骨桥蛋白及C-met在喉癌中的表达意义

目的：探讨骨桥蛋白（OPN）和C-met在喉鳞状细胞癌组织中的表达情况,及其与肿瘤发生、侵袭及转移的关系。方法：采用免疫组织化学法（ElivisionTMplus法）检测52例喉鳞状细胞癌肿瘤组织及30例癌旁组织中OPN和C-met的表达情况,分析OPN和C-met的表达水平与患者的临床分期、组织分化程度、淋巴结转移情况间的关系。结果：在喉鳞状细胞癌和癌旁组织中OPN、C-met的阳性表达率分别为7】．2％、6．7％和63．5％、16．7％,喉鳞状细胞癌临床分期I-Ⅱ期患者中的OPN和C-met阳性表达率者分别为48．1％和55．6％．III-Ⅳ期患者中的OPN和C-met阳性表达率分别为96．0％和80．0％,无转移患者中OPN阳性率为53,6％,Cmet阳性率为46．4％,转移患者中OPN阳性率为91．7％,C-met阳性率为83．3％,彼此间差异均具有统计学意义;高一中分化患者中OPN阳性率为65．7％,C-met阳性率为54．3％,17例低分化患者中OPN和C-met阳性表达率均为82．4％,二者问无显著性差异。结论：OPN和Cmet的阳性表达率随着临床分期进展而明融提高,且与淋巴结转移有一定关系,但其阳性表达与组织分化程度间未见明显联系,OPN与C-met蛋白在喉鳞状细胞癌组织中的异常表达呈正相关关系,可能对喉鳞状细胞癌的侵袭和转移起着一定的作用。     

人乳头状瘤病毒感染与喉咽鳞状细胞癌相关性的Meta分析及生物信息学分析

目的　系统评价人乳头状瘤病毒（HPV）感染与喉咽鳞状细胞癌的相关性并探索该疾病预后的潜在指标。方法  计算机检索PubMed、Embase、The Cochrane Library、中国知网、中国生物医学文献数据库、维普和万方数据库,检索时限均从建库至2020-11-30。由2位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用Stata15.1及RevMan 5.3软件进行Meta分析。从GEO数据库获取HPV相关头颈癌的芯片数据进行差异基因分析,并对这些基因进行功能注释。利用GEPIA数据库得到生存相关的关键 基因。结果　共纳入11篇文献,包含喉咽鳞状细胞癌患者1245例,合并后HPV总阳性率为12%（95%CI : 6%～19%）。亚组分析结果,国内喉咽鳞状细胞癌患者HPV阳性率为19%（95%CI : 12%～26%）,较国外患者HPV阳性率为10%（95%CI : 2%～18%）高（P <0.05）;不同检测技术,聚合酶链式反应（PCR）+原位杂交（ISH）的HPV阳性率为18%,较单纯ISH及PCR检测HPV阳性率高（P <0.05）;男女喉咽鳞状细胞癌患者HPV阳性率无明显差异（P >0.05）;合并预后HR=0.33（95%CI : 0.14~0.79）（P<0.05）。对HPV阴性及阳性的头颈癌患者差异基因进行GO和KEGG富集分析表明,这些差异基因与多种重要通路有关。GEPIA对Top10显著差异基因进行生存分析得到关键基因ZNF541、WNK3、TCP11及CCNA1。结论　国内喉咽鳞状细胞癌患者HPV阳性率高于国外,PCR+ISH组的HPV阳性率较PCR与ISH组阳性率高,HPV阳性患者预后好于HPV阴性患者。生存相关基因可与HPV共同参与头颈癌的预后评价并提供新的研究思路。     

组织蛋白酶D与下咽癌侵袭转移的相关性研究

目的研究组织蛋白酶D(CD)在下咽鳞状细胞癌组织中的表达与下咽鳞状细胞癌的侵袭转移之间的关系.方法用免疫组织化学法研究59例下咽鳞状细胞癌组织标本和9例正常的下咽黏膜中CD和ki-67的表达;分析CD在下咽鳞状细胞癌细胞中和间质细胞中的表达与肿瘤生物学特性之间的关系.结果CD在颈淋巴结转移阳性组肿瘤细胞中的表达率较阴性组织高,CD在肿瘤间质细胞中的表达在颈淋巴结转移阳性组的表达率较阴性组高.结论CD表达与肿瘤侵袭转移的生物特性密切相关,可以作为下咽鳞状细胞癌侵袭转移的预后指标.     

