Outcome differences in HPV-driven head and neck squamous cell carcinoma attributable to altered human leukocyte antigen frequencies

Gunnar Wichmann; Nathalie Vetter; Claudia Lehmann; Ramona Landgraf; Ilias Doxiadis; Rebecca Großmann; Ekaterina Vorobeva; Andreas Dietz; Veit Zebralla; Susanne Wiegand; Theresa Wald

doi:10.3389/fonc.2023.1212454

Outcome differences in HPV-driven head and neck squamous cell carcinoma attributable to altered human leukocyte antigen frequencies

Front Oncol. 2023 Dec 21:13:1212454. doi: 10.3389/fonc.2023.1212454. eCollection 2023.

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, Germany.
² Institute for Transfusion Medicine, Transplantation Immunology, University Hospital Leipzig, Leipzig, Germany.

^# Contributed equally.

Abstract

Background: Effective 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.

Methods: Leukocyte 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.

Results: Antigen 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.

Conclusion: Patients 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.

Keywords: Genetic association; haplotype; head and neck cancer; human leukocyte antigen (HLA); human papillomavirus (HPV); oropharyngeal squamous cell carcinoma (OPSCC); outcome research; progression-free survival (PFS).

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article. The authors received partial support for open access publication from the University Leipzig. This funding did not influence the design of the study, collection, interpretation and analysis of the data, the preparation of this report, or the decision to publish.