Publications by authors named "Seppo Virtanen"

10 Publications

  • Page 1 of 1

Distribution of HPV Genotypes Differs Depending on Behavioural Factors among Young Women.

Microorganisms 2021 Apr 2;9(4). Epub 2021 Apr 2.

Department of Obstetrics and Gynecology, Tampere University Hospital and Tampere University, 33100 Tampere, Finland.

Risk factors for the different human papillomavirus (HPV) genotypes are not well understood, although the risk of cancer is known to vary among them. Our aim was to evaluate the association of diverse behavioral and reproductive factors with genotype-specific HPV prevalence among 879 unvaccinated women aged 18-75 years referred to the colposcopy clinic at Helsinki University Hospital in Finland. Cervical swabs for HPV genotyping were collected in the first visit and assessed for 34 high-risk (hr) and low-risk (lr) HPV genotypes. Participants completed a questionnaire on behavioral, reproductive, and lifestyle factors. Differences in genotype-specific HPV prevalence were analyzed overall and in age groups using binary logistic regression. Smoking was associated with higher prevalence in HPV16 compared with other hrHPV genotypes together with decreasing age, being highest among younger women <30 years old, odds ratio (OR) 3.74 (95% CI 1.42-9.88). The later the sexual debut, the more it seemed to protect from HPV16 infection. The best protection was achieved when the sexual debut took place at >20 years of age, with an OR of 0.43 (95% CI 0.23-0.83). This association was not seen with other hrHPV genotypes. Methods of contraception seemed not to have an effect on hrHPV positivity, regardless of the HPV genotype. The genotype specific hrHPV prevalence differs, depending on behavioral factors, especially among younger women referred to colposcopy.
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April 2021

Bacterial and fungal profiles as markers of infliximab drug response in inflammatory bowel disease.

J Crohns Colitis 2020 Dec 10. Epub 2020 Dec 10.

Translational Immunology Research Program, University of Helsinki, Finland.

Background: Inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis (UC), are globally increasing chronic gastro-intestinal inflammatory disorders associating with altered gut microbiota. Infliximab (IFX), a TNF-alpha blocker, is used to treat IBD patients successfully though one third of the patients do not respond to therapy. No reliable biomarkers are available for prediction of IFX response.

Aims: Our aim was to investigate the faecal bacterial and fungal communities during IFX therapy and find predictors for IFX treatment response in IBD patients.

Methods: 72 IBD patients (25 CD and 47 UC) started IFX therapy and were followed for one year or until IFX treatment was discontinued. Amplicon sequencing approach targeting the bacterial 16S rRNA gene and fungal ITS 1 region separately was used to determine the microbiota profiles in faecal samples collected before IFX therapy, two, six, twelve weeks and one year after initiation of therapy. The response to IFX was evaluated by colonoscopy and clinically at twelve weeks after initiation.

Results: Both the faecal bacterial and fungal profiles differed significantly between response groups before start of IFX treatment. Non-responders had lower abundances of short chain fatty acid producers, particularly of the class Clostridia and higher abundances of pro-inflammatory bacteria and fungi, such as the genus Candida, compared to responders. This was further indicated by bacterial taxa predicting the response in both CD and UC patients (area under curve > 0.8).

Conclusions: Faecal bacterial and fungal microbiota composition could provide a predictive tool to estimate IFX response in IBD patients.
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December 2020

Role of Colposcopy after Treatment for Cervical Intraepithelial Neoplasia.

Cancers (Basel) 2020 Jun 24;12(6). Epub 2020 Jun 24.

Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland.

