| 1. |
- Elfström, Klara Miriam
(författare)
-
Optimizing cervical cancer prevention through screening and HPV vaccination
- 2015
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Effective primary and secondary prevention tools exist for cervical cancer in the form of human papillomavirus (HPV) vaccines and cervical screening. In order to maximize the impact of prevention strategies in Sweden and European countries, this thesis sought to investigate the long-term effectiveness of different screening strategies and the long-term risk associated with HPV infections, the organization and quality of existing screening programs, and the effectiveness of alternative vaccination strategies. HPV-based screening has been evaluated using intermediate outcomes while its effectiveness against cancer had not been fully examined. In Study I, the European randomized controlled trials (RCT) of screening methods were pooled to investigate the relative efficacy of HPV-based versus cytology-based screening for the prevention of invasive cervical cancer. We found that HPV-based screening provides 60-70% greater protection against invasive cervical cancer compared to cytology-based screening. To address the issue of determining intervals for HPV-based screening and to investigate concerns regarding overdiagnosis with HPV-based screening, a long-term follow-up of the Swedescreen RCT was completed in Study II. The longitudinal performance of cytology- and HPV-based screening was explored and the sensitivity for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) of HPV testing at 5 years of follow-up was similar to that of cytology testing at 3 years. Over 13 years of follow-up, we found that the increased sensitivity of HPV screening for CIN2+ reflects earlier diagnosis rather than overdiagnosis and low long-term risks among HPV negative women suggest that extending screening intervals with HPV-based screening would be possible. The incidence of low-grade cervical lesions is increasing in Sweden. Low-grade lesions require follow-up, creating a burden to the woman and the healthcare system. Examining the long-term HPV-type-specific risk for atypical squamous cells of undetermined significance (ASCUS), low grade squamous intraepithelial lesions (LSIL) and cervical intraepithelial neoplasia grade 1 (CIN1) is of interest to inform screening and vaccination programs. In Study III, we investigated the long-term type-specific absolute risk, population attributable proportion, and incidence rate ratios for ASCUS/LSIL by HPV type. The type-specific IRRs for ASCUS/LSIL were high in the first screening round but decreased over subsequent screening rounds. Type 16 contributed to the greatest proportion of low-grade lesions in the population followed by type 31. Most lesions were caused by new infections and found in the first screening round. Organized, population-based screening with quality assurance (QA) at all levels is recommended by the European Commission to ensure equity and cost-effectiveness of programs. Significant differences in cervical cancer incidence and mortality exist between European countries. In Study IV, a comprehensive questionnaire was developed and circulated among EU/EFTA countries to map current organization of programs and quality assurance efforts to understand prevention activities and inform future guidelines. The findings show that organized efforts for QA, monitoring and evaluation differed between and within countries, making it difficult to compare program effectiveness. HPV vaccination is underway in most European countries but efforts to organize and standardize vaccination program monitoring and evaluation are limited. Using the same questionnaire as in Study IV, we collected detailed information on HPV vaccination programs in EU/EFTA countries for Study V. Our findings suggest that the monitoring being performed varies across programs with regard to level of detail and the organization and quality of programs differ. There was a strong interest in the survey which affirms the significance of the issues addressed and the importance of continuing to evaluate program development and strengthen surveillance of vaccination program efforts. Since the introduction of HPV vaccination, vaccine prices have decreased significantly making upscaling of vaccination efforts more attractive. Specifically, questions have arisen regarding vaccination of older girls and extending the vaccination program to boys. Using a dynamic transmission model, in Study VI we compared different vaccination strategies and assessed the resilience of the vaccination program to a reduction in coverage. We found that vaccination strategies including an extended catch-up of women and introducing male vaccination may accelerate the prevalence reduction of vaccine HPV types among women. Further, including males in routine vaccination improved the resilience of vaccination programs. Taken together, the results of these studies seek to add evidence for the incremental optimization of prevention programs. The challenge will be translating research findings into practice and ensuring that programs have the tools they need to effectively monitor and evaluate changes.
|
|
| 2. |
- Forslund, Ola, et al.
(författare)
-
HPV-mRNA and HPV-DNA detection in samples taken up to seven years before severe dysplasia of cervix uteri
- 2019
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 144:5, s. 1073-1081
-
Tidskriftsartikel (refereegranskat)abstract
- Randomized clinical trials using human papillomavirus (HPV) DNA testing have found increased protection against cervical cancer and HPV-based screening is globally recommended for women ≥30 years of age. HPV-mRNA is a promising alternative target for cervical screening tests, but assessing equivalence requires longitudinal evaluation over at least the length of a screening interval. Our aim is to analyze the longitudinal sensitivity of HPV-mRNA and HPV-DNA in cervical samples taken up to 7 years before severe cervical intraepithelial neoplasia or worse (CIN3+). From a population-based cohort of 95,023 women in Sweden, cervical samples were frozen at −80°C between May 2007 and January 2012. Registry linkages identified that 1,204 of these women had CIN3+ 4 months to 7 years after enrolment. Baseline samples were analyzed for HPV-mRNA (Aptima, Hologic) and for HPV-DNA (Cobas 4800, Roche) and results from both tests obtained for 1,172 women. For both women <30 and ≥ 30 years, HPV-mRNA had similar sensitivity for CIN3+ as HPV-DNA (p = 0.0217 and p = 0.0123 in noninferiority testing for at least 90% relative sensitivity, respectively). Among women ≥30 years, the longitudinal sensitivities for CIN3+ occurring 5–7 years later were comparable [76.3% (95% CI: 65.8%–84.3%) and 82.5% (95% CI: 72.6%–89.4%)] as were the longitudinal negative predictive values for absence of CIN3+ [99.97% (95% CI: 99.95–99.98) and 99.98% (95% CI: 99.96–99.99)], for the HPV-mRNA and HPV-DNA test. In conclusion, HPV-mRNA testing has similar longitudinal sensitivity as HPV-DNA, implying that HPV-mRNA testing can safely be used for cervical screening.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Hortlund, Maria, et al.
