Showing papers by "Susanne K. Kjaer published in 2017"
Catherine M. Phelan, Karoline Kuchenbaecker1, Karoline Kuchenbaecker2, Jonathan Tyrer1 +440 more•Institutions (156)
TL;DR: Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
Abstract: To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
310 citations
University of Alabama at Birmingham1, Medical University of Vienna2, University of Bergen3, Haukeland University Hospital4, Federal University of Paraná5, University of Kansas6, The Ohio State University Wexner Medical Center7, University of California, Irvine8, Universidade Federal de Santa Catarina9, Karolinska University Hospital10, Université de Montréal11, Del Rosario University12, Veterans Health Administration13, University of Iowa14, University of California, Los Angeles15, McGill University16, Johns Hopkins University17, University of Virginia18, Queen Mary University of London19, University of Melbourne20, University of Copenhagen21, Merck & Co.22
TL;DR: The 9vHPV vaccine prevents infection, cytological abnormalities, high-grade lesions, and cervical procedures related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18 antibody responses when compared with quadrivalent HPV (qHPV).
277 citations
Mayo Clinic1, University of Calgary2, University College London3, Pomeranian Medical University4, University of Erlangen-Nuremberg5, Spelman College6, Carlos III Health Institute7, University of Tübingen8, German Cancer Research Center9, University of Sydney10, University of Hawaii11, Westmead Hospital12, University of São Paulo13, Heidelberg University14, University of Pittsburgh15, University of Cambridge16, Cedars-Sinai Medical Center17, University of Alcalá18, Icahn School of Medicine at Mount Sinai19, University of New South Wales20, National Health Service21, Catholic University of Health and Allied Sciences22, University of Western Sydney23, University of Texas at Austin24, QIMR Berghofer Medical Research Institute25, Stanford University26, Kunming Medical University27, University of British Columbia28, Peter MacCallum Cancer Centre29, Garvan Institute of Medical Research30, University of Melbourne31, University of Copenhagen32, Alexandra Hospital33, Alberta Health Services34, University of Hamburg35, Roswell Park Cancer Institute36, Medical University of South Carolina37, University of New Mexico38, University of California, Los Angeles39, Nottingham University Hospitals NHS Trust40, BC Cancer Agency41
TL;DR: This study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ TILs and HGSOC survival and suggests that understanding factors that drive infiltration will be the key to unraveling outcome heterogeneity in this cancer.
Abstract: Importance Cytotoxic CD8+tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+TILs by histotype and in relation to other clinical factors. Objective To define the prognostic role of CD8+TILs in epithelial ovarian cancer. Design, Setting, and Participants This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years. Exposures Following immunohistochemical analysis, CD8+TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines. Main Outcomes and Measures Overall survival time. Results The final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+TILs, respectively (Pvalue for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germlineBRCA1pathogenic mutation, but were not prognostic forBRCA2mutation carriers. Evaluation of uncategorized CD8+TIL counts showed a near-log-linear functional form. Conclusions and Relevance This study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+TILs and HGSOC survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors that drive infiltration will be the key to unraveling outcome heterogeneity in this cancer.
243 citations
TL;DR: An increasing incidence of OPSCC is driven primarily by HPV+ OPSCC, which is a high-prevalence, although the lower number of HPV- cases has yet to stabilise, and projections suggest that the number of herpes simplex virus-related OPSCC will exceed that of cervical cancer in 2016 in Eastern Denmark.
107 citations
TL;DR: In this paper, a systematic review and meta-analysis was conducted to estimate the pooled prevalence of human papillomavirus (HPV) DNA and HPV type distribution in squamous cell carcinoma of the vulva (vulvar cancer) and vulvar intraepithelial neoplasia (VIN).
Abstract: In this updated systematic review and meta-analysis we estimate the pooled prevalence of human papillomavirus (HPV) DNA and HPV type distribution in squamous cell carcinoma of the vulva (vulvar cancer) and vulvar intraepithelial neoplasia (VIN). PubMed, Embase, and Cochrane Library databases were used to identify studies published between 1990 and 2015 and using a PCR-based or hybrid capture test to evaluate the presence of HPV DNA in vulvar cancer or VIN. Pooled estimates of the HPV prevalence with corresponding 95% confidence intervals (CI) were calculated based on a random effects model. The I2 statistic was used to describe the amount of heterogeneity. In meta-regression analyses potential sources of heterogeneity were evaluated. We identified 92 eligible papers, comprising altogether 5015 cases of vulvar cancer (64 papers) and 2764 cases of VIN (48 papers). The pooled prevalence of HPV in vulvar cancer was 39.7% (95% CI: 35.1–44.4%). Overall, 76.3% (95% CI: 70.1–82.1%) of VIN lesions tested HPV-positive, while the HPV prevalence in new subcategories of VIN, uVIN and dVIN, was 86.2% (95% CI: 73.5–95.5%) and 2.0% (95% CI: 0–10.0%), respectively. Substantial between-study heterogeneity was observed (vulvar cancer: I2 = 88.4%; VIN: I2 = 90.7%) with the largest variation between geographical regions. Among HPV-positive cases the predominant high-risk HPV type was HPV16, followed by HPV33 and HPV18. HPV6 was detected as a single infection in a small subset of VIN and vulvar cancer samples. Thus, HPV vaccination targeting these HPV types may prevent a substantial number of vulvar lesions. This article is protected by copyright. All rights reserved.
