Hilary A Robbins1, Aida Ferreiro-Iglesias1, Tim Waterboer2, Nicole Brenner2, Mari Nygard3, Noemi Bender2, Lea Schroeder2, Allan Hildesheim4, Michael Pawlita2, Gypsyamber D'Souza5, Kala Visvanathan5, Hilde Langseth6,7, Nicolas F Schlecht8,9, Lesley F Tinker10, Ilir Agalliu9, Sylvia Wassertheil-Smoller9, Eivind Ness-Jensen11,12,13, Kristian Hveem14, Sara Grioni15, Rudolf Kaaks16, Maria-Jose Sánchez17,18,19,20, Elisabete Weiderpass21, Graham G Giles22,23,24, Roger L Milne22,23,24, Qiuyin Cai25, William J Blot25, Wei Zheng25, Stephanie J Weinstein4, Demetrius Albanes4, Wen-Yi Huang4, Neal D Freedman4, Aimée R Kreimer4, Mattias Johansson1, Paul Brennan1. 1. Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France. 2. Division of Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 3. Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway. 4. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD. 5. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 6. Department of Research, Cancer Registry of Norway, Oslo, Norway. 7. Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom. 8. Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY. 9. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY. 10. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA. 11. HUNT Research Center and K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger/Trondheim, Norway. 12. Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway. 13. Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. 14. HUNT Research Center and K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. 15. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy. 16. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 17. Escuela Andaluza de Salud Pública (EASP), Granada, Spain. 18. Instituto de Investigación Biosanitaria (ibs.GRANADA), Granada, Spain. 19. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. 20. Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain. 21. International Agency for Research on Cancer, Lyon, France. 22. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia. 23. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Australia. 24. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia. 25. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN.
Abstract
PURPOSE: Seropositivity for the HPV16-E6 oncoprotein is a promising marker for early detection of oropharyngeal cancer (OPC), but the absolute risk of OPC after a positive or negative test is unknown. METHODS: We constructed an OPC risk prediction model that integrates (1) relative odds of OPC for HPV16-E6 serostatus and cigarette smoking from the human papillomavirus (HPV) Cancer Cohort Consortium (HPVC3), (2) US population risk factor data from the National Health Interview Survey, and (3) US sex-specific population rates of OPC and mortality. RESULTS: The nine HPVC3 cohorts included 365 participants with OPC with up to 10 years between blood draw and diagnosis and 5,794 controls. The estimated 10-year OPC risk for HPV16-E6 seropositive males at age 50 years was 17.4% (95% CI, 12.4 to 28.6) and at age 60 years was 27.1% (95% CI, 19.2 to 45.4). Corresponding 5-year risk estimates were 7.3% and 14.4%, respectively. For HPV16-E6 seropositive females, 10-year risk estimates were 3.6% (95% CI, 2.5 to 5.9) at age 50 years and 5.5% (95% CI, 3.8 to 9.2) at age 60 years and 5-year risk estimates were 1.5% and 2.7%, respectively. Over 30 years, after a seropositive result at age 50 years, an estimated 49.9% of males and 13.3% of females would develop OPC. By contrast, 10-year risks among HPV16-E6 seronegative people were very low, ranging from 0.01% to 0.25% depending on age, sex, and smoking status. CONCLUSION: We estimate that a substantial proportion of HPV16-E6 seropositive individuals will develop OPC, with 10-year risks of 17%-27% for males and 4%-6% for females age 50-60 years in the United States. This high level of risk may warrant periodic, minimally invasive surveillance after a positive HPV16-E6 serology test, particularly for males in high-incidence regions. However, an appropriate clinical protocol for surveillance remains to be established.
PURPOSE: Seropositivity for the HPV16-E6 oncoprotein is a promising marker for early detection of oropharyngeal cancer (OPC), but the absolute risk of OPC after a positive or negative test is unknown. METHODS: We constructed an OPC risk prediction model that integrates (1) relative odds of OPC for HPV16-E6 serostatus and cigarette smoking from the human papillomavirus (HPV) Cancer Cohort Consortium (HPVC3), (2) US population risk factor data from the National Health Interview Survey, and (3) US sex-specific population rates of OPC and mortality. RESULTS: The nine HPVC3 cohorts included 365 participants with OPC with up to 10 years between blood draw and diagnosis and 5,794 controls. The estimated 10-year OPC risk for HPV16-E6 seropositive males at age 50 years was 17.4% (95% CI, 12.4 to 28.6) and at age 60 years was 27.1% (95% CI, 19.2 to 45.4). Corresponding 5-year risk estimates were 7.3% and 14.4%, respectively. For HPV16-E6 seropositive females, 10-year risk estimates were 3.6% (95% CI, 2.5 to 5.9) at age 50 years and 5.5% (95% CI, 3.8 to 9.2) at age 60 years and 5-year risk estimates were 1.5% and 2.7%, respectively. Over 30 years, after a seropositive result at age 50 years, an estimated 49.9% of males and 13.3% of females would develop OPC. By contrast, 10-year risks among HPV16-E6 seronegative people were very low, ranging from 0.01% to 0.25% depending on age, sex, and smoking status. CONCLUSION: We estimate that a substantial proportion of HPV16-E6 seropositive individuals will develop OPC, with 10-year risks of 17%-27% for males and 4%-6% for females age 50-60 years in the United States. This high level of risk may warrant periodic, minimally invasive surveillance after a positive HPV16-E6 serology test, particularly for males in high-incidence regions. However, an appropriate clinical protocol for surveillance remains to be established.
Authors: Chia-Jung Busch; Anna Sophie Hoffmann; Daniele Viarisio; Benjamin T Becker; Thorsten Rieckmann; Christian Betz; Noemi Bender; Lea Schroeder; Yassin Hussein; Elina Petersen; Annika Jagodzinski; Ines Schäfer; Eike Burandt; Krystle Lang Kuhs; Michael Pawlita; Tim Waterboer; Nicole Brenner Journal: EClinicalMedicine Date: 2022-09-17