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Somatic mutations in 3929 HPV positive cervical cells associated with infection outcome and HPV type
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Somatic mutations in 3929 HPV positive cervical cells associated with infection outcome and HPV type
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Journal Article
Somatic mutations in 3929 HPV positive cervical cells associated with infection outcome and HPV type
2024
Overview
Invasive cervical cancers (ICC), caused by HPV infections, have a heterogeneous molecular landscape. We investigate the detection, timing, and HPV type specificity of somatic mutations in 3929 HPV-positive exfoliated cervical cell samples from individuals undergoing cervical screening in the U.S. using deep targeted sequencing in ICC cases, precancers, and HPV-positive controls. We discover a subset of hotspot mutations rare in controls (2.6%) but significantly more prevalent in precancers, particularly glandular precancer lesions (10.2%), and cancers (25.7%), supporting their involvement in ICC carcinogenesis. Hotspot mutations differ by HPV type, and HPV18/45-positive ICC are more likely to have multiple hotspot mutations compared to HPV16-positive ICC. The proportion of cells containing hotspot mutations is higher (i.e., higher variant allele fraction) in ICC and mutations are detectable up to 6 years prior to cancer diagnosis. Our findings demonstrate the feasibility of using exfoliated cervical cells for detection of somatic mutations as potential diagnostic biomarkers.
Invasive cervical cancer is caused by HPV infection, but the disease itself is highly variable. Here, the authors use deep targeted sequencing to identify hotspot mutations in routine screening samples prior to diagnosis, which differed depending on HPV type.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/23
/ 45/77
/ Adult
/ Cancer
/ Female
/ High-Throughput Nucleotide Sequencing
/ Human papillomavirus 16 - genetics
/ Human papillomavirus 16 - isolation & purification
/ Humanities and Social Sciences
/ Humans
/ Mutation
/ Papillomavirus Infections - genetics
/ Papillomavirus Infections - virology
/ Science
/ Uterine Cervical Dysplasia - genetics
/ Uterine Cervical Dysplasia - pathology
/ Uterine Cervical Dysplasia - virology
/ Uterine Cervical Neoplasms - genetics
