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Schindele, AlexandraORCID iD iconorcid.org/0000-0003-0007-8716
Publications (9 of 9) Show all publications
Schindele, A., Hammarstedt-Nordenvall, L., Mäkitie, A., Martinsen, J. I., Lappi-Heikkinen, S., Hansen, J., . . . Pukkala, E. (2025). Association of sinonasal cancer incidence with occupation in the Nordic countries: elevated risk especially among woodworkers. Acta Oncologica, 64, 1672-1678
Open this publication in new window or tab >>Association of sinonasal cancer incidence with occupation in the Nordic countries: elevated risk especially among woodworkers
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2025 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 64, p. 1672-1678Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND PURPOSE: The study aims to assess the occupational variation of sinonasal cancer (SNC) incidence in the Nordic population. SNC is an aggressive disease with poor prognosis and a strong connection with occupational exposure, hence, assessing occupational risk for SNC is an essential aspect in the efforts of cancer prevention.

PATIENTS/MATERIAL AND METHODS: Standardized incidence ratios (SIR) with 95% confidence intervals (CI) for SNC were calculated for 54 occupational categories from data based on population censuses and cancer registries in the five Nordic countries Denmark, Finland, Iceland, Norway, and Sweden.

RESULTS: During 1961-2005, 5,799 SNC cases were registered, 61% men and 39% women. Male woodworkers had an SIR of 1.84 for SNC (95% CI 1.66-2.04) with 355 cases, a finding consistent across all Nordic countries. The SIR for the histological subgroup sinonasal adenocarcinoma (SNAC) among male woodworkers was 5.50 (95% CI 4.56-6.56) with 122 cases. Female woodworkers also had an elevated SIR for SNC of 1.88 (95% CI 0.90-3.46), but based on only 10 cases. Country-specific elevated SIRs for SNC in men were noted in Denmark for shoe and leather workers (SIR 3.62, 95% CI 1.33-7.87), and in Norway for smelting workers (SIR 2.24, 95% CI 1.41-3.39). Reduced SIRs were observed for male military personnel, teachers, gardeners and farmers, and female religious workers.

INTERPRETATION: According to these Nordic registry data, woodworking, which is normally based on soft wood in the Nordic countries, is a high-risk occupation for SNC and particularly for SNAC.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2025
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-247975 (URN)10.2340/1651-226X.2025.44875 (DOI)41399231 (PubMedID)2-s2.0-105024983713 (Scopus ID)
Funder
Region Jämtland Härjedalen
Available from: 2025-12-30 Created: 2025-12-30 Last updated: 2025-12-30Bibliographically approved
Schindele, A., Holm, A., Kraft, S., Nylander, K., Allard, A. & Olofsson, K. (2025). Cross-evaluating Epstein-Barr virus, human papilloma virus, human cytomegalovirus and human adenovirus in nasal polyps and turbinate mucosa. Acta Oto-Laryngologica, 145(2), 164-167
Open this publication in new window or tab >>Cross-evaluating Epstein-Barr virus, human papilloma virus, human cytomegalovirus and human adenovirus in nasal polyps and turbinate mucosa
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2025 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 145, no 2, p. 164-167Article in journal (Refereed) Published
Abstract [en]

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease in which inflammatory responses to exogenic stressors, such as viral infections, has been recognised. The role of viruses in CRSwNP pathogenesis is unclear.

Aims/objectives: We aimed to characterise Epstein-Barr virus (EBV), human papillomavirus (HPV), human cytomegalovirus (HCMV), and human adenovirus (HAdV) in nasal polyps and adjacent paired healthy turbinate mucosa.

Materials and methods: We used real-time PCR for EBV, HCMV, and HAdV DNA detection, combined PCR/microarrays for HPV detection and genotyping, in samples from 45 patients with CRSwNP. Additionally, we used EBER in situ hybridisation for EBV detection.

Results: EBV detection with EBER-ISH was significantly higher in polyps (36%) versus turbinate mucosa (12%). None of the viral comparisons with PCR between polyps and turbinate mucosa for EBV-, HCMV- or HAdV-DNA showed statistically significant differences. All samples were HPV negative.

