How would you approach an MSI-H HPV+ T2 N1 squamous cell carcinoma of the anus?

I would agree with Dr. @Dr. First Last's comments but want to add one point. Some patients with Lynch Syndrome may develop HPV+ Anal SCC and in this situation, the tumor could be dMMR (most likely) but also could be pMMR (uncommon but can happen). I am not sure if dMMR is the driver for the Anal SCC...

For non-metastatic, potentially curable anal cancer, I would use radiation/5FU/mitomycin, and strongly consider participation in the DECREASE phase II clinical trial (NCT04166318). For metastatic disease, I would consider EA2176 (NCT04444921), a phase III trial of carboplatin/Taxol +/- nivolumab.