(författare)
-
Cervical cancer screening in Sweden 2014-2016.
- 2018
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 13:12
-
Tidskriftsartikel (refereegranskat)abstract
- To enable incremental optimization of screening, regular reporting of quality indicators is required.To report key quality indicators and basic statistics about cervical screening in Sweden.We collected individual level data on all cervical cytologies, histopathologies, human papillomavirus tests and all invitations for cervical screening in Sweden during 2013-2016.There were over 2,278,000 cervical samples collected in Sweden in 2014-2016. Organized samples (resulting from an invitation) constituted 69% of samples. The screening test coverage of all resident women aged 23-60 was 82%. The coverage has slowly increased for >10 years. There is large variability between counties (from 71% to 92%) over time. There were 25,725 women with high-grade lesions in cytology during 2013-2015. Only 96% of these women had a follow-up histopathology within a year. Cervical cancer incidence showed an increasing trend.Key quality indicators such as population coverage and follow-up rates were stable or improving, but there was nevertheless an unexplained cervical cancer increase.
|
|
| 6. |
- Klevebro, Susanna, et al.
(författare)
-
Risk of SARS-CoV-2 exposure among hospital healthcare workers in relation to patient contact and type of care
- 2021
-
Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 49:7, s. 707-712
-
Tidskriftsartikel (refereegranskat)abstract
- We aimed to assess prevalence of IgG antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and factors associated with seropositivity in a large cohort of healthcare workers (HCWs). Methods: From 11 May until 11 June 2020, 3981 HCWs at a large Swedish emergency care hospital provided serum samples and questionnaire data. Presence of IgG antibodies to SARS-CoV-2 was measured as an indicator of SARS-CoV-2 exposure. Results: The total seroprevalence was 18% and increased during the study period. Among the seropositive HCWs, 11% had been entirely asymptomatic. Participants who worked with COVID-19 patients had higher odds for seropositivity: adjusted odds ratio 1.96 (95% confidence intervals 1.59–2.42). HCWs from three of the departments managing COVID-19 patients had significantly higher seroprevalences, whereas the prevalence among HCWs from the intensive care unit (also managing COVID-19 patients) was significantly lower. Conclusions: HCWs in contact with SARS-CoV-2 infected patients had a variable, but on average higher, likelihood for SARS-CoV-2 infections.
|
|
| 7. |
- Lei, Jiayao, et al.
(författare)
-
High-risk human papillomavirus status and prognosis in invasive cervical cancer : A nationwide cohort study
- 2018
-
Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 15:10
-
Tidskriftsartikel (refereegranskat)abstract
- Background: High-risk human papillomavirus (hrHPV) infection is established as the major cause of invasive cervical cancer (ICC). However, whether hrHPV status in the tumor is associated with subsequent prognosis of ICC is controversial. We aim to evaluate the association between tumor hrHPV status and ICC prognosis using national registers and comprehensive human papillomavirus (HPV) genotyping.Methods and findings: In this nationwide population-based cohort study, we identified all ICC diagnosed in Sweden during the years 2002-2011 (4,254 confirmed cases), requested all archival formalin-fixed paraffin-embedded blocks, and performed HPV genotyping. Twenty out of 25 pathology bio-banks agreed to the study, yielding a total of 2,845 confirmed cases with valid HPV results. Cases were prospectively followed up from date of cancer diagnosis to 31 December 2015, migration from Sweden, or death, whichever occurred first. The main exposure was tumor hrHPV status classified as hrHPV-positive and hrHPV-negative. The primary outcome was all-cause mortality by 31 December 2015. Five-year relative survival ratios (RSRs) were calculated, and excess hazard ratios (EHRs) with 95% confidence intervals (CIs) were estimated using Poisson regression, adjusting for education, time since cancer diagnosis, and clinical factors including age at cancer diagnosis and International Federation of Gynecology and Obstetrics (FIGO) stage. Of the 2,845 included cases, hrHPV was detected in 2,293 (80.6%), and we observed 1,131 (39.8%) deaths during an average of 6.2 years follow-up. The majority of ICC cases were diagnosed at age 30-59 years (57.5%) and classified as stage IB (40.7%). hrHPV positivity was significantly associated with screen-detected tumors, young age, high education level, and early stage at diagnosis (p < 0.001). The 5-year RSR compared to the general female population was 0.74 (95% CI 0.72-0.76) for hrHPV-positive cases and 0.54 (95% CI 0.50-0.59) for hrHPV-negative cases, yielding a crude EHR of 0.45 (95% CI 0.38-0.52) and an adjusted EHR of 0.61 (95% CI 0.52-0.71). Risk of all-cause mortality as measured by EHR was consistently and statistically significantly lower for cases with hrHPV-positive tumors for each age group above 29 years and each FIGO stage above IA. The difference in prognosis by hrHPV status was highly robust, regardless of the clinical, histological, and educational characteristics of the cases. The main limitation was that, except for education, we were not able to adjust for lifestyle factors or other unmeasured confounders.Conclusions: In this study, women with hrHPV-positive cervical tumors had a substantially better prognosis than women with hrHPV-negative tumors. hrHPV appears to be a biomarker for better prognosis in cervical cancer independent of age, FIGO stage, and histological type, extending information from already established prognostic factors. The underlying biological mechanisms relating lack of detectable tumor hrHPV to considerably worse prognosis are not known and should be further investigated.
