Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold-out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also included HPV serology showed substantially improved predictive accuracy for oropharyngeal cancer (AUC = 0.94, 95% CI = 0.92-0.95 in men and AUC = 0.92, 95% CI = 0.88-0.95 in women). The 5-year absolute risk estimates showed distinct trajectories by risk factor profiles. Based on the UK Biobank cohort, the risks of developing oropharyngeal cancer among 60 years old and HPV16 seropositive in the next 5 years ranged from 5.8% to 14.9% with an average of 8.1% for men, 1.3% to 4.4% with an average of 2.2% for women. Absolute risk was generally higher among individuals with heavy smoking, heavy drinking, HPV seropositivity and those with higher polygenic risk score. These risk models may be helpful for identifying people at high risk of developing head and neck cancer.

Bristol Dental School University of Bristol Bristol UK

Catalan Institute of Oncology IDIBELL Barcelona Spain

Centre for Oral Health Research Newcastle University Newcastle upon Tyne UK

Dalla Lana School of Public Health University of Toronto Toronto Ontario Canada

Department of Epidemiology Gillings School of Global Public Health University of North Carolina Chapel Hill North Carolina USA

Department of Medical Oncology Princess Margaret Cancer Centre University of Toronto Toronto Ontario Canada

Department of Radiation Oncology Princess Margaret Cancer Centre University of Toronto Toronto Ontario Canada

Division of Medical Oncology and Center for Cancer Research University of Tennessee Health Science Center Memphis Tennessee USA

Epidemiology Group School of Medicine Medical Sciences and Nutrition University of Aberdeen Aberdeen UK

Genetic Epidemiology Group International Agency for Research on Cancer Lyon France

Graduate School of Public Health University of Pittsburgh and UPMC Hillman Cancer Center Pittsburgh Pennsylvania USA

Infections and Cancer Epidemiology Division German Cancer Research Center Heidelberg Germany

Institute of Hygiene and Epidemiology Prague Czech Republic

International Agency for Research on Cancer Lyon France

National Cancer Institute IRCCS Milan Italy

NIHR Bristol Biomedical Research Centre Weston NHS Foundation Trust University of Bristol Bristol UK

Nutrition and Cancer Group Epidemiology Public Health Cancer Prevention and Palliative Care Program Bellvitge Biomedical Research Institute IDIBELL L'Hospitalet de Llobregat Barcelona Spain

Prosserman Centre for Population Health Research Lunenfeld Tanenbaum Research Institute Sinai Health Toronto Ontario Canada

Radiation Medicine Program Princess Margaret Cancer Centre University Health Network Toronto Ontario Canada

Reference Centre for Epidemiology and Cancer Prevention in Piemonte University of Turin Aberdeen Italy

School of Dental Science Trinity College Dublin Dublin Ireland

School of Medicine Dentistry and Nursing University of Glasgow Glasgow UK

School of Medicine National and Kapodistrian University of Athens Zografou Greece

School of Public Health University of West Attica Aigaleo Greece

Unit of Biostatistics Epidemiology and Public Health Department of Cardio Thoraco Vascular Sciences and Public Health University of Padua Padova Italy

Unit of Nutrition and Cancer Catalan Institute of Oncology ICO L'Hospitalet de Llobregat Barcelona Spain

University of North Carolina Lineberger Cancer Center Chapel Hill North Carolina USA

UPMC Hillman Cancer Center Pittsburgh Pennsylvania USA

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$a A risk prediction model for head and neck cancers incorporating lifestyle factors, HPV serology and genetic markers / $c S. Budhathoki, B. Diergaarde, G. Liu, A. Olshan, A. Ness, T. Waterboer, S. Virani, P. Basta, N. Bender, N. Brenner, T. Dudding, N. Hayes, A. Hope, SH. Huang, K. Hueniken, B. Kanterewicz, JD. McKay, M. Pring, S. Thomas, K. Wisniewski, S. Thomas, Y. Brhane, A. Agudo, L. Alemany, A. Lagiou, L. Barzan, C. Canova, DI. Conway, CM. Healy, I. Holcatova, P. Lagiou, GJ. Macfarlane, TV. Macfarlane, J. Polesel, L. Richiardi, M. Robinson, A. Znaor, P. Brennan, RJ. Hung

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$a Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold-out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also included HPV serology showed substantially improved predictive accuracy for oropharyngeal cancer (AUC = 0.94, 95% CI = 0.92-0.95 in men and AUC = 0.92, 95% CI = 0.88-0.95 in women). The 5-year absolute risk estimates showed distinct trajectories by risk factor profiles. Based on the UK Biobank cohort, the risks of developing oropharyngeal cancer among 60 years old and HPV16 seropositive in the next 5 years ranged from 5.8% to 14.9% with an average of 8.1% for men, 1.3% to 4.4% with an average of 2.2% for women. Absolute risk was generally higher among individuals with heavy smoking, heavy drinking, HPV seropositivity and those with higher polygenic risk score. These risk models may be helpful for identifying people at high risk of developing head and neck cancer.

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