Expression rates of p16,p53 in head and neck cutaneous squamous cell carcinoma based on human-papillomavirus positivity

BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanisms that target p16 and p53 proteins.However,research on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous SCC(HNCSCC),particularly in Asian populations,remains limited.This retrospective study surveyed 62 patients with HNSCC(2011-2020),excluding those with facial warts or other skin cancer.AIM To explore the prevalence of HPV and the predictive value of p16 and p53 expression in HNCSCC in Asian populations.METHODS All patients underwent wide excision and biopsy.Immunohistochemical staining for HPV,p16,and p53 yielded positive and negative results.The relevance of each marker was investigated by categorizing the tumor locations into high-risk and middle-risk zones based on recurrence frequency.RESULTS Of the 62 patients,20(32.26%)were male,with an average age of 82.27 years(range 26-103 years).High-risk included 19 cases(30.65%),with the eyelid and lip being the most common sites(five cases,8.06%).Middle-risk included 43 cases(69.35%),with the cheek being the most common(29 cases,46.77%).The p16 expression was detected in 24 patients(38.71%),p53 expression in 42 patients(72.58%),and HPV in five patients(8.06%).No significant association was found between p16 expression and the presence of HPV(P>0.99),with a positive predictive value of 8.33%.CONCLUSION This study revealed that p16,a surrogate HPV marker in oropharyngeal SCC,is not reliable in HNCSCC,providing valuable insights for further research in Asian populations.

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 HPVrelated 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 clinicalimplications. 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.

Three-dimensional collagen-based scaffold model to study the microenvironment and drug-resistance mechanisms of oropharyngeal squamous cell carcinomas

Objective:Squamous cell carcinoma(SCC)represents the most common histotype of all head and neck malignancies and includes oropharyngeal squamous cell carcinoma(OSCC),a tumor associated with different clinical outcomes and linked to human papilloma virus(HPV)status.Translational research has few available in vitro models with which to study the different pathophysiological behavior of OSCCs.The present study proposes a 3-dimensional(3 D)biomimetic collagen-based scaffold to mimic the tumor microenvironment and the crosstalk between the extracellular matrix(ECM)and cancer cells.Methods:We compared the phenotypic and genetic features of HPV-positive and HPV-negative OSCC cell lines cultured on common monolayer supports and on scaffolds.We also explored cancer cell adaptation to the 3 D microenvironment and its impact on the efficacy of drugs tested on cell lines and primary cultures.Results:HPV-positive and HPV-negative cell lines were successfully grown in the 3 D model and displayed different collagen fiber organization.The 3 D cultures induced an increased expression of markers related to epithelial–mesenchymal transition(EMT)and to matrix interactions and showed different migration behavior,as confirmed by zebrafish embryo xenografts.The expression of hypoxia-inducible factor 1α(1α)and glycolysis markers were indicative of the development of a hypoxic microenvironment inside the scaffold area.Furthermore,the 3 D cultures activated drug-resistance signaling pathways in both cell lines and primary cultures.Conclusions:Our results suggest that collagen-based scaffolds could be a suitable model for the reproduction of the pathophysiological features of OSCCs.Moreover,3 D architecture appears capable of inducing drug-resistance processes that can be studied to better our understanding of the different clinical outcomes of HPV-positive and HPV-negative patients with OSCCs.

Advanced oropharyngeal squamous cell carcinoma: Pathogenesis, treatment, and novel therapeutic approaches

