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Bergengren, Lovisa
Publications (8 of 8) Show all publications
Bergengren, L. (2020). Cervical screening with primary HPV: from research to clinical effectiveness. (Doctoral dissertation). Örebro: Örebro University
Open this publication in new window or tab >>Cervical screening with primary HPV: from research to clinical effectiveness
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Organized cervical screening has greatly reduced the incidence of cervical cancer where implemented. Human papilloma virus (HPV) is the cause of cervical cancer, and in later years, convincing evidence has led to cervical screening with HPV as the primary method being implemented around the world. The overall aim of this thesis is to improve cervical screening, with focus on HPV screening.

Papers I–III were performed with focus on postmenopausal women. Women aged, 55–59 years, excluded from the screening with a normal cytology cervical sample were found to have a high-risk HPV (hrHPV) prevalence of 5.5% in paper II. In a follow-up sample, 56% (71/126) had a persistent infection with the same genotype. Nineteen per cent of the women had dysplasia, where the majority of the high-grade squamous intraepithelial lesions (HSILs) were associated with HPV types other than HPV 16/18.

Women 55-59 has a lower attendance rate in the study region, and since self-sample has been proven to increase attendance, paper I was performed to compare self-sample and professionally collected samples in these postmenopausal women. The concordance between the sampling methods was 83%, and both tests detected all histological HSILs. When including a study with older women (aged 70 years) in paper III, 23% of histological HSILs were found in hrHPV-positive women.

Paper IV is a scientific evaluation of an implemented HPV-based screening programme, comparing clinical effectiveness and cost with cytology screening. More HSIL+ were detected in the new programme but at a higher cost than the old cytology-based programme. The screening visits for sampling accounted for two thirds of the costs.

Altogether, the results indicate the importance of having a negative HPVtest before exiting screening. Data also present the necessity to find biomarkers that are more specific than cytology and HPV 16/18 for triaging women with hrHPV to further follow-up, both among postmenopausal women and other age groups when screening with HPV, since many women without HSIL are coming for clinical follow-up and treatment. Extending the screening interval between hrHPV-negative tests as well as implementing selfsampling to a greater extent can be important changes, since two thirds of the costs in the programme come from screening visits for sampling.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2020. p. 85
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 209
Keywords
Cervical cancer, screening, human papillomavirus (HPV), HPV prevalence, HPV genotypes, precancerous lesion, HSIL, self-sampling, postmenopausal women, health economy
National Category
Surgery
Identifiers
urn:nbn:se:oru:diva-80231 (URN)978-91-7529-331-8 (ISBN)
Public defence
2020-05-15, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2020-02-27 Created: 2020-02-27 Last updated: 2020-04-24Bibliographically approved
Bergengren, L., Karlsson, M. & Helenius, G. (2020). Prevalence of HPV and pathological changes among women 70 years of age, 10 years after exclusion from the Swedish cervical cancer screening program. Cancer Causes and Control, 31(4), 377-381
Open this publication in new window or tab >>Prevalence of HPV and pathological changes among women 70 years of age, 10 years after exclusion from the Swedish cervical cancer screening program
2020 (English)In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 31, no 4, p. 377-381Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Örebro County introduced an updated screening program 2016 with primary HPV test for women over 30 years and prolonged screening, increasing the cut-off age from 56-60 to 64-70. The aim of this study was to investigate the prevalence of HPV genotypes and their correlation to histological changes in women, 10 years after exclusion from the screening program, due to an eventual implementation of a catch-up program including all women aged 60-70.

METHODS: All women in Örebro County, born 1,946 (n = 1,968), were invited to a liquid-based cell sample with primary HPV screening. Samples were analyzed for hrHPV mRNA and positive samples were genotyped. hrHPV positive women were offered to do a conization.

RESULTS: Out of 809 participants, 31 (3.8%) were hrHPV positive, of these 22 did a conization. Histologically, 5/22 (23%) had LSIL and 5/22 (23%) had HSIL. Normal histology was found in 12/22 (55%). The most prevalent genotypes were HPV 16, 33, 52, 56, and 68. Of the women with HSIL, one case of cervical cancer was confirmed in a recone biopsy after 4 months.

CONCLUSION: The study showed considerable prevalence of hrHPV and histologically confirmed LSIL/HSIL. These data led to catch-up screening for women between 60 and 70 years when overlapping two screening strategies.

