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

• Published in: Oncology reports Vol. 6; no. 2; p. 269
• Main Authors: Okamoto, A, Woodworth, C D, Yen, K, Chung, J, Isonishi, S, Nikaido, T, Kiyokawa, T, Seo, H, Kitahara, Y, Ochiai, K, Tanaka, T
• Format: Journal Article
• Language: English
• Published: Greece 01.03.1999
• Subjects: Adult; Aged; Antineoplastic Agents, Phytogenic - therapeutic use; Antiviral Agents - therapeutic use; Apoptosis; Carcinoma in Situ - drug therapy; Carcinoma in Situ - pathology; Carcinoma in Situ - virology; Cell Division - drug effects; Cells, Cultured; Female; Gene Expression Regulation, Viral - drug effects; Humans; Keratinocytes - drug effects; Keratinocytes - virology; Middle Aged; Neoplasm Staging; Papillomaviridae - drug effects; Papillomaviridae - genetics; Papillomaviridae - isolation & purification; Papillomavirus Infections - complications; Papillomavirus Infections - drug therapy; Papillomavirus Infections - pathology; Podophyllin - therapeutic use; Tumor Cells, Cultured; Tumor Virus Infections - complications; Tumor Virus Infections - drug therapy; Tumor Virus Infections - pathology; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology; Vidarabine - therapeutic use
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.6.2.269

Our aim was to establish an effective non-surgical treatment for cervical intraepithelial neoplasia (CIN) through inactivation of human papillomavirus (HPV), the major etiological agent for this disease. We show that vidarabine, a DNA polymerase inhibitor, suppressed growth and HPV gene expression in human cervical keratinocytes immortalized by HPV or in cervical cancer cell lines. Expression of HPV-16 E6 and E7 proteins in normal cervical keratinocytes sensitized cells to apoptosis in the presence of podophyllin or vidarabine. We applied vidarabine ointment and/or podophyllin to cervical epithelium in 28 cases of CIN I-II to evaluate the therapeutic effectiveness of these agents. Co-application of vidarabine and podophyllin in six treatments caused regression of lesions cytologically and histologically, and disappearance of HPV-16 or -18 DNA in 17 of 21 (81%) women. Our results suggest that the combination of vidarabine and podophyllin therapy is an effective non-surgical treatment for HPV-positive CIN.