Oropharyngeal cancer accounts for approximately 2.8% of newly cancer cases. Although classically a tobacco related disease, most cases today are related to infection with human papilloma virus(HPV) and present with locally advanced tumors. HPV related tumors have been recognized as a molecularly distinct entity with higher response rates to therapy, lower rates of relapse, and improved overall survival. Treatment of oropharyngeal cancer entails a multi-disciplinary approach with concomitant chemoradiation. The role of induction chemotherapy in locally advanced tumors continues to be controversial however large studies have demonstrated no difference in survival or time to treatment failure. Surgical approaches may be employed with low volume oropharyngeal cancers and with development new endoscopic tools, more tumors are able to be resected via an endoscopic approach. Given advances in the understanding of HPV related oropharyngeal cancer, ongoing research is looking at ways to minimize toxicities via de-intensification of therapy. Unfortunately, some patients develop recurrent or metastatic disease. Novel therapeutics are currently being investigated for this patient population including immunotherapeutics. This review discusses the current understanding of the pathogenesis of oropharyngeal cancer and treatment. We also discuss emerging areas of research as it pertains to de-intensification as well novel therapeutics for the management of metastatic disease.

An Analysis of the Potential Benefits of Metformin on Disease Recurrence in Oral and Oropharyngeal Squamous Cell Carcinoma

Objective: Diabetes mellitus type 2 has been associated with increased cancer risk and cancer related mortality. Metformin, one of the most widely used anti-diabetic medications, has been found to have important anticancer properties in addition to hypoglycemic effects. The effects of metformin on clinical outcomes in oral cavity (OC) and oropharyngeal (OP) squamous cell carcinoma (SCC) have not been thoroughly analyzed. The purpose of this study was to evaluate the effects of metformin use on cancer recurrence in diabetic patients with oral cavity and oropharyngeal squamous cell carcinoma. Design: Retrospective review. Setting: Academic tertiary medical center. Patients: Seventy-seven patients with diabetes mellitus type 2 and oral cavity or oropharyngeal squamous cell carcinoma were treated and followed at our tertiary academic institution and the Veterans Affairs Greater Los Angeles Healthcare System from 1998 to 2012. Main Outcome Measure: Cox proportional hazards models and Kaplan-Meier curves were constructed to determine if metformin has an effect on disease recurrence after primary cancer treatment. Results: Metformin does not appear to have a significant effect on disease recurrence in patients with OC/OP SCC and diabetes mellitus type 2 (p = 0.53). Even when including only patients with stage I or II disease, metformin still did not decrease recurrence (p = 0.60). Conclusion: Herein, our data suggest that metformin use does not significantly impact time until recurrence for diabetic patients with OC/OP SCC.

Therapeutic Outcomes of HPV Positive and HPV Negative Oropharyngeal Squamous Cell Carcinomas

Background & Objectives: HPV associated (HPV+) oropharyngeal cancers, compared with HPV non-associated ones (HPV?) have different characters and significantly better outcomes. HPV and cancer characteristics differ among countries and few data is available in Indian population regarding this issue. Thus, we attempted to determine the treatment response and survival rates between HPV+ versus HPV negative oropharyngeal cancers in Indian population. Methods: This prospective observational study was conducted from December 2016 - October 2018 in patients with stage III/IV oropharyngeal squamous cell carcinomas (SCC) (n = 65). The patients received induction chemotherapy with Docetaxel, Cisplatin, 5-Fluorouracil × 3 cycles, followed by concurrent chemoradiation 66 Gy as 33 fractions along with cisplatin 40 mg/m2 weekly. The primary outcome was treatment response rate, which was defined as per Response Evaluation Criteria in Solid Tumours (RECIST) criteria. Secondary outcomes were clinico-pathological differences between two groups, overall survival (OS), progression free survival (PFS). Results: Of the 65 patients included in the study, 17 were HPV positive and 48 patients were HPV negative. Median age in HPV positive arm is 48 years and HPV negative arm is 59 years. HPV positive patients presented with early T stage and advanced nodal (N) stage. Most common histopathology in both arms was moderately differentiated squamous cell carcinomas followed by well differentiated squamous cell carcinomas. HPV+ vs HPV? showed the following, treatment response 82.4% vs 52.1% (p-0.029). 1 year progression free survival (PFS) of 76.5% vs 52.1% in HPV negative arm (p-0.08) & 1 year overall survival was 82.4% vs 70.8% (p-0.353). Grade 3 or 4 toxicities did not differ significantly between HPV positive and HPV negative arms. Conclusion: HPV positive oropharyngeal SCC patients showed significantly better treatment response than HPV negative ones. Progression free survival, overall survival and toxicity profile did not differ significantly between the two groups. Although due to small size, we did not compare data stratified by the cancer characteristics, the data is worthy to further characterize this tumour especially as HPV positive versus HPV negative.

