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Gustavsson, Inger M.
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Publications (10 of 21) Show all publications
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
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
Gustavsson, I. M., Aarnio, R., Berggrund, M., Lindberg, J. H., Strand, A.-S., Sanner, K., . . . Gyllensten, U. B. (2018). Randomised study shows that repeated self-sampling and HPV test has more than two-fold higher detection rate of women with CIN2+ histology than Pap smear cytology. British Journal of Cancer, 118(6), 896-904
Open this publication in new window or tab >>Randomised study shows that repeated self-sampling and HPV test has more than two-fold higher detection rate of women with CIN2+ histology than Pap smear cytology
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2018 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 118, no 6, p. 896-904Article in journal (Refereed) Published
Abstract [en]

Background:

This randomised study compared the detection rate of cervical intraepithelial neoplasia-positive (CIN2+) based on histology in women performing repeated self-sampling of vaginal fluid (VF) for human papillomavirus (HPV) test with a control group following the ordinary screening by Pap smear cytology.

Methods:

36390 women aged 30–49 years scheduled for invitation to organised screening were randomised in two groups, one to perform self-sampling of VF for HPV test (n=17 997, HPV arm) and the other group to perform screening by PAP smear cytology (n=18 393, control arm). HPV positive women in the HPV arm repeated the self-sampling and the HPV test on average 4.4 months later and those with two consecutive positive HPV tests were referred to colposcopy. Outcome was CIN2+ based on histology during 18-month follow-up.

Results:

Participation rate was 47% in the HPV arm and 39% in the control arm. The HPV prevalence in the first self-sampling was 6.9%, and 71% of these women were HPV positive in their second test. For the per-protocol approach, cumulative prevalence of histological CIN2+ in the HPV arm was 20.2 per 1000 women screened as compared to 10.8 in the control arm. The cumulative prevalence of CIN2+ diagnosed per 1000 years screened was 160.8 in the HPV arm as compared with 25.4 in the control arm.

Conclusions:

Repeated self-sampling of VF and HPV test had more than a two-fold higher discovery rate of CIN2+ per 1000 women screened as compared with PAP smear cytology.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-367087 (URN)10.1038/bjc.2017.485 (DOI)000427945800030 ()29438367 (PubMedID)
Funder
Swedish Foundation for Strategic Research Swedish Cancer SocietySwedish Society for Medical Research (SSMF)
Available from: 2018-11-28 Created: 2018-11-28 Last updated: 2019-06-28Bibliographically approved
Sanner, K., Wikström, I., Gustavsson, I., Wilander, E., Lindberg, J. H., Gyllensten, U. & Olovsson, M. (2015). Daily self-sampling for high-risk human papillomavirus (HR-HPV) testing.. Journal of Clinical Virology, 73, 1-7
Open this publication in new window or tab >>Daily self-sampling for high-risk human papillomavirus (HR-HPV) testing.
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2015 (English)In: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 73, p. 1-7Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Self-sampling for HPV as part of primary screening is a well-tolerated method for women not attending organized Pap smear screening and could increase coverage of cervical cancer screening.

OBJECTIVE: To investigate if the prevalence of HR-HPV varies from day to day in infected women and if one single sample is reliable for detecting an ongoing infection.

STUDY DESIGN: This is a prospective cohort study on 12 premenopausal and 13 postmenopausal women performing daily self-sampling for HR-HPV testing. They were all HR-HPV-positive 1-3 months ago. Postmenopausal women were sampled for 28 days and premenopausal women sampled during bleeding-free days in one menstrual cycle. A possible difference in viral load between the estrogen-dominated proliferative phase and the progesterone-dominated secretory phase was analyzed.

RESULTS AND CONCLUSIONS: Consistent results throughout the sampling period were observed for 19 women, with either a daily presence of HPV (14 women) or no HPV at all during the sampling period (5 women). Of 607 samples from 25 women, 596 were consistently positive or negative for HPV during the sampling period and 11 were inconsistent (2%). There was no difference in HPV copy number between the estrogen dominated proliferative or progesterone dominated secretory menstrual cycle phases. The major finding was a high degree of consistency concerning HR-HPV positivity and negativity of HR-HPV in vaginal fluid during a sustained period of daily self-sampling. It does not appear to matter whether the sample is collected in the proliferative or secretory phase.

