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Objective To describe management and oncologic outcomes for patients who develop locoregional recurrence (LRR) or distant metastasis (DM) following transoral robotic surgery for human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). Study Design Case series with chart review. Setting Tertiary care referral center. Subjects and Methods A total of 286 patients with HPV-positive OPSCC who underwent transoral robotic surgery-based treatment from May 2007 to May 2015. Results Of 286 patients (12.2%), 35 met inclusion criteria. Of these, 19 experienced an LRR and 16 developed a DM; 2 patients with LRR subsequently developed DM. In those patients with an LRR, 79% had T1/T2 tumors, and 47% had N0/N1 nodal disease, compared with 75% and 6% in the DM group, respectively. The median time to LRR or DM was 0.6 years (interquartile range [IQR], 0.4-1.0) and 1.8 years (IQR, 1.0-2.1), respectively. Salvage treatment with intent to cure was attempted in 23 patients (16 LRR, 7 DM). The median time from LRR or DM to last follow-up for the 18 patients who were still alive after salvage was 1.9 years (IQR, 0.4-3.8; range, 7 days-6.2 years). Estimated cancer-specific survival rates at 3 years following intent-to-cure treatment were 63% (95% CI, 39-100; number still at risk, 5) in the LRR group and 100% (95% CI, 100-100; number still at risk, 2) in the DM group. Conclusion Overall, LRR and DM for HPV-positive OPSCC following transoral robotic surgery-based therapy are infrequent. In our subset of patients who underwent intent-to-cure treatment, cancer-specific survival rates were favorable. Therefore, aggressive salvage treatment for LRR and DM for HPV-positive OPSCC should be recommended for appropriate candidates. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis To determine the incidence of level IIB lymph node metastasis in patients with laryngeal or hypopharyngeal squamous cell carcinoma and to evaluate the need for elective and therapeutic neck dissection of level IIB. Study Design Retrospective cohort study and review of the literature. Methods Patients with laryngeal or hypopharyngeal squamous cell carcinoma (N = 65) were primarily treated with surgery at Mayo Clinic (Rochester, Minnesota) from 2004 through 2010. Neck dissection specimens were analyzed by a pathologist, and metastases to level IIB were reported. In addition, 18 previously published studies, totaling 1,114 neck dissections, were reviewed. Results Level IIB lymph node metastases were present in 4% and 17% of elective and therapeutic neck dissections, respectively. Ipsilateral IIB metastasis was more common than contralateral IIB metastasis in elective and therapeutic neck dissection specimens. Level IIB lymph node metastasis was not significantly associated with level IIA nodal metastasis, level III nodal metastasis, clinical primary tumor stage, clinical nodal stage, or pathologic confirmation of extracapsular spread in either laryngeal or hypopharyngeal squamous cell carcinoma. Conclusions The rate of occult IIB metastasis in laryngeal and hypopharyngeal squamous cell carcinoma is exceedingly low. In a clinically node-negative case, the ipsilateral and contralateral level IIB nodal packet should not be dissected. For clinically node-positive cases, ipsilateral level IIB dissection should be performed; contralateral IIB dissection should be performed only when indicated. Level of Evidence 4. Laryngoscope, 123:3032-3036, 2013 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis To determine the incidence of level IIB lymph node metastasis in patients with oropharyngeal squamous cell carcinoma (OPSCC) and to evaluate the necessity of level IIB dissection for elective and therapeutic neck dissections. Study Design Retrospective cohort study. Methods Patients with OPSCC (N = 348) were surgically managed at our institution from 2004 through 2010. Neck dissection specimens were reviewed by a pathologist, and level IIB metastases were analyzed with respect to clinical and pathologic data. Results Level IIB lymph node metastases were present in 2.5% and 25% of elective and therapeutic neck dissections, respectively. Level IIA metastasis, clinical tumor stage, clinical nodal stage, extracapsular spread, and primary tumor location in the tonsil were significantly associated with level IIB metastasis. Conclusions This study uniquely demonstrated a statistically significant association between clinical tumor stage and tonsil subsite with level IIB metastasis in OPSCC. Considering the predicted incidence of nodal metastasis, we conclude that level IIB neck dissection can be omitted in early stage (T1 or T2) clinically node negative (cN0) OPSCC. In patients with a cN0 neck and advanced OPSCC (T3 or T4), primary tumor in the tonsil, or ipsilateral clinically node positive (cN+) and contralateral cN0 neck, level IIB dissection should be considered. Level IIB dissection should be performed routinely in patients with cN+ OPSCC. Level of Evidence 4. Laryngoscope, 123:2700-2705, 2013 [ABSTRACT FROM AUTHOR]