82 citations
University of Copenhagen1, Rutgers University2, Dartmouth College3, QIMR Berghofer Medical Research Institute4, Fred Hutchinson Cancer Research Center5, University of Washington6, Cedars-Sinai Medical Center7, University of Pittsburgh8, Roswell Park Cancer Institute9, University of Virginia10, Duke University11, Memorial Sloan Kettering Cancer Center12, Radboud University Nijmegen13, University of Toronto14, University of South Florida15, University of California, Irvine16, University of Southern California17, University of Michigan18, Yale University19
TL;DR: PID was associated with an increased risk of borderline ovarian tumors, particularly among women who had had multiple episodes of PID, and the association of PID with ovarian cancer risk is still somewhat uncertain and requires further investigation.
Abstract: Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to tumor behavior and histotype. We pooled data from 13 case-control studies, conducted between 1989 and 2009, from the Ovarian Cancer Association Consortium (OCAC), including 9,162 women with ovarian cancers, 2,354 women with borderline tumors, and 14,736 control participants. Study-specific odds ratios were estimated and subsequently combined into a pooled odds ratio using a random-effects model. A history of PID was associated with an increased risk of borderline tumors (pooled odds ratio (pOR) = 1.32, 95% confidence interval (CI): 1.10, 1.58). Women with at least 2 episodes of PID had a 2-fold increased risk of borderline tumors (pOR = 2.14, 95% CI: 1.08, 4.24). No association was observed between PID and ovarian cancer risk overall (pOR = 0.99, 95% CI: 0.83, 1.19); however, a statistically nonsignificantly increased risk of low-grade serous tumors (pOR = 1.48, 95% CI: 0.92, 2.38) was noted. In conclusion, PID was associated with an increased risk of borderline ovarian tumors, particularly among women who had had multiple episodes of PID. Although our results indicated a histotype-specific association with PID, the association of PID with ovarian cancer risk is still somewhat uncertain and requires further investigation.
59 citations
TL;DR: Although invasive implants are the most important feature in predicting an adverse outcome, subclassification into APST and niLGSC is important as it stratifies women with respect to risk for advanced stage disease and invasive implants for all women and development of serous carcinoma cases.
Abstract: Ovarian serous borderline tumors (SBTs) have been the subject of considerable controversy, particularly with regard to terminology and behavior. It has been proposed that they constitute a heterogenous group of tumors composed, for the most part, of typical SBTs that are benign and designated "atypical proliferative serous tumor (APST)" and a small subset of SBTs with micropapillary architecture that have a poor outcome and are designated "noninvasive low-grade serous carcinoma (niLGSC)". It also has been argued that the difference in behavior between the 2 groups is not due to the subtype of the primary tumor but rather the presence of extraovarian disease, specifically invasive implants. According to the terminology of the 2014 WHO Classification, typical SBTs are equivalent to APSTs and SBTs displaying micropapillary architecture are synonymous with niLGSC. In addition, "invasive implants" were renamed "low-grade serous carcinoma" (LGSC). The argument as to whether it is the appearance of the primary tumor or the presence of extraovarian LGSC that determines outcome remains unsettled. The current study was initiated in 2004 and was designed to determine what factors were predictive of outcome, with special attention to the appearance of the primary tumor (APST vs. niLGSC) and that of the extraovarian disease (noninvasive vs. invasive implants). Our study is population based, involving the entire female population of Denmark. None of the women in the study were lost to follow-up, which ranged up to 36 years (median, 15 y). All the microscopic slides from the contributing hospitals were rereviewed by a panel of 2 pathologists (R.V. and R.J.K.) who were blinded to the follow-up. After excluding those that were not SBTs by the pathology panel, as well as cases with a prior or concurrent cancer or undefined stage, 942 women remained, of which 867 were APSTs and 75 were niLGSCs. The median patient age was 50 years (range, 16 to 97 y). Eight hundred nine women (86%) presented with FIGO stage I disease, whereas 133 (14%) had advanced stage disease. Compared with APSTs, niLGSC exhibited a significantly greater frequency of bilaterality, residual gross disease after surgery, microinvasion/microinvasive carcinoma, advanced stage disease, and invasive implants at presentation (P-values <0.003). Because the cause of death is difficult to accurately ascertain from death certificates, we used development of invasive serous carcinoma as the primary endpoint as following development of carcinoma, the mortality is very high. In the entire cohort, subsequent development of carcinoma occurred in 4%, of which 93% were low grade and 7% high grade (median time, 10 y; range, up to 25 y). After adjusting for age at and time since diagnosis of APST or niLGSC, occurrence of subsequent carcinoma was significantly higher with niLGSC than APST among all stages combined (hazard ratio [HR]=3.8; 95% confidence interval [CI], 1.7-8.2). This difference was still significant for stage I but not advanced stage cases. Moreover, all-cause mortality was not statistically significantly different between APST and niLGSC. Of all women with advanced stage disease, 114 (86%) had noninvasive implants, whereas 19 (14%) were invasive. Noninvasive implants were significantly associated with subsequent development of carcinoma (HR=7.7; 95% CI, 3.9-15.0), but the risk with invasive implants was significantly higher (HR=42.3; 95% CI, 16.1-111.1). In conclusion, although invasive implants are the most important feature in predicting an adverse outcome, subclassification into APST and niLGSC is important as it stratifies women with respect to risk for advanced stage disease and invasive implants for all women and development of serous carcinoma for stage I cases.