喉鳞状细胞癌P16和增殖细胞核抗原表达

目的探讨p16基因及增殖细胞核抗原(proliferatingcellnuclearantigen,PCNA)在喉鳞状细胞癌中的表达及其临床意义。方法应用免疫组织化学技术SP法检测抑癌基因p16蛋白及PCNA在40例喉鳞状细胞癌中的表达,并与癌旁组织和正常喉组织对比,结合喉鳞状细胞癌的临床病理特征进行分析。结果在喉鳞状细胞癌中p16阳性率(50.0%)明显低于癌旁组织(76.0%)和正常组织(100.0%,P<0.05);Ⅰ、Ⅱ期喉癌中p16阳性率明显高于Ⅲ、Ⅳ期。喉鳞状细胞癌中PCNA阳性率为55.0%,明显高于癌旁组织(32.0%)和正常组织(10.0%,P<0.05);Ⅰ、Ⅱ期喉鳞状细胞癌中PCNA表达明显低于Ⅲ、Ⅳ期(P<0.05)。p16阳性与阴性患者生存期≥5年的比率分别为66.7%和33.3%,P<0.05;PCNA阳性与阴性患者生存期≥5年的比率分别为37.5%和62.5%,P<0.05。结论p16和PCNA分别是喉鳞状细胞癌进展及预后判断的独立指标;p16和PCNA联合检测对喉鳞状细胞癌的预后评估可能更有价值。     

用聚合酶链反应测量鼻及鼻窦癌存档标本中的人乳头状瘤病毒

用分子生物学技术研究证明，人乳头状瘤病毒（HPV）16型与鼻腔（NC）和曼窦（PSj乳头状瘤恶性变有关，在某些NC和PS鳞状细胞癌（SCC）患者中检出HPV－16。然而在这些病例中未检出HPV－18，在其它肿瘤例如腺癌、腺样囊性癌的组织中HPV的病原学作用尚不清，＊PV引起的这些肿瘤很罕见。用已知对HPVDNA高度敏感的聚合酶链反应（PCR＞研究HPV－16和HPV－18在NC和PS各种癌中的致病作用。在HPV阳性与HPV阴性SCC患者之间的临床表现进行了比较。选择49例SCC，4例腺样细胞癌，3例腺癌，3例未分化癌和1例粘膜表皮状癌患者的存档…     

喉鳞状细胞癌组织FLIP和PTEN蛋白的表达及其临床意义

目的：研究FLIP和PTEN在喉鳞状细胞癌组织中的表达,探讨FLIP在喉鳞状细胞癌发生发展中的作用及与PTEN的关系。方法：采用免疫组织化学SP法检测45例喉癌组织以及15例癌旁组织中的FLIP和PTEN的表达。结果：FLIP在喉癌中的表达阳性率（77．8％）高于癌旁组织（33．3％）（P〈0．05）,FLIP的表达与喉鳞状细胞癌患者的临床分期及颈淋巴结转移和预后均有关。PTEN在喉癌中的表达阳性率（65．0％）高于癌旁组织（0）,（P〈0．01）,PTEN的表达与喉鳞状细胞癌的肿瘤临床分期及分化程度、颈淋巴结转移和预后有关。FLIP与PTEN在喉鳞状细胞癌中的表达呈负相关。结论：FLIP可能是喉鳞状细胞癌的一个重要的预后标记物。PTEN的表达与肿瘤临床分期、肿瘤分化和淋巴结转移有关,也可能是判断预后的一个有意义的指标。     

