ABSTRACT
Background: The correlation between head and neck squamous cell carcinoma (SCC) and human papillomavirus (HPV) has been of great interest. We aimed to study immunoexpression of the p16INK4a (p16) antigen, a surrogate marker for high-risk HPV infection, in oropharyngeal SCC among veterans to estimate HPV-related cancer and survival. Secondary aims included stratification of race and ethnicity, degree of tobacco and alcohol use, tumor location, stage, and age at diagnosis. Methods: A retrospective electronic health record review was performed between January 1, 2000, and December 31, 2008, at a tertiary-level US Department of Veterans Affairs (VA) medical center for veterans who were treated for oropharyngeal SCC, had follow-up for a minimum of 2 years, and for whom paraffin-embedded tissue was available. Paraffin-embedded tissue was analyzed for p16 expression. Results: We identified 66 veterans who met the inclusion criteria. p16 expression was observed in 29% of the patients. All patients were male with no difference in age at diagnosis between the groups. Among patients with p16-negative status, 60% were African American, whereas among patients with p16-postive status, 32% were African American (P = .04). Among patients with p16-postive status, 22% were tobacco-naïve, and 18% were alcohol-naïve vs 0% and 4%, respectively, of patients with p16-negative status (P = .005 and P = .12, respectively). Two-year survival was the same for both groups (P = .52). Conclusions: We observed p16 expression in 29% of VA patients with oropharnygeal SCC, which was less than observed in non-VA populations. At presentation, both groups demonstrated a predilection for tonsil location and late stage without significant difference in age or disease-specific survival. Disparities in racial distribution and tobacco use between patients with and without p16-positive status appear like that reported in non-VA populations; however, the frequently reported younger age at presentation, lower stage, and improved prognosis were not observed.
ABSTRACT
Successful management of laryngeal cancer depends on careful pretreatment evaluation of patient and disease factors to arrive at accurate staging, leading to appropriate treatment selection for patients with this highly impacting disease. Surgical modalities, including transoral laser microsurgery, open partial laryngectomy, and total laryngectomy, offer options, alone or in combination with radiation and chemotherapy. Treatment strategy for laryngeal cancer should strive for cure while maintaining the best quality of life possible for the patient. Achieving the goals of initial and salvage treatment for laryngeal cancer depends on executing a plan of care determined by the expertise of the multidisciplinary team.
Subject(s)
Laryngeal Neoplasms/therapy , Humans , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/rehabilitation , Laryngectomy , Laser Therapy , Microsurgery , Neck Dissection , Neoplasm Staging , Patient Selection , Quality of Life , Salvage TherapyABSTRACT
Tumor-initiating cells (TICs) in squamous cell carcinoma of the head and neck (SCCHN) are best characterized by their surface expression of CD44. Although there is great interest in identifying strategies to target this population, no marker of these cells has been found to be functionally active. Here, we examined the expression of the purported marker of normal human oral epithelial stem cells, CD271. We show that CD271 expression is restricted to a subset of the CD44+ cells. Using xenograft assays, we show that the CD44+CD271+ subpopulation contains the most tumorigenic cells. Loss of CD271 function results in a block in the G2-M phase of the cell cycle and a profound negative impact on the capacity of these cells to initiate tumor formation in vivo. Incubation with recombinant NGF results in enhanced phosphorylation of Erk, providing additional evidence that CD271 is functionally active. Finally, incubation of SCCHN cells with antibody to CD271 results in decreased Erk phosphorylation and decreased tumor formation in vivo. Thus, our data are the first to demonstrate that CD271 more specifically identifies the TIC subpopulation within the CD44+ compartment in SCCHN and that this receptor is a functionally active and targetable molecule.
Subject(s)
Antigens, Neoplasm/biosynthesis , Carcinoma, Squamous Cell/metabolism , Head and Neck Neoplasms/metabolism , Neoplastic Stem Cells/metabolism , Nerve Tissue Proteins/biosynthesis , Receptors, Nerve Growth Factor/biosynthesis , Animals , Antigens, Neoplasm/immunology , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , Cell Growth Processes/physiology , Cell Line, Tumor , Female , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/pathology , Heterografts , Humans , Hyaluronan Receptors/biosynthesis , Hyaluronan Receptors/immunology , Mice , Mice, Inbred BALB C , Neoplastic Stem Cells/immunology , Neoplastic Stem Cells/pathology , Nerve Tissue Proteins/immunology , Phosphorylation , Receptors, Nerve Growth Factor/immunology , Squamous Cell Carcinoma of Head and Neck , Xenograft Model Antitumor AssaysABSTRACT
PURPOSE OF REVIEW: Treatment of laryngeal carcinoma continues to evolve, and whereas there was a transition from total laryngectomy to chemoradiation in response to the Veterans Affairs study and Radiation Therapy Oncology Group (RTOG) 91-11, recent data suggest the role of partial laryngectomy must be revisited. RECENT FINDINGS: Recent data have shown that laryngeal preservation does not equate with laryngeal function. Data are accumulating in support of operative management of advanced laryngeal carcinoma away from chemoradiation for select patients. In particular, supracricoid laryngectomy may be a viable option for intermediate and selected advanced laryngeal carcinoma while maintaining laryngeal function. SUMMARY: The evolution of treatment for advanced laryngeal carcinoma is focusing treatment on maintaining locoregional control while also maintaining a functional larynx.
