Stability of methylation markers in head and neck squamous cell carcinoma.

BACKGROUND: As cancer progresses, methylation patterns change to promote the tumorigenic phenotype. However, stability of methylation markers over time and the extent that biopsy samples are representative of larger tumor specimens are unknown. This information is critical for clinical use of such biomarkers. METHODS: Ninety-eight patients with tumor specimens from 2 timepoints were measured for DNA methylation in the promoter regions across 4 genes. RESULTS: There were no significant differences in overall methylation of CCNA1 (cyclin A1), NDN (necdin), deleted in colorectal carcinoma (DCC), and cluster of differentiation 1a (CD1A) within paired specimens (p values = .56, .17, .66, and .58, respectively). All genes showed strong correlations between paired specimens across time. Methylation was most consistent for CCNA1 and NDN over time. CONCLUSION: This report provides the first evidence that methylation markers measured in biopsy samples are representative of gene methylation in later specimens and suggests that biopsy markers could be representative biomarkers for use in defining personalized treatment utilizing epigenetic changes. © 2015 Wiley Periodicals, Head Neck 38: E1325-E1331, 2016.

RAF inhibitors that evade paradoxical MAPK pathway activation.

Oncogenic activation of BRAF fuels cancer growth by constitutively promoting RAS-independent mitogen-activated protein kinase (MAPK) pathway signalling. Accordingly, RAF inhibitors have brought substantially improved personalized treatment of metastatic melanoma. However, these targeted agents have also revealed an unexpected consequence: stimulated growth of certain cancers. Structurally diverse ATP-competitive RAF inhibitors can either inhibit or paradoxically activate the MAPK pathway, depending whether activation is by BRAF mutation or by an upstream event, such as RAS mutation or receptor tyrosine kinase activation. Here we have identified next-generation RAF inhibitors (dubbed 'paradox breakers') that suppress mutant BRAF cells without activating the MAPK pathway in cells bearing upstream activation. In cells that express the same HRAS mutation prevalent in squamous tumours from patients treated with RAF inhibitors, the first-generation RAF inhibitor vemurafenib stimulated in vitro and in vivo growth and induced expression of MAPK pathway response genes; by contrast the paradox breakers PLX7904 and PLX8394 had no effect. Paradox breakers also overcame several known mechanisms of resistance to first-generation RAF inhibitors. Dissociating MAPK pathway inhibition from paradoxical activation might yield both improved safety and more durable efficacy than first-generation RAF inhibitors, a concept currently undergoing human clinical evaluation with PLX8394.

Economic Analysis of the Return-on-Investment of a Worksite Wellness Program for a Large Multistate Retail Grocery Organization.

OBJECTIVE: The objective of this study is to measure the return on investment (ROI) of the Price Chopper/Golub Corporation employee population who participate in wellness programs available to them. METHODS: Medical claims data, risk level, and presence of comorbidities such as diabetes and heart disease were compared in a matched retrospective cohort of participants and nonparticipants, with 2008, 2009, and 2010 serving as measurement years. Program costs and estimated savings were used to calculate an ROI of $4.33 for every dollar invested in wellness programs. RESULTS: Reductions in medical costs were observed at several risk and participation levels, with an average savings of $133 per participant and a 3-year savings estimate of $285,706. CONCLUSIONS: The positive ROI and savings estimate indicate that wellness interventions added economic value to Price Chopper/Golub Corporation.

Circulating CD4-positive lymphocyte levels as predictor of response to induction chemotherapy in patients with advanced laryngeal cancer.