Place, publisher, year, edition, pages
Springer, 2020
Keywords
Cervical cancer, HPV genotypes, HPV prevalence, Older women, Screening
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-80175 (URN)10.1007/s10552-020-01278-0 (DOI)000516473600001 ()32076907 (PubMedID)2-s2.0-85079750054 (Scopus ID)
Note

Funding Agency:

Region Örebro County Research Committee and Örebro University Hospital Research Foundation  OLL-576341 OLL-616292 OLL-639751 OLL-811061

Available from: 2020-02-25 Created: 2020-02-25 Last updated: 2020-04-23Bibliographically approved
Bergengren, L., Lillsunde-Larsson, G., Helenius, G. & Karlsson, M. G. (2019). HPV-based screening for cervical cancer among women 55-59 years of age. PLoS ONE, 14(6), Article ID e0217108.
Open this publication in new window or tab >>HPV-based screening for cervical cancer among women 55-59 years of age
2019 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 6, article id e0217108Article in journal (Refereed) Published
Abstract [en]

AIM: Many cervical cancers occurs among women over 65 and prevalence of HPV genotypes in this age cohort is sparingly studied. One aim of this study was to study the prevalence and distribution of HPV genotypes in women 55-59 years, with normal cytology when exiting the screening program. Secondly, HPV clearance as well as the value of HPV genotyping and/or liquid based cytology as triage tests for identifying histological dysplasia among women with persistent HPV was studied.

METHODS: Women that exited the screening program with normal cytology, between the years 2012-2014, in Örebro County, Sweden, were invited to this study. A total of 2946 samples were analyzed with a broad-spectrum assay to detect both hrHPV and lrHPV in order to investigate the distribution of genotypes. In the consent group, women with a positive hrHPV test were offered a follow-up test and a cone biopsy for histological confirmation, and a follow up sample 6 months post cone.

RESULTS: The overall prevalence of hrHPV was 7.4% and 59% of them remained hrHPV positive in a follow-up test after 12 months. A total of 99 women had a cone biopsy done, where 19% showed histological dysplasia. HPV 53 was the most common genotype, and among women with histology confirmed LSIL or HSIL, HPV 31 was most common. A positive hrHPV result showed a PPV of 25% for LSIL+ and 12.5%for HSIL+. Using detection of HPV 16/18 genotypes as a triage test for hrHPV positive tests, indicated FNR for histological LSIL+ and HSIL+ of 94% and 87.5% respectively, whilst triage based on cervical cytology had a FNR of 69% for LSIL+ and 37.5% for HSIL+.

CONCLUSION: The most common hrHPV genotypes among women 55-59 years of age were non HPV16/18 genotypes, and in this population, these genotypes represented most of the histological verified HSIL lesions. This result does not support the proposition of a HPV 16/18 triaging test after a positive hrHPV test as a marker of histological HSIL+ cervical lesions in women over 55 years of age. Similarly, cytological triage after a positive hrHPV showed no additional benefit in this population. Specific triaging tests should be validated to follow post-menopausal women with a positive hrHPV test.

Place, publisher, year, edition, pages
PLOS, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-74701 (URN)10.1371/journal.pone.0217108 (DOI)000471587000007 ()31199811 (PubMedID)2-s2.0-85067434997 (Scopus ID)
Note

Funding Agencies:

Region Örebro County Research Committee  

Örebro University Hospital Research Foundation  

BBMRI.se 

Available from: 2019-06-17 Created: 2019-06-17 Last updated: 2020-04-23Bibliographically approved
Helenius, G., Lillsunde-Larsson, G., Bergengren, L., Kaliff, M. & Karlsson, M. (2019). Preliminary data from a Swedish self-sampling study in postmenopausal women. In: : . Paper presented at EUROGIN 2019 – International Multidisciplinary HPV Congress, Monte Carlo, Monaco, December 4-7, 2019.
Open this publication in new window or tab >>Preliminary data from a Swedish self-sampling study in postmenopausal women
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2019 (English)Conference paper, Poster (with or without abstract) (Other academic)
Abstract [en]

Background: An updated screening algorithm was introduced in Sweden 2015. Primary HPV test for women >30 years old and a prolonged screening with the last test after 64 years of age were some of the changes. In the region of Örebro County, the previous cut-off age was 60 years and with a screening interval of 5 years, women left their last sample when they were 55-59 years old. In the shift between two screening programs, a group of women, 60-64 years old, that left the program 5-10 years ago were now included in the new screening. For re-inclusion, a two year long program was formed to catch-up this group of women and screen them according to the new screening algorithm. At the same time a research project investigating self-sampling was launched. At the same time as the women were invited for a last screening sample they were also asked to participate in a study where they should take a vaginal self-test up to one week after their ordinary screening sample was taken by a midwife.

