Patients with condyloma acuminatum (CA), a common sexually transmitted disease caused by human papillomaviruses (HPV), have several defects in their immune responses which may help explain the persistence of this virus in these persons. Since at least 90% of cervical carcinoma biopsies harbor HPV sequences, this depressed immune response may also contribute to the oncogenic potential of HPV. It has been shown repeatedly that interferon-alpha (IFN alpha) can completely eradicate CA lesions in approximately 50% of treated patients. Treatment of CA with interferon gamma (IFN gamma) has been reported only from a small series of Phase II studies. Although the activity of IFN gamma was significant, differences in study design make comparison difficult with IFN alpha trials. Combinations of IFN alpha with IFN gamma have been shown to be synergistic in both antiviral and antiproliferative systems, but this combination has not been reported in the treatment of CA. This investigation will compare the relative efficacies and toxicities of these IFNs individually and in combination. To study the mechanisms by which IFNs act against HPV, analyses of peripheral blood mononuclear cells (PBMC). Including identification of subsets as well as functional studies, will be conducted pre-, during, and post-treatment with IFNs. Lesions of CA will be biopsied pre-treatment for routine histology, and identification of HPV type. Following treatment, biopsies of the lesions, or of the skin in the area of the former lesions, will be repeated to determine if HPV is still present. Results from these studies will not only help reveal which IFN, or combination of IFNs, is the best treatment for CA, but will also contribute significantly to our understanding of HPV infection and the mechanisms of IFN action against HPV. Considering the oncogenic potential of HPV, knowledge gained from this investigation also may increase our understanding of the mechanisms by which HPV regulates the host's immune system allowing the development of cancer. Ultimately, such knowledge may lead to improved prevention and treatment of such cancers (especially cervical carcinoma).
