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  • 1.
    Abreu, Miguel Henriques
    et al.
    Department of Medical Oncology, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal; Porto Comprehensive Cancer Center Raquel Seruca (PCCC), Porto, Portugal.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Bartosch, Carla
    Porto Comprehensive Cancer Center Raquel Seruca (PCCC), Porto, Portugal; Department of Pathology, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal; Cancer Biology & Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (CI-IPO-Porto)/Health Research Network (RISE@CI-IPO-Porto), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
    Ricardo, Sara
    Differentiation and Cancer Group, Institute for Research and Innovation in Health (i3S) of the University of Porto, Porto, Portugal; 1H-TOXRUN - One Health Toxicology Research Unit, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; Department of Pathology, Faculty of Medicine from University of Porto (FMUP), Porto, Portugal.
    Editorial: New molecular approaches to improve gynecological cancer management2023Inngår i: Frontiers in Oncology, E-ISSN 2234-943X, Vol. 13, artikkel-id 1235035Artikkel i tidsskrift (Annet vitenskapelig)
  • 2.
    Bergengren, Lovisa
    et al.
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Women’s Health.
    Kaliff, Malin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine.
    Karlsson, Mats
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Comparison between professional sampling and self-sampling for HPV-based cervical cancer screening among postmenopausal women2018Inngår i: International Journal of Gynecology & Obstetrics, ISSN 0020-7292, E-ISSN 1879-3479, Vol. 142, nr 3, s. 359-364Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 3.
    Bergengren, Lovisa
    et al.
    Örebro universitet, Institutionen för hälsovetenskaper. Dept. of Women's Health.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper. Dept. of Laboratory Medicine.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Dept. of Laboratory Medicine.
    Karlsson, Mats G.
    Örebro universitet, Institutionen för medicinska vetenskaper. Dept. of Laboratory Medicine.
    HPV-based screening for cervical cancer among women 55-59 years of age2019Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 14, nr 6, artikkel-id e0217108Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 4.
    Bergengren, Lovisa
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Women’s health.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper. Department Laboratory Medicine.
    Kaliff, Malin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department Laboratory Medicine.
    Karlsson, Mats
    Örebro universitet, Institutionen för medicinska vetenskaper. Department Laboratory Medicine.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Department Laboratory Medicine.
    Concordance between self sampling and professionally taken cervical hpv test-result from population based cohort study2016Konferansepaper (Fagfellevurdert)
  • 5.
    Dorofte, L
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Davidsson, S
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Laboratory Medicine.
    Lillsunde-Larsson, G
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine.
    Karlsson, M
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Reliability of histological subtyping of penile squamous cell carcinoma in assessing HPV tumour status2022Inngår i: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 481, nr Suppl. 1, s. S168-S168, artikkel-id PS-26-003Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background & objectives: HPV-positive penile tumours have been associated with higher survival rates. However, HPV analysis is unavailable in many low-income countries. We investigated if histological assessment of penile squamous cell carcinoma subtypes can replace HPV testing in determining HPV-related/non-HPV-related tumour status.

    Methods: We reviewed paraffin-embedded tumour tissue from 345 penile cancer patients, surgically treated between 2009 and 2018 at Örebro University Hospital, Sweden. The histological subtype of squamous cell carcinoma was assessed according to the WHO criteria and ISUP recommendations. HPV-DNA genotyping was performed using the PCR method Anyplex II HPV28. Concordance was assessed by calculating Cohen’s kappa (κ).

    Results: A good concordance was found between histological subtype of squamous cell carcinoma and HPV tumour-status with a Cohen’s kappa (κ) of 0,72 corresponding to 86,6% agreement. Of the 46 discordant cases, five had HPV-related histology (mixed subtypes) but were HPV-negative. The remaining 41 cases had non-HPV- related histology (85% usual subtype, 15% mixed subtypes) but were HPV-positive. Noteworthy is that in 21 of the cases with non-HPV-related histology, foci of undifferentiated PeIN was found. In addition, four cases with both undifferentiated PeIN and lichen sclerosus et atrophicus in the tumour margin, 14 cases with both differentiated PeIN and lichen sclerosus et atrophicus and two cases without preneoplastic lesion were identified.

    Conclusion: Good concordance between histological subtype of penile squamous cell carcinoma and HPV genotyping shows that when necessary, histological assessment is a good alternative, at least in less resourceful settings, to PCR-based HPV analysis in determining if penile tumours are HPV or non-HPV-related. Discordant cases most likely depend on subjectivity in histological assessment but can also suggest a HPV infection in a non-HPV-related tumour.

  • 6.
    Dorofte, Luiza
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Grélaud, Diane
    Department of Clinical Genetics and Pathology, Skåne University Hospital and Regional Laboratories, Malmö, Sweden.
    Fiorentino, Michelangelo
    Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
    Giunchi, Francesca
    Pathology, Istituto Di Ricovero E Cure a Carattere Scientifico, Azienda Ospedaliero-Universitaria Policlinico Sant'Orsola-Malpighi, Bologna, Italy.
    Ricci, Costantino
    Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy; Pathology Unit, Maggiore Hospital, AUSL Bologna, Bologna, Italy.
    Franceschini, Tania
    Pathology Unit, Maggiore Hospital, AUSL Bologna, Bologna, Italy.
    Riefolo, Mattia
    Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy; Pathology Unit, Maggiore Hospital, AUSL Bologna, Bologna, Italy.
    Davidsson, Sabina
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology.
    Carlsson, Jessica
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine.
    Karlsson, Mats G.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Low level of interobserver concordance in assessing histological subtype and tumor grade in patients with penile cancer may impair patient care2022Inngår i: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 480, nr 4, s. 879-886Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Differentiation between penile squamous cell carcinoma patients who can benefit from limited organ-sparing surgery and those at significant risk of lymph node metastasis is based on histopathological prognostic factors including histological grade and tumor histological subtype. We examined levels of interobserver and intraobserver agreement in assessment of histological subtype and grade in 207 patients with penile squamous cell carcinoma. The cases were assessed by seven pathologists from three hospitals located in Sweden and Italy. There was poor to moderate concordance in assessing both histological subtype and grade, with Fleiss kappas of 0.25 (range: 0.02-0.48) and 0.23 (range: 0.07-0.55), respectively. When choosing HPV-associated and non-HPV-associated subtypes, interobserver concordance ranged from poor to good, with a Fleiss kappa value of 0.36 (range: 0.02-0.79). A re-review of the slides by two of the pathologists showed very good intraobserver concordance in assessing histological grade and subtype, with Cohen's kappa values of 0.94 and 0.91 for grade and 0.95 and 0.84 for subtype. Low interobserver concordance could lead to undertreatment and overtreatment of many patients with penile cancer, and brings into question the utility of tumor histological subtype and tumor grade in determining patient treatment in pT1 tumors. 

  • 7.
    Gebregzabher, Endale
    et al.
    Department of Biochemistry, St. Paul's Hospital Millennium Medical College, Ethiopia.
    Seifu, Daniel
    Department of Biochemistry, Division of Basic Sciences, University of Global Health Equity, Kigali, Rwanda.
    Tigneh, Wondemagegnhu
    Department of Oncology, School of Medicine, Addis Ababa University, Ethiopia.
    Bokretsion, Yonas
    Department of Pathology, School of Medicine, Addis Ababa University, Ethiopia.
    Bekele, Abebe
    Deputy Vice Chancellor, University of Global Health Equity, Kigali, Rwanda.
    Abebe, Markos
    Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper.
    Karlsson, Christina
    Örebro universitet, Institutionen för hälsovetenskaper.
    Karlsson, Mats
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Detection of High- and Low-Risk HPV DNA in Archived Breast Carcinoma Tissues from Ethiopian Women2021Inngår i: International Journal of Breast Cancer, ISSN 2090-3170, E-ISSN 2090-3189, Vol. 2021, artikkel-id 2140151Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Human papilloma virus (HPV) is involved in the development of cancer of the cervix, mouth and throat, anus, penis, vulva, or vagina, but it has not been much considered as a cause of breast cancer. Recently, a number of investigations have linked breast cancer to viral infections. High-risk HPV types, predominantly HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59, are established as carcinogens in humans. In this study we aimed to detect 19 high-risk and 9 low-risk HPVs from archived breast tumor tissue among Ethiopian women.

    Methods: In this study, 75 breast cancer patients from Tikur Anbassa Specialized Hospital in Addis Ababa (Ethiopia) were included. HPV detection and genotyping were done using the novel Anyplex™ II HPV28 Detection Assay at the Orebro University Hospital, Sweden. The Anyplex™ II PCR System detects 19 high-risk HPV types (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 69, 73, and 82) and 9 low-risk HPV types (6, 11, 40, 42, 43, 44, 54, 61, and 70). IHC for p16 was done using an automated system, the Dako Autostainer Link.

