Prognostic significance of serum squamous cell carcinoma antigen in patients with head and neck cancer

Conclusions: Serum squamous cell carcinoma antigen (SCC-Ag) level was an independent prognostic factor for survival in patients with head and neck squamous cell carcinoma (HNSCC), and the prognostic value depended on the carcinoma site. Objectives: To assess the value of SCC-Ag as a prognostic indicator in patients with HNSCC and to determine the effect of primary tumor site on prognosis. Methods: We reviewed 493 patients with HNSCC between 2004 and 2012. The chi-squared test was used to assess associations between SCC-Ag levels and TNM classification. A Cox proportional hazard model was used to assess the hazard ratio of SCC-Ag at different sites for death, and it was analyzed as a continuous variable. Results: The median serum level of SCC-Ag was 1.1 ng/ml (range 0–20). SCC-Ag was significantly higher in patients with advanced T and N classification tumors. Primary sites in the oral cavity, in the hypopharynx, advanced T and N classification, distant metastasis, and SCC-Ag were negatively associated with survival in univariate analysis. Multivariate analysis revealed that SCC-Ag was a significant risk factor for overall survival in cancers of the oral cavity, hypopharynx, and larynx, but not in oropharyngeal cancer.     

Improved survival in patients with head and neck cancer in the 1990s

It is generally felt amongst the medical profession and the lay public that cancer is being treated more successfully than in the past. This is certainly true for childhood malignancies and leukaemia but evidence that significantly improved survival is occurring in the common solid tumours is lacking. Since 1963 the University of Liverpool Department of Otolaryngology/Head and Neck Surgery has collected data on all patients with head and neck tumours presenting to the department. The present study investigates patients with histologically proven squamous cell carcinoma of the four main sites: larynx, hypopharynx, oral cavity and orophyarnx. From 1963 until the end of 1989, 2738 patients were seen by the department and from 1990 a further 717 patients have been seen. Since 1990 patients have tended to be in better general physical condition but, on the other hand, have tended to have more advanced disease at the primary site. The department has latterly tended to see fewer laryngeal cancers and more cancers of the oropharynx. Significantly fewer patients have presented with neck node metastases. Multiple logistic regression suggests that the most significant difference between the two groups is the great reduction in neck node recurrence rates in the group of patients seen since 1990 (P = 0.0001). The recurrence of tumours at the primary site since 1990 has been 35% compared with 41% before 1990, and recurrence in the neck nodes since 1990 has been 12%, compared with 15% before 1990. These differences are significant (P = 0.0141 and P = 0.0494, respectively). When studying survival in the 1960s, 1970s and 1980s, the 5-year cure rate was 50%, whereas since 1990 the figure has risen to 60% tumour-specific 5-year survival—a significant difference. A similar effect was noted in observed survival. This improvement in cure rate occurred for all four main sites. The results were confirmed by Cox’s proportional hazards model where year of treatment was highly significantly associated with improved survival (P = 0.0001). It has been demonstrated that locoregional recurrence has improved since 1990 and this is reflected in improved survival figures. Although there are differences in the parameters of tumours referred before 1990 and since 1990, multivariate analysis suggests that the improvement in neck node recurrence rates may be responsible for this improved survival rate. Multivariate analysis for survival also suggests that the improvement in cure rates is independent of compounding variables and dependent on the year of presentation of the tumour. This improved survival may be related to factors, such as the administration of radical postoperative radiotherapy.     

