Distinct Failure Patterns in Hypopharyngeal Cancer Patients Receiving Surgery-Based Versus Radiation-Based Treatment.

BACKGROUND: To cure advanced hypopharyngeal squamous cell carcinoma (HPSCC), primary operation followed by adjuvant (chemo-)radiotherapy (OP-CRT) or definitive chemoradiation (CCRT) are the two primary options. This study aimed to compare the failure patterns and long-term survival outcomes of HPSCC patients treated with these two strategies. PATIENTS AND METHODS: From 2007 to 2015, 198 pathologically confirmed HPSCC patients receiving either OP-CRT or CCRT were retrospectively reviewed. Failure patterns and survival outcomes stratified by the 7th American Joint Committee on Cancer staging system and treatment modalities were compared. RESULTS: One hundred and eighty-nine patients (95.4%) were stage III/IV and 62 patients (31.3%) received OP-CRT. Median follow-up duration was 4.9 years. Compared with CCRT, OP-CRT provided better 3-year local relapse-free survival for T3 (93 vs 48%, p < 0.0001), T4a (88 vs 37%, p = 0.0005) and better 3-year regional relapse-free survival for N2b+2c (93 vs 60%, p < 0.0001). Of note, for stage IVA subjects, OP-CRT provided better 3-year loco-regional relapse-free survival (85 vs 37%, p < 0.0001), marginal poor 3-year distant metastasis-free survival (62 vs 79%, p = 0.06), but comparable 3-year OS (52 vs 44%, p = 0.37) and 5-year OS (44 vs 31%, p = 0.15) compared with CCRT. CONCLUSIONS: For patients with advanced HPSCC, although OP-CRT and CCRT provided similar overall survival, failure patterns were distinct. OP-CRT provided better loco-regional control but was more likely to encounter distant metastases than CCRT. The detailed analysis of failure patterns will pave the way to improve this devastating disease.

Relationship Between Pharyngeal Residues Assessed by Bolus Residue Scale or Normalized Residue Ratio SCALE and Risk of Aspiration in Head and Neck Cancer Who Underwent Videofluoroscopy.

Dysphagia affects 60-75% of patients treated for head and neck cancer (HNC). We aimed to evaluate the association between residue severity and airway invasion severity using a videofluoroscopic swallowing study and identify risk factors for poor penetration-aspiration outcomes in patients with dysphagia treated for HNC. Penetration-Aspiration Scale (PAS) was used to assess airway invasion severity, while residue severity was assessed using both the Bolus Residue Scale (BRS) for residue location and the Normalized Residue Ratio Scale (NRRS) for residue amount. Relevant covariates were adjusted in the logistic regression models to account for potential confounding. Significantly higher abnormal PAS was reported for increased piriform sinus NRRS (NRRSp) [odds ratio (OR), 4.81; p = 0.042] with liquid swallowing and increased BRS value (OR, 1.52; p = 0.014) for semi-liquid swallowing in multivariate analysis. Tumor location, older age, and poorer Functional Oral Intake Scale (FOIS) were significant factors for abnormal PAS in both texture swallowings. After adjusting for confounding factors (sex, age, and FOIS score), NRRS model in liquid swallowing (area under the curve [AUC], 0.83; standard error = 0.04, 95% confidence interval [CI]: 0.75, 0.91) and BRS in semi-liquid swallowing (AUC, 0.83; SE = 0.04; 95% CI: 0.76, 0.91) predicted abnormal PAS. The results indicate that while assessing residue and swallowing aspiration in patients with HNC, it is important to consider age, tumor location, and functional swallowing status. The good predictability of abnormal PAS with BRS and NRRS indicated that residue location and amount were both related to the aspiration event in patients with HNC.

A new scoring system facilitating diagnosis of oral squamous malignancy on biopsy specimens.

