| Background:Oropharyngeal squamous cell carcinoma (OSCC) refers to malignant tumors occurred in the parts of the soft palate-uvula, palatine tonsil, base of the tongue and pharyngeal wall. The incidence rate of OSCC was4.4/10million, the mortality rate was2.5/10million, accounting for1.3%of the whole body malignancies. The major risk factors for OSCC were tobacco and alcohol, as well as human papilloma virus chronic infection. OSCC is extremely prone to cervical lymph node metastasis because of the richness of oropharyngeal lymphoid tissue. Although the treatment of oropharyngeal cancer continued to improve, the mortality rate didn’t decrease significantly. The factors affecting the prognosis of patients with oropharyngeal cancer:HPV infection status, smoking status, alcohol consumption, age of onset, race, tumor stage, nodal stage, and the expression of p16protein. A large number of OSCC clinical data is still rarely reported for the guidance of the diagnosis and treatment in China.Objective To investigate the clinicopathological features, treatment outcomes and prognosis of patients with OSCC.Methods Retrospective review of OSCC cases in our hospital from January1999to December2011. Demographic data and clinical charts, including presenting symptoms, histologic grade of tumor, treatment, and outcome of318consecutive patients were obtained. Survival rates and prognostic factors were calculated with SPSS19.0software using the Kaplan-Meier method and multivariate Cox model survival analysis. Of the318cases,163were tonsil carcinomas,108were base of tongue carcinomas and47were soft palate-uvula carcinomas. There were281males and37females, and the median age was56years. The presenting symptoms were pharyngalgia(40.3%), neck masses(22.3%), foreign body sensation in the pharynx(19.8%) and dental ulcer(13.8%). The median time from onset of the first symptoms until diagnosis of OSCC was3.0months. The318OSCC included75high grade tumors,110intermediate grade tumors and133low grade tumors. According to the UICC2002staging criteria,10patients were stage I,39were stage Ⅱ,68were stageⅢ and201were stageIV.Results The rates of lymph node metastasis, distant metastasis and second primary carcinoma were72.3%,13.2%and7.9%, respectively. Of the318patients,117received radiotherapy alone,66underwent surgery plus postoperative radiotherapy,59underwent preoperative radiotherapy plus surgery,33received concomitant chemotherapy and radiotherapy,20received concomitant molecular targeted therapy and radiotherapy,16underwent surgery alone and seven received induction chemotherapy plus radiotherapy. The3-year,5-year and10-year overall survival (OS) rate were58.4%,50.7%and33.4%, respectively, and the median overall survival time was60.1months. Multivariate Cox model survival analyses confirmed that ages(.P=0.034), gender(P^0.024), smoking and alcohol consumptions(P=0.008), doses of radiotherapy(P=0.046) and clinic stages(P=0.001) were independent factors for OS.Conclusions:OSCC is a malignant tumor with poor prognosis and extremely prone to cervical lymph node metastasis. Radiotherapy and salvage surgery are the main treatments for patients with OSCC. Background:Based on the etiology, Oropharyngeal squamous cell carcinoma(OSCC) can be divided into two subtypes, one is due to long-term smoking and alcoholism, the other is caused by being infected with human papilloma virus chronically. The incidence of HPV-associated OSCC was climbing up yearly. Further studies showed that HPV disrupted the normal cell cycle and leaded to tumorigenesis by encoding E6and E7oncogenic protein. Foreign studies have shown that HPV-associated OSCC has unique clinical and pathological features, and its prognosis was significantly better than non-HPV-associated OSCC. What is the reason and what is the mechanism of its etiology? How to forecast the prognosis of patients with OSCC before treatment, according to a reliable molecular indicators?Objective:1. To summarize the clinicopathological characteristics and prognostic features of HPV-associated OSCC.2. To explore the changes in molecular biology of HPV-related OSCC, and to preliminarily understand its pathogenesis.3. Attempt to predict the prognosis of OSCC by certain molecular markers.Methods:Retrospective review of OSCC cases in our hospital from January1999to