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Screening for human papillomavirus‐driven oropharyngeal cancer: Considerations for feasibility and strategies for research

INTRODUCTION Over the past 25 years, human papillomavirus (HPV) has been shown to be an important cause of oropharyngeal cancers (OPCs) in many world regions, with the great majority of HPV-driven OPC being caused by HPV type 16 (HPV-16). HPV currently is overtaking tobacco exposure as the leading cause of OPC in some countries with a high human development index, including the United States and some European and Latin American countries, in which both the incidence rate of OPC and the attributable fraction (AF) of HPV are rising. In the United States, the incidence of OPC currently is greater than that of cervical cancer, a consequence of the increasing incidence of OPC as well as reductions in the incidence of cervical cancer due to the success achieved by screening. This shift highlights the need for parallel preventive measures. Nevertheless, arguments against additional research regarding HPV-driven OPC screening have been made and include the promise of primary prevention through HPV vaccination, the currently low incidence rates, and favorable outcomes with current therapy compared with non-HPV-driven head and neck cancers. The lack of an identifiable clinical precursor lesion, insufficient diagnostic technology with which to detect small lesions, and the absence of de-escalated clinical management for patients with early-stage cancer or precancer are current barriers to screening for OPC. This article is not intended to address all the questions related to the validity and timeliness of screening for HPV-driven OPC but instead to raise important questions, guide discussions, highlight deficits and/or confusion in the existing literature, and propose needed steps in the research agenda. The following general aspects of a screening program are considered and applied to HPV-driven OPC: 1) a sufficiently high incidence, either in the general population or an enriched high-risk population; 2) a sensitive and specific screening tool or biomarker; 3) appropriate methods for accurately diagnosing the cancer (or precancer) among individuals who screen positive; 4) effective treatment for patients with early-stage lesions; and 5) evidence of mortality and/or morbidity reductions.