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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. What's new? While several potentially‐modifiable behavioural risk factors have been identified for breast cancer, estimates of the preventable future breast cancer burden are still lacking. Based on a large prospective pooled Australian cohort, here the authors reveal that regular alcohol consumption is the leading modifiable cause of breast cancer burden for premenopausal women (12.6%). Using the latest exposure prevalence information, the authors rank body fatness as the leading cause of preventable breast cancer burden for postmenopausal women (12.8%), with regular alcohol consumption also contributing substantially (6.6%). The findings provide evidence to support targeted and population‐level cancer control activities in Australia and beyond. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

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%C 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. [ABSTRACT FROM AUTHOR]

Background Estimates of the future burden of invasive cancer attributable to current modifiable causal exposures can guide cancer prevention. Methods We linked pooled data from seven Australian cohort studies (N = 367,058) to national cancer and death registries, and estimated exposure-cancer and exposure-death associations using adjusted proportional hazards models. We estimated exposure prevalence from contemporary national health surveys and calculated population attributable fractions (PAFs) and 95% confidence intervals, using advanced methods accounting for competing risk of death. Results Current levels of past and current smoking explain 36.1% (95%CI 33.2%-38.9%), body fatness 13.6% (10.9%-16.2%) and alcohol consumption exceeding two drinks/day 2.3% (1.0%-3.6%) of cancers causally related to these exposures, corresponding to 210,000, 81,300 and 14,800 cancers in Australia in the next 10 years, respectively. Ever smoking is the leading modifiable cause of lung (82.1%), bladder (49.8%), oesophageal (42.8%), liver (39.8%), head and neck (35.6%), and pancreatic (21.3%) cancer burden. Body fatness is the leading modifiable cause of corpus uteri (42.5%), gastric cardia (33.6%), renal cell (29.1%), thyroid (20.1%), colorectal (12.6%) and postmenopausal breast (12.6%) cancer burden. The absolute numbers of cancers in the next 10 years attributable to smoking are highest for lung cancer (114,000). The numbers of cancers attributable to body fatness and alcohol are highest for colorectal cancer (23,000 and 9,900, respectively). Conclusions More reliable advanced methods demonstrate large proportions and numbers of cancers are preventable by modifying behaviours. Key messages Ever smoking and body fatness are the leading causes of preventable future burden of causally related cancers in Australia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • Contemporary estimates of endometrial cancer burden attributable to body fatness. • Overweight and obesity explain 42%, and obesity alone explains 35% of endometrial cancers. • First estimates of future endometrial cancer burden for population subgroups. • Overweight and obesity explain 49–87% of the endometrial cancer burden for some subgroups of women. [ABSTRACT FROM AUTHOR]

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., (© 2022 The Authors.)

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., Competing Interests: CN receives salary funding via the project 'Optimising Early Detection of Breast Cancer in Australia', funded by the Australian Department of Health and led by Cancer Council Australia. She jointly leads the development of the AutoDensity automated breast density measurement tool, through a collaboration between the University of Melbourne and the CSIRO. PB is the Chief Executive Officer of the start-up DetectEd-X, which provides radiology training and research.

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., (Copyright © 2018. Published by Elsevier Inc.)

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 (χ 2  = 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.

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)