigated. We estimated the cumulative lifetime risk (CLR) of cervical cancer and excisional treatment, and change in adverse obstetric outcomes in HPV unvaccinated women and cohorts offered vaccination (>70% coverage in 12-13 years) for the Australian cervical screening program. Two-yearly cytology screening (ages 18-69 years) was compared to 5-yearly primary HPV screening with partial genotyping for HPV16/18 (ages 25-74 years). A dynamic model of HPV transmission, vaccination, cervical screening and treatment for precancerous lesions was coupled with an individual-based simulation of obstetric complications. For cytology screening, the CLR of cervical cancer diagnosis, death and treatment was estimated to be 0.649%, 0.198% and 13.4% without vaccination and 0.182%, 0.056% and 6.8%, in vaccinated women, respectively. For HPV screening, relative reductions of 33% and 22% in cancer risk for unvaccinated and vaccinated women are predicted, respectively, compared to cytology. Without the implementation of vaccination, a 4% increase in treatment risk for HPV versus cytology screening would have been expected, implying a possible increase in pre-term delivery (PTD) and low birth weight (LBW) events of 19 to 35 and 14 to 37, respectively, per 100,000 unvaccinated women. However, in vaccinated women, treatment risk will decrease by 13%, potentially leading to 4 to 41 fewer PTD events and from 2 more to 52 fewer LBW events per 100,000 vaccinated women. In unvaccinated women in cohorts offered vaccination as 12-13 year olds, no change to lifetime treatment risk is expected with HPV screening. In unvaccinated women in cohorts offered vaccination as 12-13 year olds, no change to lifetime treatment risk is expected with HPV screening. HPV screening starting at age 25 in populations with high vaccination coverage, is therefore expected to both improve the benefits (further decrease risk of cervical cancer) and reduce the harms (reduce treatments and possible obstetric complications) associated with cervical cancer screening.

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

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.

Human papillomavirus 16/18 seroprevalence in unvaccinated women over 30 years with normal cytology and with high grade cervical abnormalities in Australia: results from an observational study.

BACKGROUND: Australia commenced human papillomavirus (HPV) vaccination in 2007, with a two-year catch-up to the age of 26; catch-up cohorts are thus now entering their thirties. Plans for monitoring vaccine impact involve pre- and post-vaccination assessment of cervical HPV DNA in the general population and in high grade abnormalities. Although HPV serology is less sensitive than DNA genotyping, it assesses lifetime exposure and may be easier to measure in the general population. However, benchmark pre-vaccination seroprevalence of vaccine-included types in unvaccinated women with high grade abnormalities has not previously been reported. METHODS: We assessed seroprevalence for HPV16/18 from a population-based sample of 3,729 women with normal cytology and 971 women with confirmed high grade abnormalities (CIN2/3), aged 30-64 years, unvaccinated, and recruited in New South Wales in 2006-2010. We examined the variation in HPV16/18 seropositivity by age and in relation to a range of reproductive and behavioural characteristics in the subgroup of normal cytology women with no recent history of high grade cervical disease. RESULTS: The HPV 16, 18 and combined seroprevalence was 19%, 7% and 24% among women with normal cytology, and 39%, 13% and 44% among women with CIN2/3, respectively. For both groups, HPV16/18 seroprevalence was highest at age 30-39 years and decreased with age. In multivariable analysis for women with normal cytology, HPV16 and HPV18 seropositivity were each associated with the number of lifetime sexual partners (p-trend <0.001 and 0.052, respectively) and for HPV16 this was also associated with age (p-trend <0.001) and prior diagnosis of Chlamydia (adjusted OR 1.89, 95% CI 1.27-2.80). CONCLUSIONS: The findings of this study inform pre-vaccination estimates of HPV seropositivity in women with normal cytology and women with high grade abnormalities. Almost a quarter of unvaccinated women aged over 30 years with normal cytology, and more than 40% of those with CIN2/3, had seroconverted to HPV 16 or 18. These findings provide a potential additional benchmark for assessing the effects of HPV vaccination.

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.

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.

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.

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.

Lectin microarray profiling of metastatic breast cancers.

Altered protein glycosylation compared with the disease-free state is a universal feature of cancer cells. It has long been established that distinct glycan structures are associated with specific forms of cancer, but far less is known about the complete array of glycans associated with certain tumors. The cancer glycome has great potential as a source of biomarkers, but progress in this field has been hindered by a lack of available techniques for the elucidation of disease-associated glycosylation. In the present study, lectin microarrays consisting of 45 lectins with different binding preferences covering N- and O-linked glycans were coupled with evanescent-field activated fluorescent detection in the glycomic analysis of primary breast tumors and the serum and urine of patients with metastatic breast cancer. A single 50 µm section of a primary breast tumor or <1 µL of breast cancer patient serum or urine was sufficient to detect glycosylation alterations associated with metastatic breast cancer, as inferred from lectin-binding patterns. The high-throughput, sensitive and relatively simple nature of the simultaneous analysis of N- and O-linked glycosylation following minimal sample preparation and without the need for protein deglycosylation makes the lectin microarray analysis described a valuable tool for discovery phase glycomic profiling.

Significant changes in dietary intake and supplement use after breast cancer diagnosis in a UK multicentre study.

The diagnosis of cancer can motivate survivors to alter their lifestyle habits. Healthcare providers need to be aware of what changes patients are likely to make in order to derive more pertinent recommendations; however, few studies have reported pre- and post-diagnostic lifestyle behaviours. Semi-quantitative food frequency questionnaires (FFQs) completed approximately 1 year after diagnosis were used to evaluate dietary intake and supplement use before and after diagnosis in a cohort of 1,560 breast cancer patients participating in the UK, prospective DietCompLyf study. Intake of fruit and vegetables, wholegrains and lean sources of protein increased significantly post-diagnosis (P < 0.05, each). Conversely, after diagnosis consumption of high-fat, high-sugar products, red meat, coffee, some alcoholic drinks and refined grains significantly decreased (P < 0.05, each). Post-diagnostic changes in diet were accompanied by changes in the intake of macronutrients and a number of vitamins and minerals. Supplement use was highly prevalent (56.1%) pre-diagnosis, increasing to 62.8% after diagnosis (P = 0.001). Fish oils, multivitamin and minerals, and evening primrose oil were most often used and the proportion of users significantly increased (P < 0.05, each) after diagnosis. The percentage of women using oestrogenic botanical supplements (OBSs) was small but more than doubled to 8.4% after diagnosis (P < 0.05). British women participating in the DietCompLyf study reported significant changes in dietary intake and supplement use after their breast cancer diagnosis. These findings contribute to our understanding of female cancer survivors' dietary behaviours which is crucial for developing and implementing recommendations.

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.

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.

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.

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.