BACKGROUND: Tumor regression after induction chemotherapy (ICT) identifies laryngeal cancers that are responsive to chemoradiation. Patient immune parameters have recently been associated with response to chemotherapy and may identify responding patients. A retrospective analysis was performed to determine if pretreatment, circulating T lymphocyte levels predicted ICT response in patients with advanced laryngeal cancer. METHODS: Pretreatment, circulating T lymphocyte subpopulations were correlated with response to therapy and survival. Results were compared with similar data from an identical phase II trial involving patients with oropharyngeal cancer. RESULTS: An increased percentage of CD4+ cells predicted response to ICT and suggested improved survival in patients with laryngeal, but not oropharyngeal, cancer. In the combined group of patients, increased CD4 levels predicted response to ICT. CONCLUSION: These findings demonstrate the potential importance of the immune system in chemotherapy response and clinical outcome. Differences in findings between patients with advanced laryngeal and oropharyngeal cancer may reflect different cellular immunity function in the patients with human papillomavirus (HPV)-16+ oropharyngeal cancer.

Methylglyoxal evokes pain by stimulating TRPA1.

Diabetic neuropathy is a severe complication of long-standing diabetes and one of the major etiologies of neuropathic pain. Diabetes is associated with an increased formation of reactive oxygen species and the electrophilic dicarbonyl compound methylglyoxal (MG). Here we show that MG stimulates heterologously expressed TRPA1 in CHO cells and natively expressed TRPA1 in MDCK cells and DRG neurons. MG evokes [Ca(2+)]i-responses in TRPA1 expressing DRG neurons but is without effect in neurons cultured from Trpa1(-/-) mice. Consistent with a direct, intracellular action, we show that methylglyoxal is significantly more potent as a TRPA1 agonist when applied to the intracellular face of excised membrane patches than to intact cells. Local intraplantar administration of MG evokes a pain response in Trpa1(+/+) but not in Trpa1(-/-) mice. Furthermore, persistently increased MG levels achieved by two weeks pharmacological inhibition of glyoxalase-1 (GLO-1), the rate-limiting enzyme responsible for detoxification of MG, evokes a progressive and marked thermal (cold and heat) and mechanical hypersensitivity in wildtype but not in Trpa1(-/-) mice. Our results thus demonstrate that TRPA1 is required both for the acute pain response evoked by topical MG and for the long-lasting pronociceptive effects associated with elevated MG in vivo. In contrast to our observations in DRG neurons, MG evokes indistinguishable [Ca(2+)]i-responses in pancreatic ß-cells cultured from Trpa1(+/+) and Trpa1(-/-) mice. In vivo, the TRPA1 antagonist HC030031 impairs glucose clearance in the glucose tolerance test both in Trpa1(+/+) and Trpa1(-/-) mice, indicating a non-TRPA1 mediated effect and suggesting that results obtained with this compound should be interpreted with caution. Our results show that TRPA1 is the principal target for MG in sensory neurons but not in pancreatic ß-cells and that activation of TRPA1 by MG produces a painful neuropathy with the behavioral hallmarks of diabetic neuropathy.

Inactivation or loss of TTP promotes invasion in head and neck cancer via transcript stabilization and secretion of MMP9, MMP2, and IL-6.

PURPOSE: Invasion is the critical step in progression of a precancerous lesion to squamous cell carcinoma of the head and neck (HNSCC). Invasion is regulated by multiple proinflammatory mediators. Tristetraprolin (TTP) is an mRNA-degrading protein that regulates multiple proinflammatory mediators. TTP may serve as an excellent treatment target. Rap1 is a ras-like oncoprotein that induces critical signaling pathways. In this study, the role of rap1 in TTP-mediated invasion was investigated. EXPERIMENTAL DESIGN: Using complementary approaches, we modulated TTP and altered expression of interleukin (IL)-6 and matrix metalloproteinase (MMP) 2/9, which were quantified by ELISA and zymogram. Invasion was evaluated in vitro using the oral-cancer-equivalent (OCE) three-dimensional model and in vivo in the chick chorioallantoic membrane (CAM). The role of rap1 and p38 were established using knockdown strategies. RESULTS: Downregulation of TTP significantly increased invasion via secretion of MMP9/2 and IL-6. In the novel OCE and CAM invasion models of HNSCC, cells with downregulated TTP destroyed the basement membrane to invade the underlying connective tissue. Rap1 induces p38 mitogen-activated protein kinase (p38)-mediated inactivation of TTP. Inactive TTP enhances transcript stability via binding to the 3'-untranslated region (UTR). High IL-6 and MMP9 are prognostic for poor clinical outcomes in patients with HNSCC. CONCLUSIONS: Targeting the rap1-p38-TTP cascade is an attractive novel treatment strategy in HNSCC to concurrently suppress multiple mediators of invasion.

