• Korean Journal of Head & Neck Oncology
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• v.25 no.1
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• pp.28-32
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• 2009

Background : The most frequently reported risk factors for head and neck suamous cell carcinoma are smoking and alcohol. But in a recent overview, human papilloma virus(HPV) infection was revealed the important carcinogenic factor in oropharyngeal cancer. We aimed to clarify whether HPV directly effects on the oncogenesis and biologic behavior of hean and neck squamous cell carcinoma by comparison with infection prevalence, and physical status of virus. Material and Method : We used HPV genotyping DNA chip(Biocore, Korea, Seoul) arrayed by multiple oligonucleotide probes of L1 sequence of 26 types of HPV and HPV genotypes are identified by fluorescence scanner. The copy numbers of HPV E2 and E6 open reading frames(ORF) were assessed using a TaqMan-based 5'-exonuclease quantitative real-time PCR assay. The ratio of E2 to E6 copy numbers was calculated to determine the physical status of HPV-16 viral gene. Results : We observed a significant difference in HPV prevalence between tonsillar cancer group and control group(73.1% vs. 11.6%), and most of the HPVs were type 16(87.2%) and integrated(94.1%) state. In terms of oral tongue cancer, we demonstrate that 30.5% has integrated HPV-16 in cancer tissue. But Glottic cancer only 1% is related to HPV-16 integration. Conclusion : This study revealed significant relationship of HPV prevalence with oropharyngeal and oral tongue squamous cell carcinoma. Most of HPV were 16 type and integrated or mixed, HPV-16 integration could be directly related to the carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6193-6200
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• 2015

Head and neck cancer, including oral cancer, is the sixth most common cancer in humans worldwide. More than 90% of oral cancers are of squamous cell carcinoma type. Recent studies have shown a strong relationship between human papillomavirus (HPV) infection and head and neck cancer, especially oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). Moreover, the incidence of HPV-related OSCC appears to be on the rise while HPV-unrelated OSCC tends to have stabilized in the past decades. p16, a tumor suppressor gene, normally functions as a regulator of the cell cycle. Upon infection with high-risk types of HPV (HR-HPV), particularly types 16, 18, 31, 33, 34, 35, 39, 51, 52, 56, 58, 59, 66, 68, and 70, the expression of p16 is aberrantly overexpressed. Therefore, the expression of p16 is widely used as a surrogate marker for HPV infection in head and neck cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.891-896
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• 2012

This study focused on infection rates and subtypes of human papillomavirus (HPV) in patients with oropharyngeal squamous cell carcinoma (OSCC), and the relationship between HPV status and prognosis of the disease. We evaluated sixty-six OSCC patients who met the enrollment criteria during the period from January 1999 to December 2009. The presence or absence of oncogenic HPV types in tumors was determined using the SPF10 LiPA25 assay. Overall survival (OS) and disease specific survival (DSS) for HPV positive and HPV negative patients were estimated using Kaplan-Meier analysis. The Cox regression model was applied for multivariate analysis. HPV-DNA was detected in 11(16.7%) of all specimens. Among them, 7 were type HPV-16, while other types were HPV-16/11, HPV-35, HPV-58/52, and HPV-33/52/54. Patients with HPV positive tumors were more likely to be female, non-smokers and non-drinkers (p=0.002, 0.001 and 0.001, respectively). After a median follow-up of 24.5 months, patients with HPV positive tumors had significantly better overall survival (HR=0.106[95%CI=0.014-0.787], p=0.016,) and disease specific survival (HR=0.121[95%CI=0.016-0.906], p=0.030). Patients with HPV positive OSCC have significantly better prognosis than patients with HPV negative tumors. HPV infection is an independent prognostic factor.

• Korean Journal of Radiology
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• v.20 no.8
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• pp.1266-1274
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• 2019

Objective: To determine whether radiologic extranodal extension (ENE) appearing on pretreatment CT and MRI could predict the prognosis in patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). Materials and Methods: The study population was obtained from a historical cohort diagnosed with HPV-related OPSCC. A total of 134 OPSCC patients who had a metastatic lymph node on pretreatment CT or MRI were included, and radiologic ENE was evaluated by two experienced head and neck radiologists. Kaplan-Meier and multivariate Cox regression analyses were performed to evaluate the impact of radiologic ENE on progression-free survival (PFS). The diagnostic performance of CT and MRI for the diagnosis of ENE was also evaluated in patients who underwent neck dissection. Results: Seventy patients (52.2%) showed radiologic ENE-positive findings. Although patients showing radiologic ENE had a worse 3-year PFS (83.7% vs. 95.3%, p = 0.023), the association between radiologic ENE and PFS was not statistically significant on multivariate analysis (p = 0.141; hazard ratio, 2.68; 95% confidence interval, 0.72-9.97). CT or MRI had a sensitivity of 62%, specificity of 77.8%, and accuracy of 71.9% for predicting pathologic ENE. Conclusion: Radiologic ENE on CT or MRI did not predict poor PFS in patients with HPV-related OPSCC, although there was a trend towards worse PFS. Further studies are warranted to determine whether radiologic ENE is a useful imaging biomarker to risk-stratify patients with HPV-related OPSCC.

