口咽部人乳头瘤病毒感染检测方法的研究进展

人乳头瘤病毒(HPV)是一种仅感染人类的双链DNA病毒,口咽部HPV感染可引起口腔潜在恶性疾病与头颈部鳞状细胞癌等不良后果,口咽部HPV感染的检测是早期诊断与治疗的关键。近年来,以核酸检测与免疫组化(IHC)作为检测HPV的主流方法,其他多种替代方法也得到了迅速发展。本文综述了口咽部HPV感染的不良后果与检测方法的研究进展,以期为临床应用提供参考依据。     

不同HPV感染状态口咽部及头颈部原发部位不明鳞状细胞癌颈部转移性淋巴结超声鉴别诊断

目的 探讨不同人乳头状瘤病毒(HPV)感染状态下口咽部鳞状细胞癌(OPSCC)、头颈部原发部位不明鳞状细胞癌(HNSCC-UP)的颈部转移性淋巴结(CMLN)的声像图特点及鉴别诊断,对HPV感染状态进行术前预测。方法 回顾性分析39例不同HPV感染状态的OPSCC、HNSCC-UP的74个CMLN的超声图像。分析的特征包括：形态、短长径比(S/L)、边界、淋巴结门结构、内部回声、钙化、液化坏死。结果 不同HPV感染状态的OPSCC、HNSCC-UP的CMLN在形态、内部回声、钙化方面有统计学意义(P<0.05),在S/L、边界、淋巴结门结构方面的差异无统计学意义(P>0.05)。结论 HPV(-)OPSCC的CMLN内部回声多不均匀,钙化是其超声特征;而形态不规则的CMLN多与HPV(+)OPSCC、HNSCC-UP相关。     

人类乳头状瘤病毒感染与食管鳞状细胞癌发生的关系

【目的】研究人类乳头状瘤病毒感染与食管鳞状细胞癌发生的关系。【方法】利用免疫组织化学技术检测65例食管癌、14例非典型增生食管上皮和51例正常食管黏膜组织中人类乳头状瘤病毒（HPV）16／18E6蛋白的表达。【结果】在正常食管黏膜、非典型增生上皮及鳞状细胞癌组织中HPV16／18E6的阳性率分别为13．7％（7／51）、42．9％（6／14）和73．8％（48／65）．癌组织中HPV16／18E6蛋白的阳性表达率明显高于非典型增生上皮和正常食管黏膜（P〈0．05）。非典型增生上皮中HPV16,18E6蛋白的阳性表达率亦明显高于正常食管黏膜（P〈0．05）;在食管鳞状细胞癌组织中HPV16/18E6的阳性表达率与癌组织的分化程度未见明显关系（P〉0．05）。【结论】高危型HPV16／18型感染可能在食管癌的发生中起重要作用。     

人乳头状瘤病毒、p16^INK4A在宫颈鳞状上皮病变中的意义

目的 探讨人乳头状瘤病毒的不同亚型及p16INK4A p53、Ki-67、ER在不同程度宫颈鳞状上皮病变中的表达及临床病理意义.方法 采用原位杂交及免疫组化方法,检测人乳头状瘤病毒的不同亚型,p16INK4A、p53、Ki-67及ER在204例不同程度宫颈病变组织中的表达情况.结果 HPV在不同程度宫颈病变中总检出率为64.67%(119/184);在宫颈鳞癌、CIN组中检出最多的感染类型为HPV16/18,尤其在CINⅢ、CINⅡ组中阳性表达率较高;HPV31/33主要在CINI病变中表达;而HPV6/11在尖锐湿疣组检出率最高.随着官颈病变严重程度的增加,p16INK4A、p53和Ki-67的阳性表达率及染色强度呈递增趋势;但ER的阳性表达率及染色强度呈递减趋势.p16INK4A、p53、Ki-67与HPV16/18型感染关系密切;ER与HPV6/11型感染关系密切.结论 HPV16/18型及p16INK4A、p53、Ki-67在官颈鳞癌、CINⅢ、CINⅡ中表达明显升高,可能对宫颈鳞癌的发生发展具有协同作用;p16INK4A可以作为诊断宫颈肿瘤性及非肿瘤性增生的标记物.     