Conclusions and significance: We report higher expression of EBV in nasal polyps (36%) than in adjacent healthy turbinate mucosa (12%), using a valid method; EBER-ISH in 45 patients with CRSwNP. EBV might be a possible stressor that can trigger polypoid inflammation.

Place, publisher, year, edition, pages
Taylor & Francis, 2025
Keywords
Chronic rhinosinusitis with nasal polyps, EBER-ISH, Epstein-Barr virus, HAdV, HCMV, HPV, nasal mucosa
National Category
Microbiology in the medical area Otorhinolaryngology
Identifiers
urn:nbn:se:umu:diva-233990 (URN)10.1080/00016489.2024.2445025 (DOI)001387611900001 ()39921355 (PubMedID)2-s2.0-85214259351 (Scopus ID)
Funder
Cancerforskningsfonden i NorrlandRegion Jämtland HärjedalenRegion Västerbotten
Available from: 2025-01-14 Created: 2025-01-14 Last updated: 2025-05-27Bibliographically approved
Schindele, A., Al-Sabtti, S. & Olofsson, K. (2024). Human papilloma virus (HPV) vaccination is associated with reduced number of surgical treatments, an observational study on recurrent respiratory papillomatosis in Northern Sweden. Acta Oto-Laryngologica, 144(1), 71-75
Open this publication in new window or tab >>Human papilloma virus (HPV) vaccination is associated with reduced number of surgical treatments, an observational study on recurrent respiratory papillomatosis in Northern Sweden
2024 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 144, no 1, p. 71-75Article in journal (Refereed) Published
Abstract [en]

Background: Recurrent respiratory papillomatosis (RRP) is a wart-like lesion mainly affecting the larynx, caused by human papillomavirus (HPV) genotypes 6 and 11. The disease affects both children and adults, and there is no cure. Surgery is the current symptom-relieving treatment; however, HPV vaccination is used as an adjuvant treatment.

Aims and Objectives: The aims were to study effects of HPV vaccination in RRP cases and to compare juvenile-onset to adult-onset disease and high treatment frequency (TF) to low TF cases.

Material and Methods: Medical records of RRP patients were studied from May 2006 to January 2023. Eighty-five RRP cases, tested for HPV genotypes with PapilloCheck®, were included. Vaccination- onset- and treatment analysis were performed.

Results: Twelve percent of the cases were vaccinated. The number of surgeries decreased from 2.0 to 0.8/year after HPV vaccination. Most cases had an adult-onset and less than one treatment per year. Juvenile-onset cases had a higher vaccination treatment ratio compared to adult-onset.

Conclusions: HPV vaccination was associated with a lower number of treatments per year, supporting the use of vaccination as an adjuvant treatment.

Significance: Vaccination as adjuvant treatment to surgery may lead to increased quality of life for RRP patients and saved healthcare resources.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2024
Keywords
human papillomavirus viruses, papillomavirus vaccines, Recurrent respiratory papillomatosis
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:umu:diva-222345 (URN)10.1080/00016489.2024.2316264 (DOI)001177976800001 ()2-s2.0-85186863889 (Scopus ID)
Available from: 2024-03-18 Created: 2024-03-18 Last updated: 2025-04-24Bibliographically approved
Erlandsson, A., Werner, M., Holm, A., Schindele, A. & Olofsson, K. (2023). Balloon dilatation versus CO2 laser surgery in subglottic stenosis: a retrospective analysis of therapeutic approaches. Acta Oto-Laryngologica, 143(6), 528-535
Open this publication in new window or tab >>Balloon dilatation versus CO2 laser surgery in subglottic stenosis: a retrospective analysis of therapeutic approaches
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2023 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 143, no 6, p. 528-535Article in journal (Refereed) Published
Abstract [en]

Background: Subglottic stenosis (SGS) is a narrowing of the airway just below the vocal folds. The cause of SGS and the optimal care for these patients, have remained elusive. Endoscopic surgery of SGS using either balloon or CO2 laser is associated with recurrence.

Aims and objectives: Our aim is to compare surgery free intervals (SFI) between these two methods applied in two different timeframes. The knowledge gained from this project can support decision-making regarding surgical method choice.

