What is your recommended way of managing a locally advanced bulky base of tongue (BOT) p16 negative squamous cell carcinoma extending into multiple structures of the supraglottic larynx?

ChemoRT. We did pretty well with RT prior to HPV. Surgery is likely no better and more morbid.

The only randomized study that I am aware of that compares upfront surgery followed by adjuvant RT with chemoRT for locally advanced squamous cell of the head and neck is the study by Iyer et al., PMID 25639864, and it showed comparable results in non-oral cavity or maxillary sinus sites, regardless of HPV status (very few had HPV associated disease).

This study was conducted before the evidence for a trimodality approach in those with high risk features such as positive margins or ECE. Therefore, it is unknown if surgery followed by concurrent chemoradiation (when indicated) would perform better than chemoRT.

Nevertheless, given the lack of solid evidence that upfront surgical treatment is superior to chemoRT for p16 negative oropharyngeal...

Resection with free flap reconstruction performed by a surgeon experienced in microvascular surgery, preferably at a tertiary hospital, followed with RT or chemo-RT based on pathology.