Clinical decision making for human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is predominantly guided by disease stage and anatomic location, with few validated biomarkers. The epidermal growth factor receptor (EGFR) is an important therapeutic target, but its value in guiding therapeutic decision making remains ambiguous. We integrated analysis of clinically annotated tissue microarrays with analysis of data available through the TCGA, to investigate the idea that expression signatures involving EGFR, proteins regulating EGFR function, and core cell-cycle modulators might serve as prognostic or drug response–predictive biomarkers. This work suggests that consideration of the expression of NSDHL and proteins that regulate EGFR recycling in combination with EGFR provides a useful prognostic biomarker set. In addition, inactivation of the tumor suppressor retinoblastoma 1 (RB1), reflected by CCND1/CDK6-inactivating phosphorylation of RB1 at T356, inversely correlated with expression of EGFR in patient HNSCC samples. Moreover, stratification of cases with high EGFR by expression levels of CCND1, CDK6, or the CCND1/CDK6-regulatory protein p16 (CDKN2A) identified groups with significant survival differences. To further explore the relationship between EGFR and RB1-associated cell-cycle activity, we evaluated simultaneous inhibition of RB1 phosphorylation with the CDK4/6 inhibitor palbociclib and of EGFR activity with lapatinib or afatinib. These drug combinations had synergistic inhibitory effects on the proliferation of HNSCC cells and strikingly limited ERK1/2 phosphorylation in contrast to either agent used alone. In summary, combinations of CDK and EGFR inhibitors may be particularly useful in EGFR and pT356RB1-expressing or CCND1/CDK6-overexpressing HPV-negative HNSCC.

Selective second-look surgery in high-risk children did not adversely affect outcome as compared with the low-risk group. Cholesteatoma was identified endoscopically in 7 of 42 (17%) children thought to be microscopically free of disease at initial surgery. The endoscope may aid in visualization of difficult middle ear recesses when used to complement microscopy. Further investigation with multicenter data is needed.

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Background Volume loss and volume descent are complementary aspects of facial aging, although the respective contribution of each is unclear. Objectives The aim of this study was to quantify in 3 dimensions the effects of gravity on the midface in both upright and supine positions in an older and a younger group of patients. Methods A prospective study was undertaken of 53 female patients who had not undergone treatment with dermal fillers or facial cosmetic surgery. Three-dimensional photography with a VECTRA H1 camera (Canfield Scientific, Fairfield, NJ) was taken in supine and sitting positions. Volume shifts and displacement of structures in 3 dimensions were measured and analyzed. Results Morphologically, upon shifting from sitting to supine position, the tail of the brow elevated, the tear trough filled, the buccal and malar fat shifted posteriosuperiorly, the earlobe decreased in height, the nasiolabial folds and marionette lines diminished, the modiolus shifted laterally, and the jowl diminished. Volumetric analysis revealed that the infraorbital region increased in volume by a mean [SD] of 0.59 [0.55] mL, the tear trough by 0.22 [0.19] mL, and the malar region by 1.2 [1.06] mL. With subjects in the supine position, all facial topographic landmarks displaced significantly from sitting position. Conclusions Facial aging in this cohort was predominantly due to tissue descent rather than volume loss. Reversal of the gravitational force restores the 3D position of the facial subunits and leads to volumization in desirable locations that approximates a more youthful appearance. The volume restored via redistribution of facial fat is comparable to that typically injected during direct volume transfer procedures. Level of Evidence: 4