No Prognostic Effect of HPV on the Outcome of Primary Radiotherapy in Advanced Non-Oropharyngeal Cancers

Award lecture at the ESTRO 33

Patients with oropharyngeal cancer who are positive for the human papilloma virus (HPV-positive) have a good prognosis, but until now the effect of HPV status on the prognosis of tumours located elsewhere in the head and neck area was unknown. Danish researchers have now shown that HPV status appears to have no prognostic effect on the outcome of primary radiotherapy in head and neck cancer outside the oropharynx. It was a topic of the award lecture, based on analysis of 1606 patients, and presented by Dr Pernille Lassen from the Aarhus University Hospital, Aarhus, Denmark at the ESTRO 33 Congress in Vienna, Austria (4-8 April 2014).

Based on these results, head and neck cancers located outside the oropharynx should probably not be treated with the less intensive treatment strategies that are currently being investigated in clinical trials for HPV-positive oropharyngeal tumours.

DNA from HPV has been found in all types of head and neck cancers, although it is far more common in oropharyngeal tumours. The study team investigated the impact of HPV status in non-oropharyngeal cancers in the DAHANCA database, which includes all patients with head and neck cancer in Denmark.

The researchers identified in their database patients with locally-advanced cancers who had been treated primarily with radiotherapy, and 1606 of them had laryngeal and pharyngeal carcinomas. Overall, 40% of the tumours were HPV-positive, and the frequency was significantly higher in oropharyngeal cancer than in non-oropharyngeal (57% vs. 13%).

In HPV-positive cancers there was significantly improved tumour control (81% as opposed to 55% in HPV-negative tumours), as well as survival (89% and 55% respectively), and death from any cause (82% and 38% respectively), after five years. In non-oropharyngeal cancers the researchers didn’t find prognostic impact of HPV-positive status for any of these endpoints.

Previously, laboratory studies have shown that HPV-positive tumour cells are much more sensitive to radiation therapy than HPV-negative cells, and the researchers believed that they would behave similarly irrespective of tumour site. However, the data from the new analysis from Denmark indicate that it is not the case. The researchers suppose that it probably can be explained by other biological/genetic differences between the tumours rather than the HPV status.

However, the study team would like to try to elucidate the underlying mechanisms behind these different outcomes (for example, genetic changes caused by smoking tobacco, differences due to a combination of causes, such as HPV-positive status and tobacco, or perhaps simply differences due to the site).

The Danish team plans to follow-up on their findings by analysing all the tumour samples by PCR in order to analyse changes in genetic information. There are few data available on this subject at present and the study team hopes that it will enable them to understand more about why the role of HPV in non-oropharyngeal tumours is so different.

Since the foundation of the European Society for Radiotherapy & Oncology (ESTRO), more than 30 years ago, radiation oncology has fortunately seen continuous changes with virtually every aspect of the basic science and of the clinical treatment improvements for the benefit of patient care. In this context, ESTRO 33 assisted ESTRO’s recent Vision for 2020 statement that: “Every cancer patient in Europe will have access to state of the art radiation therapy, as part of a multidisciplinary approach where treatment is individualised for the specific patient’s cancer, taking account of the patient’s personal circumstances”.