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

Abstract

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.

Analogies between HPV Behavior in Oral and Vaginal Cavity: Narrative Review on the Current Evidence in the Literature

“…This finding is strengthened by other manuscripts that have correlated HLA-G expression and poor prognosis [ 61 , 62 ]. These data are consistent with other HLA class I polypeptides [ 45 , 46 ] and with other class II polypeptides [ 63 , 64 , 65 , 66 , 67 , 68 , 69 ], but also with patients with squamous cell carcinoma of the head and neck [ 21 , 70 ].…”

“…However, the prevalence of oral HPV infections with concomitant cervical HPV infection shows contradictory results, with some authors reporting high-prevalence and others not. Long-term positivity (over 24 months) of high-risk cervical and oral HPV may induce an increase in cervical and oral cancer with stratified risk according to genetic background and HPV subtype [ 21 ]. Notably, oral HPV16 DNA is commonly detected among patients with HPV-OSCC at diagnosis, yet the prevalence rate among their partners is confusing [ 22 ].…”