Measuring school level attributable risk to support school-based HPV vaccination programs.

BACKGROUND: In Australia in 2017, 89% of 15-year-old females and 86% of 15-year-old males had received at least one dose of the HPV vaccine. However, considerable variation in HPV vaccination initiation (dose one) across schools remains. It is important to understand the school-level characteristics most strongly associated with low initiation and their contribution to the overall between-school variation. METHODS: A population-based ecological analysis was conducted using school-level data for 2016 on all adolescent students eligible for HPV vaccination in three Australian jurisdictions. We conducted logistic regression to determine school-level factors associated with lower HPV vaccination initiation (< 75% dose 1 uptake) and estimated the population attributable risk (PAR) and the proportion of schools with the factor (school-level prevalence). RESULTS: The factors most strongly associated with lower initiation, and their prevalence were; small schools (OR = 9.3, 95%CI = 6.1-14.1; 33% of schools), special education schools (OR = 5.6,95%CI = 3.7-8.5; 8% of schools), higher Indigenous enrolments (OR = 2.7,95% CI:1.9-3.7; 31% of schools), lower attendance rates (OR = 2.6,95%CI = 1.7-3.7; 35% of schools), remote location (OR = 2.6,95%CI = 1.6-4.3; 6% of schools,) and lower socioeconomic area (OR = 1.8,95% CI = 1.3-2.5; 33% of schools). The highest PARs were small schools (PAR = 79%, 95%CI:76-82), higher Indigenous enrolments (PAR = 38%, 95%CI: 31-44) and lower attendance rate (PAR = 37%, 95%CI: 29-46). CONCLUSION: This analysis suggests that initiatives to support schools that are smaller, with a higher proportion of Indigenous adolescents and lower attendance rates may contribute most to reducing the variation of HPV vaccination uptake observed at a school-level in these jurisdictions. Estimating population-level coverage at the school-level is useful to guide policy and prioritise resourcing to support school-based vaccination programs.

Differences in school factors associated with adolescent HPV vaccination initiation and completion coverage in three Australian states.

BACKGROUND: Schools are the primary setting for the delivery of adolescent HPV vaccination in Australia. Although this strategy has achieved generally high vaccination coverage, gaps persist for reasons that are mostly unknown. This study sought to identify school-level correlates of low vaccination course initiation and completion in New South Wales, Tasmania, and Western Australia to inform initiatives to increase uptake. METHODS: Initiation was defined as the number of first doses given in a school in 2016 divided by vaccine-eligible student enrolments. Completion was the number of third doses given in a school in 2015-2016 divided by the number of first doses. Low initiation and completion were defined as coverage ≤ 25thpercentile of all reporting schools. We investigated correlations between covariates using Spearman's rank correlation coefficients. Due to multicollinearity, we used univariable logistic regression to investigate associations between school characteristics and low coverage. RESULTS: Median initiation was 84.7% (IQR: 75.0%-90.4%) across 1,286 schools and median completion was 93.8% (IQR: 86.0%-97.3%) across 1,295 schools. There were strong correlations between a number of school characteristics, particularly higher Indigenous student enrolments and lower attendance, increasing remoteness, higher postcode socioeconomic disadvantage, and smaller school size. Characteristics most strongly associated with low initiation in univariate analyses were small school size, location in Tasmania, and schools catering for special educational needs. Low completion was most strongly associated with schools in Tasmania and Western Australia, remote location, small size, high proportion of Indigenous student enrolments, and low attendance rates. CONCLUSION: This study provides indicative evidence that characteristics of schools and school populations are associated with the likelihood of low initiation and completion of the HPV vaccination course. The findings will guide further research and help target initiatives to improve vaccination uptake in schools with profiles associated with lower coverage.

A comparison of ThinPrep against four non-volatile transport media for HPV testing at or near the point of care.