52 citations
TL;DR: This largest population-based cohort of verified SBTs revealed that women with noninvasive LGSC are significantly more likely to develop serous carcinoma than women with APST, which could not entirely be explained by invasive implants.
42 citations
TL;DR: Adopting modern technology‐based platforms into the current organized screening program would serve as a convenient communication method between health authority and citizens, allowing easy access for the citizen and reducing the work load in administrating self‐sampling approaches.
Abstract: In organized cervical screening programs, typically 25% of the invited women do not attend. The Copenhagen Self-sampling Initiative (CSi) aimed to gain experiences on participation among screening nonattenders in the Capital Region of Denmark. Here, we report on the effectiveness of different communication platforms used in the pilot with suggestions for strategies prior to a full-implementation. Moreover, an innovative approach using self-sampling brushes with unique radio frequency identification chips allowed for unprecedented levels patient identification safety. Nonattenders from the capital region of Denmark were identified via the organized national invitation module. Screening history was obtained via the nationwide pathology registry. Twenty-four thousand women were invited, and as an alternative to the regular communication platforms (letter and phone), women could request a home test via a mobile-friendly webpage. Instruction material and video-animation in several languages were made available online. Chi-square test was used to test differences. Out of all invited, 31.7% requested a home test, and 20% returned it to the laboratory. In addition, 10% were screened at the physician after receiving the invitation. Stratified by screening history, long-term unscreened women were less likely to participate than intermittently screened women (28% vs. 16%, p < 0.001). Of all contacts received, 64% (63-65) came via letter, and 31% (95CI: 30-32%) via webpage/mobile-app. Self-sampling was well-accepted among nonattenders. Adopting modern technology-based platforms into the current organized screening program would serve as a convenient communication method between health authority and citizens, allowing easy access for the citizen and reducing the work load in administrating self-sampling approaches.
35 citations
TL;DR: This is the first study to report a strong and significantly decreased SBT risk associated with OC use and a significantly increased risk with infertility, and HRT use, and supports that SBTs and serous ovarian cancer share similar risk factors.
29 citations
TL;DR: The results indicate that PID is not a strong risk factor for ovarian cancer, and whether PID is slightly associated with risk of serous ovarian cancer has to be confirmed in other studies.
Abstract: Background: Pelvic inflammatory disease (PID) has been proposed as a risk factor for ovarian cancer. However, the existing literature on the association between PID and ovarian cancer risk is inconclusive and only few cohort studies have been conducted. Methods: Using nationwide Danish registries, we conducted a population-based cohort study including all women from the birth cohorts 1940-1970 in Denmark during 1978-2012 (n=1,318,929) to investigate the association between PID and subsequent risk of epithelial ovarian cancer. Among women in the cohort, 81,281 women were diagnosed with PID and 5,356 women developed ovarian cancer during follow-up through 2012. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between PID and ovarian cancer, both overall and according to histotype. Results: For ovarian cancer overall, we observed no association with PID (HR=1.05; 95% CI: 0.92-1.20). However, in histotype-specific analyses, we found a statistically significantly increased risk of serous ovarian cancer among women with PID (HR=1.19; 1.00-1.41; p=0.047). Conversely, PID was not convincingly associated with risk of any of the other histotypes of ovarian cancer. Conclusion: PID was associated with a modestly increased risk of serous ovarian cancer, but not other histotypes. Impact: Our results indicate that PID is not a strong risk factor for ovarian cancer. Whether PID is slightly associated with risk of serous ovarian cancer has to be confirmed in other studies.
TL;DR: Greater immunogenicity in girls and boys versus young women (the population used to establish 9vHPV vaccine efficacy in clinical studies) indicates that the anti-HPV responses generated by the vaccine in adolescents from all races or regions were sufficient to induce high-level protective efficacy.
TL;DR: No strong evidence of an association between post‐diagnostic statin use and reduced mortality in ovarian cancer patients is found, however, the finding of potential differential susceptibility to statins among patients with different histologic types of ovarian cancer warrants further evaluation.
