Recurrence of squamous cell carcinoma of the oropharynx differs by HPV status

Patients with human papillomavirus (HPV)-positive squamous cell carcinoma of the oropharynx (SCCOP) had a longer time to development of distant metastasis after initial treatment, and had more metastatic sites in more atypical locations compared with HPV-negative patients, according to new research. This study was presented at the 2014 Multidisciplinary Head and Neck Cancer Symposium in Scottsdale, Arizona.

Culled from records of an International Review Board (IRB)-approved registry, the study reviewed 285 patients with stage III-IV SCCOP (originally thought to be a smoking-related head and neck cancer) 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.

A total of 27 HPV-positive and 8 HPV-negative patients had distant metastasis and were the subjects for more detailed evaluation. They received either 3D radiation therapy or intensity-modulated radiation therapy with doses from 66 to 79 Gy. The patients received concurrent chemotherapy of cisplatin, cisplatin/5 fluorouracil, or cetuximab. One HPV-negative patient received cisplatin/paclitaxel chemotherapy. One patient in each group was treated with adjuvant chemoradiotherapy after initial resection.

Both HPV-positive and HPV-negative patients were found to have similar rates of distant metastases. However, the mean time to develop distant metastases was significantly longer for HPV-positive patients (HPV-positive = 21.6 months vs HPV-negative = 7.0 months).

The most common sites of metastasis for all patients were the lung and bone. The average number of metastatic subsites was significantly higher for HPV-positive patients (HPV-positive = 2.0 vs HPV-negative = 1.1). Although 21 of the 27 HPV-positive patients had more than one distant metastasis, and 12 of the 27 had distant metastases involving more than one organ system, only 1 of the 8 HPV-negative patients had more than one distant metastasis.

Metastases in less typical sites were more common in HPV-positive patients; sites included the liver (6), intra-abdominal lymph nodes (3), brain (2), pleura (2), and peritoneum (1). Locoregional failure (metastases in the original tumor region) was only seen in 4 of the 27 HPV-positive patients, compared with 3 of the 8 HPV-negative patients.

"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. 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 in Ohio. "We were able to learn significant characteristics of HPV-positive SCCOP that will help us provide more tailored care and surveillance strategies for these patients."

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