BACKGROUND: Morphological evaluation of oral mucosal biopsy is sometimes inconclusive, which may delay the diagnosis and treatment of oral squamous malignancy. Immunohistochemical biomarkers denoting oral squamous malignancy would be clinically helpful in such scenario. METHODS: We first studied the expression patterns of four potential biomarkers (cytokeratin 13, cytokeratin 17, Ki-67 and laminin 5 gamma 2 chain) in an exploratory cohort containing 54 surgical specimens from confirmed oral squamous malignancies. A pattern score was assigned to each specific expression pattern of these four biomarkers. A total score from each specimen was then calculated by summing up the four pattern scores. A cut-off value of total score denoting oral squamous malignancy was then determined. Another 34 oral squamous malignancies that were misdiagnosed as non-malignant lesions on their pre-treatment biopsies were used as a validation cohort to test the clinical utility of this scoring system. RESULTS: In the exploratory cohort, fifty-two (96%) of the 54 confirmed oral squamous malignancies had a total score of 9 and above. In the validation cohort, thirty-one (91%) of the 34 pre-treatment oral biopsy specimens also had a total score of 9 or above, supporting the feasibility of using this scoring system to predict immediate risk of oral squamous malignancy. CONCLUSIONS: Our four-biomarker "oral squamous malignancy scoring system" provides reliable prediction for immediate risk of oral squamous malignancy on pre-treatment oral biopsies.

Investigating the health disparities in the association between lifestyle behaviors and the risk of head and neck cancer.

Many studies have reported a positive association between lower socioeconomic status (SES) and higher head and neck cancer (HNC) risk. Fewer studies have examined the impact of SES on the association between alcohol or cigarette use and HNC risk. The current case-control study (1104 HNC cases and 1363 controls) investigated the influence of education, a SES indicator, on the association between HNC and the use of alcohol, cigarettes, or betel quids in Taiwan, a country with universal health care. Our results showed a larger increase in HNC risk associated with alcohol among those with lower educational level (odds ratio [OR] = 2.07; 95% confidence interval [CI], 1.53-2.80) than those with higher educational level (OR = 1.38; 95% CI, 1.04-1.85) (heterogeneity-P = .03). Educational level had an influence on the association between alcohol use and HNC risk among those with genetic susceptibility (ALDH2-deficient) to the carcinogenic effect of alcohol. The association between cigarette or betel quid use and HNC risk was similar between the high and low educational groups. National policies and social interventions have led to the decline in the prevalence of cigarette and betel quid users in Taiwan. In contrast, due to the lack of adequate alcohol control policies, alcohol consumption in Taiwan has continued to rise. A higher impact of alcohol on HNC risk among lower SES individuals even with universal health care could be the result of insufficient alcohol control policies in Taiwan.

Validation of Alcohol Flushing Questionnaire to Identify ALDH2 Status in a Case-Control Study of Head and Neck Cancer.

BACKGROUND: Carriers of the ALDH2*2 allele have impaired alcohol metabolism and are more susceptible to the development of alcohol-related cancers, including head and neck cancer (HNC). Screening for ALDH2*2 allele may identify high-risk individuals for alcohol health education. Although genotyping of ALDH2 is the most accurate way to identify ALDH2 deficiency, it may not be practical due to the cost and requirement for genotyping service. METHODS: This study evaluated the accuracy of the alcohol flushing questionnaire to identify ALDH2 deficiency in a case-control study of HNC conducted in Taiwan using data collected from 904 patients with HNC and 1,078 controls. RESULTS: Overall, alcohol flushing questionnaire had a high sensitivity (89%) of identifying ALDH2*2 carriers among the control subjects and a good sensitivity (79%) among the patients with HNC. The sensitivity of the alcohol flushing questionnaire in identifying ALDH2*2 carriers was affected by alcohol use, with a lower sensitivity among individuals who consumed alcohol, particularly among current regular (drinking alcohol once per week or more) alcohol drinkers. CONCLUSIONS: The current validation study showed that the alcohol flushing questionnaire may be a reasonable method to identify ALDH2-deficient individuals. However, current regular users of alcohol who reported no alcohol flushing may need to undergo genotyping of ALDH2 for a more accurate assessment of the ALDH2 status.

The interplay between oral microbiome, lifestyle factors and genetic polymorphisms in the risk of oral squamous cell carcinoma.

