Caution: de-escalating radiation on HPV status alone

This caution warns against reducing radiotherapy for HPV-positive, p16-positive head and neck cancer on the basis of HPV status alone. HPV-positive tumours are heterogeneous in smoking exposure, nodal burden and biology, so a single marker over-selects patients for less treatment. Multiple randomised trials bear this out: the 60 Gy arms of NRG-HN005, and the cetuximab-substitution trials RTOG 1016 and De-ESCALaTE, all underperformed standard cisplatin chemoradiation with modern external beam radiotherapy, with more relapses. The current approach is response-adapted selection, or selection guided by circulating tumour HPV DNA, rather than HPV status at diagnosis.