Distant Metastases Occur Later and in More Subsites in Patients With HPV-Positive Squamous Cell Carcinoma of the Oropharynx
Patients with human papillomavirus (HPV)-positive squamous cell carcinoma of the oropharynx had a longer time to development of distant metastasis after initial treatment, and had more metastatic sites in more atypical locations compared to HPV-negative patients, according to research presented today at the 2014 Multidisciplinary Head and Neck Cancer Symposium.
Study Details
Culled from records of an IRB-approved registry, the study reviewed 285 patients with stage III/IV squamous cell carcinoma of the oropharynx treated with chemotherapy and radiation from 2002 to 2013. HPV status was determined by in situ hybridization for HPV DNA and/or by strong and diffuse (> 75%) staining for p16 immunohistochemistry. There were 245 HPV-positive and 40 HPV-negative patients.
Twenty-seven HPV-positive and eight HPV-negative patients experienced distant metastases and were the subjects for more detailed evaluation. Radiotherapy was administered as either three-dimensional radiation therapy (HPV-positive = 15/27; HPV-negative = 4/8) or intensity-modulated radiation therapy (HPV-positive = 12/27; HPV-negative = 4/8) with doses from 66 to 79 Gy. Patients received concurrent chemotherapy of cisplatin (HPV-positive = 9/27; HPV-negative = 2/8), cisplatin/fluorouracil (HPV-positive = 10/27; HPV-negative = 3/8) or cetuximab (Erbitux) (HPV-positive = 8/27; HPV-negative = 2/8). One HPV-negative patient received cisplatin/paclitaxel chemotherapy. One patient in each group was treated with adjuvant chemoradiotherapy after initial resection. Student t-tests were used to compare the difference between the means of the samples.
Both HPV-positive and HPV-negative patients were found to have similar rates of distant metastasis; however, the mean time to development of distant metastases was significantly longer for HPV-positive patients (21.6 months vs 7.0 months for HPV-negative patients). The most common sites of metastasis for all patients were the lung (HPV-positive = 17/27 vs HPV-negative = 5/8) and bone (HPV-positive = 12/27 vs HPV-negative = 2/8).
More Metastatic Subsites in More Atypical Locations
The average number of metastatic subsites was significantly higher for HPV-positive patients (HPV-positive = 2.0 vs HPV-negative = 1.1, P = .026). Twenty-one HPV-positive patients had more than one metastatic deposit, and 12 had distant metastasis involving more than one organ system, compared to only one of eight HPV-negative patients.
Metastases in less typical sites were more common in HPV-positive patients; sites included the liver, intra-abdominal lymph nodes, brain, pleura, and peritoneum. Locoregional failure was only seen in 4 of the 27 HPV-positive patients, compared to 3 of the 8 HPV-negative patients.
“The late onset of distant metastasis 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. 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 imaging such as PET/CT scans may be warranted even several years after treatment,” said Samuel Trosman, MD, a resident in otolaryngology at the Cleveland Clinic. “We were able to learn significant characteristics of HPV-positive squamous cell carcinoma of the oropharynx that will help us provide more tailored care and surveillance strategies for these patients.”
The study authors reported no potential conflicts of interest.
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