Racial disparities in patients with head and neck squamous cell carcinoma

OBJECTIVES/HYPOTHESIS: Black patients are reported to have a higher incidence of advanced disease and increased mortality from head and neck squamous cell carcinoma (HNSCC) but constitute the minority of patients in large-scale studies investigating the effect of race on outcome. This study sought to determine if racial disparities exist between black and white patients with HNSCC treated at a single large institution in the South with a high proportion of black patients. STUDY DESIGN: The authors conducted a nonrandomized retrospective cohort analysis. METHODS: The tumor registry was used to identify patients diagnosed with HNSCC from 1985 to 2002. The medical records of non-Hispanic white and black adult patients were retrospectively reviewed. Median household income, percentage of population below poverty level, and education level based on census tract and block information were obtained from U.S. Census 2000 data. Standard statistical analysis, including Kaplan-Meier survival curve analysis and Cox proportional hazards models, was used to analyze the effects of covariables on survival. RESULTS: A total of 1,128 patients met study criteria (478 black, 650 white). Compared with white patients, black patients were significantly younger (mean age, 53.9 vs. 56.4 years, P<.0001), male (81.2% vs. 72.3%, P=.0005), more commonly abused alcohol (88.0% vs. 74.3%, P<.0001), and were significantly less likely to have insurance (8.6% vs. 21.7%, P<.0001). There was no difference in the incidence of tobacco use (91.7%), advanced comorbidity (35.9%), or primary tumor site. Black patients had a significantly greater incidence of stage IV disease (65.7% vs. 46.6%, P<.0001) and nonoperative treatment (48.7% vs. 30.8%, P<.0001), which was performed for inoperable disease in 57.1% of black compared with 31.0% of white patients (P<.0001). Black patients resided in census block groups with significantly lower mean education level, median income, and a higher percentage of population below poverty compared with white patients. The 5-year disease-specific survival differed significantly between black (29.3%) and white (54.7%) patients (P<.0001). Cox proportional hazards models revealed that alcohol abuse, advanced TNM stage, high tumor grade, nodal disease, extracapsular spread, advanced comorbidity, and regional or distant metastatic disease were associated with poorer survival for all patients. An interaction with race was found for insurance status, nonoperative treatment, and extracapsular spread. Stepwise variable selection adjusting for patient, tumor, and treatment characteristics showed a significant effect only for race by payor status on disease-specific survival (P=.0228). CONCLUSIONS: Insurance status, treatment, and extracapsular spread differentially affected the survival of black patients compared with white patients. Only insurance status had a significant effect on survival in black patients after controlling for other variables. These data suggest that racial differences in HNSCC outcomes are primarily related to differences in access to health care.     

Implications of tumour in resection margins following surgical treatment of squamous cell carcinoma of the head and neck

Presence of tumour at the resection margin following primary surgical treatment for squamous cell carcinoma of the head and neck is thought to adversely affect prognosis. To confirm this we performed a review of 478 patients treated by primary surgery for squamous cell carcinoma of the head and neck and sub-divided them into those exhibiting postive margins and those with negative margins following resection. Uni-variate and multi-variate statistical methods were used to analyse survival figures and a variety of parameters associated with the presence of positive resection margins. We found 5-year survival was decreased if resection margins were found to be positive (P < 0.025). The presence of positive resection margins was also significantly associated with time to tumour recurrence (P < 0.001) and survival with nodal recurrence (P < 0.001). Other factors which were significantly associated with survival using Cox's multi-variate analysis were site of tumour (P < 0.005), nodal extracapsular rupture (P < 0.05) and pathological T-stage (P < 0.05). Uni-variate analysis revealed no significant associations betweent the presence of positive margins and the patient's age, sex, tumour site, degree of tumour differentiation, and nodal status, though using multiple logistic regression, the general condition of the patient (P < 0.01) and the tumour site P < 0.05) were significantly related. The results support the concept that every effort should be made to obtain negative resection margins when undertaking primary ablative surgery for squamous cell carcinoma of the head and neck.     

