Induction Chemotherapy in Low-Risk HPV+ Oropharyngeal Cancer

Human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in incidence, and has now become the most common head and neck cancer (HNC). Studies have demonstrated that HPV associated OPSCC is associated with a favorable prognosis compared with its HPV-negative counterparts, yet standard multimodality therapy is often associated with substantial acute and late treatment-related toxicity. While locoregional control is improved in HPV+ OPSCC, distant metastasis rate has gained recognition as a major cause of death in this population, with some studies suggesting similar rates as non-HPV-related cancers. Induction chemotherapy has been of long-standing interest in locoregionally advanced HNC, yet its use in combination with concomitant chemoradiation remains an area of controversy as a survival benefit remains unproven following randomized trials. Nevertheless, response to induction chemotherapy remains an important dynamic and prognostic biomarker, with response-adaptive de-intensified therapy in HPV+ OPSCC gaining traction in single-arm phase II studies demonstrating promising results. The emergence of immunotherapy in the recurrent/metastatic setting for HNC has led to enthusiasm to incorporate in the curative setting, yet its role remains undefined. Our institutional paradigm for HPV+ OPSCC incorporates induction therapy followed by risk and response adaptive locoregional treatment. Ultimately, the role of induction therapy in HPV+ OPSCC will need to be investigated in a randomized setting to be incorporated routinely into clinical practice.