口腔及口咽癌新版TNM分期与NCCN诊治指南部分解读

美国癌症联合委员会《AJCC肿瘤分期手册》与美国国立综合癌症网(NCCN）肿瘤学临床实践指南已广泛用于临床实践中。NCCN肿瘤诊治指南与TNM分期密切相关,指南为不同TNM分期的肿瘤制定了较为详细的诊治标准,作为依据指导临床应用。2017年第8版口腔及口咽癌TNM分期新增了较多内容,如侵袭深度（DOI）、淋巴结外扩展（ENE）、人乳头瘤病毒（HPV）等指标用于了新的分期中,并且为HPV相关的口咽癌制定了一个新的TNM分期。2018年版NCCN口腔与口咽癌指南及时反映了第8版口腔及口咽癌TNM分期中新的变化,同时亦为HPV相关的口咽癌制定了相应的诊治指南。新的TNM分期及NCCN诊治指南对口腔与口咽癌患者诊疗策略的制定及治疗方案的选择具有较大的指导意义。为了临床工作的需要,本文结合两者的变化进行了部分解读。     

口腔癌及口咽癌病理诊断规范

口腔癌及口咽癌是口腔颌面部最常见的恶性肿瘤。规范化的口腔癌及口咽癌病理诊断报告不仅应提供给临床准确的病理诊断,还应包括与患者预后评估、治疗策略选择相关的信息。由中华口腔医学会口腔病理学专业委员会牵头组织成立专家组,对口腔癌及口咽癌病理标本固定、取材及报告内容等进行研讨与规范,形成《口腔癌及口咽癌病理诊断规范》。此规范涵盖了近年来在口腔癌和口咽癌临床病理方面的一些重要变化,如口腔癌肿瘤T分期应考虑肿瘤侵袭深度、肿瘤N分期应考虑有无淋巴结外扩展、口咽癌中新亚型人乳头状瘤病毒相关性鳞状细胞癌等。希望通过本规范的制定,提高我国口腔癌及口咽癌病理报告质量,为临床治疗及预后评估提供依据。     

口腔癌及口咽癌病理诊断规范

口腔癌及口咽癌是口腔颂面部最常见的恶性肿瘤。规范化的口腔癌及口咽癌病理诊断报告不仅应提供给临床准确的病理诊断,还应包括与患者预后评估、治疗策略选择相关的信息。由中华口腔医学会口腔病理学专业委员会牵头组织成立专家组,对口腔癌及口咽癌病理标本固定、取材及报告内容等进行研讨与规范,形成《口腔癌及口咽癌病理诊断规范》。此规范涵盖了近年来在口腔癌和口咽癌临床病理方面的一些重要变化,如口腔癌肿瘤T分期应考虑肿瘤侵袭深度、肿瘤N分期应考虑有无淋巴结外扩展、口咽癌中新亚型人乳头状瘤病毒相关性鳞状细胞癌等。希望通过本规范的制定,提高我国口腔癌及口咽癌病理报告质量,为临床治疗及预后评估提供依据。     

2019年NCCN口腔口咽癌诊疗指南更新解读

美国癌症联合委员会2017年第8版《AJCC肿瘤分期手册》出版,口腔及口咽癌TNM分期标准中新增侵袭深度（DOI）、淋巴结外扩展（ENE）、人乳头瘤病毒（HPV）等指标,并将口咽癌分为HPV阳性（p16+）与HPV阴性（p16-）,分别制定了不同的TNM分期标准。2018年,美国国立综合癌症网（NCCN）首次为HPV阳性（p16+）口咽癌制定了诊疗指南。2019年第1版NCCN头颈癌诊疗指南已经发布,其中对口腔口咽癌指南做了部分修订。为临床工作需要,本文结合2版变化进行部分解读。     

晚期口腔和口咽恶性肿瘤治疗后影响吞咽的因素

口腔及口咽肿瘤治疗后往往对吞咽功能造成影响,术后口腔进食能力与手术和患者相关因素有关。晚期口腔及口咽癌术后接受或不接受化放疗的114例患者,记录临床病理参数和重建方式。采用口腔进食功能评分(FOIS)对治疗前、后的数据进行比较。结果:首次获得吞咽功能的平均时间为14 d。     