端粒酶催化亚单位和c-myc在喉鳞状细胞癌组织中的表达及意义

目的：研究喉鳞状细胞癌组织中端粒酶催化亚单位（hTERT）和c-myc的表达及其与喉鳞状细胞癌临床病理参数的关系。方法：应用免疫组织化学法检测39例喉鳞状细胞癌组织和10例声带息肉组织中hTERT和c—myc蛋白的表达，并分析喉鳞状细胞癌组织中hTERT和c—myc蛋白的表达与肿瘤各项临床病理参数的关系。结果：39例喉鳞状细胞癌组织中hTERT、c—myc蛋白阳性表达率分别为84．6％（33／39）和82．1％（32／39）；10例声带息肉组织中hTERT蛋白均未见阳性表达，c—myc蛋白阳性表达率为10．0％（1／10），经统计学分析hTERT和c—myc蛋白在喉鳞状细胞癌组织与声带息肉组织中的表达差异有统计学意义（均P〈0．01）。喉鳞状细胞癌组织中hTERT蛋白阳性表达与癌组织的临床分期、肿瘤分化程度及颈淋巴结转移之间均无相关性。喉鳞状细胞癌组织中hTERT和c—myc蛋白阳性表达之间存在显著正相关关系。结论：hTERT的激活及c—myc的过度表达在喉鳞状细胞癌的发生中起重要作用，c—myc基因可能是hTERT激活的重要调控因子。     

鼻腔鼻窦鳞状细胞癌中血管内皮生长因子的表达及其与微血管和微淋巴管密度的关系

目的：研究鼻腔鼻窦鳞状细胞癌组织中血管内皮生长因子（VEGF）表达的临床病理学意义,同时探讨VEGF与微血管密度（MVD）和微淋巴管密度（MLVD）的关系。方法：采用免疫组织化学法,检测41例鼻腔鼻窦鳞状细胞癌中VEGF的表达,同时标记CD34和D2—40,分别检测鼻腔鼻窦鳞状细胞癌组织中MVD和MLVD。结果：41例鼻腔鼻窦鳞状细胞癌中VEGF表达的阳性率为82．9％（34／41）,VEGF的表达与患者性别无关（P〉0．05）,而与肿瘤的侵犯范围、组织学分级和淋巴结转移相关（P〈0．05）;VEGF表达阳性组的平均MVD高于阴性组（P〈0．05）,而平均MLVD阳性组和阴性组之间无统计学差异（P〉0．05）。结论：VEGF可能通过促进鼻腔鼻窦鳞状细胞癌的血管形成而参与癌细胞的浸润转移,没有参与鼻腔鼻窦鳞状细胞癌微淋巴管的生成。     

程序性细胞死亡因子4在喉鳞状细胞癌中的表达及其与肿瘤细胞增殖和凋亡的关系

目的:探讨喉鳞状细胞癌中程序性细胞死亡因子4(PDCD4)蛋白表达与肿瘤细胞增殖和凋亡的关系及其临床意义。方法:采用免疫组织化学技术检测60例喉鳞状细胞癌组织及21例正常喉黏膜上皮组织中PDCD4和Ki-67的表达,原位末端标记(TUNEL)法检测细胞凋亡,以细胞增殖指数(PI)和细胞凋亡指数(AI)表示增殖与凋亡。结果:喉鳞状细胞癌组织中PDCD4蛋白阳性表达率低于癌旁正常喉黏膜组织(P<0.01),喉鳞状细胞癌组织中PDCD4蛋白阳性表达和喉鳞状细胞癌临床分型(肿瘤部位)、TNM分期无关,与病理分级、淋巴结转移有关(P<0.05);喉鳞状细胞癌组织细胞PI明显高于癌旁正常喉黏膜组织(P<0.01),细胞PI与喉鳞状细胞癌临床分型(肿瘤部位)、病理分级、淋巴结转移无关,与TNM分期有关(P<0.05);喉鳞状细胞癌组织细胞AI明显高于癌旁正常喉黏膜组织(P<0.01),细胞AI与喉鳞状细胞癌临床分型(肿瘤部位)、TNM分期、淋巴结转移无关,与病理分级有关(P<0.01);喉鳞状细胞癌PDCD4阳性表达的细胞PI低于阴性组(P<0.05),细胞AI高于阴性组(P<0.05)。结论:PDCD4在喉鳞状细胞癌中低表达,可能与喉鳞状细胞癌细胞的增殖和凋亡均有一定的关联。     