Abstract: Statin use has been suggested to improve prognosis in cancer patients, however, for ovarian cancer, the evidence is sparse. From the Danish Cancer Registry, we identified patients aged 30-84 years with a histologically verified first diagnosis of epithelial ovarian cancer between 2000 and 2013. Data on filled prescriptions, death, and potential confounding factors were obtained from nationwide registers. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post-diagnostic statin use and all-cause or ovarian cancer-specific mortality. Among 4,419 patients with epithelial ovarian cancer, post-diagnostic statin use was not statistically significantly associated with all-cause (HR: 0.90, 95% CI: 0.78-1.04) or ovarian cancer-specific mortality (HR: 0.90, 95% CI: 0.76-1.08). There was little evidence of a dose-response relationship and the neutral associations persisted in sensitivity analyses. In women with endometrioid or clear cell tumour histology, cancer-specific mortality was reduced by 30-40% among statin users compared to non-users, however the analyses were limited by small numbers. Significantly reduced mortality with statin use was observed in subcohorts of new users of statins and of patients not using low-dose aspirin. In conclusion, we found no strong evidence of an association between post-diagnostic statin use and reduced mortality in ovarian cancer patients. However, our finding of potential differential susceptibility to statins among patients with different histologic types of ovarian cancer warrants further evaluation.
QIMR Berghofer Medical Research Institute1, University of Sydney2, University of Copenhagen3, Population Health Research Institute4, Cedars-Sinai Medical Center5, University of Pittsburgh6, Roswell Park Cancer Institute7, University of Rochester8, University of Kansas9, Harvard University10, Brigham and Women's Hospital11, Rutgers University12, Radboud University Nijmegen13, University of Cambridge14, University of California, Berkeley15, University College London16, Garvan Institute of Medical Research17, University of Southern California18, Kettering University19, University of Hamburg20
TL;DR: The results suggested that current smoking has a greater impact on survival among women with localized than disseminated disease and the identification of cigarette smoking as a modifiable factor associated with survival has potential clinical importance as a focus area to improve ovarian cancer prognosis.
Abstract: Cigarette smoking is associated with an increased risk of developing mucinous ovarian tumours but whether it is associated with ovarian cancer survival overall or for the different histotypes is unestablished. Furthermore, it is unknown whether the association between cigarette smoking and survival differs according to strata of ovarian cancer stage at diagnosis. In a large pooled analysis, we evaluated the association between various measures of cigarette smoking and survival among women with epithelial ovarian cancer. We obtained data from 19 case-control studies in the Ovarian Cancer Association Consortium (OCAC), including 9,114 women diagnosed with ovarian cancer. Cox regression models were used to estimate adjusted study-specific hazard ratios (HRs), which were combined into pooled hazard ratios (pHR) with corresponding 95% confidence intervals (CIs) under random effects models. Overall, 5,149 (57%) women died during a median follow-up period of 7.0 years. Among women diagnosed with ovarian cancer, both current (pHR = 1.17, 95% CI: 1.08-1.28) and former smokers (pHR = 1.10, 95% CI: 1.02-1.18) had worse survival compared with never smoking women. In histotype-stratified analyses, associations were observed for mucinous (current smoking: pHR = 1.91, 95% CI: 1.01-3.65) and serous histotypes (current smoking: pHR = 1.11, 95% CI: 1.00-1.23; former smoking: pHR = 1.12, 95% CI: 1.04-1.20). Further, our results suggested that current smoking has a greater impact on survival among women with localised than disseminated disease. The identification of cigarette smoking as a modifiable factor associated with survival has potential clinical importance as a focus area to improve ovarian cancer prognosis. This article is protected by copyright. All rights reserved.
Roswell Park Cancer Institute1, University at Buffalo2, University of Pittsburgh3, University of Texas at Austin4, University of Hamburg5, Hannover Medical School6, Medical University of South Carolina7, University of Calgary8, Alexandra Hospital9, University of Sydney10, QIMR Berghofer Medical Research Institute11, University of Queensland12, Yale University13, Fred Hutchinson Cancer Research Center14, Dartmouth College15, Cedars-Sinai Medical Center16, University of Virginia17, Brigham and Women's Hospital18, Rutgers University19, University of Medicine and Dentistry of New Jersey20, New Jersey Department of Health and Senior Services21, Radboud University Nijmegen22, Duke University23, German Cancer Research Center24
TL;DR: Histories of hypertension, diabetes, and use of diuretics, beta blockers, insulin, and oral antidiabetic medications may influence the survival of ovarian cancer patients.
Abstract: Purpose
Survival following ovarian cancer diagnosis is generally low; understanding factors related to prognosis could be important to optimize treatment. The role of previously diagnosed comorbidities and use of medications for those conditions in relation to prognosis for ovarian cancer patients has not been studied extensively, particularly according to histological subtype.
TL;DR: Whether selected factors are associated with non‐use and emergency contraceptive pill use at first sexual intercourse, among 18‐ to 26‐year‐old women from Denmark, Norway and Sweden, is examined.
