OC-011 New insights from the De-ESCALate HPV trial

EGFR overexpression increases radiotherapy response in HPV-positive head and neck cancer through inhibition of DNA damage repair and HPV E6 downregulation

“…Collectively, the analysis of DDR pathway in HNSCC cell lines identified distinct roles for EGFR in regulating DNA repair and RT response. To our knowledge this is the first report of EGFR playing a potential role in increasing radiosensitivity specifically in virally induced HNSCC, and could provide a possible answers to the surprising outcome of several recent clinical trials concluding giving EGFR inhibitor Cetuximab to HPV-positive HNSCC patients is significantly inferior [23,24]. Therefore, this data highlights the need for better understanding of this major signalling pathway in HPV-positive HNSCC and questions its therapeutic benefit in certain types of cancers [18,49].…”

“…This is particularly critical for the HPV-positive patients who are generally younger and likely to suffer longterm morbidities and experience reduced quality of life [21,22]. In the absence of HPV specific treatment modalities, the major emphasis in recent years has been to de-intensify therapy protocols to reduce the toxic side effects, while maintaining the effective treatment [23]. To this end, several clinical trials have been conducted to replace chemotherapy with other forms of more specific treatments such as EGFR inhibitors (Table 1).…”

“…Similarly, the De-ESCALaTE clinical trial concluded that the substitution of Cisplatin with Cetuximab in HPV-positive HNSCC to be detrimental to disease control [23].…”

Comparison of 3-weekly cisplatin versus 3-weekly carboplatin in patients with locally advanced nasopharyngeal carcinoma receiving concurrent chemoradiotherapy: A multicentre analysis

“…As expected, more patients in carboplatin group had comorbidity of vascular risk factors and lower baseline CCr; both factors are considered high risk for cisplatin ineligibility (15). In cisplatin-ineligible patients with locally advanced non-NPC head and neck squamous cell carcinoma, cetuximab is recommended for concurrent use with RT (16,17). However, recommendation for the agent being used in cisplatinineligible patients with LA-NPC is limited.…”

Exposure to Microbial Metabolite Butyrate Prolongs the Survival Time and Changes the Growth Pattern of Human Papillomavirus 16 E6/E7-Immortalized Keratinocytes in Vivo

“…A new cancer J o u r n a l P r e -p r o o f staging system for HPV-positive OPSCC was established to guide treatment 14 , partly due to the concept that de-escalation of treatment does not compromise the cure rate but decreases morbidity caused by adverse effects of the therapy. However, treatment de-escalation for HPV-positive OPSCC is recently discouraged after the publication of RTOG 1016 and De-ESCALaTE studies, both showing that outcomes of HPV-positive OPSCC patients strongly depend on the type of treatment received 15,16 .…”