Background Chromosome rearrangements that result in gene fusions have important roles in the initial steps of tumorigenesis, especially in leukemias and lymphomas, but the biological and clinical impact of gene fusions in common solid tumors are less understood. The purpose of this study was to discover novel translocations that could result in gene fusions in oropharyngeal squamous cell carcinomas (OPSCCs). Methods Translocations were identified using 2 different bioinformatics pipelines, SnowShoes-FTD and FusionHunter, examining data from 11 paired-end RNA sequencing (RNA-Seq) data in OPSCC. Translocations were validated by RT-PCR and Sanger sequencing analysis. Results Two novel cancer-specific translocations involving MGST3-ZMAT5 and MS4A7-C2CD3 were found in 2 of the tumor samples tested. However, these translocations were found only in the single tumor. Conclusions We hope that this integrative methodology will elucidate key aspects of tumor biology as well as generate novel targets for cancer diagnoses and therapies. Head Neck, 2012 [ABSTRACT FROM AUTHOR]

The aim of this retrospective study was to describe the oncologic and functional results of treating oropharyngeal squamous cell carcinoma with transoral robotic surgery and neck dissection as monotherapy. A review was performed, including all patients who underwent transoral robotic surgery and neck dissection as the only means of therapy for oropharyngeal carcinoma from March 2007 to July 2009 at a single tertiary care academic medical center. We reviewed all cases with ≥24- month follow-up. Functional outcomes included tracheostomy dependence and oral feeding ability. Oncologic outcomes were stratified by human papillomavirus (HPV) status and tobacco use and included local, regional, and distant disease control, as well as disease-specific and recurrence-free survival. Eighteen patients met study criteria. Ten patients (55.6%) were able to eat orally in the immediate postoperative period, and 8 (44.4%) required a temporary nasogastric tube for a mean duration of 13.6 days (range 3 to 24 days) before returning to an oral diet. No patient required placement of a gastrostomy tube, and all patients are tracheostomy-tube-free. Among the HPV-positive nonsmokers (12/18, 66.7%), Kaplan-Meier estimated 3-year local, regional, and distant control rates were 90.9%, 100%, and 100%, respectively. Kaplan-Meier estimated disease-specific survival and recurrence-free survival were 100% and 90.9%, respectively. No complications occurred. This study suggests that carefully selected patients with HPV-positive oropharyngeal carcinoma can be effectively treated with surgery alone with excellent functional and oncologic outcomes. [ABSTRACT FROM AUTHOR]

Although uncommon, cancer of an unknown primary (CUP) metastatic to cervical lymph nodes poses a range of dilemmas relating to optimal treatment. The ideal resolution would be a properly designed prospective randomized trial, but it is unlikely that this will ever be conducted in this group of patients. Accordingly, knowledge gained from retrospective studies and experience from treating patients with known head and neck primary tumors form the basis of therapeutic strategies in CUP. This review provides a critical appraisal of various treatment approaches described in the literature. Emerging treatment options for CUP with metastases to cervical lymph nodes are discussed in view of recent innovations in the field of head and neck oncology and suitable therapeutic strategies for particular clinical scenarios are presented. For pN1 or cN1 disease without extracapsular extension (ECE), selective neck dissection or radiotherapy offer high rates of regional control. For more advanced neck disease, intensive combined treatment is required, either a combination of neck dissection and radiotherapy, or initial (chemo)radiotherapy followed by neck dissection if a complete response is not recorded on imaging. Each of these approaches seems to be equally effective. Use of extensive bilateral neck/mucosal irradiation must be weighed against toxicity, availability of close follow-up with elective neck imaging and guided fine-needle aspiration biopsy (FNAB) when appropriate, the human papillomavirus (HPV) status of the tumor, and particularly against the distribution pattern (oropharynx in the majority of cases) and the emergence rate of hidden primary lesions (<10% after comprehensive workup). The addition of systemic agents is expected to yield similar improvement in outcome as has been observed for known head and neck primary tumors. Head Neck, 2013 [ABSTRACT FROM AUTHOR]

