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- Berggrund, Malin, 1989-
(författare)
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Identification and clinical implementation of biomarkers for cervical cancer
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction of organised screening programs and prophylactic vaccination against human papilloma virus (HPV) have successfully reduced the incidence of cervical cancer globally. In Sweden, the incidence has been reduced by about 50 % since the introduction of the national screening programme in the late 1960’s. Despite these efforts, cervical cancer is still a major cause of cancer deaths globally.In order to reduce cervical cancer, the screening program should have a high participation rate and be based on a sensitive and specific screening test. About 20 % of women in Sweden do not participate in the organised screening program, and during the last years we have also seen a rise in cervical cancer cases in Sweden among women who participate in the screening program. Thus, there is a need to develop improved screening strategies that result in a higher participation rate, and are based on tests that more precisely identify women with high risk of developing cervical cancer. This includes searching for novel biological markers (biomarkers) that can be used to more accurately identify women with a high risk of developing cervical cancer.By offering women self-sampling for HPV analysis through direct mailing of sample kits with a chemically treated paper card, the FTA card, we were able to increase the participation rate in the screening program. We also found that the use of repeated self-sampling for women that were HPV positive in the primary screening sample increased the number of women detected with higher risk of cervical cancer (Paper II). Self-sampling was shown to be non-inferior to assisted sampling by midwife (Paper III). Using this sample collection device, we further investigated the association between increased risk of cervical cancer and HPV viral load (Paper V) as well as the vaginal microbiota (Paper VI). We also showed that proteins in the vaginal fluid can be studied using self-sampling and the FTA card (Paper I). Lastly, we identified plasma proteins that are associated with cervical cancer and could represent future biomarkers (Paper IV).This thesis has provided novel aspects on the present screening strategy, explored opportunities to increase the participation rate as well as examined possible future biomarkers for screening of cervical cancer.
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| 2. |
- He, Wei, et al.
(författare)
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Pregnancy outcomes in women with a prior cervical intraepithelial neoplasia grade 3 diagnosis : a nationwide population-based cohort study with sibling comparison design
- 2022
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Ingår i: Annals of Internal Medicine. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0003-4819. ; 175:2, s. 210-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Treatment of cervical intraepithelial neoplasia grade 3 (CIN3) removes or destroys part of the cervix and might subsequently influence pregnancy outcomes. Objective: To investigate pregnancy outcomes in women diagnosed with CIN3. Design: Population- and sibling-matched cohort study. Setting: Sweden, 1973-2018. Participants: General population comparison included 78 450 singletons born to women diagnosed with CIN3 and 784 500 matched singletons born to women in the general population who had no CIN3 diagnosis; sibling comparison included 23 199 singletons born to women diagnosed with CIN3 and 28 135 singletons born to their sisters without a CIN3 diagnosis. Measurements: Preterm birth, including spontaneous or iatrogenic preterm birth; Infection-related outcomes, including chorioamnionitis and infant sepsis; and early neonatal death, defined as death during the first week after birth. Results: Compared with the matched general population, women previously diagnosed with CIN3 were more likely to have a preterm birth especially extremely preterm (22-28 weeks; OR, 3.00; 95% CI, 2.69-3.34) and spontaneous preterm (OR, 2.12; 95% CI, 2.05-2.20) birth, infection-related outcomes including chorioamnionitis (OR, 3.23; 95% CI, 2.89-3.62) and infant sepsis (OR, 1.72; 95% CI, 1.60-1.86), and early neonatal death (OR, 1.83; 95% CI, 1.61-2.09). Sibling comparison analyses rendered largely similar results. Over time the risk difference attenuated for all outcomes and disappeared for early neonatal death. Limitations: Lack of data on CIN3 treatment and spontaneous abortion. Conclusion: Prior history of CIN 3 is associated with adverse pregnancy outcomes even after accounting for familial factors. Decreasing risk estimates over time suggest that adverse pregnancy outcomes among women diagnosed with CIN3 may be minimized by improving treatment modalities.
