Combination therapy with podophyllin and vidarabine for human papillomavirus positive cervical intraepithelial neoplasia

Our aim was to establish an effective non-surgical treatment for cervical i ntraepithelial neoplasia (CIN) through inactivation of human papillomavirus (HPV), the major etiological agent for this disease. We show that vidarabi ne,a DNA polymerase inhibitor, suppressed growth and HPV gene expression in human cervical keratinocytes immortalized by HPV or in cervical cancer cel l lines. Expression of HPV-16 E6 and E7 proteins in normal cervical keratin ocytes sensitized cells to apoptosis in the presence of podophyllin or vida rabine. We applied vidarabine ointment and/or podophyllin to cervical epith elium in 28 cases of GIN I-II to evaluate the therapeutic effectiveness of these agents. Go-application of vidarabine and podophyllin in six treatment s caused regression of lesions cytologically and histologically, and disapp earance of HPV-16 or -18 DNA in 17 of 21 (81%) women. Our results suggest t hat the combination of vidarabine and podophyllin therapy is an effective n on-surgical treatment for HPV-positive GIN.