Clinical experience with HLA-B7 plasmid DNA/lipid complex in advanced squamous cell carcinoma of the head and neck.

OBJECTIVE: To investigate the safety and efficacy of alloantigen plasmid DNA therapy in patients with advanced head and neck squamous cell carcinoma using Allovectin-7 (Vical Inc, San Diego, Calif), a DNA/lipid complex designed to express the class I major histocompatibility complex antigen HLA-B7. DESIGN: Multi-institutional prospective trial. SETTING: Academic medical setting. PATIENTS: A total of 69 patients were enrolled in 3 sequential clinical trials: a single-center phase 1 trial and 2 multicenter phase 2 trials. Eligibility criteria included unresectable squamous cell carcinoma that failed conventional therapy, Karnofsky performance status score of 70 or greater, and no concurrent anticancer or immunosuppressive therapies. INTERVENTION: Patients received 2 biweekly intratumoral injections of 10 microg (phase 1 and first phase 2 trials) or 100 microg (second phase 2 trial) of Allovectin-7 followed by 4 weeks of observation. Patients with stable or responding disease after the observation period were given a second treatment cycle identical to the first. MAIN OUTCOME MEASURES: Patients were assessed for toxic effects, and tumor size was measured after cycles 1 (at 6 weeks) and 2 (at 16 weeks). RESULTS: Allovectin-7 treatment was well tolerated, with no grade 3 or 4 drug-related toxic effects. Of 69 patients treated, 23 (33%) had stable disease or a partial response after the first cycle of treatment and proceeded to the second cycle. After the second cycle, 6 patients had stable disease, 4 had a partial response, and 1 had a complete response. Responses persisted for 21 to 106 weeks. CONCLUSIONS: Intratumoral plasmid DNA immunotherapy for head and neck cancer with Allovectin-7 is safe, and further investigations are planned in patients with less advanced disease, where it could potentially improve patient survival and reduce the need for radical high-morbidity treatments.

Technetium 99m single positron emission computed tomography scanning for assessing mandible invasion in oral cavity cancer.

OBJECTIVES: To study the accuracy of single positron emission computed tomography (SPECT) scanning and compare its results to clinical examination, Panorex, and computed tomography (CT) scanning with respect to determining mandibular invasion by oral cavity and oropharyngeal cancer, and to define the role of SPECT scanning in the preoperative assessment of oromandibular cancer. STUDY DESIGN: Prospective study of 38 patients who underwent technetium 99m SPECT scanning as part of their preoperative clinical assessment for cancer at risk of invading the mandible. All patients underwent partial or segmental mandibulectomy as part of their surgical management. METHODS: A data protocol was used to tabulate patient demographics, tumor characteristics and results of preoperative tests as patients were enrolled into the study. Following surgical treatment, these data were correlated with histopathological findings. Detailed analysis was performed to assess the tabulated data. RESULTS: The SPECT scanning demonstrated an 87% overall accuracy in predicting bone invasion compared with 71% for clinical examination, CT scanning, and Panorex x-rays. The SPECT scanning was significantly more sensitive (95%) than either CT scans (55%) or Panorex x-rays (50%). Notably SPECT scanning demonstrated a considerable improvement in specificity (72%) compared with conventional radionuclide scanning. Although not as specific as CT scanning or plain films, SPECT scanning was significantly more effective in ruling out disease than was clinical examination. CONCLUSIONS: Preoperative SPECT scanning used in combination with clinical examination, CT scanning, and Panorex x-rays to assess patients at risk for mandible involvement by oral cavity cancer can improve the accuracy of predicting bone invasion and help in appropriate treatment planning so as to safely reduce the proportion of disease-free jaws resected.

Evaluation of 201T1 SPECT for predicting early treatment response in patients with squamous cell carcinoma of the extracranial head and neck treated with nonsurgical organ preservation therapy: initial results.

