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Sökning: WFRF:(Mints Miriam 1958 ) > Tidskriftsartikel

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1.
  • Alder, Susanna, et al. (författare)
  • Incomplete excision of cervical intraepithelial neoplasia as a predictor of the risk of recurrent disease : a 16-year follow-up study
  • 2020
  • Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier. - 0002-9378 .- 1097-6868. ; 222:2, s. 172.e1-172.e12
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Women treated for high-grade cervical intraepithelial neoplasia (CIN, grade 2 or 3) are at elevated risk of developing cervical cancer. Suggested factors identifying women at highest risk for recurrence post-therapeutically include incomplete lesion excision, lesion location, size and severity, older age, treatment modality and presence of high-risk human papilloma virus (hrHPV) after treatment. This question has been intensively investigated over decades, but there is still substantial debate as to which of these factors or combination of factors most accurately predict treatment failure.OBJECTIVES: In this study, we examine the long-term risk of residual/recurrent CIN2+ among women previously treated for CIN2 or 3 and how this varies according to margin status (considering also location), as well as comorbidity (conditions assumed to interact with hrHPV acquisition and/or CIN progression), post-treatment presence of hrHPV and other factors.STUDY DESIGN: This prospective study included 991 women with histopathologically-confirmed CIN2/3 who underwent conization in 2000-2007. Information on the primary histopathologic finding, treatment modality, comorbidity, age and hrHPV status during follow-up and residual/recurrent CIN2+ was obtained from the Swedish National Cervical Screening Registry and medical records. Cumulative incidence of residual/recurrent CIN2+ was plotted on Kaplan-Meier curves, with determinants assessed by Cox regression.RESULTS: During a median of 10 years and maximum of 16 years follow-up, 111 patients were diagnosed with residual/recurrent CIN2+. Women with positive/uncertain margins had a higher risk of residual/recurrent CIN2+ than women with negative margins, adjusting for potential confounders (hazard ratio (HR)=2.67; 95% confidence interval (CI): 1.81-3.93). The risk of residual/recurrent CIN2+ varied by anatomical localization of the margins (endocervical: HR=2.72; 95%CI: 1.67-4.41) and both endo- and ectocervical (HR=4.98; 95%CI: 2.85-8.71). The risk did not increase significantly when only ectocervical margins were positive/uncertain. The presence of comorbidity (autoimmune disease, human immunodeficiency viral infection, hepatitis B and/or C, malignancy, diabetes, genetic disorder and/or organ transplant) was also a significant independent predictor of residual/recurrent CIN2+. In women with positive hrHPV findings during follow-up, the HR of positive/uncertain margins for recurrent/residual CIN2+ increased significantly compared to women with hrHPV positive findings but negative margins.CONCLUSIONS: Patients with incompletely excised CIN2/3 are at increased risk of residual/recurrent CIN2+. Margin status combined with hrHPV results and consideration of comorbidity may increase the accuracy for predicting treatment failure.
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2.
  • Andersson, Sonia, et al. (författare)
  • Acceptance of Self-Sampling Among Long-Term Cervical Screening Non-Attenders with HPV-Positive Results : Promising Opportunity for Specific Cancer Education
  • 2021
  • Ingår i: Journal of Cancer Education. - : Springer. - 0885-8195 .- 1543-0154. ; 36:1, s. 126-133
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aims to investigate acceptance of vaginal self-sampling for high-risk human papilloma virus (HPV) among long-term screening non-attenders at increased cervical cancer risk and to identify leverage points to promote screening adherence among these women. Forty-three long-term screening non-attenders performed home vaginal self-sampling for HPV, had positive HPV results, and subsequently attended gynecologic examination. Sixteen (37.2%) had high-grade cervical intraepithelial neoplasia (CIN2 or 3), and two had invasive cervical cancer. Forty-one of these women completed a questionnaire concerning Specific Knowledge about HPV, CIN, and cervical cancer, potential barriers to screening and views about self-sampling. Results were compared with 479 women treated for CIN2+ who attended gynecologic follow-up and also performed self-sampling. Significant multivariate predictors of long-term non-attender status compared with referents were low Specific Knowledge, high confidence in self-sampling, and potential barriers-refraining from activity to attend gynecologic examination, needing another's help to attend, and long travel time. Non-attenders citing fear/refraining from gynecologic examination as why they preferred self-sampling significantly more often had lowest Specific Knowledge compared with other non-attenders. All non-attenders could envision themselves doing self-sampling again while only 74% of referents endorsed this statement (p = 0.0003). We conclude that HPV self-sampling is an acceptable option for women at increased cervical cancer risk who have been long-term screening non-attenders. Educational outreach to enhance Specific Knowledge about HPV, CIN and cervical cancer is critical. Those non-attenders who explicitly avoid gynecologic examinations need special attention. Trial Registry: Clinicaltrials.gov NCT02750124.