18例侵犯颈动脉的复发性口腔、口咽鳞状细胞癌的挽救性手术治疗效果评价

目的：评估晚期口腔及口咽鳞状细胞癌（squamous cell carcinoma,简称鳞癌）的挽救性手术及颈动脉处理的效果。方法：对18例侵犯颈总动脉的复发晚期口腔鳞癌及口咽鳞癌的患者行挽救性手术治疗,包括复发灶扩大切除术、颈总动脉结扎术、颈总动脉重建术、颈总动脉解剖术、颈总动脉包裹术,并用复合组织皮瓣修复组织缺损。结果：1例患者术后暂时性偏瘫,2例患者受区创口开裂,2例患者颈动脉爆裂,1例颈总动脉重建患者术后发生颈动脉栓塞。随访5~42个月,12例无复发,2例带瘤生存,4例死于局部复发或远处转移。结论：挽救性手术可有效治疗侵犯颈总动脉的复发晚期口腔鳞癌和口咽鳞癌。根据术前评估处理受肿瘤累及的颈动脉,术式包括颈总动脉结扎术、颈总动脉重建术、颈总动脉解剖术、颈总动脉包裹术。     

口腔鳞状细胞癌术后复发相关因素分析

目的    分析口腔鳞状细胞癌患者术后复发的相关临床因素。方法    随机抽取云南省第二人民医院口腔科2006年4月到2009年10月收治的62例口腔鳞状细胞癌患者的临床资料进行回顾性分析,记录患者原发肿瘤大小、区域淋巴结侵犯、邻近血管侵犯、邻近神经侵犯、手术切缘状况、淋巴结清扫数目、鳞状细胞癌的病理分级、年龄、性别等相关因素,并对数据进行相关分析。结果    对62例患者进行回顾性分析后,经统计学检验,不同的原发肿瘤大小、区域淋巴结侵犯、邻近血管侵犯、邻近神经侵犯、手术切缘状况、鳞癌的病理分级、年龄、性别的肿瘤复发差异均有统计学意义（均P＜0.05）。结论    口腔鳞状细胞癌术后复发与多种因素相关,应全面综合考虑,以降低患者术后的复发风险。     

708例口腔鳞状细胞癌颈淋巴转移临床病理分析

目的 探讨口腔鳞状细胞癌颈淋巴转移的规律及相关临床病理学因素。方法 对708例行颈淋巴清扫术的口腔鳞状细胞癌患者进行回顾性研究,通过单因素和多因素回归分析,寻找影响口腔鳞状细胞癌颈淋巴转移的相关临床病理学因素。采用SPSS19.0软件包对数据进行统计学分析。结果 口腔鳞状细胞癌的颈淋巴转移率为35.6%(252/708),各区的转移率分别为Ⅰ区30.7%（149/485）, Ⅱ区33.8%（164/485）,Ⅲ区22.5%（109/485）,Ⅳ区8.0%（39/485）,Ⅴ区4.9%（24/485）。在单因素分析中,年龄、肿瘤分化程度、肿瘤浸润深度、pT分级均与口腔鳞状细胞癌颈淋巴转移显著相关（P＜0.05）,而性别、原发灶部位与口腔鳞状细胞癌颈淋巴转移无显著相关性（P＞0.05）;在多因素分析中,仅肿瘤的分化程度、肿瘤的浸润深度、pT分级与口腔鳞状细胞癌颈淋巴转移有明显相关性（P＜0.05）,肿瘤浸润深度可能是口腔鳞状细胞癌发生颈淋巴转移的首要影响因素（OR=2.191）。结论 口腔鳞状细胞癌颈淋巴转移与pT分期、肿瘤浸润深度呈正相关,与肿瘤分化程度呈负相关。肿瘤浸润深度可能是口腔鳞状细胞癌颈淋巴转移的首要影响因素。     

口腔鳞状细胞癌中血管内皮生长因子和明胶酶-A的表达及肿瘤血管形成的关系

目的　研究血管内皮生长因子 (VEGF)和明胶酶 -A(matrixmetalloproteinase - 2 ,MMP - 2 )的表达与口腔鳞状细胞癌血管形成和临床病理的关系。方法　应用SABC免疫组化染色的方法检测了 4 0例口腔鳞状细胞癌手术和 2 0例正常口腔黏膜组织中VEGF、MMP - 2的表达和微血管密度 (MVD)的关系 ,同时分析了VEGF、MMP - 2的表达与口腔鳞状细胞癌临床病理的关系。结果　口腔鳞状细胞癌中VEGF、MMP - 2的表达显著高于正常口腔黏膜组织 ,与肿瘤内MVD密切正相关 (P <0 .0 5 ) ,VEGF、MMP - 2表达和口腔鳞状细胞癌中的MVD计数与口腔鳞状细胞癌病理分级和临床分期无关 ,与口腔鳞状细胞癌颈淋巴结转移密切相关 (P <0 .0 5 )。结论　VEGF和MMP - 2的表达和口腔鳞状细胞癌血管形成和转移中起重要作用 ,VEGF与MMP - 2具有某种内在联系 ,可作为反映口腔鳞状细胞癌侵袭转移的生物学指标和抗血管治疗的靶点     

