Abstract：
Human papillomavirus type 16 (HPV16) is the most common cause of cervical cancer, but most infections are transient with lesions not progressing to cancer. There is a lack of specific biomarkers for early cancer risk stratification. This study aimed to explore the intrahost HPV16 genomic variation in longitudinal samples from HPV16-infected women with different cervical lesion severity (normal, low-grade, and high-grade). The TaME-seq deep sequencing protocol was used to generate whole genome HPV16 sequences of 102 samples collected over time from 40 individuals. Single nucleotide variants (SNVs) and intrahost SNVs (iSNVs) were identified in the viral genomes. A majority of individuals had a unique set of SNVs and these SNVs were stable over time. Overall, the number of iSNVs and APOBEC3-induced iSNVs were significantly lower in high-grade relative to normal and low-grade samples. A significant increase in the number of APOBEC3-induced iSNVs over time was observed for normal samples when compared to high-grade. Our results indicates that the lower incidence of iSNVs and APOBEC3-induced iSNVs in high-grade lesions may have implications for novel biomarkers discoveries, potentially aiding early stratification of HPV-induced cervical precancerous lesions.
摘要：
人乳头瘤病毒16型（HPV16）是宫颈癌最常见的病因，但是大多数感染是短暂的，病变不会进展为癌症。缺乏用于早期癌症风险分层的特异性生物标志物。本研究旨在探讨不同宫颈病变严重程度（正常，低档,和高品位）。TaME-seq深度测序方案用于产生随时间从40个个体收集的102个样品的全基因组HPV16序列。在病毒基因组中鉴定了单核苷酸变体(SNV)和宿主内SNV(iSNV)。大多数个体具有一组独特的SNV,并且这些SNV随时间稳定。总的来说,iSNV和APOBEC3诱导的iSNV的数量在高等级样本中相对于正常和低等级样本显著更低.当与高级样品相比时,观察到正常样品的APOBEC3诱导的iSNV的数量随时间的显著增加。我们的结果表明，在高级别病变中iSNV和APOBEC3诱导的iSNV的较低发生率可能对新的生物标志物发现有影响。可能有助于HPV诱导的宫颈癌前病变的早期分层。
