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HPV16 Sublineage Associations With Histology-Specific Cancer Risk Using HPV Whole-Genome Sequences in 3200 Women.


ABSTRACT:

Background

HPV16 is a common sexually transmitted infection although few infections lead to cervical precancer/cancer; we cannot distinguish nor mechanistically explain why only certain infections progress. HPV16 can be classified into four main evolutionary-derived variant lineages (A, B, C, D) that have been previously suggested to have varying disease risks.

Methods

We used a high-throughput HPV16 whole-genome sequencing assay to investigate variant lineage risk among 3215 HPV16-infected women. Using sublineages A1/A2 as the reference, we assessed all variant lineage associations with infection outcome over three or more years of follow-up: 1107 control subjects (ResultsA4 sublineage was associated with an increased risk of cancer, specifically adenocarcinoma (OR?=?9.81, 95% CI?=?2.02 to 47.69, P?=?4.7x10(-03)). Lineage B had a lower risk of CIN3 (OR?=?0.51, 95% CI?=?0. 28 to 0.91, P?=?02) while lineage C showed increased risk (OR?=?2.06, 95% CI?=?1.09 to 3.89, P?=?03). D2/D3 sublineages were strongly associated with an increased risk of CIN3 and cancer, particularly D2 (OR for cancer = 28.48, 95% CI?=?9.27 to 87.55, P?=?5.0x10(-09)). D2 had the strongest increased risk of glandular lesions, AIS (OR?=?29.22, 95% CI?=?8.94 to 95.51, P?=?2.3x10(-08)), and adenocarcinomas (OR?=?137.34, 95% CI?=?37.21 to 506.88, P?=?1.5x10(-13)). Moreover, the risk of precancer and cancer for specific variant lineages varied by a women's race/ethnicity; those women whose race/ethnicity matched that of the infecting HPV16 variant had an increased risk of CIN3?+?(P?ConclusionsSpecific HPV16 variant sublineages strongly influence risk of histologic types of precancer and cancer, and viral genetic variation may help explain its unique carcinogenic properties.

PROVIDER: S-EPMC5939630 | BioStudies |

REPOSITORIES: biostudies

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