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Bergengren, L., Lillsunde-Larsson, G., Helenius, G. & Karlsson, M. G. (2019). HPV-based screening for cervical cancer among women 55-59 years of age. PLoS ONE, 14(6), Article ID e0217108.
Open this publication in new window or tab >>HPV-based screening for cervical cancer among women 55-59 years of age
2019 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 6, article id e0217108Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
PLOS, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-74701 (URN)10.1371/journal.pone.0217108 (DOI)000471587000007 ()31199811 (PubMedID)2-s2.0-85067434997 (Scopus ID)
Note

Funding Agencies:

Region Örebro County Research Committee  

Örebro University Hospital Research Foundation  

BBMRI.se 

Available from: 2019-06-17 Created: 2019-06-17 Last updated: 2019-07-23Bibliographically approved
Hadgu, E., Seifu, D., Tigneh, W., Bokretsion, Y., Bekele, A., Abebe, M., . . . Karlsson, M. (2018). Breast cancer in Ethiopia: evidence for geographic difference in the distribution of molecular subtypes in Africa. BMC Women's Health, 18(1), Article ID 40.
Open this publication in new window or tab >>Breast cancer in Ethiopia: evidence for geographic difference in the distribution of molecular subtypes in Africa
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2018 (English)In: BMC Women's Health, ISSN 1472-6874, E-ISSN 1472-6874, Vol. 18, no 1, article id 40Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Breast cancer is a heterogeneous disease with several morphological and molecular subtypes. Widely accepted molecular classification system uses assessment of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker Ki67. Few studies have been conducted on the incidence and molecular types of breast cancer in Sub-Saharan Africa. Previous studies mainly from Western and Central Africa, showed breast cancer to occur at younger ages and to present with aggressive features, such as high-grade, advanced stage and triple-negative phenotype (negative for ER, PR and HER2). Limited data from East Africa including Ethiopia however shows hormone receptor negative tumors to account for a lower proportion of all breast cancers than has been reported from elsewhere in Africa.

METHODS: In this study from Tikur Anbessa Specialized Hospital, 114 breast cancer patients diagnosed between 2012 and 2015 were enrolled. ER, PR, Ki67 and HER2 receptor status were assessed using immunohistochemistry from tissue microarrays. FISH was used for assessment of gene amplification in all equivocal tumor samples and for confirmation in HER2-enriched cases.

RESULTS: The distribution of molecular subtypes was: Luminal A: 40%; Luminal B: 26%; HER2-enriched: 10%; TNBC: 23%. ER were positive in 65% of all tumors and 43% the cases were positive for PR. There was statistically significant difference in median age at diagnosis between the molecular subtypes (P < 0.05). There was a bimodal distribution of molecular subtypes in different age ranges with Luminal B subtype being more common at younger ages (median = 36) and Luminal A subtype more prevalent at older ages (median = 42). There were no statistically significant differences in tumor grade, histology, and stage between the molecular subtypes of breast cancer.

CONCLUSION: The present study detected Luminal A breast cancer to be the most common subtype and reveals a relatively low rate of hormone receptor negative and TNBC. Our findings and results from other East African studies suggest geographic variability in the distribution of the molecular subtypes of breast cancer in Africa and hence have important clinical and policy implications for breast cancer control and treatment in Ethiopia.

Place, publisher, year, edition, pages
BioMed Central, 2018
Keywords
Breast cancer; Molecular subtypes; Ethiopia; Africa
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-65200 (URN)10.1186/s12905-018-0531-2 (DOI)000425159000001 ()29444670 (PubMedID)2-s2.0-85042084690 (Scopus ID)
Note

Funding Agencies:

Addis Ababa University, School of Graduate Studies  

Addis Ababa University, thematic research group "clinico-epidemiological characterization of breast cancer in Ethiopia"  

Armauer Hansen Research Institute (AHRI)  

Swedish International Developmental Agency (SIDA) 

Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2018-08-20Bibliographically approved
Bergengren, L., Kaliff, M., Lillsunde-Larsson, G., Karlsson, M. & Helenius, G. (2018). Comparison between professional sampling and self-sampling for HPV-based cervical cancer screening among postmenopausal women. International Journal of Gynecology & Obstetrics, 142(3), 359-364
Open this publication in new window or tab >>Comparison between professional sampling and self-sampling for HPV-based cervical cancer screening among postmenopausal women
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2018 (English)In: International Journal of Gynecology & Obstetrics, ISSN 0020-7292, E-ISSN 1879-3479, Vol. 142, no 3, p. 359-364Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2018
Keywords
Cervical cancer, HPV, Postmenopausal women, Professional sampling, Screening, Self-sample
National Category
Cancer and Oncology Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:oru:diva-67134 (URN)10.1002/ijgo.12538 (DOI)000440652000017 ()29856071 (PubMedID)2-s2.0-85051073715 (Scopus ID)
Note