PURPOSE: The purpose of this work was to prospectively determine the ability of 210TI single photon emission CT (SPECT) to monitor treatment response in patients with head and neck squamous cell carcinoma (HNSCCA) treated with nonsurgical organ preservation. METHOD: Nine patients with HNSCCA underwent 201T1 SPECT before and 6 weeks after completion of nonsurgical organ preservation therapy. All cases were evaluated for uptake at the primary site before and after treatment. All tumors had abnormal radiotracer uptake on the pretreatment study. The posttreatment thallium studies were evaluated for uptake and correlated with local control at the primary site in all cases. RESULTS: All patients had abnormal thallium uptake on pretreatment studies. Of the nine patients, four cases were locally controlled by nonsurgical organ preservation therapy. All of these patients had no evidence of thallium uptake on posttreatment studies. Five cases failed treatment at the primary site. All five patients demonstrated abnormal radiotracer uptake at the primary site. CONCLUSION: Our initial results suggest that 201T1 SPECT may be an accurate technique for monitoring HNSCCA treated with nonsurgical organ preservation therapy.

Subcellular immunolocalization of protein kinase CK2 in normal and carcinoma cells.

CK2 is a messenger-independent protein serine/threonine kinase that has been implicated in cell growth and proliferation. Our recent analysis of squamous cell carcinomas of the head and neck (SCCHN) revealed a significant elevation in CK2 activity in these tumor cells relative to normal mucosa of the upper aerodigestive tract and suggested a correlation with aggressive tumor behavior and poor clinical outcome. In order to further define the distribution of CK2 in these tissues, we have examined the immunohistochemical staining pattern of surgical specimens of both SCCHN tumors and normal upper aerodigestive tract mucosa using a monoclonal antibody directed against the catalytic subunit CK2-alpha of the kinase, and have compared these data with the subcellular distribution of CK2 activity in these same tissues. These measurements showed that CK2 is predominantly localized to the nuclei of the tumor cells, which agreed closely with the immunohistochemical staining pattern of CK2-alpha in tumor cells. The chiefly nuclear distribution of CK2-alpha immunostaining found consistently in SCCHN tumor cells and tumor-infiltrating lymphocytes contrasted with a relatively more predominant cytosolic staining pattern exhibited by various cellular constituents of normal oropharyngeal mucosa. The immunostaining pattern of CK2-alpha revealed that staining was observed in the cells stained for the proliferation-marker Ki-67; however, strong distinct immunostaining for CK2-alpha was also observed in large numbers of other cells in these same tumors, suggesting that CK2 elevation in these tumors is not a reflection of proliferative activity alone, but may also relate to the pathobiological behavior of the tumor.

Thallium-201 single-photon emission CT versus CT for the detection of recurrent squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: Thallium-201 single-photon emission computed tomography (SPECT) can be used to detect primary squamous cell carcinoma (SCCA) of the head and neck. Nevertheless, there have very few studies performed to evaluate the ability of thallium-201 to depict recurrent SCCA. The purpose of this study was to compare the ability of thallium-201 SPECT with CT to enable detection of recurrent SCCA of the upper aerodigestive tract. METHODS: Thirty-three patients with a history of previously treated SCCA of the extracranial head and neck underwent thallium-201 SPECT imaging and contrast-enhanced CT. A neuroradiologist and nuclear medicine physician with knowledge of the primary site evaluated all thallium-201 studies for abnormal radiotracer uptake at the primary site. These results were correlated with histologic findings and clinical follow-up in all patients. All patients were followed up for a minimum of 2 years after completion of treatment. The McNemar test was used to determine statistical significance. RESULTS: The diagnostic accuracy of thallium-201 SPECT was as follows: sensitivity, 88%; specificity, 94%; positive predictive value, 93%; and negative predictive value, 89%. The diagnostic accuracy of CT was as follows: sensitivity, 100%; specificity, 24%; positive predictive value, 55%; and negative predictive value, 100%. The diagnostic accuracy of thallium was superior to CT (P = .01). CONCLUSION: Thallium-201 SPECT is superior to CT for differentiating recurrent tumor from post-treatment changes and may complement CT in the evaluation of previously treated SCCA of the extracranial head and neck.

Preoperative permanent balloon occlusion of internal carotid artery in patients with advanced head and neck squamous cell carcinoma.

