• Korean Journal of Radiology
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• 제24권1호
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• pp.51-61
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• 2023

Objective: To develop and test a machine learning model for classifying human papillomavirus (HPV) status of patients with oropharyngeal squamous cell carcinoma (OPSCC) using ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET-derived parameters in derived parameters and an appropriate combination of machine learning methods in patients with OPSCC. Materials and Methods: This retrospective study enrolled 126 patients (118 male; mean age, 60 years) with newly diagnosed, pathologically confirmed OPSCC, that underwent ¹⁸F-FDG PET-computed tomography (CT) between January 2012 and February 2020. Patients were randomly assigned to training and internal validation sets in a 7:3 ratio. An external test set of 19 patients (16 male; mean age, 65.3 years) was recruited sequentially from two other tertiary hospitals. Model 1 used only PET parameters, Model 2 used only clinical features, and Model 3 used both PET and clinical parameters. Multiple feature transforms, feature selection, oversampling, and training models are all investigated. The external test set was used to test the three models that performed best in the internal validation set. The values for area under the receiver operating characteristic curve (AUC) were compared between models. Results: In the external test set, ExtraTrees-based Model 3, which uses two PET-derived parameters and three clinical features, with a combination of MinMaxScaler, mutual information selection, and adaptive synthetic sampling approach, showed the best performance (AUC = 0.78; 95% confidence interval, 0.46-1). Model 3 outperformed Model 1 using PET parameters alone (AUC = 0.48, p = 0.047) and Model 2 using clinical parameters alone (AUC = 0.52, p = 0.142) in predicting HPV status. Conclusion: Using oversampling and mutual information selection, an ExtraTree-based HPV status classifier was developed by combining metabolic parameters derived from ¹⁸F-FDG PET/CT and clinical parameters in OPSCC, which exhibited higher performance than the models using either PET or clinical parameters alone.

• 대한두경부종양학회지
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• 제35권2호
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• pp.1-10
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• 2019

The 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, which took place May 31-June 4 in Chicago, drew more than 32,000 oncology specialists from around the world. The theme of 2019 ASCO conference was "Caring for Every Patient, Learning from Every Patient". Among the topics of interest covered were new approaches to surmount limited access to cancer care and the latest advances in targeted therapies for pancreatic, prostate cancers and soft tissue sarcomas. In the field of head and neck cancer, 8 oral abstracts and 75 poster abstracts were presented at this meeting. In this review, we are going to summarize the eight studies that have been presented orally. The topics are recurrent and/or metastatic head and neck squamous cell carcinoma for two abstracts (#6000, #6002), salivary duct carcinoma for one abstract (#6001), locally advanced nasopharyngeal carcinoma for two abstracts (#6003, #6004), oropharyngeal carcinoma for two abstracts (#6006, #6008), and oral cavity cancer for one abstract (#6007).

• Radiation Oncology Journal
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• 제8권2호
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• pp.189-198
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• 1990

저자들은 1980년 1월부터 1980년 12월까지 원자력병원 치료방사선과에서 방사선 치료를 받은 66명의 구강인두 편평상피 종양 환자들을 대상으로 한 후향적 분석을 통하여 다음과 같이 결과를 얻었다. 구강인두 종양의 원발 부위별 환자분포를 보면 편도부위 종양이 42예로 가장 많았고 연구개 종양이 12예, 구강저 종양이 9예 그리고 측인두 및 후인두벽 종양이 3예순이었다. 구강인두 부위에 침범한 병소들을 총체적으로 분석한 경우 원발병소의 병기에 따른 국소관해율은 T1과 T2 그리고 T3와 T4 병기에서 각각 80%와 77% 그리고 73%와 40%였고 전체적으로 70%의 국소관해율를 보였다. 국소관해율은 원발병소의 병기가 낮을수록, 또한 원발부위로 볼때 연구개부위 종양에서, 그리고 분화도상에 미분화된 세포를 가진 경우에 가장 높았다. 국소적 임파선의 병기에 따른 국소임파관해율은 N1과 N2 그리고 N3 병기에서 각각 96%와 63% 그리고 40%였으며 전체적으로 70%의 국소임파관해율를 보였다. 원발병소의 병기에 따른 5년 생존율은 T1과 T2에서 73%, T3와 T4에서 46%였다(p<0.05). 또한, 편도부위에 생긴 종양의 경우 5년 생존율은 주위조직으로의 침범이 없는 군이 있는 군보다 통계적인 유의차로 높았다(p<0.01). 결론적으로 볼때 방사선 요법이 해부학적 형태 유지 및 기능적인 보존측면에서 구강인두 종양에 대한 일차적인 치료방법으로서 효과적인 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6919-6922
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• 2015

