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Olovsson, Matts
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Publications (10 of 95) Show all publications
Abujrais, S., Olovsson, M., Ahnoff, M., Rasmusson, A., Larsson, A., Åkerfeldt, T. & Kultima, K. (2019). A sensitive method detecting trace levels of levonorgestrel using LC-HRMS.. Contraception, 100(3), 247-249
Open this publication in new window or tab >>A sensitive method detecting trace levels of levonorgestrel using LC-HRMS.
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2019 (English)In: Contraception, ISSN 0010-7824, E-ISSN 1879-0518, Vol. 100, no 3, p. 247-249Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To develop a high resolution mass spectrometry (HRMS) method to quantify levonorgestrel (LNG) in serum.

STUDY DESIGN: Levonorgestrel was extracted using solid phase extraction and measured using liquid chromatography (LC) HRMS.

RESULTS: Low limit of quantification (LLOQ) was 25pg/mL and low limit of detection (LLOD) was 12.5pg/mL. Precision and accuracy bias were<10%. LNG in serum samples from Mirena® users ranged between 37 to 219pg/mL (n=12). In eight out of 22 patients with suspected intrauterine device (IUD) expulsion LNG was detected (26 to 1272pg/mL).

CONCLUSION: A sensitive, fast and simple LC-HRMS method was developed to detect trace levels of LNG.

Keywords
High resolution mass spectrometry, Intrauterine device, Liquid chromatography, Lower limit of quantification, Solid phase extraction
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-388593 (URN)10.1016/j.contraception.2019.06.001 (DOI)000483452100015 ()31216423 (PubMedID)
Available from: 2019-07-02 Created: 2019-07-02 Last updated: 2019-10-17Bibliographically approved
Gustavsson, I. M., Aarnio, R., Myrnäs, M., Lindberg, J. H., Taku, O., Meiring, T., . . . Gyllensten, U. B. (2019). Clinical validation of the HPVIR high-risk HPV test on cervical samples according to the international guidelines for human papillomavirus DNA test requirements for cervical cancer screening. Virology Journal, 16(1), Article ID 107.
Open this publication in new window or tab >>Clinical validation of the HPVIR high-risk HPV test on cervical samples according to the international guidelines for human papillomavirus DNA test requirements for cervical cancer screening
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2019 (English)In: Virology Journal, ISSN 1743-422X, E-ISSN 1743-422X, Vol. 16, no 1, article id 107Article in journal (Refereed) Published
Abstract [en]

Background

The indicating FTA card is a dry medium used for collection of cervical samples. HPVIR is a multiplex real-time PCR test that detects 12 high-risk human papillomavirus types (hrHPV) and provides single genotype information for HPV16, − 31, − 35, − 39, − 51, − 56, and − 59 and pooled type information for HPV18/45 and HPV33/52/58. The aim of this study was to evaluate whether a strategy with cervical samples collected on the FTA card and subsequently analysed with the HPVIR test complies with the criteria of the international guidelines for a clinically validated method for cervical screening.

Methods

We performed a non-inferiority test comparing the clinical sensitivity and specificity of the candidate test (FTA card and HPVIR) with a clinically validated reference test (Cobas® HPV test) based on liquid-based cytology (LBC) samples. Two clinical samples (LBC and FTA) were collected from 896 participants in population-based screening. For evaluation of the specificity we used 799 women without ≥ CIN2, and for clinical sensitivity we used 67 women with histologically confirmed ≥ CIN2. The reproducibility was studied by performing inter- and intra-laboratory tests of 558 additional clinical samples.

Results

The clinical sensitivity and specificity for samples collected on the FTA card and analysed using the HPVIR test were non-inferior to samples analysed with the Cobas® HPV test based on LBC samples (non-inferiority test score, p = 1.0 × 10− 2 and p = 1.89 × 10− 9, respectively). Adequate agreement of > 87% was seen in both the intra- and inter-laboratory comparisons.

