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Article

Genetic and Epigenetic Variations of HPV52 in Cervical Precancer

1
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2
DBV Technologies, 92120 Montrouge, France
3
Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, China
4
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
5
Division of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA
6
Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA
7
Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA
8
Microbiology & Immunology, and Obstetrics, Gynecology & Women’s Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA
*
Author to whom correspondence should be addressed.
Co-authors contributed equally.
Academic Editor: Marta del Pino
Int. J. Mol. Sci. 2021, 22(12), 6463; https://doi.org/10.3390/ijms22126463
Received: 24 May 2021 / Revised: 10 June 2021 / Accepted: 11 June 2021 / Published: 16 June 2021
The goal of this study was to identify human papillomavirus (HPV) type 52 genetic and epigenetic changes associated with high-grade cervical precancer and cancer. Patients were selected from the HPV Persistence and Progression (PaP) cohort, a cervical cancer screening program at Kaiser Permanente Northern California (KPNC). We performed a nested case-control study of 89 HPV52-positive women, including 50 cases with predominantly cervical intraepithelial neoplasia grade 3 (CIN3) and 39 controls without evidence of abnormalities. We conducted methylation analyses using Illumina sequencing and viral whole genome Sanger sequencing. Of the 24 CpG sites examined, increased methylation at CpG site 5615 in HPV52 L1 region was the most significantly associated with CIN3, with a difference in median methylation of 17.9% (odds ratio (OR) = 4.8, 95% confidence interval (CI) = 1.9–11.8) and an area under the curve of 0.73 (AUC; 95% CI = 0.62–0.83). Complete genomic sequencing of HPV52 isolates revealed associations between SNPs present in sublineage C2 and a higher risk of CIN3, with ORs ranging from 2.8 to 3.3. This study identified genetic and epigenetic HPV52 variants associated with high risk for cervical precancer, improving the potential for early diagnosis of cervical neoplasia caused by HPV52. View Full-Text
Keywords: HPV52; papillomavirus; methylation; next generation sequencing; evolution; phylogeny; precancer HPV52; papillomavirus; methylation; next generation sequencing; evolution; phylogeny; precancer
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MDPI and ACS Style

Bee, K.J.; Gradissimo, A.; Chen, Z.; Harari, A.; Schiffman, M.; Raine-Bennett, T.; Castle, P.E.; Clarke, M.; Wentzensen, N.; Burk, R.D. Genetic and Epigenetic Variations of HPV52 in Cervical Precancer. Int. J. Mol. Sci. 2021, 22, 6463. https://doi.org/10.3390/ijms22126463

AMA Style

Bee KJ, Gradissimo A, Chen Z, Harari A, Schiffman M, Raine-Bennett T, Castle PE, Clarke M, Wentzensen N, Burk RD. Genetic and Epigenetic Variations of HPV52 in Cervical Precancer. International Journal of Molecular Sciences. 2021; 22(12):6463. https://doi.org/10.3390/ijms22126463

Chicago/Turabian Style

Bee, Katharine J., Ana Gradissimo, Zigui Chen, Ariana Harari, Mark Schiffman, Tina Raine-Bennett, Philip E. Castle, Megan Clarke, Nicolas Wentzensen, and Robert D. Burk. 2021. "Genetic and Epigenetic Variations of HPV52 in Cervical Precancer" International Journal of Molecular Sciences 22, no. 12: 6463. https://doi.org/10.3390/ijms22126463

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