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Clinical and scientific impact of human papillomavirus on head and neck cancer

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World Journal of Clinical Oncology 2014年第4期5卷 781-791页

作者： Jeffrey M Friedman Mark J Stavas Anthony J Cmelak Department of Radiation Oncology Vanderbilt University Medical Center NashvilleTN 37232 United States

Head and neck cancer(HNC) arises from the skull base to the clavicles and is the fifth most common cancer in the world by incidence. Historically, in the developed world HNC was associated with tobacco use and alcohol consumption, and the combination of the two produced a synergistic increase in risk. However, beginning in 1983, investigators have found a significant and growing proportion of HNC patients with human papillomavirus-positive(HPV) tumors who neither drank nor used tobacco. Since that time, there has been increased interest in the molecular biology of HPV-positive HNC. Multiple studies now show that HPV has shifted the epidemiological landscape and prognosis of head and neck squamous cell carcinoma(HNSCC). These studies provide strong evidence for improved survival outcomes in patients with HPV-positive HNSCC compared to those with HPV-negative HNSCC. In many reports, HPV status is the strongest predictor of locoregional control, disease specific survival and overall survival. In response to these findings, there has been significant interest in the best management of HPV-positive disease. Discussions within major cooperative groups consider new trials designed to maintain the current strong survival outcomes while reducing the long-term treatment-re-lated toxicities. This review will highlight the epidemiological, clinical and molecular discoveries surrounding HPV-related HNSCC over the recent decades and we conclude by suggesting how these findings may guide future treatment approaches.

关键词： Human papilloma virus Head and neck cancer Squamous cell carcinoma Chemotherapy Radiation Molecular biology

An Overview and Comparative Evaluation of Head and neck Cancer Risk Factors in India and Australia

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International Journal of Otolaryngology and Head & neck Surgery 2018年第5期7卷 254-267页

作者： Satinder Pal Singh Robert Eisenberg Gary Hoffman Department of Otolaryngology & Head neck Surgery Swift Hospital Amritsar India Department of Otolaryngology-Head and neck Surgery John Hunter Hospital Newcastle Australia Department of Oral Maxillo Facial Surgery John Hunter Hospital Newcastle Australia

Aim: An overview and comparative evaluation of head and neck cancer risk factors in India and Australia. Method: In this review we included articles with information on head and neck cancer risk factors and its association based on: smoking tobacco, alcohol, smokeless tobacco, betel nut and areca nut chewing, viral infection like HPV, dental hygiene, diet, family history, socioeconomic status, other heavy metals and systemic conditions. Articles with clinical features, diagnosis, treatment and prognosis were excluded. Results: Head and neck cancer in India has different demographic, risk factors, dietary habits, personal and family history. Oral cancer is more common amongst all head and neck squamous cell cancers in males. This is mainly attributed with consumption of a variety of smokeless tobacco, smoking, alcohol, poverty, illiteracy, cultural, advanced stage at presentation;lack of good treatment infrastructure creates main challenge to India as compared to Australia. Conclusion: The knowledge about risk factors for HNC in public health education for general population supports health promotion and tobacco prevention, which is the main aim of the programs started by the government, as head and neck cancers are potentially preventable.

关键词： Head and neck Cancer Oral Cavity Oropharynx Smoking and Smokeless Tobacco Alcohol HPV Oral Hygiene Other Risk Factors

Comparative pilot study on the effects of pulsating and static cupping on non-specific neck pain and local skin blood perfusion

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Journal of Traditional Chinese Medical Sciences 2018年第4期5卷 400-410页

作者： Yang Yang Liangxiao Ma Tingli Niu Junxiang Wang Yue Song Yu Lu Xuezhi Yang Xin Niu Ali Mohammadi School of Acupuncture-Moxibustion and Tuina Beijing University of Chinese MedicineBeijing 100029China Dongfang Hospital Affiliated to Beijing University of Chinese Medicine Beijing 100078China School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 100029China Dr Ali Mohammadi Clinic of Acupuncture and Moxibustion No31Dr Hesabi Ave RastakhizGohardashtAlborz Province ***Iran

Objective:To compare the effects of pulsating and static cupping on non-specific neck pain and local skin microcirculation blood perfusion,which is a pilot study.Methods:Seventy participants with non-specific neck pain were randomized to the following groups:low-frequency pulsating cupping(LF,n=20);high-frequency pulsating cupping(HF,n=20);static cupping(SC,n=20),or waiting list(WL,n=10).The LF,HF,and SC received a bilateral 10-minute cupping treatment at Jianzhongshu(SI 15).Outcomes were pain intensity(visual analog scale,VAS),functional status(neck Disability Index,NDI),and skin blood perfusion at the SI 15,Dazhui(GV 14),and Shenzhu(GV 12)acupoint areas,measured using Laser Speckle Contrast Analysis technology.Results:Both LF and HF groups showed a significant reduction in VAS scores compared with the SC group(9.00,95%Cl 1.05-16.95,P=.027;8.75,95%CI 0.80-16.70,P=.031).There was no significant difference in VAS scores between the LF and HF groups(P>.05)and between NDI scores measured 3 days after intervention among the four groups(P>.05).In the SI 15 area,blood perfusion in the three treatment groups was higher than that in WL group(Pneck pain compared with static cupping,which may be related to its better effect on improving the local skin blood perfusion.

