Head and neck cancer (HNC) is the sixth most common cancer globally. Incidence and survival rates vary significantly across geographic regions and tumor subsites. This is partly due to differences in risk factor exposure, which includes tobacco smoking, alcohol consumption and human papillomavirus (HPV) infection, alongside detection and treatment strategies. The VOYAGER (human papillomaVirus, Oral and oropharYngeal cAncer GEnomic Research) consortium is a collaboration between five large North American and European studies which generated data on 10,530 participants (7,233 cases and 3,297 controls). The primary goal of the collaboration was to improve understanding of the role of HPV and genetic factors in oral cavity and oropharyngeal cancer risk and outcome. Demographic and clinical data collected by the five studies were harmonized, and HPV status was determined for the majority of cases. In addition, 999 tumors were sequenced to define somatic mutations. These activities generated a comprehensive biomedical resource that can be utilized to answer critical outstanding research questions to help improve HNC prevention, early detection, treatment, and surveillance.

Scott Bratman reports grants from AstraZeneca, personal fees and equity from Adela, patents licensed to Adela and Roche, and service on advisory board for EMD Serono. Where members are identified as personnel of the International Agency for Research on Cancer/ World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization.

VOYAGER was funded by US National Institute of Dental and Craniofacial Research (NIDCR) grant R01DE025712 (PIs: Brennan, Diergaarde, and Hayes: The role of germline and somatic DNA mutations in oral and oropharyngeal cancers). Genotyping using the OncoArray and the All of Us array was performed at the Center for Inherited Disease (CIDR) and funded by NIDCR 1X01HG007780-0 and NIDCR/NCI X01HG010743, respectively. The Alcohol-Related Cancers and Genetic Susceptibility Study in Europe (ARCAGE) was funded by the European Commissions fifth frame-work program (QLK1-2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte and Padova University (CPDA057222). The Carolina Head and Neck Cancer Epidemiology (CHANCE) study was supported in part by the National Cancer Institute (R01CA90731). The Head and Neck 5000 study was a component of independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Core funding was also provided through awards from Above and Beyond, University Hospitals Bristol and Weston Research Capability Funding and the NIHR Senior Investigator award to Professor Andy Ness. Human papilloma virus (HPV) serology was supported by a Cancer Research UK Programme Grant, the Integrative Cancer Epidemiology Programme (grant number: C18281/A19169). The University of Pittsburgh head and neck cancer case-control study was supported by US National Institutes of Health grants P50CA097190 and P30CA047904. The MSH-PMH study was supported by the Canadian Cancer Society Research Institute and the Princess Margaret Head & Neck Translational Research Program, with philanthropic funds from Joes Team and the Wharton, Elia, Riley, and Tozer families. G.L. is funded by the Alan B. Brown Chair in Molecular Genomics and the Lusi Wong Foundation Fund.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The VOYAGER project was approved by the International Association for Research on Cancer (IARC) Ethics Committee (IEC) (Project No.: 16-34). The five parent studies were all approved by the respective institutional review boards (IRBs) at each of the participating center: University of North Carolina at Chapel Hill (Study No.: 01-0390), University of Pittsburgh (STUDY19120160), The University Health Network (Project No. 07-0521), Sinai Health System (REB No.: 08-0191) and the National Health Service, Health Research Authority (Project ID: 24028).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Information on the VOYAGER Consortium can be found at https://voyager.iarc.who.int/. The contact page can be used for data and collaboration requests. Non-commercial research projects are generally approved if the proposed research complies with the signed agreements between studies and their research participants. Genotype data for the oral and pharynx cancer OncoArray study have been deposited at the database of Genotypes and Phenotypes (dbGaP) and are available under controlled access under accession phs001202.v1.p1. Genotype data for the All of Us study are also available via dbGaP under controlled access under accession phs003225.v1.p1. The oral and pharyngeal GWAS summary statistics by cancer site and world region have been deposited in the IEU Open GWAS platform (https://gwas.mrcieu.ac.uk/) under the GWAS IDs: ieu-b-89, ieu-b-90, ieu-b-94, ieu-b-96, ieu-b-93, ieu-b-97, ieu-b-91, ieu-b-95 and ieu-b-98.

https://voyager.iarc.who.int/

https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001202.v1.p1

https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs003225.v1.p1