Colposcopy is often used in follow-up after treatment for cervical intraepithelial neoplasia (CIN) despite its marked inter-observer variability and low sensitivity. Our objective was to assess the role of colposcopy in post-treatment follow-up in comparison to hrHPV (high-risk human papillomavirus) testing, cytology, and cone margin status. Altogether, 419 women treated for histological high-grade lesion (HSIL) with large loop excision of the transformation zone (LLETZ) attended colposcopy with cytology and hrHPV test at six months. Follow-up for recurrence of HSIL continued for 24 months. Colposcopy was considered positive if colposcopic impression was recorded as high grade and cytology if HSIL, ASC-H (atypical squamous cells, cannot exclude HSIL), or AGC-FN (atypical glandular cells, favor neoplasia) were present. Overall, 10 (10/419, 2.4%) recurrent HSIL cases were detected, 5 at 6 months and 5 at 12 months. Colposcopic impression was recorded at 407/419 6-month visits and was positive for 11/407 (2.7%). None of them had recurrent lesions, resulting in 0% sensitivity and 97% specificity for colposcopy. Sensitivity for the hrHPV test at 6 months was 100% and specificity 85%, for cytology 40% and 99%, and for margin status at treatment 60% and 82%, respectively. While the hrHPV test is highly sensitive in predicting recurrence after local treatment for CIN, colposcopy in an unselected population is not useful in follow-up after treatment of CIN.
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June 2020

Vaginal microbiota in pregnancy: Role in induction of labor and seeding the neonate''s microbiota?

J Biosci 2019 Oct;44(5)

Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Compared to other human microbiota, vaginal microbiota is fairly simple with low bacterial diversity and high relative abundance of Lactobacillus species. Lactobacillus dominance is even more pronounced during pregnancy. Genetic factors, such as ethnicity, along with environmental, individual and lifestyle factors all have an impact on vaginal microbiota composition. The composition of the vaginal microbiota appears to play an important role in pregnancy as recent studies have linked it to adverse obstetric outcomes such as preterm birth, a leading cause of neonatal morbidity and mortality worldwide. However, the same vaginal microbiota does not seem to cause the same response in all women, calling for future research to fully understand the complex host-microbiota interplay in normal and complicated pregnancies.
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October 2019

Age-specific HPV type distribution in high-grade cervical disease in screened and unvaccinated women.

Gynecol Oncol 2019 08 5;154(2):354-359. Epub 2019 Jun 5.

Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 2, 00290 Helsinki, Finland. Electronic address:

Background And Aim: Age-specific type-distribution of high-risk human papillomavirus (hrHPV) in cervical precancerous lesions is subject to change in the HPV vaccination era. Knowing the pre-vaccination type-distribution helps to anticipate changes induced by mass vaccination and optimize screening.

Methods: We recruited 1279 women referred to colposcopy for abnormal cytology into a population-based study on HPV type distribution in diagnostic cervical samples (ISRCTN10933736). The HPV genotyping findings were grouped as: HPV16/18+, other hrHPV+ (HPV31/33/35/39/45/51/52/56/58/59/66/68), non-vaccine targeted hrHPV+ (HPV35/39/51/56/59/66/68), low-risk HPV, and HPV negative. We estimated the HPV group-specific prevalence rates according to diagnostic histopathological findings in the age groups of <30 (n = 339), 30-44.9 (n = 614), and ≥45 (n = 326).

Results: Altogether 503 cases with high grade squamous intraepithelial lesion or worse (HSIL+) were diagnosed. More than half, 285 (56.7%) of HSIL+ cases were associated with HPV16/18: 64.3% (101/157) in women <30 years (reference group), 58.4% (157/269) in women 30-44.9 years (risk ratio (RR) 0.91, 95% confidence interval (95% CI) 0.78-1.06), and 35.1% (27/77) in women ≥45 years of age (RR 0.55, 95% CI 0.39-0.75). Conversely, other hrHPV's were associated with 191 (38.0%) of HSIL+: 31.9% (50/157) in women <30, 36.8% (99/269) in women 30-44.9 years, 54.6% (42/77) and in women ≥45 (RR 1.71, 95% CI 1.26-2.33). The proportion of non-vaccine targeted hrHPV and HPV negative HSIL+ increased with advancing age.

Conclusions: Pre-vaccination HPV type distribution in HSIL+ was distinctly polarised by age with HPV16/18 attributed disease being markedly more prevalent in women aged <30. In the older women the other hrHPV types, however, dominated suggesting a need for more age-dependent screening strategies.
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August 2019

Vaginal Microbiota Composition Correlates Between Pap Smear Microscopy and Next Generation Sequencing and Associates to Socioeconomic Status.

Sci Rep 2019 05 23;9(1):7750. Epub 2019 May 23.

Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Recent research on vaginal microbiota relies on high throughput sequencing while microscopic methods have a long history in clinical use. We investigated the correspondence between microscopic findings of Pap smears and the vaginal microbiota composition determined by next generation sequencing among 50 asymptomatic women. Both methods produced coherent results regarding the distinction between Lactobacillus-dominant versus mixed microbiota, reassuring gynaecologists for the use of Pap smear or wet mount microscopy for rapid evaluation of vaginal bacteria as part of diagnosis. Cytologic findings identified women with bacterial vaginosis and revealed that cytolysis of vaginal epithelial cells is associated to Lactobacillus crispatus-dominated microbiota. Education and socio-economic status were associated to the vaginal microbiota variation. Our results highlight the importance of including socio-economic status as a co-factor in future vaginal microbiota studies.
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May 2019

Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis.

BMJ 2018 02 27;360:k499. Epub 2018 Feb 27.

Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Objective: To estimate the regression, persistence, and progression of untreated cervical intraepithelial neoplasia grade 2 (CIN2) lesions managed conservatively as well as compliance with follow-up protocols.

Design: Systematic review and meta-analysis.

Data Sources: Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1 January 1973 to 20 August 2016.

Eligibility Criteria: Studies reporting on outcomes of histologically confirmed CIN2 in non-pregnant women, managed conservatively for three or more months.

Data Synthesis: Two reviewers extracted data and assessed risk of bias. Random effects model was used to calculate pooled proportions for each outcome, and heterogeneity was assessed using I statistics.

Main Outcome Measures: Rates of regression, persistence, or progression of CIN2 and default rates at different follow-up time points (3, 6, 12, 24, 36, and 60 months).

Results: 36 studies that included 3160 women were identified (seven randomised trials, 16 prospective cohorts, and 13 retrospective cohorts; 50% of the studies were at low risk of bias). At 24 months, the pooled rates were 50% (11 studies, 819/1470 women, 95% confidence interval 43% to 57%; I=77%) for regression, 32% (eight studies, 334/1257 women, 23% to 42%; I=82%) for persistence, and 18% (nine studies, 282/1445 women, 11% to 27%; I=90%) for progression. In a subgroup analysis including 1069 women aged less than 30 years, the rates were 60% (four studies, 638/1069 women, 57% to 63%; I=0%), 23% (two studies, 226/938 women, 20% to 26%; I=97%), and 11% (three studies, 163/1033 women, 5% to 19%; I=67%), respectively. The rate of non-compliance (at six to 24 months of follow-up) in prospective studies was around 10%.

Conclusions: Most CIN2 lesions, particularly in young women (<30 years), regress spontaneously. Active surveillance, rather than immediate intervention, is therefore justified, especially among young women who are likely to adhere to monitoring.

Systematic Review Registration: PROSPERO 2014: CRD42014014406.
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February 2018

Comparative analysis of vaginal microbiota sampling using 16S rRNA gene analysis.

PLoS One 2017 19;12(7):e0181477. Epub 2017 Jul 19.

Immunobiology Research Programme, Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.

Background: Molecular methods such as next-generation sequencing are actively being employed to characterize the vaginal microbiota in health and disease. Previous studies have focused on characterizing the biological variation in the microbiota, and less is known about how factors related to sampling contribute to the results. Our aim was to investigate the impact of a sampling device and anatomical sampling site on the quantitative and qualitative outcomes relevant for vaginal microbiota research. We sampled 10 Finnish women representing diverse clinical characteristics with flocked swabs, the Evalyn® self-sampling device, sterile plastic spatulas and a cervical brush that were used to collect samples from fornix, vaginal wall and cervix. Samples were compared on DNA and protein yield, bacterial load, and microbiota diversity and species composition based on Illumina MiSeq sequencing of the 16S rRNA gene. We quantified the relative contributions of sampling variables versus intrinsic variables in the overall microbiota variation, and evaluated the microbiota profiles using several commonly employed metrics such as alpha and beta diversity as well as abundance of major bacterial genera and species.

