The work plan of HEADSpAcE is split up into 10 Work Packages (WPs), which are described below.
The full infographics can be viewed and downloaded, courtesy of A.C.Camargo Cancer Center, São Paulo, Brazil.
WP1: Coordination, management, and expansion of large biorepositories and related data
Provide a searchable database of the biorepositories available from the existing studies and planned patient recruitments in Europe and South America.
Ensure ongoing follow-up of biorepositories for clinical outcome, with a focus on recently recruited patients from South America. Where possible, postdiagnosis blood samples will also be collected.
Develop new prospective recruitment of patients from 11 centres, including extensive biological sample collection and detailed information on the reasons for delays in presentation.
Oversee all ethical and legal documentation necessary for recruitment of new patients and for sharing of data and biological samples between partners.
Ensure appropriate access to biological samples for external groups based on requests that may be submitted, as well as the sharing of genomic data generated by HEADSpAcE.
WP2: Socioeconomic, logistical, and biological predictors of delayed head and neck cancer diagnosis in Europe and South America
Identify the main factors that result in a delay between the onset of symptoms and the time of diagnosis, including factors related to the patient and factors related to medical infrastructure.
Assess inequalities in late-stage presentation of head and neck cancer, focusing on socioeconomic, logistical (health care system), and biological (tumour) factors.
WP3: Determining the most accurate method of assessing HPV-driven oropharyngeal cancer in the clinical setting
Assess performance characteristics of routine biomarkers for identification of HPV-driven oropharyngeal cancer in the routine clinical setting, including HPV DNA and p16 immunohistochemistry.
Comprehensively describe the immunohistochemical characteristics of HPV-driven versus non-HPV-driven oropharyngeal cancers.
Validate a novel diagnostic RNA-based chromogenic in-situ hybridization technique (RNAscope) capable of reliably detecting transcriptionally active genes (including the high-risk HPV E6/E7 oncogenes) in formalin-fixed, paraffin-embedded tissue from oropharyngeal cancers, and compare assay performance with routine clinical methods.
Validate a novel diagnostic HPV ELISA assay detecting antibodies to the E6 oncoprotein of HPV16 in serum or plasma samples from patients with oropharyngeal squamous cell carcinoma, and compare assay performance with routine clinical methods.
WP4: Identifying the extent of HPV-driven oropharyngeal cancer in Europe and South America, assessing its influence on clinical outcome, and developing prognostic models
Estimate the burden of HPV-driven oropharyngeal cancer in Europe and South America.
Assess the lifestyle, sexual history, and clinical factors associated with HPV-driven oropharyngeal cancer by country and region.
Assess genetic factors associated with HPV-driven oropharyngeal cancer by country and region.
Assess time trends in the HPV-driven oropharyngeal cancer fractions by country and region.
Assess the prognostic value of lifestyle, clinical, and genetic factors in patients with oropharyngeal cancer by HPV status.
WP5: Genomic analysis of 800 cases of head and neck cancer from South America and Europe
Comprehensively assess somatic mutations in 800 cases of oral cancer, laryngeal cancer, and oropharyngeal cancer from Europe and South America by deep exome sequencing and high-density methylation arrays.
Assess gene methylation patterns in 100 cases of head and neck cancer, including both tumour and normal adjacent tissues.
Assess gene expression profiles among a subgroup of at least 400 cases of oral cancer, oropharyngeal cancer, and laryngeal cancer by RNA sequencing.
Conduct rigorous bioinformatics analysis of all 800 cases to identify mutation, methylation, and expression profiles associated with each cancer type and with disease outcome.
Incorporate these 800 cases into the parallel analysis of 1000 cases of oral cancer and oropharyngeal cancer being conducted within North America and Europe as part of the NIH-funded VOYAGER project.
WP6: Germline susceptibility to head and neck cancer and the relation to outcome
Extend genome-wide association analysis to 1300 oropharyngeal and 900 oral cancers from the HN5000 study and incorporate an additional analysis of 900 oral and oropharyngeal cancer cases from the InterCHANGE study.
Conduct complete survival analysis along with an additional 6000 cases from the VOYAGER project, resulting in a total of 9000 cases.
Analyse rare variant exomes for 1800 cases, with targeted sequencing follow-up.
Analyse HLA class and HPV infection for both oropharyngeal cancer and oral cancer, in relation to outcome.
WP7: Evaluating minimally invasive biomarkers to predict recurrence and survival in head and neck cancer cases
Determine the correlation of mutations between tumour and plasma at baseline in head and neck cancer.
Evaluate the use of circulating tumour DNA detection from plasma in predicting recurrence and outcome of head and neck cancer.
Evaluate the use of HPV16 E6 serology detection from plasma in predicting recurrence and outcome of HPV-driven oropharyngeal cancers.
Develop a targeted sequencing panel for head and neck cancer monitoring during follow-up.
WP8: Dissemination of key HEADSpAcE findings and implementation in clinical practice
Establish the identity of HEADSpAcE and develop a communication strategy based on clear goals, including targets, tools for dissemination, timing, and monitoring.Promote the project’s outcomes and activities to the scientific community, the media, the clinical community, decision-makers, stakeholders, and the general public.
Disseminate information and the results of HEADSpAcE via the project webpage, Twitter, Facebook, and other electronic media.
Evaluate the implementation of national and international treatment protocols and guidelines for head and neck cancer in Europe and South America, and develop clinical guidelines based on relevant prognostic information.
Organize a comprehensive scientific meeting, bringing together leading head and neck cancer scientists from Europe, South America, and elsewhere, to showcase the results of HEADSpAcE and stimulate further collaboration beyond the timeframe of the project.
WP9: Administration and management of HEADSpAcE
Provide effective coordination and management for the planned activities of the HEADSpAcE project and bring it to a successful conclusion.
Ensure an effective management, risk-assessment, and decision-making process among the consortium partners.
Ensure that the project’s main objectives are realized on schedule and according to budget, and ensure the completion of reporting procedures in accordance with European Commission regulations.
Facilitate the unhindered progress of the project by ensuring smooth and timely flow of samples, analysis of biological specimens, and harmonization of epidemiological and exposure data.
Ensure that the activities of all participants are compliant with the European Commission contract, the consortium agreement, and the relevant ethical and legal requirements regarding collaboration.
WP10: Ethics requirements
Ensure compliance with all ethics requirements.