Impact of stage, management and recurrence on survival rates in laryngeal cancer.

A retrospective, longitudinal study of 1,616 patients with primary laryngeal squamous cell carcinoma (LSCC) at a single center in Norway during 1983-2010 was undertaken to investigate overall survival, disease specific survival, disease-free survival, prognostic factors for overall survival, and impact of recurrence among all-stage laryngeal cancer patients over 15 years' follow-up. The prognostic impact of gender, age, smoking/alcohol, subsite, tumour, node and metastasis staging, period and modality of treatment were evaluated using Kaplan-Meier and Cox proportional hazard analyses. The importance of recurrence on survival was assessed based on case fatality rates. Five-year overall survival was 56.8%, 64.0% and 38.8%, and disease-specific survival was 80.2%, 87% and 61.6%, respectively, for the entire cohort and for glottic and supraglottic LSCC. Old age, advanced-stage LSCC and supraglottic cancer were associated with lower overall survival. The risk of disease-specific death plateaued after five years and varied significantly by subsite. Multivariate analysis of glottic LSCC revealed that surgical treatment improved overall survival, whereas old age, alcohol, T3-T4 status, positive N-status and no treatment were associated with worse survival. In supraglottic LSCC, age, alcohol, and positive N-status had a significant impact on overall survival by multivariate analysis. Five-year overall survival and disease-specific survival among patients with recurrent disease were 34% and 52%, respectively. In conclusion, marked difference in overall survival between glottic and supraglottic LSCC underline the importance of subsite-specific survival analysis. T-status and primary surgical management is essential only for glottic LSCC, emphasizing the importance of correct disease classification. Inferior outcomes in supraglottic LSCC are associated with old age, positive N-status, and improved follow-up routines are necessary. Primary tumor control is essential since recurrence impairs survival considerably in all subsites. The potential benefit of a primary surgical approach towards T3 LSCC awaits further investigation.

Low Mast Cell Density Predicts Poor Prognosis in Oral Squamous Cell Carcinoma and Reduces Survival in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: The cellular composition of the tumor microenvironment (TME) at the invading front of oral squamous cell carcinomas (OSCCs) may reflect biologically important cancer features and host responses, and thus be related to disease progression. The TME density of mast cells (MCs), macrophages, cancer-associated fibroblasts (CAFs) and endothelial cells were quantified at the invasive front and analyzed regarding their relation to disease recurrence in patients with small T1/2N0M0 OSCCs. mRNA for MC-specific proteins were analyzed in a second patient cohort with head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Samples from 62 patients with T1/2N0M0 OSCC were immunohistochemically stained and scored for the cellular expression of mast/stem cell growth factor receptor (c-KIT) (MCs), CD68 (macrophages), α-smooth muscle actin (α-SMA) (CAFs) and CD31 (endothelial cells) and this was analyzed according to disease recurrence. Data from The Cancer Genome Atlas database were used to examine mRNA expression profiles and clinical data of patients with 399 HNSCC. RESULTS: Increased MC density at the invasive front was significantly associated with reduced disease recurrence, as none of the patients with high MC density experienced relapse. Moreover, increased expression of mRNA for MC specific markers as c-KIT, and α-, ß-, and δ-tryptases and the MC-stimulating factor, stem cell factor (SCF), was significantly associated with good prognosis in patients with HNSCC. CONCLUSION: Decreased MC density at the invasive front may reflect tumor biology related to disease progression and prognosis. Counting MCs seems to be an easy and practical tool, that could be utilized for prognostic evaluation.

Risk of Recurrence in Laryngeal Cancer.

A cohort study was undertaken to analyze the risk of recurrence among 1616 patients with primary squamous cell carcinoma of the larynx from 1983 to 2010 at a single, tertiary academic center in Oslo, Norway. The cohort was followed from the date of diagnosis to September 2011. Competing risk regression analysis assessed the association between various risk factors and the risk of recurrence, where death was considered a competing event. Recurrence was observed in 368 patients (23%) during the study period. The majority (71%) of recurrences involved the location of the primary tumor. The overall risk of recurrence during the first three years after initiating treatment was 20.5%. Increased risk of recurrence was observed in patients with supraglottic cancer, younger patients, those with T2-T3 tumors and in patients treated in the earlier part of the study period. Significant factors for recurrence in glottic carcinomas were age, treatment in the earlier part of the study and T-status, whereas age was a significant factor in supraglottic cancer. N-status appeared less significant. In conclusion, follow-up of laryngeal squamous cell carcinoma should place particular emphasis on the site of the primary tumor, younger patients, cases of supraglottic cancer and T2-T4 primary tumors, especially during the first three years after treatment. More studies are needed to assess the impact of surgical versus non-surgical treatment, and eventually the significance of recurrence, for disease-specific and overall survival in cases of advanced laryngeal squamous cell carcinoma.

