Treatment de-intensification strategies for head and neck cancer

Abstract

Increasingly, squamous cell carcinoma of the oropharynx (OPSCC) is attributable to transformation resulting from high-risk human papillomavirus (HPV) infection. Such cancers are significantly more responsive to treatment than traditional tobacco- and alcohol-associated squamous cell cancers of the head and neck. Conventional management with definitive chemoradiation, surgery and adjuvant radiation, or radiation given with altered fractionation schemes, while effective, incurs long-term morbidity that escalates with treatment intensity and significantly impairs quality of life. Recent trials have suggested that less intensive treatment regimens may achieve similar efficacy with decreased toxicity. In this article, we review the primary strategies used for de-escalation of treatment, which include the reduction of radiation dose, substitution and/or elimination of concurrent radiosensitising chemotherapy, and the use of minimally invasive surgery. We discuss the rationale behind these approaches and the preliminary data demonstrating the success of de-escalation, as well as potential considerations raised by treatment de-intensification in HPV-associated OPSCC.

Enhancing radiosensitization in EphB4 receptor-expressing Head and Neck Squamous Cell Carcinomas

“…In CUHN022 tumor, radiosensitization due to EphB4 targeting was observed after radiation dose de-escalation. HPV-positive tumors are known to be less malignant234 and ongoing trials are focused on treatment de-intensification35363738. Our results with CUHN022 show no effect of EphB4 targeting on radiosensitization with high dose of radiation, but a difference was noticed when the radiation dose was decreased.…”

Absence of disruptive TP53 mutations in high‐risk human papillomavirus‐driven neck squamous cell carcinoma of unknown primary

“…Thus, hrHPV‐driven OPSCC are considered to contain sufficient intact p53 to preserve a radiosensitive phenotype . Several trials are ongoing to test if less intensive treatment regimens may achieve similar efficacy, while decreasing the toxicity in patients with hrHPV‐driven OPSCC …”

HPV status in unknown primary head and neck cancer: Prognosis and treatment outcomes

“…The incidence of HPV‐associated head and neck cancer has been rising, with recent studies suggesting that 60% to 70% of new oropharyngeal squamous cell carcinoma (OPSCC) cases in the United States are HPV‐related . Given the improved prognosis for HPV‐associated OPSCC, some have proposed deintensification of treatment for these cases, although some recent work suggests possible risk associated with this approach . A number of studies have also shown HPV‐associated cancers to both comprise a sizeable portion of HNCUP cases and to confer a significantly improved prognosis compared to HPV‐negative cases .…”