Abstract
Radiotherapy for nasopharyngeal carcinoma has been reported to cause second primary oral squamous cell carcinoma (s‐OSCC). The prognosis and pathologic characteristic of s‐OSCC are largely unknown. Bmi1 was associated with the repair of radiation‐induced DNA damage, suggesting its possible involvement in the pathologic process of s‐OSCC. Herein, we compared the prognosis between s‐OSCC and primary OSCC (p‐OSCC) and explored the involvement of Bmi1 in s‐OSCC development. In this retrospective study, s‐OSCC and p‐OSCC patients were matched by propensity scores. Their outcomes were compared by univariate and multivariate analyses. The expression of Bmi1 in s‐OSCC and p‐OSCC was detected by immunohistochemistry (IHC). Radiation‐induced Bmi1 alteration in early‐stage was explored in a rat model and HaCaT cells. After matching, 116 pairs of patients with highly balanced characteristics were included. In univariate analysis, the overall survival (OS), disease‐specific survival (DSS), and local recurrence‐free survival (LRFS) were poorer in s‐OSCC than in p‐OSCC (P < 0.05), while their regional metastasis‐free survival (RMFS) was parallel (P = 0.112). Multivariate analysis further revealed that radiotherapy history was an independent risk factor for OS, DSS, and LRFS (P < 0.05). IHC results showed that the positive rate of Bmi1 was higher in s‐OSCC (P = 0.0027). In a rat model of radiotherapy‐induced mucositis, Bmi1 upregulation was observed 8 days after irradiation. Consistently, Bmi1 was upregulated in HaCaT cells 1 h after irradiation, and its upregulation was in accord with X‐ray exposure duration. In conclusion, the prognosis of s‐OSCC is poorer as compared to p‐OSCC, which may be attributed to Bmi1 upregulation.
Highlights
Nasopharyngeal carcinoma (NPC) is a specific head and neck malignancy which occurs mainly in Southeast Asia, in south China with an age-standardized incidence of up to 27–44 per 100,000 persons (1998–2002) [1, 2]
Among all the 2,803 oral squamous cell carcinoma (OSCC) patients, 5.49% (n = 154) of them were developed from NPC patients
For the 116 s-O SCC patients enrolled in this study, the median interval from NPC radiotherapy to OSCC diagnosis was 10 years
Summary
Nasopharyngeal carcinoma (NPC) is a specific head and neck malignancy which occurs mainly in Southeast Asia, in south China with an age-standardized incidence of up to 27–44 per 100,000 persons (1998–2002) [1, 2]. Radiotherapy is the primary treatment for NPC because of its high radiosensitivity. Evolution in treatment technique, especially the development of intensity modulated radiotherapy (IMRT), have brought a dramatic improvement in the prognosis of NPC patients [3]. The 20- year cumulative incidence rate (CIR) of SPTs after radiotherapy for NPC was up to 5.37% [6]. With the highest standardized incidence ratio (SIR), oral cavity was the most common site to develop SPTs after radiotherapy for NPC [6–9]. 83.9% of the SPTs in oral cavity were oral squamous cell carcinoma (OSCC) [10]. It is highly representative to study the second primary oral squamous cell carcinoma (s-O SCC) after NPC radiotherapy, which will provide significant implications for clinical treatment and surveillance for SPTs patients
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