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| 5. |
- Samir, Raghad, 1968-
(författare)
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Tissue tumor marker expression in normal cervical tissue and in cervical intraepithelial neoplasia, for women who are at high risk of human papilloma virus infection, are smokers, contraceptive users or in fertile age
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this research was to study the correlation between tissue tumor marker expression and HR-HPV infection, smoking, hormonal contraceptive use and sex steroids in women with cervical intraepithelial neoplasia or normal epithelium. The study investigated the expression of 11 tumor markers in cervical biopsies obtained from 228 women with different diagnoses ranging from normal cervical epithelium to various stages of CIN. 188 women were recruited at our colposcopy clinic (out-patient surgery, Department of Obstetrics and Gynecology, Falun Hospital) for laser cervical conization or a directed punch biopsy, either because of a vaginal smear (Pap smear) that showed cytological findings suggesting CIN, or because of repeated findings showing atypical squamous cells of undetermined significance (ASCUS). For 40 volunteers, punch biopsies were taken from the normal cervical epithelium. The time period for this study was 2005-2007.Study I : 228 women, of whom 116 were tested, 64 were positive to HR-HPV. The results showed that Ki67 tumor cell proliferation index was the only marker that independently correlated to both the presence of HR-HPV and the severity of cervical lesions.Study II: 228 women, of whom 83 were smokers (36, 9%). Smokers showed lower expression of p53, FHIT (tumor suppressor markers) and interleukin-10 .Higher expression of Cox-2 and Ki-67 (tumor proliferation markers).Study III: 195 women who were premenopausal. There was increased p53 expression (tumor suppressor) in the progestin-IUD users compared to non-users. Decreased IL-10 expression (immunological marker) was observed in both COC users and any progestin-only users.Study IV: Serum from 80 premenopausal women was available. The main finding was that the increased levels of serum progesterone and estradiol were associated with increased Cox-2 expression (proliferation marker). Serum progesterone and estradiol levels influence cellular and extracellular proteins which have been associated with neoplastic development in normal epithelium and CIN.Conclusion: The results of these studies support previous epidemiological findings on the role of smoking, contraceptive use and sex steroids as co-factors in development of CIN and that tumor marker expression varies in different grades of CIN.
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| 8. |
- Vågerö, Denny, et al.
(författare)
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Long-Term Health Consequences Following the Siege of Leningrad
- 2013
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Ingår i: Early Life Nutrition and Adult Health and Development. - New York : Nova Science Publishers, Inc.. - 9781624171291 - 9781624171369 ; , s. 207-225
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- We are interested in the long-term health consequences associated with severe starvation and war trauma, and whether certain “age windows” exist when exposure to such events are particularly harmful. The siege of Leningrad (now St. Petersburg) during World War II provided an opportunity to study this. For 872 days, German troops prevented supplies from reaching Leningrad. Simultaneously, there was a food blockade and a steady and merciless bombardment by shells from guns and from the air. The first winter, 1941/42, represents the most severe food shortage, amounting to mass starvation or semi-starvation. Our late colleague, Professor Dimitri Shestov, had suffered the consequences of the Leningrad siege as a boy and believed that it had taken a toll on people beyond its immediate short- and medium-range consequences. He was particularly concerned about its long-term consequences for circulatory disease. A 1973 US-Soviet agreement, the so called Lipid Research Clinics Collaboration, gave him an opportunity to study this. From 1975 to 1982 men and women living in Leningrad (now St. Petersburg) were randomly sampled and invited to examine their health and cardiovascular functioning. Dimitri Shestov added a simple question to this examination: “Were you in Leningrad during the blockade?” A third of the participants were. They had experienced peak starvation (in January 1942) at ages 1-31 (women) or 6-26 (men). The mortality follow-up began immediately after the first clinical examinations in 1975 and continued for three decades, until the end of 2005. Our analyses show that the siege of Leningrad, particularly when experienced in puberty, has had long-term effects on blood pressure both in men and women.We also found a raised IHD and stroke risk among those men. This was partly mediated via blood pressure but not by any other measured biological, behavioral, or social factors. Girls experiencing the siege around puberty suffered an elevated risk of dying from breast cancer later in life. The fact that the effect of siege exposure is modified by the age at exposure is highly interesting from a scientific point of view. It may suggest that a reprogramming of physiological systems can occur at specific age windows in response to starvation and/or war trauma. The team that worked from 1975-2005 to collect clinical information and death certificates for participants in the study included Svetlana Plavinskaya, born in Leningrad during the siege. Dimitri Shestov and Svetlana Plavinskaya died in 2010 and 2011, respectively. We dedicate this chapter to their memory.
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