Keywords
Cervical cancer; Human papilloma virus (HPV); Self-sampling; Repeated sampling; Screening
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-272544 (URN)10.1016/j.jcv.2015.09.016 (DOI)000367390700001 ()26498105 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer Society
Available from: 2016-01-14 Created: 2016-01-14 Last updated: 2017-11-30Bibliographically approved
Ameur, A., Meiring, T. L., Bunikis, I., Häggqvist, S., Lindau, C., Lindberg, J. H., . . . Gyllensten, U. (2014). Comprehensive profiling of the vaginal microbiome in HIV positive women using massive parallel semiconductor sequencing. Scientific Reports, 4, 4398
Open this publication in new window or tab >>Comprehensive profiling of the vaginal microbiome in HIV positive women using massive parallel semiconductor sequencing
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2014 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, p. 4398-Article in journal (Refereed) Published
Abstract [en]

Infections by HIV increase the risk of acquiring secondary viral and bacterial infections and methods are needed to determine the spectrum of co-infections for proper treatment. We used rolling circle amplification (RCA) and Ion Proton sequencing to investigate the vaginal microbiome of 20 HIV positive women from South Africa. A total of 46 different human papillomavirus (HPV) types were found, many of which are not detected by existing genotyping assays. Moreover, the complete genomes of two novel HPV types were determined. Abundance of HPV infections was highly correlated with real-time PCR estimates, indicating that the RCA-Proton method can be used for quantification of individual pathogens. We also identified a large number of other viral, bacterial and parasitic co-infections and the spectrum of these co-infections varied widely between individuals. Our method provides rapid detection of a broad range of pathogens and the ability to reconstruct complete genomes of novel infectious agents.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-223522 (URN)10.1038/srep04398 (DOI)000332937300007 ()
Available from: 2014-04-30 Created: 2014-04-22 Last updated: 2017-12-05Bibliographically approved
Andersson, S., Mints, M., Gyllensten, U., Lindell, M., Gustavsson, I., Lambe, M. & Wilander, E. (2014). Uneven distribution of human papillomavirus 16111 cervical carcinoma in situ and squamous cell carcinoma in older females: A retrospective database study. Oncology Letters, 8(4), 1528-1532
Open this publication in new window or tab >>Uneven distribution of human papillomavirus 16111 cervical carcinoma in situ and squamous cell carcinoma in older females: A retrospective database study
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2014 (English)In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 8, no 4, p. 1528-1532Article in journal (Refereed) Published
Abstract [en]

Human papillomavirus (HPV) 16 is the dominant cofactor in cervical cancer development. The present report investigated the age-specific prevalence of HPV16 in cervical carcinoma in situ (CIS) in females attending organised cervical cancer screening. A retrospective observational study was performed based on individual data from two databases. A total of 162 females aged between 20 and 65 years from Uppsala County, Sweden with CIS and an HPV test conducted between 2010 and 2011, preceding or concomitant to CIS diagnosis, were included. Females with cervical squamous cell carcinoma (SCC; n=35) were used for comparison. In total, 96% (n=156) of females with CIS were positive for high-risk HPV; HPV16 was the most prevalent (44.5%), followed by HPV33/52/58 (19.5%), HPV31 (13.1%) and HPV18145 (9.5%). HPV16 was most frequently detected in females with CIS aged between 20 and 29 years (73.6%) and least frequently detected in those aged between 50 and 65 years (33.3%), with a statistically significant age-specific difference (P=0.001). Among the HPV16-positive females, multiple infections were most frequent in the younger age groups. The prevalence of HPV16 in females with CIS decreased with age, whereas a high prevalence of HPV16 remained in females with SCC. These results may indicate that HPV16 has increased oncogenic potential in older females.

