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Record W3186393640 · doi:10.1038/s41467-021-26151-9

Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer

2021· article· en· W3186393640 on OpenAlexafffund
Aida Ferreiro-Iglesias, James McKay, Nicole Brenner, Shama Virani, Corina Lesseur, Valérie Gaborieau, Andy Ness, Rayjean J. Hung, Geoffrey Liu, Brenda Diergaarde, Andrew F. Olshan, D. Neil Hayes, Mark C. Weissler, Lea Schroeder, Noemi Bender, Michael Pawlita, Steve Thomas, Miranda Pring, Tom Dudding, Beatriz Kanterewicz, Robert L. Ferris, Sera Thomas, Yonathan Brhane, Virginia Díez‐Obrero, Maja Milojevic, Karl Smith-Byrne, Daniela Mariosa, Mattias Johansson, Rolando Herrero, Stefania Boccia, Gabriella Cadoni, Martin Lacko, Ivana Holcátová, Wolfgang Ahrens, Παγώνα Λάγιου, Areti Lagiou, Jerry Polesel, Lorenzo Simonato, Franco Merletti, Claire M. Healy, Bo T. Hansen, Mari Nygård, David I. Conway, Sylvia Wright, Tatiana V. Macfarlane, Max Robinson, Laia Alemany, Antonio Agudo, Ariana Znaor, Christopher I. Amos, Tim Waterboer, Paul Brennan

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldMedicine
TopicHead and Neck Cancer Studies
Canadian institutionsUniversity of TorontoSinai Health SystemLunenfeld-Tanenbaum Research Institute
FundersNational Institute of Dental and Craniofacial ResearchNational Cancer InstituteMedical Research CouncilAssociazione Italiana per la Ricerca sul CancroPrincess Margaret Hospital FoundationWorld Health OrganizationEuropean CommissionUniversity of PittsburghNational Institute for Health and Care ResearchCompagnia di San PaoloCentre International de Recherche sur le CancerCanadian Cancer Society Research InstituteU.S. Department of Health and Human ServicesNational Institutes of HealthCancer Research UK
KeywordsImmune systemGermlineImmunologyHuman leukocyte antigenCancerGenetic predispositionBiologySerologyCapsidHaplotypeAntibodyVirologyVirusGeneticsGeneAlleleAntigen

Abstract

fetched live from OpenAlex

Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.664
Threshold uncertainty score0.510

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.039
GPT teacher head0.386
Teacher spread0.347 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations42
Published2021
Admission routes2
Has abstractyes

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