    Results: Out of the 75 valid tests, two were found to be positive (2.7%) for HPV. One of the cases was positive for the high-risk HPV16 genotype while the other was positive both for the high-risk HPV39 and the low-risk HPV6. The cell cycle protein p16 was highly expressed in the case positive for the high-risk HPV16, but it was not expressed in the case positive for HPV39.

    Conclusion: The prevalence of HPV is low in Ethiopian breast cancer patients, but the role played by HPV in breast carcinogenesis among Ethiopian breast cancer patients cannot be commented based on these observations.

  • 8.
    Helenius, Gisela
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper.
    Bergengren, Lovisa
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Women's Health.
    Molecular triage of cervical screening samples in women 55-59 years of age: a pilot study2023Inngår i: Infectious Agents and Cancer, E-ISSN 1750-9378, Vol. 18, nr 1, artikkel-id 31Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: With HPV screening the specificity of screening positives has decreased, even with a cytological triage test. Increases in colposcopies and detection of benign or low-grade dysplasia are reported, not least in older women. These results highlight the necessity to find other triage tests in HPV screening strategies, so that women can be more accurately selected for colposcopy, thus minimizing the clinically irrelevant findings.

    METHODS: The study included 55- to 59-year-old women who exited the screening with normal cytology, but later in a follow-up test were positive for the HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 and had a cervical cone biopsy done. To model a screening situation with hrHPV-positive women, three different triage strategies, namely, cytology, genotyping and methylation, were performed. The study considered the effect of direct referral to colposcopy for HPV genotypes 16, 18, 31, 33, 45, 52 and 58, and methylation for FAM19A4 and hsa-mir124-2 and/or any form of abnormal cytology.

    RESULTS: Seven out of 49 women aged 55-59 years with hrHPV had a cone biopsy with high-grade squamous intraepithelial lesion. No triage method found all cases, and when comparing positive and negative predictive value and false negative rate, cytology showed better results than genotyping and methylation.

    CONCLUSION: This study does not support a switch in triage strategies from cytology to hrHPV genotyping and methylation for women above 55 years of age yet, but demonstrates the need for more evidence on molecular triage strategies.

  • 9.
    Helenius, Gisela
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Lillsunde-Larsson, Gabriella
    Bergengren, Lovisa
    Örebro universitet, Institutionen för hälsovetenskaper.
    Kaliff, Malin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Karlsson, Mats
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Preliminary data from a Swedish self-sampling study in postmenopausal women2019Konferansepaper (Annet vitenskapelig)
    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.

  • 10.
    Helenius, Gisela
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Ottestig, Elin
    Kaliff, Malin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper.
    Karlsson, Mats
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Bergengren, Lovisa
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Distribution of HPV-genotypes in a Swedish screening population2018Konferansepaper (Fagfellevurdert)
  • 11.
    Hermansson, Ruth S.
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden; Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Olovsson, Matts
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Gustavsson, Inger
    Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.
    Gyllensten, Ulf
    Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.
    Lindkvist, Olga
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Lindberg, Julia Hedlund
    Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine.
    Lindström, Annika K.
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Incidence of oncogenic HPV and HPV-related dysplasia five years after a negative HPV test by self-sampling in elderly women2022Inngår i: Infectious Agents and Cancer, E-ISSN 1750-9378, Vol. 17, nr 1, artikkel-id 42Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Cervical cancer prevention for older women can be challenging since there are no specific guidelines for this group. This study aimed to determine the incidence of oncogenic HPV and HPV-related dysplasia in elderly women 5 years after being HPV negative.

    METHODS: Invited women participated five years earlier in a study where self-sampling for HPV testing was applied, at this time, they were all HPV negative. The women were now, five years later invited to perform self-sampling for HPV testing. Women with a positive result performed a repeat HPV test. Those with a positive repeat HPV test were examined by colposcopy, biopsy and cytology.

    RESULTS: Of the 804 invited women, 634 (76.9%) agreed to participate in the study and a self-sampling kit was sent to them. Of these, 99.6% (632/634) sent a sample to the HPV laboratory. The participation rate in each age group was 93.3% at age 65, 74.0% at age 70, 80.7% at age 75 and 64.6% at age 80. Overall 18 women (2.8%, 95% CI 3.2 to 6.0) were HPV positive in the first test and 8 (1.3%, 95% CI 0.6 to 2.6) in the second test. Sampling for the second test was done on average 5.4 months after the first test. Fifty per cent (4/8) of the women with a positive repeat test had dysplasia in histology.

    CONCLUSION: The incidence of HPV in previously HPV-negative elderly women was low. Among women who were HPV positive in a repeat test, there was a high prevalence of low grade dysplasia.

  • 12.
    Hälleberg Nyman, Maria
    et al.
    Örebro universitet, Institutionen för hälsovetenskaper. University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Blomberg, Karin
    Örebro universitet, Institutionen för hälsovetenskaper.
    Schröder, Agneta
    Örebro universitet, Institutionen för hälsovetenskaper. Region Örebro län. University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Health Science, Faculty of Health, Care and Nursing, Norwegian University of Science and Technology (NTNU), Gjövik, Norway.
    Older women's perceptions of HPV self-sampling and HPV-sampling performed by a midwife: a phenomenographic study2024Inngår i: BMC Public Health, E-ISSN 1471-2458, Vol. 24, nr 1, artikkel-id 211Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Cervical cancer is a global disease and it is well established that cervical cancer is caused by human papillomavirus (HPV). In Sweden self-sampling for HPV is now used as a complement to sampling performed by a midwife. However, there is a lack of knowledge on how older women perceive the self-sampling compared to the sampling performed by a midwife. Therefore, the aim of the study was to describe how women, aged 64 years and older, perceived the process of self-sampling and sampling performed by a midwife for HPV-testing.

    METHODS: Eighteen women were included in a qualitative interview study, and a phenomenographic approach was used for the analysis of the interviews.

    RESULTS: Three descriptive categories emerged: Confidence in sampling, Facilitating participation and Being informed. Within the categories, eight conceptions emerged describing the variation relating to how the women perceived the process of self-sampling and sampling performed by a midwife.

    CONCLUSIONS: Women in this study describe confidence in self-sampling for HPV-testing and that the self-sampling was saving time and money, both for themselves and for society. Information in relation to an HPV-positive test result is of importance and it must be kept in mind that women affected by HPV may feel guilt and shame, which health care professionals should pay attention to. This knowledge can be used in education of health care staff.

  • 13.
    Kaliff, Malin
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Bergengren, Lovisa
    Örebro universitet, Institutionen för hälsovetenskaper. Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Women’s Health.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Karlsson, Mats
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för medicinska vetenskaper. Örebro universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine.
    DNA methylation analysis in HPV-positive screening samples from women 30-69 years in the cervical cancer-screening program in Örebro, Sweden: a pilot study2019Inngår i: EUROGIN 2019 ABSTRACTS: POSTERS, 2019Konferansepaper (Fagfellevurdert)
  • 14.
    Kaliff, Malin
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Bohr Mordhorst, Louise
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Karlsson, Mats G.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine.
    Droplet Digital PCR for type-specific detection and quantification of nine different HPV genotypes in cervical carcinomasManuskript (preprint) (Annet vitenskapelig)
  • 15.
    Kaliff, Malin
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Ekman, Maria
    Department of Research and Development, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Ottestig, Elin
    School of Health Sciences, Örebro University, Örebro, Sweden.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Bergengren, Lovisa
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Women's Health.
    Karlsson, Mats G.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Research and Development.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine.
    Full genotyping and FAM19A4/miR124-2 methylation analysis in high-risk HPV-positive samples from women over 30 years participating in cervical cancer screening in Örebro, SwedenManuskript (preprint) (Annet vitenskapelig)
  • 16.
    Kaliff, Malin
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Karlsson, Mats
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Sorbe, Bengt
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Bohr Mordhorst, Louise
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine.
    HPV-negative Tumors in a Swedish Cohort of Cervical Cancer2020Inngår i: International Journal of Gynecological Pathology, ISSN 0277-1691, E-ISSN 1538-7151, Vol. 39, nr 3, s. 279-288Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Despite the common perception that the human papilloma virus (HPV) is a requirement for the development of cervical cancer (CC), a considerable number of CCs test HPV negative. Presently, many countries are shifting to HPV primary CC screening, and it is of importance to increase the knowledge about the group of CCs that test HPV negative. The aim of this study was to reinvestigate a proportion of cervical tumors with a primary negative or invalid test result. Reinvestigation with repeated genotyping (targeting L1) was followed by analysis with an alternative target method (targeting E6/E7) on existing or additional tumor material. Consistently negative tumors were histologically evaluated, and cases with low or lacking tumor cell content, consistent invalid test results, or with suspicion of other than cervical origin were excluded. HPV-negative cases were thereafter subjected to immunohistochemistry (Cytokeratin 5, pan cytokeratin, protein 63, P16, and P53). The HPV-negative proportion could after reinvestigation be reduced by one-half (14%-7%). Additional positive samples were often detected in late polymerase chain reaction cycles, with an alternative (E6/E7) or the same (L1) target, or with a method using shorter amplicon lengths. Confirmed HPV negativity was significantly associated with worse prognosis, high patient age, longer storage time, and adenocarcinoma histology. Some of the HPV-negative cases showed strong/diffuse p16 immunoreactivity, indicating some remaining false-negative cases. False HPV negativity in this cohort was mainly linked to methodological limitations in the analysis of stored CC material. The small proportion of presumably true HPV-negative adenocarcinomas is not a reason for hesitation in revision to CC screening with primary HPV testing.