OBJECTIVE/HYPOTHESIS: To determine the value of preoperative balloon occlusion in predicting the safety of carotid artery resection in advanced recurrent head and neck squamous cell carcinoma. STUDY DESIGN: Retrospective chart review of all cases undergoing planned carotid artery resection for recurrent disease at a major university hospital. METHODS: If the carotid artery was encased, a nonemergent carotid artery balloon test occlusion was performed for 30 minutes. If the patient tolerated this, he or she underwent permanent carotid artery occlusion. RESULTS: Twenty-three patients were prospectively evaluated for resection. Three underwent emergent carotid artery ligation. Twenty others underwent nonemergent carotid artery test occlusion. Of these, 5 patients failed preoperative carotid artery balloon occlusion and 15 patients successfully underwent permanent carotid balloon occlusion. Although eight of these patients died of recurrent disease in less than 1 year, seven patients survived more than 1 year with two patients surviving more than 2 years. CONCLUSIONS: Preoperative carotid balloon occlusion predicted patients who could tolerate permanent occlusion. All patients eventually developed recurrent disease, but in 14 of the 15 patients, no hemorrhages occurred.

Modulation of nuclear matrix protein phosphorylation by histones: possible involvement of NM-associated protein kinase CK2 activity.

Nuclear matrix (NM), a proteinaceous network of filaments, dictates nuclear morphology and the structure/function of DNA. Phosphorylation of NM proteins is a potential signal for regulating matrix functions. Histones also are intimately involved in DNA structure and transcription. Here, we report that various histones enhanced 32P incorporation into certain NM proteins. Modulation of NM protein phosphorylation by histones is mediated through regulation of protein kinase CK2, a messenger-independent serine/threonine kinase, which is significantly associated with the NM. The stimulatory effect of histones was mitigated by prior incubation of histones with DNA in the reaction. Phosphorylation of NM proteins was extensively reduced when an excess of the CK2-specific peptide substrate was included in the phosphorylation reaction as a competitor. Also, enhancement in the NM-associated CK2 activity by histones was blocked by inhibitors of CK2. Histone H1 effect appeared to be mediated mainly by charge effect since a stretch of polylysine induced a similar effect. Various histones also differentially affected the autophosphorylation of NM-associated CK2 subunits. This may contribute to the observed effects of histones on the NM, resulting in an enhancement and differential pattern of NM protein phosphorylation. Such a regional modification of NM protein phosphorylation might influence the nuclear functions that require histone displacement, namely, replication and transcription.

The role of radiotherapy in the management of carcinoma in situ of the glottic larynx.

Carcinoma in situ of the glottic larynx is a rare malignancy, comprising only 1% to 2% of laryngeal biopsy. The management of these lesions remains controversial. In this article, the authors present results and analysis of the management of 20 patients having these lesions treated by radiotherapy. A total of 20 patients who had carcinoma in situ of the glottis were treated with curative intent with radiotherapy at the Veterans Administration Medical Center, Minneapolis, Minnesota, U.S.A. from November 1972 through March 1993. Before radiotherapy, eight patients had only biopsies of the glottic larynx, five had one stripping procedure, and seven patients had two or three stripping procedures. Of the 20 patients, 19 are available for retrospective analysis, with a minimum follow-up of 4 years and a median follow-up of 7.3 years. Treatment was given to all patients by megavoltage units (cobalt 60, 2; 4-mV linear accelerator, 18). Patients were treated using bilateral opposed wedged 6-cm x 6-cm fields, with a dose of 1.75 Gy per fraction to a total median dose of 68.4 Gy in 40 fractions over 56 elapsed treatment days. The Kaplan-Meier method was used for survival analysis. The 4-year disease-free survival was 95% after irradiation. The actuarial disease-free survival for 5 and 10 years was 95%. Surgical salvage failed in one patient who had a laryngectomy for recurrent invasive squamous cell carcinoma at 34 months after radiotherapy. Two patients developed severe shortness of breath because of laryngeal edema, which required tracheostomy. Sixteen patients reported subjective significant improvement of their voice quality, and four reported no change. Radiotherapy is an excellent choice for patients who have recurrent carcinoma in situ after undergoing stripping procedures or for those patients who live too far from a medical facility to allow close follow-up and repetitive surgical procedures. These results are comparable to those of other investigators who used radiotherapy with higher dose per fraction.

Curative radiotherapy for stage II-III squamous cell carcinoma of the glottic larynx.