Self-reported Symptoms to Monitor Recurrent Head and Neck Cancer-Analysis of 1,678 Cases.

AIM: The aim of this article was to study the clinical significance of subjective symptoms of recurrence in patients treated for primary head and neck cancer. MATERIALS AND METHODS: Clinical data of 1,678 patients with squamous cell carcinoma of the head and neck admitted at the Department of Oto-rhino-laryngology-Head and Neck Surgery, Oslo University Hospital during a period of 15 years (1983-1997) were analyzed. RESULTS: A total of 525 (31%) patients had recurrence during follow-up, 74% of these within the first two years after primary treatment. Subjective symptoms indicating recurrent disease were reported by 67%. The remaining recurrences were detected in asymptomatic patients at scheduled consultations. Prognosis was better among patients with subjective symptoms of recurrent disease after treatment for primary tumors of the oral cavity and larynx. Those with recurrence from other tumor sites had no difference in prognosis between symptomatic and asymptomatic patients. CONCLUSION: The high proportion of patients with subjective symptoms indicates that there is a potential to make follow-up routines more effective. Individualized and flexible procedures, taking into account patient's self-reported symptoms, may help speed-up the process and thus improve prognosis. This could also lead to a more efficient use of resources by reducing the number of redundant examinations of low-risk patients.

Tumor Budding, EMT and Cancer Stem Cells in T1-2/N0 Oral Squamous Cell Carcinomas.

BACKGROUND: Early oral carcinomas have a high recurrence rate despite surgery with clear margins. In an attempt to classify the risk of recurrence of oral squamous cell carcinomas, we explored the significance of tumor budding, epithelial-mesenchymal transition (EMT) and certain cancer stem cell markers (CSC). MATERIALS AND METHODS: Tumor budding (single cells or clusters of ≤5 cells in the tumor front, divided into high- and low-budding tumors), EMT and CSC markers were studied in 62 immunohistochemically stained slides of T1/2N0M0 oral squamous cell carcinomas. Tissues and records of follow-up were obtained from the Oslo University Hospital, Norway. Tumor budding, EMT and CSC markers were scored and analyzed. RESULTS: The only significant prognostic marker was tumor budding (p=0.043). Expression of the EMT marker E-cadherin was lost from the invasive front and tended to be a prognostic factor (p=0.17), and up-regulation of vimentin in tumor cells in the invasive front was found; this indicates that EMT had occurred. CSC markers were not associated with recurrence rate in the present study. CONCLUSION: A high budding index was related to poor prognosis in patients with oral cancer. Budding was associated with EMT-like changes. CSC factors were detected but reflected differentiation rather than stemness. Scoring of buds in patients with oral cancer may help discriminate invasive tumors prone to relapse, and thus, provide an indication for adjuvant therapy.

High nuclear SOX2 expression is associated with radiotherapy response in small (T1/T2) oral squamous cell carcinoma.

OBJECTIVE: Expression of the stem cell transcription factor SOX2 is often used to imply stemness and poor prognosis in cancer. However, its role in oral squamous cell carcinoma (OSCC) is not fully elucidated. MATERIAL AND METHODS: Tumour tissues from 62 patients with primary, node negative and non-metastatic OSCCs were used to evaluate SOX2 expression by immunohistochemistry. The results were correlated to clinicopathology, treatment and disease recurrences. RESULTS: The majority of the OSCCs (88%) expressed SOX2. Patients with higher nuclear SOX2 staining intensity in the invasive front compared to the adjacent normal epithelium, had a remarkable longer disease-free period if they received adjuvant post-operative radiotherapy (P = 0.001). This was in particular evident for highly differentiated OSCCs, as none of the high SOX2-expressing tumours reoccurred in contrast to all low SOX2-expressing OSCCs. CONCLUSIONS: High nuclear SOX2 expression in the invasive front was associated with dramatic longer disease-free period than low SOX2-expressing carcinomas after post-operative radiotherapy in small OSCCs. The result suggested that high nuclear SOX2 expression at the invasive front may predict radiosensitivity.

Significance of self-reported symptoms as part of follow-up routines in patients treated for oral squamous cell carcinoma.

