| Objective:The clinicopathological features,human papillomavirus(HPV)infection status and use of gynostemma pentaphylla compound capsule(Gp)of oral leukoplakia(OLK)with self-control samples were analyized by retrospective study.And investigated the exposure factors and protective factors in the development or carcinogenesis of oral leukoplakia.Methods: The study collated and analyzed the clinicopathological data of 2628 OLK patients obtained from Shanghai 9th People's Hospital from 2000 to 2015.OLK with more than two surgeries or biopsies were selected for self-control study.According to inclusion criteria,258-paired samples were screened and divided into mild dysplasia group(50 cases),moderate dysplasia group(66 cases)and severe dysplasia group(35 cases)group and cancerous group(41 cases)and 66 cases were getting better.A total of 76 patients(152 tissue specimens)with severe dysplasia and cancerous lesions were selected for DNA extraction from the tissue samples.The p16INK4 A expression and HPV infection status were detected by HPV reverse dot blot(HPV-Reverse Dot Bolt),polymerase chain reaction(PCR)and immunohistochemistry(IHC).And analyze the role of gynostemma pentaphylla compound in the process of affecting OLK carcinogenesis.Clinicopathological features,HPV infection status,expression of p16INK4 A and gynostemma pentaphylla compound use were analyzed by Chi-square method.Using Kaplan-Meier univariate survival analysis and Cox multivariate analysis of different clinical and pathological features,HPV infection status,and relationship between gynostemma pentaphylla compound in treatment and progression of disease,and to establish prognostic model.Results:1.From 2000 to 2015,a total of 2628 people were diagnosed with OLK,of whom 8.0%(210/2628)were diagnosed as oral squamous cell carcinoma at first,and 1.7%(41/2628)patients with OLK progressed to oral squamous cell carcinoma.The ratio of male to female was 1.09: 1.The sites were common in buccal(28.1%),ventrum of tongue(25.6%),border of tongue(18.1%),back of tongue(8.5%),gum(7.8%),palatal(5.0%).2.According to the inclusion and exclusion criteria,258 patients were selected,and each patient had the initial and final species.Among them,there were mild dysplasia group(50 cases),moderate dysplasia group(66 cases),severe dysplasia group(35 cases)and cancerous group(41 cases)respectively,a total of 192 cases.The ratio of male to female was 0.47:1(p=0.027),and the ventrum/border of tongue(70.8%,136/192)was the most common lesion site(p<0.01),84.9%(163/192)patients without smoking history(p=0.017),91.6% patients without alcohol history(p=0.011).Moderate and severe dysplasia(p <0.01),alcohol consumption(p=0.019)were the independent predictors of OLK carcinogenesis.In addition,66 cases of 258 patients showed improvement after treatment,among which 41(41/68,60.3%)patients had received the treatment of compound gynox capsule.3.In order to study the role of HPV in OLK carcinogenesis,a total of 76 cases(152 tissue samples)were selected from the two groups of patients with OLK severe hyperplasia and cancer group.A total of 4 cases(5.3%,4/76)of HPV16 positive were detected by HPV reverse dot blot hybridization with HPV DNA PCR.There was no other subtype detected.All 4 HPV16 positive were detected in the initial species.In OLK cancerous group,the expression of p16INK4 A was 51.2% vs 24.4% in the initial and final species,respectively.In OLK with dysplasia group,the expression of p16INK4 A was 22.9% vs 20%,in which 32.9% cases were false positive for HPV16 infection.The high expression of p16INK4 A protein in OLK early stage indicated that the lesion might have a higher tendency of malignant(p=0.013,OR=3.544).4.Among the 192 self-control patients who progressed to mild dysplasia,moderate dysplasia,and severe dysplasia and oral squamous cell carcinoma(OSCC),51%(94/192)took compound gypenosides and 49% were only treated with surgury(98/192).Kaplan-Meier analysis showed that the first diagnosis of OLK with mild or moderate dysplasia and taking gynostemma pentaphylla compound were not susceptible to cancer(p =0.044,p=0.046).The first diagnosis of OLK patients with severe dysplasia who take gynostemma pentaphylla compound had little effect(p=0.741).Cox regression analyzed that OLK patients with moderate dysplasia,severe dysplasia,untreated with drugs and had a history of alcohol consumption were independent predictors for OLK malignant transformation to OSCC.5.The prognostic index model was established by Cox regression analysis: h(t)= h0(t)exp(0.767 × moderate dysplasia + 2.88 × severe dysplasia + 0.944 × drinking-0.934 × medication).Conclusion:1.From 2000 to 2015,8.0%(210/2628)patients were diagnosed as oral squamous cell carcinoma for the first time.Improving patient cognition and therapy compliance,regular follow-up may contribute to prevent OLK malignant transformation to OSCC.2.In this study,192 OLK self-controlled studies found that the tongue/tongue margin was high in the site and was prone to cancer.The degree of dysplasia,alcohol consumption and untreated were independent predictor for OLK malignant transformation.3.In this study,the detection rate of HPV was only 5.3%,and all were HPV16 positive.It is noteworthy that HPV16 were only be detected in the first biopsy samples and lesions does not with a chronic infection.This suggests that the pathogenesis of HPV-associated oropharyngeal squamous cell carcinoma is different.HPV16 positive may be only a transient infection,not a major risk factor for OLK carcinogenesis.4.Expression of p16INK4 A was used to determine the HPV status had a higher false positive rate.However,the expression of p16INK4 A had the role of "first rose then descended" in OLK progression suggested that p16INK4 A expression may be used as a dynamic indicator in the OLK carcinogenesis and has a significant diagnostic value.5.It has important clinical application value in preventing,delaying or even blocking OLK carcinogenesis by using gynostemma pentaphylla compound.6.The prognostic model was established for the development of a rational treatment program,guidance for treatment was instructive. |
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