Bruce H. Haughey

Importance The rapid increase of human papillomavirus–associated oropharyngeal cancer has demonstrated a need for new strategies in prevention, diagnosis, evaluation, and treatment. Because there are currently no available screening technologies to detect early disease, a trend of purely incidentally identified asymptomatic p16-positive squamous cell carcinoma has been observed. We identify and describe a case series of these patients. Observations A total of 134 patients with p16-positive oropharyngeal cancer were identified. Of these patients, 5 (3.7%) were identified as having completely asymptomatic primary site p16-positive tumors found during workup for other nonrelated medical problems. Four patients were found with early T-stage disease without nodal metastasis, and underwent surgical treatment as a single modality. One patient had advanced-stage disease and underwent chemoradiation. At a mean follow-up of 12.6 months, all patients remained disease free. Conclusions and Relevance With the rise of p16-positive oropharyngeal squamous cell carcinoma and lack of screening technologies for early-stage disease, purely incidentally diagnosed disease might increase in incidence. These findings underscore the importance of a comprehensive physical examination on all patients. Although follow-up is too limited for definitive conclusions, early experience suggests that these patients can be treated with unimodality therapy when presenting with stage I or II disease.

Background Amidst a rising incidence of p16‐positive (p16+) oropharyngeal cancer, a significant number of cases present as regionally metastatic disease with an “unknown” primary. Preliminary data support transoral surgery as an effective method of primary detection/treatment. Methods An observational cohort study of 65 p16+ unknown primary patients treated with transoral surgery and neck dissection (2001–2012) was performed. Adjuvant therapy and recurrence data were collected. Kaplan–Meier estimates were computed for disease‐specific survival (DSS) and overall survival (OS). Results The primary detection rate was 89% (58 of 65). Five‐year DSS and OS were 98% and 97% for the detected group and 100% for the undetected, respectively. Seventeen patients were treated with surgery alone. Of the 47 patients receiving adjuvant therapy, radiation to the pharynx was spared in 36. Conclusion The transoral approach was highly effective for the diagnosis and treatment of the p16+ unknown primary and laid the foundation for deescalated radiation by elimination of the pharyngeal field. © 2014 Wiley Periodicals, Inc. Head Neck, 2014

Background: Appreciable local recurrence rates observed in patients with margin‐negative, transoral laser microsurgery (TLM)‐treated oral cavity squamous cell carcinoma (SCC) necessitate identification of new prognosticators for local control and survival. A histopathologic index (Brandwein–Gensler score [BGS]) and intrinsic/iatrogenic/chronic conditions causing immune compromise are investigated.Methods: From a prospectively assembled database of TLM‐treated oral cavity SCC, specimens for 60 patients with a minimum of 2‐years follow‐up could undergo BGS assignment. Local control, disease‐specific survival (DSS), and overall survival (OS) were study endpoints.Results: “Low‐BGS” was recorded in 28 patients (47%) and “high‐BGS” in 32 patients (53%), whereas immune compromise was observed in 18%. In multivariate analyses, immune compromise was the only predictor for local control. T classification and immune compromise were prognostic for DSS and OS. “High‐BGS” was prognostic only for OS.Conclusion: “High‐BGS” was associated with recurrences but immune compromise was the most significant predictor of local control and survival in margin‐negative, TLM‐treated oral cavity SCC. Strategies that maintain/restore tumor‐specific immune responses in immune compromised oral cavity SCC hosts need to be developed. © 2014 Wiley Periodicals, Inc. Head Neck 37: 52–63, 2015

A lateralized pain in the neck is a common symptom encountered by the otolaryngologist. This complaint, frequently caused by lateral thyrohyoid ligament syndrome, is often misdiagnosed. The pathophysiology of this syndrome may relate to overuse and inflammation. [change made here after initial online publication]. Typically, patients present with chronic unilateral neck pain often associated with odynophagia. The point of maximum tenderness localizes over the axis of the lateral thyrohyoid ligament. We present a series of 15 patients, in whom treatment with depot steroid and local anesthetic injection (n = 14) improved symptoms in 12 (86%), with complete resolution in nine (64%) patients. Laryngoscope, 124:116–118, 2014

Background: Modest survival rates are published for treatment of oral squamous cell carcinoma (OSCC) using conventional approaches. Few cohort studies are available for transoral resection of OSCC.Methods: Analysis for recurrence, survival, and prognosis of patients with OSCC treated with transoral laser microsurgery (TLM) ± neck dissection was obtained from a prospective database.Results: Ninety‐five patients (71 patients had stages T1–T2 and 24 had stages T3–T4 disease) with minimum follow‐up of 24 months met criteria and demonstrated negative margins in 95%. Five‐year local control (LC) and disease‐specific survival (DSS) were 78% and 76%, respectively. Surgical salvage achieved an absolute final locoregional control of 92%. Immune compromise and final margins were prognostic for LC, whereas T classification, N classification, TNM stage, comorbidity, and perineural invasion were also significant for DSS.Conclusion: We document a large series of patients with OSCC treated with TLM, incorporating T1 to T4 primaries. A significant proportion of stage III/IV cases demonstrates feasibility of TLM in higher stages, with final margin positivity of 5%, LC greater than 90%, and comparable survival outcomes. © 2013 Wiley Periodicals, Inc. Head Neck 36: 340–351, 2014