BACKGROUND: There is little evidence to prove that frequent out-patient consultations lead to better prognosis in patients treated for oral squamous cell carcinoma. Furthermore, there is no consensus regarding the timing and number of follow-up consultations or the duration of monitoring after completed therapy. MATERIALS AND METHODS: We prospectively recorded demographic and clinical data of 537 patients treated over a period of 15 years with complete follow-up of 18 years in a tertiary academic Center. RESULTS: Out of 537 patients considered free of disease after treatment, 196 (36%) developed recurrent disease during follow-up. Self-reported symptoms led to diagnosis of the recurrence in 78% of the cases. Only 22% of recurrences were detected through physical examination of asymptomatic patients. There was no difference in disease-free survival in-between these two groups. CONCLUSION: Follow-up routines are indispensable as part of cancer treatment but can be more cost-efficient when patients are educated and encouraged to report subjective symptoms. Trained personnel in collaboration with head and neck specialists can handle parts of follow-up routines.

Long-term trends in gender, T-stage, subsite and treatment for laryngeal cancer at a single center.

To investigate the changes in the epidemiology of laryngeal squamous cell carcinoma (LSCC) regarding gender, T-stage and subsite distribution, and to identify the potential effect of introducing new therapeutic alternatives for early and advanced stage LSCC. A prospective cohort study of LSCC patients diagnosed and treated at a single tertiary referral center in Norway. Retrospective analysis of prospectively recorded data from 1,616 patients treated for LSCC in all subsites of the larynx during 1983-2010. Females represented an increasing proportion of cases throughout the study (p < 0.01) and presented more often than men with supraglottic cancer (p < 0.01). Marked changes in the distribution of T-stages over time were observed in both early and advanced stage LSCC. T1a glottic tumors constituted 56 % of all early-stage LSCC and were predominantly treated by transoral endoscopic laser surgery. The introduction of chemoradiotherapy for advanced stage LSCC offers a distinct advantage for laryngeal preservation. The increasing proportion of females with LSCC may be explained by changes in smoking habits. The proportion of T1a glottic LSCC gradually increased over time, while T4 supraglottic LSCC became less frequent. Videostroboscopy should be considered mandatory in the diagnosis and follow-up of LSCC. Transoral laser microsurgery is the standard first-line treatment for T1a glottic tumors. Chemoradiotherapy has reduced the number of total laryngectomies and is now regarded as the primary treatment for advanced stage tumors.

Synchronous second primary tumors in 2,016 head and neck cancer patients: role of symptom-directed panendoscopy.

OBJECTIVES/HYPOTHESIS: Second primary tumors (SPTs) are prevalent in head and neck cancer patients. Synchronous SPTs occur within the first 6 months after diagnosis of a first primary tumor. Work-up of first primary head and neck cancers may include panendoscopy if SPTs are suspected. It is unclear whether this strategy has significant impact on treatment results. STUDY DESIGN: Prospectively recorded data on head and neck cancer patients treated at an academic tertiary referral center. METHODS: The distribution of SPTs was retrieved from a database of 2,016 patients with head and neck cancer. Initial work-up included panendoscopy when an SPT was clinically suspected. RESULTS: Of 2,016 patients, 49 (2.4%) had synchronous SPTs. Of these, there were 26 diagnosed simultaneously with the first primary tumor, of which 18 (69%) were located in areas covered by panendoscopy. The remaining 23 were nonsimultaneous synchronous SPTs; 10 of them were located at sites accessible by panendoscopy, of which 6 were in the bronchial tree. Median survival after simultaneous SPTs was 9 months versus 3 months after nonsimultaneous synchronous SPTs (P = not significant). The highest frequency of synchronous SPTs was seen with first primary tumors of the hard palate, the dorsum of the tongue, and of the mandibular gingiva. CONCLUSIONS: Symptom-directed panendoscopy at initial work-up was successful at finding SPTs of the upper aerodigestive tract, but not SPTs located in the lower airways. Synchronous SPTs missed at initial work-up did not have significantly worse prognosis than simultaneous SPTs.

Outcome of local failures after oral cancer - recurrence vs. second primary.

