[The effect of vaginal administration of interferon on squamous intraepithelial cervical lesions]. / Utjecaj vaginaleta interferona na cervikalnu skvamoznu intraepitelnu leziju.

Human papillomavirus vaginal and/or cervical infections were found in 1.98 percent of mostly younger female general populations and in 26.6 percent of cases with abnormal Pap smears. Antiviral treatment with human leukocyte interferon (HLI-alpha) vaginalettes was introduced at the beginning of 1987. In 30 cases a daily dose of 1 x 10(6) IU HLI during two 21-day menstrual cycles was applied. In 137 controls without therapy and the treated group a 12-month follow-up was performed. Every third month the regression, persistence or progression of the cervical squamous intraepithelial lesion (SIL) was determined by cytology and colposcopy. Most of the cases with progression were histologically confirmed. For ethical reasons the placebo treatment of the control group with an identical spectrum of disease was not feasible. Therefore, a secondary analysis and the 2 test were used. Up to now the results show a significant regression (21 out of 30, X2 = 4.51, P less than 0.05) in the treated group and progression (23 out of 137, X2 = 18.41, P less than 0.01) in controls. HLI vaginalettes are easily applicable, without any side-effects.

[Juvenile papillomatosis of the larynx]. / Juvenilna papilomatoza larinksa.

Juvenile laryngeal papilloma is the most common childhood neoplasm of the larynx. It is most often multiple and is characterized by a strong tendency to recur. Seventy-eight children with primary juvenile laryngeal papillomatosis (JLP) were treated at the ENT Department of the Zagreb University School of Medicine in the last 20 years and in the last 6 years interferon has been introduced into the therapy. Causes of the recurrence and the resistance to the therapy have been investigated. It has been shown that the administration of interferon has a certain effect on the tumor growth, but it has no effect against tumor recurrence. In patients with a severe clinical course the epithelial atypia of basal layer of papilloma and the increased enzymatic activity have been found.

Antiviral and anti-invasive titers of human interferons.

The titers of preparations of human leukocyte and human fibroblast interferon were examined to determine their antiviral and anti-invasive activity. The examinations showed a very high correlation of these activities in human fibroblast interferon (r = 0.99), whereas the correlation for human leukocyte interferon was lower. These two interferons have also been found to differ in the relation between antiviral and anti-invasive titers. This difference is highly significant (p less than 0.001).

Histopathologic and histoenzymatic observations in carcinomas treated with human leukocyte interferon.

In this study histologic and histochemical examinations were performed on the bioptic material of 30 cases of head and neck tumors and 34 cases of uterocervical carcinomas after treatment with human leukocyte interferon (HLI). Particular attention was paid to the interaction between stromal and neoplastic cells as a possible host response to the treatment with interferon. In addition to tumor biopsies, regional lymph nodes were also examined microscopically. Stromal cells (macrophages, T and B lymphocytes, and granulocytes) were detected by enzyme-histochemical methods. Histologic and histochemical criteria for classification of tumor biopsies into five groups included the frequency, the cellular composition of peritumoral stroma, the grade of macrophage infiltration into the tumor (expressed quantitatively), and cytologic changes, followed by the regression of tumor. The overall appraisal of patients with cervical carcinoma based on histopathologic and chemical criteria showed the positive effect of HLI therapy in 70% of the cases; observations of head and neck carcinoma treated with HLI showed positive effects in 82% of the cases.

The clinical use of human leukocyte interferon in viral infections.

This review presents the results of the clinical use of human leukocyte interferon (HLI) in certain diseases with viral etiology. Viral infections with manifestations in the eye, skin, and/or mucous membranes and in the respiratory system were treated with HLI by local application. HLI was incorporated into ointment, oil suspension, powder, dilution for inhalation, and dilution for subcutaneous and subconjunctival injections. The treatment in some of the diseases yielded statistical results that were highly significant in favor of interferon.

Application of human leucocyte interferon in patients with urinary bladder papillomatosis, breast cancer, and melanoma.

Eight patients with malignant papillomaosis of the bladder, four with breast cancer, and two with malignant melanoma, all of whom had a poor prognosis, were treated with injection of crude human leucocyte interferon (HLI) into the tumour or the adjacent tissue and in some cases with intramuscular HLI injection also. All tumours showed complete or partial regression after treatment for up to 6 months. One patient with breast cancer died from distant metastases; all other patients in the trial were recurrence-free after 3--30 months of follow-up.

Application of human leucocyte interferon in patients with carcinoma of the uterine cervix.

15 patients with invasive squamous-cell carcinoma of the uterine cervix were treated with crude human leucocyte interferon (HLI) for 3 weeks before surgical removal of the tumour. 9 patients were given HLI topically and intramuscularly and 6 topically only. In 3 patients the surgical material was free from tumour cells, in 3 it showed a lower grade of carcinoma, and in 9 the findings remained unchanged. In only 1 patient the tumour metastasised to the lymph nodes. Typically a tumour regressed to about a third of its original size. There was a sharp distinction between the tumour mass and the healthy tissue manifested in the formation of a fibrous wall. On the basis of the scores--i.e., stromal response, relation between tumour-cell and macrophage activity and reactivity, and reactivity of the original lymph nodes--the overall appraisal of the response caused by HLI therapy was as follows: in 6 patients excellent, in 5 very good, in 1 moderate, in 2 poor, and in 1 no response. It is suggested that HLI is suitable for administration both before and after surgery in patients with cervical cancer of grade I or II. If stroma cannot be induced to respond within 21 days of treatment, HLI application should be discontinued.

Interferon treatment of uterine cervical precancerosis.

Human leukocyte interferon (HLI) was used in a randomized study of patients with precancerous states on the uterine cervix. The daily dose of HLI was 10(6) units and its was applied by the contraceptive pessary technique. In patients how had had only viral alterations on the cervix the treatment lasted 14 days (Singer et al. 1979) and in those with changed cytologic findings 21 days. The cytologic findings of the interferon treated patients showed no progression of the pathologic process during the ensuing 2 years. In the control group, however, they showed the aggravation of the process and the patients were directed to surgical therapy. The control of cytologic findings has been continued and in now performed at 3 month intervals.

Influence of human leukocyte interferon on squamous cell carcinoma of uterine cervix: clinical, histological, and histochemical observations. III. Communication.

Fifteen patients with invasive squamous cell carcinoma of the uterine cervix were treated with human leukocyte interferon (HLI). HLI was applied topically and i.m. to nine patients, and only topically to six. After therapy, surgical material was free from tumor cells in three patients, tumor cells were identified as invasive carcinoma in one patient and as CA in situ in two patients. Findings remained unchanged in nine patients. Tumor metastases in the lymph nodes were found in only one patient. The patients' overall response to therapy was assessed on the basis of stromal response, relation of tumor cells and macrophage activity, and the reactivity of lymph nodes.

Human leukocyte interferon in therapy of patients with urinary bladder papillomatosis, breast cancer, and melanoma.

The authors report the result of local and parenteral applications of human leukocyte crude interferon in the therapy of eight patients with urinary bladder papillomatosis, four patients with breast cancer, and two patients with melanoma. The doses and effects of treatment are presented in tables. Clinical application of human leukocyte interferon (HLI) to these three types of malignant tumors has yielded encouraging results. The authors believe that investigations on HLI applications to some malignant tumors should continue because the results obtained indicate that interferon possesses not only an antiviral but also an antitumor activity.