The Xpert HPV Test is used at point of care for cervical screening in a number of low and middle income countries (LMIC). It is validated for use with ThinPrep-PreservCyt transport medium which has a high methanol content and is therefore classified as a dangerous good for shipping, making cost, transportation and use challenging within LMIC. We compared the performance of ThinPrep against four non-volatile commercially available media for human papillomavirus (HPV) point of care testing. Ten-fold serial dilutions were prepared using three HPV cell lines each positive for 16, 18 or 31 and with each suspended in five different media types. The media types consisted of Phosphate Buffered Saline (ThermoFisher Scientific, USA), Sigma Virocult (Medical Wire and Equipment, UK), MSwab (Copan, Italy) Xpert Transport Media (Cepheid, USA) and ThinPrep-PreservCyt (Hologic, USA). A total of 105 Xpert HPV tests were conducted in a laboratory setting, with seven 10-fold dilutions of each of the three HPV genotypes tested in all five media types. The lowest HPV 10-fold dilution detected for any media, or cell line was the fifth dilution. MSwab was the only medium to detect HPV to the fifth dilution across all three cell types. MSwab transport media may be a suitable alternative to ThinPrep for Xpert HPV point of care testing. A field based, head to head comparison of both media types using the Xpert HPV assay is warranted to confirm these laboratory based findings.

Evaluation of p16/Ki-67 dual-stain cytology performed on self-collected vaginal and clinician-collected cervical specimens for the detection of cervical pre-cancer.

OBJECTIVES: To compare the performance of dual immunostaining of p16INK4a and Ki-67 proteins performed on self-collected vaginal specimens and clinician-collected cervical specimens, and to evaluate the performance of this technique in predicting high-grade disease. METHODS: Women aged 30-59 years (n = 1005) were recruited at two well-women clinics in Papua New Guinea. Each woman provided both cervical and vaginal specimens that were tested for high-risk human papillomavirus (hrHPV) DNA using the Xpert HPV Test (Cepheid) at point of care. A subset of paired cervical and vaginal specimens (n = 243) were selected to undergo CINTec® PLUS (Roche) p16/Ki-67 dual-stain cytology and liquid-based cytology (LBC). RESULTS: Fifty-five pairs (22%) were excluded from further analysis because the smears were not assessable. Of the 189 remaining paired specimens, 74 pairs (39.1%) were positive for one or more hrHPV genotypes. When comparing results of the dual stain, the overall percent agreement, positive and negative percent agreements and κ value between the cervical and vaginal specimens were 87.8% (CI 82.3-92.1%), 64.6% (CI 49.5-77.8%), 95.7% (CI 91.0-98.0%) and 0.65 (CI 0.51-0.79%) respectively. The sensitivity of the dual stain performed on the cervical specimen to predict high-grade disease, determined by LBC, was superior to that of the dual stain performed on the vaginal specimen: 100% (CI 84.6-100%) versus 68.2% (CI 45.1-86.1%). CONCLUSION: Although further evaluation may be warranted, these findings indicate that dual-stain testing of vaginal specimens cannot be advocated as part of cervical screening programmes in low- and middle-income countries. However, dual-stain cytology performed on cervical specimens may have a role in quality assurance in such settings.

Evaluation of self-collected vaginal specimens for the detection of high-risk human papillomavirus infection and the prediction of high-grade cervical intraepithelial lesions in a high-burden, low-resource setting.

OBJECTIVES: To compare the performance of self-collected vaginal (V) specimens with clinician-collected cervical (C) specimens for detection of high-risk human papillomavirus (hrHPV) and cervical disease using the Cepheid Xpert HPV, Roche Cobas 4800 HPV and Hologic Aptima HPV assays. METHODS: Women aged 30-59 years (n = 1005) were recruited at two clinics in Papua New Guinea, and they provided specimens for testing at point-of-care using the Xpert HPV Test, and for subsequent testing using the Cobas HPV (n = 981) and Aptima HPV (n = 983) assays. Liquid-based cytology was performed on C specimens to predict underlying high-grade squamous intraepithelial lesions (HSIL). V specimen results of each assay were evaluated against a constructed reference standard and for detection of HSIL or worse. RESULTS: There was substantial (κ >0.6) agreement in hrHPV detection between V and C specimens across all three assays. The sensitivity, specificity, and positive and negative predictive values of Xpert HPV using self-collected V specimens for the detection of HPV type 16 according to the constructed reference standard were 92.1%, 93.1%, 63.6% and 98.9%, respectively; compared with 90.4%, 94.3%, 67.8% and 98.7% for Cobas 4800 HPV; and 63.2%, 97.2%, 75.0% and 95.3% for Aptima HPV. Similar results were observed for all hrHPV types (combined) and for HPV types 18/45, on all three assays. The detection of any hrHPV using self-collected specimens had high sensitivity (86%-92%), specificity (87%-94%) and negative predictive value (>98%) on all assays for HSIL positivity. CONCLUSIONS: Xpert HPV, using self-collected vaginal specimens, has sufficient accuracy for use in point-of-care 'test-and-treat' cervical screening strategies in high-burden, low-resource settings.

