Steven B. Chinn

Cancer stem cells: Mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma

Cancer stem cells (CSCs) represent a subpopulation of cells responsible for tumor growth. Their role in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and metastasis remains uncertain.

Impact of Perineural Invasion in the Pathologically N0 Neck in Oral Cavity Squamous Cell Carcinoma

Objective Patients with oral cavity squamous cell carcinoma (OCSCC) undergo adjuvant radiation for pathologically high-risk features including positive nodal disease and extracapsular spread (ECS). In the absence of these high-risk features, our objective was to determine if perineural invasion (PNI) is an independent risk factor and if adjuvant radiation (XRT) improves disease control rates. Study Design Historical cohort analysis. Setting Tertiary university hospital. Methods Eighty-eight OCSCC patients (46 males, 42 females; mean age = 56.7 years; median follow-up = 4.6 years) treated surgically with pathologically N0 (pN0) necks were studied. Overall, 23% (20/88) were pN0/PNI+ and of those with PNI, 70% (14/20) underwent XRT. Survival analysis using Kaplan-Meier followed by multivariable Cox models was performed. Results Multivariate analysis verified PNI to be associated with worse disease-free interval (DFI) (P = .012) and local-regional control (LRC) (P = .005) and perivascular invasion (PVI) associated with worse DFI (P = .05). Among pN0/PNI+ patients, those who received XRT demonstrated significantly improved DFI (mean = 6.5 years vs 1.7 years; P = .014) and LRC (mean 6.7 years vs 1.9 years; P = .047). There was no improvement in overall survival (P = .68) or disease-specific survival (P = .8) in those receiving XRT. Conclusions PNI is an independent adverse risk factor in the absence of nodal metastasis and extracapsular spread. We observed a statistically significantly longer DFI and LRC when patients were treated with adjuvant radiation.

Durability of hearing preservation after microsurgical treatment of vestibular schwannoma using the middle cranial fossa approach: Clinical article

OBJECT The middle cranial fossa (MCF) approach is a microsurgical technique described as a primary option in the treatment of small, intracanalicular schwannomas involving the eighth cranial nerve. Excellent rates of complete tumor resection, hearing preservation, preservation of facial nerve function, and low complication rates have been reproduced using this technique. However, the durability of hearing preservation attained using the various treatment options has not been adequately assessed. The purpose of this study was to evaluate the durability of long-term hearing preservation in patients with vestibular schwannoma (VS) treated via the MCF approach. The authors hypothesize that hearing preservation in these patients will prove to be durable years after treatment in a high percentage of cases. METHODS Retrospective medical chart review was performed in 103 consecutive patients undergoing resection of VS via a modified MCF approach between 1999 and 2008. Patients in whom surgical goals were gross-total resection and hearing preservation were included. Preoperative and postoperative hearing assessment was performed using standard audiometric testing, and classified according to American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guidelines as a primary outcome measure. Outcomes and neurological complications initially, and at 1, 3, and 5 years following operation were analyzed. RESULTS Initial hearing preservation rates were in keeping with the best previously published results. At initial postoperative audiometric follow-up, of the patients presenting with Class A hearing, 67% remained Class A, 17% were Class B, 1% were Class C, and 15% were Class D. Of patients presenting with Class B hearing, 24% were Class A, 53% remained Class B, 6% were Class C, and 18% were Class D. Of patients presenting with Class C hearing, 100% remained Class C. To assess the durability of hearing preservation in our patients, the authors evaluated hearing function at regular intervals after the initial postoperative audiometric follow-up. Audiometric data were available for 56 patients at 5-year follow-up. Of the 20 patients with Class A hearing at initial postoperative follow-up with 5-year follow-up, 13 (65%) remained Class A, 6 (30%) were Class B, and 1 (5%) was Class C. Of the 12 patients with Class B hearing at initial postoperative follow-up with 5-year follow-up, 4 (33%) were Class A, 4 (33%) remained Class B, and 4 (33%) were Class C. Of the 3 patients with Class C hearing at initial postoperative follow-up with 5-year follow-up, all 3 (100%) remained Class C. CONCLUSIONS A majority of patients with preserved hearing following the MCF approach for treatment of VS experience durability of their preserved hearing at 5-year follow-up. The initial AAO-HNS classification was preserved in 13 (65%) of the 20 patients who had Class A hearing at 5 years, and in 8 (67%) of the 12 who had Class B hearing at 5 years. Overall, a decline in AAO-HNS classification was noted in 15% of patients with preserved Class A hearing, and in 33% of those with preserved Class B hearing. Facial nerve function was preserved in 91% of cases. Superior hearing preservation as well as good outcomes in facial nerve function and few serious complications can be accomplished using the MCF approach for resection of small VSs.

