HPV+ HEAD-NECK CANCER

SCOTTSDALE, ARIZONA — Patients with head and neck cancers who test positive for human papillomavirus (HPV) have a different pattern of disease, as well as a better prognosis, compared with those who test negative.

These HPV-positive patients tend to be younger, in their 40s to 50s, and there is a lot of interest in dose deintensification, so it is important that we learn more about the biology of this disease, commented David Raben, MD, from the University of Colorado Cancer Center in Denver. He was moderating a press briefing here at the 2014 Multidisciplinary Head and Neck Cancer Symposium, where the new studies were presented.

HPV is now responsible for the majority of oropharyngeal squamous cell cancers diagnosed in the United States, commented Carole Fakhry, MD, MPH, assistant professor in the Department of Otolaryngology–Head and Neck Surgery at Johns Hopkins Medicine in Baltimore.

"We know that HPV-positive patients live longer after primary treatment," she said, but it has not been clear if this is also true after the disease recurred. New data show that it is, and show that survival is "strikingly longer," Dr. Fakhry said.

At the plenary session, she presented data from a retrospective analysis of patients who had progressed after primary therapy, which showed that HPV-positive patients had an overall survival rate that was nearly double that for HPV-negative patients (54.6% vs 27.6% at 2 years; P < .001).

The data for this retrospective analysis come from 2 trials — the Radiation Therapy Oncology Group (RTOG) studies 0129 and 0522 — in which patients were treated with a cisplatin-based chemoradiotherapy and/or cetuximab. Dr. Fakhry and colleagues identified 181 patients with cancer recurrence (105 who were HPV-positive and 76 who were HPV-negative).

The median time to recurrence was virtually the same for the 2 groups (8.2 months in HPV-positive patients vs 7.3 months in HPV-negative patients), but the patients with HPV-positive disease lived for a median of 2.6 years after recurrence, compared with 0.8 years for patients with HPV-negative disease.

Salvage surgery significantly reduced the risk for death, Dr. Fakhry reported, noting that recurrence is seen most commonly in the lungs. However, it appears that this effect of surgery was even more pronounced among HPV-positive patients than HPV-negative patients, she said.

Table. Oropharyngeal Squamous Cell Carcinoma: Survival at 2 Years

Treatment Group	HPV-Positive	HPV-Negative
After salvage surgery	72%	45%
Without salvage surgery	47%	20.9%

"These findings have important implications for clinical trials and for physician counseling of patients," she said

Different Pattern of Disease

Another study presented at the meeting shows that these patients with HPV-positive oropharyngeal squamous cell cancers appear to have a different pattern of disease when compared with those with HPV-negative disease.

Samuel Trosman, MD, a resident in otolaryngology at the Cleveland Clinic Foundation, presented data showing that patients with HPV-positive disease developed distant metastases much later, and in atypical sites.

This information "will help us to provide more tailored care and surveillance strategies for these patients," he suggested.

The findings come from a retrospective review of registry data on 285 patients treated with chemoradiation from 2003 to 2013. Testing showed that 245 patients were HPV-positive and 40 were HPV-negative.

Dr. Trosman and colleagues identified 35 patients who had failed after developing distant metastases, and found that 27 of these patients were HPV-positive and 8 were HPV-negative.

The rate of developing distant metastases was similar in the 2 types of disease, but the mean time to developing this complication was significantly longer for HPV-positive patients (21.6 months vs 7.0 months in HPV-negative patients; P = .03).

"The late onset of distant metastases in HPV-positive patients (almost 2 years) is unusual since the majority of aerodigestive tract malignancies tend to recur within 12 to 18 months of definitive treatment," Dr. Trosman commented.

The most common sites of metastasis for all patients was the lung (17/27 HPV-positive patients and 5/8 HPV-negative patients) and bone (12/27 HPV-positive patients and 2/8 HPV-negative patients).

However, metastases in less typical sites were more common in HPV-positive patients, and sites included the liver (in 6/27 patients), intra-abdominal lymph nodes (3), brain (2), pleura (2), and peritoneum (1).

"The multiple and varied distant metastasis sites, which can present as distal localized pain, indicates that we may need to be more aggressive in working up suspicions for metastatic disease and that imagining, such as PET/CT scans, may be warranted even after several years of treatment," he said.

The authors have disclosed no relevant financial relationships.

2014 Multidisciplinary Head and Neck Cancer Symposium (MHNCS): Abstracts 3 (Fakry et al) and 125 (Trossman). Presented February 20, 2014.