BACKGROUND/OBJECTIVE: A high risk of new mucosal malignancies of the upper aerodigestive tract (UADT) is seen in patients successfully treated for oral cancer. The prognosis is unclear for these patients. A typical failure may be located at the site of the first tumor i.e. a local recurrence; or separately as a second primary tumor (SPT). It is unknown whether these two types of local failures have different prognosis. STUDY DESIGN: Longitudinal observational cohort study employing prospectively collected data over 25 years. METHODS: The rate of local recurrences and UADT SPTs was analyzed in 151 patients previously treated for T1N0M0 oral squamous cell carcinoma. Survival after failure was compared between patients with local recurrence and local SPT. RESULTS: All patients had a 5-year cancer specific survival of 86.3%. Of the 151 patients, 20 had a local recurrence, and 16 had an UADT SPT. After a local failure, survival was median 17.2 months for local recurrence and 18.9 for UADT SPT (cancer specific). Time from primary tumor treatment to local recurrence was median 42 and months vs. 125 months for UADT SPTs. A similar linear pattern of presentation over time was seen for both tumor types. CONCLUSION: Outcome was poor after the date of the local failure. No difference in survival was seen whether the failure was a local recurrence or a second primary tumor. The similarity in survival and pattern of presentation suggests that these two entities may be biologically analogous.

Radiological analysis of swallowing and functional outcomes after hypopharyngo-laryngectomy with reconstruction using a jejunal autograft.

CONCLUSION: We report a distinct pattern of tongue movement. This is interpreted as a compensatory mechanism after hypopharyngo-laryngectomy with reconstruction using a jejunal autograft. Passage through the oesophagus is mainly passive. OBJECTIVE: Swallowing is normally initiated voluntarily, and afterwards presumed to be controlled by brainstem reflexes. Resection of the hypopharynx with reconstruction may affect this control. This study attempted to perform a biomechanical analysis of the motility in the small bowel graft and suggest possible implications for surgical management. We also analysed how oesophageal passage is affected by surgery. METHODS: Five patients underwent a radiological examination of the neopharyngeal conduit and oesophagus and completed a simple questionnaire. RESULTS: The radiological examinations revealed a distinct pattern of tongue movement in all patients, resulting in varying degrees of thrust. Passage through the jejunal graft was mainly passive, but observations of progressive reduction in diameter of the graft indicated muscular tone that may preserve pressure generated by the lingual thrust. The oesophageal transport appeared to be rather passive and largely depended upon the effect of gravity. Two of five patients were unable to eat normal food. Their impaired swallowing resulted in severely reduced quality of life.

Radiotherapy or CO(2) laser surgery as treatment of T(1a) glottic carcinoma?

Both radiotherapy and laser surgery give excellent results in the treatment of T(1a) glottic carcinoma. In this study, we compared the outcome of these treatment options. Demographic details and continuous follow-up with exact cause of death have been recorded prospectively for 351 patients with T(1a) glottic carcinoma at a tertiary referral centre in two consecutive decennia 1986-2005. Patients were treated with radiotherapy (163 patients) until 1996 when laser surgery was adopted as primary treatment (188 patients). The minimum follow-up time was 29 months. Neither the estimated 5-year disease-free survival, the disease-specific survival nor the crude survival differ between the two treatment options. The incidence of mainly local recurrences was equal during the first 3 years, followed by an increase in number of recurrences in the laser-operated patients. The odds ratio for a laryngectomy was 13.5 in patients treated with radiotherapy (P = 0.002), but mortality due to recurrence did not differ between the groups. The incidence of second primaries was equal (11%) but death due to second primaries differed significantly, favouring laser-treated patients (P = 0.003). In conclusion, the relative risk for a laryngectomy when a tumour recurs is 12.7 times higher in patients primarily treated with irradiation for T(1a) laryngeal carcinoma, compared with patients treated with laser surgery. Regarding the treatment costs, treatment impact on patients and organ preservation, we consider laser therapy to be the better treatment option for patients with T(1a) glottic cancer as no difference in survival could be observed.

Human papillomavirus (HPV)-positive tonsillar carcinomas are frequent and have a favourable prognosis in males in Norway.

CONCLUSIONS: This study confirms a high prevalence of human papillomavirus (HPV)-positive tonsillar tumours (52%). The survival of the HPV-positive group was significantly better in males. OBJECTIVES: We assessed the prevalence of HPV in 137 patients with tonsillar carcinomas, measured the p53- and Ki-67-positive tumour cell fractions and correlated the results with clinical variables. PATIENTS AND METHODS: Tumour DNA from patients with squamous cell carcinoma of the tonsillar region was amplified by PCR and sequenced for detection of HPV subtypes. RESULTS: HPV was found in 71/137 (52%) of the tumours; HPV-16 was the most frequent subtype (87%). HPV positivity did not correlate with gender, stage, T- and N categories, Ki-67 expression or p53 positivity. The HPV-positive group had a significantly better survival (p < 0.01) compared with the HPV-negative group in males. In a multivariate analysis HPV status gave prognostic information in addition to the earlier established factors, i.e. age, gender and stage (p < 0.05).