Innovative approaches to cervical cancer screening in low- and middle-income countries.

The estimated cervical cancer burden is over ten-fold greater in low- and middle-income countries (LMICs) than in high-income countries. This health gap is thought to be primarily due to limited access to effective screening and treatment programs for cervical pre-cancer and cancer in such settings. The World Health Organization advocates a policy of 'screen and treat' approach to cervical screening in LMICs and subsequently visual inspection of the cervix with acetic acid (VIA) or Lugo's iodine (VILI), followed by ablative cervical cryotherapy if indicated, and this policy has been implemented in many high-burden settings. The performance of VIA/VILI as a primary screening tool for the detection of cervical pre-cancer and cancer has, however, been inconsistent. Recently, many high-income countries have integrated HPV-DNA testing into their cervical cancer screening programs. The comparatively high cost and resource requirements of HPV-based screening have to date prevented many LMICs from doing the same. A significant development has been the entrance of innovative, easy-to-use and highly accurate HPV tests that can be provided at point of care; these could enable LMICs to implement 'test and treat' approaches for cervical cancer screening.

Ambiguous bodies, uncertain diseases: knowledge of cervical cancer in Papua New Guinea.

OBJECTIVES: Within their local realities, people experience and interpret disease in diverse ways that do not necessarily correlate or converge with Western biomedical interventions. In the high cervical cancer burden setting of Papua New Guinea, understanding how people experience and interpret cervical cancer is necessary for effective intervention. Drawing on work by Street on the production of unstable biomedical knowledge, we explored how ambiguity and uncertainty, coupled with cultural taboos and linguistic limitations, affect what and how people 'know' about women's reproductive organs and their associated disease. DESIGN: A qualitative research approach was used to explore and understand how people in PNG articulate matters of health and disease as they relate to cervical cancer and HPV infection. Specifically, how unstable biomedical knowledge is produced and sustained. We employed a mixed-methods approach in collecting data from 208 (147 women) participants between 2011 and 2012 across 3 provinces in PNG. RESULTS: We found that knowledge and awareness about cervical cancer were poor. Five thematic areas emerged in our analysis, which included the gendered knowledge of women's reproductive health, the burden of cervical cancer in the community and the role (or limitation) of language. We further identified four ways in which ambiguity and uncertainty operate on both sociocultural and biological levels, and in the intersection between to produce unstable biomedical knowledge. These included poor knowledge of where the cervix is located and the uncertainty or unreliability of (lay) diagnoses of disease. CONCLUSION: Local understandings of cervical cancer reflected the limitations of Tok Pisin as a lingua franca as well as the wider uncertain biomedical environment where diagnoses are assembled and shared. There is a clear need to improve understanding of the female reproductive organs in order that people, women in particular, can be better informed about cervical cancer and ultimately better receptive to intervention strategies.

A longitudinal cohort study of HIV 'treatment as prevention' in gay, bisexual and other men who have sex with men: the Treatment with Antiretrovirals and their Impact on Positive And Negative men (TAIPAN) study protocol.

BACKGROUND: Australia has increased coverage of antiretroviral treatment (ART) over the past decade, reaching 73% uptake in 2014. While ART reduces AIDS-related deaths, accumulating evidence suggests that it could also bolster prevention efforts by reducing the risk of HIV transmission ('treatment as prevention'). While promising, evidence of community-level impact of treatment as prevention on reducing HIV incidence among gay and bisexual men is limited. We describe a study protocol that aims to determine if scale up of testing and treatment for HIV leads to a reduction in community viraemia and, in turn, if this reduction is temporally associated with a reduction in HIV incidence among gay and bisexual men in Australia's two most populous states. METHODS: Over the period 2009 to 2017, we will establish two cohorts making use of clinical and laboratory data electronically extracted retrospectively and prospectively from 73 health services and laboratories in the states of New South Wales and Victoria. The 'positive cohort' will consist of approximately 13,000 gay and bisexual men (>90% of all people living with HIV). The 'negative cohort' will consist of at least 40,000 HIV-negative gay and bisexual men (approximately half of the total population). Within the negative cohort we will use standard repeat-testing methods to calculate annual HIV incidence. Community prevalence of viraemia will be defined as the proportion of men with a viral load ≥200RNA copies/mm3, which will combine viral load data from the positive cohort and viraemia estimates among those with an undiagnosed HIV infection. Using regression analyses and adjusting for behavioural and demographic factors associated with infection, we will assess the temporal association between the community prevalence of viraemia and the incidence of HIV infection. Further analyses will make use of these cohorts to assess incidence and predictors of treatment initiation, repeat HIV testing, and viral suppression. DISCUSSION: This study will provide important information on whether 'treatment as prevention' is associated with a reduction in HIV incidence at a community level among gay and bisexual men.