关键词： Pulsating cupping Static cupping Non-specific neck pain VAS Blood perfusion

Nimotuzumab with Concurrent Chemo-Radiotherapy in Patients with Locally Advanced Squamous Cell Carcinoma of Head and neck (LASCCHN)

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Journal of Cancer Therapy 2015年第4期6卷 356-361页

作者： Naresh Somani Department of Clinical Trial and Research Bhagwan Mahaveer Cancer Hospital and Research Centre Jaipur India

Background: Head and neck cancers (HNCs) constitute 5% of all cancers globally and are the most common cancers in India. Chemotherapy and radiotherapy have not been proved to be effective in advanced cases and the prognosis remains dismal. This underscores the need for newer treatment options in these cases. Nimotuzumab, an anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, was safer when combined with chemo- or radio-therapy. Aim: To evaluate the safety and efficacy of concurrently administered nimotuzumab with chemo-radiotherapy in patients with advanced inoperable squamous cell carcinomas of head and neck (LASCCHN). Methods:?This was an open-label, single arm study evaluating 57 patients with histologically confirmed inoperable LASCCHN (stages III and IV) and eastern co-operative oncology group (ECOG) performance status < 2. Informed consent was obtained from all patients. The patients were administered IV cisplatin 30 mg/m2?and IV nimotuzumab 200 mg weekly for 6 weeks, along with radiotherapy of 6600 cGy over 33 fractions. Patients were evaluated over response evaluation criteria in solid tumors (RECIST) criteria 24 weeks after the last cycle of chemotherapy. Results: Mean age of patient was 50 years old (29 - 79 years old). The most common site of cancer was oral cavity (56.1%). Forty six patients (80.7%) completed 6 cycles of therapy. Objective response rate (ORR) was 80.7%, with 34 patients (59.6%) achieving complete response (CR), and 12 (21%) achieving partial response (PR). Stable disease (SD) was noted in 8 (14%) patients and progressive disease in 3 (5.2%) patients. Conclusion: Addition of nimotuzumab is a safe and efficacious option in patients with inoperable LASCCHN. Our observations confirm the available Phase II data. The long term survival benefits based on this encouraging response rate need to be further evaluated in this subset of cancer patients.

关键词： Nimotuzumab Anti-Epidermal Growth Factor Receptor (Anti-EGFR) Chemotherapy Radiotherapy Locally Advanced Squamous Cell Carcinoma of Head and neck (LASCCHN)

Prognostic Significance of Vascular Endothelial Growth Factor-A (VEGF-A) and Ki-67 Expression in Head and neck Cancer Patient with Negative neck

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International Journal of Otolaryngology and Head & neck Surgery 2015年第5期4卷 356-368页

作者： Vipa Boonkitticharoen Boonchu Kulapaditharom Noppadol Larbcharoensub Phurich Praneetvatakul Thongchai Bhongmakapat Department of Diagnostic and Therapeutic Radiology Ramathibodi Hospital Mahidol University Bangkok Thailand Department of Otolaryngology Ramathibodi Hospital Mahidol University Bangkok Thailand Department of Pathology Ramathibodi Hospital Mahidol University Bangkok Thailand

Background: Management of N0 neck in patients with head and neck squamous cell carcinoma (HNSCC) remains a subject of continued debate. Prognostic biomarkers might provide useful information for treatment selection and adjustment. Objective: To evaluate the prognostic relevance of VEGF-A and Ki-67 expression to types of neck management. Methods: This prospective study included 140 patients with HNSCC. Tumor expression of VEGF-A and Ki-67 was measured by immunohistochemistry. Based on tumor size and site criteria, 88 patients with N0 neck were categorized as high, intermediate and low risk of subclinical neck diseases and accordingly treated by elective neck dissection (END), irradiation (ENI) and observation. Adjuvant treatment was given to tumor with close or positive margins. A multivariate Cox regression model was used to identify prognostic factors. Impact of biomarker expression, treatment type and risk category on disease-specific survival (DSS) in the setting of N0 neck were evaluated by Kaplan-Meier survival and adjusted hazard ratio (HR). Results: Coexpression of VEGF-A and Ki-67 (HR = 2.351, p = 0.021) and positive node (HR = 2.301, p = 0.009) were independent prognostic factors for HNSCC. In the setting of N0 neck, marker coexpression has an HR of 4.97 (p = 0.004) independent of treatment modalities (p = 0.069) and risk categories (p = 0.971). Alternatively, neither marker expression was predictive of a better treatment outcome for END compared to ENI, as suggested by the odds of patients being survived 15.4 times greater (p = 0.01) and the 5-year DSS rates of 85.1% versus 44.7% (p = 0.008). Conclusion: Coexpression of VEGF-A and Ki-67 is a suggestion of tumor microinvasiveness in addition to risk of lymph node metastasis and may indicate the need of adjuvant treatment despite negative tumor margins. Neither marker expression serves an indicator for the selection of END over ENI in neck management.