Pretreatment dietary patterns, weight status, and head and neck squamous cell carcinoma prognosis.

BACKGROUND: Few studies have evaluated the association of diet and weight status with head and neck cancer outcomes. OBJECTIVE: The purpose of this study was to determine whether pretreatment dietary patterns and weight status are associated with head and neck cancer prognosis. DESIGN: This was a longitudinal study of 542 patients with newly diagnosed head and neck cancer who completed food-frequency questionnaires and health surveys before treatment. Clinical data were abstracted from medical records and the Social Security Death Index. Dietary patterns were identified by using principal component analysis. Cox proportional hazard models were used to examine the association of derived dietary patterns (fit by quintiles of exposure) and weight status with time to recurrence and survival, with control for covariates. RESULTS: During the study period, there were 229 deaths and 184 recurrences. Two dietary patterns were identified: a whole-foods pattern (characterized by high intakes of vegetables, fruit, fish, poultry, and whole grains) and a Western pattern (characterized by high intakes of red and processed meats, refined grains, potatoes, and French fries). In multivariable analyses, significantly fewer deaths were observed in subjects most adherent to the whole-foods pattern (HR: 0.56; 95% CI: 0.34, 0.92; P-trend = 0.01). Subjects classified as overweight or obese had significantly fewer deaths (HR: 0.65; 95% CI: 0.49, 0.85; P = 0.001) and recurrences (HR: 0.70; 95% CI: 0.52, 0.95; P = 0.02) than did normal-weight or underweight subjects. CONCLUSION: Consumption of a diet rich in vegetables, fruit, fish, poultry, and whole grains and being overweight before diagnosis with head and neck cancer are associated with a better prognosis.

Predictors of pain among patients with head and neck cancer.

OBJECTIVE To determine predictors of pain 1 year after the diagnosis of head and neck cancer. DESIGN Prospective, multisite cohort study. SETTING Three academically affiliated medical centers. PATIENTS The study population comprised 374 previously untreated patients with carcinoma of the upper aerodigestive tract. MAIN OUTCOME MEASURES Participants were surveyed before treatment and 1 year thereafter. Multivariate analyses were conducted to determine predictors of the 36-Item Short-Form Instrument (SF-36) bodily pain score 1 year after diagnosis. RESULTS The mean SF-36 bodily pain score at 1 year was 65, compared with 61 at the time of diagnosis (P = .004), and 75, the population norm (lower scores indicate worse pain). Variables independently associated with pain included pretreatment pain score (P < .001), less education (P = .02), neck dissection (P = .001), feeding tube (P = .05), xerostomia (P < .001), depressive symptoms (P < .001), taking more pain medication (P < .001), less physical activity (P = .02), and poor sleep quality (P = .006). The association between head and neck cancer pain and current smoking and problem drinking did not reach significance (P = .07 and P = .08, respectively). CONCLUSIONS Aggressive pain management may be indicated for patients with head and neck cancer who undergo neck dissections, complain of xerostomia, require feeding tubes, and have medical comorbidities. Treatment of modifiable risk factors such as depression, poor sleep quality, tobacco use, and alcohol abuse may also reduce pain and improve quality of life among patients with head and neck cancer.

Preoperative topical antimicrobial decolonization in head and neck surgery.

