| 1. |
- Cuzick, Jack, et al.
(author)
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Prevention and early detection of prostate cancer.
- 2014
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In: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 15:11, s. e484-92
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Journal article (peer-reviewed)abstract
- Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-specific antigen (PSA) screening is controversial, but changes in the PSA threshold, frequency of screening, and the use of other biomarkers have the potential to minimise the overdiagnosis associated with PSA screening. Several new biomarkers for individuals with raised PSA concentrations or those diagnosed with prostate cancer are likely to identify individuals who can be spared aggressive treatment. Several pharmacological agents such as 5α-reductase inhibitors and aspirin could prevent development of prostate cancer. In this Review, we discuss the present evidence and research questions regarding prevention, early detection of prostate cancer, and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer.
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| 2. |
- Scott, David R, et al.
(author)
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Use of human papillomavirus DNA testing to compare equivocal cervical cytologic interpretations in the United States, Scandinavia, and the United Kingdom
- 2002
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In: Cancer. - : John Wiley and Sons Inc.. - 1097-0142 .- 0008-543X. ; 96:1, s. 14-20
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Journal article (peer-reviewed)abstract
- BACKGROUND: Human papillomavirus (HPV) DNA testing may be useful in clarifying equivocal cervical cytologic interpretations. One application might be to standardize the meaning of equivocal interpretations from laboratories in various regions. Because international differences may be particularly marked, international comparisons of emerging data will require clear translations of "equivocal" and similar terms. METHODS: To perform a three-country comparison, the authors selected a morphologically diverse set of 188 conventional Papanicolaou tests initially classified as "squamous atypia" from a study of more than 20,000 women in Portland, Oregon (1989-1990). Previously, five U.S. expert cytopathologists independently interpreted the slides with screening cytotechnologists' marks in place. For this comparison, one British and two Scandinavian reviewers involved in HPV research reviewed the slides after original marks had been removed. The authors compared all eight reviewers' classifications of negative, equivocal, or abnormal in a series of pairwise comparisons using the kappa statistic. They then compared cytologic interpretations with HPV DNA testing. RESULTS: Oncogenic HPV DNA detection was significantly associated with increasingly abnormal interpretations for each reader. The British reader tended to rate tests as more abnormal than the American pathologists did, whereas the Scandinavians tended to rate tests as more normal. Reference to the HPV DNA standard clarified the tendency of readers to render systematically more or less severe interpretations. For example, the Scandinavian cytologists discounted subtle (often HPV-associated) changes in favor of cytologic certainty, making HPV triage of equivocal tests less applicable there. CONCLUSIONS: International research on cytopathology, particularly on the possible uses of HPV DNA testing, will require calibration of local cytologic definitions.
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| 3. |
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| 4. |
- Abe, O, et al.
(author)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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In: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Journal article (peer-reviewed)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Buus, Richard, et al.
(author)
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Novel 18-gene signature for predicting relapse in ER-positive, HER2-negative breast cancer
- 2018
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 20:1
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Journal article (peer-reviewed)abstract
- Background: Several prognostic signatures for early oestrogen receptor-positive (ER+) breast cancer have been established with a 10-year follow-up. We tested the hypothesis that signatures optimised for 0-5-year and 5-10-year follow-up separately are more prognostic than a single signature optimised for 10 years. Methods: Genes previously identified as prognostic or associated with endocrine resistance were tested in publicly available microarray data set using Cox regression of 747 ER+/HER2- samples from post-menopausal patients treated with 5 years of endocrine therapy. RNA expression of the selected genes was assayed in primary ER+/HER2- tumours from 948 post-menopausal patients treated with 5 years of anastrozole or tamoxifen in the TransATAC cohort. Prognostic signatures for 0-10, 0-5 and 5-10 years were derived using a penalised Cox regression (elastic net). Signature comparison was performed with likelihood ratio statistics. Validation was done by a case-control (POLAR) study in 422 samples derived from a cohort of 1449. Results: Ninety-three genes were selected by the modelling of microarray data; 63 of these were significantly prognostic in TransATAC, most similarly across each time period. Contrary to our hypothesis, the derived early and late signatures were not significantly more prognostic than the 18-gene 10-year signature. The 18-gene 10-year signature was internally validated in the TransATAC validation set, showing prognostic information similar to that of Oncotype DX Recurrence Score, PAM50 risk of recurrence score, Breast Cancer Index and IHC4 (score based on four IHC markers), as well as in the external POLAR case-control set. Conclusions: The derived 10-year signature predicts risk of metastasis in patients with ER+/HER2- breast cancer similar to commercial signatures. The hypothesis that early and late prognostic signatures are significantly more informative than a single signature was rejected.