关键词： Head and neck Squamous Cell Carcinoma Negative neck Node neck Management Prognostic Biomarkers VEGF-A and Ki-67

Head and neck Cancer Early Identification of Malnutrition High Risk Patients and Quality of Life Optimization

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International Journal of Otolaryngology and Head & neck Surgery 2019年第6期8卷 204-216页

作者： Joaquim Castro Silva Augusta Silveira Ana Sacau Eurico Monteiro Teresa Sequeira Portuguese Institute for Oncology (IPOP) Porto Portugal Fernando Pessoa University (UFP) Porto Portugal Centre of Health Studies and Research of the University of Coimbra (CEISUC) Coimbra Portugal

Malnutrition in Head and neck cancer (HNC) patients can be present at the moment of diagnosis. The nutritional status is determinant for the treatment success and quality of life of the patients. The nutritional status gradually declines during treatment and the majority of patients undergoing treatment will need nutritional therapy. On the other hand, HNC, like other cancers, can induce a paraneoplastic syndrome that leads to cachexia. This cachexia status is most of the times the cause of death or the cause of treatment failure. So, early identification of malnutrition high risk patients is crucial to start an adequate nutrition support intervention in HNC patients. This study aims to identify HNC patients who present malnutrition or higher risk of malnutrition;to signalize variables that support early identification of high-risk patients of becoming malnourished and to establish a dynamic relationship between malnutrition risk in these patients and Quality of Life (QoL) impacts. For six months consecutive outpatients with HNC admitted at the Head & neck Unity of Oncology Portuguese Institute—Porto were asked to participate in the research (n = 114). The European Organisation for Research and Treatment of Cancer (EORTC) cancer-specific HRQoL questionnaire-QLQ-C30 and Malnutrition Universal Screening Tool, MUST were used. At the moment of first presentation, 32 patients (28.1%) presented high-risk of malnutrition. HNC patients with oral cavity and oropharynx tumour locations, older, with low literacy or with BMI under 18.5 at the moment of diagnosis, represent a high-risk group. When HNC is considered, a dynamic and bi-directional connection between malnutrition and QoL is observed. A significant (p Emotional and social functional scales and all symptom scales—including pain, presented significant differences between high and medium risk of malnutrition patients. Fatigue, pain, insomnia, appetite loss and financial difficulties were domains directly related to high risk of malnutrition patients. Pain scores were

关键词： Oncology Head and neck Cancer Body Mass Index Malnutrition Nutritional Support Quality of Life Malnutrition Universal Screening Tool

The Survival of Head and neck Carcinoma Patients Depends on Secondary Causes of Death

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Journal of Cancer Therapy 2017年第13期8卷 1187-1193页

作者： André Buchali Winfried Huhnt Ina Maekelburg Sophia Rohrberg Dietrich Sidow Eyck Blank Christina Schroeder Achim Franzen Department of Radiooncology Ruppiner Kliniken Neuruppin Germany Medical University Theodor Fontane Neuruppin Germany Justus Liebig University Giessen Germany Department of Otorhinolaryngology Head and neck Surgery Ruppiner Kliniken Neuruppin Germany