Selective neck dissection for the treatment of neck metastasis from squamous cell carcinoma of the head and neck

OBJECTIVE: Our objective was to determine the proportion of patients disease free in the neck, with the primary site controlled, who have been treated with a selective neck dissection (SND) for squamous cell carcinoma (SCCa) of the upper aerodigestive tract, and who had cervical metastasis less than 3 cm. STUDY DESIGN: A cohort of patients who fit the inclusion/exclusion criteria was identified retrospectively. Then all surviving patients were followed for a minimum of 2 years. METHODS: A group of 52 patients who had 58 selective neck dissections for cervical metastases from SCCa of the upper aerodigestive tract were identified. The mean age was 56 years (range, 20-85 y), there were 40 males and 12 females, and mean follow-up was 24.5 months (range, 1-64 mo). Twenty-six patients had clinically negative (cNo) neck examinations and 26 had clinically positive neck examinations. Postoperative radiation was given for extracapsular spread, greater than 2 positive nodes, T3, T4, or recurrent disease if the patient had not received radiation before surgery. These radiation criteria excluded 18 patients from postoperative radiation treatment. RESULTS: Kaplan-Meier survival analysis showed that the regional control rate with the primary site controlled was 0.94. Six patients developed recurrent neck disease. Three of these 6 patientswere surgically salvaged. Four recurrences were in the dissected field and 2 were out of the dissected field (level V). CONCLUSIONS: With similar indications for radiation therapy, the regional control rate in this cohort is comparable to control rates obtained with modified radical neck dissection.     

Results of selective neck dissection in the primary management of head and neck squamous cell carcinoma

Selective neck dissection (SND) is known to be a valid procedure to stage the clinically N0 neck but its reliability to control metastatic neck disease remains controversial. This study analysed if selective neck dissection is a reliable procedure to prevent regional metastatic disease in head and neck squamous cell carcinoma (HNSCC). We retrospectively analysed the medical records of 163 previously untreated patients with squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx treated initially in our departement from January 1990 to December 2002. All patients had unilateral or bilateral SND, in combination with surgical resection of the primary tumour. SND was performed in 281 necks. Finally, 146 patients who underwent 249 SND (39 I–III, I–IV, 210 II–IV, II–V) had adequate follow-up and were assessed for the regional control. The median follow-up was 37 months (1–180 months). The end points of the study were neck control following SND and overall survival. Twenty-five percent (30/119) of patients staged cN0 had lymph node (LN) metastasis. Overall, regional recurrence was observed in 2.8% of the necks (7/249): 1.6% (4/249) in dissected field and 1.2% (3/249) in undissected field. Seventy-eight percent (194/249) of the necks were staged pN0 with a subsequent failure rate of 1.5% (3/194); 16% (39/249) were staged pN1 and postoperative radiotherapy (PORT) was proposed in 21 of these patients. The failure rate with PORT was 9.5% and 5.5% without PORT. Six percent (16/249) of the necks were staged pN2b and all had PORT with one subsequent recurrence. Extracapsular spread (ECS) was reported in 16.5% of positive SND specimens (9/55); all by one were treated by PORT with a subsequent failure rate of 22% (2/9). At 3 years, overall survival for the whole population was 70% and statistically highly correlated with pN stage (p<0.001). These results support the reliability of SND to stage the clinically N0 neck. SND is a definitive operation not only in pN0 but also in most pN1 and pN2b necks. PORT is not justified in pN1 neck without ECS. In pN2b necks, the low rate of recurrence supports adjuvant PORT. The presence of ECS, despite adjuvant PORT, remains associated with a higher risk of recurrence.     

Prevalence of synchronous bilateral tonsil squamous cell carcinoma: A retrospective study

Objectives

The prevalence of synchronous bilateral tonsil cancer remains unexplored. To date, only 38 cases have been described in the literature. With an aim to substantiate the Danish recommendation of performing bilateral tonsillectomy in patients with suspected or proven tonsil cancer and in patients with cervical carcinoma metastasis from an unknown primary tumour, this study was undertaken to determine the prevalence of synchronous bilateral tonsil cancer.

Design

A retrospective review of all patients diagnosed with tonsil cancer in the period 2000‐2015, Aarhus University Hospital, Denmark, was performed.

