Understanding the molecular biology of anal squamous cell carcinoma

Abstract

Anal squamous cell carcinomas (ASCC) are strongly associated with prior infection with high-risk human papilloma viruses (HPV).Although relatively sensitive to chemoradiotherapy, local recurrence requires salvage surgery with significant morbidity and is associated with poor outcomes. A better understanding of anal cancer biology is a recognised unmet research need 1 that Hamza and colleagues set out to address. 2 Surgical samples from 158 anal cancer patients with abdominoperineal resections following first line chemoradiotherapy (or radiotherapy alone) were assessed for pathogenic variants in 571 cancer-related genes, focusing on prognostic and targetable mutations. Mutations in PIK3CA and KMT2C were found to be associated with worse outcomes (overall survival) in HPV+ve patients, with 40% of all patients having targetable mutations. We congratulate the authors on a comprehensive analysis of a larger number of patients with a rare disease that supports including these patients in trials of precision medicine.As with other mucosal squamous cell carcinomas, the HPV status of SCCA is associated with improved outcomes after initial radical treatment 3 but does not yet alter treatment approaches or regimens.Given that 90%-95% of SCCA patients are HPV+ve, there is a higher absolute number of HPV+ve SCCA patients that relapse after firstline treatment. The differences in mutational profiles between these