  • 17.
    Kaliff, Malin
    et al.
    Department of Laboratory Medicine, Örebro University, Örebro, Sweden.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Karlsson, Mats
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Research and Development.
    Bergengren, Lovisa
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Women's Health.
    Full genotyping and FAM19A4/miR124-2 methylation analysis in high-risk human papillomavirus-positive samples from women over 30 years participating in cervical cancer screening in Örebro, Sweden2022Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 17, nr 9, artikkel-id e0274825Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Currently, cervical cancer prevention is undergoing comprehensive development regarding human papillomavirus (HPV) vaccination and cervical cancer screening. In Sweden and many other countries, high coverage vaccinated cohorts are entering screening within the next few years. This entails demands for baseline HPV genotype data across the screening age range for surveillance and a basis for screening program adjustment. In 2016, Örebro County, Sweden, changed to primary HPV screening using HPV mRNA testing followed by cytology triage. An alternative triage method to cytology could allow for a fully molecular screening algorithm and be implemented in a screening program where self-sampling is included. Hypermethylation analysis of the human genes FAM19A4/miR124-2 has been suggested as a promising triage method. HPV mRNA-positive screening samples (n = 529) were included and subjected to genotyping targeting a broad range of both low-risk and high-risk genotypes in addition to hypermethylation analysis of the two human genes FAM19A4/miR124-2. Data were connected to cytological and histological status and age. The most commonly detected genotypes were HPV31, 16, and 52. In addition, HPV18 was one of the most common genotypes in high-grade squamous intraepithelial lesions (HSILs) samples. In relation to available vaccines, 26% of the women with histological HSIL or cancer (≥HSIL) tested positive for only hrHPV included in the quadrivalent vaccine and 77% of the genotypes in the nonavalent vaccine. According to these figures, a relatively large proportion of the HSILs will probably remain, even after age cohorts vaccinated with the quadrivalent vaccine enter the screening program. Hypermethylation positivity was associated with increasing age, but no HPV-related independently predictive factors were found. Accordingly, age needs to be considered in development of future screening algorithms including triage with hypermethylation methodology.

  • 18.
    Kaliff, Malin
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Louise, Bohr Mordhorst
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Karlsson, Mats
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Optimization of droplet digital PCR assays for the type specific detection and quantification of five HPV genotypes, also including additional data on viral load of nine different HPV genotypes in cervical carcinomas2021Inngår i: Journal of Virological Methods, ISSN 0166-0934, E-ISSN 1879-0984, Vol. 294, artikkel-id 114193Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The droplet digital PCR (ddPCR) system enables high-sensitivity detection of nucleic acids and direct absolute quantification of the targets. The aim of this research was to evaluate this system for viral load (VL) analysis of the human papillomavirus (HPV) genotypes HPV31, 35, 39, 51 and 56 measured in number of viral particles per cell. The sample types used for the optimization of the ddPCR assay were formalin-fixed paraffin-embedded (FFPE) tissues and cervical liquid cytology samples. The presently optimized ddPCR assays, together with assays optimized previously for HPV16, 18, 33 and 45, with the same ddPCR method, were used for the VL analysis of cervical tumor samples. Results published previously on the present study cohort showed that women with a cervical tumor containing multiple high-risk HPV genotypes had a worse prognosis compared to women with single-genotype-infected tumors. The VL was therefore analyzed in this study for the same cohort, as a possible explanatory factor to the prognostic differences. The results of the optimization part of the study, with analysis of VL using ddPCR in DNA from varying sample types (FFPE and liquid cytology samples), showed that each of the five assays demonstrated good inter- and intra-assay means with a coefficient of variation (CV) under 8% and 6% respectably. The cohort results showed no difference in VL between tumors with multiple and single HPV infections, and therefore did most likely not constitute a contributing factor for prognostic differences observed previously. However, tumors from women aged 60 years or older or containing certain HPV genotypes and genotype genera were associated with a higher VL.

  • 19.
    Kaliff, Malin
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Sorbe, Bengt
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Mordhorst, Louise Bohr
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Karlsson, Mats G.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine.
    Findings of multiple HPV genotypes in cervical carcinoma are associated with poor cancer-specific survival in a Swedish cohort of cervical cancer primarily treated with radiotherapy2018Inngår i: Oncotarget, E-ISSN 1949-2553, Vol. 9, nr 27, s. 18786-18796Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cervical cancer (CC) is one of the most common cancers in women and virtually all cases of CC are a result of a persistent infection of human papillomavirus (HPV). For disease detected in early stages there is curing treatment but when diagnosed late with recurring disease and metastasis there are limited possibilities. Here we evaluate HPV impact on treatment resistance and metastatic disease progression. Prevalence and distribution of HPV genotypes and HPV16 variants in a Swedish CC patient cohort (n=209) was evaluated, as well as HPV influence on patient prognosis. Tumor samples suitable for analysis (n=204) were genotyped using two different real-time PCR methods. HPV16 variant analysis was made using pyrosequencing. Results showed that HPV prevalence in the total series was 93%. Of the HPV-positive samples, 13% contained multiple infections, typically with two high-risk HPV together. Primary cure rate for the complete series was 95%. Recurrence rate of the complete series was 28% and distant recurrences were most frequent (20%). Patients with tumors containing multiple HPV-strains and particularly HPV genotypes belonging to the alpha 7 and 9 species together had a significantly higher rate of distant tumor recurrences and worse cancer-specific survival rate.

  • 20.
    Kirrander, Peter
    et al.
    Örebro University Hospital, Örebro, Sweden.
    Kolaric, Aleksandra
    Örebro University Hospital, Örebro, Sweden.
    Helenius, Gisela
    Örebro University Hospital, Örebro, Sweden.
    Windahl, Torgny
    Örebro University Hospital, Örebro, Sweden.
    Andrén, Ove
    Örebro University Hospital, Örebro, Sweden.
    Stark, Jennifer Rider
    Örebro University Hospital, Örebro, Sweden; Brigham & Women’s Hospital, Boston MA, USA; Harvard Medical School, Boston MA, USA.
    Lillsunde-Larsson, Gabriella
    Örebro University Hospital, Örebro, Sweden.
    Elgh, Fredrik
    Örebro universitet, Hälsoakademin. Umeå University, Umeå, Sweden.
    Karlsson, Mats G.
    Örebro universitet, Hälsoakademin. Örebro University Hospital, Örebro, Sweden.
    Human papillomavirus prevalence, distribution and correlation to histopathological parameters in a large Swedish cohort of men with penile carcinoma2011Inngår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 108, nr 3, s. 355-359Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE To analyse the overall and type-specific human papillomavirus (HPV) prevalence and distribution in penile carcinoma and determine the correlation to histopathological parameters.

    PATIENTS AND METHODS In this retrospective study, we analysed HPV status in 241 patients with penile carcinoma, treated at Orebro University Hospital, Orebro, Sweden, between 1984 and 2008. Age and date at diagnosis was recorded. The tumour specimens were categorized according to the UICC 2002 TNM classification. A subset of patients was operatively staged with regard to lymph node status. A commercially available Real Time PCR was used to detect 13 different types of HPV (6,11,16,18,31,33,35,45,51,52,56,58 and 59).

    RESULTS We excluded 25 patients due to low DNA quality. Of the remaining 216, 179 (82.9%) tumour specimens were HPV infected. The majority of cases positive for HPV (70.4%) were infected by a single-type. The most frequent type was HPV 16 followed by HPV 18. No significant association between HPV status and pathological tumour stage, grade or lymph node status was found.

    CONCLUSION The HPV prevalence found is higher than in most other studies, further strengthening HPV as an etiological agent in penile carcinoma. Furthermore, the high prevalence of HPV 16 and 18 raises the question of what potential impact current HPV vaccines that target these specific HPV types might have on penile carcinoma. No significant association between HPV status and histopathological parameters was found in the present study. Additional investigations are needed to draw final conclusions on the prognostic value of HPV status in penile carcinoma.

