Näsman Anders, Andersson Emilia, Marklund Linda, Tertipis Nikolaos, Hammarstedt-Nordenvall Lalle, Attner Per, Nyberg Tommy, Masucci Giuseppe V, Munck-Wikland Eva, Ramqvist Torbjörn, Dalianis Tina
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
PLoS One. 2013 Oct 10;8(10):e77025. doi: 10.1371/journal.pone.0077025. eCollection 2013.
HPV-DNA positive (HPVDNA+) oropharyngeal squamous cell carcinoma (OSCC) has better clinical outcome than HPV-DNA negative (HPVDNA-) OSCC. Current treatment may be unnecessarily extensive for most HPV+ OSCC, but before de-escalation, additional markers are needed together with HPV status to better predict treatment response. Here the influence of HLA class I/HLA class II expression was explored. Pre-treatment biopsies, from 439/484 OSCC patients diagnosed 2000-2009 and treated curatively, were analyzed for HLA I and II expression, p16(INK4a) and HPV DNA. Absent/weak as compared to high HLA class I intensity correlated to a very favorable disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) in HPVDNA+ OSCC, both in univariate and multivariate analysis, while HLA class II had no impact. Notably, HPVDNA+ OSCC with absent/weak HLA class I responded equally well when treated with induction-chemo-radiotherapy (CRT) or radiotherapy (RT) alone. In patients with HPVDNA- OSCC, high HLA class I/class II expression correlated in general to a better clinical outcome. p16(INK4a) overexpression correlated to a better clinical outcome in HPVDNA+ OSCC. Absence of HLA class I intensity in HPVDNA+ OSCC suggests a very high survival independent of treatment and could possibly be used clinically to select patients for randomized trials de-escalating therapy.
人乳头瘤病毒DNA阳性（HPV-DNA+）的口咽鳞状细胞癌（OSCC）比人乳头瘤病毒DNA阴性（HPV-DNA-）的OSCC具有更好的临床结果。对于大多数HPV+的OSCC患者，目前的治疗可能过于激进，但在降低治疗强度之前，需要除HPV状态之外的其他标志物来更好地预测治疗反应。在此探讨了人类白细胞抗原I类/人类白细胞抗原II类表达的影响。对2000年至2009年确诊并接受根治性治疗的484例OSCC患者中的439例患者的治疗前活检组织进行分析，检测人类白细胞抗原I类和II类表达、p16（INK4a）和HPV DNA。在HPV-DNA+的OSCC中，与高人类白细胞抗原I类强度相比，其表达缺失/减弱与非常良好的无病生存期（DFS）、疾病特异性生存期（DSS）和总生存期（OS）相关，单因素和多因素分析均如此，而人类白细胞抗原II类则无影响。值得注意的是，HPV-DNA+且人类白细胞抗原I类表达缺失/减弱的OSCC患者，接受诱导化疗放疗（CRT）或单独放疗（RT）时反应相同。在HPV-DNA-的OSCC患者中，高人类白细胞抗原I类/II类表达总体上与更好的临床结果相关。p16（INK4a）过表达与HPV-DNA+的OSCC更好的临床结果相关。HPV-DNA+的OSCC中人类白细胞抗原I类强度缺失提示其生存率很高，与治疗无关，可能可在临床上用于选择患者进行降低治疗强度的随机试验。