Conclusions

Samples collected on the indicating FTA card and analysed with HPVIR test fulfil the requirements of the international guidelines and can therefore be used in primary cervical cancer screening.

Keywords
HPV, DNA testing, Primary cervical cancer screening, International guidelines
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:uu:diva-394268 (URN)10.1186/s12985-019-1216-7 (DOI)000483382500001 ()31438976 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and WelfareSwedish Cancer Society
Available from: 2019-10-09 Created: 2019-10-09 Last updated: 2019-10-09Bibliographically approved
Enroth, S., Berggrund, M., Lycke, M., Broberg, J., Lundberg, M., Assarsson, E., . . . Gyllensten, U. B. (2019). High throughput proteomics identifies a high-accuracy 11 plasma protein biomarker signature for ovarian cancer. Communications biology, 2, Article ID 221.
Open this publication in new window or tab >>High throughput proteomics identifies a high-accuracy 11 plasma protein biomarker signature for ovarian cancer
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2019 (English)In: Communications biology, ISSN 2399-3642, Vol. 2, article id 221Article in journal (Refereed) Published
Abstract [en]

Ovarian cancer is usually detected at a late stage and the overall 5-year survival is only 30-40%. Additional means for early detection and improved diagnosis are acutely needed. To search for novel biomarkers, we compared circulating plasma levels of 593 proteins in three cohorts of patients with ovarian cancer and benign tumors, using the proximity extension assay (PEA). A combinatorial strategy was developed for identification of different multivariate biomarker signatures. A final model consisting of 11 biomarkers plus age was developed into a multiplex PEA test reporting in absolute concentrations. The final model was evaluated in a fourth independent cohort and has an AUC = 0.94, PPV = 0.92, sensitivity = 0.85 and specificity = 0.93 for detection of ovarian cancer stages I-IV. The novel plasma protein signature could be used to improve the diagnosis of women with adnexal ovarian mass or in screening to identify women that should be referred to specialized examination.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
Keywords
Diagnostic markers, Machine learning, Ovarian cancer
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-388611 (URN)10.1038/s42003-019-0464-9 (DOI)000472439200002 ()31240259 (PubMedID)
Funder
Swedish Foundation for Strategic Research Swedish Research CouncilSwedish Cancer SocietyVinnova
Note

These authors contributed equally: Stefan Enroth, Malin Berggrund

Available from: 2019-07-02 Created: 2019-07-02 Last updated: 2019-08-07Bibliographically approved
Berggrund, M., Enroth, S., Lundberg, M., Assarsson, E., Stålberg, K., Lindquist, D., . . . Gyllensten, U. (2019). Identification of Candidate Plasma Protein Biomarkers for Cervical Cancer Using the Multiplex Proximity Extension Assay. Molecular & Cellular Proteomics, 18(4), 735-743
Open this publication in new window or tab >>Identification of Candidate Plasma Protein Biomarkers for Cervical Cancer Using the Multiplex Proximity Extension Assay
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2019 (English)In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 18, no 4, p. 735-743Article in journal (Refereed) Published
Abstract [en]

Human papillomavirus (HPV) is recommended as the primary test in cervical cancer screening, with co-testing by cytology for HPV-positive women to identify cervical lesions. Cytology has low sensitivity and there is a need to identify biomarkers that could identify dysplasia that are likely to progress to cancer. We searched for plasma proteins that could identify women with cervical cancer using the multiplex proximity extension assay (PEA). The abundance of 100 proteins were measured in plasma collected at the time of diagnosis of patients with invasive cervical cancer and in population controls using the Olink Multiplex panels CVD II, INF I, and ONC II. Eighty proteins showed increased levels in cases compared with controls. We identified a signature of 11 proteins (PTX3, ITGB1BP2, AXIN1, STAMPB, SRC, SIRT2, 4E-BP1, PAPPA, HB-EGF, NEMO and IL27) that distinguished cases and controls with a sensitivity of 0.96 at a specificity of 1.0. This signature was evaluated in a prospective replication cohort with samples collected before, at or after diagnosis and achieved a sensitivity of 0.78 and a specificity 0.56 separating samples collected at the time of diagnosis of invasive cancer from samples collected prior to diagnosis. No difference in abundance was seen between samples collected prior to diagnosis or after treatment as compared with population controls, indicating that this protein signature is mainly informative close to time of diagnosis. Further studies are needed to determine the optimal window in time prior to diagnosis for these biomarker candidates.

