"I'm Torn": Qualitative Analysis of Dental Practitioner-Perceived Barriers, Facilitators, and Solutions to HPV Vaccine Promotion.

The human papillomavirus (HPV) vaccine can prevent HPV-related oropharyngeal cancers. Dental practitioners are uniquely positioned to promote HPV vaccines during routine dental care but experience barriers to doing so. Qualitative interviews were conducted with dental practitioners to understand barriers and inform intervention strategies to promote HPV vaccines. Dental practitioners were invited to participate in phone interviews about knowledge, self-efficacy, and the fear of negative consequences related to HPV vaccine promotion as well as feedback on potential interventions to address these barriers. Interviews were audio recorded, transcribed, and analyzed using rapid qualitative analysis with a sort-and-sift matrix approach. Interviews were completed with 11 practitioners from six dental clinics (avg. 31 min). Though most thought HPV vaccination was important, they lacked detailed knowledge about when and to whom the vaccine should be recommended. This led to a hypothesized need for discussions of sexual history, feelings of limited self-efficacy to make the recommendation, and fear of patient concerns. Still, practitioners were supportive of additional training opportunities and provided input into specific interventions. The nuance of how these barriers were described by practitioners, as well as the possible solutions they identified, will help shape future interventions supporting HPV vaccine promotion in dental care.

Network meta-analysis of studies included in the Clinical Practice Guideline on the nonsurgical treatment of chronic periodontitis.

AIM: The recent ADA-commissioned Clinical Practice Guideline on the nonsurgical treatment of chronic periodontitis has provided the most exhaustive library of clinical trials on scaling and root planing (SRP) with or without adjuncts. This network meta-analysis (NMA) compared the adjuncts against each other. MATERIALS AND METHODS: A star-shaped NMA was performed based on 36 indirect comparisons of clinical attachment-level (CAL) gains among nine adjuncts in 74 studies from the Clinical Practice Guideline. RESULTS: All pairwise differences were accompanied by wide confidence intervals, and none of the adjuncts were statistically significantly superior to another. Local doxycycline hyclate and photodynamic therapy with a diode laser had the highest probabilities for ranking first and second, respectively. Publication bias was evident, with fewer than expected studies with small effects. The lack of these studies inflated the treatment effects by an estimated by 20%. CONCLUSIONS: Adjuncts improve CAL gain by about a third of a mm over 6-12 months compared with SRP alone, but no significant differences were found among the adjuncts. The patient-perceived benefit of this gain is unclear because CAL is a physical measure made by the clinician and not a patient-oriented outcome. Publication bias inflated the observed treatment effects.

Systemic Inflammatory Biomarkers and Their Association With Periodontal and Diabetes-Related Factors in the Diabetes and Periodontal Therapy Trial, A Randomized Controlled Trial.

BACKGROUND: The present study evaluates effects of non-surgical periodontal treatment on serum biomarkers in patients with type 2 diabetes mellitus (t2DM) and chronic periodontitis who participated in the Diabetes and Periodontal Therapy Trial (DPTT); and associations among diabetes markers, serum biomarkers, and periodontal measures in these patients. METHODS: DPTT participants randomized to receive immediate or delayed non-surgical periodontal therapy were evaluated at baseline and 6 months. Serum samples from 475 participants with 6-month data were analyzed for the following biomarkers: 1) high sensitivity C-reactive protein; 2) E-selectin; 3) tumor necrosis factor (TNF)-α; 4) vascular cell adhesion molecule (VCAM); 5) interleukin (IL)-6; 6) IL-8; 7) intercellular adhesion molecule; and 8) IL-10. Changes in biomarker levels from baseline and correlations among biomarker levels and clinical findings were analyzed. RESULTS: No differences between treatment and control groups were observed for any biomarkers at baseline or 6 months (P >0.05 for all variables). VCAM levels increased by an average (standard deviation) of 17.9 (99.5); ng/mL (P = 0.006) and E-selectin decreased by 2.33 (16.08) ng/mL (P = 0.03) in the treatment group after 6 months. E-selectin levels were significantly correlated with DM-related variables (hemoglobin A1c [HbA1c] and fasting glucose) at baseline and with 6-month change in both groups; no significant correlations were found among periodontal clinical parameters and serum biomarkers or DM-related variables. Neither HbA1c or body mass index varied during the study period in either study group. CONCLUSIONS: Non-surgical periodontal therapy and periodontal disease severity were not associated with significant changes in serum biomarkers in DPTT participants during the 6-month follow-up. Correlations among changes in E-selectin, IL-6, and DM-related variables suggest that t2DM may be the primary driver of systemic inflammation in these patients.