Funding Agencies:

Region Örebro County Research Committee  

Örebro University Hospital Research Foundation  

BBMRI.se

Available from: 2018-06-04 Created: 2018-06-04 Last updated: 2018-08-30Bibliographically approved
Åström, M., Tajeddinn, W., Karlsson, M. G., Linder, O., Palmblad, J. & Lindblad, P. (2018). Cytokine Measurements for Diagnosing and Characterizing Leukemoid Reactions and Immunohistochemical Validation of a Granulocyte Colony-Stimulating Factor and CXCL8-Producing Renal Cell Carcinoma. Biomarker Insights, 13, Article ID UNSP 1177271918792246.
Open this publication in new window or tab >>Cytokine Measurements for Diagnosing and Characterizing Leukemoid Reactions and Immunohistochemical Validation of a Granulocyte Colony-Stimulating Factor and CXCL8-Producing Renal Cell Carcinoma
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2018 (English)In: Biomarker Insights, ISSN 1177-2719, E-ISSN 1177-2719, Vol. 13, article id UNSP 1177271918792246Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Various paraneoplastic syndromes are encountered in renal cell carcinomas. This case report illustrates that a paraneoplastic leukemoid reaction may precede the diagnosis of renal cell carcinoma and be explained by cytokine production from the cancer cells.

CASE PRESENTATIONS: A 64-year-old man was referred for hematology workup due to pronounced leukocytosis. While being evaluated for a possible hematologic malignancy as the cause, he was found to have a metastasized renal cell carcinoma, and hyperleukocytosis was classified as a leukemoid reaction. A multiplex panel for measurement of 25 serum cytokines/chemokines showed highly elevated levels of granulocyte colony-stimulating factor (G-CSF) and CXCL8 (C-X-C-motif chemokine ligand 8, previously known as interleukin [IL]-8). By immunohistochemistry it was shown that the renal carcinoma cells expressed both these cytokines. Two additional, consecutive patients with renal cell carcinoma with paraneoplastic leukocytosis also showed elevated serum levels of CXCL8, but not of G-CSF. Nonparametric statistical evaluation showed significantly higher serum concentrations of CXCL8, IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor, but lower interferon gamma (IFN-gamma) and IL-1 alpha, for the 3 renal cell carcinoma cases compared with healthy blood donors.

CONCLUSIONS: In suspected paraneoplastic leukocytosis, multiplex serum cytokine analyses may facilitate diagnosis and provide an understanding of the mechanisms for the reaction. In the index patient, combined G-CSF and CXCL8 protein expression by renal carcinoma cells was uniquely documented. A rapidly fatal course was detected in all 3 cases, congruent with the concept that autocrine/paracrine growth signaling in renal carcinoma cells may induce an aggressive tumor phenotype. Immune profiling studies could improve our understanding for possible targets when choosing therapies for patients with metastatic renal cell carcinoma.