DNMT1基因在喉鳞状细胞癌中的表达及临床意义

目的:探讨DNA甲基转移酶1(DNMT1)基因在喉鳞状细胞癌中的表达及其与临床病理因素的关系.方法:采用免疫组织化学方法检测96例喉鳞状细胞癌中DNMT1基因蛋白的表达,其中66例喉癌组织同时进行实时定量PCR,并分析其DNMT1 mRNA的表达与临床病理因素的关系.结果:DNMT1 mRNA在喉鳞状细胞癌组织中表达上调(P<0.05).96例喉癌鳞状上皮细胞中DNMT1蛋白表达全部为阳性(96/96),36%(8/22)癌旁组织的鳞状上皮细胞中DNMT1蛋白表达为阳性,二者差异有统计学意义(P<0.05).DNMT1 mRNA在喉癌组织中表达上调,和患者年龄、性别、临床分期、淋巴结转移情况无关,但与患者吸烟史有显著相关性(P<0.05).结论:DNMT1可能在喉癌中表达增高从而引起肿瘤的发生,吸烟可能诱导DNMT1的表达增高.     

HPV status and regional metastasis in the prognosis of oral and oropharyngeal cancer

Prognostic factors are important for treatment decisions as they help adapt the therapy on a case-to-case basis. Nodal status, number of positive nodes, and presence of extracapsular spread are considered to be the important prognostic factors in head and neck cancer. Some studies suggest that human papillomavirus (HPV) status also influences the outcome of the treatment. This influence can be explained by the variation in tendency to develop regional metastases and by variation in the type of neck node involvement. The study objectives were to compare patients with HPV positive and HPV-negative tumors for survival and prevalence and type of regional metastasis, to identify prognostic factors and to test whether HPV presence is an independent factor of survival. The study included 81 patients treated by surgery including neck dissection for oral or oropharyngeal squamous cell cancer. A computerized medical report was completed for each patient. Analysis of the tumor specimen for the HPV DNA presence was done on paraffin-fixed tissue. HPV DNA detection and typing were performed by PCR with GP5 + /GP6 + BIO primers and reverse line blot hybridization. Overall, 64% (52/81) of tumors were HPV positive with 80% in the tonsillar site. HPV-positive patients had significantly better both overall (73 vs. 35%) (P = 0.0112) and disease-specific (79 vs. 45%) (P = 0.0015) survival rates than HPV-negative patients. No significant differences were found in the pN classification, in the number of positive nodes and the presence of extracapsular spread in the involved nodes between HPV positive and HPV-negative tumors. Multivariate analysis showed that significant prognostic factors of survival were the presence of HPV in the tumor, extracapsular spread and tumor size. HPV was the most significant prognostic factor in the studied group of patients with oropharyngeal tumors (HR = 0.27, 95%CI 0.12–0.61) and possibly should be considered in treatment decisions.     

Impact of HPV infection on the clinical outcome of p-CAIR trial in head and neck cancer

The purpose of the study was to analyse the influence of HPV infection on the outcome of a randomized clinical trial of conventional (CF) versus 7-days-a-week postoperative radiotherapy (p-CAIR) for squamous cell cancer of the head and neck (SCCHN). Between 2001 and 2004, 279 patients with high-risk SCC of the larynx or cancer of the oral cavity/oropharynx were randomized to receive 63 Gy in fractions of 1.8 Gy given 5 days a week or 7 days a week (Radiother Oncol 87:155–163, 2008). The presence of HPV DNA in 131 archival paraffin blocks was assessed with multiplex quantitative real-time PCR using five consensus primers for the conservative L1 region and molecular beacon probes targeting 14 high-risk HPV subtypes. Following the RT-PCR procedure, we could determine the presence and type of HPV16, HPV18 and the other 12 less frequent oncogenic subtypes. Out of 131 samples, 9 were positive for HPV infection (6.9%), all of them with HPV16 subtype. None of the 65 laryngeal tumours was HPV positive. The 5-year LRC in HPV-positive patients was 100%, compared to 58% in the HPV-negative group (p = 0.02, log-rank test). Amongst 122 patients with HPV-negative tumours, 5-year LRC was 50.3% in p-CF versus 65.2 in p-CAIR (p = 0.37). HPV infection was associated with low expression of EGFR and cyclin D. This study demonstrates a favourable outcome for HPV-positive patients with SCCHN treated with postoperative radiotherapy. While considering the small number of HPV+ tumours, the data set can be considered as hypothesis generating only, the outcome raises new questions on the necessity of aggressive postoperative treatment in HPV+ patients.     