Purpose: The study aimed to analyse causes of death and differential survival after multimodal treatment of head and neck carcinoma patients. Methods and Materials: Between September 2000 and December 2015, 935 patients received a multimodal treatment of head and neck carcinoma. Of these, 562 patients (60.1%) underwent a resection of the primary tumour and a postoperative radio- or radiochemotherapy and 373 patients (39.9%) received definitive radio- or radiochemotherapy. The median follow-up was 21.0 months (0.5 - 175.4 months). Results: At the endpoint of the investigation, 465 patients (49.7%) were alive. The median survival of all patients was 44.8 months (0.5 - 164.3 months). A total of 470 patients (50.3%) died. The causes of death were divided into five groups: 22 patients (2.4%) died of therapy-associated complications with a median of 2.2 months (1.6 - 3.3 months). The 160 patients (17.1%) with intercurrent death, 117 patients (12.5%) with deaths from locoregional progression with or without metastasis, and 86 patients (9.2%) with deaths from metastasis without locoregional recurrence showed comparable survival curves with a median survival of 13.3 months, 13.6 months, and 14.4 months. Eighty-five patients (9.1%) died from second malignant diseases and controlled treated head and neck carcinomas with a median survival of 34.5 months (P < 0.001). Conclusion: Despite a locoregional control and metastasis-free survival of 78.3% patients, only 49.7% of the patients were alive, due to a high rate of intercurrent and second malignant diseases. The short median survival rate is mainly due to the tumours (locoregional and or distant progression) and intercurrent causes of death, with the second malignant diseases leading to death later on.

关键词： Head and neck Carcinoma Radiochemotherapy Causes of Death

Usability of Deformable Image Registration for Adaptive Radiotherapy in Head and neck Cancer and an Automatic Prediction of Replanning

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International Journal of Medical Physics, Clinical Engineering and Radiation Oncology 2017年第1期6卷 10-20页

作者： Masao Tanooka Hiroshi Doi Toshihisa Ishida Kazuhiro Kitajima Tsukasa Wakayama Toshiyuki Sakai Hiroyuki Inoue Noriko Kotoura Kengo Kosaka Kazuo Tarutani Masayuki Fujiwara Norihiko Kamikonya Department of Radiological Technology Hyogo College of Medicine College Hospital Nishinomiya Japan Department of Radiology Hyogo College of Medicine Hyogo Nishinomiya Japan

Deformable image registration (DIR) has been an important component in adaptive radiotherapy (ART). Our goal was to examine the accuracy of ART using the dice similarity coefficient (DSC) and to determine the optimal timing of replanning. A total of 22 patients who underwent volume modulated arc therapy (VMAT) for head and neck (H&N) cancers were prospectively analyzed. The planning target volume (PTV) was to receive a total of 70 Gy in 33 fractions. A second planning CT scan (rescan) was performed at the 15th fraction. The DSC was calculated for each structure on both CT scans. The continuous variables to predict the need for replanning were assessed. The optimal cut-off value was determined using receiver operating characteristic (ROC) curve analysis. In the correlation between body weight loss and DSC of each structure, weight loss correlated negatively with DSC of the whole face (rs = -0.45) and the face surface (rs = -0.51). Patients who required replanning tended to have experienced rapid weight loss. The threshold DSC was 0.98 and 0.60 in the whole face and the face surface, respectively. Patients who showed low DSC in the whole face and the face surface required replanning at a significantly high rate (P < 0.05 and P < 0.01). Weight loss correlated with DSC in both the whole face and the face surface (P < 0.05 and P < 0.05). The DSC values in the face predicted the need for replanning. In addition, weight loss tended to correlate with DSC. DIR during ART was found to be a useful tool for replanning.

关键词： Deformable Image Registration Adaptive Radiotherapy Head and neck Can-cer Dice Similarity Coefficient Volume Modulated Arc Therapy

Classification of femoral neck fractures according to pauwels: interpretation and confusion ——Reinterpretation: a simplified classification based on mechanical considerations

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Journal of Biomedical Science and Engineering 2010年第6期3卷 638-643页

作者： Andrej Maria Nowakowski Peter Emil Ochsner Martin Majewski 不详

ABSTRACT The Pauwels Classification of femoral neck fractures, initially published in 1935, is used world-wide. Unfortunately, modern textbooks give varying angle and anatomic specifications between the classified fracture grades. This inconsistency is perpetuated in the literature, so that it is difficult to compare conclusions made by different authors. Pauwels himself left room for interpretation. He published two studies, one in 1935 and one in 1973, each including 3 diagrams. The 1935 version cited an angle of 8° representing the vector of static forces acting on the femoral head. The 1973 diagrams, however, cited an angle of 16° to represent dynamic forces, without changing the angle from horizontal. This already complex sche- me is complicated by the fact that it depends on other factors such as femoral neck shaft (CCD) angle, femoral neck and head diameter, and/or distance of the fracture from the center of the femoral head. The multitude of factors argues against a rigid classification based on fixed angles from horizontal. Pauwels himself did not establish fixed critical angles between the fracture grades. In his own explanation of the system, he placed more value on mechanical considerations such as compression stress, shear stress, tensile force, shearing force, and torque. We propose therefore a simplified version of the Pauwels Classification: Grade I for fractures impacted in valgus, Grade II for fractures without free torque, and Grade III for fractures with free torque.

关键词： Pauwels Garden Classification Femoral neck Fracture