The authors report the analysis and outcome of curative radiotherapy for stage II and III squamous cell carcinoma of the glottic larynx. Thirty-nine men with invasive, previously untreated squamous cell carcinoma of the glottic larynx were referred for curative radiotherapy from May 1976 through June 1991, to the Veterans Administration Medical Center in Minneapolis, Minnesota, U.S.A. Thirty-eight patients had T2N0 disease, and one had T2N1 disease. All patients were treated by megavoltage units (two by cobalt 60 and 37 by 4 mV-linear accelerator). The median fractional dose was 1.80 Gy, and the median total tumor dose was 70.20 Gy. Surgical salvage was reserved for irradiation failure. All patients had a minimum 5-year follow-up. The Kaplan-Meier method was used for survival analysis. The 5-year disease-free survival with voice preservation after radiotherapy was 70.2% (80% for T2a and 64% for T2b patients). The ultimate 5-year disease-free survival for all T2 patients after surgical salvage was 91%. In nine patients, ten second primary malignancies were diagnosed during follow-up. Nine of these second lesions occurred in the aerodigestive tract. Curative radiotherapy using conventional fractionation regimen with surgical salvage for irradiation failure is an efficacious modality for T2N0 and T2N1 squamous cell carcinoma of the glottic larynx. A high incidence of second malignancy was noted in our series.

The management of metastatic squamous cell carcinoma in cervical lymph nodes from an unknown primary.

A patient is diagnosed with an unknown primary of the head and neck when metastatic disease is present in the cervical lymph node or nodes and no primary lesion is detected by thorough physical examination, directed biopsies of suspicious or most likely primary sites, and imaging studies. The optimal management of patients who have this syndrome is still unclear and controversial. We report our results and analysis of the management of 24 patients with this syndrome. From 1976 through 1992, 24 patients who had metastatic squamous cell carcinoma in the cervical lymph nodes were seen in our medical center. A thorough search did not detect a primary lesion in any of them. Patients underwent radical neck dissection of the involved neck; 23 had unilateral and I had bilateral neck disease. Postoperative radiotherapy was delivered to both sides of the neck and to the potential primary mucosal and submucosal sites. The relation between clinical N stage, histologic findings of numerous involved lymph nodes, presence of extracapsular tumor extension, and survival were statistically analyzed. The Kaplan-Meier method was used for the survival analysis. The p values of log-rank test for the comparison of the two groups 1) N1 and N2 versus N3, and 2) presence of extracapsular tumor extension versus its absence are less than 0.005, with extracapsular tumor extension versus nonextracapsular tumor extension slightly smaller. The 5- and 10-year disease-free survival rate for the entire group was 54.2% (70.5% for N1 and N2, and 14.2% for N3). Three patients had locoregional failure, two in the primary sites, one in the nasopharynx, and the other in the oropharynx (the latter also had recurrent disease in the undissected neck). In 8 patients, distant metastases developed 7 to 38 months after radiotherapy. All 11 patients (45.8%) who had recurrent disease had advanced clinical N stage, microscopic findings of numerous involved lymph nodes, and prominent extracapsular tumor extension to the surrounding soft tissue and blood vessels. The high incidence of distant metastases shortly after treatment suggests a hematogenous spread before treatment in patients who had extensive nodal and extranodal disease. Our long-term disease-free survival beyond ten years seems to indicate combined treatment modalities, including radical neck dissection with postoperative radiotherapy of the neck, and the potential primary site in patients with N2 and N3 disease (our N1 group is too small for analysis). Further improvement of cure rate can be expected in the future with early detection and treatment.

External beam radiation therapy for squamous cell carcinoma of the soft palate.

PURPOSE: External beam radiation therapy for carcinoma of the soft palate aims to achieve loco-regional control with normal speech, nasal function, swallowing mechanism, and minimal side effects such as nasal speech and regurgitation of food into the nasopharynx. In this report we present our results of radiotherapy in the treatment of 24 patients with squamous cell carcinoma of the soft palate. METHODS AND MATERIALS: A total of 24 patients with squamous cell carcinoma of the soft palate were treated at the Veterans Administration Medical Center Minneapolis, MN, between February 1977 and May 1992. Of the 24 patients 2 had T1, 19 T2, 1 T3, and 2 had T4 lesions. Nineteen patients did not have clinical nodal disease, stage (N0), 1 had N1, 2 N2, and 2 N3 disease (Table 1). All the patients were treated by 4 MeV linear accelerator. A 1.75 Gy median dose was administered per fraction to a total of 70 Gy median dose. Bilateral opposed compensated shrinking fields technique was used. RESULTS: The 3-year disease free survival rate after external beam radiation therapy was 100% (1 out of 1), 64.7% (11 out of 17), 100% (1 out of 1), and 0%, for patients with T1, T2, T3, and T4 disease, respectively. Salvage surgery for recurrent disease was successful in 57.1% (4 out of 7 patients (Table 2). The ultimate 3-year disease free survival rate for the entire group, including surgical salvage, was 81% (17 out of 21) (Fig 1). CONCLUSION: Radiation therapy alone in our institution resulted in tumor control and survival rates compare favorably to previously published reports in the literature. Surgery can be reserved as salvage procedure.