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3.
  • Andersson, Sonia, et al. (författare)
  • Age, margin status, high-risk human papillomavirus and cytology independently predict recurrent high-grade cervical intraepithelial neoplasia up to 6 years after treatment
  • 2021
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 22:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study aimed to identify the factors that independently contribute to disease recurrence among women first-time treated for high-grade cervical intraepithelial neoplasia (CIN) during 4-6 years of follow-up. Overall, 529 of 530 eligible patients participated; these patients all attended a 1st follow-up appointment similar to 6 months post-conization, at which time high-risk human-papillomavirus (HPV) testing, liquid-based cytology and colposcopy were performed. Full data on margin excision status, other aspects of initial treatment and comorbidity were obtained. At least one subsequent follow-up was attended by 88% of patients. A total of 22 recurrent cases were detected during follow-up. Detected recurrence was the outcome of focus for multiple logistic regression analysis, with odds ratios (OR) and 95% confidence intervals (CI) computed. Four significant independent risk factors were identified: Age 45 years or above (OR=3.5, 95% CI=1.3-9.9), one or both unclear or uncertain margins (OR=5.3, 95% CI=2.0-14.2), positive HPV at 1st follow-up (OR=5.8, 95% CI=2.0-16.8), and abnormal cytology at 1st follow-up (OR=3.9, 95% CI=1.4-11.0). Bivariate analysis revealed that persistent HPV positivity was associated with recurrence (P<0.01). These findings indicated that incomplete excision of the CIN lesion may warrant more intensive subsequent screening, regardless of early post-conization HPV findings. Although early post-conization positive HPV was a powerful, independent predictor of recurrent high-grade CIN, over one-third of the patients with detected recurrence had a negative early post-conization HPV finding. These patients returned for routine screening, at which time, in most cases, HPV status was positive, thus indicating the need for repeated HPV evaluation. Especially during the on-going pandemic, home vaginal self-sampling is recommended. Particular attention is required for women aged >= 45 years. In addition, although not statistically significant, relevant comorbidities, especially autoimmune conditions, warrant consideration in clinical decision-making. Women who have been treated for high-grade CIN are at risk for recurrent disease and progression to cervical cancer; therefore, they require careful, individualized follow-up to avoid these adverse consequences.
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4.
  • Belkić, Karen, et al. (författare)
  • Predictors of treatment failure for adenocarcinoma in situ of the uterine cervix : Up to 14 years of recorded follow-up
  • 2022
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 24:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The incidence of adenocarcinoma-in-situ (AIS) of the uterine cervix is rising, with invasive adenocarcinoma becoming increasingly common relative to squamous cell carcinoma. The present study reviewed a cohort of 84 patients first-time treated by conization for histologically-confirmed AIS from January 2001 to January 2017, to identify risk factors associated with recurrent/persistent AIS as well as progression to invasive cervical cancer. Nearly 80% of the patients were age 40 or younger at conization. Endocervical and ectocervical margins were deemed clear in 42 of the patients. All but two patients had ≥1 follow-up, with post-conization high-risk human papilloma virus (HPV) results documented in 52 patients. Altogether, 12 histopathologically-confirmed recurrences (14.3%) were detected; two of these patients had microinvasive or invasive carcinoma. In three other patients cytology showed AIS, but without recorded histopathology. Eight patients underwent hysterectomy for incomplete resection very soon after primary conization; they were not included in bivariate or multivariate analyses. Having ≥1 post-follow-up positive HPV finding yielded the highest sensitivity for histologically-confirmed recurrence: 87.5 [95% confidence interval (CI) 47.4-99.7]. Current or historical smoking status provided highest specificity: 94.4 (95% CI 72.7-99.9) and overall accuracy: 88.0 (95% CI 68.8-97.5) for histologically-confirmed recurrence. With multiple logistic regression (MLR), adjusting for age at conization and abnormal follow-up cytology, positive HPV18 was the strongest predictor of histologically-confirmed recurrence (P<0.005). Having ≥2 positive HPV results also predicted recurrence (P<0.02). Any unclear margin yielded an odds ratio 7.21 (95% CI 1.34-38.7) for histologically-confirmed recurrence adjusting for age, but became non-significant when including abnormal cytology in the MLR model. The strong predictive value of HPV, particularly HPV18 and persistent HPV positivity vis-à-vis detected recurrence indicated that regular HPV testing for patients treated for AIS is imperative. In conclusion, furthering a participatory approach, including attention to smoking with encouragement to attend needed long-term follow-up, can better protect these patients at high risk for cervical cancer.