Results

Seven of 211 (3.3%) consecutive patients with tonsil cancer, who had undergone bilateral tonsillectomy (n = 180) or unilateral tonsillectomy (clinically normal side) combined with contralateral tonsil biopsy (side with suspected cancer) (n = 31), had synchronous bilateral tonsil cancer. Furthermore, dysplasia was found in the contralateral tonsil in two patients with unilateral tonsil cancer. Four of 171 (2.3%) patients with suspected unilateral tonsillar cancer had additional contralateral tonsil cancer. Three of 34 (8.8%) patients without clinical signs of tonsillar malignancy on any side (32 patients with carcinoma of unknown primary) had synchronous bilateral tonsil cancer. In none of the patients were bilateral tonsil cancer suspected. Patients with unilateral vs synchronous bilateral tonsil cancer had similar clinical and tumour characteristics.

Conclusion

Knowledge on additional contralateral synchronous tonsil cancer is crucial for avoidance of early recurrence of oropharyngeal cancer in patients with tonsil cancer. Based on our findings, we recommend bilateral tonsillectomy in all patients with suspected or proven tonsil cancer and carcinoma of unknown primary.     

Alcohol withdrawal prophylaxis in patients undergoing surgical treatment of head and neck squamous cell carcinoma

OBJECTIVES: Alcohol abuse is common in patients with squamous cell cancer of the head and neck. Postoperative alcohol withdrawal is associated with increased morbidity and prolonged hospitalization and is commonly treated with benzodiazepines. We reviewed our experience with benzodiazepine prophylaxis in high-risk patients undergoing surgical treatment of head and neck cancer. We sought to determine whether benzodiazepine prophylaxis was successful in preventing complications from alcohol withdrawal. STUDY DESIGN: Nonrandomized, retrospective patient analysis. METHODS: The medical records of all patients diagnosed with squamous cell carcinoma of the head and neck from 1999 to 2004 were retrospectively reviewed. Patients who underwent surgical resection and who were considered high risk for postoperative alcohol withdrawal received benzodiazepine prophylaxis following an established institutional protocol and comprised the study group. RESULTS: Of 96 patients who met study criteria, 13 (13.5%) patients developed alcohol withdrawal symptoms, and 9 (9.4%) patients developed delirium tremens. Patients who manifested alcohol withdrawal remained in the hospital an average of 10.8 days longer (19.0 vs. 8.2) and had an overall complication rate of 50% (11 of 22) versus a 17.6% (13 of 74) complication rate in patients that did not develop withdrawal (P < .05). CONCLUSIONS: Alcohol withdrawal is associated with a significantly greater incidence of postoperative complications and duration of hospitalization. Benzodiazepine prophylaxis does not prevent postoperative alcohol withdrawal symptoms in all patients at risk. Alternate methods of prophylaxis should be explored.     

The effect of occult nodal metastases on survival and regional control in patients with head and neck squamous cell carcinoma

Objectives: To determine factors associated with disease‐free survival (DFS) and regional control in clinically node‐negative head and neck squamous cell cancer (HNSCC) patients with occult metastasis. Study Design: Non‐randomized retrospective analysis. Materials and Methods: Patients who underwent elective neck dissection (END) from 1985 to 2002 were analyzed. Results: A total of 337 patients underwent END. The majority of patients (67%) had advanced stage disease (T3/T4). Occult metastases were present (pN+) in 168 patients (50%), with extracapsular spread (ECS) present in 72 patients (43%). Five‐year DFS for patients with histologically node negative necks was 62% versus 36% for pN+ patients (P < .0001). Postoperative radiation (XRT) did not significantly influence DFS for pN+ patients with less than three nodes involved, but had a significant association with DFS with three or more nodes involved (P < .0001). XRT showed a trend toward improved regional control rates in patients with less than three positive nodes (86% vs. 78%; P = .7579) and patients with three or more positive nodes (62% vs. 50%; P = .0014). When ECS was present, XRT did not affect DFS in patients with less than three nodes (36%), but had a significant effect on DFS in patients with three or more nodes (20% vs. 0%; P = .0075). Regional control rates were not improved with XRT in ECS‐positive patients with less than three nodes (62% vs. 75%) or with three or more nodes involved (43% vs. 50%; P = .0678). Conclusions: There is a high incidence of occult metastases in clinically node‐negative patients which adversely affects survival, regardless of the use of adjuvant XRT. Postoperative XRT did not significantly affect regional control or survival rates in patients with <3 positive nodes. When ECS was present, survival was poor regardless of the number of nodes. These data emphasize the prognostic and therapeutic role of END and highlight the need for the development of novel therapeutic regimens to improve disease control and survival in HNSCC patients with nodal metastases.     

