ZIA CP010210 10834 (ZIA) | |||
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Title | Study to Evaluate Whether Heterogeneity in Efficacy by HPV Variants Explains the | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Kreimer, Aimee | NCI Program Director | N/A |
Cancer Activity | N/A | Division | DCEG |
Funded Amount | $218,498 | Project Dates | null - null |
Fiscal Year | 2018 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Biochemical Epidemiology (45.0%) Cancer (100.0%) |
Cervical Cancer (100.0%) | ||
Research Type | |||
Endogenous Factors in the Origin and Cause of Cancer Vaccines |
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Abstract | |||
The prophylactic HPV vaccine has proven an effective means to protect against oncogenic HPV infection and risk of HPV-associated cancers. In addition to protecting against the targeted HPV types, the vaccine provides partial protection against phylogenetically related types. It is thought that HPV types that are phylogenetically related could have similarities in their epitopes to allow for partial cross-reactive immune responses. One remaining question is to determine whether the partial protection against an HPV type varies by lineage, sublineage, or specific mutations. A previous report from our group (ref. Harari et. al.) evaluated whether partial cross-protection observed in CVT could be explained at the variant level. We concluded at the time that sequence variation at the variant level did not explain the cross-protective effect of Cervarix because the phenomenon was not observed for other HPV types evaluated. However, there were several limitations of our previous, published work that have led us to believe that reexamination of this hypothesis is warranted. First, we now have a longer follow-up time and therefore a larger number of infections. Moreover, these infections occur later and advances in whole genome sequencing technology now allow for a more agnostic evaluation of cross-protection at a finer, sublineage level. Lastly, our previous effort focused on sequence variation in the upstream regulatory region and/or E6 open reading frame, which was useful for the variant lineage assignment and previous analyses at the lineage level, but using HPV genome data here will additionally allow use to evaluate if individual nucleotide variants in the L1 region effect vaccine efficacy. We hope our proposed study would allow us to better understand the basis of cross-protection and provide insights into the public health impact of vaccination with Cervarix. |