Caiyun Zhang

MicroRNA Variants Increase the Risk of HPV-Associated Squamous Cell Carcinoma of the Oropharynx in Never Smokers

Background Both microRNAs and human papillomavirus (HPV) infection play an important role in the development and progression of oral squamous cell carcinoma (OSCC). In addition, microRNAs affect all facets of the immune/inflammation responses to infection, which may control HPV clearance. We thus hypothesized that microRNA polymorphisms modify the association between HPV16 seropositivity and OSCC risk. Methods Four single-nucleotide polymorphisms in microRNAs were genotyped and HPV16 serology was determined in 325 cases and 335 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using univariate and multivariable logistic regression models. Results Overall, each polymorphism had no significant main effect on OSCC risk. Compared with the risk among individuals with both miR146 rs2910164 GG genotype and HPV16 seronegativity, risk of OSCC was increased among those with CG or CC genotype and HPV16 seronegativity (OR, 1.2; 95% CI, 0.9–1.8), GG genotype and HPV16 seropositivity (OR, 3.0; 95% CI, 1.8–5.0), and CG or CC genotype and HPV16 seropositivity (OR, 4.7; 95% CI, 2.3–9.4). Similar results were found for miR149 rs2292832, miR196 rs11614913, and miR499 rs3746444. Analyses stratified by tumor sites and smoking status showed that each polymorphism significantly increased the risk of HPV16-associated squamous cell carcinoma of the oropharynx (SCCOP), and such effect modification was particularly prominent in never smokers. Conclusions Our results indicate that microRNA polymorphisms modify the risk of OSCC associated with HPV16 seropositivity, particularly in patients with SCCOP and never smokers. Larger studies are needed to verify our findings.

Effect of duration of denervation on outcomes of ansa-recurrent laryngeal nerve reinnervation

To investigate the efficacy of laryngeal reinnervation with ansa cervicalis among unilateral vocal fold paralysis (UVFP) patients with different denervation durations.

Reinnervation of Bilateral Posterior Cricoarytenoid Muscles Using the Left Phrenic Nerve in Patients with Bilateral Vocal Fold Paralysis

Objective To evaluate the feasibility, effectiveness, and safety of reinnervation of the bilateral posterior cricoarytenoid (PCA) muscles using the left phrenic nerve in patients with bilateral vocal fold paralysis. Methods Forty-four patients with bilateral vocal fold paralysis who underwent reinnervation of the bilateral PCA muscles using the left phrenic nerve were enrolled in this study. Videostroboscopy, perceptual evaluation, acoustic analysis, maximum phonation time, pulmonary function testing, and laryngeal electromyography were performed preoperatively and postoperatively. Patients were followed-up for at least 1 year after surgery. Results Videostroboscopy showed that within 1 year after reinnervation, abductive movement could be observed in the left vocal folds of 87% of patients and the right vocal folds of 72% of patients. Abductive excursion on the left side was significantly larger than that on the right side (P < 0.05); most of the vocal function parameters were improved postoperatively compared with the preoperative parameters, albeit without a significant difference (P > 0.05). No patients developed immediate dyspnea after surgery, and the pulmonary function parameters recovered to normal reference value levels within 1 year. Postoperative laryngeal electromyography confirmed successful reinnervation of the bilateral PCA muscles. Eighty-seven percent of patients in this series were decannulated and did not show obvious dyspnea after physical activity. Those who were decannulated after subsequent arytenoidectomy were not included in calculating the success rate of decannulation. Conclusions Reinnervation of the bilateral PCA muscles using the left phrenic nerve can restore inspiratory vocal fold abduction to a physiologically satisfactory extent while preserving phonatory function at the preoperative level without evident morbidity.

Meta-Analysis of MMP2, MMP3, and MMP9 Promoter Polymorphisms and Head and Neck Cancer Risk

Background The 1306 C>T, 1171 5A>6A, and 1562C>T polymorphisms of matrix metalloproteinase (MMP) 2, MMP3, and MMP9 genes, respectively, have been found to be functional and may contribute to head and neck carcinogenesis. However, the results of case-control studies examining associations between MMP polymorphisms and head and neck cancer (HNC) risk remain inconclusive. Therefore, we performed a meta-analysis to further evaluate the role of these polymorphisms in HNC development. Methods We searched PubMed, ISI Web of Knowledge, MEDLINE, Embase, and Google Scholar to identify all published case-control studies of MMP2-1306 C>T, MMP3-1171 5A>6A, and MMP9-1562 C>T polymorphisms and HNC risk in the meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between these polymorphisms and HNC risk. Results Thirteen studies were included in this meta-analysis. For MMP2-1306 C>T polymorphism, significant associations were observed under three genetic models both in overall comparison and in a hospital-based subgroup, and in oral cavity cancer and nasopharyngeal cancer under dominant model as well. For MMP3-1171 5A>6A and MMP9-1562 C>T polymorphisms, no association was found in overall comparison; however, in subgroup analyses based on ethnicity and tumor site, significant associations were detected between the MMP3-1171 5A>6A polymorphism and HNC risk in a European population and pharyngeal/laryngeal cancer under two genetic contrasts. Conclusion This meta-analysis suggests that the MMP2-1306 C>T polymorphism is associated with HNC risk, as is the MMP3-1171 5A>6A polymorphism specifically in some subgroups. Further studies with larger sample sizes are warranted.

