TY - JOUR
T1 - Diagnostic accuracy of HPV16 early antigen serology for HPV-driven oropharyngeal cancer is independent of age and sex
AU - Kusters, Johannes M.A.
AU - Diergaarde, Brenda
AU - Ness, Andrew
AU - Schim van der Loeff, Maarten F.
AU - Heijne, Janneke C.M.
AU - Schroeder, Lea
AU - Hueniken, Katrina
AU - McKay, James D.
AU - Macfarlane, Gary J.
AU - Lagiou, Pagona
AU - Lagiou, Areti
AU - Polesel, Jerry
AU - Agudo, Antonio
AU - Alemany, Laia
AU - Ahrens, Wolfgang
AU - Healy, Claire M.
AU - Conway, David I.
AU - Robinson, Max
AU - Canova, Christina
AU - Holcátová, Ivana
AU - Richiardi, Lorenzo
AU - Znaor, Ariana
AU - Pring, Miranda
AU - Thomas, Steve
AU - Hayes, D. Neil
AU - Liu, Geoffrey
AU - Hung, Rayjean J.
AU - Brennan, Paul
AU - Olshan, Andrew F.
AU - Virani, Shama
AU - Waterboer, Tim
N1 - Funding Information:
This project was funded in part by NIH/NIDCR R01 DE025712 (Paul Brennan, Brenda Diergaarde and Neil Hayes). The Alcohol-Related Cancers and Genetic Susceptibility Study in Europe (ARCAGE) was funded by the European Commission's fifth framework program (QLK1-2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte and Padova University (CPDA057222). We thank Dr. Wolfgang Ahrens, PhD (Universität Bremen, Germany) for his support in ARCAGE study. 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). The University of Pittsburgh head and neck cancer case-control study is supported by US National Institutes of Health grants P50CA097190 and P30CA047904. The MSH-PMH study was supported by the Canadian Cancer Society Research Institute and the Lusi Wong Programs at the Princess Margaret Hospital Foundation.
Publisher Copyright:
© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
PY - 2024/1/15
Y1 - 2024/1/15
N2 - A growing proportion of head and neck cancer (HNC), especially oropharyngeal cancer (OPC), is caused by human papillomavirus (HPV). There are several markers for HPV-driven HNC, one being HPV early antigen serology. We aimed to investigate the diagnostic accuracy of HPV serology and its performance across patient characteristics. Data from the VOYAGER consortium was used, which comprises five studies on HNC from North America and Europe. Diagnostic accuracy, that is, sensitivity, specificity, Cohen's kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16
INK4a immunohistochemistry (p16), HPV in situ hybridization (ISH) and HPV PCR as reference methods. Stratified analyses were performed for variables including age, sex, smoking and alcohol use, to test the robustness of diagnostic accuracy. A risk-factor analysis based on serology was conducted, comparing HPV-driven to non-HPV-driven OPC. Overall, HPV serology had a sensitivity of 86.8% (95% CI 85.1-88.3) and specificity of 91.2% (95% CI 88.6-93.4) for HPV-driven OPC using p16 as a reference method. In stratified analyses, diagnostic accuracy remained consistent across sex and different age groups. Sensitivity was lower for heavy smokers (77.7%), OPC without lymph node involvement (74.4%) and the ARCAGE study (66.7%), while specificity decreased for cases with <10 pack-years (72.1%). The risk-factor model included study, year of diagnosis, age, sex, BMI, alcohol use, pack-years, TNM-T and TNM-N stage. HPV serology is a robust biomarker for HPV-driven OPC, and its diagnostic accuracy is independent of age and sex. Future research is suggested on the influence of smoking on HPV antibody levels.
AB - A growing proportion of head and neck cancer (HNC), especially oropharyngeal cancer (OPC), is caused by human papillomavirus (HPV). There are several markers for HPV-driven HNC, one being HPV early antigen serology. We aimed to investigate the diagnostic accuracy of HPV serology and its performance across patient characteristics. Data from the VOYAGER consortium was used, which comprises five studies on HNC from North America and Europe. Diagnostic accuracy, that is, sensitivity, specificity, Cohen's kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16
INK4a immunohistochemistry (p16), HPV in situ hybridization (ISH) and HPV PCR as reference methods. Stratified analyses were performed for variables including age, sex, smoking and alcohol use, to test the robustness of diagnostic accuracy. A risk-factor analysis based on serology was conducted, comparing HPV-driven to non-HPV-driven OPC. Overall, HPV serology had a sensitivity of 86.8% (95% CI 85.1-88.3) and specificity of 91.2% (95% CI 88.6-93.4) for HPV-driven OPC using p16 as a reference method. In stratified analyses, diagnostic accuracy remained consistent across sex and different age groups. Sensitivity was lower for heavy smokers (77.7%), OPC without lymph node involvement (74.4%) and the ARCAGE study (66.7%), while specificity decreased for cases with <10 pack-years (72.1%). The risk-factor model included study, year of diagnosis, age, sex, BMI, alcohol use, pack-years, TNM-T and TNM-N stage. HPV serology is a robust biomarker for HPV-driven OPC, and its diagnostic accuracy is independent of age and sex. Future research is suggested on the influence of smoking on HPV antibody levels.
KW - diagnostic accuracy
KW - head and neck cancer
KW - human papillomavirus
KW - oropharyngeal cancer
KW - serology
U2 - 10.1002/ijc.34710
DO - 10.1002/ijc.34710
M3 - Article
SN - 0020-7136
VL - 154
SP - 389
EP - 402
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 2
ER -