  • 21.
    Kumakech, Edward
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Makerere University College of Health Sciences, Kampala, Uganda.
    Berggren, Vanja
    Medical Faculty, Lund University, Lund; Global Health, Karolinska Institute, Stockholm.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro.
    Helenius, Gisela
    Örebro universitet, Institutionen för läkarutbildning. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro.
    Kaliff, Malin
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University.
    Karlsson, Mats
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro.
    Musubika, Carol
    Makerere University College of Health Sciences, Kampala, Uganda.
    Kirimunda, Samuel
    Makerere University College of Health Sciences, Kampala, Uganda.
    Wabinga, Henry
    Makerere University College of Health Sciences, Kampala, Uganda.
    Andersson, Sören
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University.
    Prevalence, genotypes and risk factors for vaccine and non-vaccine types of Human Papillomavirus (HPV) infections among Bivalent HPV-16/18 vaccinated and non-vaccinated young women in Ibanda district Uganda: 5 year follow up studyManuskript (preprint) (Annet vitenskapelig)
  • 22.
    Kumakech, Edward
    et al.
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Pathology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda.
    Berggren, Vanja
    Faculty of Medicine, Lund University, Lund, Sweden; Department of Public Health (Global Health/IHCAR), Karolinska Institute, Stockholm, Sweden.
    Wabinga, Henry
    Department of Pathology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Kaliff, Malin
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University Hospital and Örebro University, Örebro, Sweden.
    Karlsson, Mats
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Kirimunda, Samuel
    Department of Pathology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda.
    Musubika, Caroline
    Department of Pathology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda.
    Andersson, Sören
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Significantly Reduced Genoprevalence of Vaccine-Type HPV-16/18 Infections among Vaccinated Compared to Non-Vaccinated Young Women 5.5 Years after a Bivalent HPV-16/18 Vaccine (Cervarix®) Pilot Project in Uganda2016Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 11, nr 8, artikkel-id e0160099Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The objective of this study was to determine the prevalence and some predictors for vaccine and non-vaccine types of HPV infections among bivalent HPV vaccinated and non-vaccinated young women in Uganda. This was a comparative cross sectional study 5.5 years after a bivalent HPV 16/18 vaccination (Cervarix®, GlaxoSmithKline, Belgium) pilot project in western Uganda. Cervical swabs were collected between July 2014-August 2014 and analyzed with a HPV genotyping test, CLART® HPV2 assay (Genomica, Madrid Spain) which is based on PCR followed by microarray for determination of genotype. Blood samples were also tested for HIV and syphilis infections as well as CD4 and CD8 lymphocyte levels. The age range of the participants was 15-24 years and mean age was 18.6(SD 1.4). Vaccine-type HPV-16/18 strains were significantly less prevalent among vaccinated women compared to non-vaccinated women (0.5% vs 5.6%, p 0.006, OR 95% CI 0.08(0.01-0.64). At type-specific level, significant difference was observed for HPV16 only. Other STIs (HIV/syphilis) were important risk factors for HPV infections including both vaccine types and non-vaccine types. In addition, for non-vaccine HPV types, living in an urban area, having a low BMI, low CD4 count and having had a high number of life time sexual partners were also significant risk factors. Our data concurs with the existing literature from other parts of the world regarding the effectiveness of bivalent HPV-16/18 vaccine in reducing the prevalence of HPV infections particularly vaccine HPV- 16/18 strains among vaccinated women. This study reinforces the recommendation to vaccinate young girls before sexual debut and integrate other STI particularly HIV and syphilis interventions into HPV vaccination packages.

  • 23.
    Larsson, Gabriella Lillsunde
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats G
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    HPV testing of biobanked liquid-based cytology: a validation study2016Inngår i: International Journal of Biological Markers, ISSN 0393-6155, E-ISSN 1724-6008, Vol. 31, nr 2, s. E218-E223Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: The aim of the study was to investigate whether biobanked liquid-based cytology (LBC) vaginal samples could be reanalyzed for the biomarkers HPV DNA and mRNA without loss of sensitivity.

    Methods: One hundred LBC samples with ASCUS or CIN1 were tested for HPV DNA and mRNA before and after biobanking. DNA analysis targeted the viral genes E6 and E7, 12 high-risk and 2 low-risk HPV types together with the human control gene HBB, using real-time PCR. The Aptima HPV assay was used for mRNA analysis of 14 high-risk HPV types.

    Results: With Aptima there was 84% agreement between results before and after biobanking. The sensitivity and specificity were 0.79 (95% CI, 0.68-0.88) and 0.94 (95% CI, 0.80-0.99), respectively. With the DNA-based method, the agreement between results was 87%, the sensitivity 0.85 (95% CI, 0.75-0.92) and the specificity 0.95 (95% CI, 0.77-1.00). Both methods presented a significant difference between positive results before and after biobanking; McNemar test: p = 0.004, p = 0.003, Cohen's kappa: 0.67 (95% CI, 0.53-0.81), 0.68 (95% CI, 0.52-0.84). Cycle threshold values for the DNA method were higher for all genotypes after biobanking, except for HPV-59. Some loss of sensitivity was seen after biobanking but the concordance between HPV detection before and after biobanking was good for both evaluated methods.

    Conclusions: Biobanking of LBC vaginal samples offers a good platform for HPV testing and could be extended to further molecular analyses. However, in order to ensure a valid test result a larger portion needs to be analyzed from the biobanked sample.

  • 24.
    Lillsunde Larsson, Gabriella
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Kaliff, M.
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Bergengren, Lovisa
    Department of Women's health, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper.
    HPV Genotyping from the high risk mRNA Aptima assay: a direct approach using DNA from Aptima sample tubes2016Inngår i: Journal of Virological Methods, ISSN 0166-0934, E-ISSN 1879-0984, Vol. 235, s. 80-84Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 25.
    Lillsunde Larsson, Gabriella
    et al.
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine.
    Kaliff, Malin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Sorbe, Bengt
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Oncology.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Karlsson, Mats G.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    HPV16 viral characteristics in primary, recurrent and metastatic vulvar carcinoma2018Inngår i: Papillomavirus research, ISSN 2405-8521, Vol. 6, s. 63-69Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Vulvar carcinoma is the fourth most common gynecological malignancy. Two separate carcinogenic pathways are suggested, where one is associated with the human papillomavirus (HPV) and HPV16 the most common genotype.

    The aim of this study was to evaluate HPV-markers in a set of primary tumors, metastases and recurrent lesions of vulvar squamous cell carcinomas (VSCC). Ten HPV16-positive VSCC with metastatic regional lymph nodes, distant lymphoid/hematogenous metastases or local recurrent lesions were investigated for HPV genotype, HPV16 variant, HPV16 viral load, HPV16 integration and HPV16 E2BS3 and 4 methylation.

    In all 10 analyzed case series, the same HPV genotype (HPV16), HPV16 variant and level of viral load were detected in all lesions within a patient case. Primary tumors with a high E2/E6 ratio were found to have fewer vulvar recurrences and/or metastases after diagnosis and treatment. Also, a significantly lower viral load was evident in regional lymph nodes compared to primary tumors.

    The data presented strengthens the evidence for a clonal HPV-induced pathway for vulvar carcinoma.

  • 26.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Characterization of HPV-induced vaginal and vulvar carcinoma2014Doktoravhandling, med artikler (Annet vitenskapelig)
    Delarbeid
    1. Human Papillomavirus (HPV) and HPV 16-Variant Distribution in Vulvar Squamous Cell Carcinoma in Sweden
    Åpne denne publikasjonen i ny fane eller vindu >>Human Papillomavirus (HPV) and HPV 16-Variant Distribution in Vulvar Squamous Cell Carcinoma in Sweden
    Vise andre…
    2012 (engelsk)Inngår i: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 22, nr 8, s. 1413-1419Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Objective: To investigate the human papillomavirus (HPV) and HPV type 16-variant distribution in a series of vulvar squamous cell carcinomas (VSCC) and to evaluate the impact of HPV and HPV 16-variant on prognosis.

    Methods: A series of 133 patients who had a diagnosis of VSCC (1983-2008) was selected for the study. Detection of 11 high-risk HPV types (16, 18, 31, 33, 39, 45, 51, 52, 56, 58, and 59) and 2 low-risk HPV types (6 and 11) was performed with real-time polymerase chain reaction. Samples positive for HPV 16 were further analyzed for variant determination of 7 positions in the E6 gene with polymerase chain reaction and pyrosequencing.

    Results: Forty (30.8%) of 130 tumors were found to be HPV positive. Human papillomavirus type 16 was found in 31 cases, HPV 18 was found in 2 cases, HPV 33 was found in 5 cases, and HPV 56 and HPV 59 were found in one case each. All but one tumor harboring HPV 16 were of European linage, and the 3 most common variants were E-p (n = 13), E-G350 (n = 7), and E-G131 (n = 5). HPV positivity was associated with the basaloid tumor type and occurred in significantly younger patients. Overall and recurrence-free survival rates were better in HPV-positive cases, but after correction for age and tumor size, HPV status was no longer an independent and significant prognostic factor. The survival rates of the various HPV 16 variants were not significantly different, but there was a trend of worse outcome for the E-G131-variant group.