Background: The treatment selection for the oral squamous cell carcinoma remains controversial. Radiation therapy or surgical excision of the lesion can be applied as the sole treatment or it can be used in combination with other treatment modalities. Radiotherapy is considered to be the safest of all the treatment modalities and can be used in several situations for oral and oropharyngeal cancers. The aim of this study was to evaluate the survival outcome differences in patients treated with radical and palliative radiotherapy as the primary treatment modality. Materials and Methods: The study included a total of 47 patients with oral cancer reporting to our hospital between years 2009 to 2010. The age group for the selected patients was more than 65 years, treated with radical and palliative radiotherapy with no prior surgical interventions. Patients were evaluated till Dec 2013 for overall survival time. Results: Twenty nine patients were treated with radical radiotherapy as main stay of treatment, out of which 21 died during the follow up time with median survival of $352{\pm}281.7$ days with 8 patients alive. All the 16 patients were dead who received palliative radiotherapy with a median survival time of $112{\pm}144.0$ days. Conclusions: This retrospective study showed improved overall survival time, loco regional control rates and reduced morbidity in patients treated with radical radiotherapy when compared to patients treated with palliative radiotherapy.

• Archives of Plastic Surgery
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• 제42권4호
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• pp.453-460
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• 2015

Background Reconstruction of oropharyngeal defects after resection of oropharyngeal cancer is a significant challenge. The purpose of this study is to introduce reconstruction using a combination of a buccinator myomucosal flap and a buccal fat pad flap after cancer excision and to discuss the associated anatomy, surgical procedure, and clinical applications. Methods In our study, a combination of a buccinator myomucosal flap with a buccal fat pad flap was utilized for reconstruction after resection of oropharyngeal cancer, performed between 2013 and 2015. After oropharyngectomy, the defect with exposed vital structures was noted. A buccinator myomucosal flap was designed and elevated after an assessment of the flap pedicle. Without requiring an additional procedure, a buccal fat pad flap was easily harvested in the same field and gently pulled to obtain sufficient volume. The flaps were rotated and covered the defect. In addition, using cadaver dissections, we investigated the feasibility of transposing the flaps into the lateral oropharyngeal defect. Results The reconstruction was performed in patients with squamous cell carcinoma. The largest tumor size was $5cm{\times}2cm(length{\times}width)$. All donor sites were closed primarily. The flaps were completely epithelialized after four weeks, and the patients were followed up for at least six months. There were no flap failures or postoperative wound complications. All patients were without dietary restrictions, and no patient had problems related to mouth opening, swallowing, or speech. Conclusions A buccinator myomucosal flap with a buccal fat pad flap is a reliable and valuable option in the reconstruction of oropharyngeal defects after cancer resection for maintaining functionality.

• BMB Reports
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• 제51권11호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.4049-4057
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• 2016

