Search

To inform novel personalized medicine approaches for race and socioeconomic disparities in head and neck cancer, we examined germline and somatic mutations, immune signatures, and epigenetic alterations linked to neighborhood determinants of health in Black and non-Latino White (NLW) patients with head and neck cancer. Cox proportional hazards revealed that Black patients with squamous cell carcinoma of head and neck (HNSCC) with PAX5 ( P = 0.06) and PAX1 ( P = 0.017) promoter methylation had worse survival than NLW patients, after controlling for education, zipcode, and tumor-node-metastasis stage ( n = 118). We also found that promoter methylation of PAX1 and P AX5 ( n = 78), was correlated with neighborhood characteristics at the zip-code level ( P < 0.05). Analyses also showed differences in the frequency of TP53 mutations ( n = 32) and tumor-infiltrating lymphocyte (TIL) counts ( n = 24), and the presence of a specific C → A germline mutation in JAK3 , chr19:17954215 (protein P132T), in Black patients with HNSCC ( n = 73; P < 0.05), when compared with NLW ( n = 37) patients. TIL counts are associated ( P = 0.035) with long-term (>5 years), when compared with short-term survival (<2 years). We show bio-social determinants of health associated with survival in Black patients with HNSCC, which together with racial differences shown in germline mutations, somatic mutations, and TIL counts, suggests that contextual factors may significantly inform precision oncology services for diverse populations., (©2019 American Association for Cancer Research.)

Metastatic cutaneous squamous cell carcinoma (SCC) of the head and neck poses a significant therapeutic challenge due to its aggressive biologic behavior. We conducted a retrospective study of 71 patients-58 men and 13 women, aged 28 to 88 years (mean: 71)-who had been treated at our university-affiliated tertiary care medical center for metastatic cutaneous SCC over a 15-year period. In addition to demographic data, we compiled and analyzed information on tumor characteristics, the site and extent of metastasis, treatment, follow-up, and outcome. Among the tumor factors, poorly differentiated carcinoma was an independent predictor of poorer disease-free survival, and older age was found to be an independent predictor of poorer overall survival. We found no significant difference in disease-free or disease-specific survival among patients with parotid involvement, neck involvement, or both. In our series, the site of nodal involvement appeared to have no prognostic significance in patients with metastatic cutaneous SCC of the head and neck.

Objectives/hypothesis: Despite advances in radiotherapy and chemotherapy treatments for head and neck cancers, the local failure rate is high. In most radiotherapy-resistant cases, surgery is performed; however, some cases are considered unresectable. No standard treatment for these situations has been established. In this study, we review our experience with brachytherapy (BT), which has a different biological mechanism than standard radiotherapy., Methods: All patients received prior radiation to the recurrence area. Median high-dose radiation BT dose was 50 Gy, administered in 5 to 10 Gy fractions twice daily for 5 days. High-dose radiation was given via four to 10 catheters inserted under local anesthesia (3 patients) or general anesthesia with preventive tracheostomy (10 patients)., Results: Thirteen patients received BT from 2010 to 2014. Male:female ratio was 1.6:1, and median age was 66 years (range 23-89). Of those 13 patients, 10 patients were diagnosed with squamous cell carcinoma (SCC) of the oral cavity, two patients with SCC of the nasal mucosa, and one patient with eccrine duct carcinoma. Prior radiation dose ranged from 60 to 70 Gy. Local control was achieved in 11 of 13 patients; only 15.3% (2 of 13) had in-field recurrence. Five patients developed local out-of-field recurrence, and two developed distant metastases. Five patients are alive with no evidence of disease. No major toxicities were encountered. Two patients had severe mucositis and recovered within several weeks., Conclusion: Brachytherapy for radiotherapy-resistant head and neck cancers is feasible with minor adverse events, which enables good local control. However, many advanced head and neck cancers develop regional or distant metastases; therefore, additional treatment should be suggested., Level of Evidence: 4. Laryngoscope, 126:2246-2251, 2016., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Tumor suppressor genes (TSGs) are commonly inactivated by somatic mutation and/or promoter methylation; yet, recent high-throughput genomic studies have not identified key TSGs inactivated by both mechanisms. We pursued an integrated molecular analysis based on methylation binding domain sequencing (MBD-seq), 450K Methylation arrays, whole exome sequencing, and whole genome gene expression arrays in primary head and neck squamous cell carcinoma (HNSCC) tumors and matched uvulopalatopharyngoplasty tissue samples (UPPPs). We uncovered 186 downregulated genes harboring cancer specific promoter methylation including PAX1 and PAX5 and we identified 10 key tumor suppressor genes (GABRB3, HOXC12, PARP15, SLCO4C1, CDKN2A, PAX1, PIK3AP1, HOXC6, PLCB1, and ZIC4) inactivated by both promoter methylation and/or somatic mutation. Among the novel tumor suppressor genes discovered with dual mechanisms of inactivation, we found a high frequency of genomic and epigenomic alterations in the PAX gene family of transcription factors, which selectively impact canonical NOTCH and TP53 pathways to determine cell fate, cell survival, and genome maintenance. Our results highlight the importance of assessing TSGs at the genomic and epigenomic level to identify key pathways in HNSCC, deregulated by simultaneous promoter methylation and somatic mutations.