The role of head and neck squamous cell carcinoma cancer stem cells in tumorigenesis, metastasis, and treatment failure

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Despite advances in diagnostic and therapeutic methods, survival of HNSCC remains unchanged over the last 30 years with treatment failure and metastases being the strongest indicators of poor outcome. Cancer stem cells (CSC) have been identified in multiple other solid tumors, including breast, prostate, and pancreatic carcinoma. Recently, a subpopulation of tumor cells has been identified in HNSCC based on the overexpression of the cellular marker CD44 and increased activity of aldehyde dehydrogenase. These cells have been designated CSC based on their stem cell-like properties: self-renewal, tumorigenesis, and the ability to recapitulate a heterogeneous tumor. Recent work looking at the role of HNSCC CSC in tumorigenesis has shown that CSC have a greater capacity for tumor growth, increased motility, and invasive characteristics; in vivo experiments confirm greater metastatic potential in CSC compared to non-CSC. Clinically, CSC enrichment has been shown to be enhanced in recurrent disease, treatment failure, and metastasis. CSC represent a novel target of study given their slow growth and innate mechanisms conferring treatment resistance. Further understanding of their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomes in patients with HNSCC.

Patterns of Nodal Metastasis and Prognosis in Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinoma

The current American Joint Committee on Cancer (AJCC) staging system may not accurately reflect survival in patients with human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinoma (SCC). The purpose of this study was to develop a system that more precisely predicts survival.

Diagnostic modalities for distant metastasis in head and neck squamous cell carcinoma: are we changing life expectancy?

To determine if the various imaging modalities for distant metastasis (DM) diagnosis alters life expectancy in head and neck squamous cell carcinoma (HNSCC).

Matted nodes as a predictor of distant metastasis in advanced-stage III/IV oropharyngeal squamous cell carcinoma

We recently described the imaging characteristics of multiple confluent regional metastases (matted nodes) and found that this characteristic was associated with distant metastasis in patients with oropharyngeal squamous cell carcinoma (SCC). The purpose of this study was to determine if matted nodes are a predictive marker for distant metastasis.

Epidermal growth factor receptor, p16, cyclin D1, and p53 staining patterns for inverted papilloma

The aim of this study was better characterize the staining patterns of inverted papilloma (IP) with and without carcinoma by performing immunohistochemistry for p16, epidermal growth factor receptor (EGFR), p53, and cyclin D1 antibodies in a large patient cohort.

Efficacy of Staged Excision With Permanent Section Margin Control for Cutaneous Head and Neck Melanoma

Importance Melanoma arising in chronically photodamaged skin, especially on the head and neck, is often characterized by poorly defined clinical margins and unpredictable occult extension. Staged excision techniques have been described to treat these challenging melanomas. Objective To investigate the local recurrence rates and margin to clearance end points using staged excision with comprehensive hematoxylin-eosin–stained permanent section margin control. Design, Setting, and Participants In this observational cohort study performed from October 8, 1997, to December 31, 2006, with a median follow-up of 9.3 years, 806 patients with melanoma on the head and neck, where clinical occult extension is common, were studied at an academic medical center. Interventions Staged excision with comprehensive hematoxylin-eosin–stained permanent section margin control commonly known as the square technique. Main Outcomes and Measures Local recurrence rates and margin to clearance end points. Results A total of 806 patients (276 women [34.2%]; 805 white [99.9%]) with a median age at the time of first staged excision procedure of 65 years (range, 20-94 years) participated in the study. The estimated local recurrence rates were 1.4% at 5 years, 1.8% at 7.5 years, and 2.2% at 10 years. For each 50-mm2 increase in the size of the clinical lesion, there was a 9% increase in the rate of local recurrence (hazard ratio, 1.09; 95% CI, 1.02-1.15; P = .02). The mean (SD) margin from lesion to clearance for melanoma in situ was 9.3 (5.1) mm compared with 13.7 (5.9) mm for invasive melanoma. For melanoma in situ, margins were clear after 5 mm or less in 232 excisions (41.1%) and after 10 mm or less in 420 excisions (74.5%). For invasive melanoma, margins were clear after 5 mm or less in 8 excisions (3.0%) and after 10 mm or less in 141 excisions (52.2%). Conclusions and Relevance Staged excision with comprehensive permanent section margin control of melanomas arising in chronically sun-damaged skin on the head and neck has favorable recurrence rates when melanoma margins are difficult to assess, and recurrence rates are high with traditional techniques.

Integration of high-risk human papillomavirus into cellular cancer-related genes in head and neck cancer cell lines: HPV integration into cancer genes in HNSCC cell lines

Human papillomavirus (HPV)‐positive oropharyngeal cancer is generally associated with excellent response to therapy, but some HPV‐positive tumors progress despite aggressive therapy. The purpose of this study was to evaluate viral oncogene expression and viral integration sites in HPV16‐ and HPV18‐positive squamous cell carcinoma lines.