Background: High-risk human papillomaviruses (HR-HPV), particularly types 16 and 18, have been found to play an important role in head and neck cancer, including oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). p16, a cell cycle inhibitor, has been postulated as a surrogate marker for HR-HPV, since p16 is aberrantly overexpressed in such lesions, especially in HR-HPV-positive OPSCC. However, p16 as a surrogate marker for HR-HPV infection in cancers of the oral cavity remains controversial. Objective: The objectives of the study were to investigate the expression of p16 and the presence of HR-HPV in OSCC and oral verrucous carcinoma (VC) and to determine if p16 could be used as a surrogate marker for HR-HPV. Materials and Methods: Forty one formalin-fixed, paraffin-embedded tissues of OSCC (n=37) or VC (n=4) with clinical and histopathologic data of each case were collected. Expression of p16 was determined by immunohistochemistry, focusing on both staining intensity and numbers of positive cells. The presence of HPV types 16 and 18 was detected by polymerase chain reaction (PCR). Descriptive statistics were employed to describe the demographic, clinical, and histopathologic parameters. Associations between p16 overexpression, HR-HPV and all variables were determined by Fisher's exact test, odds ratios (ORs) and corresponding 95% confidence intervals (CIs). In addition, the use of p16 as a surrogate marker for HR-HPV was analyzed by sensitivity and specificity tests. Results: p16 was overexpressed in 8/37 cases (21.6%) of OSCC and 2/4 cases (50%) of VC. HPV-16 was detected in 4/34 OSCC cases (11.8%) and HPV-18 was detected in 1/34 OSCC cases (2.9%). Co-infection of HPV-16/18 was detected in 1/4 VC cases (25%). Both p16 overexpression and HR-HPV were significantly associated with young patients with both OSCC and VC (p<0.05, OR 20, 95% CI 1.9-211.8; p<0.05, OR 23.3, 95% CI 2.4-229.7, respectively). p16 was able to predict the presence of HPV-16/18 in OSCC with 40% sensitivity and 79.3% specificity and in VC with 100% sensitivity and 66.7% specificity, respectively. Conclusions: p16 overexpression was found in 24.4% of both OSCC and VC. HR-HPV, regardless of type, was detected in 15.8% in cases of OSCC and VC combined. The results of sensitivity and specificity tests suggest that p16 can be used as a surrogate marker for HR-HPV in OSCC and VC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8351-8359
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• 2014

Background: Recent epidemiological data have implicated human papilloma virus (HPV) infection in the pathogenesis of head and neck cancers, especially oropharyngeal cancers. Although, HPV has been detected in varied amounts in persons with oral dysplasia, leukoplakias and malignancies, its involvement in oral tongue carcinogenesis remains ambiguous. Materials and Methods: HPV DNA prevalence was assessed by PCR with formalin fixed paraffin embedded sections (n=167) of oral tongue squamous cell carcinoma patients and the physical status of the HPV16 DNA was assessed by qPCR. Immunohistochemistry was conducted for p16 evaluation. Results: We found the HPV prevalence in tongue cancers to be 51.2%, HPV 16 being present in 85.2% of the positive cases. A notable finding was a very poor concordance between HPV 16 DNA and p16 IHC findings (kappa<0.2). Further molecular classification of patients based on HPV16 DNA prevalence and p16 overexpression showed that patients with tumours showing p16 overexpression had increased hazard of death (HR=2.395; p=0.005) and disease recurrence (HR=2.581; p=0.002) irrespective of their HPV 16 DNA status. Conclusions: Our study has brought out several key facets which can potentially redefine our understanding of tongue cancer tumorigenesis. It has emphatically shown p16 overexpression to be a single important prognostic variable in defining a high risk group and depicting a poorer prognosis, thus highlighting the need for its routine assessment in tongue cancers. Another significant finding was a very poor concordance between p16 expression and HPV infection suggesting that p16 expression should possibly not be used as a surrogate marker for HPV infection in tongue cancers. Interestingly, the prognostic significance of p16 overexpression is different from that reported in oropharyngeal cancers. The mechanism of HPV independent p16 over expression in oral tongue cancers is possibly a distinct entity and needs to be further studied.

