The impact of HPV testing for oropharyngeal cancers: Why the addendum matters

Abstract

There has been a revolution in the population of waiting rooms of head and neck cancer specialists within the last 2 decades. Historically, the majority of our patients waiting for evaluation and treatment were elderly men, with significant comorbidities related to excessive alcohol and tobacco use (which also contributed to the development of their cancers). Now, our patients are younger (“middle-aged”) professionals, still mostly men, with excellent health, taking few if any medications, and with no history of significant alcohol or tobacco use.1 This is the era of human papillomavirus (HPV). The standard-of-care treatment for the majority of patients who are newly diagnosed with oropharyngeal squamous cell cancer is a combination of radiotherapy and concurrent chemotherapy. The radiotherapy consists of a planning session to create an immobilizing mask, the development of a treatment plan to allocate doses to different targets and simultaneously protect normal tissues as much as possible, and treatment delivery (Fig. 1). Radiotherapy is delivered through daily treatments (Monday-Friday) for approximately 6 to 7 weeks. Patients typically receive chemotherapy weekly or every 3 weeks during treatment. During concurrent chemoradiation, patients may develop mucositis, dysphagia, skin desquamation, and pain, which improve after the completion of therapy. However, patients may have long-term side effects from this treatment, including xerostomia, dysphagia, and skin changes. New techniques, including the use of intensity-modulated radiotherapy, are designed to minimize these short-term and long-term side effects. However, the emergence of HPV has completely transformed not only the patient population, but the prognosis and appropriate treatment of patients, with newly diagnosed oropharyngeal cancers. Patients diagnosed with HPV-positive squamous cell cancers of the oropharynx have improved locoregional control, progression-free survival, and overall survival compared to individuals with HPV-negative cancers.2 Hence, not only are these patients younger and healthier, but they have much higher cure rates and longer life expectancies. The HPV status of a patient newly diagnosed with oropharyngeal cancer is crucial to our counselling of patients at the time of diagnosis. Because multiple trials have demonstrated improved prognosis with standard treatment, identifying patients with HPV-positive disease and informing them of this status is especially important in this cohort of well-educated and well-researched patients. The clinical behavior of HPV-associated oropharyngeal cancers is so dramatically different from historic (largely HPV-negative) oropharyngeal cancers that there is a pending change in the staging system for these cancers. All previous staging systems, up to the seventh edition of the American Joint Committee on Cancer staging system, do not take into account HPV status for patients with oropharyngeal cancer. As a result, the majority of patients with HPV-associated cancers, who typically have multiple ipsilateral lymph nodes, are deemed to have at least stage IVA disease. Despite this designation, they have excellent prognoses (as mentioned above). In an attempt to modify the staging system so that the group stages are meaningful and correlated with prognosis, multiple groups have proposed revised staging algorithms for patients with HPV-associated cancers only. The eighth edition of the American Joint Committee on Cancer staging system, which is scheduled for full implementation on January 1, 2018, will use separate staging systems for patients with HPV-positive and HPV-negative oropharyngeal cancers.3 Fundamentally, the excellent prognosis of patients with HPV-positive tumors has begged the question of whether we can de-escalate the standard-of-care treatment, and hopefully reduce its associated toxicity. There are an enormous number of clinical trials available for patients with HPV-positive oropharyngeal cancers in w