    Conclusions: Human papillomavirus positivity of 30.8% is similar to other reports on VSCC. To our knowledge, this first variant determination of HPV 16 in vulvar carcinoma in a Swedish cohort indicated that the variant E-G131 may have an increased oncogenic potential in patients with VSCC.

    Emneord
    Vulvar carcinoma, Human papillomavirus, HPV 16 variants
    HSV kategori
    Identifikatorer
    urn:nbn:se:oru:diva-43018 (URN)10.1097/IGC.0b013e31826a0471 (DOI)000309543700023 ()23013732 (PubMedID)2-s2.0-84867268780 (Scopus ID)
    Tilgjengelig fra: 2015-02-27 Laget: 2015-02-27 Sist oppdatert: 2024-01-03bibliografisk kontrollert
    2. Prognostic impact of human papilloma virus (HPV) genotyping and HPV-16 subtyping in vaginal carcinoma
    Åpne denne publikasjonen i ny fane eller vindu >>Prognostic impact of human papilloma virus (HPV) genotyping and HPV-16 subtyping in vaginal carcinoma
    Vise andre…
    2013 (engelsk)Inngår i: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 129, nr 2, s. 406-411Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Objective

    The objectives of this study are to investigate the human papilloma virus (HPV) distribution in vaginal cancer and to evaluate HPV-genotype as well as HPV16-variant impact on prognosis.

    Methods

    Sixty-nine patients diagnosed with primary vaginal carcinoma (1975-2002) were included in the study. Detection of twelve high-risk HPV (hr HPV) and two low-risk HPV (lr HPV) was performed with realtime-PCR. Samples positive for HPV-16 were analyzed for variants in the E6-gene with PCR and pyrosequencing.

    Results

    53.6% (37/69) of the tumors were found to be HPV-positive, mostly for HPV-16 (N=26). Other HPV-types were HPV-18 (N=2), HPV-31 (N=2), HPV-33 (N=2), HPV-45 (N=1), HPV-52 (N=2), HPV-56 (N=1) and HPV-58 (N=1). Only European subtypes of HPV-16 were represented and the two most common HPV-16-variants were E-p (N=13) and E-G350 (N=11). Patients with HPV-positive tumors (N=37) had a significantly (log-rank test=3341; p = 0.0008) superior 5-year overall survival rate as well as cancer-specific survival rate and progression-free survival rate (p = 0.0002; p = 0.0004), compared with patients with HPV-negative tumors (N=32). Interestingly, patients with HPV-16-positive tumors had a superior overall survival compared with patients with tumors containing other HPV-genotypes. In a Cox proportional multivariate analysis age, tumor size, and HPV-status were independent and significant prognostic factors with regard to overall survival rate.

    Conclusions

    HPV-status is of prognostic importance in vaginal carcinoma and varies with viral genotype. In this era of HPV-vaccination, genotypes other than those included in the vaccination program could still lead to vaginal carcinoma with unfavorable prognosis.

    Emneord
    Vaginal carcinoma, Human papilloma virus, HPV-16-variants, Prognosis
    HSV kategori
    Forskningsprogram
    Biomedicin
    Identifikatorer
    urn:nbn:se:oru:diva-29270 (URN)10.1016/j.ygyno.2013.02.004 (DOI)000318058600024 ()23402906 (PubMedID)2-s2.0-84876292443 (Scopus ID)
    Tilgjengelig fra: 2013-05-31 Laget: 2013-05-31 Sist oppdatert: 2024-01-03bibliografisk kontrollert
    3. Viral Load, Integration and Methylation of E2BS3 and 4 in Human Papilloma Virus (HPV) 16-Positive Vaginal and Vulvar Carcinomas
    Åpne denne publikasjonen i ny fane eller vindu >>Viral Load, Integration and Methylation of E2BS3 and 4 in Human Papilloma Virus (HPV) 16-Positive Vaginal and Vulvar Carcinomas
    2014 (engelsk)Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 9, nr 11, artikkel-id e112839Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Objective: To investigate if viral load, integration and methylation of E2BS3 and 4 represent different ways of tumor transformation in vaginal and vulvar carcinoma and to elucidate its clinical impact.

    Methods: Fifty-seven samples, positive for HPV16, were selected for the study. Detection of viral load was made with realtime-PCR using copy numbers of E6 and integration was calculated from comparing E2 to E6-copies. Methylation of E2BS3 and 4 was analysed using bisulphite treatment of tumor DNA, followed by PCR and pyrosequencing.

    Results: Vaginal tumors were found to have a higher viral load (p=0.024) compared to vulvar tumors but a high copy number (> median value, 15 000) as well as high methylation (> 50%) was significantly (p=0.010 and p=0.045) associated with a worse cancer-specific survival rate in vulvar carcinoma, but not in vaginal carcinoma. Four groups could be defined for the complete series using a Cluster Two step analysis; (1) tumors holding episomal viral DNA, viral load below 150 000 copies not highly methylated (n=25, 46.3%); (2) tumors harboring episomal viral DNA and being highly methylated (>50%; n=6, 11.1%); (3) tumors with viral DNA fully integrated (n=11, 20.4%), and (4) tumors harboring episomal viral DNA and being medium-or unmethylated (< 50%) and having a high viral load (> total mean value 150 000; n=12, 22.2%). The completely integrated tumors were found to be distinct group, whilst some overlap between the groups with high methylation and high viral load was observed.

    Conclusion: HPV16-related integration, methylation in E2BS3 and 4 and viral load may represent different viral characteristics driving vaginal and vulvar carcinogenesis. HPV16-related parameters were found to be of clinical importance in the vulvar series only.

    sted, utgiver, år, opplag, sider
    Public Library Science, 2014
    HSV kategori
    Identifikatorer
    urn:nbn:se:oru:diva-42542 (URN)10.1371/journal.pone.0112839 (DOI)000347709300111 ()2-s2.0-84911948854 (Scopus ID)
    Merknad

    Funding Agency:

    Örebro County Council Research Committee OLL-324811 OLL-259341

    Tilgjengelig fra: 2015-02-09 Laget: 2015-02-09 Sist oppdatert: 2021-06-14bibliografisk kontrollert
    4. HPV genotyping assays for archival clinical samples: an evaluation study
    Åpne denne publikasjonen i ny fane eller vindu >>HPV genotyping assays for archival clinical samples: an evaluation study
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:oru:diva-43020 (URN)
    Tilgjengelig fra: 2015-02-27 Laget: 2015-02-27 Sist oppdatert: 2022-02-11bibliografisk kontrollert
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  • 27.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för medicinska vetenskaper. Örebro universitet, Institutionen för hälsovetenskaper.
    HPV-induced cancers: a field overview with some research examples2021Konferansepaper (Annet vitenskapelig)
  • 28.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper.
    Kompetensväxling på laboratoriet med hjälp av masterprogram i Örebro: ett bra exempel på professionsutveckling och karriärvägar2022Inngår i: Laboratoriet, ISSN 0345-696X, Vol. 4, s. 9-12Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 29.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Örebro universitet, Institutionen för hälsovetenskaper.
    Masterprogram i metoder inom medicinsk diagnostik vid Örebro universitet: en möjlighet till ökad kompetens för framtidens laboratorier2021Inngår i: HP-bladet, ISSN 1401-7601, s. 29-33Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 30.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för medicinska vetenskaper. Örebro universitet, Institutionen för hälsovetenskaper.
    Molecular triage in the HPV screening era: experiences from a Swedish study2021Konferansepaper (Fagfellevurdert)
  • 31.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för medicinska vetenskaper. Örebro universitet, Institutionen för hälsovetenskaper.
    Molecular triage in the HPV screening era: experiences from a Swedish study2021Konferansepaper (Annet vitenskapelig)
  • 32.
    Lillsunde-Larsson, Gabriella
    et al.
    Region Örebro län. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Carlsson, Jessica
    Region Örebro län. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats G.
    Region Örebro län. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Helenius, Gisela
    Region Örebro län. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Evaluation of HPV Genotyping Assays for Archival Clinical Samples2015Inngår i: Journal of Molecular Diagnostics, ISSN 1525-1578, E-ISSN 1943-7811, Vol. 17, nr 3, s. 293-301Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Human papillomavirus (HPV) testing and genotyping of FFPE tissue samples is important in epidemiological investigations. Here, we compare four different HPV genotyping methods for use in FFPE clinical samples. Comparative testing was performed on 99 samples with a clinical suspicion of HPV. Specimens were analyzed with Anyplex II HPV28 detecting 28 genotypes using real-time PCR and melting curve analysis, CLART HPV2 detecting 35 genotypes using PCR and microarray detection, and MGP5+/6+ consensus primer system together with pyrosequencing. Results were compared to a real-time PCR reference protocol detecting 14 genotypes. In total, 68% of the samples were positive for an HPV genotype using the reference protocol and MGP5+/6+ primer system. Anyplex II HPV28 analysis and CLART HPV2 had 82% and 72% positive samples, respectively. All four methods showed good agreement when comparing the 14 genotypes included in the reference protocol. When evaluating all genotypes, the Anyplex II HPV28 assay and the CLART assay changed the status of the sample (individually or together) from negative with respect to the reference protocol to positive for either a Group 1 (n = 4) or Group 2 (n = 6) genotype. We conclude from this study that for an extended genotyping approach with a high sensitivity for FFPE specimens, both the Anyplex II HPV28 and CLART HPV2 assays are suitable alternatives despite minor intra-assay differences.