Use of Holmium:Yag laser in early stage oropharyngeal squamous cell cancer

AIM: To evaluate the efficacy of Holmium:Yag laser resection for oropharyngeal squamous cell cancer.METHODS: A prospectively collected case series of all patients with oropharyngeal squamous cell carcinoma undergoing laser resection using the Holmium:Yag laser technique only over a 15 year period at a tertiary referral centre. All patients underwent long term follow up with regular clinical and radiological surveillance, when indicated. All patients were operated on under general anaesthetic with a laser-safe endotracheal tube. Typically laser resection was performed first using an operating microscope, followed by neck dissection. The tumour was held with a Luc's forceps or Allis clamp. The Holmium:Yag laser was implemented via a fibre delivery system. The Holmium:Yag laser fibre, of 550 micron diameter, was inserted through a Zoellner sucker and attached via steri-strips to a second Zoellner suction to provide smoke evacuation. The settings were 1J/pulse, 15 Hz, 15 W in a continuous delivery modality via a foot pedal control. The procedure is simple, bloodless, effective and quick. All surgeries were performed as day cases. RESULTS: Twenty-seven oropharyngeal squamous cell cancer patients were identified, at the following subsites:23 lateral pharyngeal wall/tonsil, 2 anterior faucal and 2 tongue base. Of the 23 tonsil tumours,19 required no further treatment(83% therefore had negative histopathological margins) and 4 required chemoradiotherapy(17% were incompletely excised or had aggressive histopathological features such as discohesive, perineural spread, vascular invasion). The 2 patients with anterior faucal pillar neoplasia needed no further treatment. Both tongue base cancer cases required further treatment in the form of chemoradiotherapy(due to positive histopathological margins). Postoperatively, patients complained of pain locally, which resolved with regular analgesia. There were no postoperative haemorrhages. Swallowing and speech were normal after healing(10-14 d). There was one case of fistula when neck dissection was carried out simultaneously; this resolved with conservative management. All patients were followed up with serial imaging and clinical examination for a minimum of five years. Median follow up was 84 mo.CONCLUSION: Holmium:Yag lasers are a safe and effective treatment for Stage 1 and 2 squamous cell carcinoma of the oropharynx, excluding the tongue base.

Squamous Cell Carcinoma of the Oropharynx Presenting with Distant Metastasis to the Ulna

Squamous cell carcinomas are the commonest malignancies of the head and neck. Metastases from stage III and stage IV tumors occur most commonly in the cervical lymph nodes. The incidence of distant metastases occurring from such advanced tumors is anywhere between 10% and 40%. Distant metastases occur most commonly to the lungs followed by the bone and liver. The bone metastasis occurs commonly in the axial skeleton. We report a rather unusual case of squamous cell carcinomas from the Head and Neck region in a 77-year-old male metastasizing to the ulna. This case is even more interesting because the presenting symptom was a pathological fracture of the ulna for which he had reported to the orthopedic department. The immunohistochemistry of the metastatic tumor had shown an unmistakable squamous cell carcinoma with positive cytokeratin elements within the tumor. He referred to the ENT department where he was diagnosed with T2N0M1 squamous cell carcinoma of the oropharynx. The patient was treated with internal fixation and bone cementing for the metastatic lesion, and primarily treated with chemoradiation.