Although rare, recalcitrant cerebrospinal fluid (CSF) leak after skull base tumor resection or major head trauma is a difficult therapeutic challenge, often complicated by lack of local vascularized tissue in a scarred, radiated field. Craniotomy with a free tissue transfer has been described for CSF leak repair from these complicated skull base defects. We present our experience with a novel extracranial approach to manage refractory CSF leaks with a radial forearm free flap set in through a transantral and ethmoid sinus approach. Five patients with recalcitrant CSF leaks in the anterior skull base underwent radial forearm free tissue transfer via a hybrid transantral-endoscopic approach. There were 4 female patients and 1 male patient. Average age was 58 years (range, 30-72 years). Four patients had previous neurosurgical anterior skull base tumor resections, and 1 patient had significant head trauma leading to a recalcitrant CSF leak. All 5 patients had undergone multiple prior endoscopic and/or open repairs. All 5 patients had successful resolution of their leak after undergoing radial forearm free tissue transfer. Two of 5 patients required a second minor endoscopic procedure. No patients required a craniotomy. An extracranial transantral-endoscopic approach for the inset of radial forearm free flap is a safe treatment technique that precludes the need for a craniotomy and promotes effective repair of CSF leaks refractory to traditional endoscopic procedures.

Objectives/Hypothesis: Current head and neck epidemiology demonstrates a steadily increasing incidence of p16+ human papillomavirus‐related oropharynx squamous cell cancer (OPSCC). This distinct tumor subtype is associated with better survival outcomes. There is a growing recognition of the need to define management regimens that take into account the inherent patho‐biological attributes of these cancers and provide optimum oncological control with minimum morbidity. This is facilitated by a clear understanding of the prognostic variables that predict disease outcome in patients with p16+ OPSCC. To provide prognostic estimates, pathological staging and histopathological parameters are usually superior to clinical staging. However, knowledge of pathological predictors is sparse, mainly because of commonly employed nonsurgical management policies utilizing chemoradiotherapy. Minimally invasive approaches to the oropharynx, particularly transoral laser microsurgery (TLM), are well‐reported effective primary treatments for oropharynx cancers. From such series, it is feasible to conduct a detailed appraisal based on pathologic information from surgical specimens of both the primary and neck, to establish prognosticators unique to p16+ oropharynx cancer patients.Study Design: A prospectively assembled database of oropharynx cancer patients treated with primary TLM ± neck dissection ± adjuvant therapy from 1996 to 2010, analyzed retrospectively for survival and recurrence.Methods: The fundamental inclusion criteria were: 1) previously untreated biopsy‐proven OPSCC treated with primary TLM ± neck dissection, 2) diffuse p16 positivity in the surgical specimen, 3) availability for adjuvant therapy, if indicated, and 4), minimum follow‐up of 12 months or to death. Cox proportional hazard regression analyses were used to identify variables that were prognostic for disease‐free survival (DFS), the primary end point of the study, as well as disease‐specific survival (DSS) and overall survival. Kaplan‐Meier survival estimates and patterns of disease recurrence were also assessed. We also explored concordance for T and N staging, when assessed by clinical (cT, cN) and pathological (cT, pT) measures.Results: Of 211 patients in the TLM database, 171 met all the eligibility criteria. The median follow‐up was 47 months. The 3‐ and 5‐year Kaplan‐Meier estimates for DFS were 91% and 88%, respectively, whereas for DSS they were 95.5% and 94.4%, respectively. A total of 12 (7%) recurrences occurred: two local, four regional, and six distant. Of all T‐stage categories, pT4 tumors were strongest predictors of poorer DFS. cT4 tonsil primaries, ever smoking status, three or more metastatic nodes, pN2b+ stage, and radiation‐based adjuvant therapy were other prognosticators for DFS. Angioinvasion and T3‐T4 tumors were prognostic for reduced DSS, although smoking parameters were not. Extracapsular spread, N stage, and margins were nonprognosticators. Recursive partitioning analysis defined high‐ and low‐risk groupings of prognosticators. Downstaging of clinical T stage was observed for 31% of tumors on application of pathological classification.Conclusions: We document a well‐delineated set of prognostic variables that specifically and accurately identify individuals at risk of reduced outcomes in an otherwise good prognosis p16+ OPSCC cohort. Based on these prognosticators, appropriate patient counseling, adjuvant treatment recommendations, and stratification for trials can more accurately be made. We also observed an additional edge conferred by TLM toward more accurate clinical as well as pathological T staging.