OBJECTIVES/HYPOTHESIS: Surgical site infections (SSIs) are an important cause of morbidity and mortality after head and neck surgery. Our primary objective was to determine the efficacy of preoperative topical antimicrobial decolonization before head and neck surgery. STUDY DESIGN: Prospective, randomized controlled trial. METHODS: This study was conducted among 84 patients presenting for head and neck surgery requiring admission to an academic medical center. Preoperative cultures were performed to identify Staphylococcus aureus carriers. Patients were randomized to preoperative topical antimicrobial decolonization with a 5-day regimen of chlorhexidine skin rinses and intranasal mupirocin coupled with standard perioperative systemic antimicrobial prophylaxis, versus standard prophylaxis alone. The main outcome was the incidence of SSIs. RESULTS: Despite a trend suggesting a decrease in SSIs with perioperative topical antimicrobial decolonization (24% vs. 10%), there was no significant difference (odds ratio, 0.34; 95% confidence interval, 0.10-1.18; P = .079). Patients with a higher American Society of Anesthesiologists score (3 vs. 1; P = .02), with more operative blood loss (P = .05), and who required operative takeback (P = .04) had a higher rate of SSIs; there was a trend suggesting a higher rate of SSIs among patients undergoing clean-contaminated surgery compared to clean cases (P = .08) and among those having received prior radiation (P = .07) or chemotherapy (P = .06). CONCLUSIONS: Preoperative antimicrobial decolonization did not significantly decrease the incidence of SSIs after head and neck surgery, but might be considered for high-risk groups despite the lack of conclusive evidence confirming efficacy. Risk factors for SSIs after head and neck surgery are identified for the first time in a prospective study.

Matted nodes: poor prognostic marker in oropharyngeal squamous cell carcinoma independent of HPV and EGFR status.

BACKGROUND: Despite better prognosis, there is a group of oropharyngeal squamous cell carcinoma (SCC) human papillomavirus (HPV)+ patients who experience treatment failure and succumb to distant metastasis. METHODS: Seventy-eight previously untreated patients nested in a concurrent chemoradiation protocol were reviewed to correlate patterns of local-regional tumor extent to distant metastasis. Biomarker assessment was: HPV in situ hybridization and epidermal growth factor receptor (EGFR) immunointensity. RESULTS: The 3-year disease-specific survival (DSS) for patients presenting with and without matted nodes was 69% and 94%, respectively (p = .003). Matted nodes were a poor prognostic factor independent of T classification, HPV, EGFR, and smoking status. For patients who were HPV+, 7 of 11 died of distant metastasis and 6 of 7 with distant metastasis had matted nodes. CONCLUSION: Matted nodes are a novel marker of poor prognosis in oropharyngeal SCC independent of established prognostic factors. Matted nodes may identify patients at risk for the development of distant metastasis who could benefit from systemic therapy, whereas patients without matted nodes may be candidates for de-escalation of therapy.

Infiltrating lymphocytes and human papillomavirus-16--associated oropharyngeal cancer.

OBJECTIVES/HYPOTHESIS: Human papillomavirus-16 (HPV-16)-associated carcinoma of the oropharynx has a favorable prognosis. Such patients have elevated CD8+ T-lymphocyte levels that correlate with response to chemotherapy and survival. Tumor-infiltrating lymphocyte (TIL) subpopulations were assessed in pretreatment biopsies from a prospective patient cohort to determine if TIL subsets differed by HPV status, clinical factors, or patient outcome or correlated with peripheral blood T-cell levels. STUDY DESIGN: Retrospective immunological correlative study of patients entered in a prospective Phase 2 clinical trial. METHODS: Measured were CD8, CD4, CD68, and Treg (FoxP3) lymphocytes by immunohistochemistry in a tissue microarray created from patients (n=46) with advanced oropharyngeal cancer. Correlations with peripheral blood levels, HPV status, expression of epidermal growth factor receptor (EGFR), clinical tumor, and patient characteristics and outcome were determined. Median follow-up was 6.6 years. RESULTS: HPV-16-positive patients had improved survival (P=.016). Degree of T-cell infiltration did not differ by HPV status but was significantly related to disease-specific survival (DSS) and overall survival (OS). Even after adjusting for HPV status, we found that CD8, FoxP3, and total T cells were significantly associated with DSS (P=.0236, P=.0040, and P=.0197, respectively) and OS (P=.0137, P=.0158, and P=.0115, respectively). Less T-cell infiltration (P=.0130) and CD4 cells in particular (P=.0792) were associated with higher EGFR expression. CONCLUSIONS: Improved outcomes are associated with increased TILs independent of HPV status and suggest the local immune response may be more related to factors such as tumor size, EGFR expression, or performance status than HPV status. Further study of larger numbers of patients and infiltrates combined with functional analysis of individual subsets may be necessary to detect significant differences in local immunity in HPV-16-related cancers.