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5.
  • Castro Wersäll, Ofra, et al. (författare)
  • Dietary Habits and Daily Routines as Prognostic Factors in Endometrial Cancer : A Machine Learning Approach
  • 2023
  • Ingår i: Nutrition and Cancer. - : Routledge. - 0163-5581 .- 1532-7914. ; 75:1, s. 310-319
  • Tidskriftsartikel (refereegranskat)abstract
    • Endometrial cancer (EC) is becoming more common worldwide, primarily due to an increase in life expectancy and obesity. As several modifiable factors may affect EC incidence and progression, we aimed to elucidate how dietary habits and daily routines influence recurrence and survival among women with EC, using a Random Survival Forest (RSF) approach. 481 women who previously underwent hysterectomy due to EC completed two extensive questionnaires on dietary habits and daily routines, and we used RSF to identify risky or protective variables. Among the 186 variables considered, consumption of sugar-sweetened beverages and fried potatoes increased the risk of EC recurrence and death, while physical activity decreased the risk of death. We conclude that RSF is a suitable approach to study survival in multivariable datasets.
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6.
  • Govorov, Igor, et al. (författare)
  • STK4 protein expression pattern follows different trends in endometrioid and serous endometrial adenocarcinoma upon tumor progression
  • 2022
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • In a previous study, we showed that serine/threonine-protein kinase 4 (STK4) is involved in the control on proliferation and migration of endometrial cancer (EC) cells in vitro. In the present paper, we studied STK4 expression in EC tissues from a large cohort of patients to determine whether STK4 can serve as a marker for the aggressiveness and prognosis of EC. Tissue samples from patients with EC were examined for tumor type, grade, and stage. The STK4 protein expression in EC cells was assessed by immunohistochemistry and related to clinicopathological data of patients, such as progression and patient survival rate. The STK4 mRNA levels and its relation to the survival rate were analyzed also in publicly available databases. The STK4 gene expression was low at both, the mRNA and protein levels in EC, especially in serous tumors. Comparison of STK4 expression with the patient survival rate shows that the higher expression is associated with worse prognosis in serous EC, while no such dependence was found in endometrioid EC. Hence, the determination of the SKT4 expression pattern could be used as a putative prognostic marker for serous EC.
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7.
  • Govorov, Igor, et al. (författare)
  • Upregulation of PKN1 as a Prognosis Biomarker for Endometrial Cancer
  • 2022
  • Ingår i: Cancer Control. - : Sage Publications. - 1073-2748 .- 1526-2359. ; 29
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Several markers of survival among endometrial cancer (EC) patients have been proposed, namely, the oncoprotein stathmin, RAF kinase inhibitor (RKIP), Cyclin A, GATA-binding protein 3 (GATA3), and growth and differentiation factor-15 (GDF-15). Their elevated expression correlated significantly with a high stage, serous papillary/clear cell subtypes, and aneuploidy. In a previous study, we reported the elevated expression of the serine/threonine protein kinase N1 (PKN1) in cancerous cells. In the present paper, we studied PKN1 expression in EC tissues from a large cohort of patients, to determine whether PKN1 can serve as a marker for the aggressiveness and prognosis of EC, and/or as a marker of survival among EC patients.METHODS: Tissue samples from EC patients were examined retrospectively for tumor type, tumor size, FIGO stage and grade, depth of invasion in the myometrium, and presence of lymph node metastasis. The PKN1 protein expression in EC cells was assessed by immunohistochemistry. PKN1 mRNA levels were analyzed in publicly available databases, using bioinformatic tools.RESULTS: We found that expression of PKN1 at the mRNA and proteins levels tended to increase in high-grade EC samples (P = .0001 and P = .06, respectively). In addition, patients with metastatic disease had higher PKN1 mRNA levels (P = .02). Moreover, patients with high PKN1 expression could be characterized by poorer survival.CONCLUSIONS: We have shown a trend of the higher PKN1 expression levels in EC patients with poor prognosis. Therefore, PKN1 might be considered as a candidate prognostic marker for EC.
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8.
  • Razumova, Zoia, et al. (författare)
  • Cadmium intake as a prognostic factor in endometrial cancer : a Swedish cohort-based study
  • 2022
  • Ingår i: Nutrition and Cancer. - Stockholm : Karolinska Institutet, Dept of Women's and Children's Health. - 0163-5581 .- 1532-7914.