Human papillomaviruses in lymph node neck metastases of head and neck cancers

CONCLUSION: The results of this study corroborate earlier findings that human papillomavirus (HPV)16 is the most prevalent type of HPV in squamous cell carcinomas of the head and neck (SCCHNs) and reinforce a possible influence of HPV on SCCHN progression by showing that the majority of HPV-positive patients harbor HPV16 (or HPV33) both in their primary tumors and in lymph node neck metastases (LNNMs). OBJECTIVE: HPVs are causally associated with carcinomas of the uterine cervix and have also been linked to a subset of SCCHNs. In order to further investigate the predicted causative role of HPV in SCCHNs, we analyzed pairs of primary tumors and LNNMs or LNNMs alone for the presence of HPV DNA using polymerase chain reaction (PCR). MATERIAL AND METHODS: DNA was extracted from fresh frozen tissue samples of primary tumors and the corresponding LNNMs of 18 patients and from LNNMs alone in 17 patients. For the detection and typing of HPV, PCR was performed using both type-specific and consensus primer pairs, followed by Southern hybridization and, in selected cases, sequencing of the PCR products. RESULTS: Of the 35 patients investigated, 22 (63%) were found to have HPV DNA in their tumors: HPV16 DNA in 21 cases and HPV33 in 1. The highest HPV prevalence was detected in tumors of Waldeyer's tonsillar ring (8/9 patients; 89%). Of the 18 patients in whom primary tumors and LNNMs were analyzed, 7 (39%) were HPV-positive in both samples (HPV16, n = 6; HPV33, n = 1), in 3 (17%) the primary tumors were HPV-negative and the LNNMs HPV16-positive and in 1 (5.5%) the primary tumor contained HPV16 and the LNNM was negative. Interestingly, of the 7 patients in whom LNNMs had been detected only several months after diagnosis and treatment of the primary tumors, only 1 showed infection with HPV (HPV33).     

Humane Papillomavirusinfektionen bei Plattenepithelkarzinomen des Kopf- und Halsbereichs

There is increasing evidence worldwide that human papillomavirus is a major risk factor for head and neck cancer. Only few studies on this association have been performed in Germany to date. For the purposes of the present study, tumor specimens from 223 patients with squamous cell cancer of the oral cavity, oropharynx, hypopharynx and larynx were analyzed for HPV DNA and p16INK4a expression. The prevalence of HPV genotype 16 (HPV16) DNA in the study population was 17.5?%. Further high-risk HPV types were not detected. All HPV16-positive tumors showed intense p16INK4a expression. HPV16 prevalence was highest in tonsillar carcinoma (37.5?%) and lowest in laryngeal cancer (2.8?%). We observed a significantly higher incidence of cervical lymph node metastases in patients with HPV16-positive tonsillar carcinoma in comparison to HPV-negative tumors (p?<?0.016). Tobacco and/or alcohol consumption was significantly lower in patients with HPV-positive tumors (p?<?0.0001).     

Visual gravitational vertical perception in peripheral vestibular hypofunction

Conclusion The results of this study corroborate earlier findings that human papillomavirus (HPV)16 is the most prevalent type of HPV in squamous cell carcinomas of the head and neck (SCCHNs) and reinforce a possible influence of HPV on SCCHN progression by showing that the majority of HPV-positive patients harbor HPV16 (or HPV33) both in their primary tumors and in lymph node neck metastases (LNNMs).

Objective HPVs are causally associated with carcinomas of the uterine cervix and have also been linked to a subset of SCCHNs. In order to further investigate the predicted causative role of HPV in SCCHNs, we analyzed pairs of primary tumors and LNNMs or LNNMs alone for the presence of HPV DNA using polymerase chain reaction (PCR).

