| 1. |
- Aarnio, Riina, 1971-, et al.
(författare)
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Cost-effectiveness analysis of repeated self-sampling for HPV testing in primary cervical screening: a randomized study
- 2020
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407 .- 1471-2407. ; 20:1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundHuman papillomavirus (HPV) testing is recommended in primary cervical screening to improve cancer prevention. An advantage of HPV testing is that it can be performed on self-samples, which could increase population coverage and result in a more efficient strategy to identify women at risk of developing cervical cancer. Our objective was to assess whether repeated self-sampling for HPV testing is cost-effective in comparison with Pap smear cytology for detection of cervical intraepithelial neoplasia grade 2 or more (CIN2+) in increasing participation rate in primary cervical screening.MethodsA cost-effectiveness analysis (CEA) was performed on data from a previously published randomized clinical study including 36 390 women aged 30–49 years. Participants were randomized either to perform repeated self-sampling of vaginal fluid for HPV testing (n = 17 997, HPV self-sampling arm) or to midwife-collected Pap smears for cytological analysis (n = 18 393, Pap smear arm).ResultsSelf-sampling for HPV testing led to 1633 more screened women and 107 more histologically diagnosed CIN2+ at a lower cost vs. midwife-collected Pap smears (€ 228 642 vs. € 781 139). ConclusionsThis study projected that repeated self-sampling for HPV testing increased participation and detection of CIN2+ at a lower cost than midwife-collected Pap smears in primary cervical screening. Offering women a home-based self-sampling may therefore be a more cost-effective alternative than clinic-based screening.
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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, 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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| 4. |
- 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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| 5. |
- Ranhem, Cecilia, et al.
(författare)
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Expression of LRIG proteins as possible prognostic factors in primary vaginal carcinoma
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary vaginal carcinoma (PVC) is a rare malignancy. Established prognostic factors include tumour stage and age at diagnosis. The leucine-rich repeats and immunoglobuline-like domains (LRIG)-1 protein functions as a tumour suppressor, but less is known about the functions of LRIG2 and LRIG3. The present study aimed to evaluate the expression of LRIG proteins and analyse their possible associations with clinical characteristics and survival in a cohort of PVC patients.Methods: We used immunohistochemistry to investigate LRIG1, LRIG2, and LRIG3 expression in tumour samples from a consecutive cohort of 70 PVC patients. The association between LRIG protein expression and clinical characteristics and cancer-specific survival was investigated using univariate and multivariate analyses.Results: The majority of PVC patients (72%) had > 50% LRIG1-and LRIG2-positive cells, and no or low LRIG3-positive cells. HPV status was significantly correlated with LRIG1 expression (p = 0.0047). Having high LRIG1 expression was significantly correlated with superior cancer-specific survival in univariate and multivariate analyses. LRIG2 and LRIG3 expression did not significantly correlate with clinical characteristics or survival.Conclusion: LRIG1 expression might be of interest as a prognostic marker in PVC patients, whereas the role of LRIG2 and LRIG3 expression remains to be clarified.
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| 6. |
- Razumova, Zoia, et al.
(författare)
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Cadmium intake as a prognostic factor in endometrial cancer : a Swedish cohort-based study
- 2022
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Ingår i: Nutrition and Cancer. - Stockholm : Karolinska Institutet, Dept of Women's and Children's Health. - 0163-5581 .- 1532-7914.
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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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| 7. |
- 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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| 8. |
- Silfverschiöld, Maria, et al.
