Abstract
BackgroundThe proxy marker for human papillomavirus (HPV), p16, is included in the new AJCC 8th/UICC 8th staging system, but due to incongruence between p16 status and HPV infection, single biomarker evaluation could lead to misallocation of patients. We established nomograms for overall survival (OS) and progression-free survival (PFS) in patients with oropharyngeal squamous cell carcinoma (OPSCC) and known HPV-DNA and p16 status, and validated the models in cohorts from high- and low-prevalent HPV countries.MethodsConsecutive OPSCC patients treated in Denmark, 2000–2014 formed the development cohort. The validation cohorts were from Sweden, Germany, and the United Kingdom. We developed nomograms by applying a backward-selection procedure for selection of variables, and assessed model performance.ResultsIn the development cohort, 1313 patients, and in the validation cohorts, 344 German, 503 Swedish and 463 British patients were included. For the OS nomogram, age, gender, combined HPV-DNA and p16 status, smoking, T-, N-, and M-status and UICC-8 staging were selected, and for the PFS nomogram the same variables except UICC-8 staging. The nomograms performed well in discrimination and calibration.ConclusionsOur nomograms are reliable prognostic methods in patients with OPSCC. Combining HPV DNA and p16 is essential for correct prognostication. The nomograms are available at www.orograms.org.
Highlights
In most parts of the Western world, the main risk factor for oropharyngeal squamous cell carcinoma (OPSCC) is infection with high-risk human papillomavirus (HPV); while, a smaller proportion is related to a high consumption of alcohol and smoking tobacco.[1,2,3,4] Patients with HPV-associated OPSCCs have improved survival probably related to a different mutational profile,[5,6] immune response[7,8,9] and clinical features.[10]p16 overexpression is a proxy marker for HPV-driven carcinogenesis which is the main prognostic factor in patients with OPSCC
overall survival (OS) was for the HPV +/p16+ patients 95% after 1 year, 86% after 3 years and 80% after 5 years of follow-up, and for the HPV–/p16– patients 71% after 1 year, 46% after 3 years and 34% after 5 years (Fig. 1, Table 2)
Overall survival Five-year OS for the HPV+/p16+ patients in the Swedish cohort was 81% and for the HPV–/p16– patients 40%; for the German cohort 81% and 35% and in the United Kingdom (UK) cohort it was 82% and 42%
Summary
In most parts of the Western world, the main risk factor for oropharyngeal squamous cell carcinoma (OPSCC) is infection with high-risk human papillomavirus (HPV); while, a smaller proportion is related to a high consumption of alcohol and smoking tobacco.[1,2,3,4] Patients with HPV-associated OPSCCs have improved survival probably related to a different mutational profile,[5,6] immune response[7,8,9] and clinical features.[10]p16 overexpression is a proxy marker for HPV-driven carcinogenesis which is the main prognostic factor in patients with OPSCC. The proxy marker for human papillomavirus (HPV), p16, is included in the new AJCC 8th/UICC 8th staging system, but due to incongruence between p16 status and HPV infection, single biomarker evaluation could lead to misallocation of patients. We established nomograms for overall survival (OS) and progression-free survival (PFS) in patients with oropharyngeal squamous cell carcinoma (OPSCC) and known HPV-DNA and p16 status, and validated the models in cohorts from high- and low-prevalent HPV countries.
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