Field Evaluation of Xpert HPV Point-of-Care Test for Detection of Human Papillomavirus Infection by Use of Self-Collected Vaginal and Clinician-Collected Cervical Specimens.

The World Health Organization has recommended that testing for high-risk human papillomavirus (HPV) (hrHPV) infection be incorporated into cervical screening programs in all settings worldwide. In many high-burden, low-income countries, it will not be feasible to achieve high cervical screening coverage using hrHPV assays that require clinician-collected samples. We conducted the first evaluation of self-collected vaginal specimens compared with clinician-collected cervical specimens for the detection of hrHPV infection using the Xpert HPV test. Women aged 30 to 54 years attending two well-woman clinics in Papua New Guinea were invited to participate and provided self-collected vaginal and clinician-collected cervical cytobrush specimens. Both specimen types were tested at the point of care by using the Xpert HPV test. Women were given their cervical test result the same day. Those with a positive hrHPV test and positive examination upon visual inspection of the cervix with acetic acid were offered same-day cervical cryotherapy. A total of 1,005 women were enrolled, with 124 (12.3%; 95% confidence interval [CI], 10.3%, 14.4%) being positive for any hrHPV infection. There was a 99.4% overall percent agreement (OPA) between vaginal and cervical tests for HPV-16 (95% CI, 98.9%, 99.9%), a 98.5% OPA for HPV-18/45 (95% CI, 97.7%, 99.3%), a 94.4% OPA for other hrHPV infections (95% CI, 92.9%, 95.9%), and a 93.4% OPA for all hrHPV types combined (95% CI, 91.8%, 95.0%). Self-collected vaginal specimens had excellent agreement with clinician-collected cervical specimens for the detection of hrHPV infection using the Xpert HPV test. This approach provides for the first time an opportunity to incorporate point-of-care hrHPV testing into clinical cervical screening algorithms in high-burden, low-income settings.

The acceptability and cost of a home-based chlamydia retesting strategy: findings from the REACT randomised controlled trial.

BACKGROUND: Chlamydia retesting three months after treatment is recommended to detect reinfections, but retesting rates are typically low. The REACT (retest after Chlamydia trachomatis) randomised trial demonstrated that home-based retesting using postal home-collection kits and SMS reminders, resulted in substantial improvements in retesting rates in women, heterosexual men and men who have sex with men (MSM), with detection of more repeat positive tests compared with SMS reminder alone. In the context of this trial, the acceptability of the home-based strategy was evaluated and the costs of the two strategies were compared. METHODS: REACT participants (200 women, 200 heterosexual men, 200 MSM) were asked to complete an online survey that included home-testing acceptability and preferred methods of retesting. The demographics, sexual behaviour and acceptability of home collection were compared between those preferring home-testing versus clinic-based retesting or no preference, using a chi-square test. The costs to the health system of the clinic-based and home retesting strategies and the cost per infection for each were also compared. RESULTS: Overall 445/600 (74 %) participants completed the survey; 236/445 from the home-testing arm, and 141 of these (60 %) retested at home. The majority of home arm retesters were comfortable having the kit posted to their home (86 %); found it easy to follow the instructions and collect the specimens (96 %); were confident they had collected the specimens correctly (90 %); and reported no problems (70 %). Most (65 %) preferred home retesting, 21 % had no preference and 14 % preferred clinic retesting. Comparing those with a preference for home testing to those who didn't, there were significant differences in being comfortable having a kit sent to their home (p = 0.045); not having been diagnosed with chlamydia previously (p = 0.030); and living with friends (p = 0.034). The overall cost for the home retest pathway was $154 (AUD), compared to $169 for the clinic-based retesting pathway and the cost per repeat infection detected was $1409 vs $3133. CONCLUSIONS: Among individuals initially diagnosed with chlamydia in a sexual health clinic setting, home-based retesting was shown to be highly acceptable, preferred by most participants, and cost-efficient. However some clients preferred clinic-based testing, often due to confidentiality concerns in their home environment. Both options should be provided to maximise retesting rates. TRIAL REGISTRATION: The trial was registered with the Australia New Zealand Clinical Trials Registry on September 9, 2011: ACTRN12611000968976.