Poor oral hygiene may lead to overgrowth of pathogenic oral bacteria, which may induce chronic inflammation to promote the oncogenesis of oral squamous cell carcinoma (OSCC). This study investigated the association between oral bacterial profile and OSCC risk in a case-control study of 138 OSCC cases and 151 controls (88 cases and 90 controls for the discovery group and 50 cases and 61 controls for the validation group). Oral bacterial profiles were characterized by targeted sequencing of the 16S rRNA gene. Three species of periodontopathogenic bacteria, Prevotella tannerae, Fusobacterium nucleatum, and Prevotella intermedia, were associated with an increased OSCC risk. This association was modified by the genetic polymorphisms of TLR2 and TLR4. Use of alcohol, betel quids and cigarettes and poor oral hygiene were associated with a higher percentage of oral periodontopathogenic bacteria. The association between alcohol and periodontopathogenic bacteria was modified by the genetic polymorphism of ALDH2, with a stronger positive association observed among the ALDH2-deficient individuals. The percentage of periodontopathogenic bacteria was positively correlated with the level of salivary IL1ß, an inflammatory cytokine. Overall, our results showed a positive association between periodontopathogenic bacteria and OSCC risk and this relationship may be influenced by lifestyle and genetic factors. Our results provided further biological support for the established association between poor oral hygiene and OSCC risk. This suggested that improving oral hygiene may reduce OSCC risk and should be part of a public health campaign to prevent the occurrence of OSCC.

Regular recreational physical activity and risk of head and neck cancer.

BACKGROUND: Although substantial evidence supports a 20-30% risk reduction of colon cancer, breast cancer, and endometrial cancer by physical activity (PA), the evidence for head and neck cancer (HNC) is limited. Three published studies on the association between PA and HNC have generated inconsistent results. The current study examined the association between recreational PA (RPA) and HNC risk with a more detailed assessment on the intensity, frequency, duration, and total years of RPA. METHODS: Data on RPA were collected from 623 HNC cases and 731 controls by in-person interview using a standardized questionnaire. The association between RPA and HNC risk was assessed using unconditional logistic regression, adjusted for sex, age, educational level, use of alcohol, betel quid, and cigarette, and consumption of vegetables and fruits. RESULTS: A significant inverse association between RPA and HNC risk was observed in a logistic regression model that adjusted for sex, age, and education (odds ratio (OR) = 0.65, 95% confidence interval (CI): 0.51-0.82). However, after further adjustment for the use of alcohol, betel quid, and cigarette, and consumption of vegetables and fruits, RPA was no longer associated with HNC risk (OR =0.97, 95% CI: 0.73-1.28). No significant inverse association between RPA and HNC risk was observed in the analysis stratified by HNC sites or by the use of alcohol, betel quid, or cigarette. CONCLUSION: Results from our study did not support an inverse association between RPA and HNC risk. The major focus of HNC prevention should be on cessation of cigarette smoking and betel chewing, reduction of alcohol drinking, and promotion of healthy diet that contains plenty of fruits and vegetables.

Allergy symptoms, serum total immunoglobulin E, and risk of head and neck cancer.

PURPOSE: Allergy symptoms have been associated with a reduced head and neck cancer (HNC) risk, while elevated blood immunoglobulin E (IgE) levels have been associated with an increased HNC risk. According to the "prophylaxis hypothesis," allergic reaction is the body's way of expelling carcinogens. IgE level may be increased by exposure to environmental carcinogens, including alcohol and cigarette smoke. We hypothesized that individuals with elevated serum IgE without allergy symptoms (i.e., asymptomatic atopic) would have the highest HNC risk. METHODS: A case-control study of HNC (576 cases and 740 controls) was conducted to evaluate the association between allergy symptoms or serum total IgE and HNC risk and the effect modification of allergy symptoms on the association between serum total IgE and HNC risk. RESULTS: Elevated serum total IgE was associated with a significantly increased HNC risk [odds ratio (OR) 1.71, 95 % confidence interval (CI) 1.21-2.42]. Having allergy symptoms was associated with a significantly reduced HNC risk (OR 0.56, 95 % CI 0.43-0.73). Compared to subjects with normal serum total IgE and no allergy symptoms, asymptomatic atopic individuals had a significantly increased HNC risk (OR 2.12, 95 % CI 1.33-3.35). CONCLUSIONS: Our results provided further evidence to support the "prophylaxis hypothesis." Further investigations regarding the immune profiles of asymptomatic atopic individuals may provide additional clues for the biological mechanisms underlying the association between allergy symptoms, IgE, and HNC risk.