Reduced risk of head and neck second primary tumors after radiotherapy.

BACKGROUND AND PURPOSE: With radiotherapy of primary tumors of the head and neck, a significant dose reaches the surrounding mucosa. The field cancerization and second field tumor theories state that premalignant lesions are present in the mucosa even at the time of primary tumor treatment. We tested the hypothesis that exposure to irradiation stabilizes subclinical premalignant lesions. This would reduce the rate of second primary tumors in the upper aerodigestive tract (UADT). MATERIALS AND METHODS: The cohort consisted of 346 patients treated for small localized squamous cell carcinoma of the oral cavity (T1-2, N0, and M0). The rate of UADT second primary tumors was compared between 247 patients exposed to radiation (case subjects) and 99 patients unexposed to radiation (control subjects). RESULTS: Median time to UADT second primary tumor was 8.6 years for irradiated patients and 3.9 years for controls (p=0.007). Through the first 5 years after the treatment of the primary tumor, the relative risk of developing a new UADT tumor for irradiated patients compared to controls was 0.12 (p<0.001). After 5 years the risk increased for irradiated cases. A corresponding change in risk was not found for controls. CONCLUSIONS: A slower rate of second primary tumors was seen within UADT mucosa exposed to irradiation. This could suggest a preventive effect by radiation on malignant transformation of subclinical premalignant foci.

Angiographic balloon test occlusion and therapeutic sacrifice of major arteries to the brain.

OBJECTIVE: Treatment of certain cerebral aneurysms, caroticocavernous fistulae, and tumors of the neck or cranial base may involve therapeutic arterial sacrifice, which requires preoperative knowledge of the feasibility of permanent occlusion of the internal carotid artery (ICA) or vertebral artery or arteries. METHODS: Retrospective study of transcranial Doppler ultrasonography-monitored angiographic balloon test occlusion and therapeutic sacrifice of the ICA or vertebral artery. RESULTS: We performed transcranial Doppler-guided balloon test occlusion in 136 patients at a procedural risk equivalent to that of conventional neuroangiography, and with correct prediction of the hemodynamic result of therapeutic arterial sacrifice in all instances. Patients with an immediate drop in ipsilateral middle cerebral artery (MCA) velocity to 65% or more of baseline values upon ICA balloon occlusion tolerated ICA sacrifice well, whereas hemodynamic infarction is likely in those with a corresponding drop in MCA velocity to 54% or less. When ICA balloon occlusion caused a drop in MCA velocity to between 55 and 64% of baseline, the pulsatility of the MCA signal had to be analyzed. Patients who tolerated bilateral vertebral artery closure had reversal of flow and an increase in velocity in the P1 section of the posterior cerebral artery. In 212 patient-years of observation after therapeutic arterial sacrifice, no de novo aneurysms formed. CONCLUSION: Angiographic balloon test occlusion with transcranial Doppler monitoring can be performed ultra-swiftly at a risk equal to conventional neuroangiography and with correct prediction of the hemodynamic outcome of arterial sacrifice. Elective therapeutic arterial occlusion is a safe and efficient treatment of large cerebral aneurysms and caroticocavernous fistulae.

Impact of second primary tumors on survival in head and neck cancer: an analysis of 2,063 cases.

OBJECTIVE/HYPOTHESIS: To investigate the impact of second primary tumors on prognosis for patients with head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Prospectively recorded data on HNSCC patients treated at an academic tertiary referral center. METHODS: An analysis of 2,063 patients treated over a 15 year period for tumors of the upper aerodigestive tract, with a minimum follow-up of 10 years. RESULTS: A total of 351 (17%) patients developed a second primary, mean time to diagnosis of the second tumor being more than 4 years from the date of the initial tumor. Median overall survival from the date of the first tumor among patients who later developed a second primary was 6 years versus 3 years among all other patients (P < .05). During the first 6 years after treatment of the initial tumor, cancer specific survival was better in the second primary group. After diagnosis of a second primary tumor, median survival was 12 months. A positive correlation was found between second primaries and stage I/II primary disease, low patient age, and initial tumors of the larynx and oral cavity. CONCLUSIONS: The group of patients with the highest risk of a second primary tumor was younger patients with limited initial tumors. A high proportion of patients who later developed a second primary were complete responders after treatment of the first tumor. However, prognosis was poor after the actual diagnosis of the second primary tumor.

