Are we ready for deintensification in human papillomavirus-positive oropharyngeal carcinomas?

Abstract

Purpose of review Excellent outcomes following contemporary treatment of human papillomavirus (HPV)-positive oropharyngeal carcinoma (HPV+ OPC) have prompted the exploration of deintensification approaches to minimize treatment-related toxicities. This review describes the landscape of deintensification to date (up to November 2022). Recent findings Although several deintensification trials have been published, none are practice changing. Three phase III randomized-controlled trials studying cetuximab and radiation therapy vs. standard chemoradiotherapy all showed inferior outcomes. Although some phase II trials reported favourable outcomes, they are often single-arm trials without an adequate control arm, thereby limiting the ability to modify practice. Summary Substantial effort has been expended to explore deintensification options for selected HPV+ OPC patients aiming to avoid unnecessary toxicity. Strategies have included replacing cisplatin with cetuximab, reduced chemotherapy or radiotherapy intensity, reduction of radiotherapy volumes and risk stratification after trans-oral surgery or following induction chemotherapy. Challenges remain in the current deintensification landscape, including identifying the most suitable candidates along with a choice of most appropriate deintensification strategies. Promising selection criteria included either static baseline features or kinetic characteristics of clinical-biological parameters. Practice-changing trials remain elusive, and the search continues to attempt optimization of the therapeutic ratio for these patients.