Serum Markers of Bone Turnover and Angiogenesis in Patients With Bisphosphonate-Related Osteonecrosis of the Jaw After Discontinuation of Long-Term Intravenous Bisphosphonate Therapy.

PURPOSE: To analyze serum markers of bone turnover, angiogenesis, endocrine function, and inflammation in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) who discontinued long-term intravenous bisphosphonate (BP) therapy. PATIENTS AND METHODS: Serum samples were obtained from 25 BRONJ patients who had discontinued long-term intravenous BP therapy for an average of 11.4 ± 8.7 months and 48 non-BRONJ controls who continued receiving intravenous BP therapy. Samples were analyzed for total alkaline phosphatase, bone-specific alkaline phosphatase, osteocalcin, C-telopeptide, vascular endothelial growth factor, triiodothyronine, thyroxine, thyroid-stimulating hormone, 25-hydroxyvitamin D, and C-reactive protein. RESULTS: The mean number of BP infusions was significantly higher in BRONJ patients compared with controls (38.4 ± 26.3 infusions vs 18.8 ± 7.2 infusions, P < .0001); however, the duration of BP therapy was not significantly different between the groups (P = .23). Overall, there were no significant differences in any of the markers between BRONJ patients and controls (all P values ≥ .16). In a subgroup analysis that matched BRONJ patients and controls according to mean age and number of BP infusions (10 BRONJ patients and 48 controls), log10 vascular endothelial growth factor (2.9 ± 0.4 pg/mL vs 2.4 ± 0.4 pg/mL, P < .001) and C-reactive protein (34 ± 26 mg/L vs 13 ± 8 mg/L, P < .01) levels were significantly higher in BRONJ patients compared with controls. Within BRONJ patients, none of the serum markers were correlated with duration of BP discontinuation. CONCLUSIONS: Levels of bone turnover and endocrine markers in BRONJ patients who discontinue long-term intravenous BP therapy are similar to those in non-BRONJ controls receiving intravenous BP therapy. However, levels of angiogenesis and inflammation markers are higher in BRONJ patients who discontinue long-term intravenous BP therapy. The prolonged skeletal half-life of BPs may suppress bone turnover markers in BRONJ patients for several years after discontinuation of intravenous BP therapy, suggesting an extended effect on bone homeostasis.

Association between low-dose aspirin and periodontal disease: results from the continuous national health and nutrition examination survey (NHANES) 2011-2012.

AIM: Low-dose aspirin has been hypothesized as being a potential host modulatory agent for periodontitis treatment. We investigated the relationship between low-dose aspirin use and periodontitis prevalence in the continuous National Health and Nutrition Examination Survey, 2011-2012. METHODS: We analysed n = 2335 adult men and women who received a full-mouth periodontal examination and responded to an aspirin use questionnaire. Periodontal disease was defined as severe, moderate or mild according to established case definitions. Mean full-mouth probing depth, attachment loss and tooth loss were also considered. Low-dose aspirin was defined by any self-reported, physician prescribed aspirin use of ≤162 mg/day. RESULTS: Participants had mean age (SE) 55.8 years (0.42). The prevalences of periodontitis and low-dose aspirin use were 49.5% and 25% respectively. In multivariable logistic regression models controlling for age, sex, race, socioeconomic variables and comorbidities, the odds ratios [95%CI] for moderate or severe periodontitis among low-dose aspirin users (versus non-users) were: 0.91 [0.56-1.50] and 1.06 [0.74-1.50] respectively. Results were unchanged among participants without diabetes or coronary heart disease. CONCLUSIONS: Within the limitations of this cross-sectional study we conclude that low-dose aspirin is not associated with prevalent periodontal status in a nationally representative sample of US adults.