  • Tidskriftsartikel (refereegranskat)abstract
    • Metalloendocrinology is a new interdisciplinary field, which was established due to the importance of connections between inorganic chemicals and hormonal mechanisms. The role of cadmium in hormone-related tumors is an excellent example of this connection, as cadmium mimics estrogen in the human body. Since endometrial cancer (EC) is hormonerelated, it is well-suited for assessing the estrogenic effects of cadmium. Therefore, the present study aims to explore the role of dietary cadmium intake in the progression-free survival (PFS) and overall survival (OS) in women with EC. Dietary cadmium intake was estimated based on a large cohort of Swedish women (n ¼ 416) with EC. Median dietary cadmium intake was then analyzed in relation to different tumor characteristics and clinical outcomes. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Median daily dietary cadmium intake in the cohort was 13.1 lg (interquartile range 25%-75%¼6.4). High dietary cadmium intake (lg/day) was associated with significantly decreased OS in the study cohort (HR ¼ 0.956, 95% CI ¼ 0.914- 1.001, p ¼ 0.05). Dietary cadmium intake was not associated with PFS (HR ¼ 0.975, 95% CI ¼ 0.924-1.028, p ¼ 0.348). Therefore, our results indicate that high dietary cadmium intake could be associated with poor outcome in women with EC.
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9.
  • Razumova, Z., et al. (författare)
  • The prognostic role of LRIG proteins in endometrial cancer
  • 2019
  • Ingår i: International Journal of Gynecological Cancer. - : BMJ Publishing Group Ltd. - 1048-891X .- 1525-1438. ; 29, s. A358-A358
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction/Background Endometrial cancer (EC) is the most common gynaecological malignancy in Sweden. The disease has several prognostic factors. Still, the high amount of EC develops into more aggressive forms of cancer, even though being first considered to be non-aggressive. The LRIG proteins are a family of three integral surface proteins that have a similar domain organisation. The current study evaluated the role of LRIG proteins as prognostic biomarkers in EC.Methodology The cohort included 75 women who underwent a hysterectomy and bilateral salpingo-oophorectomydue to EC at the Department of Women's and Children's Health, Karolinska University Hospital Solna between 2007 and 2012. The expression of LRIG1, LRIG2, and LRIG3 in paraffin biopsies was analysed by immunohistochemistry (IHC) with applying specific polyclonal antibodies. Evaluation of immunostainings was performed by two senior pathologists without knowledge of the disease outcome. The percentage of positive cells was divided in two groups with median percentage as cut off to have two groups of equal size included in the statistical analysis. Then the groups were assessedin connection with different tumour characteristics and clinical outcomes of EC.Results The majority of women in the cohort had >50% LRIG1-, LRIG2-, and LRIG3-positive cells. Among 6047 person-months of follow-up a total, of 14 incident cases of relapsed EC were identified. A statistically significant association between high LRIG3 expression and superior overall survival was observed in the cohort (IRR=2.559, 95 CI=1.054–6.210, p=0.038). LRIG1 and LRIG2 expression did not significantly correlate with survival.Conclusion Our results support the hypothesis that LRIG3 expression may have a prognostic role in women with EC. The significance of LRIG1 and LRIG2 expression remains to be clarified.
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10.
  • Razumova, Zoia, et al. (författare)
  • The Prognostic Role of LRIG Proteins in Endometrial Cancer
  • 2021
  • Ingår i: Cancers. - Stockholm : MDPI. - 2072-6694. ; 13:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Endometrial cancer (EC) is the most common gynecologic malignancy in Sweden and it has various prognostic factors. The LRIG family is a group of three integral surface proteins with a similar domain organization. The study aimed to explore LRIG family as prognostic factor proteins in EC. The initial study cohort included 100 women with EC who were treated at the Department of Women’s and Children’s Health, Karolinska University Hospital Solna, between 2007 and 2012. We assessed the associations between LRIG protein expression and type, grade, and stage of EC, as well as progression-free and overall survival. Immunohistochemistry results revealed that most women in the analytical sample had >50% LRIG1-, LRIG2- and LRIG3-positive cells. A statistically significant association was observed between having a high number of LRIG3-positive cells and superior overall survival (incidence rate ratio = 0.977; 95% confidence interval: 0.958–0.996, p = 0.019). Moreover, positive LRIG3 staining of the cell membrane was associated with reducing in the risk of death (hazard ratio = 0.23; 95% confidence interval: 0.09–0.57). Our results show that LRIG3 expression might be a prognostic factor in EC. The role of LRIG1 and LRIG2 expression remains to be further investigated.
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