Abstract: Introduction
The aim of this study was to describe recent patterns of contraceptive use at first sexual intercourse and to examine whether selected factors are associated with non-use and emergency contraceptive pill use at first sexual intercourse, among 18- to 26-year-old women from Denmark, Norway and Sweden.
Material and methods
This was a population-based, questionnaire study of randomly chosen 18- to 26-year-old Scandinavian women. The prevalence of contraception methods used at first sexual intercourse was calculated. Factors associated with contraceptive non-use and emergency contraceptive pill use at first sexual intercourse were determined using log binomial models.
Results
The prevalence of contraceptive non-use and emergency contraceptive pill use was lowest in Denmark (9.6 and 2.1%, respectively) compared with Norway (14.1 and 4.4%) and Sweden (16.6 and 4.5%). The risk of contraceptive non-use increased in women who had first sexual intercourse at or before 14 years of age (13–14 years: prevalence ratio 1.40; 95% confidence interval 1.24–1.58). The risk of both non-use and emergency contraceptive pill use increased when the partner at first sexual intercourse was 20 years or older, and with increasing age difference between the partner and the woman at her first sexual intercourse. Smoking initiation prior to first sexual intercourse increased risk of contraceptive non-use (prevalence ratio 1.70; 95% confidence interval 1.50–1.92), and alcohol initiation prior to first sexual intercourse increased risk of emergency contraceptive pill use at first sexual intercourse (prevalence ratio 1.95; 95% confidence interval 1.49–2.54).
Conclusions
Contraceptive non-use at first sexual intercourse was strongly associated with early age at first sexual intercourse. Emergency contraceptive pill and contraceptive non-use at first sexual intercourse were both strongly associated with increasing partner age and an increasing difference in age between the woman and her partner. Hence, young women should be educated to negotiate contraceptive use with their partners.
University of Cambridge1, University of Southern California2, Cedars-Sinai Medical Center3, University of California, Irvine4, Rutgers University5, University of Erlangen-Nuremberg6, Duke University7, Hannover Medical School8, National Institutes of Health9, University of Helsinki10, Peter MacCallum Cancer Centre11, University of Melbourne12, Beatson West of Scotland Cancer Centre13, University of Hamburg14, German Cancer Research Center15, University of New Mexico16, Harvard University17, Mayo Clinic18, Curie Institute19, Dartmouth College20, University of Jena21, University of Southampton22, University of California, Los Angeles23, Imperial College London24, University College London25, Pomeranian Medical University26, University of Duisburg-Essen27, University of Texas MD Anderson Cancer Center28, University of Copenhagen29, University of British Columbia30, Medical University of South Carolina31, Radboud University Nijmegen32, Katholieke Universiteit Leuven33, Flanders Institute for Biotechnology34, Memorial Sloan Kettering Cancer Center35, Xiamen University36, Stanford University37, University of Glasgow38, University of Pittsburgh39, University of South Florida40, Roswell Park Cancer Institute41, University of Texas Health Science Center at Houston42, University of Michigan43, Oregon Health & Science University44, University of New South Wales45, Yale University46, University of Washington47, Fred Hutchinson Cancer Research Center48, University of Bergen49, Glasgow Royal Infirmary50, Vanderbilt University51, Broad Institute52
TL;DR: Putative PAX8 target genes are enriched for common SOC risk variants, of particular interest given that PAX8 is well-established as a specific marker for the cell of origin of SOC.
Abstract: Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci
TL;DR: Use of selective serotonin reuptake inhibitors was associated with a decreased risk of epithelial ovarian cancer; thereby implying potential chemopreventive properties of these drugs.
Abstract: Antidepressants are widely prescribed among women to treat depression and anxiety disorders, but studies of their effects on gynecological cancer risk are sparse. We assessed associations between various antidepressants and risk of epithelial ovarian cancer. By using Danish nationwide registers, we identified all women (cases) aged 30 to 84 years with incident epithelial (serous, endometrioid, clear cell or mucinous) ovarian cancer during 2000-2011 (n= 4,103) and matched each case to 20 population controls (n=58,706) by risk-set matching. Data on drug use (including tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants, and potential confounder drugs), medical and reproductive history, and socioeconomic parameters, were obtained from nationwide registries. We used conditional logistic regression models to estimate adjusted odds ratios (ORs) and two-sided 95% confidence intervals (CIs) for epithelial ovarian cancer associated with antidepressive drug use. Compared with non-use, use of selective serotonin reuptake inhibitors was associated with a decreased risk of ovarian cancer (OR, 0.85; 95% CI, 0.74-0.96), whereas the associations for other antidepressants were close to unity [tricyclic and related antidepressants: OR, 0.99 (95% CI, 0.78-1.26); other antidepressants: OR, 1.05 (95% CI, 0.76-1.46)]. For individual types of SSRI, reduced ORs were observed for citalopram OR, 0.78 (95% CI, 0.66-0.93), paroxetine 0.79 (95% CI, 0.56-1.12) and sertraline 0.80 (95% CI, 0.60-1.08). Among postmenopausal women, the inverse association was restricted to users of menopausal hormone therapy. In conclusion, use of selective serotonin reuptake inhibitors was associated with a decreased risk of epithelial ovarian cancer; thereby implying potential chemopreventive properties of these drugs. This article is protected by copyright. All rights reserved.