Method: Postmenopausal women between 64-70 years was included in the study. HPV status in samples from midwife sampling (MS) was compared to self-sampling (SS) samples. HPV was analyzed using HPV Aptima and all HPV positive samples, independent of sampling method, was triaged with cytology and followed-up according to national guidelines.

Results: So far, 585 women with paired samples have been included in the study. In the MS, 4% of the women are positive for hrHPV compared to 11% in the SS group. In 486/585 women, the results of the two samples are concordant. Among the non-concordant samples (13%), 62% were positive in SS and negative in MS. The opposite, negative in SS and positive in MS were seen in 4% of the samples. Among the MS negative samples, 32% were invalid in SS. Cytology was used as a triage test for HPV positive women, both for MS and SS. Of 23 hrHPV positive, 18 had normal cytology, 2 ASCUS, 1 LSIL and 1 HSIL. In the samples with abnormal cytology, 4/5 were hrHPV positive in both SS and MS. One sample was positive in SS but negative in MS.

Discussion: In this age group, more women are hrHPV positive in SS compared to MS. This is in line with what other have seen. Among the very few hrHPV positive samples with abnormal cytology, the majority was hrHPV positive in both MS and SS. But since cytology is a poor triage marker in this age group clinical follow-up is needed before the effectiveness of the both sampling methods can be concluded.

National Category
Medical and Health Sciences Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:oru:diva-77781 (URN)
Conference
EUROGIN 2019 – International Multidisciplinary HPV Congress, Monte Carlo, Monaco, December 4-7, 2019
Available from: 2019-11-05 Created: 2019-11-05 Last updated: 2020-02-03Bibliographically approved
Bergengren, L., Kaliff, M., Lillsunde-Larsson, G., Karlsson, M. & Helenius, G. (2018). Comparison between professional sampling and self-sampling for HPV-based cervical cancer screening among postmenopausal women. International Journal of Gynecology & Obstetrics, 142(3), 359-364
Open this publication in new window or tab >>Comparison between professional sampling and self-sampling for HPV-based cervical cancer screening among postmenopausal women
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2018 (English)In: International Journal of Gynecology & Obstetrics, ISSN 0020-7292, E-ISSN 1879-3479, Vol. 142, no 3, p. 359-364Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To investigate whether self-sampling is as reliable as professional sampling for HPV testing and genotype detection among postmenopausal women.

METHODS: In the present prospective cross-sectional study, women in Örebro County, Sweden, who had high-risk HPV (hrHPV) and normal cytology results in exit screening tests conducted in between January 1, 2012, and December 31, 2014, were invited to follow-up screenings between February 24, 2015 and May 15, 2015, that included professional sampling and self-sampling. HPV genotypes were identified by a DNA-based assay that could detect 35 HPV genotypes. Findings between the different sampling methods were compared.

RESULTS: Of 143 women who participated, 119 returned a self-sample. Completely concordant results were observed in 67 of these samples when both hrHPV and low-risk HPV genotypes were analyzed. Overall, 99 (83.2%) women had the same clinically relevant finding from both sampling methods. Twenty women had discordant hrHPV results (hrHPV detected in 10 self-samples vs 10 professionally collected samples; Cohen κ 0.66, 95% confidence interval 0.53-0.80). There was no significant difference between the two sampling methods for clinically significant infections (P>0.99) or extended genotyping (P=0.827).