Recurrent oropharyngeal cancer: Analysis of surgical treatment outcomes

BACKGROUND The main goal of our research is to introduce transoral robotic surgery and laser resection(TLR)as a considerable way of treating patients with recurrent oropha-ryngeal malignancies.AIM To develop a foundation of minimally invasive transoral surgical technique for patients with oropharyngeal recurrence.METHODS This study prospectively and retrospectively included patients with recurrent tumors from 2003 to 2018.Subjects were allocated into two groups:(1)Group I;underwent TLR;and(2)Group II(control);underwent open surgeries of varying volume.Evaluation was done with intraoperative blood loss,postoperative infection incidence,and quality of life using the scale for patients with head and neck tumors known as the Functional Assessment of Cancer Therapy-Head&Neck Scale.RESULTS One-hundred and forty one patients were included(103 males and 38 females),in 82 cases(85.4%),a recurrent tumor developed earlier than a year after primary tumor therapy;forty-six were in group I and 69 in group II,age ranging from 18 years to 86 years(average:57.6 years).The first group showed a statistically significant less amount of blood loss and a decreased incidence of infectious complications(P<0.05).Additionally,there was a significant difference in functional outcomes(quality of life scores)but no significant difference in survival curves.CONCLUSION In properly elected patients,TLR is not just reasonable but tends to be a favorable alternative for recurrent oropharyngeal cancers compared to the outcomes of the open surgery group.

Detection of human papillomavirus in oropharyngeal squamous cell carcinoma

Worldwide there has been a significant increase in the incidence of oropharyngeal squamous cell carcinoma(OPSCC)etiologically attributed to oncogenic human papillomavirus(HPV).Reliable and accurate identification and detection tools are important as the incidence of HPV-related cancer is on the rise.Several HPV detection methods for OPSCC have been developed and each has its own advantages and disadvantages in regard to sensitivity,specificity,and technical difficulty.This review summarizes our current knowledge of molecular methods for detecting HPV in OPSCC,including HPV DNA/RNA polymerase chain reaction(PCR),loop-mediated isothermal amplification(LAMP),p16 immunohistochemistry(IHC),and DNA/RNA in situ hybridization(ISH)assays.This summary may facilitate the selection of a suitable method for detecting HPV infection,and therefore may help in the early diagnosis of HPV-related carcinoma to reduce its mortality,incidence,and morbidity.

Clinical and Histological Patterns of Oropharyngeal Tumors in Selected Health Institutions in North Western Nigeria

Background: Tumors of the oropharynx affect a common pathway for deglutition, respiration and speech and therefore pose a challenge to both the patient and clinician. This paper attempts to present clinical and histologic patterns, and therapeutic challenges of oropharyngeal tumors from three selected health facilities in North Western Nigeria. Materials and Methods: The medical records of patients seen in the Usmanu Danfodiyo University Teaching Hospital, Sokoto, Federal Medi- cal Centre Birnin Kebbi and Shepherd Specialist Hospital, Sokoto with oropharyngeal tumors over a fourteen-year period were reviewed (January 2000 to December 2013). Results: A total of 36 patients were seen. Twenty (56%) were males and 16 (44%) were females, making the male:female ratio, 1.3:1, (P value of 0.004 for the null hypothesis). The age range was 3 to 80 years, with a mean age of 45.5 years. Majority of patients were in their 5th decade of life (33%). Nineteen (53%) patients presented with dysphagia, 11 (28%) with mass in the mouth (soft palate), 7 (17%) with neck swelling, while 3 patients (7%) presented with upper airway obstruction. Twenty-six patients (72%) presented at an advanced stage. Squamous cell carcinoma accounted for 31% of the cases, followed by lymphoma 14%, adenoid cystic carcinoma 8%, pleomorphic adenoma 5%, mucoepidermoid carcinoma 5%, peripheral nerve sheath tumour 3%, alveolar rhabdomyosarcoma (3%), tuberculoma (3%) and inflammatory polyp (3%). Surgery was carried out in 31 cases (86.1%) for the purpose of obtaining biopsy and removal of tumour, followed by chemotherapy (5.5%) and radiotherapy (5.5%) where histologic diagnosis was malignant. Five (13.9%) did not consent for any intervention. Conclusion: Oropharyngeal tumours are varied in presentation. Squamous cell carcinoma (31%) was the commonest histologic type followed by lymphoma (14%) and adencystic carcinoma (8%). About 72% of the cases were in advanced stages (T4). More than half of the tumours (53%) were of soft palate origin.

