Diagnostic Accuracy of HPV16 Early Antigen Serology For HPV-Driven Oropharyngeal Cancer is Independent of Age and Sex

Johannes MA  Kusters; Brenda  Diergaarde; Andrew R. Ness; Maarten F Schim  van der Loef; Janneke CM  Heijne; Lea Schroeder; Katrina Hueniken; James D. Mckay; Gary Macfarlane; Pagona Lagiou; Areti Lagiou; Jerry Polesel; Antonio Agudo; Laia Alemany; Wolfgang Ahrens; Claire M Healy; David I Conway; Max Robinson; Christina  Canova; Ivana Holcátová; Lorenzo Richiardi; Ariana Znaor; Miranda Pring; Steve Thomas; Neil Hayes; Geoffrey Liu; Rayjean J. Hung; Paul Brennan; Andrew F Olshan; Shama Virani; Tim Waterboer

doi:10.1002/ijc.34710

Diagnostic Accuracy of HPV16 Early Antigen Serology For HPV-Driven Oropharyngeal Cancer is Independent of Age and Sex

Johannes MA Kusters, Brenda Diergaarde, Andrew R. Ness, Maarten F Schim van der Loef, Janneke CM Heijne, Lea Schroeder, Katrina Hueniken, James D. Mckay, Gary Macfarlane, Pagona Lagiou, Areti Lagiou, Jerry Polesel, Antonio Agudo, Laia Alemany, Wolfgang Ahrens, Claire M Healy, David I Conway, Max Robinson, Christina Canova, Ivana HolcátováLorenzo Richiardi, Ariana Znaor, Miranda Pring, Steve Thomas, Neil Hayes, Geoffrey Liu, Rayjean J. Hung, Paul Brennan, Andrew F Olshan, Shama Virani, Tim Waterboer^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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 of the VOYAGER consortium was used, which
comprises five studies on HNC from North America and Europe. Diagnostic accuracy, i.e., sensitivity, specificity, Cohen’s kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16INK4a 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 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

Original language	English
Pages (from-to)	289-402
Number of pages	13
Journal	International Journal of Cancer
Volume	154
Issue number	2
Early online date	11 Sept 2023
DOIs	https://doi.org/10.1002/ijc.34710
Publication status	Published - 15 Jan 2024

Bibliographical note

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 Canadian Cancer Society Research Institute and Lusi Wong Programs at the Princess Margaret Hospital Foundation.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request

Keywords

Human papillomavirus
oropharyngeal cancer
head and neck cancer
serology
diagnostic accuracy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

Kusters, J. MA., Diergaarde, B., Ness, A. R., van der Loef, M. F. S., Heijne, J. CM., Schroeder, L., Hueniken, K., Mckay, J. D., Macfarlane, G., Lagiou, P., Lagiou, A., Polesel, J., Agudo, A., Alemany, L., Ahrens, W., Healy, C. M., Conway, D. I., Robinson, M., Canova, C., ... Waterboer, T. (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), 289-402. https://doi.org/10.1002/ijc.34710

Kusters, JMA, Diergaarde, B, Ness, AR, van der Loef, MFS, Heijne, JCM, Schroeder, L, Hueniken, K, Mckay, JD, Macfarlane, G, Lagiou, P, Lagiou, A, Polesel, J, Agudo, A, Alemany, L, Ahrens, W, Healy, CM, Conway, DI, Robinson, M, Canova, C, Holcátová, I, Richiardi, L, Znaor, A, Pring, M, Thomas, S, Hayes, N, Liu, G, Hung, RJ, Brennan, P, Olshan, AF, Virani, S & Waterboer, T 2024, 'Diagnostic Accuracy of HPV16 Early Antigen Serology For HPV-Driven Oropharyngeal Cancer is Independent of Age and Sex', International Journal of Cancer, vol. 154, no. 2, pp. 289-402. https://doi.org/10.1002/ijc.34710

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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 of the VOYAGER consortium was used, whichcomprises five studies on HNC from North America and Europe. Diagnostic accuracy, i.e., sensitivity, specificity, Cohen{\textquoteright}s kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16INK4a immunohistochemistry (p16), HPV in-situ hybridization (ISH) andHPV 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 asensitivity 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 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 ",

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author = "Kusters, {Johannes MA} and Brenda Diergaarde and Ness, {Andrew R.} and {van der Loef}, {Maarten F Schim} and Heijne, {Janneke CM} and Lea Schroeder and Katrina Hueniken and Mckay, {James D.} and Gary Macfarlane and Pagona Lagiou and Areti Lagiou and Jerry Polesel and Antonio Agudo and Laia Alemany and Wolfgang Ahrens and Healy, {Claire M} and Conway, {David I} and Max Robinson and Christina Canova and Ivana Holc{\'a}tov{\'a} and Lorenzo Richiardi and Ariana Znaor and Miranda Pring and Steve Thomas and Neil Hayes and Geoffrey Liu and Hung, {Rayjean J.} and Paul Brennan and Olshan, {Andrew F} and Shama Virani and Tim Waterboer",

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AU - van der Loef, Maarten F Schim

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Diagnostic Accuracy of HPV16 Early Antigen Serology For HPV-Driven Oropharyngeal Cancer is Independent of Age and Sex

Abstract

Bibliographical note

Data Availability Statement

Keywords

UN SDGs

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