December2012. Demographic data and clinical charts, including presenting symptoms, histologic grade of tumor, treatment and outcome of the patients were obtained. HPV-DNA will be detected using SPF10-DNA enzyme immunoassay and LiPA genotyping method. In addition, we will test E6, p16and p53protein expression by immunohistochemical methods. Survival rates and prognostic factors will be calculated with SPSS19.0software using the Kaplan-Meier method and multivariate Cox model survival analysis.Results:1. HPV infection rate of OSCC was21.7%(31/143). A total of eight kinds of HPV subtypes were involved, which including six kinds of high-risk and two kinds of low-risk, and high-risk HPV-16subtype was accounted for80.6%(25/31).2. HPV-associated OSCC of the female patient ratio was significantly higher than non-HPV-associated OSCC(16.1%Vs3.6%, χ2=6.492, P=0.011). HPV-associated OSCC was more likely to occur in non-smoking and non-drinking patients(smoking:45.2%Vs73.2%, χ2=8.660, P=0.003; drinking:25.8%Vs57.1%,χ2=9.537,P=0.002).3. T stage of HPV-positive patients was significantly earlier than HPV-negative patients(T1-2:T3-T4:71.0%Vs45.5%, x2=6.284, P=0.012). However, tumors were more likely to poorly differentiated(41.9%Vs20.5%,χ2=5.903, P=0.015)4. HPV-associated OSCC was more sensitive to radiotherapy (primary tumor: χ2=7.590, P=0.022; lymph node:x2=6.983,P=0.030), and had a better prognosis than non-HPV-associated OSCC (5-year DSS:83.3%Vs45.4%,χ2=7.192, P=0.007).5. The p53protein low expression rate was71.0%(22/31) in HPV-associated OSCC, which has a statistically significant difference compared to non-HPV-associated OSCC(71.0%Vs46.4%, χ2=5.855, P=0.016).6. The E6protein expression rate was73.1%in HPV16/18type-associated OSCC, which had a statistically significant difference compared with the non-HPV16/18associated OSCC(73.1%Vs6.8%, x2=60.940, P<0.000).7. The p53protein was mostly low expression in E6protein positive HPV16/18-associated OSCC, which had a statistically significant difference (84.2%Vs42.9%, χ2=4.446, P=0.035) compared to the E6protein negative HPV16/18-associated OSCC8. The patients with OSCC of low expression of p53protein had a better prognosis than the patients with high expression of p53protein (3-year disease-specific survival rate:73.6%vs.56.6%), but no statistically significant difference (x2=3.004, P=0.083) was found between them.9. The p16protein of HPV-associated OSCC was mostly positive expression, about83.9%(26/31). There was a statistically significant difference (P<0.000) compared to non-HPV-associated OSCC. The p16protein expression had a good consistency with HPV infection status of OSCC (κ=0.575, P<0.000).10. The p16protein high expression OSCC of the female patient ratio was significantly higher than pl6protein low expression OSCC(15.6%Vs2.0%, x2=9.551, P=0.002). The p16protein high expression OSCC was more likely to occur in non-smoking and non-drinking patients(smoking:53.3%Vs73.5%,χ2=5.661, P=0.017; drinking:28.9%Vs60.2%, χ2=12.097, P=0.001) and the tumors were more likely to poorly differentiated(37.8%Vs19.4%, x2=5.537, P=0.019).11. The prognosis of patients with OSCC of high expression of p16protein was significantly better than the patients with the low p16protein expression OSCC (P<0.000), and5-year local control rate, disease-specific survival and overall survival were89.3%,86.2%and77.3%, respectively. 12. Based on the expression of p16and smoking and alcohol consumption, patients were divided into three groups:low-risk group, moderate risk group and the high-risk group. The5-year disease-specific survival rates were84.4%,62.0%, and21.1%, respectively, and a statistically significant difference was found among these three groups(x2=16.362, P<0.000).Conclusions:HPV-associated OSCC had unique clinical and pathological features, which was more sensitive to radiotherapy, and the prognosis was significantly better. The p16protein can be used not only as a surrogate marker of HPV infection, but also as one of the important molecular indicators to forecast the prognosis of OSCC. Based on the expression of p16protein and smoking and alcohol consumption, the patients with OSCC can be divided into three prognostic risk groups, and the this grouping method might be simple and reliable. |
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