Material and methods: Participants were retrospectively identified using medical records between 1999–2021. We used pre-defined broad inclusion criteria to identify cases using the International Classification of Disease (ICD-10). Primary outcome was surgery free intervals.

Results: 141 patients were identified, 63 met the criteria for SGS, and were included in the analysis. Results show no significant difference in SFI, comparing balloon dilatation and CO2 laser.

Conclusion: These findings demonstrate no detected difference in treatment intervals (SFI) when comparing these two commonly used surgical alternatives for SGS.

Significance: The outcome of this report supports surgical freedom of choice based on the surgeon’s experience and skill and ushes for further studies on patient experience regarding these two therapeutic approaches.

Place, publisher, year, edition, pages
Taylor & Francis, 2023
Keywords
balloon dilatation, CO2 laser, idiopathic subglottic stenosis, Subglottic stenosis, surgery free intervals
National Category
Otorhinolaryngology Surgery
Identifiers
urn:nbn:se:umu:diva-212260 (URN)10.1080/00016489.2023.2222756 (DOI)001011786800001 ()37343275 (PubMedID)2-s2.0-85164105528 (Scopus ID)
Funder
Cancerforskningsfonden i Norrland, AMP 18-925Cancerforskningsfonden i Norrland, AMP-19-973Region Västerbotten, RV 967352Region Västerbotten, RV 979607
Available from: 2023-07-20 Created: 2023-07-20 Last updated: 2023-07-20Bibliographically approved
Schindele, A., Holm, A., Nylander, K., Allard, A. & Olofsson, K. (2022). Mapping human papillomavirus, Epstein–Barr virus, cytomegalovirus, adenovirus, and p16 in laryngeal cancer. Discover Oncology, 13(1), Article ID 18.
Open this publication in new window or tab >>Mapping human papillomavirus, Epstein–Barr virus, cytomegalovirus, adenovirus, and p16 in laryngeal cancer
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2022 (English)In: Discover Oncology, E-ISSN 2730-6011, Vol. 13, no 1, article id 18Article in journal (Refereed) Published
Abstract [en]

Purpose: Apart from tobacco and alcohol, viral infections are proposed as risk factors for laryngeal cancer. The occurrence of oncogenic viruses including human papilloma virus (HPV) and Epstein–Barr virus (EBV), in laryngeal squamous cell carcinoma (LSCC) varies in the world. Carcinogenesis is a multi-step process, and the role of viruses in LSCC progression has not been clarified. We aimed to analyze the presence and co-expression of HPV, EBV, human cytomegalovirus (HCMV) and human adenovirus (HAdV) in LSCC. We also investigated if p16 can act as surrogate marker for HPV in LSCC.

Methods: Combined PCR/microarrays (PapilloCheck®) were used for detection and genotyping of HPV DNA, real-time PCR for EBV, HCMV and HAdV DNA detection, and EBER in situ hybridization (EBER-ISH) for EBV detection in tissue from 78 LSCC patients. Additionally, we analyzed p16 expression with immunohistochemistry.

Results: Thirty-three percent (26/78) of LSCC tumor samples were EBV positive, 9% (7/78) HCMV positive and 4% (3/78) HAdV positive. Due to DNA fragmentation, 45 samples could not be analyzed with PapilloCheck®; 9% of the remaining (3/33) were high-risk HPV16 positive and also over-expressed p16. A total of 14% (11/78) of the samples over-expressed p16.

Conclusion: These findings present a mapping of HPV, EBV, HCMV and HAdV, including the HPV surrogate marker p16, in LSCC in this cohort. Except for EBV, which was detected in a third of the samples, data show viral infection to be uncommon, and that p16 does not appear to be a specific surrogate marker for high-risk HPV infection in LSCC.

