Impact of HPV on Oropharyngeal Cancer Biology and Response to Therapy: Implications for Treatment

In the past decade, otolaryngologists and related specialists have seen the emergence and characterization of a new entity, HPV–positive oropharyngeal cancer, which has changed the way we understand and manage cancer of the head and neck. HPV-positive OPSCC has a distinct pathogenesis and develops in a localized environment of genomic instability and malignant transformation driven by the expression of the E6 and E7 viral oncoproteins. In contrast to HPV-negative OPSCC, it is a disease of younger patients with a distinct subset of risk factors related to sexual practices that have evolved over the past several decades. Fortunately, these patients show better oncologic outcomes than their historical cohort, as demonstrated by their favorable response to treatment and improved PFS and OS, although the exact mechanism underlying this benefit remains unknown. There are several important treatment implications. Could we identify OPSCC patients who will show complete response to treatment a priori and decrease the morbidity of treatment safely and with the same oncologic outcomes to achieve better quality of life? Can we also predict which patients will fail treatment, allowing us to test more intensified regimens in the population at risk to increase the probability of initial cure? What should these intensified and de-intensified regimens be? Which biomarkers will allow us to make these predictions to be able to offer personalized therapy? Does organ-preservation therapy work in the absence of HPV infection? Different organ preservation regimens, surgical approaches, and novel targeted therapy strategies that address cancer-related pathways and HPV–specific targets are being studied to begin offering some insight into these challenging questions. Some changes to clinical practice have already been recommended, such as determining HPV status for all patients with oropharyngeal cancer or unknown primary. OPSCC patients should also be strongly encouraged to participate in clinical trials. The success of trials evaluating different treatment modalities as well as de-escalation of therapy will depend on adequate recruitment; thus we encourage active enrollment of patients to be able to determine new standards of care. There is great potential for the prevention of this disease through modification of risk factors and potentially with vaccination such that we may be able to stabilize or decrease the impact of this cancer epidemic.