| [Objective]HPV related oral squamous cell carcinoma (OSCC) represents a unique biological and clinical disease. Efficient and accurate detection of HPV in OSCC clinical samples is helpful to judge tumor stage and prognosis, so as to guide the best treatment for patients. p16 can be used as a surrogate marker of HPV infection in cervical cancer and oropharyngeal squamous cell carcinoma. But its significance in OSCC is unknown. We aim to study the expression of p16 and its clinicopathological significance in OSCC, and analyze the correlation between p16 expression and HPV infection and their influence on the prognosis of OSCC patients. Thus we will explore the comprehensive strategy of HPV detection in OSCC.[Method]217 cases of OSCC which had complete clinicopathological data and follow-up results were obtained from the biological sample library at Nanjing Stomatology Hospital, Medical School of Nanjing University between February 2013 to January 2015. We detected the expression of p16, p53, Ki67 in 217 OSCC samples by IHC. Then we selected the cell staining of p16>25% smaples to detect HPV by reverse transcription quantitative polymerase chain reaction(RT-qPCR) and PCR-reverse dot blot method.[Results]1. In 217 OSCC smaples, there were 30 with p16 staining> 25% and 70 with p16 staining> 75%. Among the 30 p16>25% samples, we detected 5 HPV positive smaples. They were further catogerized into HPV 16 (3 cases) and HPV18 (2 cases) by RT-qPCR. Among the same 30 cases, we detected 2 HPV positive smaples by PCR-reverse dot blot method, among them 1 was HPV16 and 1 was HPV82. The infection of HPV was positively correlated with the expression of p16 (P<0.05). All the HPV positive cases had more than 70% p16 positive cells, but not all p16 positive cell number>70% cases were HPV-positive.2. Among 217 OSCC samples,7.4% were p16 positive. The expression of p16 was significantly correlated with lesion sites (P<0.05). There were 59.4% p53 positive cases. The expression of p53 was significantly higher in OSCC I group than in OSCC Ⅱ group (P<0.05). There were 32.3% Ki67 positive cases. It was increased in N1/N2 group compared with NO group (P<0.05). The expression of Ki67 was significantly higher in OSCC Ⅱ group than in OSCC I group (P<0.05). Whether HPV infected or not was not correlated with sex, age, sites, TNM or histological grade (P> 0.05). The expression of p53 was negatively correlated with the expression of p16 (P <0.05). There was a negative correlation trend between the expression of p16 and Ki67, but without statistical significance (P>0.05). The prognosis of OSCC patients was significantly worse in Ki67 positive group than that in Ki67 negative group (P< 0.05). HPV infection and the expression of p16, p53 were not significantly related to the prognosis of OSCC patients (P> 0.05). Meanwhile, p16(+)/HPV(+) OSCC patients had the best prognosis (P<0.05). The combination of p16 and p53 or p16 and Ki67 had no correlation with the prognosis of OSCC patients (P>0.05).[Conclusion]1. p16 could not serve as a surrogate marker for HPV status in OSCC independently. However, p 16 IHC could be used to detect the initial screening of HPV infection in OSCC. If there are more than 70% p16-positive cells in IHC, we should apply HPV PCR or HPV ISH to determine HPV infection.2. In our OSCC samples, the expression of p16 was significantly related to the lesion site. The expression of p53 was closely related to the histological grade. The expression of Ki67 was closely related to lymph node metastasis and histological grade. The status of HPV was not correlated with clinicopathological parameters. The expression of p16 was negatively correlated with the expression of p53. The Ki67 positive patients have poorer prognosis. The expression of p16 and p53 and HPV infection had no effect on prognosis. p16(+)/HPV(+) OSCC patients had the best prognosis. The combination of p16 and p53 or p16 and Ki67 had no correlation with the prognosis of OSCC. The combination of p16 and HPV may be a useful index to judge the prognosis of OSCC. |
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