Metronomic dosing of BH3 mimetic small molecule yields robust antiangiogenic and antitumor effects.

Bcl-2 is an antiapoptotic protein that has also been found to function as a proangiogenic signaling molecule. Improvements in antiangiogenic therapy can be engendered by metronomic dosing. Thus, we hypothesized that BH3-mimetic drugs that antagonize Bcl-2 family proteins may exert a greater efficacy when dosed metronomically. To examine this hypothesis, we employed AT101, an orally available and well-tolerated BH3-mimetic drug that has been established as effective. In a mouse xenograft model of human squamous cell carcinomas (SCC) that includes a humanized vasculature, we explored the effects of docetaxel in combination with either daily (metronomic) or weekly (bolus) doses of AT101. In addition, we explored the effect of single or combination therapy on angiogenesis and survival of endothelial or SCC cells in vitro. Metronomic AT101 therapy increased mouse survival, decreased tumor mitotic index, and decreased tumor microvessel density, compared with bolus therapy. Therapeutic potentiation was achieved by similar overall drug exposure and without altering systemic toxicities. Combinations of AT101 and docetaxel produced additive toxicity in both endothelial and SCC tumor cells. Notably, subapoptotic concentrations of AT101 potently inhibited the angiogenic potential of endothelial cells. Taken together, our findings unveil the efficacious benefits that can be achieved by metronomic delivery of BH3-mimetic drugs, in particular suggesting that SCC patients with might benefit from low-dose continuous administration of these drugs.

Higher micronutrient intake is associated with human papillomavirus-positive head and neck cancer: a case-only analysis.

No studies have investigated dietary differences between head and neck squamous cell carcinoma (HNSCC) patients with human papillomavirus (HPV)-positive tumors and patients with HPV-negative tumors. This study was designed to investigate the relationship between diet and HPV status in HNSCC patients. Cases of HNSCC were recruited from 2 clinical centers participating in the University of Michigan Head and Neck Specialized Program of Research Excellence (SPORE). HPV tissue genotyping was performed, and epidemiological and dietary data collected. Multivariable logistic regression tested whether pretreatment consumption of 12 selected micronutrients was significantly associated with HPV-positive status in 143 patients newly diagnosed with cancer of the oral cavity or pharynx. After controlling for age, sex, body mass index, tumor site, cancer stage, problem drinking, smoking, and energy intake, significant and positive associations were observed between vitamin A, vitamin E, iron, ß-carotene, and folate intake and HPV-positive status (P(trend) < 0.05), suggesting that diet may be a factor in the improved prognosis documented in those with HPV-positive HNSCC. Dietary differences by HPV status should be considered in prognostic studies to better understand the influence of diet on HNSCC survival.

Sensitization of head and neck cancer to cisplatin through the use of a novel curcumin analog.

