Abstracts

HspE7 Treatment of High Grade Anal Dysplasia: Updated Results of an Ongoing Open Label Trial

19th International Papillomavirus Conference - Florianopolis, Brazil - September 3, 2001

Stephen E. Goldstone (1), John R. Neefe (2), Mark T. Winnett (2), Joel M. Palefsky (3)

1) Mt. Sinai School of Medicine, New York City, NY, USA
2) Stressgen Biotechnologies, Inc., Collegeville, PA, USA
3) University of California at San Francisco, San Francisco, CA, USA

Background:
Human papillomavirus (HPV) causes anogenital squamous intraepithelial lesions (SIL) and anogenital cancer. Since treatment of SIL often requires surgery, we tested a novel HPV-specific immunotherapy.

Methods:
We made HspE7, fusing heat shock protein Hsp65 from BCG to E7 protein from HPV16. Patients (pts) with high grade SIL (HSIL) entered a randomized, placebo controlled trial of HspE7, 100mcg monthly x3 (9901). One month (m) after the completion of treatment, pts with persistent SIL were eligible to cross to an open label trial of HspE7, 500 mcg monthly x3 (9902). Pts usually crossed at this time or at the six month evaluation point. Response was taken as the highest grade dysplasia after cytology and high resolution anoscopy with biopsy. A Global Physicianês Assessment (GPA) scored each pt on an analog scale in reference to baseline. Physicians quantified over all clinical improvement given all information available. A score of 50 represented no change and a score of 100 represented complete resolution. HPV was typed by PCR analysis of anal swab.

Results:
We report 6 m results from the first 56 consecutive pts and safety from all 82 pts in 9902. By histopathology and cytology at 6 m in 9902, 40/56 (71%) pts responded with improvement to low grade SIL (LSIL). The median GPA was 81 (range, 50-99). Clinical improvement was defined as a minimum score of 65, and 83% of pts achieved this score. 76/82 subjects in 9902 reported adverse experiences (AE) related to HspE7: most commonly, injection site reactions and asthenia, but no severe or serious AE. 12/48 pts and 8/35 responders were HPV16+ (HPV typing data were missing for 8/56 pts and 5/40 responders). Most pts typed for one or more high or low risk HPV types other than type 16. HPV DNA was not detected in 8/48 pts. Some pts had concomitant genital warts, but warts were not a study parameter. As reported elsewhere, a retrospective review of records of the first 14 pts with warts indicated disappearance of warts in 3/14 patients and major improvement in 10 of the remaining 11 pts.

Conclusions:
Pathological data suggest that HspE7 (500 mcg x3) is active in treatment of anal HSIL, converting most pts from HSIL to LSIL. This observation is being tested in a new double blind, placebo-controlled trial. Response appears not to be HPV16-specific. HspE7 500 mcg monthly x 3 is well tolerated in this population.