A study of phosphorylated ERK1/2 and COX-2 in early stage (T1-T2) oral squamous cell carcinomas.

BACKGROUND: Histomorphological grading at the invasive front of oral squamous cell carcinomas (OSCCs) may provide useful prognostic information. In the present study, we investigated the presence and prognostic value of activated phosphorylated extracellular signal-regulated kinases 1 and 2 (p-ERK1/2) and cyclo-oxygenase-2 (COX-2) both at the invasive front and in central/superficial parts of OSCCs. METHODS: Using immunohistochemistry, we assessed the presence of p-ERK1/2 and COX-2 in 53 early stage OSCCs. Clinical data were recorded prospectively. The end point was disease-free survival. RESULTS: p-ERK1/2 staining was present in almost all tumours. The staining was mostly nuclear in the cells of the invasive front and either nuclear or nuclear/cytoplasmic in central/superficial tumour parts. COX-2 was observed in almost all tumours (98%) and the staining was often restricted to focal areas. Most tumours were COX-2 negative at the invasive front. The lowest P-value in survival analyses was P = 0.06 for p-ERK1/2 at the invasive front. COX-2, the histomorphological grading systems and TNM stage were of no prognostic value. CONCLUSION: p-ERK1/2 was present in almost all tumours and p-ERK1/2 may be a prognostic marker at the invasive front of OSCCs. In early stage OSCCs, most tumours did not express COX-2 at the invasive front.

Quality of life in oral carcinoma: a 5-year prospective study.

BACKGROUND: We conducted this prospective longitudinal multicenter study to evaluate the health-related quality of life (HRQL) of patients with oral carcinoma at diagnosis, and after 1 and 5 years in relation to tumour location and treatment modality. METHODS: One hundred twenty-two patients (mean age, 61; 62% males) with oral carcinoma were evaluated with standardized HRQL questionnaires, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core30 (EORTC QLQ-C30) and the EORTC Head and Neck Cancer Module (EORTC QLQ-H&N35). RESULTS: Problems with teeth, dry mouth, and sticky saliva got worse between diagnosis and 5 years after diagnosis. Problems with dry mouth remained a problem between 1 and 5 years after diagnosis, except for the patients treated with surgery only. This group had fewer problems over time compared with patients receiving other treatment regimes. Survivors reported better HRQL than the nonsurvivors at diagnosis and at the 1-year follow-up. HRQL at diagnosis was associated with survival. CONCLUSIONS: HRQL at diagnosis for patients with oral carcinoma seems to be an important factor for the prognosis of both HRQL over time and survival. Treatment of oral carcinoma often results in long-term side effects such as dry mouth, problems with teeth, and sticky saliva.

Correlation of numerical aberrations of chromosomes X and 11 and poor prognosis in squamous cell carcinomas of the head and neck.

OBJECTIVE: To investigate the prognostic significance of chromosomal aberrations of chromosomes X and 11 in relation to disease-specific survival in head and neck squamous cell carcinoma. SETTING: University hospital. DESIGN: A 10-year retrospective clinical study. Information about clinical findings, treatment, and follow-up has been recorded prospectively. PATIENTS: By means of the fluorescence in situ hybridization technique with centromeric probes for chromosomes X and 11, we analyzed 40 randomly selected patients before treatment for T1 to T4 head and neck squamous cell carcinoma. Numerical aberrations were scored and evaluated in frozen sections. MAIN OUTCOME MEASURES: The significance of prognostic parameters was tested by the log-rank and Kaplan-Meier methods for the univariate analysis. The Cox proportional hazards regression model was used for multivariate analysis. RESULTS: Numerical aberrations of chromosome 11 correlated positively with T and N classification (P = .03 and P = .02, respectively) and with clinical stage (P = .02). Patients with higher frequencies of numerical aberrations for both chromosome X (>48%, mean) and chromosome 11 (>57%, mean) had shortened disease-specific survival compared with those with lower frequencies of numerical aberrations (P = .008 and P<.001, respectively). Of patients who died from disease within 3 years, 7 (50%) had a trisomic value of chromosome 11 of 35% or higher of nuclei (P<.001). Moreover, patients with a higher value (>or=8%) of amplification of chromosome 11 (>4 signals) were associated with having poor prognosis compared with those with a lower value (P = .02). CONCLUSION: Numerical aberrations of chromosomes X and 11 had prognostic value in head and neck squamous cell carcinoma, and higher frequencies of numerical aberrations correlated with poor prognosis.