A 16-year experience in treating thyroglossal duct cysts with a "conservative" Sistrunk approach.

Although Sistrunk operation is the standard method to treat thyroglossal duct cyst, the reported recurrence rates after a "classic" or "modified" Sistrunk procedure still varied from 0 to 15.8 %, indicating the existence of some technical uncertainties. While simple cystectomy has been recognized as the most important prognostic factor predicting thyroglossal duct cyst recurrence, whether other clinico-pathological parameters also affect disease recurrence has not been well studied. We retrospectively reviewed the medical records of all patients who underwent thyroglossal duct cyst surgery between June 1998 and June 2014 at our institution. Among the 180 primary patients, 160 patients received a "conservative" Sistrunk operation, while the remaining 20 patients received simple cystectomy only. Five patients (2.8 %, 5/180) had recurrence. Four of them received simple cystectomy while 1 had "conservative" Sistrunk operation. In univariable analysis, age (p = 0.02), history of previous infection (p = 0.004) and the type of resection (p = 0.001) were significantly correlated with disease recurrence. In multivariable analysis, the type of resection turned out to be the most important factor (p = 0.03) related to recurrence. In the most parsimonious model selected by backward elimination, both history of infection (p = 0.048) and the type of resection (p = 0.02) were important predictors of postoperative recurrence. Our results demonstrated that a "conservative" Sistrunk approach could provide a comparably low recurrence rate (0.6 %, 1/160) in dealing with primary thyroglossal dust cysts. Routine dissection of suprahyoid tissue may not be imperative. Overall, the type of resection and history of infection are the most important predictors of recurrence for thyroglossal duct cyst.

The interplay between alcohol consumption, oral hygiene, ALDH2 and ADH1B in the risk of head and neck cancer.

Alcohol consumption is an established risk factor for head and neck cancer (HNC). The major carcinogen from alcohol is acetaldehyde, which may be produced by humans or by oral microorganisms through the metabolism of ethanol. To account for the different sources of acetaldehyde production, the current study examined the interplay between alcohol consumption, oral hygiene (as a proxy measure for the growth of oral microorganisms), and alcohol-metabolizing genes (ADH1B and ALDH2) in the risk of HNC. We found that both the fast (*2/*2) and the slow (*1/*1+ *1/*2) ADH1B genotypes increased the risk of HNC due to alcohol consumption, and this association differed according to the slow/non-functional ALDH2 genotypes (*1/*2+ *2/*2) or poor oral hygiene. In persons with the fast ADH1B genotype, the HNC risk associated with alcohol drinking was increased for those with the slow/non-functional ALDH2 genotypes. For those with the slow ADH1B genotypes, oral hygiene appeared to play an important role; the highest magnitude of an increased HNC risk in alcohol drinkers occurred among those with the worst oral hygiene. This is the first study to show that the association between alcohol drinking and HNC risk may be modified by the interplay between genetic polymorphisms of ADH1B and ALDH2 and oral hygiene. Although it is important to promote abstinence from or reduction of alcohol drinking to decrease the occurrence of HNC, improving oral hygiene practices may provide additional benefit.

Evaluation of Fine Needle Aspiration Cytopathology in Salivary Gland Tumors under Milan System: Challenges, Misdiagnosis Rates, and Clinical Recommendations.