National Category
Cancer and Oncology Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-383873 (URN)10.1074/mcp.RA118.001208 (DOI)000466934700009 ()30692274 (PubMedID)
Funder
Swedish Foundation for Strategic Research Swedish Research CouncilSwedish Cancer Society
Available from: 2019-06-14 Created: 2019-06-14 Last updated: 2019-06-14Bibliographically approved
Edelstam, G., Makdessi, L., Hagmar, M., Moberg, C., Olovsson, M. & Spira, J. (2019). Optimised gynaecological examination with a new pelvic examination chair. Sexual & Reproductive HealthCare, 19, 84-87
Open this publication in new window or tab >>Optimised gynaecological examination with a new pelvic examination chair
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2019 (English)In: Sexual & Reproductive HealthCare, ISSN 1877-5756, E-ISSN 1877-5764, Vol. 19, p. 84-87Article in journal (Refereed) Published
Abstract [en]

Objective: The present aim was to contribute to improving the traditional pelvic examination chair with vertical leg support and to evaluate patients' and examiners' experience of a new gyneacological and urological examination chair with heated upholstery.

Study design: A new gynaecological and urological examination chair was constructed with laterally adjustable leg support, a foot-plate and the perineum exposed only during the examination procedure. Patients (n = 131) with or without endometriosis were invited to participate in an anonymous questionnaire survey concerning how they experienced a gynaecological examination.

Main outcome measures: The patients and the gynaecologists who performed the examinations answered questionnaires evaluating the examination procedure in the traditional and in the new gynaecological and urological examination chair, respectively. The questionnaires asked about comfort, heating, integrity and the experience of pelvic examination with vertical or lateral leg support. The examination times were measured with a stopwatch.

Results: The majority of the answers (n = 131) were significantly (p < 0.05-0.001) in favour of the new concept with lateral leg support and with increased comfort and integrity. The average examination time was significantly shortened and the patients more relaxed in the new gynaecological and urological examination chair.

Conclusion: The traditional gynaecological chair with vertical leg support has remained basically unchanged for many years. The present study showed that the pelvic examination procedure can be significantly optimized with easy patient-friendly adaptations.

Keywords
Pelvic examination chair, Leg support, Comfort, Questionnaire, Examination
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-383882 (URN)10.1016/j.srhc.2019.01.001 (DOI)000465365500014 ()30928140 (PubMedID)
Funder
Vinnova, 2015-03834
Available from: 2019-05-29 Created: 2019-05-29 Last updated: 2019-05-29Bibliographically approved
Gustavsson, I. M., Aarnio, R., Berggrund, M., Lindberg, J. H., Sanner, K., Wikström, I., . . . Gyllensten, U. B. (2019). Randomised study of HPV prevalence and detection of CIN2+ in vaginal self-sampling compared to cervical specimens collected by medical personnel.. International Journal of Cancer, 144(1), 89-97
Open this publication in new window or tab >>Randomised study of HPV prevalence and detection of CIN2+ in vaginal self-sampling compared to cervical specimens collected by medical personnel.
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 1, p. 89-97Article in journal (Refereed) Published
Abstract [en]