头颈部鳞癌及癌旁组织端粒酶活性检测

目的：研究原发头颈部鳞癌及相关癌旁组织中端粒酶活性表达,探讨春作为头颈部鳞癌分子生物学标志物的可能性。方法：采用ＴＲＡＰ－ＰＣＲ－ＥＬＩＳＡ,对３２例原发头颈部鳞癌及１５例癌旁组织进行端粒酶活性检测。结果：３２例原发头颈部鳞癌中,２７例端粒酶活化,阳性率为８４．４％;１５例癌旁组织中５例端粒酶活化,阳性率为３３．３％。有淋巴结累及者端粒酶阳性率（８６．７％）高于无淋巴结累及者（８２．４％）,低分化     

The significance of immunohistochemically demonstrated nodal micrometastases in patients with squamous cell carcinoma of the head and neck

OBJECTIVES/HYPOTHESIS: Patients with primary squamous cell carcinoma of the head and neck have a relatively high risk of occult lymph node metastases. Pathological demonstration of these metastases may be difficult, and the detection of such occult metastases may identify patients who are at an increased risk for early recurrence or reduced survival. Immunohistochemistry may be applied in the identification of occult metastases that may be missed on routine (H&E) histological examination. The aim of the study is to determine the prevalence and prognostic significance of immunohistochemically identified micrometastases in squamous cell carcinoma of the head and neck. STUDY DESIGN: A retrospective analysis of neck dissection specimens having no evidence of metastatic disease. METHODS: Lymph nodes from neck dissections performed on 10 patients with squamous cell carcinoma of the head and neck without conventional histological evidence of nodal metastases were subsequently stained for cytokeratins by the monoclonal antibody cocktail AE1/AE3 to detect micrometastases. RESULTS: Occult micrometastases were found in the lymph nodes 5 of 10 patients examined. There was no association between the site of primary tumor, or T tage, and the presence of occult metastases. Three of five patients found to have occult metastases developed recurrence in the neck, whereas only one of five patients with no evidence of micrometastases had regional recurrence. There was no significant discrepancy in the patient survival rate. CONCLUSIONS: Metastatic tumor cells are frequently present in lymph nodes, even in patients without histological evidence of nodal metastases by conventional methods. The presence of micrometastases may identify patients at increased risk for recurrence and may indicate poorer prognosis. The true clinical significance of these occult metastases will be determined by a long-term follow-up.     

Whole-body MRI for staging patients with head and neck squamous cell carcinoma

Conclusions. Whole-body MRI is feasible for the tumor staging of patients with malignant head and neck tumors and appears to be a quick, reliable and proven alternative in general and for patients with contraindications to CT. This examination minimizes the logistical effort required compared to multimodality strategies. Its economic impact remains to be determined. Objective. To assess the performance of whole-body MRI for staging patients with squamous cell carcinoma of the head and neck region. Material and methods. This was a randomized, prospective clinical study. For tumor staging, 21 patients (mean age 56.7 years; range 43–80 years) with advanced malignant head and neck tumors underwent whole-body MRI in addition to routinely performed imaging investigations, including sonography, chest X-ray, CT of the head, neck and thorax and endoscopy. All investigations were accomplished within a period of 10±3 days in a random order. A randomized, blinded, consensus assessment of all the whole-body MRI examinations was performed by two radiologists. The localization and extent of the primary tumor and metastases were documented for whole-body MRI and compared to the standard of reference (all other imaging modalities as well as histology). Point estimates of the diagnostic accuracy of whole-body MRI were calculated. Results. In accordance with the standard of reference, the overall TNM category was correctly determined with whole-body MRI in all 21 patients. However, four patients were classified as having carcinoma of unknown primary, as the primary tumor was not found with any imaging modality. Two patients had mediastinal, pulmonary and hepatic metastases.     

