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Impact of human papillomavirus on distant metastatic failure patterns in squamous cell cancer of the oropharynx in patients treated with chemoradiation


HPV initiated ( HPV+ ) squamous cell carcinoma of oropharynx ( SCCOP ) has a unique epidemiology, biology, and genetic profile compared to HPV- disease and is associated with excellent outcomes after chemoradiation Whether there are differences in the patterns and timing of distant metastatic failure in HPV+ disease is unclear.

Researchers have reviewed 285 patients with stage III-IV squamous cell carcinoma of oropharynx treated with chemoradiation between 2002-2013 from an IRB approved registry. 27/245 HPV+ and 8/40 HPV- adult patients ( pts ) who failed with distant metastases were identified.
HPV positivity was determined by in situ hybridization for HPV DNA and/or by strong and diffuse ( greater than 75% ) staining for p16 immunohistochemistry.

Radiotherapy was performed using either 3DRT ( 15/27 HPV+, 4/8 HPV- ) or intensity modulated radiation therapy ( 12/27 HPV+, 4/8 HPV- ) with doses from 66-79 Gy.
Concurrent chemotherapy was given with Cisplatin ( 9/27 HPV+, 2/8 HPV- ), Cisplatin / 5FU ( 10/27 HPV+, 3/8 HPV- ), or Cetuximab ( 8/27 HPV+, 2/8 HPV- ).
One HPV- patient received chemotherapy with Cisplatin / Paclitaxel. One patient in each group was treated with adjuvant chemoradiotherapy after initial resection.

While the distant metastasis rate for HPV+ vs HPV- squamous cell carcinoma of oropharynx was similar ( 11% vs 20% ), the mean time to develop distant metastasis was significantly longer after the completion of treatment for HPV+ patients ( 21.6 months, range 2.7-79.8 ) than for HPV- patients ( 7.0 months, range 2.1-14.4; p=0.03 ).

The most common site of metastasis in both HPV+ and HPV- patients was the lung ( 17/27 HPV+, 5/8 HPV- ) followed by bone ( 12/27 HPV+, 2/8 HPV- ).
The average number of metastatic subsites involved was significantly higher for HPV+ patients than HPV- pts ( 2.0 vs 1.1; p = 0.026 ).

Of the HPV+ patients, 21/27 ( 78% ) presented with greater than 1 metastatic deposit, and 12/27 ( 44% ) had distant metastasis involving greater than 1 organ system, compared to only 1/8 ( 12.5% ) HPV-patients.

Dissemination to less typical metastatic sites was common in HPV+ patients, including liver ( 6 ), intra-abdominal lymph nodes ( 3 ), brain ( 2 ), pleura ( 2 ), and peritoneum ( 1 ).

Only 4/27 (15%) HPV+ patients also had locoregional failure at any point during their post-treatment course vs 3/8 ( 38% ) HPV-patients.

In conclusion, while the rates of distant metastasis appear similar between pts with HPV+ and HPV- squamous cell carcinoma of oropharynx treated with chemoradiotherapy, distant metastasis occur significantly later and involves more subsites in the HPV+ group.
HPV+ distant metastasis failure appears to more frequently involve sites that are atypical for smoking related head and neck cancer.
Distant metastasis disease in HPV+ squamous cell carcinoma of oropharynx has unique characteristics and a unique natural history that may require alternative treatment strategies. ( Xagena )

Source: Multidisciplinary Head and Neck Cancer Symposium, 2014

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