Junfeng Wu

Oral human papillomavirus infection, sexual behaviors and risk of oral squamous cell carcinoma in southeast of China: A case-control study

BACKGROUND The causal association between human papillomavirus (HPV) and oral squamous cell carcinoma (OSCC) remains controversial. Most of previous studies did not consider the potential modification effect of sexual behaviors when evaluating the role of HPV infection in OSCC risk. OBJECTIVES To explore the independent and joint effects of oral HPV infection and sexual behaviors on OSCC in Chinese population. STUDY DESIGN A case-control study was conducted from September 2012 to September 2015 in Fujian, China. HPV DNA genotypes were detected in tumor tissues of 178 OSCC patients and oral exfoliated cells of 189 frequency-matched controls using flow-through hybridization and gene chip. Epidemiologic data were collected with a structured questionnaire by face-to-face interviews. Odds ratios (ORs) and 95% confidence interval (CI) were estimated with unconditional logistic regression models. RESULTS The overall HPV prevalence was 14.04% in OSCC patients and 3.17% in controls. HPV-18 was the most prevalent type in cases and controls (10.67% vs. 2.12%). Oral HPV infection was strongly associated with an increased risk of OSCC: the ORs were 7.21 (95% CI: 2.61-19.88) for HPV16/18 and 7.59 (95% CI: 2.34-24.64) for HPV-18. Moreover, the significant associations were only observed in females, young adults, married population, merchants, non-smokers, non-alcohol drinkers and non-tea drinkers. Additionally, the first intercourse below 22years of age and oral sex practice did not show an association with OSCC. But there was a significantly multiplicative interaction between HPV 16/18 and age at first intercourse for OSCC (Pinteraction<0.001). CONCLUSIONS Oral HPV infection (specifically type 18) is an independent risk factor for OSCC in Fujian area. Furthermore, there might be a combined effect of HPV 16/18 and age at first intercourse on OSCC.

Dietary score and the risk of oral cancer: a case-control study in southeast China

This study aims to develop a simple dietary score to comprehensively evaluate the role of diet in the risk of oral cancer. A case-control study including 930 oral cancer cases and 2667 frequency-matched controls was performed in Fujian, China. Unconditional logistic regression model was used to estimate the effects of dietary factors on oral cancer. After adjustment for potential confounders, less intake of domestic meat (< 3 times per week), fish (< 3 times per week), seafood (< 3 times per week), leafy vegetables (< 1 time per day), other vegetables (< 1 time per day), fruits (< 3 times per week), milk and dairy products (< 1 time per week) and eggs (< 5 times per week) were significant risk factors for oral cancer. Then these variables were incorporated to establish dietary risk score. Assessed by the receiver operating characteristic curve, the score showed a satisfactory discriminatory capacity, with an area under the curve of 0.682 (95% CI: 0.662–0.702). Moreover, the score was positively associated with the risk of oral cancer as quartiles, and the association was apparently stronger in tobacco smokers or alcohol drinkers. Additionally, there were significant multiplicative interactions between the score and tobacco smoking or alcohol drinking for oral cancer. In the present study, a convenient dietary score with satisfactory discriminatory capacity was developed to assess the collected effect of dietary factors on oral cancer, which could provide a new strategy for the prevention of oral cancer through changing in dietary habits.

Novel polymorphism in FADS1 gene and fish consumption on risk of oral cancer: A case-control study in southeast China

The aim of this study was to investigate the independent and combined effects of fatty acid desaturase 1 (FADS1) gene polymorphism and fish consumption on oral cancer. A hospital-based case-control study was performed including 305 oral cancer patients and 579 cancer-free controls. The genotypes were determined by TaqMan genotyping assay. Non-conditional logistic regression model was used to assess the effects of FADS1 rs174549 polymorphism and fish intake. Subjects carrying A allele of rs174549 significantly reduced the risk of oral cancer (AA VS GG, OR: 0.65, 95% CI: 0.42-0.99; AA VS AG+GG, OR: 0.67, 95% CI: 0.46-0.98). Moreover, the statistically significant reverse associations were especially evident in men, smokers, alcohol drinkers and those age ≤ 60 years. Additionally, fish intake ≥7 times/week showed a 73% reduction in risk for oral cancer compared to those who ate fish less than 2 times/week (OR: 0.27, 95% CI: 0.18-0.42). Furthermore, a significant gene-diet multiplicative interaction was observed between FADS1 rs174549 polymorphism and fish intake for oral cancer (P=0.028). This preliminary study suggests that FADS1 rs174549 polymorphism and fish consumption may be protective factors for oral cancer, with a gene-diet multiplicative interaction. Functional studies with larger samples are required to confirm our findings.