OBJECTIVE: To determine whether a novel small molecule inhibitor derived from curcumin (FLLL32) that targets signal transducer and activator of transcription (STAT) 3 would induce cytotoxic effects in STAT3-dependent head and neck squamous cell cancer (HNSCC) cells and would sensitize tumors to cisplatin. DESIGN: Basic science. Two HNSCC cell lines, UM-SCC-29 and UM-SCC-74B, were characterized for cisplatin [cis-diammineplatinum(II) dichloride] sensitivity. Baseline expression of STAT3 and other apoptosis proteins was determined. The FLLL32 50% inhibitory concentration (IC(50)) dose was determined for each cell line, and the effect of FLLL32 treatment on the expression of phosphorylated STAT3 and other key proteins was elucidated. The antitumor efficacy of cisplatin, FLLL32, and combination treatment was measured. The proportion of apoptotic cells after cisplatin, FLLL32, or combination therapy was determined. RESULTS: The UM-SCC-29 cell line is cisplatin resistant, and the UM-SCC-74B cell line is cisplatin sensitive. Both cell lines express STAT3, phosphorylated STAT3 (pSTAT3), and key apoptotic proteins. FLLL32 downregulates the active form of STAT3, pSTAT3, in HNSCC cells and induces a potent antitumor effect. FLLL32, alone or with cisplatin, increases the proportion of apoptotic cells. FLLL32 sensitized cisplatin-resistant cancer cells, achieving an equivalent tumor kill with a 4-fold lower dose of cisplatin. CONCLUSIONS: FLLL32 monotherapy induces a potent antitumor effect and sensitizes cancer cells to cisplatin, permitting an equivalent or improved antitumor effect at lower doses of cisplatin. Our results suggest that FLLL32 acts by inhibiting STAT3 phosphorylation, reduced survival signaling, increased susceptibility to apoptosis, and sensitization to cisplatin.

Clinical and pathologic predictors of recurrence and survival in spindle cell squamous cell carcinoma.

OBJECTIVE: To determine clinicopathologic predictors of recurrence and survival in patients with spindle cell squamous cell carcinoma (SpSCC). STUDY DESIGN: Historical cohort study. SETTING: Tertiary care hospital. SUBJECTS AND METHODS: Forty-eight patients (mean age, 65.2 years; 35 men, 13 women) who underwent definitive treatment for pathologically confirmed SpSCC between 1987 and 2009 were identified and reviewed. The main outcome measures were time to recurrence and overall survival, while controlling for clinical and pathologic parameters (age, sex, TNM classification, stage, tumor subsite, smoking status, treatment modality, margin status). RESULTS: Of 48 patients, there were 25 oral cavity, 15 laryngeal, 7 oropharyngeal, and 1 maxillary sinus tumors. Treatment included surgery in 32, radiation in 9, and concurrent chemoradiation in 7 patients. The 3-year overall survival for the cohort was 62% with a median follow-up of 59 months; 52.1% (25/48) of patients developed a recurrence, and 88% (22/25) recurred locally or locoregionally. Recurrence occurred within 2 years in 72% (18/25) of patients. Age, sex, initial T and N classification, overall stage, tumor subsite, smoking status, treatment modality, and margin status were not predictive of recurrence or overall survival. CONCLUSION: Patients with SpSCC are at high risk of developing locoregional recurrence, but no measured clinical or pathologic parameter was predictive of survival. Although overall survival is similar to that of patients with conventional SCC, closer follow-up should be considered in these patients to allow earlier detection and treatment of these locally aggressive tumors.

Mucosal melanoma of the head and neck: predictors of prognosis.