We conducted a randomised study to compare vaginal self-sampling with assisted sampling by medical personnel on the cervix for HPV testing in primary screening. The first aim was to determine if the HPV prevalence is independent of sampling location (vagina versus cervix) and the person performing the sampling. The second aim was to evaluate if the two sampling strategies differed in the detection rate of CIN2+. In total, 19,523 women were randomised into two groups, with 9926 invited to perform self-sampling (SS arm) using the Rover VIBA-brush and 9597 offered assisted sampling using the cytobrush (AS arm). All samples were applied to the indicating FTA elute card and analysed for high-risk HPV using the hpVIR real-time PCR assay. The outcome for the first aim was HPV prevalence and for the second aim the number of CIN2+ based on histology. In the SS arm, 52.7% of invited women participated in the study, as compared to 34.2% in the AS arm. All samples contained sufficient amount of nuclear DNA for a valid HPV result, with vaginal samples having a higher DNA amount than cervical samples (p < 4.62 × 10-11 ). HPV prevalence was 4.6% in the SS arm and 4.1% in the AS arm (p = 5.5 × 10-2 ), and the distribution of HPV types similar between arms. There was no difference in the prevalence of CIN2+ per 1000 women screened between arms (p = 0.86). The results show that vaginal self-sampling is an equivalent alternative to sampling by medical personnel for HPV typing and identification of CIN2+.

Keywords
HPV test, cervical cancer, randomised study, screening, self-sampling
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-367086 (URN)10.1002/ijc.31637 (DOI)000451479900009 ()29943822 (PubMedID)
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research Swedish Cancer Society
Available from: 2018-11-28 Created: 2018-11-28 Last updated: 2019-01-28Bibliographically approved
Zeisler, H., Llurba, E., Chantraine, F. J., Vatish, M., Staff, A. C., Sennstrom, M., . . . Verlohren, S. (2019). Soluble fms-like tyrosine kinase-1 to placental growth factor ratio: ruling out pre-eclampsia for up to 4weeks and value of retesting. Ultrasound in Obstetrics and Gynecology, 53(3), 367-375
Open this publication in new window or tab >>Soluble fms-like tyrosine kinase-1 to placental growth factor ratio: ruling out pre-eclampsia for up to 4weeks and value of retesting
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2019 (English)In: Ultrasound in Obstetrics and Gynecology, ISSN 0960-7692, E-ISSN 1469-0705, Vol. 53, no 3, p. 367-375Article in journal (Refereed) Published
Abstract [en]

Objectives

The soluble fms-like tyrosine kinase-1 ( sFlt-1) to placental growth factor ( PlGF) ratio is generally elevated some time before and at the clinical onset of pre-eclampsia. The PROGNOSIS study validated a sFlt-1/PlGF ratio cut-off of = 38 to rule out the onset of pre-eclampsia within 1week of testing in women with suspected disease. The aim of this study was to assess the predictive value of the sFlt-1/PlGF ratio to rule out the onset of pre-eclampsia for up to 4 weeks, and to assess the value of repeat measurements.

Methods

This was an exploratory post-hoc analysis of data from the PROGNOSIS study performed in pregnant women aged = 18 years with suspected pre-eclampsia, who were at 24+ 0 to 36+ 6weeks' gestation at their first clinic visit. Serum samples were collected at the first visit and weekly thereafter. sFlt-1 and PlGF levels were measured using Elecsys (R) sFlt-1 and PlGF immunoassays. Whether the sFlt-1/PlGF ratio cut-off of = 38 used to rule out the onset of pre-eclampsia within 1week could predict the absence of pre-eclampsia 2, 3, and 4 weeks post-baseline was assessed. The value of repeat sFlt-1/PlGF testing was assessed by examining the difference in sFlt-1/PlGF ratio 2 and 3 weeks after the first measurement in women with, and those without, pre-eclampsia or adverse fetal outcome.

Results

On analysis of 550 women, sFlt-1/PlGF ratio = 38 ruled out the onset of pre-eclampsia 2 and 3weeks post-baseline with high negative predictive values (NPV) of 97.9% and 95.7%, respectively. The onset of pre-eclampsia within 4weeks was ruled out with a high NPV (94.3%) and high sensitivity and specificity (66.2% and 83.1%, respectively). Compared with women who did not develop pre-eclampsia, those who developed pre-eclampsia had significantly larger median increases in sFlt-1/PlGF ratio at 2 weeks (., 31.22 vs 1.45; P< 0.001) and at 3 weeks (., 48.97 vs 2.39; P< 0.001) after their initial visit. Women who developed pre-eclampsia and/or adverse fetal outcome compared with those who did not had a significantly greater median increase in sFlt-1/PlGF ratio over the same period (., 21.22 vs 1.40; P< 0.001 at 2weeks;., 34.95 vs 2.30; P< 0.001 at 3weeks).