Notch4 mRNA在口咽鳞癌组织中表达变化及其敲降癌细胞株增殖迁移侵袭能力观察

目的 观察Notch4 mRNA在口咽鳞癌组织和细胞株中的表达变化及敲降Notch4 mRNA表达的口咽鳞癌细胞株增殖、迁移和侵袭能力。方法 收集12对口咽鳞癌组织与癌旁组织,采用RT-q PCR法检测癌组织、癌旁组织中Notch4 mRNA。培养口咽鳞癌细胞株Detroit 562、WSU-HN-30及对照细胞株Ha CaT、2BS,检测细胞株中Notch4 mRNA。将人口咽鳞癌细胞株Detroit 562和WSU-HN-30随机分为si-NC组、si-Notch4-1组和si-Notch4-2组,分别转染si-NC双链核苷酸、si-Notch4-1双链核苷酸、si-Notch4-2双链核苷酸,检测各组细胞株中Notch4 mRNA,使用RTCA法观察各组细胞株的增殖能力(CI值),通过Transwell实验观察各组细胞株的侵袭和迁移能力。结果 与癌旁组织相比,口咽鳞癌组织中Notch4 mRNA相对表达量高(P<0.01);在对照细胞株Ha CaT和2BS中Notch4 mRNA相对表达量差异无统计学意义;与对照细胞株Ha CaT相比,口咽鳞癌细胞株Detroit 562、WSU-HN-30中Notch4 mRNA相对表达量高(P均<0.001)。在口咽鳞癌细胞株Detroit 562、WSU-HN-30中,与si-NC组相比,si-Notch4-1和si-Notch4-2组的细胞株增殖、迁移和侵袭能力降低(P均<0.01)。结论 Notch4 mRNA在口咽鳞癌组织和细胞株中均高表达,敲降Notch4 mRNA表达的口咽鳞癌细胞株增殖、迁移和侵袭能力降低。

TSC22D1在口咽鳞状细胞癌中的表达及其与HPV感染的相关性探讨

目的分析TSC22D1在口咽鳞状细胞癌(OPSCC)中的表达情况,并探讨其与人乳头状瘤病毒(HPV)感染(p16+)的相关性。方法回顾性分析55例OPSCC患者的临床资料和组织样本,包括扁桃体癌27例,舌根癌25例,软腭癌3例,另收集12例舌鳞状细胞癌(TSCC)组织样本进行分析。选择11例扁桃体炎标本和2例癌旁舌上皮标本作为对照。通过免疫组化染色检测TSC22D1和p16的表达。分析TSC22D1表达情况与OPSCC患者临床病理指标的关系。结果TSC22D1在癌旁舌根Von Ebner′s腺管开口处的柱状上皮区以及转化区的基底层连续表达,在癌旁舌上皮组织仅散在表达于基底细胞,在部分TSCC及舌根癌中有密集表达。TSCC组织和舌根癌组织TSC22D1表达差异无统计学意义(P>0.05)。TSC22D1在扁桃体的网状上皮连续表达,在部分扁桃体癌中呈阳性表达。TSC22D1在扁桃体非癌组织(扁桃体炎组织)的阳性表达率高于扁桃体癌组织,差异有统计学意义(P<0.05)。TSC22D1阳性OPSCC的低分化率显著高于TSC22D1阴性OPSCC(P<0.05),TSC22D1表达情况与患者性别、年龄、吸烟数、民族、病发部位、N分期、T分期、临床分期以及HPV感染(p16+)无显著关联(P>0.05)。结论TSC22D1可能是OPSCC的易感区域标志物,在口咽癌变过程中表达降低,其与p16表达可能无明显关联。