In an era of advanced diagnostics, metastasis to cervical lymph nodes from an occult primary tumor is a rare clinical entity and accounts for approximately 3% of head and neck malignancies. Histologically, two thirds of cases are squamous cell carcinomas (SCCs), with other tissue types less common in the neck. With modern imaging and tissue examinations, a primary tumor initially undetected on physical examination is revealed in >50% of patients and the site of the index primary can be predicted with a high level of probability. In the present review, the range and limitations of diagnostic procedures are summarized and the optimal diagnostic workup is proposed. Initial preferred diagnostic procedures are a fine-needle aspiration biopsy (FNAB) and imaging. This allows directed surgical biopsy (such as tonsillectomy), based on the preliminary findings, and prevents misinterpretation of postsurgical images. When no primary lesion is suggested after imaging and panendoscopy, and for patients without a history of smoking and alcohol abuse, molecular profiling of an FNAB sample for human papillomavirus (HPV) and/or Epstein-Barr virus (EBV) is important. Head Neck, 2013 [ABSTRACT FROM AUTHOR]

Objectives: We assessed the long-term quality of life (QOL) in patients who survived oral cavity squamous cell cancer when they were young and looked for any clinical factors that might adversely affect function and QOL. Methods: We performed a retrospective case series and questionnaire survey in a tertiary care center. The subjects were consecutive patients treated for oral cancers during a 25-year period, when they were 40 years of age or less. The patients completed the University of Washington Quality of Life questionnaire and the M. D. Anderson Dysphagia Inventory (MDADI). We made an overall descriptive report of swallowing and QOL measures in the study population and looked for any clinical factors associated with functional outcomes. Results: Among the 62 patients treated over the course of 25 years, 46 were alive and disease-free. Twenty-six participated. The median follow-up duration was 14.7 years (range, 3 to 27 years). Age at diagnosis and duration of follow-up did not correlate with overall QOL or health-related QOL. Seventy-seven percent rated their overall QOL as outstanding, very good, or good. The key domains affected by cancer were appearance, mood, saliva, and shoulder function. Radiotherapy significantly adversely affected the QOL. The median MDADI scores on all 4 subscales were at least 85%. Higher T-stage and radiotherapy were significantly associated with lower scores on all subscales. Conclusions: The long-term health-related QOL in this cohort was quite good. Radiotherapy and tumor stage correlated with swallowing outcomes, and only radiotherapy seemed to adversely affect the overall QOL. [ABSTRACT FROM AUTHOR]

Surgery is the preferred modality for curative treatment of recurrent laryngeal cancer after failure of nonsurgical treatments. Patients with initial early-stage cancer experiencing recurrence following radiotherapy often have more advanced-stage tumors by the time the recurrence is recognized. About one third of such recurrent cancers are suitable for conservation surgery. Endoscopic resection with the CO2 laser or open partial laryngectomy (partial vertical, supracricoid, or supraglottic laryngectomies) have been used. The outcomes of conservation surgery appear better than those after total laryngectomy, because of selection bias. Transoral laser surgery is currently used more frequently than open partial laryngectomy for treatment of early-stage recurrence, with outcomes equivalent to open surgery but with less associated morbidity. Laser surgery has also been employed for selective cases of advanced recurrent disease, but patient selection and expertise are required for application of this modality to rT3 tumors. In general, conservation laryngeal surgery is a safe and effective treatment for localized recurrences after radiotherapy for early-stage glottic cancer. Recurrent advanced-stage cancers should generally be treated by total laryngectomy. © 2011 Wiley Periodicals, Inc. Head Neck, 2012. [ABSTRACT FROM AUTHOR]