人乳头状瘤病毒相关头颈颌面部鳞癌的研究进展

头颈部鳞状细胞癌（head and neck squamous cell carcinoma，HNSCC）发病率占头颈部恶性肿瘤的90%，死亡率为40%~50%，来源于口腔、口咽、鼻咽、下咽及喉。通常认为烟草、酒精的过度使用与HNSCC有关，但越来越多的研究表明，人乳头状瘤病毒（human papillomavirus，HPV）感染与HNSCC的发生发展高度相关，尤其是口咽鳞状细胞癌（oropharyngeal squamous cell carcinoma，OPSCC）。本文对HPV相关HNSCC的分子生物学表现、致病机制、治疗进展、预防策略作一综述，为临床及个体化治疗提供新的思路。     

冷冻喷射法治疗口咽部乳头状瘤的疗效观察

口咽部乳头状瘤是较常见的良性肿瘤,多发生于悬雍垂、软腭、腭弓、扁桃体表面及舌部。常规治疗方法有手术切除、激光、微波、射频等。2007年1月-2008年6月本科采用冷冻喷射法治疗口咽部乳头状瘤30例,疗效满意,报告如下。     

宫颈癌根治术后高危型人乳头瘤病毒、鳞状细胞癌抗原及鳞状细胞癌相关抗原检测对宫颈癌复发的预测价值

目的探讨宫颈癌根治术后高危型人乳头瘤病毒(HR-HPV)、鳞状细胞癌抗原(SCC-Ag)及鳞状细胞癌相关抗原(SCCA)水平检测在预测宫颈癌复发的价值。方法选择50例宫颈癌患者,所有患者术后第1～2年内每3个月进行1次随访,术后第2～5年内每半年进行1次随访。随访时对患者的HR-HPV、SCC-Ag、SCCA水平进行检测,分析其预测复发的价值。结果 5例宫颈癌术后复发患者HR-HPV与SCC-Ag阳性率显著高于未复发患者(P 0. 05)。复发患者血清SCCA的表达水平阳性率显著高于未复发患者(P 0. 05)。结论宫颈癌根治术后HR-HPV、SCC-Ag、SCCA联合检测在宫颈癌辅助诊断、疗效评估以及预后监测方面具有重要的临床参考价值。     

人乳头状瘤病毒疫苗接受现状及其影响因素的研究进展

宫颈癌是最常见的妇科恶性肿瘤之一,人乳头状瘤病毒（HPV）已经证实是宫颈癌的主要致病病毒,HPV疫苗自2006年上市以来,其安全性和有效性已被证实。尽管很多国家实施大规模疫苗接种计划,但最终的效果却不尽相同。 H PV疫苗要实现其有效性,必须保证较高水平的接种率,公众接受度是实现高接种率的前提。因此了解全球范围内公众的疫苗接受度、接种率的现状及其影响因素,为疫苗的全面推广指明方向。     

宫颈癌与人乳头状瘤病毒相关研究进展

宫颈癌严重威胁女性健康,已成为发展中国家的第二位最常见的肿瘤死亡原因.宫颈癌的发生、发展与人乳头状瘤病毒感染密切相关,进一步明确人乳头状瘤病毒感染在宫颈癌发病机制中所起的作用,具有重大的研究价值.寻找宫颈癌早期的最佳筛查方案,研制有效的预防人乳头状瘤病毒感染疫苗将为人类攻克宫颈癌带来新的希望.     