Results: The total DNA yield was strongly dependent on the sampling device and to a lesser extent on the anatomical site of sampling. The sampling strategy did not affect the protein yield or the bacterial load. All tested sampling methods produced highly comparable microbiota profiles based on MiSeq sequencing. The sampling method explained only 2% (p-value = 0.89) of the overall microbiota variation, markedly surpassed by intrinsic factors such as clinical status (microscopy for bacterial vaginosis 53%, p = 0.0001), bleeding (19%, p = 0.0001), and the variation between subjects (11%, p-value 0.0001).

Conclusions: The results indicate that different sampling strategies yield comparable vaginal microbiota composition and diversity. Hence, past and future vaginal microbiota studies employing different sampling strategies should be comparable in the absence of other technical confounders. The Evalyn® self-sampling device performed equally well compared to samples taken by a clinician, and hence offers a good-quality microbiota sample without the need for a gynecological examination. The amount of collected sample as well as the DNA and protein yield varied across the sampling techniques, which may have practical implications for study design.
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September 2017

Group Factor Analysis.

IEEE Trans Neural Netw Learn Syst 2015 Sep 18;26(9):2136-47. Epub 2014 Dec 18.

Factor analysis (FA) provides linear factors that describe the relationships between individual variables of a data set. We extend this classical formulation into linear factors that describe the relationships between groups of variables, where each group represents either a set of related variables or a data set. The model also naturally extends canonical correlation analysis to more than two sets, in a way that is more flexible than previous extensions. Our solution is formulated as a variational inference of a latent variable model with structural sparsity, and it consists of two hierarchical levels: 1) the higher level models the relationships between the groups and 2) the lower models the observed variables given the higher level. We show that the resulting solution solves the group factor analysis (GFA) problem accurately, outperforming alternative FA-based solutions as well as more straightforward implementations of GFA. The method is demonstrated on two life science data sets, one on brain activation and the other on systems biology, illustrating its applicability to the analysis of different types of high-dimensional data sources.
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September 2015

Identification of structural features in chemicals associated with cancer drug response: a systematic data-driven analysis.

Bioinformatics 2014 Sep;30(17):i497-504

Department of Information and Computer Science, Helsinki Institute for Information Technology HIIT, Aalto University, 00076 Espoo, Institute for Molecular Medicine Finland FIMM, University of Helsinki, 00014 Helsinki, School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70211 Kuopio and Department of Computer Science, Helsinki Institute for Information Technology HIIT, University Of Helsinki, 00014 Helsinki, Finland Department of Information and Computer Science, Helsinki Institute for Information Technology HIIT, Aalto University, 00076 Espoo, Institute for Molecular Medicine Finland FIMM, University of Helsinki, 00014 Helsinki, School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70211 Kuopio and Department of Computer Science, Helsinki Institute for Information Technology HIIT, University Of Helsinki, 00014 Helsinki, Finland.

Motivation: Analysis of relationships of drug structure to biological response is key to understanding off-target and unexpected drug effects, and for developing hypotheses on how to tailor drug therapies. New methods are required for integrated analyses of a large number of chemical features of drugs against the corresponding genome-wide responses of multiple cell models.

Results: In this article, we present the first comprehensive multi-set analysis on how the chemical structure of drugs impacts on genome-wide gene expression across several cancer cell lines [Connectivity Map (CMap) database]. The task is formulated as searching for drug response components across multiple cancers to reveal shared effects of drugs and the chemical features that may be responsible. The components can be computed with an extension of a recent approach called Group Factor Analysis. We identify 11 components that link the structural descriptors of drugs with specific gene expression responses observed in the three cell lines and identify structural groups that may be responsible for the responses. Our method quantitatively outperforms the limited earlier methods on CMap and identifies both the previously reported associations and several interesting novel findings, by taking into account multiple cell lines and advanced 3D structural descriptors. The novel observations include: previously unknown similarities in the effects induced by 15-delta prostaglandin J2 and HSP90 inhibitors, which are linked to the 3D descriptors of the drugs; and the induction by simvastatin of leukemia-specific response, resembling the effects of corticosteroids.

Availability And Implementation: Source Code implementing the method is available at:

Supplementary Information: Supplementary data are available at Bioinformatics online.
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September 2014