Objectives: The tonsillar fossa is the most common subsite of the oropharynx to be afflicted with squamous cell carcinoma (SCCA). Accepted treatments include any combination of surgery, radiotherapy, and chemotherapy. We review the oncologic and functional outcomes of patients with tonsillar carcinoma who underwent transoral tumor resection and neck dissection with or without postoperative radiotherapy or chemoradiotherapy. Study Design: Retrospective chart review. Methods: From 1996 through January 2005, 102 patients with tonsillar SCCA underwent transoral resection. Overall survival, disease-specific survival, local control, and locoregional control rates were analyzed using the Kaplan-Meier method. Immediate and long-term speech and swallowing function and treatment-related morbidity were analyzed. Results: Twenty-six patients had surgery only, 71 had surgery and radiotherapy, and five had surgery and chemoradiotherapy. Twenty patients had stage III disease, 63 had stage IVA disease, and two had stage IVB disease. The Kaplan-Meier overall survival estimate was 92.2% at 2 years and 85.0% at 5 years. The 5-year local control estimate was 91.8%, and the 5-year Kaplan-Meier disease-specific survival estimate was 93.9%. The median hospital stay was 3 days. Tracheostomy was required for 14 patients, and 13 of these patients had decannulation. Temporary feeding tubes were placed in 35 patients. Sixteen patients received a percutaneous endoscopic gastrostomy tube; of these, 12 had the tubes removed. Conclusions: Transoral resection of tonsillar SCCA with or without postoperative adjuvant therapy provided excellent locoregional control and minimized treatment-related morbidity. We believe that transoral resection is the optimal treatment for patients with oropharyngeal SCCA. Laryngoscope, 119:508-515, 2009 [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma of the temporal bone usually presents with tumor and edema occluding the external auditory canal. Accurate evaluation of the extent of such a tumor is therefore difficult. Assessment of these tumors and subsequent surgical management depends primarily on the preoperative radiographic findings. This paper discusses the evolution of the radiographic assessment of carcinomas of the ear canal. Certain cases have been selected to demonstrate the advantages and disadvantages of the radiographic studies in use. Mastoid x-ray views and petrous tomograms have been the standard methods of studying these lesions. Their interpretation, however, often exaggerates or underestimates the true extent of these carcinomas. Early and later generation computed tomography (CT) scans offered improvement in determining tumor involvement but still did not give the needed detail for surgical planning. High-resolution CT scanning of the petrous bones now offers the surgeon excellent views of these tumors. This paper places special emphasis on this technique and also discusses indications for operability. [ABSTRACT FROM AUTHOR]

Background: Larynx cancer is a common site for tumors of the upper aerodigestive tract. In cases with a clinically negative neck, the indications for an elective neck treatment are still debated. The objective is to define the prevalence of occult metastasis based on the subsite of the primary tumor, T classification and neck node levels involved. Methods: All studies included provided the rate of occult metastases in cN0 larynx squamous cell carcinoma patients. The main outcome was the incidence of occult metastasis. The pooled incidence was calculated with random effects analysis. Results: 36 studies with 3803 patients fulfilled the criteria. The incidence of lymph node metastases for supraglottic and glottic tumors was 19.9% (95% CI 16.4–23.4) and 8.0% (95% CI 2.7–13.3), respectively. The incidence of occult metastasis for level I, level IV and level V was 2.4% (95% CI 0–6.1%), 2.0% (95% CI 0.9–3.1) and 0.4% (95% CI 0–1.0%), respectively. For all tumors, the incidence for sublevel IIB was 0.5% (95% CI 0–1.3). Conclusions: The incidence of occult lymph node metastasis is higher in supraglottic and T3–4 tumors. Level I and V and sublevel IIB should not be routinely included in the elective neck treatment of cN0 laryngeal cancer and, in addition, level IV should not be routinely included in cases of supraglottic tumors. [ABSTRACT FROM AUTHOR]

The association between Human Papillomavirus (HPV) DNA and oropharyngeal squamous cell carcinoma (SCC) has been supported by numerous studies strongly implicating HPV infection as a factor in the development of this cancer. In contrast, squamous cell carcinoma of the oral cavity has not been associated with HPV DNA, suggesting alternate aetiologic factors. The possibility that viral agents other than HPV could contribute to the development of oral cavity SCC should be given consideration, especially given the association of Epstein-Barr virus (EBV) with nasopharyngeal cancer. We used quantitative polymerase chain reaction (qPCR) studies to compare the expression levels of genes that may act as indicators of persistent stimulation by viral antigen in both oral cavity and oropharyngeal squamous cell cancers. Our results demonstrate that HPV-positive oropharyngeal tumours displayed gene expression patterns indicative of a viral signature and that HPV-negative oropharyngeal tumours do not display similar expression patterns. In contrast, we saw no evidence of either a viral or bacterial signature in the oral tumours examined. This would suggest that either an as of yet unidentified virus present in the oral tumour samples is not eliciting a typical immune response, or that there are no novel viral sequences or viruses present in the oral tumours examined. [Copyright &y& Elsevier]