  • 33.
    Lillsunde-Larsson, Gabriella
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Carlsson, Jessica
    Karlsson, Mats G.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Örebro University Hospital.
    Helenius, Gisela
    Örebro universitet, Institutionen för läkarutbildning. Örebro University Hospital.
    HPV genotyping assays for archival clinical samples: an evaluation studyManuskript (preprint) (Annet vitenskapelig)
  • 34.
    Lillsunde-Larsson, Gabriella
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Digital droplet PCR (ddPCR) for the detection and quantification of HPV 16, 18, 33 and 45: a short report2017Inngår i: Cellular Oncology, ISSN 2211-3428, E-ISSN 2211-3436, Vol. 40, nr 5, s. 521-527Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Human papilloma virus (HPV) infection is associated with several anogenital malignancies. Here, we set out to evaluate digital droplet PCR (ddPCR) as a tool for HPV 16, 18, 33 and 45 viral load quantification and, in addition, to compare the efficacy of the ddPCR assay for HPV 16 detection with that of quantitative real-time PCR (qPCR).

    Clinical samples, positive for HPV genotypes 16, 18, 33 and 45 were analyzed for viral load using ddPCR. Sample DNA was cleaved before droplet generation and PCR. Droplets positive for VIC and FAM fluorescence were read in a QX200 Droplet reader (TM) (BIO-RAD) after which the viral load was calculated using Quantasoft software.

    We found that DNAs extracted from formalin fixed paraffin embedded (FFPE) tissue samples yielded lower amplification signals compared to those obtained from liquid based cytology (LBC) samples, but they were clearly distinguishable from negative background signals. The viral limit of detection was 1.6 copies of HPV 16, 2.8 copies of HPV 18, 4.6 copies of HPV 33 and 1.6 copies of HPV 45. The mean inter-assay coefficients of variability (CV) for the assays ranged from 3.4 to 7.0%, and the mean intra-assay CV from 2.6 to 8.2%. The viral load in the different cohorts of tumor samples ranged from 154 to 340,200 copies for HPV 16, 244 to 31,300 copies for HPV 18 and 738 to 69,100 copies for HPV 33. One sample positive for HPV 45 contained 1331 viral copies. When comparing qPCR data with ddPCR copy number data, the qPCR values were found to be 1 to 31 times higher.

    Separation of fragments in nanodroplets may facilitate the amplification of fragmented human and viral DNA. The method of digital droplet PCR may, thus, provide a new and promising tool for evaluating the HPV viral load in clinical samples.

  • 35.
    Lillsunde-Larsson, Gabriella
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Örebro University Hospital, Örebro, Sweden.
    Helenius, Gisela
    Örebro universitet, Institutionen för läkarutbildning. Örebro University Hospital, Örebro, Sweden.
    Andersson, Sören
    Örebro University Hospital, Örebro, Sweden.
    Elgh, Fredrik
    Umeå University Hospital, Umeå, Sweden.
    Sorbe, Bengt
    Örebro universitet, Hälsoakademin. Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro University Hospital, Örebro, Sweden.
    Human Papillomavirus (HPV) and HPV 16-Variant Distribution in Vulvar Squamous Cell Carcinoma in Sweden2012Inngår i: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 22, nr 8, s. 1413-1419Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To investigate the human papillomavirus (HPV) and HPV type 16-variant distribution in a series of vulvar squamous cell carcinomas (VSCC) and to evaluate the impact of HPV and HPV 16-variant on prognosis.

    Methods: A series of 133 patients who had a diagnosis of VSCC (1983-2008) was selected for the study. Detection of 11 high-risk HPV types (16, 18, 31, 33, 39, 45, 51, 52, 56, 58, and 59) and 2 low-risk HPV types (6 and 11) was performed with real-time polymerase chain reaction. Samples positive for HPV 16 were further analyzed for variant determination of 7 positions in the E6 gene with polymerase chain reaction and pyrosequencing.

    Results: Forty (30.8%) of 130 tumors were found to be HPV positive. Human papillomavirus type 16 was found in 31 cases, HPV 18 was found in 2 cases, HPV 33 was found in 5 cases, and HPV 56 and HPV 59 were found in one case each. All but one tumor harboring HPV 16 were of European linage, and the 3 most common variants were E-p (n = 13), E-G350 (n = 7), and E-G131 (n = 5). HPV positivity was associated with the basaloid tumor type and occurred in significantly younger patients. Overall and recurrence-free survival rates were better in HPV-positive cases, but after correction for age and tumor size, HPV status was no longer an independent and significant prognostic factor. The survival rates of the various HPV 16 variants were not significantly different, but there was a trend of worse outcome for the E-G131-variant group.

    Conclusions: Human papillomavirus positivity of 30.8% is similar to other reports on VSCC. To our knowledge, this first variant determination of HPV 16 in vulvar carcinoma in a Swedish cohort indicated that the variant E-G131 may have an increased oncogenic potential in patients with VSCC.

  • 36.
    Lillsunde-Larsson, Gabriella
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län.
    Helenius, Gisela
    Örebro universitet, Institutionen för läkarutbildning. Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Andersson, Sören
    Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Sorbe, Bengt
    Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Karlsson, Mats G.
    Region Örebro län. Örebro universitet, Institutionen för hälsovetenskap och medicin. Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Prognostic impact of human papilloma virus (HPV) genotyping and HPV-16 subtyping in vaginal carcinoma2013Inngår i: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 129, nr 2, s. 406-411Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective

    The objectives of this study are to investigate the human papilloma virus (HPV) distribution in vaginal cancer and to evaluate HPV-genotype as well as HPV16-variant impact on prognosis.

    Methods

    Sixty-nine patients diagnosed with primary vaginal carcinoma (1975-2002) were included in the study. Detection of twelve high-risk HPV (hr HPV) and two low-risk HPV (lr HPV) was performed with realtime-PCR. Samples positive for HPV-16 were analyzed for variants in the E6-gene with PCR and pyrosequencing.

    Results

    53.6% (37/69) of the tumors were found to be HPV-positive, mostly for HPV-16 (N=26). Other HPV-types were HPV-18 (N=2), HPV-31 (N=2), HPV-33 (N=2), HPV-45 (N=1), HPV-52 (N=2), HPV-56 (N=1) and HPV-58 (N=1). Only European subtypes of HPV-16 were represented and the two most common HPV-16-variants were E-p (N=13) and E-G350 (N=11). Patients with HPV-positive tumors (N=37) had a significantly (log-rank test=3341; p = 0.0008) superior 5-year overall survival rate as well as cancer-specific survival rate and progression-free survival rate (p = 0.0002; p = 0.0004), compared with patients with HPV-negative tumors (N=32). Interestingly, patients with HPV-16-positive tumors had a superior overall survival compared with patients with tumors containing other HPV-genotypes. In a Cox proportional multivariate analysis age, tumor size, and HPV-status were independent and significant prognostic factors with regard to overall survival rate.

    Conclusions

    HPV-status is of prognostic importance in vaginal carcinoma and varies with viral genotype. In this era of HPV-vaccination, genotypes other than those included in the vaccination program could still lead to vaginal carcinoma with unfavorable prognosis.

  • 37.
    Lillsunde-Larsson, Gabriella
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Helenius, Gisela
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Sorbe, Bengt
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Viral Load, Integration and Methylation of E2BS3 and 4 in Human Papilloma Virus (HPV) 16-Positive Vaginal and Vulvar Carcinomas2014Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 9, nr 11, artikkel-id e112839Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To investigate if viral load, integration and methylation of E2BS3 and 4 represent different ways of tumor transformation in vaginal and vulvar carcinoma and to elucidate its clinical impact.

    Methods: Fifty-seven samples, positive for HPV16, were selected for the study. Detection of viral load was made with realtime-PCR using copy numbers of E6 and integration was calculated from comparing E2 to E6-copies. Methylation of E2BS3 and 4 was analysed using bisulphite treatment of tumor DNA, followed by PCR and pyrosequencing.

    Results: Vaginal tumors were found to have a higher viral load (p=0.024) compared to vulvar tumors but a high copy number (> median value, 15 000) as well as high methylation (> 50%) was significantly (p=0.010 and p=0.045) associated with a worse cancer-specific survival rate in vulvar carcinoma, but not in vaginal carcinoma. Four groups could be defined for the complete series using a Cluster Two step analysis; (1) tumors holding episomal viral DNA, viral load below 150 000 copies not highly methylated (n=25, 46.3%); (2) tumors harboring episomal viral DNA and being highly methylated (>50%; n=6, 11.1%); (3) tumors with viral DNA fully integrated (n=11, 20.4%), and (4) tumors harboring episomal viral DNA and being medium-or unmethylated (< 50%) and having a high viral load (> total mean value 150 000; n=12, 22.2%). The completely integrated tumors were found to be distinct group, whilst some overlap between the groups with high methylation and high viral load was observed.