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| 9. |
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| 10. |
- Cuzick, Jack, et al.
(author)
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Overview of Human Papillomavirus-Based and Other Novel Options for Cervical Cancer Screening in Developed and Developing Countries
- 2008
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In: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 26, s. 29-41
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Journal article (peer-reviewed)abstract
- Screening for cervical cancer precursors by cytology has been very successful in countries where adequate resources exist to ensure high quality and good coverage of the population at risk. Mortality reductions in excess of 50% have been achieved in many developed countries; however the procedure is generally inefficient and unworkable in many parts of the world where the appropriate infrastructure is not achievable. A summary and update of recently published meta-analyses and systematic reviews on four possible clinical applications of human papillomavirus (HPV) DNA testing is provided in this article: (1) triage of women with equivocal or low-grade cytological abnormalities; (2) follow-up of women with abnormal screening results who are negative at colposcopy/biopsy; (3) prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN), and most importantly (4) primary screening HPV DNA test, solely or in combination with Pap smear to detect cervical cancer precursors. There are clear benefits for the use of HPV DNA testing in the triage of equivocal smears, low-grade smears in older women and in the post-treatment surveillance of women after treatment for CIN. However, there are still issues regarding how best to use HPV DNA testing in primary screening. Primary screening with Hybrid Capture (R) 2 (HC2) generally detects more than 90% of all CIN2, CIN3 or cancer cases, and is 25% (95% CI): 15-36%) relatively more sensitive than cytology at a cut-off of abnormal squamous cells of undetermined significance (ASCUS) (or low-grade squamous intraepithelial lesions (LSIL) if ASC-US unavailable), but is 6% (95% CI: 4-7%) relatively less specific. Several approaches are currently under evaluation to deal with the lower specificity of HPV DNA testing as associated with transient infection. These include HPV typing for HPV-16 and -18/45, markers of proliferative lesions such as p16 and mRNA coding for the viral E6 and/or E7 proteins, with a potential clinical use recommending more aggressive management in those who are positive. In countries where cytology is of good quality, the most attractive option for primary screening is to use HPV DNA testing as the sole screening modality with cytology reserved for triage of HPV-positive women. Established cytology-based programmes should also be gradually moving towards a greater use of HPV DNA testing to improve their efficacy and safely lengthen the screening interval. The greater sensitivity of HPV DNA testing compared to cytology argues strongly for using HPV DNA testing as the primary screening test in newly implemented programmes, except where resources are extremely limited and only programmes based on visual inspection are affordable. In such countries, use of a simple HPV DNA test followed by immediate 'screen and treat' algorithms based on visual inspection in those who are HPV-positive are needed to minimise the number of visits and make best use of limited resources. A review of studies for visual inspection methods is presented. The fact that HPV is a sexually transmitted infection may lead to anxiety and concerns about sexual relationships. These psychosocial aspects and the need for more information and educational programmes about HPV are also discussed in this article. (C) 2008 Elsevier Ltd. All rights reserved.
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| 11. |
- Dillner, Joakim, et al.
(author)
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Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study.
- 2008
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In: BMJ: British Medical Journal. - : BMJ. - 1756-1833 .- 0959-8138 .- 1468-5833. ; 337
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To obtain large scale and generalisable data on the long term predictive value of cytology and human papillomavirus (HPV) testing for development of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+). DESIGN: Multinational cohort study with joint database analysis. SETTING: Seven primary HPV screening studies in six European countries. PARTICIPANTS: 24,295 women attending cervical screening enrolled into HPV screening trials who had at least one cervical cytology or histopathology examination during follow-up. MAIN OUTCOME MEASURE: Long term cumulative incidence of CIN3+. RESULTS: The cumulative incidence rate of CIN3+ after six years was considerably lower among women negative for HPV at baseline (0.27%, 95% confidence interval 0.12% to 0.45%) than among women with negative results on cytology (0.97%, 0.53% to 1.34%)). By comparison, the cumulative incidence rate for women with negative cytology results at the most commonly recommended screening interval in Europe (three years) was 0.51% (0.23% to 0.77%). The cumulative incidence rate among women with negative cytology results who were positive for HPV increased continuously over time, reaching 10% at six years, whereas the rate among women with positive cytology results who were negative for HPV remained below 3%. CONCLUSIONS: A consistently low six year cumulative incidence rate of CIN3+ among women negative for HPV suggests that cervical screening strategies in which women are screened for HPV every six years are safe and effective.
