| 1. |
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| 2. |
- 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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| 3. |
- Andersson, Emil, et al.
(författare)
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Low pericyte coverage of endometrial microvessels in heavy menstrual bleeding correlates with the microvessel expression of VEGF-A.
- 2015
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Ingår i: International Journal of Molecular Medicine. - : Spandidos Publications. - 1791-244X .- 1107-3756. ; 35:2, s. 433-438
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Tidskriftsartikel (refereegranskat)abstract
- A prospective clinical study was carried out to investigate whether endometrial microvessels in patients with idiopathic heavy menstrual bleeding (HMB) of endometrial origin (HMB-E) are fragile due to low pericyte coverage. Idiopathic HMB-E is characterized by large endothelial cell gaps related to the microvascular overexpression of vascular endothelial growth factor (VEGF)-A and VEGF receptors 1-3. A total of 10 women with a normal menstrual cycle and a history of HMB of <5 years, and 17 healthy women with a normal menstrual cycle were recruited from the Karolinska University Hospital. Blood samples were obtained for hormone analysis and coagulation tests. Endometrial biopsies were collected in the proliferative or in the secretory phase. Pericyte coverage was assessed using immunohistochemical staining for smooth muscle actin-α (SMAα) and by image analysis (microvascular density) of endometrial biopsies from 10 patients with HMB-E and 17 healthy ovulating women (control subjects). Previously published data on endothelial cell gap size and the expression of VEGF receptors were used. Although microvascular density did not differ between the patients with HMB-E and the control subjects, the number of SMAα-positive microvessels in the proliferative phase was significantly (P=0.005) lower in the patients with HMB-E than in the control subjects. Moreover, the number of SMAα-positive microvessels in the control subjects was significantly fewer in the secretory (P=0.04) than in the proliferative phase, whereas this number did not differ among the patients with HMB-E regardless of phase. A significant negative correlation was observed between the number of VEGF-A-positive microvessels and microvessels with pericyte coverage (r=0.8; P=0.04). Finally, the endothelial cell layer was significantly thicker in the patients with HMB-E than in the control subjects. Thus, the upregulation of VEGF-A in idiopathic HMB-E is associated with a low pericyte coverage during the proliferative phase of intense angiogenesis, which may confer vessel fragility, possibly leading to excessive blood loss.
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| 4. |
- 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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| 5. |
- 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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| 6. |
- Andersson, Sonia, et al.
(författare)
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Results of cytology and high-risk human papillomavirus testing in females with cervical adenocarcinoma in situ
- 2013
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 6:1, s. 215-219
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Tidskriftsartikel (refereegranskat)abstract
- The incidence rates of cervical adenocarcinoma have been increasing over the last two decades, contrary to those of squamous cell carcinoma. This trend is particularly evident among females aged <40 years and has occurred despite extensive cytology-based screening programs. The aim of the present retrospective database study was to investigate adenocarcinoma in situ (AIS) with respect to previous cytological results, high-risk (HR) human papillomavirus (HPV) infections and histological results from AIS-adjacent squamous mucosa. Databases were used to identify 32 female patients with AIS treated for various conditions between 2009 and 2012 at the Department of Gynecology, Uppsala University Hospital (Uppsala, Sweden) and previous cytological, HPV and histological results. Of the individuals in the study, 64.3% had a previously recorded cytological result showing squamous cell abnormalities; five had glandular cell abnormalities (18%) and two had AIS (7.1%). Among the patients with available HPV results, 95% were HR-HPV-positive; HPV18/45 predominated (77%), followed by HPV16 (27%). The patients with multiple HPV infections were aged <= 32 years, while patients aged >= 38 years were only infected with HPV18/45. All but three patients had cervical intraepithelial neoplasia (CIN) in the AIS-adjacent squamous mucosa, 79% of which was CIN2 or worse. The present retrospective database study suggests that AIS is detected at screening mainly due to simultaneous squamous precursor lesions and that HPV18/45 infection is an increasing co-factor for AIS in older patients. HPV analyses of glandular precursor lesions aid in the identification of female individuals at risk of progression to invasive disease, and thus have a favorable effect on adenocarcinoma prevention, together with vaccination.
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| 7. |
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| 8. |
- Andersson, Sonia, et al.
(författare)
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Uneven distribution of human papillomavirus 16111 cervical carcinoma in situ and squamous cell carcinoma in older females : A retrospective database study
- 2014
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 8:4, s. 1528-1532
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus (HPV) 16 is the dominant cofactor in cervical cancer development. The present report investigated the age-specific prevalence of HPV16 in cervical carcinoma in situ (CIS) in females attending organised cervical cancer screening. A retrospective observational study was performed based on individual data from two databases. A total of 162 females aged between 20 and 65 years from Uppsala County, Sweden with CIS and an HPV test conducted between 2010 and 2011, preceding or concomitant to CIS diagnosis, were included. Females with cervical squamous cell carcinoma (SCC; n=35) were used for comparison. In total, 96% (n=156) of females with CIS were positive for high-risk HPV; HPV16 was the most prevalent (44.5%), followed by HPV33/52/58 (19.5%), HPV31 (13.1%) and HPV18145 (9.5%). HPV16 was most frequently detected in females with CIS aged between 20 and 29 years (73.6%) and least frequently detected in those aged between 50 and 65 years (33.3%), with a statistically significant age-specific difference (P=0.001). Among the HPV16-positive females, multiple infections were most frequent in the younger age groups. The prevalence of HPV16 in females with CIS decreased with age, whereas a high prevalence of HPV16 remained in females with SCC. These results may indicate that HPV16 has increased oncogenic potential in older females.
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| 9. |
- Belkic, Karen, et al.
(författare)
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Imaging surveillance programs for women at high breast cancer risk in Europe : Are women from ethnic minority groups adequately included?
- 2015
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Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 47:3, s. 817-839
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Tidskriftsartikel (refereegranskat)abstract
- Women from ethnic minority groups, including immigrants and refugees are reported to have low breast cancer (BC) screening rates. Active, culturally-sensitive outreach is vital for increasing participation of these women in BC screening programs. Women at high BC risk and who belong to an ethnic minority group are of special concern. Such women could benefit from ongoing trials aimed at optimizing screening strategies for early BC detection among those at increased BC risk. Considering the marked disparities in BC survival in Europe and its enormous and dynamic ethnic diversity, these issues are extremely timely for Europe. We systematically reviewed the literature concerning European surveillance studies that had imaging in the protocol and that targeted women at high BC risk. The aim of the present review was thereby to assess the likelihood that women at high BC risk from minority ethnic groups were adequately included in these surveillance programs. Twenty-seven research groups in Europe reported on their imaging surveillance programs for women at increased BC risk. The benefit of strategies such as inclusion of magnetic resonance imaging and/or more intensive screening was clearly documented for the participating women at increased BC risk. However, none of the reports indicated that sufficient outreach was performed to ensure that women at increased BC risk from minority ethnic groups were adequately included in these surveillance programs. On the basis of this systematic review, we conclude that the specific screening needs of ethnic minority women at increased BC risk have not yet been met in Europe. Active, culturally-sensitive outreach is needed to identify minority women at increased BC risk and to facilitate their inclusion in on-going surveillance programs. It is anticipated that these efforts would be most effective if coordinated with the development of European-wide, population-based approaches to BC screening.
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| 10. |
- Belkić, Karen, et al.
(författare)
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Predictors of treatment failure for adenocarcinoma in situ of the uterine cervix : Up to 14 years of recorded follow-up
- 2022
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 24:4
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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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