TL;DR: This study aims to assess the degree to which a Short Message Service (SMS) intervention can increase attendance at appointments among women who have tested positive for high-risk Human Papillomavirus (HPV) during cervical cancer screening in Tanzania.
Abstract: Cervical cancer is a major health concern in Tanzania, caused by poor attendance for cervical cancer screening and follow-up of women at risk. Mobile telephone health interventions are proven effective tools to improve health behaviour in African countries. So far, no knowledge exists on how such interventions may perform in relation to cervical cancer screening in low-income settings. This study aims to assess the degree to which a Short Message Service (SMS) intervention can increase attendance at appointments among women who have tested positive for high-risk (HR) Human Papillomavirus (HPV) during cervical cancer screening. Connected2Care is a non-blinded, multicentre, parallel-group, randomised controlled trial. Tanzanian women testing positive to HR HPV at inclusion are randomly assigned in an allocation ratio of 1:1 to the SMS intervention or the control group (standard care). In a period of 10 months, the intervention group will receive 15 one-directional health educative text messages and SMS reminders for their appointment. The total sample size will be 700 with 350 women in each study arm. Primary outcome is attendance rate for follow-up. Secondary objectives are cost-effectiveness, measured through incremental ratios, and knowledge of cervical cancer by a 16-item true/false scale questionnaire at baseline and follow-up. Barriers against implementing the intervention will be assessed in a mixed-methods sub-population study. This study may provide information on the potential effects, costs, and barriers in implementing an SMS intervention targeting a group of women who are followed up after testing positive for HR HPV and are, therefore, at increased risk of developing cervical cancer. This can guide decision-makers on the effective use of mobile technology in a low-income setting. Trial status: recruiting. ClinicalTrials.gov, ID: NCT02509702
. Registered on 15 June 2015.
Harvard University1, Brigham and Women's Hospital2, Medical University of South Carolina3, University of Calgary4, Alexandra Hospital5, QIMR Berghofer Medical Research Institute6, University of Sydney7, Université catholique de Louvain8, Cedars-Sinai Medical Center9, University of Copenhagen10, Mayo Clinic11, Oregon Health & Science University12, University of Glasgow13
TL;DR: The results suggest that high BMI and race may influence CA125 levels independent of tumor characteristics, and validation is needed in studies that use a single assay for CA125 measurement and have a diverse study population.
Abstract: Cancer antigen 125 (CA125) is a glycoprotein expressed by epithelial cells of several normal tissue types and overexpressed by several epithelial cancers. Serum CA125 levels are mostly used as an aid in the diagnosis of ovarian cancer patients, to monitor response to treatment and detect cancer recurrence. Besides tumor characteristics, CA125 levels are also influenced by several epidemiologic factors, such as age, parity, and oral contraceptive use. Identifying factors that influence CA125 levels in ovarian cancer patients could aid in the interpretation of CA125 values for individuals. We evaluated predictors of pretreatment CA125 in 13 studies participating in the Ovarian Cancer Association Consortium. This analysis included a total of 5,091 women with invasive epithelial ovarian cancer with pretreatment CA125 measurements. We used probit scores to account for variability in CA125 between studies and linear regression to estimate the association between epidemiologic factors and tumor characteristics and pretreatment CA125 levels. In age-adjusted models, older age, history of pregnancy, history of tubal ligation, family history of breast cancer, and family history of ovarian cancer were associated with higher CA125 levels while endometriosis was associated with lower CA125 levels. After adjusting for tumor-related characteristics (stage, histology, grade), body mass index (BMI) higher than 30 kg/m2 was associated with 10% (95% CI 2, 19%) higher CA125 levels, while race (non-white vs. white) was associated with 15% (95% CI 4, 27%) higher CA125 levels. Our results suggest that high BMI and race may influence CA125 levels independent of tumor characteristics. Validation is needed in studies that use a single assay for CA125 measurement and have a diverse study population.
TL;DR: Results indicate that, although recurrent NRAS mutations are present, their low prevalence indicates that NRAS plays a limited role in the development of LGSC, and further studies to identify other oncogenic events that drive LGSC progression are warranted.
Fred Hutchinson Cancer Research Center1, Harvard University2, QIMR Berghofer Medical Research Institute3, Peter MacCallum Cancer Centre4, University of Queensland5, Yale University6, University of Washington7, Huntsman Cancer Institute8, Cedars-Sinai Medical Center9, University of Pittsburgh10, University of Texas at Austin11, Roswell Park Cancer Institute12, University of Copenhagen13, University of Virginia14, Duke University15, Brigham and Women's Hospital16, Rutgers University17, University of Toronto18, University of California, Irvine19, University of Southern California20, University of Michigan21
TL;DR: It is suggested that menstrual cycle characteristics influence ovarian cancer risk differentially based on histotype, with decreased risk of invasive ovarian cancer compared with women reporting cycle length ≤35 days.
