背景:人乳头瘤病毒(HPV)+口咽癌(OPC)比HPV阴性疾病具有更良好的预后,但特定HPV基因型和系统进化枝对患者结局的影响尚不清楚,这对降低治疗强度具有深远意义.
方法:这项单机构队列研究的目的是调查HPV基因型(16vs高危非16)和进化枝(A9vsA7)与OPC结果的相关性。主要终点是治愈性M0疾病患者的总生存期(OS)和无事件生存期(EFS)。
结果:该队列包括598名患者(87%HPV16,98%A9)。与HPV16OPC相比,非HPV16OPC患者年龄较高,合并症指数,以及非白人的比例,HIV+患者,T4肿瘤,和IV期疾病(AJCC第7版)。非HPV16基因型与单变量OS较差相关(HR=2.17,95%CI,1.24-3.80,P=.0066),但在多变量分析中没有(HRadj=0.84,95%CI,0.43-1.62,P=.5921)。A7进化枝与单变量OS较差相关(HR=4.42,95%CI,1.60-12.30,P=.0041),但在多变量分析中没有(HRadj=2.39,95%CI,0.57-9.99,P=.2325)。HPV基因型(HR=1.60,95%CI,0.99-2.60,P=.0566)和系统进化枝(HR=2.47,95%CI,0.91-6.72,P=.0761)均与EFS无关。
结论:在单变量分析中,非HPV16基因型和A7进化枝与OS更差相关,并倾向于EFS更差。系统进化枝的生存差异比HPV16状态更明显,这表明前者可能是未来研究更有用的分类。然而,当调整患者和肿瘤协变量时,HPV16状态和系统发育枝都不是预后的,这就提出了一个问题,即结局的可能差异是否与不同的临床特征有关,而不是与固有的病毒特性有关。
BACKGROUND: Human papillomavirus (HPV)+ oropharynx cancer (OPC) has a more favorable prognosis than HPV-negative disease, but the impact of specific HPV genotype and phylogenic clade on patient outcomes is not well understood and has profound implications for treatment de-intensification.
METHODS: The objective of this single-institution cohort study was to investigate the association of HPV genotype (16 vs high-risk non-16) and clade (A9 vs A7) with OPC outcomes. The primary endpoints were overall survival (OS) and event-free survival (EFS) in patients with M0 disease treated with curative intent.
RESULTS: The cohort included 598 patients (87% HPV16, 98% A9). Compared to those with HPV16 OPC, individuals with non-HPV16 OPC had a higher age, comorbidity index, and proportion of non-whites, HIV+ patients, T4 tumors, and stage IV disease (AJCC 7th edition). Non-HPV16 genotype was associated with worse OS in univariate (HR = 2.17, 95% CI, 1.24-3.80, P = .0066), but not in multivariate analysis (HRadj = 0.84, 95% CI, 0.43-1.62, P = .5921). A7 clade was associated with worse OS in univariate (HR = 4.42, 95% CI, 1.60-12.30, P = .0041), but not in multivariate analysis (HRadj = 2.39, 95% CI, 0.57-9.99, P = .2325). Neither HPV genotype (HR = 1.60, 95% CI, 0.99-2.60, P = .0566) nor phylogenic clade (HR = 2.47, 95% CI, 0.91-6.72, P = .0761) was associated with EFS.
CONCLUSIONS: Non-HPV16 genotype and A7 clade were associated with worse OS and trended toward worse EFS in univariate analyses. The survival differences were more pronounced by phylogenic clade than by HPV16 status, suggesting that the former may be a more useful classification for future studies. However, neither HPV16 status nor phylogenic clade was prognostic when adjusting for patient and tumor covariates, raising the question as to whether possible differences in outcomes are related to distinct clinical profiles rather than inherent viral properties.