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HPV-based screening for cervical cancer among women 55-59 years of age
Örebro University, School of Health Sciences. Dept. of Women's Health.
Örebro University, School of Health Sciences. Dept. of Laboratory Medicine.ORCID iD: 0000-0001-9992-266x
Örebro University, School of Medical Sciences. Dept. of Laboratory Medicine.ORCID iD: 0000-0003-2317-5738
Örebro University, School of Medical Sciences. Dept. of Laboratory Medicine.ORCID iD: 0000-0001-6881-237X
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. Vol. 14, no 6, article id e0217108
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:oru:diva-74701DOI: 10.1371/journal.pone.0217108ISI: 000471587000007PubMedID: 31199811Scopus ID: 2-s2.0-85067434997OAI: oai:DiVA.org:oru-74701DiVA, id: diva2:1325714
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
In thesis
1. Cervical screening with primary HPV: from research to clinical effectiveness
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

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Bergengren, LovisaLillsunde-Larsson, GabriellaHelenius, GiselaKarlsson, Mats G.

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