Association between MMP1 -1607 1G>2G polymorphism and head and neck cancer risk: a meta-analysis.

Background MMP1 is an important member of the MMP endopeptidase family that plays a critical role in the development of head and neck cancer (HNC). Several studies have investigated the association between the MMP1 -1607 1G>2G polymorphism and risk of HNC, but their results have been inconsistent. Here, we conducted a meta-analysis to further explore the role of the MMP1 -1607 1G>2G polymorphism in HNC development. Methods We identified all eligible studies in the electronic databases of PubMed, ISI Web of Knowledge, MEDLINE, Embase, and Google Scholar (from January 2000 to June 2012). A meta-analysis was performed to evaluate the association between the MMP1 -1607 1G>2G polymorphism and risk of HNC by calculating odds ratios (OR) and 95% confidence interval (CIs). Results Twelve studies were included in this meta-analysis. In overall comparison, significant associations were found using the recessive and allelic contrast models (OR, 1.38; 95% CI, 1.07–1.79 and OR, 1.27; 95% CI, 1.05–1.53, respectively), but no association was detected using the dominant model. In the stratified analyses by several variables, significant associations were observed using the recessive, dominant, and allelic contrast models in the Asian population (OR, 1.64; 95% CI, 1.29–2.08; OR, 1.39; 95% CI, 1.06–1.82; and OR, 1.41; 95% CI, 1.21–1.65, respectively), European population (OR, 0.58; 95% CI, 0.40–0.84; OR, 0.64; 95% CI, 0.44–0.92; and OR, 0.68; 95% CI, 0.54–0.85, respectively), and population-based subgroup (OR, 1.24; 95% CI,1.05–1.47; OR,1.48; 95% CI,1.04–2.12; and OR, 1.22; 95% CI, 1.07–1.38, respectively). Furthermore, significant associations were detected in oral cavity cancer and nasopharyngeal cancer under the recessive model. Conclusion Our results suggest that the MMP1 -1607 1G>2G polymorphism is associated with risk of HNC and that it plays different roles in Asian and European populations. Further studies with large sample size are needed to validate our findings.

Modified partial superficial parotidectomy versus conventional superficial parotidectomy improves treatment of pleomorphic adenoma of the parotid gland

BACKGROUND Surgical treatment of pleomorphic adenoma of the parotid gland remains a subject of major debate. The investigators compared postoperative complications and surgical parameters between modified partial superficial parotidectomy and conventional superficial parotidectomy. METHODS Clinical records of 129 patients were reviewed and analyzed for clinical characteristics. RESULTS Compared with the conventional superficial parotidectomy group, the modified partial superficial parotidectomy group had significantly lower rates of auricular numbness, Freys syndrome, and obvious facial asymmetry (all P values <.05). The distance between the primary tumor capsule and satellite nodules ranged from .06 to 8.48 mm, and the greatest distance between the primary tumor capsule and satellite nodules was observed in tumors >4 cm. Furthermore, satellite nodules were more common in tumors >4 cm than in tumors <2 cm or tumors between 2 and 4 cm (all P values <.05). CONCLUSIONS Modified partial superficial parotidectomy compares favorably surgically and clinically with conventional superficial parotidectomy in certain patients.

Genetic variants in TNF-α promoter are predictors of recurrence in patients with squamous cell carcinoma of oropharynx after definitive radiotherapy

The promoter variants of TNF‐α, a major regulator of immune and inflammation responses, have been implicated in cancer development and prognosis. Thus, we investigated associations between four TNF‐α promoter variants and risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated associations of four TNF‐α polymorphisms with risk of recurrence in a cohort of 846 patients with SCCOP. Log‐rank test and multivariable Cox models were used to evaluate associations. Compared with patients with variant genotypes of the TNF‐α ‐308 and TNF‐α ‐863 polymorphisms, patients with common homozygous genotypes had worse disease‐free survival (log‐rank p = 0.0002 and p < 0.0001, respectively) and increased risk of SCCOP recurrence (HR, 1.9, 95% CI, 1.3–2.8 and HR, 1.9, 95% CI, 1.3–2.7, respectively) after multivariable adjustment. Furthermore, among patients with HPV16‐positive tumors, those with common homozygous genotypes of the TNF‐α ‐308 and ‐863 polymorphisms had worse disease‐free survival (log‐rank p = 0.005 and p = 0.007, respectively) and higher recurrence risk than patients with variant genotypes of these polymorphisms (HR, 5.1, 95% CI, 1.4–18.4 and HR, 3.7, 95% CI, 1.5–9.1, respectively), while no such significant associations were found for TNF‐α ‐857 or ‐1031 polymorphisms. Our findings suggest that TNF‐α ‐308 and ‐863 polymorphisms may modulate the risk of SCCOP recurrence in patients with HPV16‐positive tumors. However, larger studies are needed to validate these results.