Conclusion

The Elecsys (R) immunoassay sFlt-1/PlGF ratio can help to rule out the onset of pre-eclampsia for 4 weeks in women with suspected pre-eclampsia.

Keywords
angiogenic factors, PlGF, pre-eclampsia, PROGNOSIS, retesting, rule out, sFlt-1, sFlt-1/PlGF
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-379936 (URN)10.1002/uog.19178 (DOI)000460331800012 ()30014562 (PubMedID)
Available from: 2019-03-26 Created: 2019-03-26 Last updated: 2019-03-26Bibliographically approved
Enroth, S., Berggrund, M., Lycke, M., Lundberg, M., Assarsson, E., Olovsson, M., . . . Gyllensten, U. B. (2018). A two-step strategy for identification of plasma protein biomarkers for endometrial and ovarian cancer. Clinical Proteomics, 15, Article ID 38.
Open this publication in new window or tab >>A two-step strategy for identification of plasma protein biomarkers for endometrial and ovarian cancer
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2018 (English)In: Clinical Proteomics, ISSN 1542-6416, E-ISSN 1559-0275, Vol. 15, article id 38Article in journal (Refereed) Published
Abstract [en]

Background: Over 500,000 women worldwide are diagnosed with ovarian or endometrial cancer each year. We have used a two-step strategy to identify plasma proteins that could be used to improve the diagnosis of women with an indication of gynecologic tumor and in population screening.

Methods: In the discovery step we screened 441 proteins in plasma using the proximity extension assay (PEA) and five Olink Multiplex assays (CVD II, CVD III, INF I, ONC II, NEU I) in women with ovarian cancer (n=106), endometrial cancer (n=74), benign ovarian tumors (n=150) and healthy population controls (n=399). Based on the discovery analyses a set of 27 proteins were selected and two focused multiplex PEA assays were developed. In a replication step the focused assays were used to study an independent set of cases with ovarian cancer (n=280), endometrial cancer (n=228), women with benign ovarian tumors (n=76) and healthy controls (n=57).

Results: In the discovery step, 27 proteins that showed an association to cancer status were identified. In the replication analyses, the focused assays distinguished benign tumors from ovarian cancer stage III-IV with a sensitivity of 0.88 and specificity of 0.92 (AUC=0.92). The assays had a significantly higher AUC for distinguishing benign tumors from late stage ovarian cancer than using CA125 and HE4 (p=9.56e-22). Also, population controls could be distinguished from ovarian cancer stage III-IV with a sensitivity of 0.85 and a specificity of 0.92 (AUC=0.89).

Conclusion: The PEA assays represent useful tools for identification of new biomarkers for gynecologic cancers. The selected protein assays could be used to distinguish benign tumors from ovarian and endometrial cancer in women diagnosed with an unknown suspicious pelvic mass. The panels could also be used in population screening, for identification of women in need of specialized gynecologic transvaginal ultrasound examination.

Place, publisher, year, edition, pages
BMC, 2018
Keywords
Ovarian cancer, Endometrial cancer, Proximity extension assay (PEA), Sensitivity, Specificity, Diagnostics
National Category
Obstetrics, Gynecology and Reproductive Medicine Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-372376 (URN)10.1186/s12014-018-9216-y (DOI)000451777900001 ()30519148 (PubMedID)
Funder
Swedish Foundation for Strategic Research Swedish Research CouncilVINNOVASwedish Cancer Society
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-01-08Bibliographically approved
Lindström, A., Sanchez Hermansson, R., Gustavsson, I. M., Lindberg, J. H., Gyllensten, U. B. & Olovsson, M. (2018). Cervical dysplasia in elderly women performing repeated self-sampling for HPV testing. PLoS ONE, 13(12), Article ID e0207714.
Open this publication in new window or tab >>Cervical dysplasia in elderly women performing repeated self-sampling for HPV testing
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 12, article id e0207714Article in journal (Refereed) Published
Abstract [en]