Factors associated with the clinical response to nonsurgical periodontal therapy in people with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a growing health problem worldwide. People with T2DM are at risk of experiencing periodontitis and likely require treatment. Using data from the national multicenter Diabetes and Periodontal Therapy Trial (DPTT), the authors assessed patient-based characteristics associated with the clinical response to nonsurgical therapy. METHODS: The DPTT investigators randomly assigned adults with T2DM (hemoglobin A1c [HbA1c] ≥ 7 percent and < 9 percent) and moderate to advanced periodontitis to receive immediate or delayed therapy (scaling and root planing, oral hygiene instruction, chlorhexidine rinse). The investigators assessed probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and medical conditions at baseline, three months and six months. Six-month changes in mean PD, CAL and BOP defined the treatment response. Complete data were available for 473 of 514 DPTT participants. The authors used multiple regression models to evaluate participant-level factors associated with the response. RESULTS: More severe baseline PD, CAL and BOP were associated with greater improvements in these same measurements (P < .0001). Hispanic participants experienced greater improvements in PD and CAL than did non-Hispanic participants (P < .0001). Obese participants (those with a body mass index > 30 kilograms per square meter) experienced greater reductions in PD and BOP than did participants who were not obese (P < .001). Age, sex, HbA1c values, diabetes duration, and smoking were not associated with change in any outcome (P > .1). CONCLUSIONS: In patients with T2DM, baseline disease severity was associated with the clinical response to nonsurgical periodontal therapy. Body mass index and Hispanic ethnicity-but not glycemic control, diabetes duration or smoking-also may be useful in predicting clinical changes in this population.

Periodontal disease as a risk factor for bisphosphonate-related osteonecrosis of the jaw.

BACKGROUND: Previous case reports and animal studies suggest that periodontitis is associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ). This case-control study is conducted to evaluate the association between clinical and radiographic measures of periodontal disease and BRONJ. METHODS: Twenty-five patients with BRONJ were matched with 48 controls. Trained examiners measured probing depth, clinical attachment level (CAL), and bleeding on probing on all teeth except third molars and gingival and plaque indices on six index teeth. Alveolar bone height was measured from orthopantomograms. Most patients with BRONJ were using antibiotics (48%) or a chlorhexidine mouthrinse (84%) at enrollment. Adjusted comparisons of patients with BRONJ versus controls used multiple linear regression. RESULTS: The average number of bisphosphonate (BP) infusions was significantly higher in patients with BRONJ compared with controls (38.4 versus 18.8, P = 0.0001). In unadjusted analyses, patients with BRONJ had more missing teeth (7.8 versus 3.1, P = 0.002) and higher average CAL (2.18 versus 1.56 mm, P = 0.047) and percentage of sites with CAL ≥3 mm (39.0 versus 23.3, P = 0.039) than controls. Also, patients with BRONJ had lower average bone height (as a fraction of tooth length, 0.59 versus 0.62, P = 0.004) and more teeth with bone height less than half of tooth length (20% versus 6%, P = 0.001). These differences remained significant after adjusting for age, sex, smoking, and number of BP infusions. CONCLUSIONS: BRONJ patients have fewer teeth, greater CAL, and less alveolar bone support compared with controls after adjusting for number of BP infusions. Group differences in antibiotics and chlorhexidine rinse usage may have masked differences in the other clinical measures.

Teriparatide therapy for bisphosphonate-related osteonecrosis of the jaw: a case report and narrative review.

Bisphosphonates (BP), potent antresorptive agents, play a key role in managing osteolytic bone disorders including osteoporosis, Paget's disease, bone metastasis, and multiple myeloma. However, their long-term administration is associated with increased risk for bisphosphonate-related osteonecrosis of the jaw (BRONJ) development. At present, there is no curative therapy for BRONJ, and patients are often treated palliatively with antibiotics, antimicrobial mouth rinses, and debridement of necrotic bone. This article highlights a new treatment modality that may be beneficial to a subset of osteoporosis patients suffering from BRONJ. Here we report a BRONJ case that was initially unresponsive to conservative treatment, but subsequently responded to teriparatide (recombinant human PTH1-34) therapy.

Dental procedures and risk of experiencing a second vascular event in a Medicare population.

BACKGROUND: Practice guidelines historically have recommended postponing dental care after ischemic vascular events. The authors examined an administrative data set to determine whether dental procedures increased patients' risk of experiencing a second vascular event. METHODS: The authors examined a data set of 50,329 participants in the Medicare Current Beneficiary Survey to identify those who had had a vascular event (n = 2,035) and a second event (n = 445) while in the survey. They used Cox proportional hazards regression to study associations between dental procedures performed within 30, 60, 90 or 180 days after a first event and the risk of experiencing a second vascular event. RESULTS: Dental procedures of any kind, and invasive procedures considered separately, were not associated with patients' risk of experiencing second vascular events across all periods examined. Most hazard ratios associated with dental procedures were less than 1.0, although none differed significantly from 1.0. CONCLUSIONS: The authors found that community-dwelling Medicare beneficiaries who underwent dental procedures within 30 to 180 days after an ischemic vascular event, including those that produce a bacteremia consistently, were not at an increased risk of experiencing a second event. CLINICAL IMPLICATIONS: The results of this study suggest that clinicians should reassess historical recommendations that dental care in this population be postponed for as long as six months after an ischemic vascular event.

