Translational studies of HEAD and neck cancer in South America and Europe

Informations projet

HEADSpAcE

N° de convention de subvention: 825771

DOI

10.3030/825771

Projet clôturé

Date de signature de la CE 14 Decembre 2018

Date de début 1 Janvier 2019

Date de fin 30 Juin 2024

Financé au titre de

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Coût total

€ 4 097 233,75

Contribution de l’UE

€ 3 153 447,50

Coordonné par

CENTRE INTERNATIONAL DE RECHERCHE SUR LE CANCER
France

Periodic Reporting for period 4 - HEADSpAcE (Translational studies of HEAD and neck cancer in South America and Europe)

Période du rapport: 2023-07-01 au 2024-06-30

Résumé du contexte et des objectifs généraux du projet

Worldwide, more than 550,000 new cases of head and neck cancer (HNC) occur each year, resulting in approximately 300,000 deaths annually. It is the 6th most common cancer in both Europe and South America. A major reason for the high mortality rate for this cancer is the late stage of diagnosis for many patients. Accurate assessment of the prognosis of HNC cases also allows for appropriate treatment decisions. HEADSpAcE brought together a consortium of 18 partners with a long and successful record of collaboration in HNC. The primary objectives of HEADSpAcE were:
1) Assess the socio-economic and logistical reasons behind delay to diagnosis.
2) Determine the most accurate way to assess HPV positive oropharynx cancer in the clinical setting.
3) Identify the extent of HPV positive OPC in Europe and South America and assess lifestyle and genetic predictors of HPV infection.
4) Conduct comprehensive genomic evaluation HNC cases from South America and Europe.
5) Perform an analysis of germline variation to identify susceptibility loci for HNC outcome.
6) Identify whether liquid biopsies can be informative for HNC clinical care.
7) Identify guidelines for implementation into clinical care.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

HEADSpAcE successfully recruited approximately 1,500 cases across all project centers, creating the largest and most diverse contemporary case series of head and neck cancers (HNC) to date. The project harmonized epidemiological data from existing biorepositories and prospective recruitments with various data types, including genotyping, whole exome sequencing, and methylation sequencing. These samples, prepared by institutions in Europe and South America, were centralized at IARC to form the HEADSpAcE Data Centre, which will be made available to the international research community in accordance with HEADSpAcE Data access policies.

Quantitative analysis revealed that about half of the cases were diagnosed at advanced stage. A system-level survey on healthcare system, while qualitative interviews with HNC patients, clinicians, and service managers highlighted themes related to advanced-stage diagnosis. These findings informed recommendations for health system policy, governance frameworks, and future research.

The project tested various HPV reference assays, including p16 Immunohistochemistry (IHC), HPV serology, and HPV genotyping in oropharyngeal cancer (OPC) cases, aiming to improve the accuracy of diagnosing HPV-driven OPCs. Results showed that serology could serve as a gold standard for classifying HPV-driven OPCs due to its high sensitivity and specificity, with a potential to enhance clinical diagnostic methods.

Additionally, methylation targets identified from somatic profiles were tested in plasma samples to monitor disease status and track treatment response, revealing significant findings with potential therapeutic and prognostic importance. HEADSpAcE also conducted the largest genome-wide association study (GWAS) on HNC survival, including non-European populations for the first time. This study identified numerous novel risk loci affecting certain HNC subsites across populations.

Funded by the H2020 mechanism, the project created the most comprehensive dataset of HNC patients to date, covering over 15,000 individuals from diverse populations. This resource, which includes harmonized genetic, genomic, epidemiological, and clinical data, will now be sustained through the evolution of the infrastructure into the HEADSpAcE Data Centre, ensuring its continued utilization for future research.

The dissemination of the HEADSpAcE project's results have been strategically managed to maximize the reach of our findings. We are publishing manuscripts in scientific journals, ensuring that our research contributes to the global body of knowledge on HNC. We are presenting our findings at international conferences, engaging with the scientific community and fostering collaborations to enhance the project's visibility.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The disruptions caused by the Covid-19 pandemic presented a unique opportunity to incorporate critical insights into our assessment of risk factors for late-stage head and neck cancer (HNC) diagnoses. Specifically, we examined the pandemic's impact on patient care across different centers in Europe and South America. To address these challenges, WP2 developed a Covid disruption form to monitor interruptions in patient recruitment and hospital services, resulting in numerous scientific publications on the subject. Initially, the HEADSpAcE initiative aimed to genotype approximately 3,000 new samples. However, additional grants increased the number of new samples with germline genotype data to 10,000, greatly enhancing the power of WP6 analyses and improving the quality of publicly available deliverables for future research.

The achievements of the HEADSpAcE project contribute directly to the third Sustainable Development Goal (SDG) to “Ensure healthy lives and promote well-being for all at all ages.” By focusing on understanding the factors leading to advanced-stage HNC diagnoses and proposing actions to promote earlier detection, our work will have a profound impact on well-being and cancer survival rates. Additionally, by developing accurate prognostic models, we aim to ensure appropriate and effective treatment. The global relevance of this work extends far beyond Europe and Latin America. A key milestone in this regard was the publication of a major manuscript “Latin American Consensus On The Treatment Of Head And Neck Cancer,” in the Journal of Global Oncology.
Overall, the societal and socioeconomic impact of the HEADSpAcE project is significant and far-reaching, with implications extending across healthcare, research, and public policy. By assembling the largest and most diverse dataset of HNC patients to date—encompassing over 15,000 individuals from Europe and South America—HEADSpAcE has provided an unprecedented resource for the global research community. This harmonized dataset enables researchers to address critical questions related to HNC, with the potential to improve early diagnosis, treatment outcomes, and survival rates.

Economically, the project has paved the way for cost-effective studies in diagnostic accuracy and treatment strategies. The validation of serology as a gold-standard method for diagnosing HPV-driven oropharyngeal cancers (OPCs) is a notable example, with the potential to enhance diagnostic precision and optimize treatment pathways, thereby reducing healthcare costs associated with misdiagnosis and ineffective treatment. Moreover, the project's exploration of methylation targets as biomarkers for disease monitoring and treatment response could lead to more personalized and effective therapeutic interventions, further reducing the economic burden of HNC.

By including non-European populations in the largest genome-wide association study (GWAS) on HNC survival, HEADSpAcE has uncovered novel genetic risk loci and expanded the understanding of HNC across diverse populations. In summary, the HEADSpAcE project has made a strong impact on both society and the economy by advancing the understanding of HNC, improving diagnostic and treatment approaches, informing public health policies, and promoting research equity across populations. The establishment of the HEADSpAcE Data Centre further ensures that these benefits will continue to accrue, supporting ongoing research and innovation in the fight against HNC.

Logo_Headspace_RGB

Logo_Headspace_Header