(1) Background: Salivary gland tumors are rare in the head and neck. To determine the need and extent of surgical intervention, fine needle aspiration (FNA) is a widely accepted tool to approach salivary gland lesions. However, the FNA cytology varies between entities, while the lack of uniform terminology makes diagnosis more challenging. Since establishing the Milan system for reporting salivary gland cytopathology (MSRSGC) has become an increasingly accepted reporting standard, further examination and detailed recommendations were needed. (2) Methods: Between April 2013 and October 2021, 375 cases with FNA and salivary gland resection were retrospectively collected. All FNA specimens were reclassified according to the criteria of MSRSGC. After surgical excision, the FNA data were compared with the histological diagnosis to estimate the risk of malignancy (ROM), the risk of neoplasm (RON), and the diagnostic accuracy for each diagnostic category. (3) Results: Our cohort's distribution of ROM and RON was similar to the MSRSGC's recommendation. Carcinoma ex pleomorphic adenoma (CXPA) has the highest rate (66.7%) of misdiagnosed as a nonneoplastic lesion or benign salivary gland tumor. Pleomorphic adenoma (PA) and Warthin's tumor were the most common benign salivary gland tumors, while the cytology diagnosis of Warthin's tumor seems more challenging than PAs. (4) Conclusions: Despite the convenience and effectiveness of MSRSGC, we suggest close follow-up, re-biopsy, or surgical removal for salivary lesions even in Milan IVA-Benign for possibly missing FNA of malignancy, mixed lesions, or prevention of malignant transformation.

Evaluation of Objective and Subjective Swallowing Outcomes in Patients with Dysphagia Treated for Head and Neck Cancer.

We evaluated objective and subjective swallowing function outcomes in patients with dysphagia treated for head and neck cancer (HNC) and identified risk factors for poor swallowing outcomes. Patients undergoing videofluoroscopic swallowing studies (VFSS) between January 2016 and March 2021 were divided into four groups according to primary tumor sites; post-treatment dysphagia was assessed. The penetration-aspiration scale (PAS) and bolus residue scale (BRS) were used to objectively assess swallowing function through VFSS. The Functional Oral Intake Scale (FOIS) was used for subjective analyses of swallowing statuses. To account for potential confounding, important covariates were adjusted for in logistic regression models. Oropharyngeal tumors were significantly more likely to have poor PAS and BRS scores than oral cavity tumors, and the patients with nasopharyngeal tumors were significantly less likely to have poor FOIS scores. Old age, having multiple HNCs, and a history of radiotherapy were associated with an increased odds of poor PAS scores (for all types of swallows), poor BRS scores (for semiliquid and solid swallows), and poor FOIS scores, respectively. This indicates using only subjective assessments may not allow for accurate evaluations of swallowing function in patients treated for HNC. Using both objective and subjective assessments may allow for comprehensive evaluations.

The Additive Effectiveness of Inspiratory Muscle Training on Glottic Closure and Subjective Voice Outcomes of Patients With Benign Lesion After Hyaluronic Acid Laryngoplasty.

OBJECTIVES: For patients with glottic insufficiency disease, injection laryngoplasty is a rapid and efficient management option that complements voice therapy. Some studies have indicated that respiratory muscle training may also show promise in patients with voice disorders. However, the effect of respiratory muscle training in patients with glottic insufficiency was reported to be limited, and whether it provides additional benefit after standard management requires further evaluation. We aimed to investigate the effectiveness of inspiratory muscle training on glottis closure and patient-reported voice quality in glottic insufficiency patients who had been treated with hyaluronic acid injection. STUDY DESIGN: Retrospective observational study. METHODS: We included 46 patients with glottic insufficiency who had undergone hyaluronic acid injection. Twenty of them had undergone inspiratory muscle training during three months. We measured patients' changes in glottic status according to the normalized glottal gap area and bowing index, as well as voice quality of life according to the voice handicap index 10 and the voice outcome survey, before and after training. RESULTS: Patients who underwent inspiratory muscle training had higher odds of experiencing better improvement in all scores. The range of odds ratios ranged from 2.5 to 6.3 for changes in scores, and from 3.8 to 22.2 for changes in score percentages. Of note, the effect of training on percentage changes in the normalized glottal gap area score was significant (P= 0.0127) after adjustment for the duration of vocal disease, body mass index and BMI, and history of gastroesophageal reflux disease. CONCLUSIONS: Inspiratory muscle training can improve the glottal gap after injection laryngoplasty, and may be applied in clinical practice.

Alternative splicing in Acad8 resulting a mitochondrial defect and progressive hepatic steatosis in mice.