• Imaging Science in Dentistry
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• v.46 no.4
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• pp.285-290
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• 2016

In this report, we describe the incidental finding of an oropharyngeal mass in a patient who presented with a chief complaint of temporomandibular pain. The patient was initially evaluated by an otorhinolaryngologist for complaints of headaches, earache, and sinus congestion. Due to worsening headaches and trismus, he was further referred for the management of temporomandibular disorder. The clinical evaluation was uneventful except for limited mouth opening (trismus). An advanced radiological evaluation using magnetic resonance imaging revealed a mass in the nasopharyngeal/oropharyngeal region. The mass occupied the masticatory space and extended superioinferiorly from the skull base to the mandible. A diagnostic biopsy of the lesion revealed a long­standing human papilloma virus (HPV­16)­positive squamous cell carcinoma of the oropharynx. This case illustrates the need for the timely radiological evaluation of seemingly innocuous orofacial pain.

• Korean Journal of Head & Neck Oncology
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• v.23 no.1
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• pp.21-25
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• 2007

Background：Squamous cell carcinoma(SCC)of the palatine tonsils represents approximately 15-23% of all intraoral SCC. The most frequently reported risk factors for oropharyngeal cancer are smoking and alcohol. In a recent overview of HPV and tonsillar squamous cell carcinoma(TC), 51% contained HPV DNA, and HPV-16 being the most frequent type. We aimed to clarify whether HPV directly effects on the oncogenesis and biologic behavior of TC by comparison with infection prevalence, and physical status of virus. Material and Method：We used HPV genotyping DNA chip(Biocore, Korea, Seoul) arrayed by multiple oligonucleotide probes of L1 sequence of 26 types of HPV and HPV genotypes are identified by fluorescence scanner. The copy numbers of HPV E2 and E6 open reading frames(ORF) were assessed using a TaqMan-based 5'-exonuclease quantitative real-time PCR assay. The ratio of E2 to E6 copy numbers was calculated to determine the physical status of HPV-16 viral gene. Results：We observed a significant difference in HPV prevalence between 52 TCs and 69 CFTs(73.1% vs. 11.6%), and most of the HPVs were type 16(87.2%)and non-episomal(94.1%) state. Conclusions：This study regarding HPV infection prevalence and mechanism in the largest population of palatine tonsillar squamous cell carcinoma with chronic follicular tonsillitis revealed significant difference pf HPV prevalence between TC and CFT. Most of HPV were 16 type and integrated or mixed, HPV-16 integration could be directly related to tonsillar carcinogenesis.

• Radiation Oncology Journal
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• v.35 no.3
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• pp.233-240
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• 2017

Purpose: To validate the 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system for human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) and investigate whether a modified classification better reflects the prognosis. Materials and Methods: Medical records of patients diagnosed with non-metastatic HPV-related OPSCC between 2010 and 2016 at a single institution were retrospectively reviewed. HPV status was determined by immunohistochemical analysis of p16 and/or HPV DNA polymerase chain reaction (PCR). We reclassified TNM stage T0-1 and N0-1 as group A, T2-3 or N2 as B, and T4 or N3 as C. Survival analysis according to 8th AJCC/UICC TNM staging and the modified classification was performed. Results: Of 383 OPSCC patients, 211 were positive for HPV DNA PCR or p16. After exclusion, 184 patients were included in this analysis. Median age was 56 years (range, 31 to 81 years). Most primary tumors were in the palatine tonsil (148 tumors, 80%). The eighth AJCC/UICC TNM classification could not differentiate between stage I and II (p = 0.470) or II and III (p = 0.209). Applying modified grouping, the 3-year overall survival rate of group A was significantly higher than that of group B and C (98% vs. 91%, p = 0.039 and 98% vs. 78%, p < 0.001, respectively). Differentiation between group B and C was marginally significant (p = 0.053). Conclusion: The 8th AJCC/UICC TNM staging system did not clearly distinguish the prognosis of stage II from that of other stages. Including the T2N0-1 group in stage II may improve prognostic stratification.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10289-10292
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• 2015

Background: The involvement of HPV in oral and oropharyngeal carcinogenesis was first proposed in 2004, based on epithelial HPV tropism and detection of HPV genotypes in oral squamous cell carcinoma samples. While 60-70% of oropharynx tumors may be HPV-positive, only 10 to 19% of tumors of the oral cavity, larynx and hypopharynx appear to have HPV infection. The aim of the study was to evaluate HPV infection associated with oropharyngeal cancer. Materials and Methods: Seventy-eight cases were selected for p16 immunoexpression reactions, and demographic data were collected for comparisons. Results: Most patients were over 60 years old, and 64.1% were smokers. Immunohistochemistry results showed that 86.3% of cases stained positive for p16 protein. Conclusion: The oropharyngeal cancer profile at Erasto Gaertner Hospital presented a high index of smokers over 60 years as well a high number of p16+ tumors, for what we can not determinate the main etiologic factor, but can be aware of the number of patients that presented HPV infection. Since prevention is still the best way to deal with cancer disease, it is important to analyze the interaction of these two etiologic factors and how to detect lesions at an early stage.

• 대한두경부종양학회:학술대회논문집
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• 1990.11a
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• pp.20.2-22
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• 1990

• Korean Journal of Radiology
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• v.24 no.1
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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.