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Thirty patients with operable epidermoid carcinoma of the head and neck were treated with intravenous high dose methotrexate and leucovorin rescue prior to resection. Their clinical courses were compared with those of thirty randomly selected patients matched for tumors site and clinical stage who were treated by surgery alone. No medical or surgical complications associated with methotrexate were encountered. An objective decrease in tumor size (primary lesion or nodal metastases) was noted prior to resection in twenty-three patients (77 per cent). The number of recurrences in the two groups was similar. However, these was a significantly greater disease-free interval in the methotrexate-treated patients (p less than 0.05). No significant differences in survival have been noted to date between the two groups. In view of the absence of complications, the regressions in tumor size, and the increase in postoperative disease-free interval in this trial, evaluation as preoperative adjuvants of higher doses of methotrexate and of other chemotherapeutic agents in combination with methotrexate appears warranted.

The differences seen in levels of antibody response to HSV-TAA between non-laryngeal and laryngeal cancers in cured and untreated patient populations were due to the use of filtered sera. In previous and present studies using unfiltered sera, these differences were not noted. Of unfiltered sera from patients with squamous-cell carcinomas of the head and neck, 89% (49 out of 55) were positive for CF reactivity to HSV-TAA, and 44% of these unfiltered sera had titres of 1:4 or greater to 44 microng of antigen. The upper band of the antigen appears to be present in early provirus formation and is highly unstable whereas the lower band does not seem to be part of the assembly process.

Immune competence was evaluated in cured patients who had been treated by irradiation for carcinoma of the laryngopharynx, and compared with that of similar patients treated by surgery alone, and normal controls. Cellular immunity was determined by quantitation of in vitro phytohemagglutinin (PHA)-induced lymphocyte reactivity and peripheral blood thymus-dependent lymphocyte (T cell) levels. Humoral immunity was assessed by measurement of serum immunoglobulin levels and by the effect of serum on in vitro normal lymphocyte reactivity to PHA. In 21 patients who were studied for 4-23 years (mean 8.4) after surgical treatment alone for laryngopharyngeal carcinoma, neither cellular nor humoral immunity differed from that of 44 controls. In contrast, 14 patients who had been irradiated and subsequently cured for 4-15 years (mean 9.0) prior to evaluation displayed significantly impaired cellular immune competence when compared to normals and patients treated by surgery alone. Since previous determinations of the effects of radiation therapy have been in patients who received irratiation to the thymic region or large area of bone marrow, this study indicates that radiation therapy for cancer administered via portals that encompass a minimal area of the immune system may be associated with prolonged impairment of cellular immunity.

Comparisons of the results obtained in a study of fifty-two patients with genitourinary malignancies using three assays to monitor the thymus-dependent immune system (delayed cutaneous hypersensitivity to DNCB, PHA-induced lymphocyte blastogenesis, and peripheral blood E rosette-forming lymphocyte counts) yielded statistically significant positive correlations between the DNCB and PHA assays in twenty-one of twenty-eight instances, the DNCB and E rosette assays in thirteen of sixteen instances, the PHA and E rosette assays in twenty-eight of thirty-six instances, and among the DNCB, PHA and E rosette assays in ten of fourteen instances. The results suggest that both PHA-stimulated lymphocyte blastogenesis and peripheral blood E rosette-forming lymphocyte levels provide meaningful in vitro correlates of cell-mediated immunity.

To evaluate the relation between histocompatibility antigen phenotypes and solid malignant neoplasms, HL-A type was determined in 633 cancer patients and compared with those of 489 normal controls. HL-A8 was elevated in patients with squamous cancer, melanoma, and adenocarcinoma. The highest incidence occurred in patients with salivary gland adenocarcinoma (67% vs only 17% in normal controls). A threefold increase in HL-A5 was detected in patients with connective tissue sarcomas (28% incidence vs 9% in normal controls). Antigen frequencies did not vary when analyzed by time of diagnosis or interval after treatment. The finding that certain malignant neoplasms have associations with increased frequency of individual HL-A antigens may give clues to cause and genesis for these tumors.

The T rosette assay, based on the capacity of thymus-derived lymphocytes (mediators of tumor-inhibiting immunity) to bind sheep erythrocytes in vitro, was used to quantitate percentages of T rosette-forming lymphocytes in the peripheral blood of 38 patients with urologic cancer. Results obtained using the T rosette assay yielded statistically significant direct correlations with those obtained using two other assays which have been widely employed to monitor cellular immunity: elicitation of delayed hypersensitivity to DNCB (dinitrochlorobenzene) and the proliferative response of lymphocytes to PHA (phytohemagglutinin). The findings suggest the T rosette assay provides a meaningful in vitro correlate of cellular immunity.

Serums from tumor-bearing patients, cured patients, and normal subjects were examined for antibodies to the separated complement-fixing reactive components of nonvirion antigens of herpesvirus type 1 and type 2. The occurrence of antibodies to the antigens was similar in serums from tumor-bearing patients and cured patients. Antibodies to the antigens were observed among 21 of 24 (87 percent) cervical cancer cases, 44 of 49 (90 percent) laryngeal cancer cases, 15 of 24 (62 percent) cases of squamous cell carcinomas of the head and neck excluding the larynx, 2 of 24 (8 percent) nonsquamous cell cancer cases, and 3 of 51 (6 percent) normal subjects. By contrast, no differences were found in the titers of neutralizing antibodies to the virus in serums from laryngeal cancer patients and controls. The observations support an etiologic role of herpesviruses in cervical cancer and in laryngeal cancer, and possibly other squamous cell cancers of the head and neck.