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Comparison of detection methods for HPV status as a prognostic marker for loco-regional control after radiochemotherapy in patients with HNSCC.

Linge, A.; Schötz, U.; Löck, S.; Lohaus, F.; von Neubeck, C.; Gudziol, V.; Nowak, A.; Tinhofer, I.; Budach, V.; Sak, A.; Stuschke, M.; Balermpas, P.; Rödel, C.; Bunea, H.; Grosu, A.; Abdollahi, A.; Debus, J.; Ganswindt, U.; Lauber, K.; Pigorsch, S.; Combs, S.; Mönnich, D.; Zips, D.; Baretton, G.; Buchholz, F.; Krause, M.; Belka, C.; Baumann, M.

Abstract

OBJECTIVE:

To 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 METHODS:

HPV 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.
RESULTS:

Correlation 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.
CONCLUSIONS:

The 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.

Keywords: DKTK-ROG; HNSCC; HPV; Loco-regional control; Radiochemotherapy; p16

Permalink: https://www.hzdr.de/publications/Publ-26970