Abstract
Purpose/objective
To assess the interaction of HPV/p16 status and therapy rendered in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx.
Materials and methods
Forty-seven consecutive patients receiving definitive treatment between 2009 and 2011 for locally advanced larynx or hypopharynx cancer with high-risk HPV and/or p16 testing performed were identified and retrospectively investigated. Overall survival (OS), disease-free survival (DFS), and local recurrence-free survival (LRFS) were assessed.
Results
Of 47 evaluable patients, there were 38 (81%) with laryngeal and 9 (19%) with hypopharyngeal tumors, 13 (28%) of which were found to be either HPV or p16 positive. At a median follow-up of 24 months, comparing HPV/p16 + versus HPV/p16 − patients, there was no difference in OS, DFS, or LRFS. There was an improvement in 2-year DFS (60% vs 100%, P = .03) and LRFS (80% vs 100%, P = .08), in HPV/p16 + patients treated with chemo/RT versus surgery. There was an improvement in 2-year DFS (100% vs 68%, P = .04) and LRFS (100% vs 72%, P = .05) in HPV/p16 + versus HPV/p16 − patients who received chemo/RT.
Conclusions
Patients with HPV/p16 + tumors fared more favorably with chemo/RT than up-front surgery, with improvements in DFS and LRFS. In patients treated with the intent of organ preservation therapy, HPV/p16 + patients had no observed treatment failures. HPV/p16 status should be taken into account when considering organ preservation for locally advanced larynx and hypopharynx cancers.
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Introduction
Historically, locally advanced laryngeal and hypopharyngeal cancers have been treated with up-front laryngectomy with consideration for adjuvant radiotherapy. With the advent of several large randomized clinical trials , laryngeal preservation, through a combination of chemotherapy and radiotherapy for properly selected patients, has emerged as a viable alternative. While this has not been shown to alter overall survival positively or negatively, it does allow a subset of patients to maintain a functional larynx, thus improving quality of life.
Eligibility for treatment is contingent upon several factors, including expected maintenance of a functional larynx and ability to tolerate the toxic effects of treatment, which are largely dependent on pretreatment laryngeal function, disease stage and performance status . Some of these patients inevitably experience local disease failure, after which they may be considered for salvage laryngectomy. Although concurrent chemoradiotherapy appears to confer the best chance at larynx preservation , predicting that treatment response is difficult. Creating a more robust methodology for selecting appropriate patients for organ preservation is important. As shown in prior randomized studies, induction chemotherapy may allow for the determination of responders versus non-responders in the setting of organ preservation.
The role of molecular markers has become exceedingly important in the management of locally advanced head and neck cancer. A more recent advance in the field of head and neck cancer has been the recognition of HPV as not only a positive prognostic factor , but also a potential predictor of treatment response , particularly in oropharyngeal carcinoma. As HPV positivity has been shown to predict response to treatment in oropharyngeal tumors, it may be one more factor to consider when determining a patient’s candidacy for larynx preservation.
In this study, we examined our cohort of laryngeal and hypopharyngeal cancer patients who have had HPV or p16 testing performed. Our intent was to examine the prognostic effect of HPV/p16 as well as HPV/p16 status’s interaction with treatment rendered and the resultant trends in recurrence and survival. If HPV status can truly predict response, it may become a more critical piece of information in guiding management decisions in patients with cancer of the larynx and hypopharynx.
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