阴道镜联合高危型人乳头瘤病毒检测在宫颈非典型鳞状细胞中的意义

目的 探讨宫颈液基细胞学检查(TCT)报告为性质未定的不典型鳞状细胞(ASCUS)的临床意义及处理.方法 对宫颈薄层液基细胞学诊断为ASCUS的1658例患者分别进行HR-HPV检测、阴道镜下活组织检查.结果 在ASCUS患者中,HR-HPV阳性组CIN及浸润癌的检出率为68.22％,在HR-HPV阴性组CIN及浸润癌的检出率为8.74％,两组间差异有显著性(P ＜0.001).阳性组发生CIN和浸润癌的风险是阴性组的22.4065倍[OR(9％CI)=22.4065].阴道镜拟诊CIN和浸润癌842例,检出率为88.82％(802/903),其中高级别CIN和浸润癌134例,检出率为87.01％(134/154).结论 阴道镜联合HR-HPV检测在宫颈癌前病变,特别是在高级别宫颈上皮内瘤变及浸润癌诊断中阳性预测值较理想,敏感性较好,漏诊率低,具有较高的推广价值.     

Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review

Human papillomavirus (HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPV-related oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinical implications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities.     

Retrospective study of the clinicopathological characteristics and prognosis of elderly patients with oropharyngeal squamous cell carcinoma

ObjectiveOropharyngeal squamous cell carcinoma (OPSCC) is a malignant tumor that occurs at the tongue base, soft palate, palatine tonsil, and pharyngeal wall. Few studies of OPSCC have been performed in elderly patients.MethodsPatients with human papilloma virus (HPV)-related OPSCC were extracted from the Head and Neck with HPV Status Database of the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. We identified 355 patients with HPV-positive status, and we retrospectively evaluated elderly (≥65 years) and younger (30–64 years) patient groups to compare the differences.ResultsOf the 355 patients who were diagnosed with HPV-related OPSCC, 113 constituted the elderly group. Comparing the elderly group with the younger group, the 3-year HPV-positive overall survival (OS) rates were 62.4% and 70.2%, respectively, and the 5-year OS rates were 50.4% and 59.2%, respectively. Cox regression analysis demonstrated that tumor (T) stage and chemotherapy were prognostic factors for OS.ConclusionElderly patients with OPSCC had different clinicopathological characteristics. T stage and chemotherapy should be priorities when evaluating the OS of elderly patients with OPSCC.     

口咽鳞状细胞癌患者预后影响因素分析

目的探讨口咽鳞状细胞癌患者的预后现状和影响因素。方法采用自制问卷收集2005年12月—2009年12月作者所在医院收治的69例口咽鳞状细胞癌患者的临床资料,根据口咽鳞状细胞癌患者的预后情况将其分为A组和B组。采用SPSS 19.0统计软件进行描述性统计和二分类Logistic回归分析口咽鳞状细胞癌预后现状和影响因素。结果所有患者中,死亡患者42例,预后不良患者比例为60.87%;人乳头瘤病毒感染(OR=12.167)、淋巴结转移(OR=24.184)、情绪紧张(OR=8.576)、治疗并发症(OR=11.470)和基础疾病种数多(OR=12.198)是口咽鳞状细胞癌患者预后不良的危险因素;肿瘤组织分化程度高(OR=0.118)是口咽鳞状细胞癌患者预后良好的保护因素。结论口咽鳞状细胞癌患者预后较差,预后结局受多方面因素影响,治疗中应采取针对性的预防干预措施来提高疗效,改善患者的预后。     

Evolving role of human papillomavirus as a clinically significant biomarker in head and neck squamous cell carcinoma

Introduction: The majority of squamous cell carcinoma (SCC) of the oropharynx, one of the sites within the head and neck region, is now associated with high-risk human papillomavirus (HPV) in North America. Several modalities are available to determine the HPV status, however, the understanding of each assay in its application and limitations is essential for accurate interpretation and appropriate utilization of results in management of these patients.

