• Cancer morbidity in British military veterans included in chemical warfare agent experiments at Porton Down: cohort study

    3 July 2018

    To determine cancer morbidity in members of the armed forces who took part in tests of chemical warfare agents from 1941 to 1989.

  • Mortality in British military participants in human experimental research into chemical warfare agents at Porton Down: cohort study.

    3 July 2018

    To investigate any long term effects on mortality in participants in experimental research related to chemical warfare agents from 1941 to 1989.

  • Normal endometrial cells in cervical cytology: systematic review of prevalence and relation to significant endometrial pathology.

    3 July 2018

    OBJECTIVES: To estimate the prevalence of normal endometrial cells (NECs) and the proportion of NECs associated with significant endometrial pathology in conventional and liquid-based cytology (LBC) cervical smears; and to assess the association between NECs and clinical symptoms in women with endometrial hyperplasia or carcinoma. METHODS: Systematic review of the literature and meta-analysis of prevalence and proportion data. The review was confined to studies reporting on NECs in smears from postmenopausal women or women aged 40+. RESULTS: A total of 22 relevant primary studies were identified from 1970 to 2007. The overall summary estimate for the prevalence of NECs in smears from postmenopausal women or women aged 40+ in all screening smears was 0.4% (95% CI 0.2-0.7%); this was 0.3% (95% CI 0.1-0.5%) and 0.9% (95% CI 0.5-1.4%) for conventional and LBC smears, respectively; P = 0.003 for difference. The overall estimate for the proportion of NECs associated with significant endometrial pathology was 7% (95% CI 4-10%); this was 11% (95% CI 8-14%) and 2% (95% CI 1-2%) for conventional and LBC smears, respectively; P < 0.001 for difference. In women with significant endometrial pathology, the presence of NECs in followed-up women was associated with abnormal uterine bleeding in 79% (95% CI 68-87%) of cases. CONCLUSION: Compared with conventional cytology, LBC may be associated with a higher prevalence of NECs but these are less likely to be associated with endometrial pathology. This finding might be explained by more consistent use of sampling instruments for LBC with better access to the endocervical canal or alternatively by changes over time, broadly coincident with the introduction of LBC, in the population in which NECs are reported. In followed-up women with NECs, most endometrial pathology is accompanied by symptoms, implying that a relatively smaller number of additional cases are identified through follow-up of asymptomatic women.

  • Diabetes and modifiable risk factors for cardiovascular disease: the prospective Million Women Study.

    3 July 2018

    To compare the effect of potentially modifiable lifestyle factors on the incidence of vascular disease in women with and without diabetes. In 1996-2001 over one million middle-aged women in the UK joined a prospective study, providing medical history, lifestyle and socio-demographic information. All participants were followed for hospital admissions and deaths using electronic record-linkage. Adjusted relative risks (RRs) and incidence rates were calculated to compare the incidence of coronary heart disease and stroke in women with and without diabetes and by lifestyle factors. At recruitment 25,915 women (2.1% of 1,242,338) reported current treatment for diabetes. During a mean follow-up of 6.1 years per woman, 21,928 had a first hospital admission or death from coronary heart disease (RR for women with versus without diabetes = 3.30, 95% CI 3.14-3.47) and 7,087 had a first stroke (RR = 2.47, 95% CI 2.24-2.74). Adjusted incidence rates of these conditions in women with diabetes increased with duration of diabetes, obesity, inactivity and smoking. The 5-year adjusted incidence rates for cardiovascular disease were 4.6 (95% CI 4.4-4.9) per 100 women aged 50-69 in non-smokers with diabetes, 5.9 (95% CI 4.6-7.6) in smokers with diabetes not using insulin and 11.0 (95% CI 8.3-14.7) in smokers with diabetes using insulin. Non-smoking women with diabetes who were not overweight or inactive still had threefold increased rate for coronary disease or stroke compared with women without diabetes. Of the modifiable factors examined in middle aged women with diabetes, smoking causes the greatest increase in cardiovascular disease, especially in those with insulin treated diabetes.

  • Screening for breast cancer in England: past and future.