Apoptotic variants as predictors of risk of oropharyngeal cancer recurrence after definitive radiotherapy

Single nucleotide polymorphisms (SNPs) in the promoter region of FAS and FASLG may alter their transcriptional activity. Thus, we determined the associations between four FAS and FASLG promoter variants (FAS1377G>A, rs2234767; 670A>G, rs1800682; FASLG844T>C, rs763110 and 124A>G, rs5030772) and the risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated the associations between FAS and FASLG genetic variants and the risk of recurrence in a cohort of 1,008 patients. The log‐rank test and multivariate Cox models were used to evaluate the associations. Compared with patients with common homozygous genotypes of FAS670 and FASLG844 polymorphisms, patients with variant genotypes had lower disease‐free survival rates (log‐rank p < 0.0001 and p < 0.0001, respectively) and an approximately threefold higher risk of SCCOP recurrence (HR, 3.2;95% CI, 2.2–4.6; and HR, 3.1; 95% CI, 2.2–4.4, respectively) after multivariate adjustment. Furthermore, among patients with HPV16‐positive tumors, those with variant genotypes of these two polymorphisms had lower disease‐free survival rates (log‐rank, p < 0.0001 and p < 0.0001, respectively) and a higher recurrence risk than did patients with common homozygous genotypes (HR, 12.9; 95% CI, 3.8–43.6; and HR, 8.1; 95% CI, 3.6–18.6, respectively), whereas no significant associations were found for FAS1377 and FASLG124 polymorphisms. Our findings suggest that FAS670 and FASLG844 polymorphisms modulate the risk of recurrence of SCCOP, particularly in patients with HPV16‐positive tumors. Larger studies are needed to validate these results.

TNF-α promoter polymorphisms and risk of recurrence in patients with squamous cell carcinomas of the nonoropharynx

Functional polymorphisms of tumor necrosis factor‐alpha (TNF‐α) may play a critical role in the regulation of immune and inflammatory responses and could affect transcriptional levels of the TNF‐α gene and thus contribute to carcinogenesis and outcomes of cancer patients. In a cohort study, we explored the associations between TNF‐α polymorphisms and risk of recurrence of squamous cell carcinoma of the nonoropharynx (SCCNOP). We used log‐rank test and multivariable Cox models to evaluate the associations between TNF‐α polymorphisms and risk of recurrence. In overall comparisons, patients with the TNF‐α ‐857 CC, TNF‐α ‐863 CC and TNF‐α ‐1031 TT genotypes had significantly worse disease‐free survival (log‐rank, p = 0.014, log‐rank, p = .020, and log‐rank, p = .002, respectively) and higher risk of disease recurrence than patients with the corresponding variant genotypes, respectively (hazard ratio [HR], 1.4, 95% CI, 1.1–1.9, HR, 1.4, 95% CI, 1.0–1.8 and HR, 1.6, 95% CI, 1.2–2.2, respectively). However, no significant association was detected for the TNF‐α ‐308 polymorphism. Moreover, in further stratified analyses based on smoking status and treatment, we found that the associations of the TNF‐α ‐857, TNF‐α ‐863 and TNF‐α ‐1031 polymorphisms with risk of recurrence were more pronounced in smokers and patients treated with chemoradiation. Our findings support a significant role of the TNF‐α ‐857, TNF‐α ‐863 and TNF‐α ‐1031 polymorphisms in recurrence of SCCNOP, especially in smokers and patients treated with chemoradiation. Future prospective studies with larger sample size are needed to confirm these findings.

Free flap combined with pectoralis major flap for reconstruction after total laryngopharyngectomy in patients with advanced hypopharyngeal carcinoma

Abstract Conclusion: The findings suggest that a pectoralis major flap combined with a free flap is a safe and reliable method of reconstruction after total pharyngolaryngectomy; with this technique, one can help these patients remain disease free, with normal swallowing function, for a relatively acceptable survival duration. Objectives: To determine the functional and oncological outcomes of a combined flap for the extensive defects after total pharyngolaryngectomy in patients with advanced squamous cell carcinoma of the hypopharynx (SCCHP). Method: This study determined the perioperative morbidity and functional and oncologic outcomes of 21 patients with advanced SCCHP who underwent total laryngopharyngectomy and reconstruction using a combination of a pectoralis major flap and a free flap. Results: The free flap and pectoralis major flap were used to reconstruct the defects for all 21 patients. Fourteen patients were reconstructed with jejunal free flaps and pectoralis major flaps; in the remaining seven patients, anterolateral thigh flaps and pectoralis major flaps were used. All the combined flaps worked well, and patients recovered normal swallowing function a mean 19.4 days after surgery. After an overall mean follow-up time of 31.3 months, 30% of patients were still alive at the time of this analysis, with no evidence of disease.