Background: Solid organ recipients are at an increased risk of developing various malignancies. We investigated the incidence, clinical features, and outcome of patients diagnosed with head and neck cancer after organ transplantation., Methods: A retrospective analysis was undertaken of patients who underwent solid organ transplantation (kidney, liver, lung, heart) treated at our institution from 1992 to 2010., Results: Of 2817 organ recipients, 175 patients (6.1%) developed 391 head and neck malignancies. Cutaneous malignancies were the most common (93%): squamous cell carcinoma (SCC; 51%) and basal cell carcinoma (BCC; 42%). The average interval from transplantation to diagnosis of head and neck malignancy was 7.3 years, with liver recipients diagnosed earlier. Eighteen percent of patients presented with an aggressive pattern of head and neck cancer, including 24% of patients with cutaneous SCC., Conclusion: Organ transplantation recipients are at a higher risk to develop head and neck cancer with an aggressive behavior characterized by multiple recurrences and decreased survival., (Copyright © 2013 Wiley Periodicals, Inc.)

The TNM classification is not specific for head and neck skin cancer and makes no allowance for disease extent. Studies have shown that the relative number of metastatic-to-examined lymph nodes, termed the Nodal ratio, is a reliable independent prognosticator in several types of cancer. The study was designed as a retrospective analysis in a university affiliated tertiary care center setting. The files of all patients (n = 71) with cutaneous head and neck squamous cell carcinoma and regional lymph node metastasis who attended a tertiary medical center between 1990 and 2008 were reviewed for clinical variables and outcome, and Nodal ratio was calculated. Data were analyzed for impact on survival. On multivariate analysis Nodal ratio and age were found to be significant predictors of overall survival. The N-ratio was the only significant predictor of disease-specific survival. Age, type of treatment (selective/modified neck dissection), pathologic N stage, and radiotherapy had no effect. The Nodal ratio is a potentially valuable prognostic index in cutaneous squamous cell carcinoma. The minimal number of nodes that need to be excised has to be determined.

Radiotherapy to the neck is frequently employed in the treatment of malignancies, sometimes alone and sometimes before or after surgery or with or without chemotherapy. We checked the histopathological changes in the neck after radiotherapy, dividing the changes into two groups. One with short-term changes between six months to one year, and the second group with long-term changes after more than six years. We compared these two groups with a control group without radiotherapy. The changes in the long-term group were more pronounced than in the short-term group, with more stromal fibrosis, vascular changes, and specially lymph nodes smaller than one centimeter. Thus, bigger lymph nodes (more then one centimeter) are more radiosensitive and become smaller after six years.

Heterotopic salivary tissue and branchial sinuses occur not infrequently (Goodman et al., 1981; Stingle and Priebe, 1974), caused probably by heteroplasia within remnants of the second cleft (Stingle, 1974). Bilateral lesions which presented clinically as branchial cleft sinuses have been removed from a patient's neck; both of them proved to be branchial cleft sinuses with elements of salivary tissue. The paper describes salivary tissue and branchial sinuses along the anterior border of the sternocleidomastoid muscle on both sides of the neck and bilateral preauricular fistulae occurring in a boy and probably in his sister.