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| 12. |
- Franceschi, Silvia, et al.
(author)
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EUROGIN 2008 roadmap on cervical cancer prevention
- 2009
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:10, s. 2246-2255
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Journal article (peer-reviewed)abstract
- The EUROGIN 2008 Roadmap represents a continuing effort to provide updated information on primary and secondary prevention of cervical cancer. The report addresses several areas including the progress made toward global implementation of currently licensed human papillomavirus (HPV) vaccines, the possibilities and value of future-generation HPV vaccines. endpoints under consideration for evaluation of candidate HPV vaccines, and monitoring impact of HPV vaccination programmes that can be implemented within developed and less-developed countries. For the sake of completeness, a short update on the evolution of HPV testing in primary screening programmes at present and after HPV vaccine introduction has also been included. The report is available on the EUROGIN website (www.eurogin.com). (C) 2009 UICC
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| 13. |
- Jack, Cuzick, et al.
(author)
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Frequency estimation from crossings of an unknown level
- 1980
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In: Biometrika. - : Oxford University Press (OUP). - 0006-3444 .- 1464-3510. ; 67:1, s. 65-72
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Journal article (peer-reviewed)abstract
- By counting the number of upcrossings of the mean level by a stationary Gaussian process one can estimate the mean frequency of the process. Here we present a frequency estimator based on the number of upcrossings of one unknown level hoped to be near the mean, and the percentage of the total observation time spent above the level. This is equivalent to observing upcrossings of a known level in a process with unknown mean and variance. Formulae are given for the bias and variance of the estimator, and conditions for its asymptotic normality. Numerical examples show that the estimator behaves reasonably for levels within one standard deviation from the process mean.
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| 14. |
- Meijer, Chris J. L. M., et al.
(author)
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Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older
- 2009
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:3, s. 516-520
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Journal article (peer-reviewed)abstract
- Given the strong etiologic link between high-risk HPV infection and cervical cancer high-risk HPV testing is now being considered as an alternative for cytology-based cervical cancer screening. Many test systems have been developed that can detect the broad spectrum of hrHPV types in one assay. However, for screening purposes the detection of high-risk HPV is not inherently useful unless it is informative for the presence of high-grade cervical intraepithelial neoplasia (CIN 2/3) or cancer. Candidate high-risk HPV tests to be used for screening should reach an optimal balance between clinical sensitivity and specificity for detection of high-grade CIN and cervical cancer to minimize redundant or excessive follow-up procedures for high-risk HPV positive women without cervical lesions. Data from various large screening studies have shown that high-risk HPV testing by hybrid capture 2 and GP5+/6+-PCR yields considerably better results in the detection of CIN 2/3 than cytology. The data from these studies can be used to guide the translation of high-risk HPV testing into clinical practice by setting standards of test performance and characteristics. On the basis of these data we have developed guidelines for high-risk HPV test requirements for primary cervical screening and validation guidelines for candidate HPV assays. (C) 2008 Wiley-Liss, Inc.
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| 15. |
- Møller, Henrik, et al.
(author)
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Prostate cancer incidence, clinical stage and survival in relation to obesity : A prospective cohort study in Denmark.
- 2015
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:8, s. 1940-1947
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Journal article (peer-reviewed)abstract
- There is no clear link between obesity and prostate cancer incidence but an association has been reported between obesity and fatal prostate cancer. We report on two prospective cohort analyses on (i) the incidence of prostate cancer in relation to obesity in a cohort of men with no previous cancer, and on (ii) the stage distribution and prostate cancer specific mortality in relation to obesity among men with prostate cancer. The "Diet, Cancer and Health" prospective cohort study was established in Denmark in 1993-1997 and accrued 26,944 men aged 50-64 years. Data were extracted on height, weight, body mass index (BMI), waist circumference and body fat percentage. Information on cancer incidence and deaths were obtained by record linkage with the Danish Cancer Register and the Danish Death Register. The incidence rate of prostate cancer was similar or slightly lower in obese men compared with nonobese men, but obese men tended to be diagnosed with more advanced prostate cancer. The proportion of Stage 3-4 cancers was 37% in the lowest BMI quartile and 48% in the highest (p = 0.006). Obese men with prostate cancer had higher prostate cancer specific mortality. The hazard ratio comparing the highest and the lowest quartiles of BMI was 1.48 (95% confidence interval: 1.06-2.05; p-value for trend: 0.002). The association was attenuated but not eliminated by statistical adjustment for stage, and the data are suggestive of a stage-independent causal pathway where prostate cancer in obese men has higher fatality, even in early-stage disease.
