Influence of HPV-status on survival of patients with tonsillar carcinomas (TSCC) treated by CO2-laser surgery plus risk adapted therapy - A 10 year retrospective single centre study

• Published in: Cancer letters Vol. 413; pp. 59 - 68
• Main Authors: Hoffmann, Markus, Quabius, Elgar Susanne, Tribius, Silke, Gebhardt, Stephan, Görögh, Tibor, Hedderich, Jürgen, Huber, Karen, Dunst, Jürgen, Ambrosch, Petra
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 28.01.2018
• Subjects: De-escalation; HPV; OSCC; Smoking; Survival; TSCC; TSCC; OSCC; De-escalation; Survival; Smoking; HPV
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2017.10.045

The positive prognostic value of HPV-infections in oropharyngeal squamous cell cancer (OSCC) patients has led to the initiation of prospective clinical trials testing the value of treatment de-escalation. It is unclear how to define patients potentially benefiting from de-escalated treatment, whether a positive smoking history impacts survival data and what kind of de-escalation might be best. Here, we investigate the effect of HPV-status, smoking habit and treatment design on overall survival (OS) and progression free survival (PFS) of 126 patients with tonsillar SCC (TSCC) who underwent CO2-laser-surgery and risk adapted adjuvant treatment. HPV-DNA-, HPV-mRNA-, and p16INK4A-expression were analysed and results were correlated to OS and PFS. Factors tested for prognostic value included HPV-status, p16INK4A-protein expression, therapy and smoking habit. Log rank test and p-values ≤0.05 defined significant differences between groups. The highest accuracy of data with highest significance in this study is given when the HPV-RNA-status is considered. Using p16INK4A-expression alone or in combination with HPV-DNA-status, would have misclassified 23 and 7 patients, respectively. Smoking fully abrogates the positive impact of HPV-infection in TSCC on survival. Non-smoking HPV-positive TSCC patients show 10-year OS of 100% and 90.9% PFS when treated with adjuvant RCT. The presented data show that high-precision HPV-detection methods are needed, specifically when treatment decisions are based on the results. Furthermore, smoking habit should be included in all studies and clinical trials testing HPV-associated survival. Adjuvant RCT especially for HPV-positive non-smokers may help to avoid distant failure. •p16-status alone or in combination with HPV-DNA misclassifies 18% and 5% of patients.•HPV-RNA detection is the best option to identify HPV-driven cancers.•HPV and smoking affect survival after surgery and risk adapted adjuvant therapy.•High-precision HPV-detection and smoking are crucial in HPV-based survival-studies.•Adjuvant RCT for HPV-positive non-smokers may avoid distant failure.