口腔鳞状细胞癌组织乏氧状况的初步研究

目的 检测口腔鳞状细胞癌组织乏氧程度,探讨口腔鳞状细胞癌组织乏氧影响因素,认识和利用肿瘤乏氧区域的特性,为治疗提供依据.方法 经临床和病理证实的口腔鳞状细胞癌组织石蜡标本42例,建立口腔鳞状细胞癌动物移植瘤模型,采用单光子发射计算机断层成像(single photon emission computerized tomography,SPECT)乏氧显像技术检测癌组织的乏氧程度;采用免疫组织化学方法检测肿瘤乏氧标志物(hypoxia inducible factorla,HIF-1α)在口腔鳞状细胞癌组织中的分布,并分析与临床病理资料的相关性.结果 乏氧显像剂在动物模型鳞状细胞癌组织内高浓度聚集,与肿瘤体积呈线性相关,相关指数为0.926(P＜0.05),呈全层乏氧;口腔鳞状细胞癌组织中HIF-1α蛋白高表达,且在低分化、淋巴结转移及高临床分期组中的表达较高分化、无淋巴结转移及低临床分期组高(P＜0.05);正常口腔黏膜组织巾HIF-1α无表达.结论 口腔鳞状细胞癌组织乏氧区域分布广泛.HIF-1α在口腔鳞状细胞癌组织中高表达,可能在口腔鳞状细胞癌的发生和发展中起重要作用.     

An update on squamous carcinoma of the oral cavity, oropharynx, and maxillary sinus

There are more than 45,000 new cancer cases involving the head and neck diagnosed each year within the United States. Squamous cell carcinoma accounts for the majority of cases, often occurring within the oral cavity and oropharynx. This article reviews current literature and various controversial topics involving the diagnosis and treatment strategies for patients with oral cavity/oropharyngeal cancers. Although not considered cancer within the oral cavity, maxillary sinus squamous cell carcinoma is discussed.     

Oral and oropharyngeal cancer in the West of Scotland—long-term outcome data of a prospective audit 1999-2001

We prospectively studied patients from the west of Scotland who presented with a primary cancer of the oral cavity or oropharynx over a period of 24 months from November 1999, and report long-term outcomes and prognostic factors. A total of 481 patients had squamous cell carcinoma (SCC), 5-year disease-specific survival (DSS) was 50%, and overall survival (OS) was 35%. One hundred were not suitable for treatment with curative intent, and factors other than stage were important in this decision. Of those treated with curative intent, 249 had SCC of the oral cavity (5-year DSS 67%; OS 42%), and 132 had SCC of the oropharynx (5-year DSS 62%; OS 42%). Multivariate analysis showed that pathological nodal stage (p = 0.051, 95% CI 0.998-1.955), and perineural invasion (p = 0.001, 95% CI 0.186-0.666) were prognostic indicators. Improved results using intensive treatment protocols that have been seen in trials are not likely to translate directly into a general population of patients with head and neck cancer. Algorithms that allow several pathological prognostic indicators to be incorporated into decisions about adjuvant treatment should be used.     

Sites of recurrence in oral and oropharyngeal cancers according to the treatment approach