Public health implications of molecular point-of-care testing for chlamydia and gonorrhoea in remote primary care services in Australia: a qualitative study.

OBJECTIVES: With accurate molecular tests now available for diagnosis of chlamydia and gonorrhoea (Chlamydia trachomatis (CT)/Neisseria gonorrhoeae (NG)) at the point-of-care (POC), we aimed to explore the public health implications (benefits and barriers) of their integration into remote primary care in Australia. METHODS: Qualitative interviews were conducted with a purposively selected group of 18 key informants reflecting sexual health, primary care, remote Aboriginal health and laboratory expertise. RESULTS: Participants believed that POC testing may decrease community prevalence of sexually transmitted infections (STIs), and associated morbidity by reducing the time to treatment and infectious period and expediting partner notification. Also, POC testing could improve acceptability of STI testing, increase testing coverage and result in more targeted prescribing, thereby minimising the risk of antibiotic resistance. Conversely, some felt the immediacy of diagnosis could deter certain young people from being tested. Participants also noted that POC testing may reduce the completeness of communicable disease surveillance data given the current dependence on reporting from pathology laboratories. Others expressed concern about the need to maintain and improve the flow of NG antibiotic sensitivity data, already compromised by the shift to nucleic acid-based testing. This is particularly relevant to remote areas where culture viability is problematic. CONCLUSIONS: Results indicate a high level of support from clinicians and public health practitioners for wider access to CT/NG POC tests citing potential benefits, including earlier, more accurate treatment decisions and reductions in ongoing transmission. However, the data also highlight the need for new systems to avoid adverse impact on disease surveillance. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry: ACTRN12613000808741.

Risk factors for herpes zoster in a large cohort of unvaccinated older adults: a prospective cohort study.

We analysed data from a prospective cohort of 255,024 adults aged ⩾45 years recruited from 2006-2009 to identify characteristics associated with a zoster diagnosis. Diagnoses were identified by linkage to pharmaceutical treatment and hospitalization records specific for zoster and hazard ratios were estimated. Over 940,583 person-years, 7771 participants had a zoster diagnosis; 253 (3·3%) were hospitalized. After adjusting for age and other factors, characteristics associated with zoster diagnoses included: having a recent immunosuppressive condition [adjusted hazard ratio (aHR) 1·58, 95% confidence interval (CI) 1·32-1·88], female sex (aHR 1·36, 95% CI 1·30-1·43), recent cancer diagnosis (aHR 1·35, 95% CI 1·24-1·46), and severe physical limitation vs. none (aHR 1·33, 95% CI 1·23-1·43). The relative risk of hospitalization for zoster was higher for those with an immunosuppressive condition (aHR 3·78, 95% CI 2·18-6·55), those with cancer (aHR 1·78, 95% CI 1·24-2·56) or with severe physical limitations (aHR 2·50, 95% CI 1·56-4·01). The novel finding of an increased risk of zoster diagnoses and hospitalizations in those with physical limitations should prompt evaluation of the use of zoster vaccine in this population.

Patterns and characteristics of hepatitis C transmission clusters among HIV-positive and HIV-negative individuals in the Australian trial in acute hepatitis C.