Keywords
cervix, carcinoma in situ, human papillomavirus 16, prevalence, old age
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-235626 (URN)10.3892/ol.2014.2347 (DOI)000342725400023 ()
Available from: 2014-11-11 Created: 2014-11-06 Last updated: 2017-12-05Bibliographically approved
Chen, D., Juko-Pecirep, I., Hammer, J., Ivansson, E., Enroth, S., Gustavsson, I., . . . Gyllensten, U. (2013). Genome-wide Association Study of Susceptibility Loci for Cervical Cancer. Journal of the National Cancer Institute, 105(9), 624-633
Open this publication in new window or tab >>Genome-wide Association Study of Susceptibility Loci for Cervical Cancer
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2013 (English)In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 105, no 9, p. 624-633Article in journal (Refereed) Published
Abstract [en]

Background Cervical carcinoma has a heritable genetic component, but the genetic basis of cervical cancer is still not well understood. Methods We performed a genome-wide association study of 731 422 single nucleotide polymorphisms (SNPs) in 1075 cervical cancer case subjects and 4014 control subjects and replicated it in 1140 case subjects and 1058 control subjects. The association between top SNPs and cervical cancer was estimated by odds ratios (ORs) and 95% confidence intervals (CIs) with unconditional logistic regression. All statistical tests were two-sided. Results Three independent loci in the major histocompatibility complex (MHC) region at 6p21.3 were associated with cervical cancer: the first is adjacent to the MHC class I polypeptide-related sequence A gene (MICA) (rs2516448; OR = 1.42, 95% CI = 1.31 to 1.54; P = 1.6 x 10(-18)); the second is between HLA-DRB1 and HLA-DQA1 (rs9272143; OR = 0.67, 95% CI = 0.62 to 0.72; P = 9.3 x 10(-24)); and the third is at HLA-DPB2 (rs3117027; OR=1.25, 95% CI = 1.15 to 1.35; P = 4.9 x 10(-8)). We also confirmed previously reported associations of B*0702 and DRB1*1501-DQB1*0602 with susceptibility to and DRB1*1301-DQA1*0103-DQB1*0603 with protection against cervical cancer. The three new loci are statistically independent of these specific human leukocyte antigen alleles/haplotypes. MICA encodes a membrane-bound protein that acts as a ligand for NKG2D to activate antitumor effects. The risk allele of rs2516448 is in perfect linkage disequilibrium with a frameshift mutation (A5.1) of MICA, which results in a truncated protein. Functional analysis shows that women carrying this mutation have lower levels of membrane-bound MICA. Conclusions Three novel loci in the MHC may affect susceptibility to cervical cancer in situ, including the MICA-A5.1 allele that may cause impaired immune activation and increased risk of tumor development.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-202385 (URN)10.1093/jnci/djt051 (DOI)000318681200009 ()
Available from: 2013-06-24 Created: 2013-06-24 Last updated: 2017-12-06Bibliographically approved
Ostensson, E., Hellstrom, A.-C., Hellman, K., Gustavsson, I., Gyllensten, U., Wilander, E., . . . Andersson, S. (2013). Projected cost-effectiveness of repeat high-risk human papillomavirus testing using self-collected vaginal samples in the Swedish cervical cancer screening program. Acta Obstetricia et Gynecologica Scandinavica, 92(7), 830-840
Open this publication in new window or tab >>Projected cost-effectiveness of repeat high-risk human papillomavirus testing using self-collected vaginal samples in the Swedish cervical cancer screening program
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2013 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 7, p. 830-840Article in journal (Refereed) Published
Abstract [en]

Background Human papillomavirus (HPV) testing is not currently used in primary cervical cancer screening in Sweden, and corresponding cost-effectiveness is unclear. Objective From a societal perspective, to evaluate the cost-effectiveness of high-risk (HR)-HPV testing using self-collected vaginal samples. Design A cost-effectiveness analysis. Setting The Swedish organized cervical cancer screening program. Methods We constructed a model to simulate the natural history of cervical cancer using Swedish data on cervical cancer risk. For the base-case analysis we evaluated two screening strategies with different screening intervals: (i) cytology screening throughout the woman's lifetime (i.e. conventional cytology strategy) and (ii) conventional cytology screening until age 35years, followed by HR-HPV testing using self-collected vaginal samples in women aged 35years (i.e. combination strategy). Sensitivity analyses were performed, varying model parameters over a significant range of values to identify cost-effective screening strategies. Main outcome measures Average lifetime cost, discounted and undiscounted life-years gained, reduction in cervical cancer risk, incremental cost-effectiveness ratios with and without the cost of added life-years. Results Depending on screening interval, the incremental cost-effectiveness ratios for the combination strategy ranged from Euro43000 to Euro180000 per life-years gained without the cost of added life-years, and from Euro74000 to Euro206000 with costs of added life-years included. Conclusion The combination strategy with a 5-year screening interval is potentially cost-effective compared with no screening, and with current screening practice when using a threshold value of Euro80000 per life-years gained.