Areas covered: This expert review will cover the role of HPV in head and neck squamous cell carcinoma (HNSCC), indications for HPV testing, HPV detection methods in tumors, saliva and serum, and exploiting HPV status as a prognostic biomarker of clinical outcome in HNSCC.

Expert commentary: The HPV status is the most significant diagnostic and prognostic biomarker in HNSCC, specifically in the oropharynx. Research underway is currently delineating the role of HPV and p16 testing in non-oropharyngeal sites. While the feasibility of non-invasive serum and saliva testing for HPV detection has been established, the clinical application of these assays is still evolving.     

食管鳞癌患者血清血红素氧合酶-1和鳞状细胞癌抗原水平与临床病理特征及预后的关系

目的观察不同临床病理特征食管鳞癌患者血清血红素氧合酶-1(heme oxygenase-1,HO-1)、鳞状细胞癌抗原(squamous cell carcinoma antigen,SCCA)水平变化,探讨HO-1、SCCA与食管鳞癌患者预后的关系。方法食管鳞癌患者93例为食管鳞癌组,同期体检健康者72例为对照组,采用ELISA法检测2组血清HO-1、SCCA水平。比较食管鳞癌组与对照组及不同临床病理特征食管鳞癌患者血清HO-1、SCCA水平。食管鳞癌患者根据病情程度采用内镜治疗、食管癌根治术治疗及放化疗综合治疗,并依据HO-1、SCCA水平分为高水平HO-1(HO-1≥2.43μg/L)组47例和低水平HO-1(HO-1<2.43μg/L)组46例,高水平SCCA(SCCA≥2.76μg/L)组49例和低水平SCCA(SCCA<2.76μg/L)组44例。随访5年,比较食管鳞癌患者高、低水平HO-1组,高、低水平SCCA组5年总生存率,多因素Cox回归分析食管鳞癌患者死亡的危险因素。结果食管鳞癌组血清HO-1[(2.43±0.55)μg/L]、SCCA[(2.76±0.61)μg/L]水平高于对照组[(0.23±0.09)、(0.42±0.13)μg/L](P<0.05)。肿瘤分期Ⅲ期、病理分级低分化者血清HO-1[(2.75±0.64)、(2.57±0.57)μg/L]、SCCA[(3.22±0.71)、(2.93±0.64)μg/L]水平高于肿瘤分期Ⅰ~Ⅱ期[(2.32±0.43)、(2.60±0.52)μg/L]、病理分级高中分化者[(2.30±0.51)、(2.61±0.58)μg/L](P<0.05);不同年龄、性别、肿瘤大小、肿瘤位置及淋巴结有无转移者血清HO-1、SCCA水平比较差异均无统计学意义(P>0.05)。随访至2020年2月,均未失访,高水平HO-1组5年总生存率(10.6%)低于低水平HO-1组(30.4%)(P<0.05),高水平SCCA组5年总生存率(8.2%)低于低水平SCCA组(34.1%)(P<0.05)。肿瘤分期Ⅲ期(OR=3.054,95%CI=1.021~6.141,P=0.004)、病理分级低分化(OR=3.011,95%CI:1.003~5.051,P=0.023)、高血清HO-1水平(OR=2.407,95%CI:1.123~4.989,P=0.022)、高血清SCCA水平(OR=2.025,95%CI:1.003~8.077,P=0.019)是食管鳞癌患者死亡的危险因素。结论食管鳞癌患者血清HO-1及SCCA水平升高,其增高程度与肿瘤分期、病理分级有关,是食管鳞癌患者死亡的危险因素。     

A case of difficult‐to‐diagnose non‐invasive papillary squamous cell carcinoma of the uterine cervix infected with human papilloma virus 6: A diagnostic pitfall

We encountered HPV6‐positive cervical papillary squamous cancer (PSCC) that was difficult to diagnose. The case was initially diagnosed and treated for condyloma. To the best of our knowledge, this is the first report of HPV6 infection in PSCC.     