Abstract: Background: Polycystic ovary syndrome (PCOS), and one of its distinguishing characteristics, oligomenorrhea, have both been associated with ovarian cancer risk in some but not all studies. However, these associations have been rarely examined by ovarian cancer histotypes, which may explain the lack of clear associations reported in previous studies.Methods: We analyzed data from 14 case-control studies including 16,594 women with invasive ovarian cancer (n = 13,719) or borderline ovarian disease (n = 2,875) and 17,718 controls. Adjusted study-specific ORs were calculated using logistic regression and combined using random-effects meta-analysis. Pooled histotype-specific ORs were calculated using polytomous logistic regression.Results: Women reporting menstrual cycle length >35 days had decreased risk of invasive ovarian cancer compared with women reporting cycle length ≤35 days [OR = 0.70; 95% confidence interval (CI) = 0.58-0.84]. Decreased risk of invasive ovarian cancer was also observed among women who reported irregular menstrual cycles compared with women with regular cycles (OR = 0.83; 95% CI = 0.76-0.89). No significant association was observed between self-reported PCOS and invasive ovarian cancer risk (OR = 0.87; 95% CI = 0.65-1.15). There was a decreased risk of all individual invasive histotypes for women with menstrual cycle length >35 days, but no association with serous borderline tumors (Pheterogeneity = 0.006). Similarly, we observed decreased risks of most invasive histotypes among women with irregular cycles, but an increased risk of borderline serous and mucinous tumors (Pheterogeneity < 0.0001).Conclusions: Our results suggest that menstrual cycle characteristics influence ovarian cancer risk differentially based on histotype.Impact: These results highlight the importance of examining ovarian cancer risk factors associations by histologic subtype. Cancer Epidemiol Biomarkers Prev; 27(2); 174-82. ©2017 AACR.
TL;DR: The importance of comprehensive exposure definitions and evaluation of potential effect modification according to user characteristics is discussed, with the aim of identifying women who may experience the largest benefit of aspirin or non-aspirin NSAID use on risk or prognosis of ovarian and endometrial cancer.
TL;DR: Over a period of more than 35 years, the incidence of type 1 endometrial cancer decreased, mainly in pre- and perimenopausal women, while type 2 endometrian cancer incidence increased.
TL;DR: In a nationwide registry‐based case–control study, the association between statin use and risk of endometrial cancer was examined.
Abstract: Introduction
Laboratory and epidemiological evidence have suggested that statin use may protect against the development of certain cancers, including endometrial cancer. In a nationwide registry-based case–control study, we examined the association between statin use and risk of endometrial cancer.
Material and methods
Cases were female residents of Denmark with a primary diagnosis of endometrial cancer during 2000–2009. For each case, we selected 15 female population controls matched on date of birth (±one month) using risk-set sampling. Ever use of statin was defined as two or more prescriptions on separate dates. Conditional logistic regressions were used to estimate age-matched (by design) and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CI) for endometrial cancer associated with statin use. The multivariable-adjusted models included parity, hormone replacement therapy (HRT), obesity, diabetes, chronic obstructive pulmonary disease and education. We evaluated whether the association between statin use and endometrial cancer varied with duration and intensity of statin use, type of endometrial cancer or patient characteristics.
Results
The study population comprised 5382 endometrial cancer cases and 72 127 population controls. We observed no association between ever use of statins and endometrial cancer risk (OR 1.03, 95% CI 0.94–1.14). In addition, endometrial cancer risk did not vary substantially with duration or intensity of statin use. Stratification by type of endometrial cancer also yielded neutral ORs.
Conclusions
In our nationwide case–control study, we found no association between statin use and risk of endometrial cancer.
TL;DR: It is suggested that further validation of HPV assays on self-taken samples is needed for optimal HPV detection and correct clinical management of HPV-positive women.
Abstract: The Copenhagen Self-Sampling Initiative (CSi) has shown how human papillomavirus (HPV)-based self-sampling can be used to increase screening participation among 23,632 nonattenders in the Capital Region of Denmark. In this study, we describe HPV prevalence and genotype frequency in 4,824 self-samples as determined by three HPV assays (the CLART, Onclarity, and Hybrid Capture 2 [HC2] assays) and compare the results with those for physician-taken follow-up samples. The HPV self-sample findings were also compared to the findings for a reference population of 3,347 routinely screened women from the Horizon study, which had been undertaken in the same screening laboratory. Nonattenders had an HPV prevalence of 11.3% as determined by the CLART assay, which was lower than that for women from the Horizon study (18.5%). One-third of the CSi women who tested HPV positive by self-sampling tested HPV negative on the physician-taken follow-up sample. The CLART and Onclarity assays agreed on 64% (95% confidence interval [CI], 60 to 68%) of the HPV-positive self-taken samples. When the HC2 assay results were added into a three-way comparison, the level of agreement decreased to 27% (95% CI, 24 to 29%). Our findings suggest that further validation of HPV assays on self-taken samples is needed for optimal HPV detection and correct clinical management of HPV-positive women.
