• BMB Reports
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• v.51 no.11
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• pp.584-589
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• 2018

Secondary prevention via earlier detection would afford the greatest chance for a cure in premalignant lesions. We investigated the exomic profiles of non-malignant and malignant changes in head and neck squamous cell carcinoma (HNSCC) and the genomic blueprint of human papillomavirus (HPV)-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC). Whole-exome (WES) and whole-genome (WGS) sequencing were performed on peripheral blood and adjacent non-tumor and tumor specimens obtained from eight Korean HNSCC patients from 2013 to 2015. Next-generation sequencing yielded an average coverage of $94.3{\times}$ for WES and $35.3{\times}$ for WGS. In comparative genomic analysis of non-tumor and tumor tissue pairs, we were unable to identify common cancer-associated early mutations and copy number alterations (CNA) except in one pair. Interestingly, in this case, we observed that non-tumor tonsillar crypts adjacent to HPV-positive OPSCC appeared normal under a microscope; however, this tissue also showed weak p16 expression. WGS revealed the infection and integration of high-risk type HPV16 in this tissue as well as in the matched tumor. Furthermore, WES identified shared and tumor-specific genomic alterations for this pair. Clonal analysis enabled us to infer the process by which this transitional crypt epithelium (TrCE) evolved into a tumor; this evolution was accompanied by the subsequent accumulation of genomic alterations, including an ERBB3 mutation and large-scale CNAs, such as 3q27-qter amplification and 9p deletion. We suggest that HPV16-driven OPSCC carcinogenesis is a stepwise evolutionary process that is consistent with a multistep carcinogenesis model. Our results highlight the carcinogenic changes driven by HPV16 infection and provide a basis for the secondary prevention of OPSCC.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.189-198
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• 1990

Sixty-six patients with squamous cell carcinoma of the oropharynx were treated with radiation therapy and retrospectively analyzed to evaluate the treatment result in the Department of Therapeutic Radiology, Korea Cancer Center Hospital between January 1980 and December 1986. There were 42 patients with carcinoma of the tonsil including the fossa and pillar, 9 patients with carcinoma of the base of tongue,12 patients with carcinoma of the soft palate, and 3 patients with carcinoma of the posterior and lateral pharyngeal walls. Considering all oropharyngeal sites of involvement together, response rates for T1, T2, T3, and T4 were 80%, 77%, and 40%, respectively, with a overall response rate of 70%. The response rate for N1, N2, and N3 were 69%, 63%, and 40%, respectively, with the overall regional response rate of 70%. In lower T status, undifferentiated carcinoma and primary tumor arising from the soft palate, higher response rates were obtained. The S year overall and disease-free survival rate were 56%, 55%, respectively. A better prognosis was obtained in early T stage (T1+T2) (p<0.01) and in patients without tumor extension into adjacent structures in carcinomas arising from tonsillar area (p<0.01). Through this study we suggest that, in terms of anatomical and functional preservation, radiation therapy seems to be an effective method for the primary treatment of patients with oropharyngeal carcinoma.

• Radiation Oncology Journal
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• v.14 no.2
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• pp.95-103
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• 1996

Purpose : A retrospective analysis for patients with oropharyngeal carcinoma who were treated with radiation was performed to assess the results of treatment and patterns of failure, and to identify the factors that might influence survival. materials and methods : From March 1985 through June 1993, 53 patients with oropharyngeal carcinoma were treated with either radiation therapy alone or combination of neoadjuvant chemotherapy and radiation therapy at the Department of Radiation Oncology, Kyungpook National University Hospital. Patients' ages ranged from 31 to 73 years with a median age of 54 years. There were 47 men and 6 women, Forty-two Patients ($79.2\%$) had squamous cell carcinoma, 10 patients ($18.9\%$) had undifferentiated carcinoma and 1 patient ($19\%$) had adenoid cystic carcinoma. There were 2 patients with stage I, 12 patients with stage II, 12 Patients with stage III and 27 patients with stage IV. According to the TNM classification, patients were distributed as follows: T1 7, T2 28, T3 10, T4 7, TX 1, and N0 17, Nl 13, N2 21, N3 2. The primary tumor sites were tonsillar region in 36 patients ($67.9\%$), base of the tongue in 12 patients ($22.6\%$), and soft palate in 5 patients ($9.4\%$). Twenty-five patients were treated with radiation therapy alone and twenty-eight Patients were treated with one to three courses of chemotherapy followed by radiation therapy. Chemotherapeutic regimens used were either CF (cisplatin and 5-fluorouracil) or CVB (cisplatin, vincristine and bleomycin). Radiation therapy was delivered 180-200 cGy daily, five times a week using 6 MV X-ray with or without 8-10 MeV electron beams A tumor dose ranged from 4500 cGy to 7740 cGy with a median dose of 7100 cGy. The follow-up time ranged from 4 months to 99 months with a median of 21 months. Results : Thirty-seven patients ($69.8\%$) achieved a CR (complete response) and PR (partial response) in 16 patients ($30.2\%$) after radiation therapy. The overall survival rates were $47\%$ at 2 years and $42\%$ at 3 years, respectively. The median survival time was 23 months. Overall stage (p=0.02) and response to radiation therapy (p=0.004) were significant prognostic factors for overall survival. The 2-year disease-free survival rate was $45.5\%$. T-stage (p=0.03), N-stage (p=0.04) and overall stage (P=0.04) were significant prognostic factors for disease-free survival. Age, sex, histology, primary site of the tumor, radiation dose, combination of chemotherapy were not significantly associated with disease-free survival. Among evaluable 32 Patients with CR to radiation therapy, 12 patients were considered to have failed Among these, 8 patients failed locoregionally and 4 Patients failed distantly. Conclusion : T-stage, N-stage and overall stage were significant prognostic factors for disease-free survival in the treatment of oropharyngeal cancer Since locoregional failure was the predominant pattern of relapse, potential methods to improve locoregional control with radiation therapy should be attempted. More controlled clinical, trials should be completed before acceptance of chemotherapy as a part of treatment of oropharyngeal carcinoma.