Association of protein kinase CK2 with nuclear matrix: influence of method of preparation of nuclear matrix.

Nuclear matrix (NM) plays a role of fundamental structural and functional significance as the site of replication, transcription, and RNA processing and transport, acting as an anchor or attachment site for a variety of enzymes and other proteins involved in these activities. We have previously documented that protein kinase CK2 translocates from the cytosol to the nucleus, where it associates preferentially with chromatin and NM, in response to certain growth stimuli. Considering that characteristics of the isolated NM can depend on the procedural employed for its isolation, we compared three standard methods for NM preparation to confirm the association of intrinsic CK2 with this structure. Our data suggest that the method used for isolating the NM can qualitatively influence the measurable NM-associated CK2. However, all three methods employed yielded qualitatively similar results with respect to the stimulus-mediated modulation of NM-associated CK2, thus further supporting the notion that NM is an important site for physiologically relevant functions of CK2. In addition, core filaments and cytoskeleton that were isolated by two of the preparative methods had a small but significant level of associated CK2 activity.

Nuclear matrix proteins as malignant markers in squamous cell carcinoma of the head and neck.

OBJECTIVE: To test the hypothesis that transformation of normal upper aerodigestive mucosa to squamous cell carcinoma of the head and neck (SCCHN) is associated with specific changes in nuclear matrix (NM) proteins. DESIGN: Retrospective, nonrandomized investigation using a cellular fractionation sequence followed by 2-dimensional gel electrophoresis analysis of NM proteins. SUBJECTS: Nuclear matrix proteins were extracted from a cohort of 12 pathologic SCCHN specimens and 5 normal specimens of oropharyngeal mucosa. RESULTS: All SCCHN specimens examined expressed 11 NM proteins that were not detected in normal mucosa. Conversely, at least 4 NM proteins that were expressed by all specimens of normal mucosa were absent from all SCCHN tumors. Seven NM proteins were common to carcinomas and normal specimens. Spindle cell histological variants of squamous cell carcinoma had distinct NM patterns. CONCLUSIONS: Malignant transformation of normal upper aerodigestive mucosa to SCCHN is associated with specific changes in NM composition. These data suggest that different NM proteins might serve as specific tumor markers.

Radiation therapy in early carcinoma of the glottic larynx T1N0M0.

PURPOSE: The Purpose of this report is to present the local control rate and survival of patients treated by radiation therapy for T1N0M0 squamous cell carcinoma of the glottic larynx. METHODS AND MATERIALS: A total of 41 patients with squamous cell carcinoma of the glottis were treated at the Veterans Administration Medical Center Minneapolis, MN, between 1976 and 1990. Of the 41 patients, 40 are available for retrospective analysis with a minimum of a 2-year follow-up and a median follow-up of 5.8 years. Treatment was given to all the patients by a 4 MeV linear accelerator. The vast majority of the patients were treated with bilateral laryngeal opposed wedged 6 x 6 cm fields with a dose of 1.75 Gy per fraction to a total of 70 Gy in 40 fractions over 56 elapsed treatment days. RESULTS: The data indicated local control and survival of 92.3 % at 2 years and 91.8 % at 3 years, post irradiation, with ultimate disease-free survival after surgical salvage of 97.4 % and 97.2 % at 2 years and 3 years, respectively. These local control and survival rates are comparable to those published in the literature when a higher fractional dose was given. No patients developed notable complications with our technique. CONCLUSIONS: A dose of 1.75 Gy to 1.8 Gy per fraction to a total of 70 Gy in 56 elapsed treatment days is well tolerated and yields ultimate disease free-survival of 97.2% at 3 years. This time-dose fractionation could be used safely for treating patients who demonstrate low tolerance to irradiation with a risk of laryngitis, laryngeal edema, or difficulty of swallowing, with a higher fractional dose.

