De-Escalating Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma.

Panagiota Economopoulou,Amanda Psyrri,Ioannis Kotsantis

doi:10.3390/v13091787

Abstract

HPV-related head and neck squamous cell carcinoma (HNSCC) has emerged as a diverse clinical and biological disease entity, mainly in young patients with oropharyngeal tumors who are nonsmokers and nondrinkers. Indeed, during the past few years, the pendulum has shifted towards a new epidemiological reality, the “HPV pandemic”, where the majority of oropharyngeal squamous cell carcinomas (OPSCCs) are attributed to HPV. The oncogenic potential of the virus is associated to its capacity of integrating oncogenes E6 and E7 into the host cell, leading to the inactivation of several tumor suppressor genes, such as Rb. HPV status can affect prognosis in OPSCC, but its role as a predictive biomarker remains to be elucidated. Given the favorable prognosis associated with HPV-positive disease, the concept of de-escalation treatment strategies has been developed with the primary intent being the reduction of treatment-related long-term toxicities. In this review, we aim to depict current data regarding treatment de-escalation in HPV-associated OPSCC and discuss ongoing clinical trials.

Highlights

Viruses 2021, 13, 1787. https://Recent epidemiological evidence suggests a substantial rise of Human Papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC), which accounts for more than 60% of oropharyngeal squamous cell carcinomas (OPSCCs) cases in the contemporary area [1,2,3]
Given the remarkably better survival rates observed in HPV+ OPSCC, juxtaposed with the substantial morbidity caused by the standard of care treatment of cisplatin and RT combination in locally advanced disease, the concept of treatment de-escalation has been proposed as a new treatment paradigm
Given the significant toxicity correlated with cisplatin-based CRT and the promising efficacy of cetuximab-based bioradiotherapy in patients with OPSCC demonstrated in the IMCL 9815 trial [43], the idea of substituting cisplatin with cetuximab in patients with

Summary

Introduction

Recent epidemiological evidence suggests a substantial rise of Human Papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC), which accounts for more than 60% of OPSCC cases in the contemporary area [1,2,3]. Oncology Group (RTOG) 0129 trial in which patients with locally advanced head and neck squamous cell carcinoma (HNSCC) were randomized to radiotherapy (RT) with either accelerated fractionation with concomitant boost or standard fractionation with concurrent cisplatin, Ang et al correlated HPV status with clinical outcome based on assessment of HPV DNA using in situ hybridization (ISH) [12]. Ang et al suggested a patient risk stratification based on smoking status and TNM stage that defined patients with low- and intermediate-risk HPV+ OPSCC. Given the remarkably better survival rates observed in HPV+ OPSCC, juxtaposed with the substantial morbidity caused by the standard of care treatment of cisplatin and RT combination in locally advanced disease, the concept of treatment de-escalation has been proposed as a new treatment paradigm. We seek to summarize current data on deintensification approaches in HPV+ OPSCC and discuss the goals of future de-escalation studies in this regard

History and Rationale for Treatment De-Escalation-Selection of Patients

De-Escalation Strategies

Chemotherapy Replacing

Findings

Conclusions and Future Directions