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  • 1.
    Bergengren, Lovisa
    et al.
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Women’s Health, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    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 hälsovetenskaper. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Karlsson, Mats
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    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.

  • 2.
    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.

  • 3.
    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)
  • 4.
    Kaliff, Malin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Human papillomavirus and cellular biomarkers in cervical cancer2020Doktoravhandling, med artikler (Annet vitenskapelig)
  • 5.
    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.

  • 6.
    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, ISSN 1949-2553, 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.

  • 7.
    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, ISSN 1932-6203, 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.

  • 8.
    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.

  • 9.
    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)
  • 10.
    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)
  • 11.
    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)
  • 12.
    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, ISSN 2044-6055, 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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