Changes in intrahost genetic diversity according to lesion severity in longitudinal HPV16 samples

Area of Science:

• Virology
• Oncology
• Genomics

Background:

• Human papillomavirus type 16 (HPV16) is a primary cause of cervical cancer.
• Most HPV16 infections are transient, and progression to cancer is not inevitable.
• Current biomarkers for early cervical cancer risk stratification are insufficient.

Purpose of the Study:

• To investigate HPV16 genomic variation within individuals over time.
• To correlate HPV16 intrahost variation with cervical lesion severity (normal, low-grade, high-grade).
• To explore potential novel biomarkers for early cervical cancer risk.

Main Methods:

• Longitudinal sampling from 40 HPV16-infected women with varying lesion severities.
• TaME-seq deep sequencing protocol for whole-genome HPV16 sequencing (102 samples).
• Identification and analysis of single nucleotide variants (SNVs) and intrahost SNVs (iSNVs).

Main Results:

• Most individuals harbored unique and temporally stable sets of HPV16 SNVs.
• Significantly lower numbers of iSNVs and APOBEC3-induced iSNVs were found in high-grade lesions compared to normal and low-grade lesions.
• Normal samples showed a significant increase in APOBEC3-induced iSNVs over time, unlike high-grade samples.

Conclusions:

• The reduced incidence of iSNVs, particularly APOBEC3-induced variants, in high-grade cervical lesions is a key finding.
• These genomic variations may serve as potential biomarkers for early stratification of HPV-induced cervical precancerous lesions.
• Further research into HPV16 genomic variation could enhance early detection and management strategies for cervical cancer.