Head & Neck Cancer HPV Status - No Impact Beyond Oropharynx

Kate Johnson

April 14, 2014

VIENNA — The favorable prognosis of patients with head and neck tumors that test positive for human papilloma virus (HPV) compared with the prognosis with HPV-negative ones may be restricted to patients with oropharyngeal disease only and not those with tumors outside the oropharynx, suggest new data from the Danish Head and Neck Cancer Group (DAHANCA).

"The new and somewhat surprising result of this study was that if you focus on tumors arising outside the oropharynx, we see no difference whatsoever in terms of locoregional tumor control, whether they were HPV-16-positive or -negative," reported researcher Pernille Lassen, MD, PhD, from the Aarhus University Hospital, Denmark. This lack of impact of HPV status was also seen in terms of survival in patients with nonoropharyngeal disease.

"Based on this, it's pretty tempting to assume that the prognostic impact of HPV/p16 status is restricted to tumors arising in the oropharynx," she ventured at the European Society for Radiotherapy and Oncology (ESTRO) 33.

"The findings will have an important impact on the treatment of HPV-positive head and neck cancers and are likely to lead to a change in current practice," said ESTRO president Vincenzo Valentini, a radiation oncologist at the Policlinico Universitario A. Gemelli, Rome, Italy, in a written statement.

The study included a large cohort of patients (n = 1606) from the DAHANCA database, all with advanced (stage III-IV) head and neck squamous cell carcinoma (HNSCC) of the pharynx and larynx. All patients were treated between 1992 and 2012 using primary radiotherapy.

"The cornerstone of treatment was primary radiotherapy with curative intent, but within this 20-year period we have changed treatment rather dramatically," explained Dr. Lassen. "In the beginning, patients were treated with conventionally fractionated radiotherapy alone; that was exchanged with moderately accelerated fractionation, and on top of that we now treat patients also with hypoxic modification ― using the radiosensitizer, nimorazole ― and in the latest period we also add weekly cisplatinum (40 mg/m2) in advanced disease."

During the 20-year period, the majority of the tumors (n = 1002) were oropharyngeal, said Dr. Lassen, with 57% of these being HPV-positive. "Outside of the oropharynx, only about 13% of the tumors were HPV-positive, with the majority of these tumors occurring in the larynx, followed by the hypopharyngeal region, with a minor contribution from the nasopharyngeal region."

Tumors Outside the Oropharynx Region

The study found that in oropharyngeal cancer, HPV/p16-positive disease compared with negative disease was significantly correlated with improved locoregional tumor control (5-year actuarial values, 81% vs 55%; adjusted hazard ratio [HR], 0.32; P < .001), disease-specific survival (HR, 0.19; P < .001 ), and overall survival (HR, 0.24; P < .001).

However, outside of the oropharynx, patients with HPV/p16-negative disease showed no difference in locoregional control (57% for HPV-positive vs 51% for HPV-negative; HR, 0.89; P = .53), disease-specific survival (HR, 0.91), or overall survival (HR, 1.10).

"In nonoropharynx cancer, no prognostic impact of HPV/p16 was found, indicating that the prognostic impact of HPV/p16 status is restricted to tumors of orpharyngeal origin only," she concluded. "This indicates that HPV status does not help us in predicting response to treatment, and hence the outcome of these cancers," she added in a written statement.

"We know from laboratory studies that HPV-positive tumor cells are much more sensitive to radiation therapy than HPV-negative cells, so until now, we believed that they would behave similarly irrespective of site," she said. "However, these data indicate that this is not the case, and at present we do not understand why this should be, though it probably can be ascribed to other biological/genetic differences between the tumors rather than the HPV status. We would now like to try to elucidate the underlying mechanisms behind these different outcomes."

Dr. Lassen and Dr. Valentini have reported no relevant financial relationships.

European Society for Radiotherapy and Oncology (ESTRO) 33: Abstract OC-0316. Presented April 6, 2014.

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