Source:Radiotherapy and Oncology
Author(s): Annett Linge, Ulrike Schötz, Steffen Löck, Fabian Lohaus, Cläre von Neubeck, Volker Gudziol, Alexander Nowak, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Hatice Bunea, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Kirsten Lauber, Steffi Pigorsch, Stephanie E. Combs, David Mönnich, Daniel Zips, Gustavo B. Baretton, Frank Buchholz, Mechthild Krause, Claus Belka, Michael Baumann
ObjectiveTo compare six HPV detection methods in pre-treatment FFPE tumour samples from patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who received postoperative (N = 175) or primary (N = 90) radiochemotherapy.Materials and methodsHPV analyses included detection of (i) HPV16 E6/E7 RNA, (ii) HPV16 DNA (PCR-based arrays, A-PCR), (iii) HPV DNA (GP5+/GP6+ qPCR, (GP-PCR)), (iv) p16 (immunohistochemistry, p16 IHC), (v) combining p16 IHC and the A-PCR result and (vi) combining p16 IHC and the GP-PCR result. Differences between HPV positive and negative subgroups were evaluated for the primary endpoint loco-regional control (LRC) using Cox regression.ResultsCorrelation between the HPV detection methods was high (chi-squared test, p < 0.001). While p16 IHC analysis resulted in several false positive classifications, A-PCR, GP-PCR and the combination of p16 IHC and A-PCR or GP-PCR led to results comparable to RNA analysis. In both cohorts, Cox regression analyses revealed significantly prolonged LRC for patients with HPV positive tumours irrespective of the detection method.ConclusionsThe most stringent classification was obtained by detection of HPV16 RNA, or combining p16 IHC with A-PCR or GP-PCR. This approach revealed the lowest rate of recurrence in patients with tumours classified as HPV positive and therefore appears most suited for patient stratification in HPV-based clinical studies.
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