OBJECTIVE: The purpose of this study is to evaluate the rates and the sites of tumour recurrence in patients with oral and oropharyngeal carcinomas. DESIGN: This is a retrospective study of a series of cases treated in a single institution. PATIENTS AND METHODS: A series of 2067 patients with oral and oropharyngeal squamous carcinoma, treated from 1954 to 1998 were analysed. The treatment approach was: surgery, 624 cases (30.2%); radiotherapy alone, 729 cases (35.3%); radiotherapy and surgery, 552 cases (26.7%) and radiotherapy and chemotherapy, 162 cases (7.8%). MAIN OUTCOME MEASURES: Tumour recurrence was observed in 1079 patients (52.2%): 561 cases of local recurrences (27.1%); 168 neck recurrences (8.1%); 252 locoregional recurrences (12.2%); 59, distant metastasis (2.9%) and 39 (1.9%), combination of distant metastasis with local, neck or locoregional recurrence. RESULTS: The rates of recurrence varied significantly according to the treatment performed. Oral cavity cancer patients undergoing radiotherapy alone or in combination with chemotherapy presented the highest rates of neck recurrences (22.5 and 40.0%, respectively) for clinical stage (CS) I/II and of local (41.2 and 30.1%) and locoregional (21.7 and 31.1%) recurrences for CS III/IV; yet, for CS III/IV, surgery without neck dissection was associated with the highest rates of neck recurrences (20.7%), but no differences were observed in the rates of local or locoregional recurrences for CS I/II patients. For oropharynx cancer patients with CS I/II there was no difference in the rate of locoregional failures according to the treatment. However, patients with CS III/IV undergoing radiotherapy present a highest rate of local (42.3%) and locoregional (28.8%) failures. CONCLUSION: The results suggest that surgery should be the first option for initial clinical stage oral and oropharyngeal cancers. For advanced cases independently of the site of the tumour, surgery and postoperative radiotherapy should be the standard of care because it is associated with the lowest rates of locoregional recurrence.     

Assessment of quality of life in oral cancer

Quality of life (QL) in oral cancer patients has become one of the most important parameters to consider in the diagnosis and post-treatment follow-up. The purpose of this article has been to review the papers published that study the QL in oral cancer patients, the different QL questionnaires used, the clinical results obtained, and the systematic revisions available in the indexed literature for the last 10 years. The term QL appears as a keyword in an increasing number of articles throughout the past 10 years; however, few studies focus on oral cancer. Most of them assess all head and neck cancers, which conform to a heterogeneous group with several different features depending on location (oral cavity, oropharynx, larynx, hypopharynx, nasopharynx and salivary glands). Most studies evaluate QL in short periods of time, normally within the first year after the diagnosis. Series do not discern between different therapeutic options, and they generally center on Northern European or Northern American populations. There are few instruments translated and validated into Spanish that measure QL, a fundamental characteristic to link QL to own patients' socio-cultural parameters. Data related with QL are mostly related to patient (age, sex, co-morbidity), tumour (location, size), and treatment (surgical treatment, radiotherapy association, reconstruction, cervical dissection, and/or feeding tube). Nowadays QL's assessment is considered an essential component of an oral cancer patient as well as the survival, morbidity and years free of disease. Although many aspects related to QL in oral cancer patients have been published throughout the past 10 years, more systematic research is needed to be able to apply it on a daily basis.     

Admission patterns and outcomes of postoperative oral cavity and oropharyngeal cancer patients admitted to critical care in the UK: an analysis of the Intensive Care National Audit and Research Centre Case Mix Programme database

Surgery for head and neck malignancy may be complex with postoperative admission to critical care units (CCUs) often required. There are, however, increasing demands on this resource. We examined a national intensive care database to assess patterns of admission and outcomes for patients following surgery for malignancies of the oral cavity and oropharynx. An analysis was performed of the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme database. Data were extracted on case mix and outcomes for patients coded as ‘malignant neoplasm of the oropharynx requiring surgery’ admitted to critical care between 2010 and 2019. Data included admission numbers, demographics, comorbidities, physiology scores, and outcomes including length of stay and mortality. There were 9,843 admissions for patients with malignancies of the oral cavity and oropharynx from 156 CCUs over the ten-year period. Admissions increased from 486 in 2010 to 1,381 in 2019. These admissions accounted for 0.42% of overall admissions in 2010 and 0.78% in 2019. The median age of patients was 63 years and 63.5% were male. The median length of stay in critical care was 38 hours (Interquartile range (IQR) 20.4-64.3 hours). The median length of total hospital stay was 15 days (IQR 10-23 days). Mortality in critical care was low (0.7%). Admissions to CCUs following surgery for malignancies of the oral cavity and oropharynx have increased over the last decade but remain low overall. With increasing demand for this resource, ongoing monitoring of utilisation is important.     

A survey of head and neck surgical oncologists regarding the inclusion of level IIb in a neck dissection of the node negative neck

There is controversy as to whether IIb should be dissected in the node negative neck. The aim of this survey was to ascertain how often head and neck surgical oncologists performed a level IIb neck dissection for node negative T2 and T4 tumours of the oral cavity, oropharynx and larynx, and to gauge how many might be willing to take part in a RCT of sparing IIb. A convenience sample of 110 MFU colleagues and 125 members of the ENTUK head and neck group were questioned. Response rate for the MFU was 62% and ENT 30%. A clear majority from MFU had a strong preference for including IIb in all clinical scenarios apart from laryngeal T2 tumours whilst ENT included IIb with oral cavity T4, oropharyngeal T2 and oropharyngeal T4 tumours. This survey would support the need for a multicentre study with 53 responders interested in taking part.     