Background About 30% of the cervical cancer cases in Sweden occur in women older than 60. The primary aim was to evaluate the acceptability of repeated self-sampling at home for HPV-testing in elderly women. The prevalence of HPV and HPV related dysplasia as well as the sensitivity of cytology was evaluated. Methods Repeated self-sampling at home for HPV testing was offered 375 women in each of the four age groups 60, 65, 70 and 75 years. Women with two consecutive positive HPV tests were examined with sampling for histology and cytology. Findings A self-sample was provided by 59.5% (893/1500) of the invited women. The overall prevalence of HPV was 4.4% (95% CI 3.2-6.0, n = 39) in the first test, and 2.5% were persistent positive in the second test (95% C 1.6-3.8, n = 22) collected on average 5.5 months later. Dysplasia, was found in 1.8% (16/893) (95% CI 1.1-3.0) and CIN 2+ in 1.0% (9/893) (95% CI 0.5-2.0) of the women. Of the 16 women with dysplasia in histology, 13 (81.2%) had a normal cytology. Interpretation Repeated self-sampling at home combined with HPV testing was well accepted among elderly women. A high prevalence of CIN was diagnosed by histology. Cytology showed extremely low sensitivity and should not be recommended for this age group.

National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-372761 (URN)10.1371/journal.pone.0207714 (DOI)000452212400061 ()30517176 (PubMedID)
Available from: 2019-01-14 Created: 2019-01-14 Last updated: 2019-01-14Bibliographically approved
Hermansson, R. S., Olovsson, M., Hoxell, E. & Lindström, A. K. (2018). HPV prevalence and HPV-related dysplasia in elderly women. PLoS ONE, 13(1), Article ID e0189300.
Open this publication in new window or tab >>HPV prevalence and HPV-related dysplasia in elderly women
2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 1, article id e0189300Article in journal (Refereed) Published
Abstract [en]

Introduction: In Sweden, where screening ends at the age of 60, about 30% of the cervical cancer cases occur in women older than 60. The aim of the present study was to investigate the prevalence of HPV and cervical dysplasia in women of 60 years and above.

Patients and methods: From September 2013 until June 2015, 1051 women aged 60-89 years (mean 68 years) were sampled for an HPV test when attending an outpatient gynecology clinic. Women with positive results had a second HPV test and liquid based cytology (LBC), after 3.5 months on average. Those with a positive second HPV test were examined by colposcopy, and biopsy and a sample for LBC was obtained.

Results: The prevalence of HPV was 4.1%, (95% CI 3.0-5.5, n = 43) at the first test, and at the second test 2.6% remained positive (95% CI 1.7-3.8, n = 27). The majority of women positive in both HPV tests, had dysplasia in histology, 81.5% (22/27) (4 CIN 2-0.4%, 18 CIN 1-1.7%). HPV-related dysplasia was found in 2.1%, (95% CI 1.3-3.2,n = 22) of the 1051 women. Four of the 22 women with positive HPV tests also had abnormal cytology, one ASCUS and three CIN 1. No cancer or glandular dysplasia was detected.

Conclusion: A significant proportion of elderly women were found to have a persistent cervical HPV infection. Among them there was a high prevalence of CIN diagnosed by histology. The HPV test showed high sensitivity and specificity in detecting CIN in elderly women, while cytology showed extremely low sensitivity.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2018
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-341575 (URN)10.1371/journal.pone.0189300 (DOI)000419689600008 ()29320507 (PubMedID)
Available from: 2018-02-12 Created: 2018-02-12 Last updated: 2018-02-12Bibliographically approved
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