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

A Okamoto; C D Woodworth; K Yen; J Chung; S Isonishi; T Nikaido; T Kiyokawa; H Seo; Y Kitahara; K Ochiai; T Tanaka

doi:10.3892/or.6.2.269

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

Oncol Rep. 1999 Mar-Apr;6(2):269-76. doi: 10.3892/or.6.2.269.

Authors

A Okamoto¹, C D Woodworth, K Yen, J Chung, S Isonishi, T Nikaido, T Kiyokawa, H Seo, Y Kitahara, K Ochiai, T Tanaka

Affiliation

¹ Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Minato-ku, Tokyo 105-0003, Japan.

PMID: 10022988
DOI: 10.3892/or.6.2.269

Abstract

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.

Publication types

Clinical Trial

MeSH terms

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*

Substances

Antineoplastic Agents, Phytogenic
Antiviral Agents
Podophyllin
Vidarabine