Cidofovir, a new approach for the treatment of cervix intraepithelial neoplasia grade III (CIN III)

Abstract

Cervix intraepithelial neoplasia grade III (CIN III) is an intraepithelial proliferative process with different levels of severity depending on both the extension of the proliferation in the epithelium and the presence of cellular atypia. Human papillomavirus (HPV) has been clearly associated with such lesions. The results of a preliminary study are described on the local application of cidofovir, an acyclic nucleoside phosphonate derivative with broad-spectrum anti-DNA virus activity for the treatment of CIN III. Cidofovir 1% in gel was applied three times, every other day, on the cervix of each of 15 women with biopsy proven CIN III. Within 1 month after the start of treatment, the cervix was removed surgically. Histology and human papillomavirus polymerase chain reaction (HPV-PCR) were carried out. In 7 of the 15 patients the histology showed a complete response, whereas 5 patients had a partial response characterized by the persistence of CIN II-III lesions, 1 patient had a dysplasia of lower grade (CIN I), and 2 patients did not show differences in the histology. Complete response was confirmed by PCR in 4 of the 7 patients, with complete response histologically. Cidofovir was not toxic to the normal epithelium. Cidofovir 1% gel was able to inhibit partially or completely cervical dysplasia lesions after only three applications (every other day). This effect was specific and tissue other than the dysplastic epithelium was not affected by the treatment.

Clinical Potential of the Acyclic Nucleoside Phosphonates Cidofovir, Adefovir, and Tenofovir in Treatment of DNA Virus and Retrovirus Infections

“…Initial clinical trials with 1% cidofovir topical gel also point to its efficacy in the treatment of cervical intraepithelial neoplasia grade III (196): partial to complete responses were observed histologically in the majority of the patients and were confirmed by PCR, and this effect was seen after only three applications (every other day) (196). Complete and permanent eradication of vulvar intraepithelial neoplasia grade III was achieved with topical 1% cidofovir in a patient who did not respond to interferon and isotretinoin (114).…”

An Armamentarium of Wart Treatments

“…[163][164][165] It has been used successfully in HIV-positive patients for the topical treatment of genital warts. [166][167][168][169][170] A case has been reported in which a homosexual man with HIV had multiple extensive warts. When treated with oral antiretroviral therapy (didanosine, stavudine and efavirenz or abacavir), there was a nearly total regression of the viral warts along with a significant improvement in the patient's immune status.…”

An overview of early investigational drugs for the treatment of human papilloma virus infection and associated dysplasia

“…It has also been used to treat HR-HPV related cervical dysplasia 21 and more recently with some success where 14/23 (>60%) of women with pre-treatment biopsy confirmed CIN2 were found to be histologically normal following 3 physician-applied local applications of cidofovir 22 . However, since this drug is both mutagenic 23 and carcinogenic in animals its use for the treatment of HPV related benign and pre-malignant pathologies has proved controversial 24 .…”