Keywords
Cervical cancer, cost-effectiveness, human papillomavirus (HPV), screening, self-sampling
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-204091 (URN)10.1111/aogs.12143 (DOI)000320549400014 ()
Available from: 2013-07-23 Created: 2013-07-22 Last updated: 2017-12-06Bibliographically approved
Phongsavan, K., Gustavsson, I., Marions, L., Phengsavanh, A., Wahlstrom, R. & Gyllensten, U. (2012). Detection of Human Papillomavirus Among Women in Laos Feasibility of Using Filter Paper Card and Prevalence of High-Risk Types. International Journal of Gynecological Cancer, 22(8), 1398-1406
Open this publication in new window or tab >>Detection of Human Papillomavirus Among Women in Laos Feasibility of Using Filter Paper Card and Prevalence of High-Risk Types
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2012 (English)In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 22, no 8, p. 1398-1406Article in journal (Refereed) Published
Abstract [en]

Background: Persistent infection with high-risk (HR) human papillomavirus (HPV) is a well-recognized cause of cervical cancer, but little is known about the situation in Laos. The aims of the study were to determine the prevalence of HR-HPV among Lao women and to evaluate the use of a filter paper card (FTA Elute Micro Card) for collection of cervical cells in the humid tropical climate. Methods: This is a cross-sectional study including 1922 women from 3 provinces in Laos. During a gynecological examination, cervical cells were collected and applied to the FTA card followed by HPV typing using a real-time polymerase chain reaction (PCR)-based assay. Results: Overall, 213 of the 1922 women were positive for HR-HPV (11%). The most common type was the group HPV33/52/58 (3%), followed by the single type 16 (2%) and the group 18/45 (1%), respectively. Only 11 cards (0.6%) did not contain a sufficient amount of genomic DNA for polymerase chain reaction-based analysis. Conclusions: The prevalence of HR-HPV infections in Laos is similar to other Asian countries, and 40% of the women with an HR-HPV infection will be target of the present HPV vaccines. The FTA card is suitable for collection of cervical cells for HR-HPV typing in tropical conditions. This information is important for planning and establishing primary and secondary prevention of cervical cancer in Laos.

Keywords
Human papillomavirus, High-risk types, Cervical cancer, FTA card, Laos
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-185200 (URN)10.1097/IGC.0b013e3182664b6b (DOI)000309543700021 ()
Available from: 2012-11-22 Created: 2012-11-21 Last updated: 2017-12-07Bibliographically approved
Marincevic-Zuniga, Y., Gustavsson, I. & Gyllensten, U. (2012). Multiply-primed rolling circle amplification of human papillomavirus using sequence-specific primers. Virology, 432(1), 57-62
Open this publication in new window or tab >>Multiply-primed rolling circle amplification of human papillomavirus using sequence-specific primers
2012 (English)In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 432, no 1, p. 57-62Article in journal (Refereed) Published
Abstract [en]

Multiply-primed rolling circle amplification (RCA) is a suitable technique for amplification of circular templates and has been used to identify novel human papillomaviruses (HPV). In this study we develop an efficient RCA for whole genome amplification of HPV using HPV-specific primers in clinical samples and establish a protocol for whole genome sequencing using the Sanger method. Amplification of cloned HPV-genomes by RCA was compared using specific primers against random hexamers. Using HPV-specific primers increased the effectiveness on average 15.2 times and the enrichment of HPV relative to human gDNA on average 62.2 times, as compared to using random hexamer. RCA products were sequenced without need for cloning, even when using low-input amounts. The technique was successfully used on 4 patient samples from FTA cards, to generate whole HPV-genome sequences. Degenerated HPV-specific primers for RCA produce DNA of sufficient quality and quantity suitable for sequencing and other potential downstream analyses.

Keywords
Human papillomavirus, Rolling circle amplification, Degenerated primers, Sanger sequencing
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-181993 (URN)10.1016/j.virol.2012.05.030 (DOI)000307027100007 ()
Available from: 2012-10-09 Created: 2012-10-02 Last updated: 2017-12-07Bibliographically approved
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