Place, publisher, year, edition, pages
Springer, 2022
National Category
Cancer and Oncology Otorhinolaryngology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-193581 (URN)10.1007/s12672-022-00475-4 (DOI)000771496000002 ()35312853 (PubMedID)2-s2.0-85126886934 (Scopus ID)
Available from: 2022-04-19 Created: 2022-04-19 Last updated: 2022-10-12Bibliographically approved
Schindele, A. (2022). Mapping viruses in non-malignant tonsils, nasal polyps, sinonasal inverted papilloma and laryngeal cancer. (Doctoral dissertation). Umeå: Umeå University
Open this publication in new window or tab >>Mapping viruses in non-malignant tonsils, nasal polyps, sinonasal inverted papilloma and laryngeal cancer
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Kartläggning av virus i godartade halsmandlar, näspolyper och inverterat papillom i näsa-bihålor samt cancer i struphuvudet
Abstract [en]

Background: The upper respiratory tract is exposed to viruses, which can lead to infection and cancer development. We chose to study common and/or chronic diseases along with common and cancer related viruses in the upper airway. High-risk human papillomavirus (HPV) causes cancer in tonsils and base of tongue, and Epstein-Barr virus (EBV) in the nasopharynx. p16 is used as a site-specific tumor marker for HPV. Human cytomegalovirus (HCMV) and human adenovirus (HAdV) are proposed to be oncomodulatory. It is unclear what significance these viruses have in benign tonsillar disease, chronic rhinosinusitis with nasal polyps (CRSwNP), sinonasal inverted papillomas (SIP) and laryngeal squamous cell carcinoma (LSCC). If virus is identified, it could make possible the use of current vaccines in prevention and treatment, as well as protection of healthcare providers.

Material and Methods: We analyzed 40 benign tonsils, 45 paired nasal polyp and healthy nasal mucosa samples, 53 SIP and 78 LSCC samples. We used PCR/microarrays (PapilloCheck®) for HPV detection and genotyping, immunohistochemistry (IHC) for p16 expression and real-time PCR for EBV, HCMV and HAdV detection. Additionally, Epstein-Barr encoding region (EBER) in situ hybridization (ISH) was used for EBV localization and count.

Results: HPV and p16 were not co-expressed, and p16 levels were low in benign tonsils, nasal polyps, and paired controls. Also, 9% of LSCC samples were high-risk HPV 16 positive and over-expressed p16.

EBV-positive cells were detected in 65% of the tonsils, nasal polyps (36%) versus controls (12%), 30% of SIP cases and 33% of LSCC samples.

Conclusions: EBV is commonly identified in benign tonsils, nasal polyps, SIP and LSCC, when using sensitive and robust detection methods. At the same time, viral infection with HPV, HCMV or HAdV appears to be uncommon in these conditions. p16 does not emerge as a reliable marker for HPV infection in LSCC.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2022. p. 72
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2188
Keywords
Human papilloma virus, Epstein-Barr virus, Human cytomegalovirus, Human adenovirus, p16 tumor suppressor protein, Non-malignant tonsillar disease, Chronic rhino sinusitis with nasal polyps, sinonasal inverted papilloma, laryngeal cancer, EBER-ISH
National Category
Otorhinolaryngology
Research subject
Oto-Rhino-Laryngology
Identifiers
urn:nbn:se:umu:diva-200180 (URN)978-91-7855-841-4 (ISBN)978-91-7855-842-1 (ISBN)
Public defence
2022-11-25, Hörsalen Snäckan, Hus 16, Östersunds Sjukhus, Östersunds sjukhus, Kyrkgatan 16, Östersund, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2022-11-04 Created: 2022-10-12 Last updated: 2022-10-13Bibliographically approved
Schindele, A., Holm, A., Nylander, K., Allard, A. & Olofsson, K. (2020). Low Epstein-Barr virus count in sinonasal inverted papilloma. Acta Oto-Laryngologica, 140(5), 413-417
Open this publication in new window or tab >>Low Epstein-Barr virus count in sinonasal inverted papilloma
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2020 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 140, no 5, p. 413-417Article in journal (Refereed) Published
Abstract [en]

Background: Sinonasal inverted papilloma (SIP) is a benign tumour originating from the sinonasal mucosa showing an extensive growth pattern, a high risk of recurrence and a 5–10% risk to malignify. Epstein-Barr virus (EBV) is an oncogenic herpesvirus which infects most individuals via the saliva eliciting a latent infection. Previous studies have been reporting variable data on EBV in SIP, and there is no present appreciation regarding the association between these.

Aims/objectives: The aims were to investigate the presence and count of EBV in SIP and map the viral distribution in the epithelium versus the connective tissue.

