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Changes in intra-host genetic diversity according to lesion severity in longitudinal HPV16 samples.
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  • Jean-Marc Costanzi,
  • Milan Stosic S,
  • Alexander Hesselberg Løvestad,
  • Ole Herman Ambur,
  • Trine Rounge B,
  • Irene Kraus Christiansen
Jean-Marc Costanzi
Akershus Universitetssykehus HF

Corresponding Author:[email protected]

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Milan Stosic S
Akershus Universitetssykehus HF
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Alexander Hesselberg Løvestad
Akershus Universitetssykehus HF
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Ole Herman Ambur
OsloMet - storbyuniversitetet
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Trine Rounge B
Universitetet i Oslo
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Irene Kraus Christiansen
Akershus Universitetssykehus HF
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Abstract

Human papillomavirus type 16 (HPV16) is the most common cause of cervical cancer, but most infections are transient and with lesions not progressing to cancer. There is a lack of specific biomarkers for diagnosis and risk stratification. This study aimed to explore the intra-host 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 intra-host single nucleotide variants (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, respectively. A significant increase in the number of APOBEC3-induced iSNVs over time was observed for normal samples when compared to high-grade. Our results provide new insight into the dynamics of HPV16 within-hosts evolution. Low number of iSNVs and APOBEC3-induced iSNVs, characteristics of high-grade lesions, could potentially serve as biomarkers to guide triage of HPV-induced cervical precancerous lesions.
Submitted to Journal of Medical Virology
29 Jan 2024Review(s) Completed, Editorial Evaluation Pending
01 Feb 2024Editorial Decision: Revise Minor
18 Apr 2024Assigned to Editor
18 Apr 2024Submission Checks Completed
18 Apr 2024Review(s) Completed, Editorial Evaluation Pending
21 Apr 2024Editorial Decision: Accept