A risk prediction model for head and neck cancers incorporating lifestyle factors, HPV serology and genetic markers

Sanjeev Budhathoki, Brenda Diergaarde, Geoffrey Liu, Andrew Olshan, Andrew Ness, Tim Waterboer, Shama Virani, Patricia Basta, Noemi Bender, Nicole Brenner, Tom Dudding, Neil Hayes, Andrew Hope, Shao Hui Huang, Katrina Hueniken, Beatriz Kanterewicz, James D McKay, Miranda Pring, Steve Thomas, Kathy WisniewskiSera Thomas, Yonathan Brhane, Antonio Agudo, Laia Alemany, Areti Lagiou, Luigi Barzan, Cristina Canova, David I Conway, Claire M Healy, Ivana Holcatova, Pagona Lagiou, Tatiana V Macfarlane, Gary J Macfarlane, Jerry Polesel, Lorenzo Richiardi, Max Robinson, Ariana Znaor, Paul Brennan, Rayjean J Hung* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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 5,254 controls from 5 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. 

Original languageEnglish
Pages (from-to)2017-2223
Number of pages12
JournalInternational Journal of Cancer
Issue number10
Early online date1 Feb 2023
Publication statusPublished - 15 May 2023

Bibliographical note

Genotyping of cases and controls was performed at the Center for Inherited Disease Research (CIDR) and funded by NIH/NIDCR 1X01HG007780-0. The MSH-PMH study was supported by Canadian Cancer Society Research Institute and Lusi Wong Programs at the Princess Margaret Hospital Foundation. The University of Pittsburgh head and neck cancer case-control study is supported by US National Institutes of Health grants P50CA097190 and P30CA047904. The Carolina Head and Neck Cancer Epidemiology (CHANCE) study was supported in part by the National Cancer Institute (R01-CA90731). 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 papillomavirus (HPV) serology was supported by a Cancer Research UK Programme Grant, the Integrative Cancer Epidemiology Programme (grant number: C18281/A19169). Sanjeev Budhathoki is supported by the Hold'em for Life Oncology Fellowship. We thank Dr. Wolfgang Ahrens, PhD (Universität Bremen, Germany) for his support in ARCAGE study.

This project was funded in part by NIH/NIDCR R01 DE025712 (Paul Brennan, Brenda Diergaarde and Neil Hayes) and the Canada Research Chair from the Canadian Institute of Health Research (Rayjean J. Hung).

Data Availability Statement

Data sources and handling of the publicly available datasets used in our study are described in the Materials and Methods. Further details and other data that support the findings of our study are available from the corresponding authors upon request.


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