TL;DR: The present paper gives an overview of the part regarding biomarkers and/or prognostic markers, with a focus on rationale and design, and describes the study described, which has 3 major branches: microRNAs, epigenetics and Next Generation Sequencing.
Abstract: Ovarian cancer is a silent killer and, due to late diagnosis, the primary cause of death amongst gynecological cancers, killing approximately 376 women annually in Denmark. The discovery of a specific and sensitive biomarker for ovarian cancer could improve early diagnosis, but also treatment, by predicting which patients will benefit from specific treatment strategies. The Mermaid III project is consisting of 3 parts including "Early detection, screening and long-term survival," "Biomarkers and/or prognostic markers" and "The infection theory." The present paper gives an overview of the part regarding biomarkers and/or prognostic markers, with a focus on rationale and design. The study described has 3 major branches: microRNAs, epigenetics and Next Generation Sequencing. Tissue and blood from ovarian cancer patients, already enrolled in the prospective ongoing pelvic mass cohort, will be examined. Relevant microRNAs and DNA methylation patterns will be investigated using array technology. Patient exomes will be fully sequenced, and identified genetic variations will be validated with Next Generation Sequencing. In all cases, data will be correlated with clinical information on the patient, in order to identify possible biomarkers. A thorough investigation of biomarkers in ovarian cancer, including large numbers of different markers, has never been done before. Besides from improving diagnosis and treatment, other outcomes could be markers for screening, knowledge of the molecular aspects of cancer and the discovery of new drugs. Moreover, biomarkers are a prerequisite for the development of precision medicine. This study will attack the ovarian cancer problem from several angles, thereby increasing the chance of successfully contributing to saving lives.
Roswell Park Cancer Institute1, University at Buffalo2, Brigham and Women's Hospital3, University of Pittsburgh4, Dartmouth College5, Hannover Medical School6, University of Sydney7, Cedars-Sinai Medical Center8, University of Copenhagen9, QIMR Berghofer Medical Research Institute10, University of Queensland11, University of Medicine and Dentistry of New Jersey12, New Jersey Department of Health and Senior Services13, Fred Hutchinson Cancer Research Center14, University of Virginia15, University of Hamburg16, University of Texas at Austin17, Rutgers University18, German Cancer Research Center19
TL;DR: In this large study of women with ovarian cancer, it is found that recent history of hyperthyroidism and overall history of hypothyroidism were associated with worse 5-year survival.
Abstract: Findings from in vitro studies suggest that increased exposure to thyroid hormones can influence progression of ovarian tumours. However, epidemiologic evidence on this topic is limited. We pooled data from 11 studies from the Ovarian Cancer Association Consortium. Using multivariate Cox proportional hazards models, we estimated associations between hyper- and hypothyroidism and medications prescribed for these conditions with 5-year all-cause survival among women diagnosed with invasive ovarian cancer. Overall, there was a nonsignificant association with history of hyperthyroidism (n=160 cases) and mortality (HR=1.22; 95% CI=0.97–1.53). Furthermore, diagnosis of hyperthyroidism within the 5 years before ovarian cancer diagnosis was associated with an increased risk of death (HR=1.94; 95% CI=1.19–3.18). A more modest association was observed with history of hypothyroidism (n=624 cases) and mortality (HR=1.16; 95% CI=1.03–1.31). Neither duration of hypothyroidism nor use of thyroid medications was associated with survival. In this large study of women with ovarian cancer, we found that recent history of hyperthyroidism and overall history of hypothyroidism were associated with worse 5-year survival.
QIMR Berghofer Medical Research Institute1, University of Queensland2, Vanderbilt University3, Duke University4, Roswell Park Cancer Institute5, University of Sydney6, Yale University7, Fred Hutchinson Cancer Research Center8, Dartmouth College9, Cedars-Sinai Medical Center10, University of Pittsburgh11, University of Texas at Austin12, University of Copenhagen13, Brigham and Women's Hospital14, Harvard University15, Rutgers University16, University of California, Irvine17, University College London18, University of Southern California19, University of New South Wales20, University of Michigan21, Memorial Sloan Kettering Cancer Center22
TL;DR: This study did not show a clear association between analgesic use and ovarian cancer survival, and further investigation with clearer definitions of use and information about post-diagnosis use is warranted.
Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited. Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths). Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95% confidence intervals): aspirin 0.96 (0.88–1.04); non-aspirin NSAIDs 0.97 (0.89–1.05); acetaminophen 1.01 (0.93–1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0.89 (0.82–0.98)). Although this study did not show a clear association between analgesic use and ovarian cancer survival, further investigation with clearer definitions of use and information about post-diagnosis use is warranted.
TL;DR: A long-term follow-up (LTFU) study has been initiated as an extension of the Phase III clinical study to assess effectiveness of the 9vHPV vaccine up to at least 14years after the start of vaccination and uses a control chart method to determine whether vaccine effectiveness may be waning.