Human papillomavirus (HPV) infections are well known causes of anogenital cancers. Recent studies show that HPV also plays a role in oropharyngeal cancer (OPC). A review on the role of HPV vaccination in the prevention of head and neck squamous cell carcinoma (HNSCC) with special emphasis on OPC was conducted and available vaccines and vaccination strategies in HNSCC and OPC are discussed. Prophylactic vaccination is known to be effective for prevention of anogenital HPV infection and precursor lesions in the cervix and anus. While the value of vaccination for prevention of OPC and possibly as an adjuvant treatment is still an open question, evidence to date supports the possibility that HPV vaccination may prove to be effective in reducing the incidence of this malignancy. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Standard treatment for patients with poor-risk, resected head and neck squamous cell carcinoma (HNSCC) is adjuvant radiation therapy combined with high-dose cisplatin. Many patients are treated with weekly cisplatin; it is not known whether weekly and high-dose cisplatin are equivalent. This study compares the outcomes of patients with locally-advanced HPV-negative HNSCC and HPV/p16-positive oropharynx HNSCC treated with adjuvant chemoradiation therapy with either high-dose or weekly cisplatin. Materials and methods: Retrospective review of patients with Stage III/IV HNSCC who had surgery followed by adjuvant chemoradiation therapy at Mayo Clinic, Rochester. HPV and/or p16 status was available for all oropharynx patients. Results: 104 Patients (51 high-dose, 53 weekly) were analyzed. The 3-year overall survival was 84% and 75% for patients who received high dose and weekly cisplatin, respectively (p =0.30). The 3-year recurrence free survival was 71% and 74% in the high dose and weekly cisplatin group, respectively (p =0.95). Patients with HPV/p16-positive oropharynx cancer who received adjuvant chemoradiation therapy with high-dose and weekly cisplatin had three-year overall survival rates of 91% and 86% (p =0.56), and 3-year recurrence free survival of 84% and 82% (p =0.93). Extracapsular extension did not affect prognosis in either group. Conclusions: No significant survival difference was seen between patients with locally advanced HNSCC treated with adjuvant chemoradiation therapy with high-dose or weekly cisplatin, although there was a trend for improved survival with high-dose cisplatin. Weekly cisplatin in the adjuvant setting may be a better treatment for patients with HPV-positive oropharynx cancer to preserve survival and minimize toxicity. [Copyright &y& Elsevier]

Summary: To increase awareness of the potential of oral and oropharyngeal squamous cell carcinoma (SCC) to metastasize to the parotid region. We retrospectively reviewed patients who had undergone parotidectomy for metastatic oral or oropharyngeal SCC at a single tertiary care facility from January 1988 to January 2004. Exclusion criteria were a history of cutaneous SCC of head and neck or extension of primary tumor into the parotid gland. Twelve patients met study criteria. Parotid metastasis represented the initial disease manifestation in 4 cases. In 1 case, parotid metastasis presented synchronously with the primary tumor. Parotid metastasis represented recurrent disease in the other 7 cases. Primary subsites included tongue base (n =4), tonsil (n =3), lateral pharyngeal wall (n =2), oral floor (n =1), maxillary alveolus (n =1), and retromolar trigone (n =1). Pathologic findings showed grade 3 or 4 SCC in all patients. Parotid metastasis was located in the inferior parotid nodes in 7 cases; multiple superficial nodes, 3 cases; and both deep and superficial nodes, 2 cases. Oral and oropharyngeal SCC can metastasize to the intraparotid lymph nodes. The inferior parotid nodes are most commonly involved, and patients generally have substantial associated cervical metastases. When treating patients who have oral or oropharyngeal cancer with substantial cervical metastasis, physicians should consider removing the inferior parotid lymph nodes. We recommend that when intraparotid lymph node metastasis is detected, total parotidectomy and multidisciplinary adjuvant therapy should be conducted. [ABSTRACT FROM AUTHOR]