Cancers of the head & neck最新文献

The current treatment paradigm in head and neck cancer does not adequately address its clinical and biological heterogeneity. Data from genomic profiling studies in head and neck squamous cell carcinoma (HNSCC) have revealed the molecular features that are unique to HNSCC subgroups. This progress in the understanding of HNSCC biology provides an opportunity to develop personalized therapies for patients with distinct molecular subtypes to achieve better clinical outcomes including survival. However there are several well-recognized challenges that need to be overcome before genotype-matched therapies make precision medicine a reality for patients with HNSCC. Selection of appropriate patients for biomarker directed clinical trials based on sound scientific rationale will be critical in making cancer genomics more applicable in this malignancy.

Background: Human papillomavirus (HPV)-positive oropharyngeal cancer primarily affects working-age adults. Chemotherapy and radiation (CTRT) used to treat this disease may adversely impact a survivors' ability to work after treatment.

Methods: We surveyed participants with HPV-positive oropharyngeal cancer who completed CTRT regarding employment. We examined the associations between 1) sociodemographic and clinical factors and employment outcomes, and 2) health-related quality of life and satisfaction with ability to work.

Results: 102 participants were employed full-time at diagnosis for pay and surveyed at a median of 23 months post-CTRT (range 12-57 months). The median age at diagnosis was 57 years (range 25-76 years). During CTRT, 8 % stopped working permanently, 89 % took time off or reduced responsibility but later returned, and 3 % reported no change. For those who took time off but returned, median time to return to work was 14.5 weeks. In multivariable analysis, younger age predicted for needing more than the median time off. At time of survey, 85 % participants were working, 7 % had retired, and 8 % were not working for other reasons. Seventeen percent of participants were not satisfied with their current ability to work, which was associated with poorer health-related quality of life and persistent treatment toxicities (p < 0.001).

Conclusions: CTRT interrupts employment in the majority of working patients with HPV-positive oropharyngeal cancer but most return. However, treatment-related toxicities might lead to dissatisfaction with ability to work.

The objective of this article is to review and summarize the extant literature on head and neck cancer (HNC) patients' informational needs and to characterize emerging issues in this patient population in order to define priorities for future research. HNC patients may undergo challenging treatment regimens and experience treatment-related alterations in primary daily functions such as speech and eating. These changes often persist following treatment and may lead to significant deficits in quality of life and interpersonal relations. Despite empirical evidence demonstrating that receipt of adequate information and support is predictive of improved outcomes post-treatment, relatively limited attention has been paid to the informational and support needs of HNC patients. This review focuses primarily on three topic domains: (1) managing treatment-related side effects; (2) addressing alcohol and tobacco dependence; and (3) informational needs in the areas of human papillomavirus (HPV) and clinical trials. While there is increasing awareness of the rehabilitation and survivorship needs in this patient population, patients note that the impact of treatment on social activities and interactions is under-discussed and of key concern. In addition, there is a significant gap in addressing communication and informational needs of caregivers and family members who are integral for promoting healthy behaviors and self-care post-treatment. Greater integration of programs that address tobacco or alcohol dependency within a comprehensive treatment and support plan may increase patient motivation to seek help and enhance patient success in maintaining long-term abstinence. Finally, emerging patient-provider communication needs, particularly in the context of decision making about clinical trials or surrounding an HPV-related diagnosis, have been noted among both patients and healthcare providers. Future research on the development of novel programs that offer feasible and acceptable methods for addressing unmet informational and support needs is warranted and may yield benefit for improving patient-reported outcomes.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is frequently impervious to curative treatment efforts. Similar to other cancers associated with prolonged exposure to carcinogens, HNSCCs often have a high burden of mutations, contributing to substantial inter- and intra-tumor heterogeneity. The heterogeneity of this malignancy is further increased by the rising rate of human papillomavirus (HPV)-associated (HPV+) HNSCC, which defines an etiological subtype significantly different from the more common tobacco and alcohol associated HPV-negative (HPV-) HNSCC. Since 2011, application of large scale genome sequencing projects by The Cancer Genome Atlas (TCGA) network and other groups have established extensive datasets to characterize HPV- and HPV+ HNSCC, providing a foundation for advanced molecular diagnoses, identification of potential biomarkers, and therapeutic insights. Some genomic lesions are now appreciated as widely dispersed. For example, HPV- HNSCC characteristically inactivates the cell cycle suppressors TP53 (p53) and CDKN2A (p16), and often amplifies CCND1 (cyclin D), which phosphorylates RB1 to promote cell cycle progression from G1 to S. By contrast, HPV+ HNSCC expresses viral oncogenes E6 and E7, which inhibit TP53 and RB1, and activates the cell cycle regulator E2F1. Frequent activating mutations in PIK3CA and inactivating mutations in NOTCH1 are seen in both subtypes of HNSCC, emphasizing the importance of these pathways. Studies of large patient cohorts have also begun to identify less common genetic alterations, predominantly found in HPV- tumors, which suggest new mechanisms relevant to disease pathogenesis. Targets of these alterations including AJUBA and FAT1, both involved in the regulation of NOTCH/CTNNB1 signaling. Genes involved in oxidative stress, particularly CUL3, KEAP1 and NFE2L2, strongly associated with smoking, have also been identified, and are less well understood mechanistically. Application of sophisticated data-mining approaches, integrating genomic information with profiles of tumor methylation and gene expression, have helped to further yield insights, and in some cases suggest additional approaches to stratify patients for clinical treatment. We here discuss some recent insights built on TCGA and other genomic foundations.