BACKGROUND: Injecting drug users remain the population at greatest risk of acquiring hepatitis C virus (HCV) infection, although a recent increase in cases of sexually transmitted HCV infection has been observed among human immunodeficiency virus (HIV)-infected individuals. The extent to which these separate epidemics overlap is unknown. METHODS: The Australian Trial in Acute Hepatitis C (ATAHC) enrolled 163 individuals (29% of whom were HIV infected) with recent HCV infection. E1/HVR1 sequences were used to construct phylogenetic trees demonstrating monophyletic clusters or pairs, and viral epidemic history and phylogeography were assessed using molecular clock analysis. Individual clusters were characterized by clinical and demographic characteristics. RESULTS: Transmission through injection drug use occurred for 73% of subjects, with sexual transmission occurring for 18% (92% of whom were HIV infected). Among 112 individuals with available E1/HVR1 sequences, 23 (20%) were infected with a strain of HCV identical to that of another subject, comprising 4 homologous clusters and 3 monophyletic pairs, the majority of which (78%) were HIV infected. Clusters contained individuals with both injection drug use-related and sex-related acquisition, and in all clusters (except for 1 female HIV-uninfected pair), individuals identified as men who have sex with men, irrespective of HIV status. CONCLUSIONS: This large unique study of HIV-infected and HIV-uninfected individuals with recently acquired HCV infection demonstrates that clustering is common in the HIV-infected population and that it occurred almost invariably among men who have sex with men, irrespective of the actual mode of acquisition. These findings suggest the coexistence of both injection drug use and sexual risk behaviors for individuals in the same social networks and have implications for the development of public health messages. Clinical trial registration. NCT00192569.

Estimating the risk of blood donation associated with HIV risk behaviours.

A blood donor questionnaire and declaration, with deferral of potential donors at a higher risk of blood-borne infections, was introduced in Australia in the mid-1980s to reduce the risk of donation of HIV-infected blood. However, the absolute risk of HIV transmission through blood donation from high-HIV-risk donors has not been estimated. This study presents a new method of assessing the risk posed to the blood supply by selected HIV risk behaviours. A model was developed to estimate the probability of blood donation during the window period for HIV infection. Five scenarios for blood donors were considered: (1) men who have sex with men (MSM), (2) men who have sex with women in Australia, (3) women who have sex with partners from countries with a high HIV prevalence, (4) men who have sex with commercial sex workers in Australia and (5) people injecting drugs used once in a year. Those estimated to be at highest risk of becoming infected and donating in the window period were MSM. Women who have sex with men from countries of high HIV prevalence are at greater risk than men who have sex with female sex workers from Australia. These three groups under current Australian guidelines are deferred from donating blood for 12 months. In Australia, a single episode of injecting drug use is associated with very low risk of HIV transmission. The model presented in this study can be used to assess the impact of selected individual risk behaviours on the safety of the blood supply.

Prior antiretroviral therapy experience protects against zidovudine-related anaemia.

OBJECTIVE: We investigated the use of antiretroviral therapy regimens containing zidovudine or stavudine, using data from the TREAT Asia HIV Observational Database (TAHOD), a multicentre, prospective, observational study of an HIV-infected cohort in the Asia-Pacific Region. METHODS: A proportional hazards regression analysis of factors associated with the time to discontinuation of initial regimens containing zidovudine or stavudine and a logistic regression analysis to identify factors associated with a diagnosis of anaemia within 6 months of commencement of zidovudine in initial or subsequent regimens were performed. RESULTS: Patients who started zidovudine were more likely to stop within the first 9 months of treatment than those who started on stavudine; the reverse was true after 9 months. Anaemia (haemoglobin

The 15-Country Collaborative Study of Cancer Risk among Radiation Workers in the Nuclear Industry: estimates of radiation-related cancer risks.

A 15-Country collaborative cohort study was conducted to provide direct estimates of cancer risk following protracted low doses of ionizing radiation. Analyses included 407,391 nuclear industry workers monitored individually for external radiation and 5.2 million person-years of follow-up. A significant association was seen between radiation dose and all-cause mortality [excess relative risk (ERR) 0.42 per Sv, 90% CI 0.07, 0.79; 18,993 deaths]. This was mainly attributable to a dose-related increase in all cancer mortality (ERR/Sv 0.97, 90% CI 0.28, 1.77; 5233 deaths). Among 31 specific types of malignancies studied, a significant association was found for lung cancer (ERR/Sv 1.86, 90% CI 0.49, 3.63; 1457 deaths) and a borderline significant (P = 0.06) association for multiple myeloma (ERR/Sv 6.15, 90% CI <0, 20.6; 83 deaths) and ill-defined and secondary cancers (ERR/Sv 1.96, 90% CI -0.26, 5.90; 328 deaths). Stratification on duration of employment had a large effect on the ERR/Sv, reflecting a strong healthy worker survivor effect in these cohorts. This is the largest analytical epidemiological study of the effects of low-dose protracted exposures to ionizing radiation to date. Further studies will be important to better assess the role of tobacco and other occupational exposures in our risk estimates.