    3 July 2018

    The NHS Breast Screening Programme (NHSBSP) began in 1988. It aims to invite all women aged 50-70 years for mammographic screening once every three years. The programme now screens 1.3 million women each year, about 75% of those invited, and diagnoses about 10,000 breast cancers annually. Although some have questioned the value of screening for breast cancer, the scientific evidence demonstrates clearly that regular mammographic screening between the ages of 50 and 70 years reduces mortality from the malignancy. Screened women are slightly more likely than unscreened women to be diagnosed with breast cancer. The cancers in screened women are smaller and are less likely to be treated with mastectomy than they would have been if diagnosed without screening. For every 400 women screened regularly by the NHSBSP over a 10-year period, one woman fewer will die from breast cancer than would have died without screening. The current NHSBSP saves an estimated 1400 lives each year in England. The screening programme spends about pound sterling 3000 for every year of life saved.

  • The agreement between self-reported cervical smear abnormalities and screening programme records.

    3 July 2018

    SETTING: The Million Women Study is a cohort study of women aged 50-64 years in England and Scotland. As a component of the follow-up questionnaire, participants were asked to indicate if they had an abnormal cervical smear in the previous five years. This study compared self-reported cervical abnormalities with screening records obtained from the National Health Service Cervical Screening Programme. METHODS: For 1944 randomly selected Million Women Study participants in Oxfordshire, screening records were assessed over a six-year period prior to the date of self-reporting. The six-year period was chosen to allow for errors in the recall of timing of abnormal smears. RESULTS: A total of 68 women (3.5%) had a record of at least one equivocal or abnormal smear within the last six years, whereas 49 women (2.5%) self-reported an abnormality. There was a strong trend for an increased probability of self-reporting a history of an abnormal smear as the severity of the recorded abnormality increased (P <0.001). For women with an NHS record of borderline dyskaryosis, mild dyskaryosis, or moderate dyskaryosis/severe dyskaryosis/invasive cancer, the proportions reporting an abnormality were 40%, 58% and 77%, respectively. For women with negative and inadequate smears, the proportion self-reporting an abnormality were 0.6% and 0.7%, respectively. CONCLUSIONS: These results indicate that among women whose screening programme records show an abnormal smear, the proportion self-reporting an abnormality increases with the severity of the recorded lesion. Almost all women with a record of negative or inadequate smear(s) correctly interpret the result and do not self-report an abnormality.

  • Hormone replacement therapy and false positive recall in the Million Women Study: patterns of use, hormonal constituents and consistency of effect.

    3 July 2018

    INTRODUCTION: Current and recent users of hormone replacement therapy (HRT) have an increased risk of being recalled to assessment at mammography without breast cancer being diagnosed ('false positive recall'), but there is limited information on the effects of different patterns of HRT use on this. The aim of this study is to investigate in detail the relationship between patterns of use of HRT and false positive recall. METHODS: A total of 87,967 postmenopausal women aged 50 to 64 years attending routine breast cancer screening at 10 UK National Health Service Breast Screening Units from 1996 to 1998 joined the Million Women Study by completing a questionnaire before screening and were followed for their screening outcome. RESULTS: Overall, 399 (0.5%) participants were diagnosed with breast cancer and 2,629 (3.0%) had false positive recall. Compared to never users of HRT, the adjusted relative risk (95% CI) of false positive recall was: 1.62 (1.43-1.83), 1.80 (1.62-2.01) and 0.76 (0.52-1.10) in current users of oestrogen-only HRT, oestrogen-progestagen HRT and tibolone, respectively (p (heterogeneity) < 0.0001); 1.65 (1.43-1.91), 1.49 (1.22-1.81) and 2.11 (1.45-3.07) for current HRT used orally, transdermally or via an implant, respectively (p (heterogeneity) = 0.2); and 1.84 (1.67-2.04) and 1.75 (1.49-2.06) for sequential and continuous oestrogen-progestagen HRT, respectively (p (heterogeneity) = 0.6). The relative risk of false positive recall among current users appeared to increase with increasing time since menopause, but did not vary significantly according to any other factors examined, including duration of use, hormonal constituents, dose, whether single- or two-view screening was used, or the woman's personal characteristics. CONCLUSION: Current use of oestrogen-only and oestrogen-progestagen HRT, but not tibolone, increases the risk of false positive recall at screening.