Treatment de‐escalation in HPV‐positive oropharyngeal carcinoma: Ongoing trials, critical issues and perspectives

Abstract

Due to the generally poor prognosis of head and neck squamous cell carcinoma (HNSCC), treatment has been intensified, these last decades, leading to an increase of serious side effects. High‐risk human papillomavirus (HR‐HPV) infection has been recently etiologically linked to a subset of oropharyngeal squamous cell carcinoma (OPSCC), which is on the increase. These tumors are different, at the clinical and molecular level, when compared to tumors caused by traditional risk factors. Additionally, their prognosis is much more favorable which has led the medical community to consider new treatment strategies. Indeed, it is possible that less intensive treatment regimens could achieve similar efficacy with less toxicity and improved quality of life. Several clinical trials, investigating different ways to de‐escalate treatment, are currently ongoing. In this article, we review these main approaches, discuss the rationale behind them and the issues raised by treatment de‐escalation in HPV‐positive OPSCC.

Ectopic Myoglobin Expression Is Associated with a Favourable Outcome in Head and Neck Squamous Cell Carcinoma Patients

“…Furthermore, recent research has shown that patients with HPV-positive oropharyngeal tumours have a better prognosis (24)(25)(26). A favourable outcome for HPV-positive HNSCC patients could also be confirmed in this study.…”

A Multi-institution Pooled Analysis of G-Tube Dependence in Patients With Oropharyngeal Cancer Treated With Definitive IMRT

“…24 Despite no significant difference in the receipt of concurrent chemotherapy (57.4% vs 58.9%), patients in the third group (T3-4 or N3) were significantly more likely to be g-tube dependent at 1 year than those in the second, 10.1% (95%CI: 7.9-12.3%) vs 5.2% (95%CI: 3.8-6.6%), reflecting an underlying difference in these two patient cohorts (Figure 3). …”

Validation of Human Papillomavirus as a Favourable Prognostic Marker and Analysis of CD8+ Tumour-infiltrating Lymphocytes and Other Biomarkers in Cancer of Unknown Primary in the Head and Neck Region

“…Treatment de-escalation may be attainable in patients with HPV-positive HNCUP, similar to that discussed for patients with HPV-positive oropharyngeal SCC (12). Still, before HPV status of HNCUP can be used to guide treatment, more knowledge on the biology and clinical behaviour of the disease is needed, especially due to the debate on whether CUP in different parts of the body share common traits or whether they behave more like normal metastases (13).…”