Outcome differences in HPV-driven head and neck squamous cell carcinoma attributable to altered human leukocyte antigen frequencies
BackgroundEffective immune surveillance requires a functioning immune system and natural killer (NK) and T cells for adequate innate and antigen-specific immune responses critically depending on human leukocyte antigens (HLAs) and haplotypes representing advantageous combinations of HLA antigens. Re...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1212454/full |
| _version_ | 1797384248375640064 |
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| author | Gunnar Wichmann Nathalie Vetter Claudia Lehmann Ramona Landgraf Ilias Doxiadis Rebecca Großmann Ekaterina Vorobeva Andreas Dietz Veit Zebralla Susanne Wiegand Theresa Wald |
| author_facet | Gunnar Wichmann Nathalie Vetter Claudia Lehmann Ramona Landgraf Ilias Doxiadis Rebecca Großmann Ekaterina Vorobeva Andreas Dietz Veit Zebralla Susanne Wiegand Theresa Wald |
| author_sort | Gunnar Wichmann |
| collection | DOAJ |
| description | BackgroundEffective immune surveillance requires a functioning immune system and natural killer (NK) and T cells for adequate innate and antigen-specific immune responses critically depending on human leukocyte antigens (HLAs) and haplotypes representing advantageous combinations of HLA antigens. Recently, we reported a link between altered frequencies of HLA alleles and haplotypes and developing head and neck squamous cell carcinoma (HNSCC). Whereas the majority of HNSCCs seem to be related to classical risk factors alcohol and tobacco, a subset of HNSCC and especially oropharyngeal squamous cell carcinoma (OPSCC) were etiologically linked to human papillomavirus (HPV) recently. Here, we demonstrate in HPV-driven (p16-positive high risk-HPV DNA-positive) HNSCC a deviating distribution of HLA antigens and haplotypes and their relevance to outcome.MethodsLeukocyte DNA of n = 94 HPV-driven HNSCC patients (n = 57 OPSCC, n = 37 outside oropharynx) underwent HLA SSO typing, allowing allele, antigen (allele group), and haplo-typing. Besides comparing these frequencies with those of German blood donors, we analyzed their impact on outcome using Kaplan–Meier plots and Cox proportional hazard regression.ResultsAntigen and haplotype frequencies demonstrate enrichment of rare antigens and haplotypes. The HLA score for unselected HNSCC patients was not predictive for outcome here. However, together with alcohol consumption, tobacco smoking, T category, and extranodal extension of locoregional metastases and treatment applied, eight HLA traits allow for predicting progression-free and tumor-specific survival.ConclusionPatients can be categorized into low, intermediate-low, intermediate-high, and high risk groups. Using a new PFS risk score for HPV-driven HNSCC may allow to improve prognostication. |
| first_indexed | 2024-03-08T21:32:41Z |
| format | Article |
| id | doaj.art-ea812ba7f3f84ff885cec369b7a57e3c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-08T21:32:41Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-ea812ba7f3f84ff885cec369b7a57e3c2023-12-21T04:50:41ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-12-011310.3389/fonc.2023.12124541212454Outcome differences in HPV-driven head and neck squamous cell carcinoma attributable to altered human leukocyte antigen frequenciesGunnar Wichmann0Nathalie Vetter1Claudia Lehmann2Ramona Landgraf3Ilias Doxiadis4Rebecca Großmann5Ekaterina Vorobeva6Andreas Dietz7Veit Zebralla8Susanne Wiegand9Theresa Wald10Department of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyDepartment of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyInstitute for Transfusion Medicine, Transplantation Immunology, University Hospital Leipzig, Leipzig, GermanyInstitute for Transfusion Medicine, Transplantation Immunology, University Hospital Leipzig, Leipzig, GermanyInstitute for Transfusion Medicine, Transplantation Immunology, University Hospital Leipzig, Leipzig, GermanyInstitute for Transfusion Medicine, Transplantation Immunology, University Hospital Leipzig, Leipzig, GermanyDepartment of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyDepartment of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyDepartment of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyDepartment of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyDepartment of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyBackgroundEffective immune surveillance requires a functioning immune system and natural killer (NK) and T cells for adequate innate and antigen-specific immune responses critically depending on human leukocyte antigens (HLAs) and haplotypes representing advantageous combinations of HLA antigens. Recently, we reported a link between altered frequencies of HLA alleles and haplotypes and developing head and neck squamous cell carcinoma (HNSCC). Whereas the majority of HNSCCs seem to be related to classical risk factors alcohol and tobacco, a subset of HNSCC and especially oropharyngeal squamous cell carcinoma (OPSCC) were etiologically linked to human papillomavirus (HPV) recently. Here, we demonstrate in HPV-driven (p16-positive high risk-HPV DNA-positive) HNSCC a deviating distribution of HLA antigens and haplotypes and their relevance to outcome.MethodsLeukocyte DNA of n = 94 HPV-driven HNSCC patients (n = 57 OPSCC, n = 37 outside oropharynx) underwent HLA SSO typing, allowing allele, antigen (allele group), and haplo-typing. Besides comparing these frequencies with those of German blood donors, we analyzed their impact on outcome using Kaplan–Meier plots and Cox proportional hazard regression.ResultsAntigen and haplotype frequencies demonstrate enrichment of rare antigens and haplotypes. The HLA score for unselected HNSCC patients was not predictive for outcome here. However, together with alcohol consumption, tobacco smoking, T category, and extranodal extension of locoregional metastases and treatment applied, eight HLA traits allow for predicting progression-free and tumor-specific survival.ConclusionPatients can be categorized into low, intermediate-low, intermediate-high, and high risk groups. Using a new PFS risk score for HPV-driven HNSCC may allow to improve prognostication.https://www.frontiersin.org/articles/10.3389/fonc.2023.1212454/fullhuman papillomavirus (HPV)oropharyngeal squamous cell carcinoma (OPSCC)head and neck canceroutcome researchhuman leukocyte antigen (HLA)haplotype |
| spellingShingle | Gunnar Wichmann Nathalie Vetter Claudia Lehmann Ramona Landgraf Ilias Doxiadis Rebecca Großmann Ekaterina Vorobeva Andreas Dietz Veit Zebralla Susanne Wiegand Theresa Wald Outcome differences in HPV-driven head and neck squamous cell carcinoma attributable to altered human leukocyte antigen frequencies Frontiers in Oncology human papillomavirus (HPV) oropharyngeal squamous cell carcinoma (OPSCC) head and neck cancer outcome research human leukocyte antigen (HLA) haplotype |
| title | Outcome differences in HPV-driven head and neck squamous cell carcinoma attributable to altered human leukocyte antigen frequencies |
| title_full | Outcome differences in HPV-driven head and neck squamous cell carcinoma attributable to altered human leukocyte antigen frequencies |
| title_fullStr | Outcome differences in HPV-driven head and neck squamous cell carcinoma attributable to altered human leukocyte antigen frequencies |
| title_full_unstemmed | Outcome differences in HPV-driven head and neck squamous cell carcinoma attributable to altered human leukocyte antigen frequencies |
| title_short | Outcome differences in HPV-driven head and neck squamous cell carcinoma attributable to altered human leukocyte antigen frequencies |
| title_sort | outcome differences in hpv driven head and neck squamous cell carcinoma attributable to altered human leukocyte antigen frequencies |
| topic | human papillomavirus (HPV) oropharyngeal squamous cell carcinoma (OPSCC) head and neck cancer outcome research human leukocyte antigen (HLA) haplotype |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1212454/full |
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