Prospective study on factors affecting the prognosis of oral cancer in a Chinese population

This study was performed to identify the factors affecting prognosis of oral cancer patients. 1240 pathologically confirmed oral cancer patients were included. The sociodemographic and clinical characteristics of all patients were collected. Univariate and multivariate Cox proportional hazards models were used to assess potential prognostic factors for survival. 1240 oral cancer patients were followed up for 49235.00 person months, and the 5-year overall survival rate was 64.38%. Both univariate and multivariate Cox regression analysis indicated that Body Mass Index < 18.5 kg/m2 (vs 18.5–23.9 kg/m2), age ≥ 55 years (vs < 55 years), clinical stages of II-IV (vs stage I), and poor differentiation (vs well differentiation) were associated with worse survival of oral cancer patients. While surgery (vs non-surgery) and origin of urban area (vs rural area) were protective factors. However, no significant association was found between adjuvant therapy and survival in oral cancer patients.

Serum copper and zinc levels and the risk of oral cancer: A new insight based on large-scale case-control study

OBJECTIVE Limited evidence exists on the roles of serum copper (Cu) and zinc (Zn) in oral cancer risk. We aimed to preliminarily explore the association between serum Cu and Zn levels and oral cancer risk with relatively large-scale samples. METHODS Serum Cu and Zn levels of 344 oral cancer patients and 1,122 matched healthy controls in this case-control study were measured by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS Restricted cubic spline revealed the U-shaped relationship between serum Cu or Zn levels and the risk of oral cancer. Serum deficient or elevated levels of Cu were significantly associated with the risk of oral cancer: The ORs were 1.38 (95% CI: 1.01-1.89) and 2.82 (95% CI: 1.60-4.98), respectively. The positive association of serum low or high levels of Zn with oral cancer risk was also observed: The ORs were 2.72 (95% CI: 1.60-4.62) and 12.41 (95% CI: 9.09-16.93), respectively. Additionally, there were multiplicative interactions between the aforementioned trace elements and smoking. CONCLUSIONS This preliminary study suggests that both serum excess and deficient levels of Cu or Zn were significant correlation with oral cancer risk, which may provide a new insight on the roles of serum Cu and Zn in oral cancer.

Nomograms and risk scores for predicting the risk of oral cancer in different sexes: a large-scale case-control study

Background: Although previous studies have explored the associations of modifiable lifestyle factors with oral cancer risk, few studies integrated these factors and established predictive tools for oral cancer risk in different sexes. Methods: Using a case-control study design, a total of 978 oral cancer cases and 2646 healthy controls were recruited in this study. Nomograms were constructed according to significant factors in multivariable logistic regression. Risk scores were calculated based on the nomograms and quantified the risk of oral cancer using restricted cubic spline. Results: Multivariate analyses demonstrated that smoking, alcohol drinking, tea, intake of fish, seafood, vegetables, fruits, teeth loss, regular dental visits and repetitive dental ulcer were independent factors for male oral cancer. Passive smoking, age at first intercourse, cooking oil fumes exposure, tea, intake of beans, vegetables, fruits, teeth loss, regular dental visits and repetitive dental ulcer were associated with female oral cancer. Then, two nomograms were developed for predicting the probability of oral cancer in men and women with the C-index of 0.768 (95% CI: 0.723-0.813) and 0.700 (95% CI: 0.635-0.765), respectively. Restricted cubic splines graphically revealed the risk of oral cancer in individuals with different risk scores. Moreover, the risk escalated continuously with the increasing number of the risk scores among both sexes. Conclusions: Combining nomograms with risk scores developed in this study could precisely predict oral cancer occurrence and provide an accurate risk assessment.

A functional haplotype of NFKB1 influence susceptibility to oral cancer: a population-based and in vitro study

Genetic variations of NF‐κB and its inhibitor IκB genes and their biological mechanism in oral cancer were not well recognized. The purpose of this study was to evaluate the associations of polymorphisms in NFKB1 and NFKBIA with oral cancer susceptibility, and further explore their potential mechanism in vitro. First, the polymorphisms of NFKB1 and NFKBIA were genotyped through iPLEX Sequenom MassARRAY platform in a case–control study with 425 oral cancer patients and 485 healthy controls. Then, the function was explored by a luciferase reporter assay and an electrophoretic mobility shift assay (EMSA) in human tongue squamous cell carcinoma cell lines. The results indicated that NFKB1 rs28362491 Del/Del and rs72696119 G/G genotypes were associated with the risk of oral cancer, with a strong linkage disequilibrium (D′ = 0.991, r2 = 0.971). Moreover, DG haplotype of NFKB1 also showed a significant increased risk (OR = 1.25, 95% CI: 1.02–1.53, P = 0.030). Dual‐luciferase reporter assays further revealed that the plasmids with DG or IG or DC haplotype transfected with Tca‐8113 cells or CAL‐27 cells had a lower luciferase expression than that with IC haplotype. EMSA demonstrated that 4‐bp ATTG deletion in the promoter of NFKB1 abolished the binding site of transcription factor. Our preliminary findings suggest that the haplotype of rs28362491 and rs72696119 in NFKB1 could act as a novel genetic marker to predict oral cancer risk in the southeast of China, but much more extensive researches still need to be conducted.

