How do you manage patients with history of multiple perianal condylomas who develop focal high grade squamous intraepithelial lesions in the anal margin?

In the absence of invasive disease, surgical resection is always the treatment of choice for in-situ disease.  If the recommendation is APR, it should be well documented. If the patient refuses the surgical option, then radiation can be offered with very careful documentation. The reason for that is that these cases are a setup for medicolegal action. The cancer related morality is extremely low. Patients live a very long time with the consequences of  any late effects of radiation that might happen. For instance, sexual function could be affected, especially in females.  There could be fecal incontinence that may or may not be related to radiation. There could be chronic discomfort or pain.  All of these consequences are more defensible in the setting of invasive cancer. 

If a decision is made to treat, 50-60Gy in 25-30 fx to the anal margin area alone have been shown to be  very effective for SCCa in situ (Bowen's disease). Condyloma responds but commonly recurs. There are no data about HPV in this setting, so no it would not infrom clinical decisions based on any evidence.

In the era of AIDS related malignancies, this was not an uncommon problem.  We would get a PET/CT and would be surprised by those results.  For instance, we had a patient with no evidence of invasion on any biopsies in the anus, and a node in the inguinal area was PET hot, resulting in a diagnosis of invasive cancer.  What do you biopsy? 

We treated a few patients like this.  Expect severe reactions.  They generally did well.  We also followed some patients closely, which is what most of the institutions that treated many AIDS patients did.

I agree with the above.  If the choice is an APR, then treat.  But do consider a PET/CT, if covered by insurance.