Citation
Kusters, Johannes M. A.; Diergaarde, Brenda; Ness, Andrew R.; Schim van der Loeff, Maarten F.; Heijne, Janneke C. M.; Schroeder, Lea; Hueniken, Katrina; McKay, James D.; Macfarlane, Gary J.; & Lagiou, Pagona, et al. (2024). Diagnostic Accuracy of HPV16 Early Antigen Serology for HPV-Driven Oropharyngeal Cancer Is Independent of Age and Sex. International Journal of Cancer, 154(2), 359-402.Abstract
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.URL
http://dx.doi.org/10.1002/ijc.34710Reference Type
Journal ArticleYear Published
2024Journal Title
International Journal of CancerAuthor(s)
Kusters, Johannes M. A.Diergaarde, Brenda
Ness, Andrew R.
Schim van der Loeff, Maarten F.
Heijne, Janneke C. M.
Schroeder, Lea
Hueniken, Katrina
McKay, James D.
Macfarlane, Gary J.
Lagiou, Pagona
Lagiou, Areti
Polesel, Jerry
Agudo, Antonio
Alemany, Laia
Ahrens, Wolfgang
Healy, Claire M.
Conway, David I.
Robinson, Max
Canova, Christina
Holcátová, Ivana
Richiardi, Lorenzo
Znaor, Ariana
Pring, Miranda
Thomas, Steve
Hayes, D. Neil
Liu, Geoffrey
Hung, Rayjean J.
Brennan, Paul
Olshan, Andrew F.
Virani, Shama
Waterboer, Tim