Periodontal disease, tooth loss and incident rheumatoid arthritis: results from the First National Health and Nutrition Examination Survey and its epidemiological follow-up study.

AIMS: Infection may be a rheumatoid arthritis (RA) risk factor. We examined whether signs of periodontal infection were associated with RA development in the First National Health and Nutrition Examination Survey and its epidemiological follow-up study. MATERIAL AND METHODS: In 1971-1974, 9702 men and women aged 25-74 were enrolled and surveyed longitudinally (1982, 1986, 1987, 1992). Periodontal infection was defined by baseline tooth loss or clinical evidence of periodontal disease. Baseline (n = 138) and incident (n = 433) RA cases were defined via self-report physician diagnosis, joint pain/swelling, ICD-9 codes (714.0-714.9), death certificates and/or RA hospitalization. RESULTS: Adjusted odds ratios (ORs) (95% CI) for prevalent RA in gingivitis and periodontitis (versus healthy) were 1.09 (0.57, 2.10) and 1.85 (0.95, 3.63); incident RA ORs were 1.32 (0.85, 2.06) and 1.00 (0.68, 1.48). The ORs for prevalent RA among participants missing 5-8, 9-14, 15-31 or 32 teeth (versus 0-4 teeth) were 1.74 (1.03, 2.95), 1.82 (0.81, 4.10), 1.45 (0.62, 3.41) and 1.30 (0.48, 3.53); ORs for incident RA were 1.12 (0.77, 1.64), 1.67 (1.12, 2.48), 1.40 (0.85, 2.33) and 1.22 (0.75, 2.00). Dose-responsiveness was enhanced among never smokers. The rate of death or loss-to-follow-up after 1982 was two- to fourfold higher among participants with periodontitis or missing ≥9 teeth (versus healthy participants). CONCLUSIONS: Although participants with periodontal disease or ≥5 missing teeth experienced higher odds of prevalent/incident RA, most ORs were non-statistically significant and lacked dose-responsiveness. Differential RA ascertainment bias complicated the interpretation of these data.

Serum inflammatory mediators in pregnancy: changes after periodontal treatment and association with pregnancy outcomes.

BACKGROUND: The purposes of this study were to determine: 1) if periodontal treatment in pregnant women before 21 weeks of gestation alters levels of inflammatory mediators in serum; and 2) if changes in these mediators are associated with birth outcomes. METHODS: A total of 823 pregnant women with periodontitis were randomly assigned to receive scaling and root planing before 21 weeks of gestation or after delivery. Serum obtained between 13 and 16 weeks, 6 days (study baseline) and 29 to 32 weeks of gestation was analyzed for C-reactive protein; prostaglandin E(2); matrix metalloproteinase-9; fibrinogen; endotoxin; interleukin (IL)-1 beta, -6, and -8, and tumor necrosis factor-alpha. Cox regression, multiple linear regression, and the t, chi(2), and Fisher exact tests were used to examine associations among the biomarkers, periodontal treatment, and gestational age at delivery and birth weight. RESULTS: A total of 796 women had baseline serum data, and 620 women had baseline and follow-up serum and birth data. Periodontal treatment did not significantly alter the level of any biomarker (P >0.05). Neither baseline levels nor the change from baseline in any biomarker were significantly associated with preterm birth or infant birth weight (P >0.05). In treatment subjects, the change in endotoxin was negatively associated with the change in probing depth (P <0.05). CONCLUSIONS: Non-surgical mechanical periodontal treatment in pregnant women, delivered before 21 weeks of gestation, did not reduce systemic (serum) markers of inflammation. In pregnant women with periodontitis, levels of these markers at 13 to 17 weeks and 29 to 32 weeks of gestation were not associated with infant birth weight or a risk for preterm birth.

Bisphosphonate-related osteonecrosis of the jaw: clinical features, risk factors, management, and treatment outcomes of 26 patients.

