Radiotherapy Use and Effectiveness in Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma

A study of adjuvant chemoradiotherapy (CRT) and boost doses of postoperative radiotherapy (B-PORT) in oropharyngeal squamous cell carcinoma (OSCC) has found that outcomes depend on a number of pathologic and environmental factors.

Optimal use and intensity of PORT and CRT for OPSCC have been controversial topics among health care professionals. PORT has been established as an important component of the treatment paradigm following surgical resections but has also been associated with locoregional failure risk in the context of high-risk pathologic features such as positive surgical margins and extracapsular extension. For that reason, National Comprehensive Cancer Network guidelines recommend adjuvant CRT for patients with certain pathologic features, with consideration for patients with adverse characteristics such as multiple nodes or low-neck disease. However, this type of treatment has also been found to have considerable toxic effects and may be considerably less effective in patients with Human Papillomavirus (HPV)-positive disease. 

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In a study published in JAMA Otolaryngology–Head & Neck Surgery, researchers led by David J Sher, MD, MPH, University of Texas Southwest Medical Center (Dallas, TX), reviewed recent patterns of care and survival outcomes with CRT and dose escalation for patients with OPSCC. 

A retrospective analysis of patients in the National Cancer Database with stage III to IVA-B OPSCC treated with surgery and adjuvant radiotherapy was conducted. All patients included in the study were males with a median age of 57 years. The primary outcomes were prevalence of CRT and B-PORT, and overall survival.

A total of 1409 patients were identified as eligible for study inclusion, with 873 patients (62%) and 789 patients (56%) receiving CRT and B-PORT, respectively. Results revealed that patients with HPV-positive OPSCC were significantly less likely to receive CRT than those not HPV-positive. Additionally, patients were less likely to receive CRT at academic institutions than those that were non-academic (59% and 67% of patients at each respective institution). In contrast, HPV statues did not influence the likelihood of B-PORT use. However, certain pathologic features did have a strong correlation with whether B-PORT was used or not, with the most influential variables being those indicating more advanced disease. 

Further analysis showed that, after a median follow-up of 27 months for surviving patients, the 2-year rate of overall survival for the entire cohort was 92%. The rate for patients with HPV-positive disease was even higher (95%). Neither CRT nor B-PORT was associated with improved overall survival, even in the subset of patients with high-risk features. These findings were confirmed after statistical analyses. 

Researchers concluded that the intensity of therapy for the treatment of OPSCC was often dependent on HPV statues, where patients received treatment (academic vs nonacademic) and certain pathologic features.

Researchers noted that their study was limited by an inability to account for several important confounding variables, including pretreatment imaging, smoking status, and patients’ pre- and post-surgery performance status. Additionally, HPV status was not standardized and often did not incorporate p16 status, though they did not believe this would have meaningfully affected treatment decision-making.—Sean McGuire

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Sher DJ, Nedzi L, Khan S. Patterns of Care and Comparative Effectiveness of Intensified Adjuvant Therapy for Resected Oropharyngeal Squamous Cell Carcinoma in the Human Papillomavirus Era [published online ahead of print June 30, 2016]. JAMA Otolaryngol Head Neck Surg. doi: 10.1001/jamaoto.2016.1162.