OBJECTIVES: To identify significant clinical and pathological predictors of survival in mucosal melanoma of the head and neck. DESIGN: Retrospective case series. We reviewed cases of mucosal melanoma of the head and neck from a prospectively collected database after institutional review board approval. SETTING: A single academic institution. PATIENTS: Fifty-two patients with mucosal melanoma of the head and neck. RESULTS: With a median follow-up of 97 months, the median overall survival was 52 months, with a 5-year overall survival of 38%. The median disease-free survival was 15 months, with a 5-year disease-free survival of 22%. Younger age (P = .02), lower T status (P = .003), and lower American Joint Committee on Cancer stage (P < .001) were associated with better overall survival. Positive surgical margins predicted poorer overall survival (P = .01), but patients who required reexcision to achieve negative margins had outcomes that were not significantly different from those with initially negative surgical margins (P = .71). Sex, smoking history, and primary site did not affect disease-free or overall survival. Adjuvant radiotherapy and/or chemotherapy did not predict improved outcomes. Fewer mitoses (P = .02) and the absence of ulceration (P = .01) predicted improved overall survival. CONCLUSIONS: Our experience confirms the utility of current staging systems in predicting outcomes of mucosal melanoma of the head and neck and stresses the importance of achieving negative surgical margins. Pathologically, fewer mitoses and the absence of ulceration predict better outcomes and should be reported as part of routine histological profiles of mucosal melanoma. Further studies are necessary to change the paradigm of care for this rare and deadly disease.

Correlation of cellular immunity with human papillomavirus 16 status and outcome in patients with advanced oropharyngeal cancer.

OBJECTIVE: to determine whether the favorable outcome associated with human papillomavirus (HPV) 16-positive oropharyngeal cancer is related to a patient's adaptive immunity. SETTING: academic medical center. PATIENTS: forty-seven of 66 previously untreated patients (6 of 20 patients with stage III and 41 of 46 with stage IV cancer) in a prospective clinical trial of chemoradiotherapy. INTERVENTION: all patients were treated with a single course of neoadjuvant chemotherapy followed by either surgery (for nonresponders) or chemoradiotherapy. MAIN OUTCOME MEASURES: pretreatment levels (percentages and absolute counts) of CD3, CD4, CD8, natural killer, and B cells and overall white blood cell counts were measured by flow cytometry. Correlations of subsets with HPV-16 status, tumor subsite, cancer stage, T class, N class, smoking status, performance status, sex, response to chemoradiotherapy, p53 mutation type, epidermal growth factor receptor expression, and disease-specific and overall survival were determined. RESULTS: after a median follow-up of 6.6 years, improved survival was associated with an elevated percentage of CD8 cells (P = .04), a low CD4:CD8 ratio (P = .01), low epidermal growth factor receptor expression (P = .002), and HPV status (P = .02). The percentage of CD8 cells was significantly higher (P = .04) and the CD4:CD8 ratio was significantly lower (P = .02) in HPV-16-positive patients. A higher percentage of CD8 cells was associated with response to induction chemotherapy (P = .02) and complete tumor response after chemoradiotherapy (P = .045). CONCLUSION: these findings confirm previous correlations of outcome with circulating CD8 cell levels and support the conjecture that improved adaptive immunity may play a role in the favorable prognosis of patients with HPV-16-positive cancers.

Caregiver's social relations and children's oral health in a low-income urban setting.

AIM: This paper seeks to describe the social networks and support available to caregivers of young children, and their links to behavioural and clinical dimensions of children's oral health. DESIGN: A cross-sectional study was conducted on the third wave of a cohort of 612 child-caregiver pairs of the Detroit Dental Health Project (DDHP). Caregivers and their children came to a central location in Detroit where they completed interviewer-administered questionnaires, health and nutritional assessments, and received an oral examination. Caregiver's social networks were measured using the hierarchical mapping technique. Child's oral health measures included previous dental visits and untreated decay. RESULTS: Caregivers reported an average network size of approximately seven people, who on average were 37 years old. Ninety percent of members in the network lived within an hour's drive, and contact frequency occurred on average between once a week and daily. Caregivers reported receiving emotional support most frequently and money support least frequently. Caregivers with larger networks had a slightly higher probability of reporting frequent errand support. Child's age interacted with money support to predict whether or not the child had visited the dentist since the last DHHP visit and to predict the number of untreated decayed surfaces. CONCLUSIONS: The association between network characteristics and types of social support appear to be limited. There are no main effects of caregiver social network characteristics or support type on child's oral health. Having no money support appears most influential on children's oral health depending on their age.