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| 16. |
- Romild, Ulla, 1959-
(author)
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Essays on Distance Based (Non-Euclidean) Tests for Spatial Clustering in Inhomogeneous Populations : Adjusting for the Inhomogeneity through the Distance Used
- 2006
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Doctoral thesis (other academic/artistic)abstract
- This thesis consits of four papers dealing with distance based (non-Euclidean) tests for spatial clustering in inhomogeneous populations. The density adjusted distance (DAD), which considers the underlying density, is defined in the first paper. The proposed distance can be used together with any of the old distance based methods developed for traditional homogeneous spatial patterns. The test statistics in distance based tests can all be seen as a weighted sum of distance measures for distances between n cases with known co-ordinates. DAD based test statistics are developed and their performance is compared with the performance of previously suggested tests by simulation in the second paper. The tests are compared in different types of data set and for various kinds of clustering. It is shown that no test is the optimal choice for all alternative hypotheses and that the tests are unequally sensitive to the structure of the underlying data. Tests based on the DAD are often a good alternative. Test statistics and graphical tools for the Empirical Distribution Function of DAD are developed and examined in the third paper. We show that the result of an EDF test combined with EDF plots provides more information about the possible nature of clustering in a sample than the result of a parametric test only.
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| 17. |
- Roobol, Monique J., et al.
(author)
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Prostate Cancer Mortality Reduction by Prostate-Specific Antigen-Based Screening Adjusted for Nonattendance and Contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC)
- 2009
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In: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 56:4, s. 584-591
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Journal article (peer-reviewed)abstract
- Background: Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. Objective: To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. Design, setting, and participants: We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162 243 men 55-69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent). Intervention: Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam. Measurements: Relative risks (RRs) with 95% confidence intervals (Cis) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose. Results and limitations: In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68-0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58-0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51-0.92) to 0.71 (95% CI, 0.55-0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres. Conclusions: PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of over diagnosis and overtreatment inherent in PCa screening. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 18. |
- Trinh, Thang, et al.
(author)
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Background risk of breast cancer and the association between physical activity and mammographic density
- 2015
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In: Breast Cancer Research. - : BIOMED CENTRAL LTD. - 1465-5411 .- 1465-542X. ; 17
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Journal article (peer-reviewed)abstract
- Introduction High physical activity has been shown to decrease the risk of breast cancer, potentially by a mechanism that also reduces mammographic density. We tested the hypothesis that the risk of developing breast cancer in the next 10 years according to the Tyrer-Cuzick prediction model influences the association between physical activity and mammographic density. Methods We conducted a population-based cross-sectional study of 38,913 Swedish women aged 4074 years. Physical activity was assessed using the validated web-questionnaire Active-Q and mammographic density was measured by the fully automated volumetric Volpara method. The 10-year risk of breast cancer was estimated using the Tyrer-Cuzick (TC) prediction model. Linear regression analyses were performed to assess the association between physical activity and volumetric mammographic density and the potential interaction with the TC breast cancer risk. Results Overall, high physical activity was associated with lower absolute dense volume. As compared to women with the lowest total activity level (<40 metabolic equivalent hours [MET-h] per day), women with the highest total activity level (>= 50 MET-h/day) had an estimated 3.4 cm(3) (95% confidence interval, 2.3-4.7) lower absolute dense volume. The inverse association was seen for any type of physical activity among women with <3.0% TC 10-year risk, but only for total and vigorous activities among women with 3.0-4.9% TC risk, and only for vigorous activity among women with >= 5.0% TC risk. The association between total activity and absolute dense volume was modified by the TC breast cancer risk (P-interaction = 0.05). As anticipated, high physical activity was also associated with lower non-dense volume. No consistent association was found between physical activity and percent dense volume. Conclusions Our results suggest that physical activity may decrease breast cancer risk through reducing mammographic density, and that the physical activity needed to reduce mammographic density may depend on background risk of breast cancer.
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