AI Article Synopsis
- HPV31 is related to HPV16 and accounts for only 4% of cervical cancer cases, yet its genetic and methylation differences remain under-researched.
- Researchers sequenced 2093 HPV31 genomes from studies in the U.S. and internationally and examined methylation in 175 samples, finding significant associations with cervical cancer.
- The study revealed that HPV31's A/B clade is linked to a higher risk of cervical intraepithelial neoplasia (CIN3+), with specific genetic variants like H23Y playing a critical role in increasing oncogenicity.
Article Abstract
Human papillomavirus (HPV) type 31 (HPV31) is closely related to the most carcinogenic type, HPV16, but only accounts for 4% of cervical cancer cases worldwide. Viral genetic and epigenetic variations have been associated with carcinogenesis for other high-risk HPV types, but little is known about HPV31. We sequenced 2093 HPV31 viral whole genomes from two large studies, one from the U.S. and one international. In addition, we investigated CpG methylation in a subset of 175 samples. We evaluated the association of HPV31 lineages/sublineages, single nucleotide polymorphisms (SNPs) and viral methylation with cervical carcinogenesis. HPV31 A/B clade was >1.8-fold more associated with cervical intraepithelial neoplasia grade 3 and cancer (CIN3+) compared to the most common C lineage. Lineage/sublineage distribution varied by race/ethnicity and geographic region. A viral genome-wide association analysis identified SNPs within the A/B clade associated with CIN3+, including H23Y (C626T) (odds ratio = 1.60, confidence intervals = 1.17-2.19) located in the pRb CR2 binding-site within the E7 oncogene. Viral CpG methylation was higher in lineage B, compared to the other lineages, and was most elevated in CIN3+. In conclusion, these data support the increased oncogenicity of the A/B lineages and suggest variation of E7 as a contributing risk factor.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540939 | PMC |
| http://dx.doi.org/10.3390/v13101948 | DOI Listing |
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