Contralateral neck recurrence of squamous cell carcinoma of oral cavity and oropharynx.

PURPOSE: Contralateral neck failure after therapy for squamous cell carcinoma of the oral cavity and oropharynx has rarely been studied in detail. We aimed to examine the pattern and outcome of contralateral neck relapse and possible predictive clinicopathologic factors. PATIENTS AND METHODS: Seventy-three patients undergoing surgery for cancer of oral cavity/oropharynx with curative intent were recruited from the hospital head and neck cancer registry. The age, gender, tumor site, primary tumor laterality, TNM status, clinical N status, pathologic T status, ipsilateral pathologic N status, tumor stage, status of residual disease, histopathologic differentiation, postoperative radiotherapy, local relapse, distant relapse, extracapsular spread of lymph node metastasis and neck dissection were evaluated for association with contralateral neck relapse. RESULTS: Seven patients developed ipsilateral, 5 patients developed contralateral, and 3 patients developed bilateral neck recurrence after therapy. Only 1 patient with contralateral or bilateral neck relapse survived after salvage therapy. Ipsilateral positive nodal status was the only significant clinicopathologic parameter associated with contralateral neck relapse, which occurred rather commonly in well-lateralized tumors. CONCLUSION: Contralateral and ipsilateral neck relapses are similar in occurrence. Pathologic positive nodal status is associated with a higher incidence of contralateral neck relapse. Aggressive and comprehensive adjuvant radiotherapy to the neck plus close surveillance in the first 2 years postoperatively might curtail the frequency and mortality due to contralateral neck failure.     

The INHANCE consortium: toward a better understanding of the causes and mechanisms of head and neck cancer

The International Head and Neck Cancer Epidemiology (INHANCE) consortium is a collaboration of research groups leading large epidemiology studies to improve the understanding of the causes and mechanisms of head and neck cancer. The consortium includes investigators of 35 studies who have pooled their data on 25 500 patients with head and neck cancer (i.e., cancers of the oral cavity, oropharynx, hypopharynx, and larynx) and 37 100 controls. The INHANCE analyses have confirmed that tobacco use and alcohol intake are key risk factors of these diseases and have provided precise estimates of risk and dose response, the benefit of quitting, and the hazard of smoking even a few cigarettes per day. Other risk factors include short height, lean body mass, low education and income, and a family history of head and neck cancer. Risk factors are generally similar for oral cavity, pharynx, and larynx, although the magnitude of risk may vary. Some major strengths of pooling data across studies include more precise estimates of risk and the ability to control for potentially confounding factors and to examine factors that may interact with each other. The INHANCE consortium provides evidence of the scientific productivity and discoveries that can be obtained from data pooling projects.     

Elective management of the neck in oral cavity squamous carcinoma: current concepts supported by prospective studies

The incidence of occult cervical metastasis in oral cavity cancer, even in early stages, is significant, necessitating elective treatment of the neck in a majority of cases. There is no method of imaging or other examination that will detect microscopic foci of metastatic disease in cervical lymph nodes. Immunohistochemical and molecular analysis of neck specimens reveals the incidence of occult metastases to be higher than revealed by light microscopy with ordinary hematoxylin and eosin staining. The neck may be treated electively by surgery or irradiation. Surgery has the advantage of permitting pathological staging of the neck, avoiding unnecessary radiation treatment and indicating cases where adjuvant therapy should be employed. As oral cavity cancer rarely metastasizes to level V, a radical or modified radical neck dissection of all five node levels is not necessary. Selective dissection of levels I–III (“supraomohyoid neck dissection”) is the usual procedure of choice for elective dissection of the neck. Most of the relatively small number of isolated metastasis to level IV are from primary tumours of the tongue, which are known to produce “skip” metastases. Thus an “extended supraomohyoid neck dissection” of levels I–IV is recommended by some authors for elective treatment of the neck in tongue cancer. A number of recent prospective multi-institutional studies have demonstrated that sublevel IIB is rarely involved with isolated metastasis from oral cavity primary tumours, except from some tongue cancers. Thus it is justifiable to omit dissection of sublevel IIB in elective treatment of most cases of oral cavity cancer. Bilateral neck dissection should be performed in elective treatment of tumours involving midline structures, and in patients with ipsilateral neck metastasis.