Material and method: Fifty-three SIP patients were identified in the Pathology Department register at the University Hospital of Umeå. The biopsies were analysed with Epstein-Barr Encoded Region (EBER) in situ hybridization. EBER-positive cells were counted in the epithelium and connective tissue.

Results: We found EBER-stained cells in 30% of the cases, where 19% of these had an abundance of stained cells, and the rest showed a low count.

Conclusions/significance: These findings demonstrate a low EBV count in SIP. EBV is less likely to be a causative agent in the formation of SIP, or its malignant transformation.

Place, publisher, year, edition, pages
Taylor & Francis, 2020
Keywords
Epstein-Barr virus, sinonasal inverted papilloma, EBER-ISH
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:umu:diva-168828 (URN)10.1080/00016489.2020.1724330 (DOI)000514736300001 ()32068495 (PubMedID)2-s2.0-85079719070 (Scopus ID)
Funder
Region Västerbotten
Available from: 2020-03-19 Created: 2020-03-19 Last updated: 2023-03-24Bibliographically approved
Holm, A., Schindele, A., Allard, A., Eriksson, I., Sandström, K., Laurell, G., . . . Olofsson, K. (2019). Mapping of Human Papilloma Virus, p16, and Epstein-Barr Virusin Non-Malignant Tonsillar Disease. Laryngoscope Investigative Otolaryngology (LIO), 4(3), 285-291
Open this publication in new window or tab >>Mapping of Human Papilloma Virus, p16, and Epstein-Barr Virusin Non-Malignant Tonsillar Disease
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2019 (English)In: Laryngoscope Investigative Otolaryngology (LIO), E-ISSN 2378-8038, Vol. 4, no 3, p. 285-291Article in journal (Refereed) Published
Abstract [en]

Objectives: Due to their location in the entrance of the aero‐digestive tract, tonsils are steadily exposed to viruses. Human papilloma virus (HPV) and Epstein‐Barr virus (EBV) are two potentially oncogenic viruses that tonsils encounter. The incidence of HPV positive tonsillar cancer is on the rise and it is unknown when infection with HPV occurs.

Aim: To investigate if tonsils are infected with HPV and EBV, to study the co‐expression of HPV and its surrogate marker p16, and to evaluate the number of EBV positive cells in benign tonsillar disease.

Materials and Methods: Tonsils from 40 patients in a university hospital were removed due to hypertrophy, chronic or recurrent infection. These were analyzed for presence of HPV, its surrogate marker p16, and EBV. HPV was studied using PapilloCheck (a PCR method), while p16 was identified in epithelial and lymphoid tissue with immunohistochemistry and EBV using EBER‐ISH (Epstein‐Barr encoding region–in situ hybridization).

Results: HPV was not detected, and p16 was present at low numbers in all epithelial samples as well as in 92.5% of the lymphoid tonsillar samples. At least one EBER‐positive cell was seen in 65% of cases. Larger numbers of EBER‐expressing cells were only seen in two cases.

Conclusion: These findings demonstrate that EBV and HPV infect tonsils independently, but further studies are warranted to confirm their infectious relationship.

Level of Evidence: Cross‐sectional study

Place, publisher, year, edition, pages
Wiley-Blackwell, 2019
Keywords
Human papillomavirus, Epstein-Barr virus, non-malignant tonsillar disease, EBER-ISH, PapilloCheck, immunohistochemistry
National Category
Otorhinolaryngology
Research subject
Oto-Rhino-Laryngology
Identifiers
urn:nbn:se:umu:diva-158485 (URN)10.1002/lio2.260 (DOI)000471907200002 ()31236460 (PubMedID)
Funder
Västerbotten County Council
Available from: 2019-04-29 Created: 2019-04-29 Last updated: 2024-07-02Bibliographically approved
Schindele, A., Holm, A., Kraft, S., Nylander, K., Allard, A. & Olofsson, K.Epstein-Barr virus in patients with chronic rhinosinusitis and nasal polyps.
Open this publication in new window or tab >>Epstein-Barr virus in patients with chronic rhinosinusitis and nasal polyps
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(English)Manuscript (preprint) (Other academic)
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:umu:diva-200177 (URN)
Available from: 2022-10-11 Created: 2022-10-11 Last updated: 2022-10-12
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-0007-8716

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