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HPV-initiated OPSCC associated with longer time to metastasis development
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Patients with HPV-initiated oropharyngeal squamous cell carcinoma remained free of distant metastases following completion of chemoradiotherapy longer than patients with HPV-negative disease, according to study results.
HPV-initiated disease also tended to present with a greater number of metastatic sites uncommon to oropharyngeal squamous cell carcinoma (OPSCC), results showed.
“HPV-initiated OPSCC has a unique etiology, histopathology and clinical behavior compared with tobacco-related head and neck squamous cell carcinoma,” Samuel J. Trosman, MD, of the department of otolaryngology at Cleveland Clinic, and colleagues wrote. “Despite a high prevalence of advanced nodal disease at presentation, large randomized clinical trials have shown 3-year locoregional control rates of greater than 85% with multimodality treatment compared with 65% of OPSCC that is negative for HPV, with an estimated 60% reduction in the risk for death from cancer.”
Trosman and colleagues retrospectively evaluated data from 291 patients with OPSCC treated between 1996 and 2013. The majority (86.6%; n = 252) of patients had the HPV-initiated form of the disease. The median age was similar among HPV-initiated patients (56 years; range, 36-81) and HPV-negative patients (59 years; range, 37-73).
Median follow-up was 3.1 years.
Following chemoradiotherapy, 11.1% (n = 28) of the HPV-initiated group developed distant metastatic disease, compared with 23.1% (n = 9) of the HPV-negative group. The 3-year projected distant control rate was significantly greater among HPV-initiated patients (88% vs. 74%; P = .01).
The median time to development of distant metastases was significantly longer among the HPV-initiated cohort (16.4 months vs. 7.2 months; P = .008). However, patients with HPV-initiated disease tended to have more sites of distant metastases (2.04 vs. 1.33).
The most common sites of distant metastases among both HPV-initiated and HPV-negative patients were the lungs (82% vs. 78%) and bones (43% vs. 22%).
Metastatic subsites atypical to head and neck squamous cell carcinoma occurred in more patients with HPV-initiated disease. These sites included the brain (n = 2), kidney (n =2), skin (n = 2), skeletal muscle (n = 2), axillary lymph nodes (n = 2) and intra-abdominal lymph nodes (n = 3).
Patients with HPV-initiated disease achieved significantly longer median OS (25.6 months vs. 11.1 months), as well as a significantly greater rate of 3-year OS (89.9% vs. 62%; P ˂ .001 for both).
“Patients with [HPV-initiated] disease have a longer interval to distant metastases than those with [HPV-negative] disease, with a significant number of patients experiencing distant failure more than 2 years after completion of treatment,” Trosman and colleagues wrote. “Distant metastases in [HPV-initiated] disease also appear to involve a greater number of subsites as well as metastatic sites infrequently seen in malignant neoplasms of the aerodigestive tract. These findings emphasize the importance of more extended multidisciplinary surveillance after completion of chemoradiotherapy in patients with [HPV-initiated] disease.” – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures.
Perspective
Back to TopBarbara A. Burtness, MD
The increasing incidence of HPV-associated cancers of the oropharynx cancer has been documented by many groups. Trosman and colleagues from Cleveland Clinic add to this literature with a detailed study of 291 patients with oropharynx cancer treated at their institution from 1996 through 2013.
The predominance of HPV-associated cancers was striking at 86.6%. Among the HPV-associated cancers, this was a very favorable risk cohort, with 50% of patients having smoked no more than 10 pack-years.
Consistent with other series, the authors found that HPV-associated cancers have a somewhat longer natural history than HPV-negative cancers, with the median time to failure 16.4 months for HPV-associated cancers compared with 7.2 months for HPV-negative cancers. They also determined patients with HPV-associated cancers experienced longer survival after failure, consistent with the reports from ECOG and RTOG.
The study had a median follow up of 3.1 years, which may not be long enough for a full picture of the events among the HPV-associated cancers, given that they observed distant recurrences as long as 6 years from diagnosis. Again consistent with other reports, the authors describe unusual patterns of metastasis.
Recent data from Huang and colleagues describe patients with metachronous metastases and oligometastatic disease who achieve long-term survival, consistent with anecdotal observations at a number of centers (Huang S. Abstract OC-044. Presented at: International Conference on Innovative Approaches in Head & Neck Oncology; Feb. 12-14, 2015; Nice, France).
This publication adds to the evidence that relapsed HPV-associated cancer can have a longer course than historically observed in head and neck cancers, and that aggressive strategies with resection or radiation may sometimes be of value.
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