Department of Otolaryngology-Head and Neck Surgery, The University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, North Carolina.
Linberger Comprehensive Cancer Center, The University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, North Carolina.
Mol Cancer Res. 2022 Oct 4;20(10):1489-1501. doi: 10.1158/1541-7786.MCR-21-0443.
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.
HPV16 genotype is a potential biomarker that could be easily adopted to guide therapeutic decision-making related to deescalation therapy.
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（HPV16）引起。由于治疗效果良好，人们越来越关注降低治疗强度以减少与治疗相关的发病率。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。在单一中心治疗的 104 例 HPV16+OPSCC 患者的肿瘤中进行了靶向 DNA 测序，包括所有 HPV16 开放阅读框。与 HPV16-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）降低相关。与 HPV16-A1 不同的基因型与良好的 RFS 相关。这些发现与吸烟无关。对第二个独立的 89 例 HPV16+OPSCC 病例的独立队列进行了总 RNA 测序。在这个独立队列中，再次验证了与 HPV16-A1 不同的 HPV16 基因型，对于中度（少于 30 包年）或低度（不超过 10 包年）吸烟暴露的患者，HPV16 基因型与改善的 RFS 相关。总之，我们在两个独立的队列中表明，与 HPV16-A1 参考相比，病毒序列的差异与中度或低度吸烟暴露患者的 RFS 改善相关。
HPV16 基因型是一种潜在的生物标志物，可用于指导与降级治疗相关的治疗决策。