|
|
| 8. |
- Lei, Jiayao, et al.
(författare)
-
HPV vaccination and the risk of invasive cervical cancer
- 2020
-
Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 383:14, s. 1340-1348
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The efficacy and effectiveness of the quadrivalent human papillomavirus (HPV) vaccine in preventing high-grade cervical lesions have been shown. However, data to inform the relationship between quadrivalent HPV vaccination and the subsequent risk of invasive cervical cancer are lacking. METHODS We used nationwide Swedish demographic and health registers to follow an open population of 1,672,983 girls and women who were 10 to 30 years of age from 2006 through 2017. We assessed the association between HPV vaccination and the risk of invasive cervical cancer, controlling for age at follow-up, calendar year, county of residence, and parental characteristics, including education, household income, mother’s country of birth, and maternal disease history. RESULTS During the study period, we evaluated girls and women for cervical cancer until their 31st birthday. Cervical cancer was diagnosed in 19 women who had received the quadrivalent HPV vaccine and in 538 women who had not received the vaccine. The cumulative incidence of cervical cancer was 47 cases per 100,000 persons among women who had been vaccinated and 94 cases per 100,000 persons among those who had not been vaccinated. After adjustment for age at follow-up, the incidence rate ratio for the comparison of the vaccinated population with the unvaccinated population was 0.51 (95% confidence interval [CI], 0.32 to 0.82). After additional adjustment for other covariates, the incidence rate ratio was 0.37 (95% CI, 0.21 to 0.57). After adjustment for all covariates, the incidence rate ratio was 0.12 (95% CI, 0.00 to 0.34) among women who had been vaccinated before the age of 17 years and 0.47 (95% CI, 0.27 to 0.75) among women who had been vaccinated at the age of 17 to 30 years. CONCLUSIONS Among Swedish girls and women 10 to 30 years old, quadrivalent HPV vaccination was associated with a substantially reduced risk of invasive cervical cancer at the population level.
|
|
| 9. |
|
|
| 10. |
- Sundström, Karin, et al.
(författare)
-
Follow-up of women with cervical cytological abnormalities showing atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion : a nationwide cohort study
- 2017
-
Ingår i: American Journal of Obstetrics and Gynecology. - : MOSBY-ELSEVIER. - 0002-9378 .- 1097-6868. ; 216:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion in abnormal cervical cytology among young women in cervical cancer screening is an increasing health burden, and comparative effectiveness studies of different management options for such diagnoses are needed. OBJECTIVE: The objective of the study was to compare the incidence of invasive cervical cancer, following different management options pursued after an atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion index smear. STUDY DESIGN: In this nationwide cohort study, we included all women aged 22-50 years and resident in Sweden 1989-2011 and with at least 1 cervical smear registered during the study period ( n = 2,466,671). Followup of a first atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion cytological diagnosis within 25 months was classified as repeat cytology, colposcopy/biopsy, or without further assessment. Incidence rate ratios and 95% confidence intervals of subsequent cervical cancer within 6.5 years following atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion were estimated using Poisson regression by age group and management strategy. RESULTS: Women managed with repeat cytology within 6 months after atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion cytology had a similar risk of cervical cancer compared with colposcopy/biopsy ( incidence rate ratio, 1.1, 95% confidence interval, 0.5-2.5, and incidence rate ratio, 2.0, 95% confidence interval, 0.6-6.5, respectively) among women aged 22-27 years. For women aged 28 years and older, women managed with repeat cytology had a higher risk for cervical cancer than women managed with colposcopy/biopsy. CONCLUSION: Our findings suggest that women with a first cytological diagnosis of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion up to age 27 years may indeed be safely followed up with repeat cytology within 6 months. A large amount of colposcopies that are currently performed in this group, therefore, could safely be discontinued.
|
|