Independent and joint effects of tea and milk consumption on oral cancer among non-smokers and non-drinkers: a case-control study in China

This study aims to evaluate the independent and joint effects of tea and milk consumption on oral cancer risk among non-smokers and non-drinkers (NS/ND). A hospital-based case-control study was performed in Fujian, China. 421 cases and frequency-matched 1398 controls were included without tobacco smoking and alcohol drinking habits. Unconditional logistic regression model was used to assess the relationship of tea and milk consumption with oral cancer risk. Tea and milk consumption were significantly associated with decreased risk of oral cancer, the adjusted odds ratios (aORs) were 0.73 (95% CI: 0.54-0.97) and 0.69 (95% CI: 0.55-0.88), respectively. According to subgroup analysis, the inverse associations between tea consumption and oral cancer risk were only observed among the elders (>60 years) and urban residents. While the protect effect of milk drinking was more obvious in males, normal body mass index population (18.5–23.9), urban residents and those age ≤ 60 years. Additionally, a significantly multiplicative interaction between tea and milk consumption was observed for oral cancer risk (P = 0.001). The present study is the first to simultaneously assess the association of tea consumption and milk drinking with oral cancer risk. The results suggest that tea and milk consumption are independent protective factors for oral cancer among NS/ND, with a joint effect between them.

A novel prognostic index for oral squamous cell carcinoma patients with surgically treated

This study aims to develop an applicable prognostic index with conventional factors for predicting outcome of patients with oral squamous cell carcinoma (OSCC). We performed a prospective study in a large cohort of 892 OSCC patients in Fujian, China. All patients were randomly divided into a discovery group and validation group. A prognostic index was developed based on β value of each significant variable obtained from the multivariate Cox regression model. The results from discovery and validation set demonstrated thatthe model-4(included clinical stage, tumor differentiation, ill-fitting denture, oral hygiene and cigarette smoking) was the optimal model. The optimal cutoff points of prognostic index (1.88 and 2.80) were determined by X-tile program which categorized all subjects into low, middle and high risk subsets. Patients in high risk group were at the greatest risk of death compared with those in low risk group (HR: 6.02; 95%CI: 4.33-8.38). Moreover, there was a significant tendency of the worse overall survival with the higher prognostic index (Ptrend <0.001). The discriminatory capacity of prognostic index was 0.661(95%CI: 0.621-0.701). This study developed and validated a prognostic index that is an economical and useful tool for predicting the clinical outcomes of OSCC patients in Southeast China. Future randomized trials with larger cohort are required to confirm our results.This study aims to develop an applicable prognostic index with conventional factors for predicting outcome of patients with oral squamous cell carcinoma (OSCC). We performed a prospective study in a large cohort of 892 OSCC patients in Fujian, China. All patients were randomly divided into a discovery group and validation group. A prognostic index was developed based on β value of each significant variable obtained from the multivariate Cox regression model. The results from discovery and validation set demonstrated thatthe model-4(included clinical stage, tumor differentiation, ill-fitting denture, oral hygiene and cigarette smoking) was the optimal model. The optimal cutoff points of prognostic index (1.88 and 2.80) were determined by X-tile program which categorized all subjects into low, middle and high risk subsets. Patients in high risk group were at the greatest risk of death compared with those in low risk group (HR: 6.02; 95%CI: 4.33-8.38). Moreover, there was a significant tendency of the worse overall survival with the higher prognostic index (Ptrend <0.001). The discriminatory capacity of prognostic index was 0.661(95%CI: 0.621-0.701). This study developed and validated a prognostic index that is an economical and useful tool for predicting the clinical outcomes of OSCC patients in Southeast China. Future randomized trials with larger cohort are required to confirm our results.

Differences in modifiable factors of oral squamous cell carcinoma in the upper and lower of oral fissure

The aim of this study was to explore differences in the effects of modifiable factors on oral squamous cell carcinoma (OSCC) occurring in the lower oral fissure (LOF) and upper oral fissure (UOF). We conducted a case-control study with 697 OSCC patients (119 UOF and 578 LOF) and 1910 frequency-matched controls in Fujian province, China. Data on demographic characteristics and possible modifiable factors was collected using a structured questionnaire. Unconditional logistic regression was utilized to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Alcohol drinking was more strongly associated with an increased risk of OSCC-LOF than OSCC-UOF. Tobacco smoking, the number of teeth lost ≥5, wearing denture, and recurrent oral ulceration showed similarly associations with OSCC-LOF and -UOF risk. Similarly, the beneficial effects of tea consumption, tooth-brushing ≥2times per day, high intake of fresh fish, seafood, green-leafy vegetables, other vegetables and fruits were not significantly different on OSCC-LOF and -UOF. Although most of the modifiable factors exert similar effects on both OSCC sites, this study suggests that the sites of oral cavity in LOF may be affected more by alcohol drinking than the sites in UOF. Further studies with larger samples are warranted to confirm our findings.