口咽部鳞癌中人乳头瘤病毒感染的检测

目的检测口咽鳞癌组织标本人乳头瘤病毒(HPV)感染情况,获得其型别分布及肿瘤临床病理特点。方法选择1999年1月至2009年12月在中国医学科学院肿瘤医院病理科存档的满足条件的口咽鳞癌活检或手术标本共66例,采用SPF10-DNA LiPA分型方法进行检测。结果 66例标本中,11例(16.7%)检测出HPV,其中HPV-16型7例,HPV-16/11型1例,HPV-35、PV-58/52和HPV-33/52/54型各1例,HPV-16型占所有感染者的比例为72.7%(8/11)。HPV阳性标本中,女性(36.4%比1.8%,P=0.002)、非吸烟(36.4%比0,P=0.001)及非饮酒者(45.5%比1.8%,P=0.001)所占的比例均明显高于HPV阴性标本;低分化所占为81.8%,与HPV阴性标本的63.7%比较,差异无统计学意义(P=0.409);HPV阳性和阴性标本在T分级、N分级及临床分期方面差异均无统计学意义(P均>0.05)。结论口咽鳞癌患者HPV感染率为16.7%,HPV相关口咽鳞癌具有独特的流行病学和临床病理特点。

局部晚期复发口腔癌挽救性手术近期疗效分析

目的 :挽救性手术是复发口腔口咽癌一种有可能根治的治疗方法。肿瘤复发灶切除后巨大缺损的修复重建是治疗的难点,本研究对局部晚期复发口腔口咽癌行挽救性手术切除及延长下斜方肌皮瓣修复,并评估其近期疗效。方法:选取中山大学孙逸仙纪念医院23例局部晚期复发口腔口咽癌患者,男17例,女6例,行挽救性手术切除肿瘤并以延长下斜方肌皮瓣修复缺损。19例口腔癌,4例口咽癌;复发癌临床分期为3例r CS III期,20例r CS IV期;在首次治疗方面,15例行手术治疗,4例放疗,4例手术后辅以放疗;之后的再次治疗方面,11例患者进行手术治疗,10例进行根治性放疗,2例行手术治疗辅以术后放疗。所有患者均无远处转移。其中21例患者行肿瘤复发灶的广泛切除,2例患者进行颅颌面切除。肿瘤切除术后缺损采用延长下斜方肌皮瓣修复,皮岛大小6 cm×7 cm^10 cm×22 cm,9例患者采用折叠延长下斜方肌皮瓣修复颌面洞穿性缺损。采用SPSS 12.0软件包对数据进行统计学分析。结果:所有患者术后均未出现严重并发症,出现远端皮瓣局部坏死、供区切口裂开及口内外瘘道各1例。4例患者(17.4%)术后可正常进食固体食物,11例患者(47.8%)可进食软食,4例患者(17.4%)可进食流质食物,4例患者(17.4%)需留置经鼻胃管,鼻饲流质饮食。9例患者(39.2%)术后发音正常,8例患者(34.8%)术后发音尚清楚,3例患者(13.0%)术后语音不清,3例患者(13.0%)术后需永久性气管造瘘。随访3~72个月(中位时间15.7个月),15例患者(65.2%)无复发生存,2例患者(8.7%)复发生存,6例患者(26.1%)在随访3~18个月时死于肿瘤复发和转移。无复发生存患者的第二次治疗至复发时间为7.40±0.53个月,复发、转移、死亡患者的时间为4.83±0.42个月,两者间差异显著。结论:挽救性手术治疗局部晚期复发口腔口咽癌是一种有效的治疗方案,延长下斜方肌皮瓣是修复此类手术后巨大缺损简单、可靠的大型组织瓣。

口咽鳞状细胞癌新鲜冰冻组织中人乳头状瘤病毒的检测及分型

人乳头状瘤病毒（human papillomavirus,HPV）中有些型别与癌前病变相关,称为高危型HPV。国际癌症研究机构已认定HPV-16和HPV-18对人有致癌作用[1]。近年来有研究表明,高危型HPV感染与部分头颈部鳞状细胞癌（head and neck squamous cell carcinoma,HNSCC）关系密切,HPV感染与否对HNSCC患者的预后有着显著影响,无论是治疗效果还是生存率,

