Initial Experience Treating HPV-Related Laryngeal Diseases with Oral Brincidofovir: A Pilot Study

Abstract

Objective: To determine if brincidofovir, an oral analog of cidofovir that achieves high tissue levels of the active metabolite with low systemic toxicity, has an observable effect on HPV-related disease of the larynx. Methods: Two patients with laryngeal recurrent respiratory papillomatosis (one each of genotypes 6 and 11) and 1 with recurring aryepiglottic fold carcinoma in situ (genotype 16) received oral brincidofovir according to protocol. Close-range videoendoscopic examinations were done during and after the study period to observe disease behavior in the absence of other interventions, and after subsequent surgical intervention. Disease character and magnitude of recurrence for each patient were compared to their patterns prior to brincidofovir. Results: Brincidofovir reduced papilloma burden in 1 patient and markedly attenuated the rate and magnitude of recurrence in both. After surgical intervention, Patient 1 remains disease-free at 10 years (7 years from last intervention) and Patient 2 has no symptoms at 8 years. Patient 3 with recurring carcinoma in situ has required less frequent resections and specimens show reduced degrees of dysplasia present only in islands amid normal mucosa at 8 years (currently no evidence of disease at 21 months from last intervention). Conclusion: Brincidofovir appears to attenuate HPV disease of the larynx in this small pilot study, though further investigation is required because of the highly variable nature of the disease and potential confounding factors.