Vascular priming enhances chemotherapeutic efficacy against head and neck cancer.

PURPOSE: The need to improve chemotherapeutic efficacy against head and neck squamous cell carcinomas (HNSCC) is well recognized. In this study, we investigated the potential of targeting the established tumor vasculature in combination with chemotherapy in head and neck cancer. METHODS: Experimental studies were carried out in multiple human HNSCC xenograft models to examine the activity of the vascular disrupting agent (VDA) 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in combination with chemotherapy. Multimodality imaging (magnetic resonance imaging, bioluminescence) in conjunction with drug delivery assessment (fluorescence microscopy), histopathology and microarray analysis was performed to characterize tumor response to therapy. Long-term treatment outcome was assessed using clinically-relevant end points of efficacy. RESULTS: Pretreatment of tumors with VDA prior to administration of chemotherapy increased intratumoral drug delivery and treatment efficacy. Enhancement of therapeutic efficacy was dependent on the dose and duration of VDA treatment but was independent of the chemotherapeutic agent evaluated. Combination treatment resulted in increased tumor cell kill and improvement in progression-free survival and overall survival in both ectopic and orthotopic HNSCC models. CONCLUSION: Our results show that preconditioning of the tumor microenvironment with an antivascular agent primes the tumor vasculature and results in enhancement of chemotherapeutic delivery and efficacy in vivo. Further investigation into the activity of antivascular agents in combination with chemotherapy against HNSCC is warranted.

Chronic periodontitis-human papillomavirus synergy in base of tongue cancers.

OBJECTIVE: To assess whether chronic periodontitis history predicts human papillomavirus (HPV) status in patients with base of tongue cancers. DESIGN: Case-control study using existing patient data. SETTING: Roswell Park Cancer Institute. PATIENTS: Thirty patients newly diagnosed with base of tongue squamous cell carcinoma between 1999 and 2005 for whom both tumor samples and periodontal records were available. Patients younger than 21 years, edentulous, immunocompromised, and those with a history of cancer were excluded. Periodontitis history was assessed on the basis of alveolar bone loss (in millimeters) from panoramic radiographs by one examiner who was blinded to cancer status. MAIN OUTCOME MEASURE: HPV-16 and HPV-18 DNA were identified on paraffin-embedded tumor samples by polymerase chain reaction. Multiple logistic regression was used to estimate odds ratios and 95% confidence intervals. RESULTS: The prevalence of tumors positive for HPV-16 DNA was 21 of 30 (70%). None of the samples were positive for HPV-18 DNA. Compared with participants with HPV-negative tumors, patients with HPV-positive tumors had significantly higher mean alveolar bone loss (3.90 mm vs 2.85 mm, P = .01). After adjustment for age at diagnosis, sex, race/ethnicity, alcohol use, smoking status, and number of missing teeth, every millimeter of alveolar bone loss was associated with an approximately 4-fold (odds ratio, 3.96; 95% confidence interval, 1.18-13.36) increased risk of HPV-positive tumor status. Number of missing teeth was not associated with tumor HPV status (odds ratio, 0.95; 95% confidence interval, 0.74-1.21). CONCLUSIONS: Chronic periodontitis may be a significant factor in the natural history of HPV infection in patients with base of tongue cancers. Additional confirmation in larger studies is required.

Increased human buccal cell autofluorescence is a candidate biomarker of tobacco smoking.

Human buccal cells display diverse changes that are associated with smoked and smokeless tobacco, and clinicopathologic studies have correlated human buccal cell changes with oral cancer. Reported herein are the results of studies that were undertaken to identify a high-throughput technology that would advance efforts to use human buccal cells. We report that (a) a relatively large (mean +/- SD, 2.1 +/- 1.4 x 10(5) cells) population of human buccal cells can be collected in a noninvasive manner with a toothbrush and purified (>98% human buccal cells; n = 138 samples of the oral mucosa; n = 69 donors); (b) despite their large size (diameter, approximately 65 microm), the human buccal cells were analyzed successfully with a single laser cytometer (FACScan) and an advanced multispectral cytometer (FACSAria) having three lasers (excitation = 488, 633, and 407 nm wavelengths) and nine distinct emission channels; (c) cytometry revealed that the buccal cells expressed a high level of autofluorescence that was displayed over a broad spectrum (450-780 nm wavelength); (d) autofluorescence of human buccal cells collected from the left and right cheek was consistent, illustrating the reproducibility of the sample collection and assay procedure; (e) human buccal cell autofluorescence differed significantly among 69 adult subjects; and (f) a statistical difference (P = 0.018) between current, former, and never smokers. Summarily, this report is thought to be the first to show the application of flow cytometry for assaying human buccal cells and identifies buccal cell autofluorescence as a candidate biomarker of tobacco smoking.