CONCLUSION: Postmenopausal women could be offered self-sampling devices to increase screening-program coverage while maintaining test quality.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2018
Keywords
Cervical cancer, HPV, Postmenopausal women, Professional sampling, Screening, Self-sample
National Category
Cancer and Oncology Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:oru:diva-67134 (URN)10.1002/ijgo.12538 (DOI)000440652000017 ()29856071 (PubMedID)2-s2.0-85051073715 (Scopus ID)
Note

Funding Agencies:

Region Örebro County Research Committee  

Örebro University Hospital Research Foundation  

BBMRI.se

Available from: 2018-06-04 Created: 2018-06-04 Last updated: 2020-04-23Bibliographically approved
Helenius, G., Ottestig, E., Kaliff, M., Lillsunde-Larsson, G., Karlsson, M. & Bergengren, L. (2018). Distribution of HPV-genotypes in a Swedish screening population. In: : . Paper presented at Eurogin 2018 International multidisciplinary HPV Congress, Lisabon Portugal, December 2-5, 2018.
Open this publication in new window or tab >>Distribution of HPV-genotypes in a Swedish screening population
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-69348 (URN)
Conference
Eurogin 2018 International multidisciplinary HPV Congress, Lisabon Portugal, December 2-5, 2018
Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2018-10-08Bibliographically approved
Lillsunde Larsson, G., Kaliff, M., Bergengren, L., Karlsson, M. G. & Helenius, G. (2016). HPV Genotyping from the high risk mRNA Aptima assay: a direct approach using DNA from Aptima sample tubes. Journal of Virological Methods, 235, 80-84
Open this publication in new window or tab >>HPV Genotyping from the high risk mRNA Aptima assay: a direct approach using DNA from Aptima sample tubes
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2016 (English)In: Journal of Virological Methods, ISSN 0166-0934, E-ISSN 1879-0984, Vol. 235, p. 80-84Article in journal (Refereed) Published
Abstract [en]

The underlying cause of cervical cancer is infection with the human papilloma virus (HPV) and HPV testing can be used for cervical cancer screening. The Aptima HPV assay from Hologic is an mRNA HPV test used to identify clinically relevant infections but the method does not discriminate between the different high risk genotypes. The aim of the current study was to evaluate if analyzed Aptima sample transfer tubes could be used as a source for HPV genotyping, using sample DNA. Study samples (n=108); were HPV-tested with mRNA Aptima assay and in parallel DNA was extracted and genotyped with Anyplex II HPV28. Analyzed mRNA Aptima tubes were thereafter used as source for a second DNA extraction and genotyping. Using mRNA Aptima result as reference, 90% of the samples (35/39) were high risk positive with the Anyplex II HPV28. Cohen's kappa 0.78 (95% CI: 0.66-0.90), sensitivity 0.90 (95% CI: 0.76-0.97) and specificity 0.90 (95% CI: 0.80-0.96). Two discordant samples carried low-risk genotypes (HPV 82 and HPV 44) and two were negative. DNA-genotyping results, in parallel to and after mRNA testing, were compared and differed significantly (McNemar test: P=0.021) possibly due to sample extraction volume difference. Cohen's kappa 0.81 (95% CI: 0.70-0.92), sensitivity 0.85 (95% CI: 0.74-0.93) and specificity 0.98 (95% CI: 0.88-1.00). In conclusion, analyzed mRNA Aptima sample tubes could be used as a source for DNA HPV genotyping. The sample volume used for extraction needs to be further explored.

Place, publisher, year, edition, pages
Amsterdam, Netherlands: Elsevier, 2016
Keywords
HPV, Genotype, mRNA testing, DNA‐testing
National Category
Microbiology Biochemistry and Molecular Biology
Research subject
Microbiology
Identifiers
urn:nbn:se:oru:diva-50487 (URN)10.1016/j.jviromet.2016.05.015 (DOI)000382417800012 ()27233487 (PubMedID)2-s2.0-84973131436 (Scopus ID)
Available from: 2016-05-30 Created: 2016-05-30 Last updated: 2018-09-11Bibliographically approved
Bergengren, L., Flodström, L., Flodström, C., Fadl, H., Udumyan, R., Karlsson, M. & Helenius, G.Effectiveness and costs of implemented primary HPV cervical screening: a populationbased cohort study.
Open this publication in new window or tab >>Effectiveness and costs of implemented primary HPV cervical screening: a populationbased cohort study
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(English)Manuscript (preprint) (Other academic)
National Category
Surgery
Identifiers
urn:nbn:se:oru:diva-81302 (URN)
Available from: 2020-04-23 Created: 2020-04-23 Last updated: 2020-04-24Bibliographically approved
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