PURPOSE: To report the clinical features, risk factors, management, and treatment outcomes of nitrogen-containing bisphosphonate (n-BIS)-related osteonecrosis of the jaw (BRONJ). PATIENTS AND METHODS: Patients with suspected BRONJ were referred to the School of Dentistry for evaluation and treatment. RESULTS: A total of 26 patients (9 men and 17 women, mean age 64 years) were diagnosed with BRONJ. Of the 26 patients, 23 had received n-BIS therapy for cancer and 3 for osteoporosis. BRONJ lesions were noted more frequently in the mandible and in the posterior sextants. Of the 26 patients, 16 had developed BRONJ after dentoalveolar procedures, and 10 had developed it spontaneously. The mean interval to development of BRONJ was shorter in the patients with cancer receiving intravenous n-BIS than in the patients with osteoporosis receiving oral n-BIS (37.1 versus 77.7 months, P = .02). Using the American Association of Oral and Maxillofacial Surgeons staging system, 2 patients were diagnosed with stage I lesions, 19 with stage II, and 5 with stage III lesions. The initial management of BRONJ was nonsurgical, with debridement performed at subsequent visits, if needed. The BRONJ lesions healed completely in 4 patients, healed partially in 8, remained stable in 7, and progressed in 7. The spontaneous lesions responded favorably to BRONJ management compared with lesions that developed after dentoalveolar procedures (P = .01). No significant difference was found in response to BRONJ management between patients who had continued or discontinued n-BIS therapy after the BRONJ diagnosis (P = .54). CONCLUSIONS: Long-term n-BIS therapy and recent dental procedures are consistent findings in patients with BRONJ. Spontaneous BRONJ lesions respond favorably to current BRONJ treatment strategies.

A pilot study of glycosylated hemoglobin levels in periodontitis cases and healthy controls.

BACKGROUND: Periodontitis is associated with glycemic control in patients with diabetes. The purpose of this study was to determine if glycosylated hemoglobin is elevated in patients with periodontitis who have not been diagnosed with diabetes. METHODS: Glycosylated hemoglobin (HbA1c) was assessed using a chairside test in 59 adults without diabetes but with periodontitis (having at least five teeth with probing depth [PD] > or =5 mm, bleeding on probing [BOP], and clinical attachment or radiographic bone loss) and 53 healthy controls (PDs < or =4 mm and BOP < or =15%). Groups were compared using the t test and linear regression. Patients with HbA1c levels > or =6% were compared using the Fisher exact test and logistic regression. RESULTS: Periodontitis cases were more likely than controls to be male (68% versus 38%; P = 0.002) and current or former smokers (P = 0.002). Cases had significantly higher body mass index (BMI) than controls (27.6 kg/m(2) versus 25.5 kg/m(2); P = 0.018) but were of similar age (51.3 years versus 50.9 years; P = 0.89). Unadjusted mean HbA1c levels did not differ significantly between cases and controls (5.66% +/- 0.56% versus 5.51% +/- 0.44%; P = 0.12). After adjustments for age, gender, BMI, and current smoking, mean HbA1c was significantly higher in cases (between-group difference, 0.21%; P = 0.046). A higher proportion of cases (27.3%) than controls (13.2%) had HbA1c values > or =6%, although this difference was not statistically significant (P >0.1). CONCLUSIONS: Periodontitis is associated with a slight elevation in glycosylated hemoglobin. The clinical significance of this difference remains to be determined. This preliminary finding is consistent with earlier reports that periodontitis is associated with elevated blood glucose in adults without diabetes and may increase one's risk for type 2 diabetes.

Utility of panoramic radiographs in detecting cervical calcified carotid atheroma.

OBJECTIVE: The objective of this study was to determine the utility of panoramic radiographs for detecting extracranial calcified carotid atheroma and carotid luminal stenosis. STUDY DESIGN: Panoramic radiographs were obtained on 52 adult participants who had carotid ultrasound examination. Extent of carotid calcification and stenosis was determined by a cardiologist from ultrasound reports, which were considered gold standard assessments. A trained and calibrated oral and maxillofacial radiologist interpreted the radiographs for presence or absence of carotid calcifications. We examined the utility of panoramic radiographs to diagnose any carotid artery changes (diagnostic scheme 1) or only moderate to severe changes (scheme 2). Generalized estimating equations were used to account for clustering of observations within subjects. RESULTS: Under diagnostic schemes 1 and 2, radiographs had low sensitivity to detect carotid calcifications (31.1% and 25.0%, respectively) and stenoses (22.7% and 21.4%, respectively). CONCLUSIONS: When compared to ultrasonography, panoramic radiography is not a reliable means to detect carotid artery calcifications or stenoses.

No association between selected candidate gene polymorphisms and severe chronic periodontitis.

