As can be seen from the prognostic classifiers, the low-risk HPV-positive patients have excellent survival. These patients tend to be younger than the traditional head and neck cancer patient. This means that as they have a higher chance of cure, they will live longer with the substantial effects of treatment. Indeed, we know that chemoradiotherapy results in considerable early and late toxicities (Trotti et al. 2007), and that late toxicity is cumulative (Machtay et al. 2008). Therefore, it would seem reasonable to try to reduce the toxicity profile in these patients who have excellent long-term survival to improve their overall quality of life and reduce the long-term burden of treatment.

In addition, it would appear that patients are supportive of de-intensification of chemoradiotherapy regimens for HPV-positive low-risk disease. However, the majority of them are supportive only if there is little or no chance of detriment to their overall survival. Furthermore, it should be noted that over a quarter do not want de-intensification. In addition, the majority of those who are in favour of de-intensification would reduce the chemotherapy part of the treatment, and only 20 % would wish to reduce radiotherapy (Brotherston et al. 2013).

The overall principle guiding treatment is primum non nocere—first do no harm. These patients have excellent survival, and are in the main, cured of their disease. Many studies, including the one quoted above by Brotherstone, show that patients’ most important aim for treatment is cure followed by prolonged survival. Therefore, in all our discussions on de-intensification the maintenance of the very high cure rates for patients should be paramount.

When considering what the causes of treatment failure are in patients with high-risk disease, one identifies that they most often fail locoregionally. This was apparent in the RTOG 0129 study by Ang et al. (2010). In that study, distant metastatic failure did not differ significantly between HPV-positive and HPV-negative disease. Other studies e.g. by O’Sullivan et al. (2013) have shown that HPV-positive disease and HPV-negative disease have similar distant control rates. Work by the same group in Toronto has shown that the risk of distant metastasis in HPV-positive patients is highest in those who were treated with radiotherapy alone [with N2b disease and who are heavy smokers, or who have N2c or N3 disease]. Distant metastasis is also high in patients who have HPV-positive T4 disease. Therefore, we should be aware of de-intensifying treatment, especially by removing chemotherapy, in these patients who in the main constitute the intermediate HPV-positive risk category.