口咽鳞癌中HPV感染与血管生成的关系

目的:研究口咽鳞癌(oropharyngeal squamous cell carcinomas,OSCC)中人乳头瘤病毒(human papillomavirus,HPV)感染与血管内皮生长因子(vascular endothelial growth factor,VEGF)、CD31标记的微血管密度(microvessel density,MVD)表达的关系,探讨它们在口咽鳞癌发生中的相互关系。方法:采用多重实时荧光定量聚合酶链反应(multiplex real-time polymerase chain reaction,MT-PCR)检测60例口咽鳞癌HPV DNA及型别,通过HPV DNA分析进行HPV感染状况的测定;同时采用半定量免疫组化检测HPV(+)组和HPV(-)组中VEGF、CD31(MVD标志)蛋白表达情况。结果:口咽鳞癌中HPV感染率36.7%(22/60),HPV-16型占所有感染者的比例86.4%(19/22),明显高于其他型别;VEGF高度表达者出现MVD>15个/高倍视野的几率较VEGF低度表达者高(P=0.001);MVD>15个/高倍视野的肿瘤为低分化的可能性较高(P=0.004);VEGF和MVD表达与患者年龄、性别、TNM分期、HPV感染状况之间无相关性。结论:HPV感染与口咽鳞癌的发生存在相关性。口咽鳞癌中HPV感染状况和VEGF之间无相关性。

口咽鳞癌p16蛋白以及EGFR表达在放疗中的临床意义

目的探索口咽鳞癌患者中p16蛋白状态以及EGFR表达对放疗近期和远期疗效的影响。方法回顾性分析首程治疗为本中心放疗且留存有放疗前肿瘤病理标本的39例口咽鳞癌患者,将患者按照p16蛋白状态和EGFR表达进行分组,比较放疗近期疗效以及总生存情况。结果 39例口咽鳞癌患者以Ⅳ期为主(84.6%),其中23例患者(59.0%)p16蛋白表达阳性。p16(+)者放疗后可以获得更好的肿瘤退缩,而EGFR的表达不同未发现与肿瘤退缩情况相关,多因素分析显示p16蛋白是影响总生存的独立预后因素。结论 p16蛋白阳性的口咽癌患者较阴性者放疗敏感性更高、预后更好,但需要扩大样本量进行验证。

^(125)Ⅰ放射性粒子联合EGFR抑制剂治疗晚期舌根鳞癌的疗效分析

舌根鳞癌是预后较差的头颈部恶性肿瘤之一,通常发现时已属晚期。本文报告2例合并全身系统性疾病的晚期舌根鳞癌患者,经^(125)I放射性粒子联合表皮生长因子受体抑制剂治疗取得较好的疗效。

人乳头状瘤病毒相关性p16INK4A在口咽鳞状细胞癌中的表达及对其疗效的影响

目的探讨人乳头状瘤病毒在口咽鳞状细胞癌(OPSCC)中的表达及其临床意义。方法采用免疫组化法检测p16^INK4A表达,评估58例口咽鳞状细胞癌人乳头状瘤病毒(HPV)感染状态,根据HPV感染状态、临床因素如年龄、抽烟、饮酒等对总生存率(OS)等方面是否存在显著性差异。结果58例OPSCC HPV感染率24.1%(14/58)。中位随访时间33个月(3.0~99.0个月),Kaplan-Meier统计分析,患者3年总体生存率为42.3%,其中HPV阳性组3年总生存率为47.6%,HPV阴性组为39.3%。HPV阳性患者与HPV阴性者的总体生存率不存在显著性差异(P=0.7190)。通过单因素分析发现年龄、是否合并基础疾病、是否接受根治性放疗对总生存率有显著影响;通过多因素分析,年龄、根治性放疗对总体生存率均有显著影响。结论通过本项研究显示OPSCC患者中存在HPV感染率,HPV阳性与阴性对患者总生存率没有显著性影响,但患者年龄、根治性放疗等对总生存率有显著性影响。