Material and methods DNA was extracted from fresh frozen tissue samples of primary tumors and the corresponding LNNMs of 18 patients and from LNNMs alone in 17 patients. For the detection and typing of HPV, PCR was performed using both type-specific and consensus primer pairs, followed by Southern hybridization and, in selected cases, sequencing of the PCR products.

Results Of the 35 patients investigated, 22 (63%) were found to have HPV DNA in their tumors: HPV16 DNA in 21 cases and HPV33 in 1. The highest HPV prevalence was detected in tumors of Waldeyer's tonsillar ring (8/9 patients; 89%). Of the 18 patients in whom primary tumors and LNNMs were analyzed, 7 (39%) were HPV-positive in both samples (HPV16, n=6; HPV33, n=1), in 3 (17%) the primary tumors were HPV-negative and the LNNMs HPV16-positive and in 1 (5.5%) the primary tumor contained HPV16 and the LNNM was negative. Interestingly, of the 7 patients in whom LNNMs had been detected only several months after diagnosis and treatment of the primary tumors, only 1 showed infection with HPV (HPV33).     

Presenting symptoms and clinical findings in HPV-positive and HPV-negative oropharyngeal cancer patients

Objectives: Oropharyngeal squamous cell carcinoma (OPSCC) is divided in two different disease entities depending on HPV involvement. We investigated differences in presenting symptoms and clinical findings in patients with HPV-positive and -negative OPSCC tumors.

Methods: Altogether 118 consecutive patients diagnosed with primary OPSCC between 2012 and 2014 at the Helsinki University Hospital were included. HPV-status of the tumors was assessed by PCR detection of HPV DNA and immunostaining with p16-INK4a antibody.

Results: Fifty-one (47.7%) of the patients had HPV-positive and 56 (52.3%) HPV-negative tumors. Forty-nine (49/51, 96.1%) of the HPV+ tumors were also p16+ showing high concordance. The most common presenting symptom among HPV+/p16+ patients was a neck mass (53.1%), whereas any sort of pain in the head and neck area was more frequently related to the HPV?/p16? (60.0%) group. HPV+/p16+ tumors had a tendency to locate in the tonsillar complex and more likely had already spread into regional lymph nodes compared with HPV?/p16? tumors. Smoking and heavy alcohol consumption were significantly more common among HPV?/p16? patients but also rather common among HPV+/p16+ patients.

Conclusions: This analysis of symptoms and signs confirm that OPSCC can be dichotomized in two distinct disease entities as defined by HPV status.     

Rising incidence of oropharyngeal cancer and the role of oncogenic human papilloma virus

OBJECTIVES/HYPOTHESIS: To document the increasing incidence of oropharyngeal (OP) cancer and to provide evidence that this increase is caused by oncogenic human papilloma virus (HPV). STUDY DESIGN: Epidemiologic review and retrospective case series analysis. METHODS: We collected data from Colorado and the United States comparing the average annual age-adjusted incidence rates of OP and non-OP head and neck cancer between the periods 1980 to 1990 and 1991 to 2001. We obtained data on 72 patients with OP cancer from a single county in Colorado, from 1980 through 2004. HPV status was determined by DNA-polymerase chain reaction. We assessed disease-specific survival. RESULTS: The average annual age-adjusted incidence of OP cancer in males in Colorado increased from 2.54 per 100,000 to 3.47 (P < .05) or 36.6%, whereas the U.S. rate increased from 4.34 to 4.81 (P < .05) or 10.8%. The rates in females and the rates of non-OP head and neck cancer decreased. Of the 72 cases, 50 (69%) were positive for HPV subtype 16. The ratio of HPV-positive to HPV-negative cases prior to 1995 was 0.72 (8:11) but was 3.81 (42:11) afterward. Survival was positively affected by HPV status (hazard ratio of 0.15, confidence intervals 0.07-0.36, P < .001). Disease-specific survival was 83% in the HPV-positive patients and 15% in the HPV-negative group. CONCLUSIONS: OP cancer incidence is increasing in Colorado males and to a lesser extent in U.S. males. The HPV-positive OP cancer cases were more frequent in the later years of the study. Disease-specific survival was much better in the HPV-positive patients, confirming that HPV testing defines a unique subset of patients. These findings suggest that HPV oncogenesis accounts for the increase in average annual age-adjusted incidence of OP cancer.     

