Objectives

To compare the incidence rates of nasopharyngeal carcinoma (NPC) among US black, white, and Asian/Pacific Islander (Asian) populations, with a focus on those diagnosed before age 20 years and between ages 20 and 29 years. Our secondary objective was to determine differences in survival rates between US blacks, whites, and Asians with NPC who were younger than 30 years.

Design

Data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) tumor registry system were used to determine incidence and survival rates for cases of NPC diagnosed in the specified age groups between 1973 and 2002.

Patients

Blacks, whites, and Asians younger than 30 years with NPC.

Main outcome measures

Incidence rates and 2- and 5-year survival rates.

Results

From 1973 to 2002, incidence rates per 1 million persons, adjusted to the 2000 standard population, for blacks, whites, and Asians younger than 20 years with NPC were 1.61 (n=43), 0.61 (n=99), and 0.95 (n=18), respectively. The incidence rate ratio of blacks to Asians younger than 20 years was 1.69 (95% confidence interval [CI], 0.96-3.12) (P=.07), while the rate ratio for blacks to whites was 2.66 (95% CI, 1.82-3.85) (P<.001). From ages 20 to 29 years, rates increased slightly in blacks (1.87) and whites (0.96), while increasing dramatically in Asians (7.18). Two- and 5-year relative survival rates in blacks younger than 30 years were 84% and 64%, respectively, with little variation between races in this age group.

Conclusions

Blacks younger than 20 years have increased incidence rates of NPC relative to whites and may be the only group having a higher NPC incidence rate than Asians. Two- and 5-year survival rates of blacks, whites, and Asians younger than 30 years with NPC are similar.

Objective

To determine survival outcomes and locoregional control rates in patients with locoregional head and neck squamous cell cancer (HNSCC) who failed primary concomitant chemoradiation (CRT) intended for cure and underwent attempted surgical salvage.

Study design and setting

Design was a nonrandomized retrospective cohort study. Of 204 patients with HNSCC who received primary concomitant chemoradiation intended for cure between 1995 and 2004, 38 recurred and underwent attempted salvage surgery at a tertiary care academic center.

Results

Among the 38 patients undergoing surgical salvage, 12- and 24-month overall survival rates were 60 percent and 27 percent. Locoregional control at 24 months was 42 percent. Lower survival was seen with initial N3 disease (P = 0.0115). Overall surgical morbidity was 24 percent.

Conclusion/significance

The results of salvage surgery after failed chemoradiation for HNSCC are poor. Those with N3 disease fare least well. Patients should be well informed about the realistic chances of cure and potential morbidity of surgery.

Purpose

Cancer cachexia is a devastating and understudied illness in patients with head and neck squamous cell carcinoma (HNSCC). The primary objective was to identify clinical characteristics and serum levels of cytokines and cachexia-related factors in patients with HNSCC. The secondary objective was to detect the occurrence of cytokine and cachexia-related factor gene expression in HNSCC tumors.

Experimental design

For the primary objective, cross-sectional data were obtained from prospectively recruited patients identified as cachexia cases and matching cachexia-free controls. For the secondary objective, a retrospective cohort design with matched controls was used.

Results

Clinical characteristics associated with cancer cachexia in HNSCC were T(4) status (P = 0.01), increased C-reactive protein (P = 0.01), and decreased hemoglobin (P < 0.01). Exploratory multiplex analysis of serum cytokine levels found increased interleukin (IL)-6 (P = 0.04). A highly sensitive ELISA confirmed the multiplex result for increased IL-6 in cachectic patients (P = 0.02). Quality of life was substantially reduced in patients with cachexia compared with noncachectic patients (P < 0.01). All tumors of HNSCC patients both with and without cachexia expressed RNA for each cytokine tested and the cachexia factor lipid-mobilizing factor. There were no statistically significant differences between the cytokine and cachexia factor RNA expression of cachectic and noncachectic patients (each P > 0.05). No tumors expressed the cachexia factor proteolysis-inducing factor.

Conclusion

We have identified clinical characteristics and pathophysiologic mechanisms associated with cancer cachexia in a carefully defined population of patients with HNSCC. The data suggest that the acute-phase response and elevated IL-6 are associated with this complex disease state. We therefore hypothesize that IL-6 may represent an important therapeutic target for HNSCC patients with cancer cachexia.

Previous studies have established that a subset of head and neck tumors contains human papillomavirus (HPV) sequences and that HPV-driven head and neck cancers display distinct biological and clinical features. HPV is known to drive cancer by the actions of the E6 and E7 oncoproteins, but the molecular architecture of HPV infection and its interaction with the host genome in head and neck cancers have not been comprehensively described. We profiled a cohort of 279 head and neck cancers with next generation RNA and DNA sequencing and show that 35 (12.5%) tumors displayed evidence of high-risk HPV types 16, 33, or 35. Twenty-five cases had integration of the viral genome into one or more locations in the human genome with statistical enrichment for genic regions. Integrations had a marked impact on the human genome and were associated with alterations in DNA copy number, mRNA transcript abundance and splicing, and both inter- and intrachromosomal rearrangements. Many of these events involved genes with documented roles in cancer. Cancers with integrated vs. nonintegrated HPV displayed different patterns of DNA methylation and both human and viral gene expressions. Together, these data provide insight into the mechanisms by which HPV interacts with the human genome beyond expression of viral oncoproteins and suggest that specific integration events are an integral component of viral oncogenesis.

The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53. Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours. Therapeutic candidate alterations were identified in most HNSCCs.