头颈部鳞癌端粒酶活性的定量检测

目的：了解头颈部鳞癌及其颈淋巴结转移癌端粒酶的表达情况,探讨粒酶活性定量分析在头颈鳞癌诊断中的价值。方法：采用端粒重复序列液体闪烁计数法检测端粒酶活性。共检测取自２５例头颈部鳞癌患者的组织样本５５份,其中７例患者同时取有原发癌及其颈淋巴结转移癌两份样本,以２３份正常组织为对照。结果：①３２份原发鳞癌组织中端粒酶活性（ｃｐｍ值）在１０００以上的２８份,除２份外,均明显高于正常组织;２３份正常组织的端     

Proteolytic patterns of head and neck squamous cell carcinoma

The significance of plasminogen activators and matrix metalloproteases for clinical outcome, growth and metastatic behavior of head and neck squamous cell carcinoma (SCC) is still controversial. The majority of studies has been based on either immunohistological stainings, which provide only limited quantitative information, or in vitro experiments. We analyzed 44 head and neck SCC and 11 mucosa tissue samples for the expression of gelatinolytic or fibrinolytic proteases by quantitative zymographic analysis and compared lytic activities to clinical and histopathological data. We calculated activation ratios for matrix metalloproteinases-2 and –9 (MMP-2 and MMP-9) by separate evaluations of inactive and activated MMP forms. Increased gelatinolytic and fibrinolytic activity was found in head and neck SCC when compared to mucosa. Increased values were caused by MMP-9 and urokinase type plasminogen activator, respectively. No statistically significant correlations of either protease lytic activity or activation ratio could be related to T-stage, metastasis, tissue necrosis or the differentiation stage of tumors. The data recorded are compared with previously published reports. Received: 27 August 1998 / Accepted: 6 January 1999     

Basaloid squamous cell carcinoma of the head and neck

OBJECTIVE/HYPOTHESIS: Basaloid squamous cell carcinoma (BSCC), an uncommon tumor with predilection for the upper aerodigestive tract, is a distinct variant of squamous carcinoma, because of its unique histological features and ominous clinical behavior. This study reviews the experience in treating BSCC from two institutions. STUDY DESIGN: Retrospective. METHODS: H&E-stained sections from 20 patients with BSCC of the head and neck were reviewed and clinical follow-up was obtained for all patients. RESULTS: The study group consisted of 14 male and 6 female patients. Their ages ranged from 43 to 85 years, with a mean age of 62 years. Sites of origin included the larynx (4), tongue (3), pyriform sinus (3), nose (2), floor of mouth (2), mastoid (1), tonsil (1), epiglottis (1), nasopharynx (1), trachea (1), and palate (1). Pain was the most common presenting symptom (5 cases), followed by hoarseness and bleeding (3 cases each). Tobacco and alcohol abuse was noted in 17 patients. Treatment modalities included surgery with or without chemotherapy or radiotherapy in 13 patients, chemotherapy with irradiation in 2, chemotherapy alone in 2, and radiotherapy alone in 3. Clinical follow-up revealed no evidence of disease in 11 patients. Four were alive with disease at the time of writing and five died of disease. CONCLUSION: BSCC is a highly aggressive malignant tumor that presents in elderly patients who have a history of abuse of tobacco or alcohol, or both. Greater number of patients must be studied and compared with age-matched and stage-matched controls of conventional squamous cell carcinoma to determine whether the poor clinical outcome is related more to high-stage presentation or to the tumor's high-grade malignant cytological features.