Resultados de la radioterapia en los carcinomas de orofaringe

ObjectiveTo present the results of radiotherapy treatment in patients with oropharyngeal carcinomas.Material and methodsRetrospective study of a cohort of 359 patients treated with radiotherapy, including chemo- and bio-radiotherapy, during the period 2000-2019. Information on human papillomavirus (HPV) status was available for 202 patients, of whom 26.2% were HPV-positive.ResultsFive-year local recurrence-free survival was 73.5% (95% CI: 68.8-78.2%). The variables that were related to local disease control in a multivariate study were the local tumor extension category and the HPV status. Five-year local recurrence-free survival for patients with cT1 tumors was 90.0%, for cT2 88.0%, for cT3 70.6%, and for cT4 42.3%. Five-year local recurrence-free survival for HPV-negative tumors was 67.2% and for HPV-positive tumors 93.3%. Five-year specific-disease survival was 64.4% (95% CI: 59.1-69.7%). Variables that were related to specific survival in a multivariate study were the patient's general condition, local and regional extent of the tumor, and HPV status.ConclusionsFive-year local recurrence-free survival of patients with oropharyngeal carcinomas treated with radiotherapy was 73.5%. Variables that were related to local control were local tumor extension and HPV status.     

Human papilloma virus and p53 expression in carcinomas associated with sinonasal papillomas: a Danish Epidemiological study 1980-1998

OBJECTIVES: To determine a putative role and relation between human papilloma virus (HPV) and p53 in the etiology of sinonasal carcinomas associated with papillomas. STUDY DESIGN: The study group consists of all patients with sinonasal carcinomas associated with papillomas diagnosed in Denmark from 1980 to 1998. After reviewing our national pathological files, tumor tissues from 36 patients were collected, comprising 15% of the total cases of sinonasal carcinomas. In 35 cases a squamous cell carcinoma was demonstrated and in one case an adenocarcinoma was evident. Inverted papilloma was associated with carcinoma in 31 cases and exophytic papillomas in 5 cases. The material was investigated for HPV using polymerase chain reaction analyses with two sets of consensus primers (GP5+/GP6+ and MY09/MY11). The HPV-positive cases were submitted to dot-blot hybridization to establish the HPV type. Using immunohistochemistry, the p53 expression was determined. A p53 overexpression is defined as positive staining in 10% or more of the tumor cells. RESULTS: Among 30 examined cases of carcinomas associated with inverted papillomas, 4 cases were HPV-positive (13%). P53 overexpression was not shown among the HPV-positive cases, whereas p53 overexpression was seen in 21 of the 24 (88%) examined HPV-negative cases. Among the 5 carcinomas associated with exophytic papillomas, HPV was demonstrated together with p53 overexpression in 3 cases (60%). In addition, one case more was with p53 overexpression. CONCLUSION: An inverse relation between HPV and p53 overexpression in sinonasal carcinomas associated with inverted papillomas appears to have been demonstrated. HPV and p53 might also have an etiological role among the carcinomas associated with exophytic papillomas.     

Association of HPV status with survival after surgical salvage of oropharyngeal cancers

ObjectivesThis study used the National Cancer Database to determine the effect of human papillomavirus (HPV) on survival outcomes for recurrent oropharyngeal cancer treated with salvage surgery after initial treatment with radiation therapy or chemoradiation therapy.MethodsPatients with recurrent oropharyngeal cancer receiving salvage surgery after initial treatment with adjuvant therapy were identified through the National Cancer Database. Demographics, tumor characteristics, and survival data were collected. The data were analyzed to identify factors that may be associated with survival.ResultsA total of 169 patients were included, 59% of which were HPV-positive cases and 41% were HPV-negative. On univariate analysis, HPV-positive cases had higher overall survival compared to HPV-negative cases. However, on multivariate analysis, the association with HPV status was no longer statistically significant while positive surgical margins, higher T-stage at initial diagnosis, and a greater comorbidity burden were significantly associated with poorer survival.ConclusionIn the salvage setting for treatment of recurrent oropharyngeal squamous cell carcinoma, HPV status may not be associated with improved survival.