    Conclusion: HPV16-related integration, methylation in E2BS3 and 4 and viral load may represent different viral characteristics driving vaginal and vulvar carcinogenesis. HPV16-related parameters were found to be of clinical importance in the vulvar series only.

  • 38.
    Lillsunde-Larsson, Gabriella
    et al.
    Örebro universitet, Institutionen för hälsovetenskaper. Region Örebro län. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Kaliff, Malin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Hansen, Marit
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Comparison of mRNA and DNA HPV levels in HRHPV-positive primary screening samples using digital droplet PCR2017Konferansepaper (Fagfellevurdert)
  • 39.
    Lillsunde-Larsson, Gabriella
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Örebro universitet, Institutionen för hälsovetenskaper.
    Kaliff, Malin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Ottestig, Elin
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper.
    HPV genotyping of HPV primary screening positive samples in Örebro, Sweden2019Konferansepaper (Fagfellevurdert)
  • 40.
    Lillsunde-Larsson, Gabriella
    et al.
    Örebro universitet, Institutionen för hälsovetenskaper.
    Kaliff, Malin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Ottestig, Elin
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper.
    HPV genotyping of HPV primary screening positive samples in Örebro, Sweden2018Konferansepaper (Annet vitenskapelig)
  • 41.
    Lillsunde-Larsson, Gabriella
    et al.
    Örebro universitet, Institutionen för hälsovetenskaper. Dep. of Laboratory Medicine.
    Kaliff, Malin
    Örebro universitet, Institutionen för medicinska vetenskaper. Dep. of Laboratory Medicine.
    Sorbe, Bengt
    2Faculty of Medicine and Health- Örebro University, Dep. Of Oncology, Örebro, Sweden.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Dep. of Laboratory Medicine.
    Karlsson, Mats
    Örebro universitet, Institutionen för medicinska vetenskaper. Dep. of Laboratory Medicine.
    HPV16 VIRAL CHARACTERISTICS IN PRIMARY AND RECURRENT VULVAR CARCINOMA2018Konferansepaper (Annet vitenskapelig)
  • 42.
    Lillsunde-Larsson, Gabriella
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Örebro universitet, Institutionen för hälsovetenskaper.
    Wijkmark, Tanja
    Rhenberg, Marcus
    BLS student survey on the student perspective and their professional expectations2019Konferansepaper (Fagfellevurdert)
  • 43.
    Quttineh, Maysae
    et al.
    The Swedish Institute of Biomedical Laboratory Science (IBL), Stockholm, Sweden; Department of Laboratory Medicine, Region Jönköping County, Jönköping, Sweden.
    Heldestad, Victoria
    The Swedish Institute of Biomedical Laboratory Science (IBL), Stockholm, Sweden; Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Wijkmark, Tanja
    The Swedish Institute of Biomedical Laboratory Science (IBL), Stockholm, Sweden.
    Rehnberg, Marcus
    The Swedish Institute of Biomedical Laboratory Science (IBL), Stockholm, Sweden.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för medicinska vetenskaper. Örebro universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine, Örebro University, Örebro, Sweden; The Swedish Institute of Biomedical Laboratory Science (IBL), Stockholm, Sweden.
    Great interest in a Swedish nationally regulated specialist education among biomedical laboratory scientists and biomedical laboratory scientist students2021Inngår i: International Journal of Biomedical Laboratory Science, E-ISSN 2308-7706, Vol. 10, nr 1, s. 28-35Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Biomedical laboratory scientists (BLS) work in many different disciplines but one common denominator for all the fields within the profession is the rapid development in biomedicine and the corresponding increase of advanced technology. A nationally regulated specialist training for BLS is a way for the profession to gain advanced skills and to create career opportunities. From a larger study set, the aims of this sub-study were to investigate BLS student’s and professional’s view on education, choice of workplace, career development, advanced studies and a potential nationally regulated specialist training program. Two surveys were designed using webbenkater.com. The surveys were sent to BLS student members (n=483) and professional members (n=2083) of The Swedish Institute of Biomedical Laboratory Science (IBL), the professional organization of BLS´s in Sweden. Response rate was 57% (276/483) for the student sub-survey and 44% (n=923/2083) for the professional sub-survey. Students from all semesters (1-6, n=272) were represented, with a majority from semester 2, 4 and 6. Top reasons for choosing the BLS education were; easy to get a job (65%), stimulating work tasks (59%) and a good education for further studies (39%). A majority of the students planned for further advanced academic studies (64%) and 54% percent were interested in a potential nationally regulated specialist training. Among professionals, 21% stated there were explicit career paths at their workplace. The individual interest for a potential nationally regulated specialist training was 53% and most responders (93%) stated a need for such an education in Sweden. Among IBL members, there is great interest in a nationally regulated specialized training among both future and present professionals in Sweden. In relation to a future shortage, we also show that in order to attract students to BLS training, we need to be able to offer advanced training as well.

  • 44.
    Qvick, Alvida
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Sorbe, Bengt
    Region Örebro län. Örebro universitet, Institutionen för hälsovetenskaper. Department of Oncology.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Laboratory Medicine.
    Karlsson, Mats G.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Laboratory Medicine.
    Lillsunde Larsson, Gabriella
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Laboratory Medicine.
    Does p53 codon 72 polymorphism have a prognostic value in carcinoma of the vulva and vagina?2017Inngår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 34, nr 3, artikkel-id 36Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Human papilloma virus (HPV) is considered to be responsible for a large part of vaginal and vulvar carcinomas, and the p53 codon 72 polymorphism has been implicated in susceptibility to cancer induced by this virus, but with contradicting results. In this study, we have investigated the prognostic value of the codon 72 polymorphism by real-time PCR (qPCR) in two cohorts of vaginal (n = 66) and vulvar (n = 123) carcinomas. In vaginal carcinoma, arginine homozygous patients were significantly associated with a higher primary cure rate (p = 0.023) but also associated with a higher recurrence rate (p = 0.073), significant at distant locations (p = 0.009). No significant differences were found in overall survival rate (p = 0.499) or cancer-specific survival rate (p = 0.222). A higher frequency of arginine homozygosity was noted in HPV-positive tumors (p = 0.190) in comparison with HPV-negative tumors. In vulvar carcinoma, the genotype homozygous for arginine was significantly associated with a larger tumor size at diagnosis in the entire cohort (p = 0.015) and a lower cancer-specific survival rate (p = 0.024) compared with heterozygous (arginine/proline) in HPV-negative tumors. Our results indicate that the relation between HPV and the p53 codon 72 polymorphism is complex and the significance and mechanisms responsible for this relationship need to be further elucidated.

  • 45.
    Ranhem, Cecilia
    et al.
    Karolinska Institutet, Västerås, Sweden.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för medicinska vetenskaper. Örebro universitet, Institutionen för hälsovetenskaper. Örebro University Hospital, Örebro, Sweden.
    Farnebo, Marianne
    Karolinska Institutet, Stockholm, Sweden.
    Kashuba, Elena
    Karolinska Institutet, Stockholm, Sweden.
    Andersson, Sonia
    Karolinska Institutet, Stockholm, Sweden.
    Evaluation of dyskerin expression and the Cajal body protein WRAP53ß as potential prognostic markers for patients with primary vaginal carcinoma2021Inngår i: EUROGIN 2021 ABSTRACTS: FREE COMMUNICATIONS SESSIONS, 2021Konferansepaper (Fagfellevurdert)
  • 46.
    Ranhem, Cecilia
    et al.
    Department of Women’s and Children ’s Health, Karolinska Institutet, Stockholm, Sweden; Centre for Clinical Research, Hospital of Västmanland Västerås, Uppsala University, Västerås, Sweden; Region Västmanland, Västerås, Sweden.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Hedman, Håkan
    Department of Radiation Sciences, Umeå University, Umeå , Sweden.
    Lindquist, David
    Department of Radiation Sciences, Umeå University, Umeå , Sweden.
    Karlsson, Mats G.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Hellström, Ann-Cathrin
    Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Östensson, Ellinor
    Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden; Department of Medical Epidem iology and Biostatistics, Karolinsk a Institutet, Stockholm, Sweden.
    Sorbe, Bengt
    Department of Oncology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Hellman, Kristina
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Sonia
    Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Expression of LRIG proteins as possible prognostic factors in primary vaginal carcinoma2017Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 12, nr 8, artikkel-id e0183816Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Primary vaginal carcinoma (PVC) is a rare malignancy. Established prognostic factors include tumour stage and age at diagnosis. The leucine-rich repeats and immunoglobuline-like domains (LRIG)-1 protein functions as a tumour suppressor, but less is known about the functions of LRIG2 and LRIG3. The present study aimed to evaluate the expression of LRIG proteins and analyse their possible associations with clinical characteristics and survival in a cohort of PVC patients.