The 15-Country Collaborative Study of Cancer Risk Among Radiation Workers in the Nuclear Industry: design, epidemiological methods and descriptive results.

Radiation protection standards are based mainly on risk estimates from studies of atomic bomb survivors in Japan. The validity of extrapolations from the relatively high-dose acute exposures in this population to the low-dose, protracted or fractionated environmental and occupational exposures of primary public health concern has long been the subject of controversy. A collaborative retrospective cohort study was conducted to provide direct estimates of cancer risk after low-dose protracted exposures. The study included nearly 600,000 workers employed in 154 facilities in 15 countries. This paper describes the design, methods and results of descriptive analyses of the study. The main analyses included 407,391 nuclear industry workers employed for at least 1 year in a participating facility who were monitored individually for external radiation exposure and whose doses resulted predominantly from exposure to higher-energy photon radiation. The total duration of follow-up was 5,192,710 person-years. There were 24,158 deaths from all causes, including 6,734 deaths from cancer. The total collective dose was 7,892 Sv. The overall average cumulative recorded dose was 19.4 mSv. A strong healthy worker effect was observed in most countries. This study provides the largest body of direct evidence to date on the effects of low-dose protracted exposures to external photon radiation.

Occupational exposure to power frequency magnetic fields and risk of non-Hodgkin lymphoma.

OBJECTIVES: To investigate the risk of non-Hodgkin lymphoma (NHL) using a job-exposure matrix (JEM) to assess exposure to occupational magnetic fields at the power frequencies of 50/60 Hz. METHODS: The study population consisted of 694 cases of NHL, first diagnosed between 1 January 2000 and 31 August 2001, and 694 controls from two regions in Australia, matched by age, sex and region of residence. A detailed occupational history was given by each subject. Exposure to power frequency magnetic fields was estimated using a population-based JEM which was specifically developed in the United States to assess occupational magnetic field exposure. The cumulative exposure distribution was divided into quartiles and adjusted odds ratios were calculated using the lowest quartile as the referent group. RESULTS: For the total work history, the odds ratio (OR) for workers in the upper quartile of exposure was 1.48 (95% CI 1.02 to 2.16) compared to the referent (p value for trend was 0.006). When the exposure was lagged by 5 years the OR was 1.59 (95% CI 1.07 to 2.36) (p value for trend was 0.003). Adjusting for other occupational exposures did not significantly alter the results. CONCLUSIONS: These findings provide weak support for the hypothesis that occupational exposure to 50/60 Hz magnetic fields increases the risk of NHL.

Occupational exposure to pesticides and risk of non-Hodgkin's lymphoma.

Pesticide exposure may be a risk factor for non-Hodgkin's lymphoma, but it is not certain which types of pesticides are involved. A population-based case-control study was undertaken in 2000-2001 using detailed methods of assessing occupational pesticide exposure. Cases with incident non-Hodgkin's lymphoma in two Australian states (n = 694) and controls (n = 694) were chosen from Australian electoral rolls. Logistic regression was used to estimate the risks of non-Hodgkin's lymphoma associated with exposure to subgroups of pesticides after adjustment for age, sex, ethnic origin, and residence. Approximately 10% of cases and controls had incurred pesticide exposure. Substantial exposure to any pesticide was associated with a trebling of the risk of non-Hodgkin's lymphoma (odds ratio = 3.09, 95% confidence interval: 1.42, 6.70). Subjects with substantial exposure to organochlorines, organophosphates, and "other pesticides" (all other pesticides excluding herbicides) and herbicides other than phenoxy herbicides had similarly increased risks, although the increase was statistically significant only for "other pesticides." None of the exposure metrics (probability, level, frequency, duration, or years of exposure) were associated with non-Hodgkin's lymphoma. Analyses of the major World Health Organization subtypes of non-Hodgkin's lymphoma suggested a stronger effect for follicular lymphoma. These increases in risk of non-Hodgkin's lymphoma with substantial occupational pesticide exposure are consistent with previous work.

Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries.

OBJECTIVES: To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. DESIGN: Multinational retrospective cohort study of cancer mortality. SETTING: Cohorts of workers in the nuclear industry in 15 countries. PARTICIPANTS: 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. MAIN OUTCOME MEASUREMENTS: Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. RESULTS: The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv (< 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. CONCLUSIONS: These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.