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Human papillomavirus type 16 genomic variation in women with subsequent in situ or invasive cervical cancer: prospective population-based study

BACKGROUND: HPV genomic variation may be involved in viral carcinogenesis. METHODS: In a national register-based nested case–control study, we retrieved archival smears from baseline cytologically normal women who later developed cancer in situ (CIS), squamous cervical cancer (SCC) or remained free...

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Autores principales: Arroyo-Mühr, Laila Sara, Lagheden, Camilla, Hultin, Emilie, Eklund, Carina, Adami, Hans-Olov, Dillner, Joakim, Sundström, Karin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219482/
https://www.ncbi.nlm.nih.gov/pubmed/30344308
http://dx.doi.org/10.1038/s41416-018-0311-7
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author Arroyo-Mühr, Laila Sara
Lagheden, Camilla
Hultin, Emilie
Eklund, Carina
Adami, Hans-Olov
Dillner, Joakim
Sundström, Karin
author_facet Arroyo-Mühr, Laila Sara
Lagheden, Camilla
Hultin, Emilie
Eklund, Carina
Adami, Hans-Olov
Dillner, Joakim
Sundström, Karin
author_sort Arroyo-Mühr, Laila Sara
collection PubMed
description BACKGROUND: HPV genomic variation may be involved in viral carcinogenesis. METHODS: In a national register-based nested case–control study, we retrieved archival smears from baseline cytologically normal women who later developed cancer in situ (CIS), squamous cervical cancer (SCC) or remained free of disease. These smears were previously HPV tested by PCR and HPV16 was the strongest risk factor. We now used the Illumina NextSeq platform to sequence HPV16 genomes in cervical smears from 242 women who later developed CIS/CIN3 (n = 134), SCC (n = 92) or remained healthy (n = 16). RESULTS: The median sequence depth per sample was high (11,288×). For 218/242 samples (>90%), we covered ≥80% of the complete HPV16 genome with sequencing median depths of >200×. We identified a wide range of unique isolates and 147 novel SNPs across the 218 samples. Most women (97%) had HPV16 lineage A infection, with the sublineages being A1 (66.1%), A2 (28.9%) and A4 (1.8%), respectively. The least variable gene was the E7 (3.4% variability), where 170/204 case women (83%) displayed a fully conserved sequence. There were no obvious differences by disease outcome (CIS or SCC). CONCLUSIONS: We found a high number of novel SNPs. The E7 gene was hypovariable both among women later developing CIN3/CIS, and SCC, respectively.
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spelling pubmed-62194822020-01-16 Human papillomavirus type 16 genomic variation in women with subsequent in situ or invasive cervical cancer: prospective population-based study Arroyo-Mühr, Laila Sara Lagheden, Camilla Hultin, Emilie Eklund, Carina Adami, Hans-Olov Dillner, Joakim Sundström, Karin Br J Cancer Article BACKGROUND: HPV genomic variation may be involved in viral carcinogenesis. METHODS: In a national register-based nested case–control study, we retrieved archival smears from baseline cytologically normal women who later developed cancer in situ (CIS), squamous cervical cancer (SCC) or remained free of disease. These smears were previously HPV tested by PCR and HPV16 was the strongest risk factor. We now used the Illumina NextSeq platform to sequence HPV16 genomes in cervical smears from 242 women who later developed CIS/CIN3 (n = 134), SCC (n = 92) or remained healthy (n = 16). RESULTS: The median sequence depth per sample was high (11,288×). For 218/242 samples (>90%), we covered ≥80% of the complete HPV16 genome with sequencing median depths of >200×. We identified a wide range of unique isolates and 147 novel SNPs across the 218 samples. Most women (97%) had HPV16 lineage A infection, with the sublineages being A1 (66.1%), A2 (28.9%) and A4 (1.8%), respectively. The least variable gene was the E7 (3.4% variability), where 170/204 case women (83%) displayed a fully conserved sequence. There were no obvious differences by disease outcome (CIS or SCC). CONCLUSIONS: We found a high number of novel SNPs. The E7 gene was hypovariable both among women later developing CIN3/CIS, and SCC, respectively. Nature Publishing Group UK 2018-10-22 2018-10-30 /pmc/articles/PMC6219482/ /pubmed/30344308 http://dx.doi.org/10.1038/s41416-018-0311-7 Text en © Cancer Research UK 2018 https://creativecommons.org/licenses/by/4.0/This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
spellingShingle Article
Arroyo-Mühr, Laila Sara
Lagheden, Camilla
Hultin, Emilie
Eklund, Carina
Adami, Hans-Olov
Dillner, Joakim
Sundström, Karin
Human papillomavirus type 16 genomic variation in women with subsequent in situ or invasive cervical cancer: prospective population-based study
title Human papillomavirus type 16 genomic variation in women with subsequent in situ or invasive cervical cancer: prospective population-based study
title_full Human papillomavirus type 16 genomic variation in women with subsequent in situ or invasive cervical cancer: prospective population-based study
title_fullStr Human papillomavirus type 16 genomic variation in women with subsequent in situ or invasive cervical cancer: prospective population-based study
title_full_unstemmed Human papillomavirus type 16 genomic variation in women with subsequent in situ or invasive cervical cancer: prospective population-based study
title_short Human papillomavirus type 16 genomic variation in women with subsequent in situ or invasive cervical cancer: prospective population-based study
title_sort human papillomavirus type 16 genomic variation in women with subsequent in situ or invasive cervical cancer: prospective population-based study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219482/
https://www.ncbi.nlm.nih.gov/pubmed/30344308
http://dx.doi.org/10.1038/s41416-018-0311-7
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