(författare)
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Societal cost of oropharyngeal cancer by human papillomavirus status, cancer stage, and subsite
- 2019
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- Background The incidence of oropharyngeal cancer (OPC) is increasing, particularly human papillomavirus (HPV)-associated OPC. The aim of this study was to specify the total societal cost of OPC by HPV status, cancer stage, and subsite using a bottom-up cost-of-illness approach. Methods We analyzed 121 consecutive patients with OPC from the Southern Health Care Region of Sweden. We estimated the direct medical costs and indirect costs (e.g., disease-related morbidity and premature death) from 1 month prior to OPC diagnosis until 3 years after treatment completion. Results The mean total cost per patient was 103 386 for HPV-positive and 120 244 for HPV-negative OPC. Eighty-one percent of the patients analyzed were HPV-positive: Accordingly, HPV-positive OPC represented 79% of the total cost of OPC. The mean total cost of stage I, II, III, IVA, IVB, and IVC, regardless of HPV status, was 59 424, 57 000, 69 246, 115 770, 234 459, and 21 930, respectively, of which indirect costs were estimated at 22 493 (37.8%), 14 754 (25.9%), 28 681 (41.4%), 67 107 (58%), 166 280 (70.9%), and 0. Tonsillar cancer represented 64% of OPC, with a mean total cost of 117 512 per patient. Conclusion The societal cost of OPC is substantial. HPV-associated OPC comprises 79% of the total cost of this disease. The data presented in this study may be used in analytical models to aid decision makers in determining the potential value of gender-neutral HPV vaccination.
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| 9. |
- Östensson, Ellinor
(författare)
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Health economic aspects of cervical cancer screening
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Healthcare reform and rising costs are driving demand for resource efficiency to facilitate better-informed healthcare decisions. Health economics represent an interdisciplinary set of tools and concepts to assess the value of everyday decisions, taken in complex healthcare settings, to improve healthcare. Many alternative screening methods are currently available, but knowledge about costs and the value of potential health gains is inadequate. The aims of the thesis were to study the efficiency in the allocation of resources to cervical cancer screening of importance for setting priorities: the cost of the most prevalent Human Papillomavirus (HPV) related diseases namely cervical dysplasia, cervical cancer and genital warts, modeling the cost-effectiveness of cervical cancer screening and exploring knowledge of HPV, compliance with screening and its correlates. In one study, we estimated the costs from a societal perspective, of the HPV-related diseases namely cervical dysplasia, cervical cancer and genital warts. Results provided an estimate of €108 million annually showing a significant economic burden on the Swedish welfare system appointed by the most prevalent HPV-related diseases attributable to HPV 6, 11, 16 and 18 infections. A Markov model was developed to simulate the natural history of HPV, cervical dysplasia and cervical cancer to project the cost-effectiveness of HPV self-sampling within the framework of the Swedish organized screening program. Projected results showed that screening with conventional cytology up to age 35 and thereafter screening with HPV self-sampling at home with five-year time intervals between screening opportunities is potentially cost-effective compared with either no screening or with current cytology based screening practice. A decision analytic model was developed to evaluate cost-effectiveness of follow-up with HPV triage compared with repeat cytology and immediate colposcopy with biopsy on women with index smear diagnosis of ASCUS and LSIL within the Swedish organized screening program. Model results showed that immediate colposcopy with biopsy was a cost effective follow-up strategy compared with the alternatives. Given the improvement in HPV testing techniques at lower costs, HPV triage can become a cost-effective alternative for follow-up of minor cytological abnormalities. A descriptive study approach was used to assess possible barriers to and facilitators of cervical cancer screening by estimating time and travel costs and other direct non-medical costs incurred in clinic-based screening, investigating compliance with screening and reasons for noncompliance, determining women’s knowledge of human papillomavirus (HPV), and investigating correlates of HPV knowledge and compliance with screening. Via self-administered questionnaires, data were obtained from 1 510 women attending the Swedish organized cervical cancer screening program. The study concluded that time and travel costs of clinic-based screening can be substantial, may influence overall cost effectiveness of screening programs and constitute barriers to screening. Women with knowledge of HPV and who did not take time off work to attend screening were more likely to comply with screening. Altogether, this thesis has contributed new health economic data on the societal cost of HPV related diseases; cervical dysplasia, cervical cancer and genital warts on a national level, and patient-level data of indirect costs and other direct non-medical costs for women attending the Swedish organized screening program. This together with data on women's knowledge about HPV and their compliance with screening are valuable information for further policy decisions on revising the organized screening program. By assessing the impact of HPV-related diseases in terms of costs is one important step towards efficient allocation of resources to reduce the economic burden of these diseases. These data are also valuable contribution to economic evaluations, providing information for resource allocation when choosing among different screening methods to reduce disease burden, as well as contributing to knowledge of compliance with population-based preventive health programs.
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| 10. |
- 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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