Nuclear matrix as an anchor for protein kinase CK2 nuclear signalling.

Nuclear matrix (NM) is not only the structural basis for nuclear shape but also is intimately involved in nuclear functional activities. Among the modulatory factors that may affect these diverse activities are the signals that may influence the state or composition of the NM proteins. One such mechanism for altering the functional activity of at least some NM proteins may be the extent of their phosphorylation. Protein kinase CK2 appears to associate with NM and to phosphorylate a number of NM-associated proteins. Chromatin- and NM-associated CK2 is rapidly modulated by mitogenic signals. We propose that NM serves as a physiological anchor for nuclear signalling of protein kinase CK2 which may influence functions of NM such as transcription of active genes and growth.

Elevated protein kinase CK2 activity in chromatin of head and neck tumors: association with malignant transformation.

We hypothesized that malignant transformation of normal mucosa of the upper aerodigestive tract to squamous cell carcinoma of the head and neck (SCCHN) might be associated with altered CK2 activity in the chromatin compartment of these tumors. We measured CK2 activity in the cytosol and chromatin of 7 surgical specimens of SCCHN, and 5 specimens of normal oropharyngeal mucosa from non-smokers/non-drinkers. CK2 activity in SCCHN tumors was significantly elevated in both the nuclear chromatin (P < 0.0005) and cytosolic (P <0.04) compartments relative to normal mucosa. These data suggest that activation of dysregulation of the chromatin-associated CK2 signal may play a role in the pathobiology od SCCHN.

Microcystic adnexal carcinoma: management options based on long-term follow-up.

Microcystic adnexal carcinoma (MAC), a recently described neoplasm that frequently affects the head and neck, presents a confusing problem for the clinician due to its unusual behavior. The individual cells have a bland microscopic appearance, and there is a predilection for neural invasion. Four cases of MAC are reported. All four cases demonstrate the difficulty with pathologic diagnosis. Follow-up of as long as 33 years begins to delineate the protracted nature of MAC. In addition, this paper includes the first report of a case of lymph node metastasis. Although resection may result in a significant defect, negative margins may not be achieved. Despite this, the defect can heal, as demonstrated by the cases described. In addition, MAC may recur many years later, irrespective of the status of the margins at the time of surgery. Given these unusual characteristics and the slowly progressive nature of MAC, strong consideration must be given to less radical surgical procedures, with close follow-up for grossly recurrent disease.

Association of elevated protein kinase CK2 activity with aggressive behavior of squamous cell carcinoma of the head and neck.

BACKGROUND: Protein kinase CK2 (also known as casein kinase 2) is a messenger-independent protein serine/threonine kinase ubiquitously distributed in eukaryotes. CK2 has been found to phosphorylate a wide variety of cytosolic and nuclear substrates which are intimately involved in regulation of DNA, RNA, and protein synthesis, and differentiation. We therefore addressed the hypothesis that malignant transformation of upper aerodigestive tract mucosa to squamous cell carcinoma of the head and neck (SCCHN) might be associated with altered CK2 activity. MATERIALS AND METHODS: To this end, we subjected surgical specimens of SCCHN tumors and of normal oropharyngeal mucosa to subcellular fractionation. We then quantitated CK2 activity in cytosol and nuclei of these specimens using a CK2-specific peptide substrate (Arg-Arg-Arg-Glu-Glu-Glu-Thr-Glu-Glu-Glu). RESULTS: We found that CK2 activity was significantly elevated in both nuclear (p < 0.0005) and cytosolic (p < 0.0034) compartments of SCCHN tumors, relative to normal oropharyngeal mucosa. Moreover, CK2 activity in the cellular cytosolic fraction of SCCHN tumors was associated with less differentiated histologic grade (p < 0.037), positive nodal metastatic status (p < 0.056), and a poor clinical outcome (p < 0.028). Kaplan-Meier cumulative survival analysis revealed greatly reduced survival in the high-CK2 activity patient group, with high statistical significance (p < 0.023). CONCLUSIONS: These preliminary data reveal that malignant transformation of the upper aerodigestive tract mucosa is associated with altered CK2 activity. The results further suggest that dysregulation of this protein kinase may play a significant role in the pathobiology of SCCHN, and that CK2 activity may be a prognostic indicator in this malignancy.