A Safety and Tolerability of Circumferential Anal Canal Radiofrequency Ablation For Anal Intraepithelial Neoplasia

Inclusion criteria

Candidates for this study must meet all of the following criteria:

• Age 18-75 years
• HRA 2 to 8 weeks prior to the 0 month RFA visit yielding one or more flat, non-condylomatous biopsy-proven HSILs that are

• Located entirely within the eligible treatment zone AND
• Contiguous with the squamocolumnar junction
• Eligible treatment zone (ETZ) is defined as

• 3 cm above the dentate line to the anocutaneous line AND
• Full anorectal circumference
• If female of child-bearing age, negative pregnancy test within 8 weeks of the 0 month RFA visit and declared intent to remain on birth control throughout the trial, or declaration of infertility defined as subject report of status as post-menopausal or surgically sterile (status post hysterectomy or tubal ligation).
• If HIV positive

• HIV positive on antiretroviral therapy for at least 3 months with laboratory blood work within 12 weeks prior to the 0 month visit demonstrating viral load < 50
• CD4 count ≥ 250/mm3
• ANC > 750/mm3
• Platelet count ≥ 75,000/mm3
• Hemoglobin ≥ 9.0 g/dl
• INR and PTT normal

Exclusion criteria

Candidates will be ineligible for enrollment in the study if any of the following conditions apply:

• Any biopsy-proven HSIL partially outside of the ETZ (for example, an HSIL lesion with extension to the perianal skin)
• Any condylomas in the eligible treatment zone > 1/2 cm diameter

• Note: Condylomas in the eligible treatment zone < 1/2 cm in diameter must be excised or cauterized (not treated topically) before or during Visit 1 (0 month RFA visit)
• Any anal or rectal pathology requiring treatment including ulcer, fistula, fissure, or proctitis
• Any anal stricture or stenosis in patient history or upon examination.
• Symptomatic scarring in anal canal (i.e. not pliable, hyperkeratosis)
• History of or present anal or rectal cancer
• History of pelvic radiation therapy
• History of HPV vaccination or plans to initiate HPV vaccination during the trial
• History of ablation or resection therapy within the ETZ within 6 months prior to the 0 month RFA visit (other than cauterization or excision of condyloma(s))
• Prior ablation or resection therapy consisting of ≥ 75% circumference within the ETZ of anal canal.
• History of topical therapy (e.g. Imiquimod, 5-FU, Trichloroacetic acid) within the ETZ within 3 months prior to the 0 month RFA visit
• Hemorrhoids > grade III
• Fecal incontinence
• Concurrent disease requiring systemic immunosuppression therapy
• Concurrent malignancy requiring systemic therapy
• Life expectancy < 2 years
• Subject is on a platelet inhibiting agent (i.e. Aspirin, Clopidogrel, NSAIDS) and/or anti-thrombotic agent (Heparin, Warfarin) and unable to discontinue 7 days before and after treatment for 14 days total.

• Exception: Aspirin 81 mg PO daily does not need to be discontinued