Comprehensive Viral Genotyping Reveals Prognostic Viral Phylogenetic Groups in HPV16-Associated Squamous Cell Carcinoma of the Oropharynx.
Comprehensive Viral Genotyping Reveals Prognostic Viral Phylogenetic Groups in HPV16-Associated Squamous Cell Carcinoma of the Oropharynx.
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综合病毒基因分型揭示了 HPV16 相关口咽鳞状细胞癌的预后病毒系统发育群。
DOI：
10.1158/1541-7786.mcr-21-0443
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Yarbrough,WendellG
中科院分区：
文献类型：
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作者：
Schrank,TravisP;Landess,Lee;Stepp,WesleyH;Rehmani,Hina;Weir,WilliamH;Lenze,Nicholas;Lal,Asim;Wu,Di;Kothari,Aditi;Hackman,TrevorG;Sheth,Siddharth;Patel,Shetal;Jefferys,StuartR;Issaeva,Natalia;Yarbrough,WendellG
人乳头瘤病毒阳性（HPV+）口咽鳞状细胞癌（OPSCC）是美国最常见的HPV相关恶性肿瘤，主要由HPV亚型16（HPV 16）引起。有利的治疗结局导致对治疗降级以降低治疗相关发病率的兴趣增加。需要预后生物标志物来识别适当的低风险患者，以降低治疗强度。对在一个中心接受治疗的104例HPV 16 +OPSCC患者的肿瘤进行靶向DNA测序，包括所有HPV 16开放阅读框。与HPV 16-A1参考密切相关的基因型与人类基因组中体细胞拷贝数变异的数量增加和无复发生存率（RFS）差相关。与HPV 16-A1不同的基因型与良好的RFS相关。这些发现与烟草烟雾暴露无关。对89例HPV 16 +OPSCC病例的第二个独立队列进行总RNA测序。在这个独立的队列中再次验证了与HPV 16-A1不同的HPV 16基因型，其是中度（小于30包-年）或低度（不超过10包-年）烟草烟雾暴露患者RFS改善的预后。总之，我们在两个独立的队列研究中发现，与HPV 16-A1参考序列的病毒序列差异与中度或低度吸烟患者RFS改善相关。提示HPV 16基因型是一种潜在的生物标志物，可以很容易地用于指导降阶梯治疗相关的治疗决策。
Human papillomavirus–positive (HPV+) squamous cell carcinoma of the oropharynx (OPSCC) is the most prevalent HPV-associated malignancy in the United States and is primarily caused by HPV subtype 16 (HPV16). Favorable treatment outcomes have led to increasing interest in treatment deescalation to reduce treatment-related morbidity. Prognostic biomarkers are needed to identify appropriately low-risk patients for reduced treatment intensity. Targeted DNA sequencing including all HPV16 open reading frames was performed on tumors from 104 patients with HPV16+OPSCC treated at a single center. Genotypes closely related to the HPV16-A1 reference were associated with increased numbers of somatic copy-number variants in the human genome and poor recurrence-free survival (RFS). Genotypes divergent from HPV16-A1 were associated with favorable RFS. These findings were independent of tobacco smoke exposure. Total RNA sequencing was performed on a second independent cohort of 89 HPV16+OPSCC cases. HPV16 genotypes divergent from HPV16-A1 were again validated in this independent cohort, to be prognostic of improved RFS in patients with moderate (less than 30 pack-years) or low (no more than 10 pack-years) of tobacco smoke exposure. In summary, we show in two independent cohorts that viral sequence divergence from the HPV16-A1 reference is correlated with improved RFS in patients with moderate or low tobacco smoke exposure.ImplicationsHPV16 genotype is a potential biomarker that could be easily adopted to guide therapeutic decision-making related to deescalation therapy.