| 1. |
- Alder, Susanna, et al.
(författare)
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Incomplete excision of cervical intraepithelial neoplasia as a predictor of the risk of recurrent disease : a 16-year follow-up study
- 2020
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier. - 0002-9378 .- 1097-6868. ; 222:2, s. 172.e1-172.e12
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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)
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Acceptance of Self-Sampling Among Long-Term Cervical Screening Non-Attenders with HPV-Positive Results : Promising Opportunity for Specific Cancer Education
- 2021
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Ingår i: Journal of Cancer Education. - : Springer. - 0885-8195 .- 1543-0154. ; 36:1, s. 126-133
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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)
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Age, margin status, high-risk human papillomavirus and cytology independently predict recurrent high-grade cervical intraepithelial neoplasia up to 6 years after treatment
- 2021
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 22:3
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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. |
- Razumova, Zoia, et al.
(författare)
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The Prognostic Role of LRIG Proteins in Endometrial Cancer
- 2021
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Ingår i: Cancers. - Stockholm : MDPI. - 2072-6694. ; 13:6
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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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| 5. |
- Wersäll, Ofra Castro, et al.
(författare)
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PGC1α and VDAC1 expression in endometrial cancer
- 2021
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Ingår i: Molecular and clinical oncology. - : Spandidos Publications. - 2049-9450 .- 2049-9469. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- Endometrial cancer (EC) is one of the ten most common gynecological cancers. As in most cancers, EC tumour progression involves alterations in cellular metabolism and can be associated with, for instance, altered levels of glycolytic enzymes. Mitochondrial functions and proteins are known to serve key roles in tumour metabolism and progression. The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1α) is a major regulator of mitochondrial biogenesis and function, albeit of varying prognostic value in different cancers. The voltage-dependent anion channel type 1 (VDAC1) regulates apoptosis as well as metabolite import and export over the mitochondrial outer membrane, and is often used for comparative quantification of mitochondrial content. Using immunohistochemistry, the present study examined protein expression levels of PGC1α and VDAC1 in tumour and paired benign tissue samples from 148 patients with EC, in order to examine associations with clinical data, such as stage and grade, Ki-67, p53 status, clinical resistance and overall survival. The expression levels of both PGC1α and VDAC1, as well as a PGC1α downstream effector, were significantly lower in tumor tissues than in benign tissues, suggesting altered mitochondrial function in EC. However, Kaplan-Meier, log rank and Spearman's rank correlation tests revealed that their expression was not correlated with survival and clinical data. Therefore, PGC1α and VDAC1 are not of major prognostic value in EC.
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| 6. |
- Wersäll, Ofra Castro, et al.
(författare)
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Which dietary and everyday life habits affect endometrial cancer recurrence? The machine gives the answer
- 2020
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Ingår i: International Journal of Gynecological Cancer. - : Lippincott Williams & Wilkins. - 1048-891X .- 1525-1438. ; 30:Suppl. 4, s. A32-A33
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction/Background: The increased life expectancy and westernization of the lifestyle are considered the major contributors to a sustainable rise in endometrial cancer (EC) rates. The factors predicting EC recurrence include patient age and tumour characteristics, such as type, differentiation, and depth of invasion. At the same time, recent studies testify the impact of meal and exercises on the course of various diseases. What are the food preferences and activities that could influence the ultimate risk of EC relapse and death?Methodology: The study included 481 women who previously underwent a hysterectomy due to EC at Karolinska University Hospital. The participants filled an extensive questionnaire on their dietary habits and everyday routines. Related clinical data was obtained through the National e-health system. It resulted in a large dataset with more than 180 variables, which was processed using the Random Survival Forest (RSF) approach. The latter is applied to a right-censored data and uses a collection of decision trees to rank the variables by their importance for the occurrence of an event. The top-ranked variables were further investigated with the Cox proportional hazards model. Analyzes were performed using the RandomForestSRC package for Python.Results: The consumption of the fried potatoes significantly increased the risk of EC relapse and death [HR=8.62 (2.22–33.56), p=0.002; HR=6.00 (1.06–34.01), p=0.043, respectively), the latter persisted after adjustment for body mass index, age and smoking status. Besides, each additional serving of sweetened soda drinks increased the risk of death [3.262 (1.834–5.800), p=0.0001]. In contrast, physical activity was beneficial with each additional Metabolic Equivalent per day decreasing the risk of death by 7.3% [HR=0.927 (0.892–0.964), p< 0.0001).Conclusion: We hypothesise that the fried potatoes’ detrimental effect may be related to the acrylamide, which is formed in starch-rich foods under high-temperature conditions. It acts as a carcinogen and endocrine disruptor, causing the endometrial hyperplasia and EC in animal studies. Sweetened beverages cause a rise in insulin, which in turn inhibits sex-hormone binding protein. This results in higher levels of circulating free oestrogens. Also, insulin has mitogenic and anti-apoptotic properties, further inducing the endometrium proliferation. The favorable influence of regular physical activity on EC relapse and death is in accordance with previous studies, including recent meta-analysis.Therefore, we encourage women treated for EC to consider reducing sweetened beverages and fried potatoes consumption and increasing physical activity.
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| 7. |
- Östensson, Ellinor, et al.
(författare)
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Self-sampling for high-risk human papillomavirus as a follow-up alternative after treatment of high-grade cervical intraepithelial neoplasia
- 2021
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 21:4
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Tidskriftsartikel (refereegranskat)abstract
- Women treated for high-grade cervical-intraepithelial-neoplasia (CIN) require long-term follow-up with high-risk human-papillomavirus (HPV) testing. Self-sampling for HPV is well-accepted among these patients, but its role in follow-up for this group requires investigation. The present study examined how well HPV findings from self-sampled vaginal (VSS) and urine specimens correctly identified women from this cohort with recurrent CIN2+ compared with samples collected by clinicians. At 1st post-conization follow-up, 531 patients (99.8% participation) gave urine samples, performed VSS, underwent colposcopy with punch biopsy of visible lesions and clinician-collected cervical sampling for HPV analysis and liquid-based cytology. A total of 113 patients with positive HPV and/or abnormal cytology at 1st follow-up underwent 2nd follow-up. At 1st follow-up, all patients with recurrent CIN3 had positive HPV results by all methods. Clinician sampling and VSS revealed HPV16 positivity in 50% of recurrent cases and urine sampling revealed HPV16 positivity in 25% of recurrent cases. At 2nd follow-up, all 7 newly-detected CIN2/3 recurrences were associated with HPV positivity on VSS and clinician-samples. Only clinician-collected samples detected HPV positivity for two adenocarcinoma-in-situ recurrences, and both were HPV18 positive. A total of 77 patients had abnormal cytology at 1st follow-up, for which HPV positivity via VSS yielded highest sensitivity. The HPV findings were positive from VSS in 12 patients with high-grade squamous-intraepithelial-lesions (HSIL), and 11 patients with HSIL had positive HPV findings in clinician-collected and urine samples. All methods for assessing HPV presence yielded significant age-adjusted odds ratios for predicting abnormal lesions at 1st follow-up. For overall HPV results, Cohen's kappa revealed substantial agreement between VSS and clinician sampling, and moderate agreement between urine and clinician sampling. Clinician sampling and VSS were highly concordant for HPV16. Insofar as the pathology was squamous (not glandular), VSS appeared as sensitive as clinician sampling for HPV in predicting outcome among the present cohort. Since VSS can be performed at home, this option can maximize participation in the required long-term follow-up for these women at high-risk.
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