倾向性评分匹配分析口咽癌PD-L1的表达与HPV感染及预后的相关性研究

目的探讨口咽鳞癌中程序性细胞死亡配体1(PD-L1)与HPV感染状态及患者预后的相关性。方法采用倾向性评分匹配,纳入HPV阳性及HPV阴性口咽癌各50例,对患者进行长期随访,通过免疫荧光检测PD-L1的表达,分析其与HPV感染状态及临床预后的相关性。结果 HPV阳性组及HPV阴性组5年总生存率分别为66%和40%(P=0.003),5年疾病特异性生存率分别为73%和44%(P=0.001)。PD-L1表达率在HPV阳性组较HPV阴性组明显升高(70%vs 42%,P=0.005)。PD-L1与除年龄(P=0.020)外的其他临床病理特征无明显相关性,PDL1阳性为口咽癌独立良好预后因素(DSS,P<0.001;OS,P<0.001)。进一步预后分析提示HPV+/PD-L1+患者较HPV+/PD-L1-者(DSS,P<0.001;OS,P=0.004),HPV-/PD-L1+者(DSS,P=0.010;OS,P=0.047)以及HPV-/PD-L1-者(DSS,P<0.001;OS,P<0.001)具有显著的预后优势。结论 HPV阳性口咽癌患者预后较好,PD-L1在HPV阳性口咽癌中的表达升高,PD-L1阳性可能与HPV阳性口咽癌患者较好的临床预后相关。     

血清中肝细胞生长因子含量对食管鳞状细胞癌的影响

目的探讨血清中肝细胞生长因子（HGF）含量对食管鳞状细胞癌的影响。方法用ELISA方法研究6例食管良性疾患和42例食管鳞状细胞癌患者血清中肝细胞生长因子（HGF）含量。结果12例正常健康体检和6例食管良性疾患病人血清中都有一定量的肝细胞生长因子（HGF）,而食管鳞状细胞癌患者血清中HGF含量（397．4±339．9pg／ml）明显高于正常健康人和食管良性疾患患者（P〈0．05）,其含量与病理类型、病理组织分级和临床病理分期、淋巴结转移情况无关。3年随访36例病例中死亡（23例）,其血清HGF含量明显高于生存（30例）者（P〈0．05）。结论增高的血清HGF在食管鳞状细胞癌中预示了一种更具有侵袭性的生物学行为。血清HGF含量水平可作为食管鳞状细胞癌的高危因素指标。     

Lesion human leukocyte antigen-E is associated with favourable prognosis for patients with oesophageal squamous cell carcinoma

ObjectiveTo investigate the clinical significance of human leukocyte antigen (HLA)-E levels in oesophageal squamous cell carcinoma (ESCC).MethodsThe levels of HLA-E immunostaining in ESCC lesions and 47 corresponding adjacent normal tissues were measured using immunohistochemistry. The correlation between the levels of immunostaining and clinical parameters was analysed.ResultsThis study analysed 110 paraffin-embedded primary tumour lesions and 47 case–controlled paracancerous tissues that were surgically resected from 110 patients with ESCC. Positive immunostaining for HLA-E was observed in 88.2% (97 of 110) of ESCC lesions and 29.8% (14 of 47) of normal oesophageal tissues. There was no correlation between HLA-E immunostaining in ESCC lesions and clinicopathological characteristics such as lymph node metastasis, tumour–node–metastasis stage and differentiation grade. Kaplan–Meier survival analysis revealed a significantly better prognosis in patients with higher levels of HLA-E immunostaining than in those with lower levels of HLA-E immunostaining; overall survival was 28.6 months (95% confidence interval [CI], 23.2, 34.0) versus 15.3 months (95% CI, 11.5, 19.1), respectively. Furthermore, multivariate analysis showed that the HLA-E level was an independent prognostic factor in patients with ESCC.ConclusionA higher level of HLA-E immunostaining was associated with favourable survival in patients with ESCC.