    Methods: We used immunohistochemistry to investigate LRIG1, LRIG2, and LRIG3 expression in tumour samples from a consecutive cohort of 70 PVC patients. The association between LRIG protein expression and clinical characteristics and cancer-specific survival was investigated using univariate and multivariate analyses.

    Results: The majority of PVC patients (72%) had > 50% LRIG1-and LRIG2-positive cells, and no or low LRIG3-positive cells. HPV status was significantly correlated with LRIG1 expression (p = 0.0047). Having high LRIG1 expression was significantly correlated with superior cancer-specific survival in univariate and multivariate analyses. LRIG2 and LRIG3 expression did not significantly correlate with clinical characteristics or survival.

    Conclusion: LRIG1 expression might be of interest as a prognostic marker in PVC patients, whereas the role of LRIG2 and LRIG3 expression remains to be clarified.

  • 47.
    Ranhem, Cecilia
    et al.
    Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Centre for Clinical Research Region Västmanland, Uppsala University, Västmanlands Hospital Västerås, Västerås, Sweden.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Lindqvist, David
    Department of Radiation Sciences, Umeå Universitet, Umeå, Sweden.
    Sorbe, Bengt
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Farnebo, Marianne
    Department of Bioscience and Nutrition, Karolinska Institutet, Stockholm, Sweden; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
    Hellman, Kristina
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Kovaleska, Larysa
    R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of National Academy of Sciences of Ukraine, Kiev, Ukraine.
    Kashuba, Elena
    R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of National Academy of Sciences of Ukraine, Kiev, Ukraine; Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Sonia
    Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Evaluation of dyskerin expression and the Cajal body protein WRAP53β as potential prognostic markers for patients with primary vaginal carcinoma2022Inngår i: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 23, nr 1, artikkel-id 30Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Primary vaginal cancer (PVC) is a rare gynaecological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53β), both of which exert their functions in the telomerase holoenzyme complex, have been shown to be upregulated in different cancer types. These proteins have also been proposed as prognostic markers in some types of cancer. The aim of the present study was to examine the expression patterns of dyskerin and WRAP53β in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prognosis in PVC, the expression of these two proteins and their potential association with clinical variables and survival were also evaluated. The expression of dyskerin and WRAP53β was assessed in PVC tumour samples from 68 patients using immunohistochemistry. The majority of tumour samples showed low and moderate expression levels of dyskerin. Upregulation of dyskerin in tumour samples was significantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53β was also expressed in most of the cells but was not significantly associated with clinical variables or survival. This study demonstrates that upregulation of dyskerin is significantly associated with poor prognosis. Thus, dyskerin may serve as a promising prognostic marker and a potential putative therapeutic target in PVC.

  • 48.
    Ricci, Costantino
    et al.
    S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
    Dorofte, Luiza
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Franceschini, Tania
    Bologna, Italy.
    Riefolo, Mattia
    S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
    Giunchi, Francesca
    S.Orsola-Malpighi Hospital, Bologna, Italy.
    Fiorentino, Michelangelo
    Department of Pathology, Sant’Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy.
    Davidsson, Sabina
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för hälsovetenskaper.
    HPV Status and World Health Organization 2016 Classification of Penile Squamous Cell Carcinoma and Penile Intraepithelial Neoplasia: 206 Cases from a Single, Contemporary, Western Cohort of Patients with Emphasis on the "Discordant Cases"2020Inngår i: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 33, nr Suppl 2, s. 960-961Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background: Penile squamous cel carcinoma (pSCC) cancer has been considered a rare tumour in the western world. Although some conflicting results, the most recent meta-analyses report an increase in its incidence and in the percentage of HPV(+) cases in numerous western countries. This scenario mirrors what observed for HPV(+) oropharynx cancer and could be explained by changes in sexual practice and in exposure of men to HPV. In this study, we analyzed pathological features and HPV-DNA prevalence in a contemporary, western pSCC cohort.

    Design: This study enrolled 206 patients with pSCC from Örebro University. DNA was extracted from paraffin-embedded tumor tissue samples, and HPV-DNA genotyping were performed using PCR method Anyplex II HPV28. In a subset of cases, HPV-DNA was also assessed in penile intraepithelial neoplasia (PeIN), lymph node metastasis (LnM) or both (51%, 11.6% and 18.9%). All the cases have been histologically re-classified according to the WHO 2016 classification of pSCC.

    Results: HPV -DNA was detected in 92/206 (44.7%) pSCC, 78/141 (55.3%) PeIN and 28/61 LnM (45.9%), respectively. HPV16 was the predominant type, representing 78.3% for pSCC, 79.5% for PeIN and 96.4% for LnM. In 7.8% of the cases, more than a HPV genotype has been detected in the same specimen or in different specimens of the same patients. Curiously, we found 8.5% of cases (14/164) with discordance of HPV-DNA detection in different specimens from the same patient (pSCC, PeIN and/or /LnM). In HPV(+) pSCC the predominant histologic subtype was “warty” (41.3%); in HPV(-) pSCC it was “usual” (65.8%). For PeIN, “warty” was the predominant subtype in HPV(+) PeIN (39.7%) and “differentiated” in HPV(-) PeIN (79.4%). For pSCC, we observed disagreement between histology and HPV status in 23.8% of cases: 13.1% HPV(+)/Non-HPV -related histology and 10.7% HPV(-)/HPV-related histology.

    Conclusions: HPV -DNA was observed in a relevant portion of pSCC and PeIN in our case series, confirming an increasing role of HPV in the pathogenesis of this disease. These results are particularly relevant, as they reflect the current epidemiological trend in the western world. Future studies are needed to clarify the exact role of HPV in cases with discordance between histology and HPV status and in cases with disagreement of HPV detection in different specimens from the same patient (pSCC, PeIN and/or LnM).

  • 49.
    Viegas, Edna Omar
    et al.
    Instituto Nacional de Saúde, Maputo, Mozambique; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden; Eduardo Mondlane University, Maputo, Mozambique; .
    Augusto, Orvalho
    Eduardo Mondlane University, Maputo, Mozambique.
    Ismael, Nália
    Instituto Nacional de Saúde, Maputo, Mozambique.
    Kaliff, Malin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Lillsunde-Larsson, Gabriella
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Ramqvist, Torbjörn
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, Charlotta
    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden; Department of Microbiology, Public Health Agency of Sweden, Stockholm, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Falk, Kerstin
    Department of Microbiology, Public Health Agency of Sweden, Stockholm, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Osman, Nafissa
    Eduardo Mondlane University, Maputo, Mozambique; Hospital Central de Maputo, Maputo, Mozambique.
    Jani, Ilesh Vindorai
    Instituto Nacional de Saúde, Maputo, Mozambique.
    Andersson, Sören
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Human papillomavirus prevalence and genotype distribution among young women and men in Maputo city, Mozambique2017Inngår i: BMJ Open, E-ISSN 2044-6055, Vol. 7, nr 7, artikkel-id e015653Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Human papillomavirus (HPV) is a well-known cause of cervical cancer, the second most frequent cancer in female African populations. This study aimed at determining the prevalence of HPV infections and the genotype distribution in young adults aged 18-24, in Maputo city, Mozambique, and to assess the suitability of commercially available HPV vaccines.

    METHODS: This cross-sectional study was conducted between 2009 and 2011 at a youth clinic in Maputo Central Hospital. Cervical and urethral samples were obtained from 236 women and 176 men, respectively. Demographic and behavioural data were collected using structured questionnaires. HPV genotyping was performed for 35 different high, probably or possibly high-risk and low-risk HPV types using the CLART Human Papillomavirus 2.

    RESULTS: HPV prevalence was 168/412 (40.8%; 95% CI 36.0 to 45.5) and was significantly higher in women than in men (63.6%vs10.2%). HPV52 was the most frequent type found in women, followed by HPV35, -16,-53, -58,-6 and -51. In men, HPV51 ranked the highest, followed by HPV6, -11,-52, -59 and -70. HIV infection and sexual debut before 18 years of age were associated with multiple HPV infections (OR 3.03; 95% CI 1.49 to 6.25 and OR 6.03; 95% CI 1.73 to 21.02, respectively). Women had a significantly higher HPV infection prevalence than men (p<0.001). The 9-valent HPV vaccine would cover 36.8% of the high-risk genotypes circulating in women in this study, compared with 26.3% and 15.8% coverage by the bivalent and quadrivalent vaccines, respectively.

    CONCLUSION: This study confirmed the high burden of HPV infections in young women in Maputo city, Mozambique. The HPV prevalence was associated with high-risk sexual behaviour. Sex education and sexually transmitted infection prevention interventions should be intensified in Mozambique. Only a proportion of the high-risk HPV genotypes (37%) were covered by currently available vaccines.

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