• 대한두경부종양학회지
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• 제20권2호
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• pp.172-176
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• 2004

Background and Objectives: Standard treatment of locally advanced laryngeal, hypopharyngeal, and some oropharyngeal cancers includes total laryngectomy. In an attempt to preserve the larynx through induction chemotherapy, we designed induction chemotherapy followed by definitive radiation in patients with potentially respectable head and neck cancer to determine whether organ preservation is feasible without apparent compromise of survival. Materials and Methods: The twenty-six patients diagnosed advanced head and neck squamous cell carcinoma, Stage III or IV (AJCC 2002) and performed organ preservation protocols in Ajou university hospital from 1994 to 2001 were included in this study. Results: Neoadjuvant chemotherapy showed an overall response rate of 84.6% and a complete remission (CR) rate was 59.1% following neoadjuvant chemotherapy and radiation. Seven of thirteen patients were able to preserve their larynges for more than two years by chemotherapy and radiation. There were no treatment related mortality after 2 cycles of induction chemotherapy. Conclusion: Although Organ preservation protocol through neoadjuvant chemotherapy and radiation need more controlled randomized study, it was considered alternative treatment modality in advanced head and neck cancer.

• Radiation Oncology Journal
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• 제14권2호
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• pp.95-103
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• 1996

목적 : 구인두암으로 방사선치료를 받은 환자들을 대상으로 후향적 분석을 시행하여 생존율, 치료 실패 양상 및 생존율에 미치는 요인 등을 알아보고자 하였다. 방법 : 1985년 3월부터 1993년 6월까지 경북대학교병원 치료방사선과에서 구인두암으로 방사선치료를 시행한 53예의 환자를 대상으로 후향적 분석을 시행하였다. 환자의 연령은 31세에서 73세로 중간값은 54세였으며 남자 47예 여자 6예였다. 조직학적으로 편평세포암종이 42예, 미분화암종 이 10예, 선양 낭성암종이 1예였다. 병기별 분포는 I기 2예, II기 12예, III기 12예, IV기 27예이었다. T1 7예, T2 28예, t3 10예, T4 7예, T병기가 불명확한 경우가 1예이었고, N0 17예, Nl 13예, N2 21예, N3 2예였다. 원발병소는 편도 36예, 설기저부 12예, 그리고 연구개 5예였다. 방사선 단독치료가 25예, 유도화학요법 및 방사선치료 병용요법이 28예였다. 유도화학요법은 CF (cisplatln, 5-fluorouracil) 또는 CVB (cisplatin, vincristine, bleomycin) 약제로 1-3회 시행하였다 방사선치료는 6MV X선 및 8-10MeV 전자선을 이용하였고 방사선 치료선량은 일일 180-200 cGy씩 총 4500-7740 cGy로 중간값은 7100 cGy였다. 환자의 추적기간은 4개월에서 99개월로 중간추적기간이 21개월이었다. 결과 : 방사선치료 후 37예 ($69.8\%$)에서 완전관해를 보였고 16예 ($30.2\%$) 에서 부분관해를 보였다. 전체 환자에서 2년생존율은 $47\%$, 3년생존율은 $42\%$였고 중앙생존기간은 23개월이었다. 치료에 대한 반응 (p=0.004) 및 전체병기가 (p=0.02) 통계적으로 의미있게 생존율에 영향을 미치는 것으로 나타났다. 2년 무병생존율은 $45.5\%$였고 T 병기 (p=0.03), N 병기 (p=0.04) 및 전체병기가 (p=0.04) 의미있게 무병생존을에 영향을 미치는 것으로 나타났다. 환자의 나이, 성별, 조직학적 소견, 원발병소, 방사선량 및 화학요법과의 병합치료는 무병생존율에 영향을 주지 않았다. 방사선치료 후 완전관해를 보인 36예 중 추적조사가 가능했던 32예에서의 치료 실패양상은 국소재발이 8예, 원격전이가 4예로 주된 치료 실패 원인은 국소재발이었다. 결론 : 본 연구에서는 N 병기, 7 병기 및 전체병기가 무병 생존율에 영향을 미치는 인자로 나타났으며, 국소재발이 주된 실패 요인이 되고 있어 국소완치를 위한 노력이 절실히 요구된다. 현재까지 구인두암의 치료는 방사선 단독치료가 가장 효과적인 치료방법으로 여겨지며 화학요법은 좀더 많은 비교 대조군 연구를 통해서만 역할을 평가할 수 있을 것으로 사료된다.