Using a combination of N-ethyl-N-nitrosourea-mediated mutagenesis and metabolomics-guided screening, we identified mice with elevated blood levels of short-chain C4-acylcarnitine and increased urine isobutyryl-glycine. Genome-wide homozygosity screening, followed by fine mapping, located the disease gene to 15-25 Mb of mouse chromosome 9 where a candidate gene, Acad8, encoding mitochondrial isobutyryl-CoA dehydrogenase was located. Genomic DNA sequencing revealed a single-nucleotide mutation at -17 of the first intron of Acad8 in affected mice. cDNA sequencing revealed an intronic 28-bp insertion at the site of the mutation, which caused a frame shift with a premature stop codon. In vitro splicing assay confirmed that the mutation was sufficient to activate an upstream, aberrant 3' splice site. There was a reduction in the expression of Acad8 at both the mRNA and protein levels. The mutant mice grew normally but demonstrated cold intolerance at young age with a progressive hepatic steatosis. Homozygous mutant mice hepatocytes had abnormal mitochondria with crystalline inclusions, suggestive of mitochondriopathy. This mouse model of isobutyryl-CoA dehydrogenase deficiency could provide us a better understanding of the possible role of IBD deficiency in mitochondriopathy and fatty liver.

Investigating the association between serum human papillomavirus type 16 E7 antibodies and risk of head and neck cancer.

Human papillomavirus (HPV) is recognized as a major cause of oropharyngeal cancer (OPC) in Western countries. Less is known regarding its contribution to the OPC occurring in Asia. The current study aimed to investigate the association between antibody responses to HPV16 E7 and head and neck cancer (HNC) risk in a hospital-based case-control study conducted in Taiwan with 693 HNC cases and 1,035 controls. A positive association was observed between seropositivity to HPV16 E7 and OPC risk, whereas no significant association was found in the non-OPC cases. The increased OPC risk associated with seropositivity to HPV16 E7 was more significant among nonbetel quid or noncigarette users. Seropositivity to HPV16 E7 showed moderate agreement with P16 expression in OPC. OPC patients that were seropositive to HPV16 E7 or p16 positive were more highly educated and less likely to use alcohol, betel quids, and cigarettes compared to HPV16 E7 seronegative or p16 negative OPC patients. Furthermore, patients with p16 positive OPC were more likely to be women compared to patients with p16 negative OPC, likely owing to the low prevalence of alcohol, betel quid, and cigarette users among women. Overall, this study suggested that similar to Western countries, HPV may also be an important risk factor of OPC in Taiwan. With the declining consumption of betel quids and cigarettes in Taiwan, a higher percentage of OPC cases in Taiwan will be attributed to HPV in the future. Public health measures, including HPV vaccination, need to be implemented to prevent the occurrence of HPV-positive OPC.

PrimerZ: streamlined primer design for promoters, exons and human SNPs.

PrimerZ (http://genepipe.ngc.sinica.edu.tw/primerz/) is a web application dedicated primarily to primer design for genes and human SNPs. PrimerZ accepts genes by gene name or Ensembl accession code, and SNPs by dbSNP rs or AFFY_Probe IDs. The promoter and exon sequence information of all gene transcripts fetched from the Ensembl database (http://www.ensembl.org) are processed before being passed on to Primer3 (http://frodo.wi.mit.edu/cgi-bin/primer3/primer3_www.cgi) for individual primer design. All results returned from Primer 3 are organized and integrated in a specially designed web page for easy browsing. Besides the web page presentation, csv text file export is also provided for enhanced user convenience. PrimerZ automates highly standard but tedious gene primer design to improve the success rate of PCR experiments. More than 2000 primers have been designed with PrimerZ at our institute since 2004 and the success rate is over 70%. The addition of several new features has made PrimerZ even more useful to the research community in facilitating primer design for promoters, exons and SNPs.

Cost-effectiveness analysis of the oral cancer screening program in Taiwan.