BACKGROUND: Chronic periodontitis (CP) risk is influenced by environmental and genetic factors. Using a case-control design, we tested for associations between CP and selected DNA sequence variations (single nucleotide polymorphisms [SNPs]) in or near genes coding for proteins that play a role in the pathogenesis of this disease. METHODS: DNA was analyzed from 219 whites who were examined clinically. Cases (N=137) were >or=35 years of age with eight or more teeth having >or=5 mm of proximal clinical attachment loss. Controls (N=82) were >or=45 years of age with minimal or no proximal attachment loss or pocketing. Nine diallelic polymorphisms (gene and SNP descriptor) were studied in subjects: cytotoxic T-lymphocyte antigen-4 (CTLA-4, 49 A>G), human beta-defensin-1 (DEFB1, 692 G>A), intercellular adhesion molecule-1 (ICAM-1, 1548 A>G), Fas ligand (fasL, -844 C>T), inducible costimulator (ICOS, 3990 G>T), interleukin-6 (IL-6, -174 G>C), cysteine-cysteine chemokine receptor-5 (CCR5, 59653 C>T), osteoprotegerin (OPG, 245 T>G), and osteopontin (OPN, 707 C>T). Genotypes were determined using an automated fluorogenic 5'-nuclease, polymerase chain reaction-based assay. Gender and smoking history (pack-years) were included as covariates in logistic regression analyses. RESULTS: Heavy smoking (>10 pack-years) and male gender were significantly associated with disease (P<0.001). For all SNPs tested, the allele frequencies and distributions of genotypes did not differ between cases and controls (P>0.05). No unadjusted or adjusted odds ratios (comparing genotypes in cases versus controls) were significantly different than 1.0 (P>0.05) under any additive, dominant, or recessive inheritance model. CONCLUSIONS: None of the SNPs tested were strongly associated with generalized severe chronic periodontitis in North American whites. A potentially more fruitful approach in future studies will be to test for associations between periodontitis and haplotype blocks constructed from either multiple SNPs in candidate gene regions or from panels of markers that span the entire genome.

Periodontal diseases.

The periodontal diseases are highly prevalent and can affect up to 90% of the worldwide population. Gingivitis, the mildest form of periodontal disease, is caused by the bacterial biofilm (dental plaque) that accumulates on teeth adjacent to the gingiva (gums). However, gingivitis does not affect the underlying supporting structures of the teeth and is reversible. Periodontitis results in loss of connective tissue and bone support and is a major cause of tooth loss in adults. In addition to pathogenic microorganisms in the biofilm, genetic and environmental factors, especially tobacco use, contribute to the cause of these diseases. Genetic, dermatological, haematological, granulomatous, immunosuppressive, and neoplastic disorders can also have periodontal manifestations. Common forms of periodontal disease have been associated with adverse pregnancy outcomes, cardiovascular disease, stroke, pulmonary disease, and diabetes, but the causal relations have not been established. Prevention and treatment are aimed at controlling the bacterial biofilm and other risk factors, arresting progressive disease, and restoring lost tooth support.

Identification of a gene expression signature associated with recurrent disease in squamous cell carcinoma of the head and neck.

Molecular studies of squamous cell carcinoma of the head and neck (HNSCC) have demonstrated multiple genetic abnormalities such as activation of various oncogenes (Ras, Myc, epidermal growth factor receptor, and cyclin D1), tumor suppressor gene inactivation (TP53 and p16), and loss of heterozygosity at numerous chromosomal locations. Despite these observations, accurate and reliable biomarkers that predict patients at highest risk for local recurrence have yet to be defined. In an effort to identify gene expression signatures that may serve as biomarkers, we studied 41 squamous cell carcinoma tumors (25 primary and 16 locally recurrent) from various anatomical sites and 13 normal oral mucosal biopsy samples from healthy volunteers with microarray analysis using Affymetrix U133A GeneChip arrays. Differentially expressed genes were identified by calculating generalized t tests (P < 0.001) and applying a series of filtering criteria to yield a highly discriminant list of 2890 genes. Hierarchical clustering and image generation using standard software were used to visualize gene expression signatures. Several gene expression signatures were readily identifiable in the HNSCC tumors, including signatures associated with proliferation, extracellular matrix production, cytokine/chemokine expression, and immune response. Of particular interest was the association of a gene expression signature enriched for genes involved in tumor invasion and metastasis with patients experiencing locally recurrent disease. Notably, these tumors also demonstrated a marked absence of an immune response signature suggesting that modulation of tumor-specific immune responses may play a role in local treatment failure. These data provide evidence for a new gene expression-based biomarker of local treatment failure in HNSCC.