Place, publisher, year, edition, pages
Sage Publications, 2018
Keywords
chemokine, IL-6, IL-10, monocytosis, paraneoplastic leukocytosis, autocrine signaling, multiplex, inflammatory response, precision medicine, biomarker
National Category
Immunology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:oru:diva-68648 (URN)10.1177/1177271918792246 (DOI)000441829800001 ()30147294 (PubMedID)
Available from: 2018-08-31 Created: 2018-08-31 Last updated: 2018-08-31Bibliographically approved
Helenius, G., Ottestig, E., Kaliff, M., Lillsunde-Larsson, G., Karlsson, M. & Bergengren, L. (2018). Distribution of HPV-genotypes in a Swedish screening population. In: : . Paper presented at Eurogin 2018 International multidisciplinary HPV Congress, Lisabon Portugal, December 2-5, 2018.
Open this publication in new window or tab >>Distribution of HPV-genotypes in a Swedish screening population
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-69348 (URN)
Conference
Eurogin 2018 International multidisciplinary HPV Congress, Lisabon Portugal, December 2-5, 2018
Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2018-10-08Bibliographically approved
Kaliff, M., Sorbe, B., Mordhorst, L. B., Helenius, G., Karlsson, M. G. & Lillsunde-Larsson, G. (2018). 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 radiotherapy. OncoTarget, 9(27), 18786-18796
Open this publication in new window or tab >>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 radiotherapy
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2018 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 9, no 27, p. 18786-18796Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Impact Journals LLC, 2018
Keywords
HPV, cervical cancer, recurrences, survival
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-71672 (URN)10.18632/oncotarget.24666 (DOI)29721161 (PubMedID)2-s2.0-85045206587 (Scopus ID)
Available from: 2019-01-22 Created: 2019-01-22 Last updated: 2019-01-24Bibliographically approved
Lillsunde-Larsson, G., Kaliff, M., Sorbe, B., Helenius, G. & Karlsson, M. (2018). HPV16 VIRAL CHARACTERISTICS IN PRIMARY AND RECURRENT VULVAR CARCINOMA. In: : . Paper presented at 32nd International Papillomavirus Conference IPVC 2018, Sydney, Australia, 2-6 October, 2018.
Open this publication in new window or tab >>HPV16 VIRAL CHARACTERISTICS IN PRIMARY AND RECURRENT VULVAR CARCINOMA
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2018 (English)Conference paper, Poster (with or without abstract) (Other academic)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-73753 (URN)
Conference
32nd International Papillomavirus Conference IPVC 2018, Sydney, Australia, 2-6 October, 2018
Available from: 2019-04-15 Created: 2019-04-15 Last updated: 2019-04-16Bibliographically approved
Lillsunde Larsson, G., Kaliff, M., Sorbe, B., Helenius, G. & Karlsson, M. G. (2018). HPV16 viral characteristics in primary, recurrent and metastatic vulvar carcinoma. Papillomavirus research, 6, 63-69
Open this publication in new window or tab >>HPV16 viral characteristics in primary, recurrent and metastatic vulvar carcinoma
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2018 (English)In: Papillomavirus research, ISSN 2405-8521, Vol. 6, p. 63-69Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Vulvar carcinoma, human papillomavirus, integration, metastases, recurrences, viral load
National Category
Cancer and Oncology Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:oru:diva-69992 (URN)10.1016/j.pvr.2018.10.008 (DOI)000452069800012 ()30391517 (PubMedID)2-s2.0-85056569332 (Scopus ID)
Note

Funding Agency:

Örebro County Council Research Committee

Available from: 2018-11-07 Created: 2018-11-07 Last updated: 2018-12-17Bibliographically approved
Qvick, A., Sorbe, B., Helenius, G., Karlsson, M. G. & Lillsunde Larsson, G. (2017). Does p53 codon 72 polymorphism have a prognostic value in carcinoma of the vulva and vagina?. Medical Oncology, 34(3), Article ID 36.
Open this publication in new window or tab >>Does p53 codon 72 polymorphism have a prognostic value in carcinoma of the vulva and vagina?
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2017 (English)In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 34, no 3, article id 36Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Heidelberg, Germany: Springer, 2017
Keywords
P53, Codon 72, Polymorphism, Vagina, Vulva, Carcinoma, HPV
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-55410 (URN)10.1007/s12032-017-0893-6 (DOI)000394277700006 ()28144815 (PubMedID)2-s2.0-85011707902 (Scopus ID)
Note

Funding Agencies:

Region Örebro County through ALF

Örebro County Council Research Committee

Available from: 2017-03-10 Created: 2017-03-10 Last updated: 2019-03-22Bibliographically approved
Ranhem, C., Lillsunde-Larsson, G., Hedman, H., Lindquist, D., Karlsson, M. G., Hellström, A.-C., . . . Andersson, S. (2017). Expression of LRIG proteins as possible prognostic factors in primary vaginal carcinoma. PLoS ONE, 12(8), Article ID e0183816.
Open this publication in new window or tab >>Expression of LRIG proteins as possible prognostic factors in primary vaginal carcinoma
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 8, article id e0183816Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Public Library of Science, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-61041 (URN)10.1371/journal.pone.0183816 (DOI)000408370700059 ()28841699 (PubMedID)2-s2.0-85029173894 (Scopus ID)
Funder
Swedish Cancer Society, 070623 CAN 2007/1044 11 0544 CAN 2011/471Swedish Research Council, 521-2008-2899
Note

Funding Agencies:

Karolinska Institutet Cancer Strategic Grants  5888/05-722

Stockholm County Council  20130097 

Region Örebro County  OLL-526041 

Lion's Cancer Research Foundation  

University of Umeå  

Gustaf V Jubilee Fund  154022 

Region Västmanland - Uppsala University Centre for Clinical Research Hospital of Västmanland Västerås 

Available from: 2017-09-19 Created: 2017-09-19 Last updated: 2018-08-06Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0001-6881-237X

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