OBJECTIVES: We assess the incremental cost-effectiveness ratio (ICER) of the oral cancer (OC) screening program in Taiwan. MATERIALS AND METHODS: We interlinked the Cancer Registry, Mortality Registry, National Vital Statistics, reimbursement database of National Health Insurance, and the National Oral Cancer Screening database of Taiwan. A total of 40,092 pathologically verified OC patients were identified and followed during 2002-2014. After stratification by stages, lifetime survival curves were estimated by a rolling extrapolation algorithm to obtain life expectancy (LE), expected years of life lost (EYLL), and lifetime medical costs (LMC). RESULTS: The LE for stages I-IV were 19.5, 14.0, 11.9, and 7.7 life-years, respectively, while those of EYLL were 7.3, 12.2, 15.4, and 18.7 life-years, respectively. The LMC for stages I-IV were US$ 65,752, 60,086, 53,675, and 47,570, respectively. We assumed no life loss for stage 0 with LMC of US$ 5380 spent for the first year after diagnosis. During 2010-2013, 967 out of the 28,018 cases detected with abnormal oral pathology by screening were found to develop OC. The ICER of the screening program was US$ 28,516 per life-year saved, which could be improved to US$ 5579 per life-year saved if all cancers transformed from abnormal oral pathology were detected before stage I. CONCLUSION: The ICER of the current OC screening program in Taiwan slightly exceeds 1 GDP (gross domestic product) per capita per life-year saved. Intensive follow-up and treatment for all patients with abnormal oral pathology would improve screening efficiency and effectiveness of prevention.

Resected specimen size: A reliable predictor of severe Frey syndrome after parotidectomy.

BACKGROUND: Frey syndrome is a common complication after parotidectomy. This study aimed to investigate the potential predictors for developing severe Frey syndrome after parotidectomy and to identify patients who may benefit from additional preventive maneuvers. METHODS: A total of 485 patients received parotidectomy because of parotid tumors at the Otolaryngology Department of the National Cheng Kung University Hospital, from July 2009 to November 2015. Only 115 of 485 patients were included in this study and to fill in a questionnaire to determine the occurrence and severity of Frey syndrome. RESULTS: A total of 115 parotidectomies were identified. 84 (73%, 84/115) patients were aware of the discomfort and were thus considered symptomatic. 39 (34%, 39/115) patients considered the symptoms apparently affected their quality of life. MSI tests showed that 56 (49%, 56/115) patients had a positive MSI test. By combining the results from symptom questionnaire and MSI test, 23 patients (20%, 23/115) had a severe form of Frey syndrome. Among all clinicopathological variables, the resected specimen size was the only significant predictor of the severe Frey syndrome group (P = 0.04). Disease pathology, tumor size, and adjuvant radiotherapy did not correlate with the severe Frey syndrome. Using receiver operating curve analysis, the best cutoff value of the resected specimen size (in largest dimension) for predicting severe Frey syndrome was 40 mm(sensitivity: 71.7%, specificity: 42.0%; area under the curve = 0.6483). The odds ratio of severe Frey syndrome with every 10 mm increase in the largest diameter of resected specimen was 1.30 (95% confidence interval, 1.01-1.68; P = 0.04). CONCLUSIONS: Resected specimen size is the only significant predictor of developing severe Frey syndrome after parotidectomy. Preventive interventions may have to be considered in high-risk patients whose resected specimen size (in largest dimension) is greater than 40 mm.

Oral hygiene and the overall survival of head and neck cancer patients.

Poor oral hygiene is an established risk factor of head and neck cancer (HNC); however, its role in the survival of HNC patients is unclear. This study evaluated the association between oral hygiene habits, including regular dental visits, frequency of tooth brushing, and use of dental floss, and the overall survival (OS) of HNC patients using interview data collected from 740 HNC patients. In addition, the interactions between oral hygiene and the polymorphisms of TLR2 and TLR4 on the OS of HNC patients were assessed. The analysis indicated that poor oral hygiene was significantly associated with poorer OS of HNC patients (hazard ratio (HR) = 1.38, 95% confidence interval (CI): 1.03-1.86). This association was modified by a single nucleotide polymorphism, rs11536889, of TLR4. A significant association between poor oral hygiene and worse survival of HNC was observed among those with the CG or CC genotype (HR = 2.32, 95% CI: 1.41-3.82) but not among those with the GG genotype (HR = 0.95, 95% CI: 0.65-1.40). Our results suggested that poor oral hygiene is not only a risk factor but may also be a prognostic factor of HNC.