William M. Lydiatt

Head and Neck Cancers

Recent evidence suggests that dysregulated translation and its control significantly contribute to the etiology and pathogenesis of the head and neck cancers, specifically to that of squamous cell carcinoma (HNSCC). eIF4E is one of the most studied components of the translation machinery implicated in the development and progression of HNSCC. It appears that dysregulation of eIF4E levels and activity, namely by the PI3K/AKT/mTOR pathway, plays an important role in the etiology and pathogenesis of HNSCC and correlates with clinical outcomes. In this chapter, we will discuss the role of eIF4E and some other translation factors as they relate to the biology and treatment of HNSCC.

Fusion of the ALK Gene to the Clathrin Heavy Chain Gene, CLTC, in Inflammatory Myofibroblastic Tumor

Inflammatory myofibroblastic tumor (IMT) is a rare, but distinctive mesenchymal neoplasm composed of fascicles of bland myofibroblasts admixed with a prominent inflammatory component. Genetic studies of IMTs have demonstrated chromosomal abnormalities of 2p23 and rearrangement of the anaplastic lymphoma kinase (ALK) gene locus. In a subset of IMTs, the ALK C-terminal kinase domain is fused with a tropomyosin N-terminal coiled-coil domain. In the current study, fusion of ALK with the clathrin heavy chain (CTLC) gene localized to 17q23 was detected in two cases of IMT. One of these cases exhibited a 2;17 translocation in addition to other karyotypic anomalies [46,XX,t(2;17)(p23;q23),add(16)(q24)].

Head and neck cancers, version 1.2015 featured updates to the NCCN guidelines

These NCCN Guidelines Insights focus on nutrition and supportive care for patients with head and neck cancers. This topic was a recent addition to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers. The NCCN Guidelines Insights focus on major updates to the NCCN Guidelines and discuss the new updates in greater detail. The complete version of the NCCN Guidelines for Head and Neck Cancers is available on the NCCN Web site (NCCN.org).

Molecular support for field cancerization in the head and neck

Two competing concepts, field cancerization and micrometastatic lesions, have been postulated to account for the high frequency of second primary tumors and multicentric dysplasia in patients with head and neck carcinoma.

A randomized, placebo-controlled trial of citalopram for the prevention of major depression during treatment for head and neck cancer.

OBJECTIVE To determine whether prophylactic treatment with the antidepressant citalopram hydrobromide, compared with placebo, could prevent major depressive disorder in patients undergoing therapy for head and neck cancer (HNC). DESIGN Prospective, randomized, placebo-controlled trial. SETTING Academic medical center. PATIENTS Thirty-six subjects were randomized, and 23 completed the study. INTERVENTIONS Subjects were randomized to receive 40 mg of citalopram hydrobromide or matching placebo (herein after, citalopram group and placebo group, respectively) for 12 weeks with a final visit at 16 weeks. MAIN OUTCOME MEASURES The Hamilton Depression Rating Scale, psychiatric interview, and the University of Washington Quality of Life (UW-QOL) and Clinician Global Impression-Severity (CGI-S) scales. RESULTS The numbers of subjects who met predefined cutoff criteria for depression during the 12 weeks of active study were 5 of 10 (50%) taking placebo and 2 of 12 (17%) taking citalopram (Fisher exact test, P = .17). No patients in the citalopram group became suicidal, compared with 2 in the placebo group. Global mood state at the conclusion of the study as measured by the CGI-S scale was rated as at least mildly ill in 15% of those receiving citalopram compared with 60% in the placebo group (Fisher exact test, P = .04). Quality of life, measured by the UW-QOL, deteriorated in both groups from baseline but less so in the citalopram group. CONCLUSIONS This study reports data from the first depression prevention trial in HNC and suggests that prophylactic treatment may decrease the incidence of depression during HNC therapy. The clinical significance of the reduction in depression was best demonstrated by the CGI-S scale, which showed a notable difference in global psychiatric and physical well-being.

Synovial sarcoma of the head and neck : Chromosomal translocation (X;18) as a diagnostic aid

Synovial sarcoma, a rare tumor in the head and neck, has been historically diagnosed by its characteristic biphasic histologic pattern. Monophasic variants exist which can be difficult to diagnose.

Human papilloma virus positive oropharyngeal squamous cell carcinoma: A growing epidemic

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing despite a decrease in tobacco use. Almost 20-30% of patients with OPSCC do not have the traditional risk factors of smoking and alcohol use and in a vast majority of these patients, the human papilloma virus (HPV) appears to drive the malignant transformation. HPV induced malignant transformation is attributed to two viral oncogenes and their non-structural protein products (E6 and E7). These two proteins appear to affect carcinogenesis by their inhibitory effects on p53 and retinoblastoma proteins (Rb). Patients with HPV mediated OPSCC seem to have a better prognosis compared to their non-HPV counterparts. However, in the absence of strong evidence, standard of care at this time for OPSCC does not differ based on HPV status. Current research is focused on the role of de-escalation of treatment and elucidation of prognostic markers in this unique population. This review focuses on the pathogenesis of HPV mediated OPSCC and details the current evidence in the management of these patients.

NCCN Guidelines Insights: Head and Neck Cancers, Version 2.2017

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panels discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.

Association between depression and survival or disease recurrence in patients with head and neck cancer enrolled in a depression prevention trial.

To determine if depression portends a worse prognosis in patients with head and neck cancer, we conducted a retrospective chart analysis of subjects who participated in a randomized placebo‐controlled trial of citalopram for the prevention of depression during head and neck cancer treatment. Thirty‐five patients were randomized, 34 with 1 or more evaluations form the basis of this report.

9p21 deletion correlates with recurrence in head and neck cancer

Deletion of 9p21 is a common event in many human tumors, including head and neck squamous cell carcinoma (HNSCC). The gene CDKN2, which encodes the protein p16, a cyclin‐dependent kinase‐4 inhibitor, maps to 9p21. The role of CDKN2 as the tumor suppressor gene in these neoplasms is unclear. The role of loss of heterozygosity (LOH) as a prognostic tool has not been described in HNSCC.