Clinical impact of gastrointestinal endoscopy on the early detection of pharyngeal squamous cell carcinoma: A retrospective cohort study.

BACKGROUND: In recent years, with the growing availability of image-enhanced gastrointestinal endoscopy, gastroenterologists have contributed to the early detection of pharyngeal squamous cell carcinomas (SCC). AIM: To clarify the clinical characteristics of pharyngeal SCCs detected by gastrointestinal endoscopy. METHODS: This is a retrospective cohort study conducted in a single-center, a university hospital in Japan. We retrospectively assessed the clinical records of 522 consecutive patients with oropharyngeal or hypopharyngeal SCC who were examined in our hospital between 2011 and 2018. The lesions were classified into two groups: Group GE (detected by gastrointestinal endoscopy) and Group non-GE (detected by means other than gastrointestinal endoscopy). The clinical characteristics were compared between the two groups. Continuous data were compared using the Mann-Whitney U test. Pearson's χ 2 test or Fisher's exact test was used to analyze the categorical data and compare proportions. The Kaplan-Meier method was used to estimate the cumulative patient survival rates. RESULTS: In our study group, the median age was 65 years and 474 patients (90.8%) were male. One hundred and ninety-six cases (37.5%) involved the oropharynx and 326 cases (62.5%) involved the hypopharynx. Three hundred and ninety-five cases (75.7%) had some symptoms at the time of diagnosis. One hundred and forty-five (27.8%) cases had concurrent ESCC or a history of ESCC. One hundred and sixty-four (31.4%) cases were detected by gastrointestinal endoscopy and classified as Group GE. The proportions of asymptomatic cases, cTis-1 cases and cases with no lymph node metastasis were significantly higher in Group GE than Group non-GE (61.6% vs 7.3%, P < 0.001, 32.9% vs 12.0%, P < 0.001 and 69.5% vs 19.0%, P < 0.001). Endoscopic laryngo-pharyngeal surgery or endoscopic submucosal dissection were performed in only 0.6% of the lesions in Group non-GE but in 21.3% of the lesions in Group GE (P < 0.001). Overall survival was significantly longer in Group GE than in Group non-GE (P = 0.018). The 2-year and 4-year survival rates were 82.5% and 70.7% in Group GE, and 71.5% and 59.0% in Group non-GE, respectively. CONCLUSION: Gastrointestinal endoscopy plays an important role in the early detection and improving the prognosis of pharyngeal SCCs.

Survival Benefits From Surgery for Stage IVa Head and Neck Squamous Cell Carcinoma: A Multi-institutional Analysis of 1,033 Cases.

OBJECTIVES: Head and neck squamous cell carcinomas (HNSCs) are frequently diagnosed at the locoregional advanced stage (stage IVa), but controversy remains regarding whether stage IVa HSNCs should be treated with upfront surgery or definitive chemoradiation therapy (CRT). The purpose of this study was to compare overall survival (OS) and disease-free survival (DFS) in patients with stage IVa HNSC treated primarily by surgery with curative intent with/without (neo)adjuvant treatment (surgery group) versus those treated primarily with CRT (CRT group). METHODS: We reviewed data of 1,033 patients with stage IVa HNSC treated with curative intent at 17 cancer centers between 2010 and 2016. RESULTS: Among 1,033 patients, 765 (74.1%) received upfront surgery and 268 (25.9%) received CRT. The 5-year OS and DFS rates were 64.4% and 62.0% in the surgery group and 49.5% and 45.4% in the CRT group, respectively. In multivariate analyses, OS and DFS were better in the surgery group than in the CRT group (odds ratio [OR] for death, 0.762; 95% confidence interval [CI], 0.592-0.981; OR for recurrence, 0.628; 95% CI, 0.492-0.802). In subgroup analyses, the OS and DFS of patients with oropharyngeal cancer were better in the surgery group (OR for death, 0.548; 95% CI, 0.341-0.879; OR for recurrence, 0.598; 95% CI, 0.377-0.948). In the surgery group, patients with laryngeal cancer showed better OS (OR for death, 0.432; 95% CI, 0.211-0.882), while those with hypopharyngeal cancer DFS was improved (OR for recurrence, 0.506; 95% CI, 0.328-0.780). CONCLUSION: A survival benefit from surgery may be achieved even in patients with stage IVa HNSC, particularly those with oropharyngeal and laryngeal cancer. Surgery led to a reduction in the recurrence rate in patients with hypopharyngeal cancer.

Incidence and clinical predictors of cystic squamous cell carcinoma metastases in lateral cervical cysts.

OBJECTIVE: This study aimed to determine the incidence of metastatic squamous cell carcinoma in patients with an isolated cervical cystic mass, and to describe the clinical features that might predict the origin of cystic tumours. METHOD: Adult patients with isolated lateral cervical cystic masses who were scheduled for surgery from 1st January 2010 to 31st August 2016 in two tertiary care referral centres in Slovakia were analysed retrospectively. RESULTS: The incidence of cystic metastases in the whole cohort and in patients aged over 40 years were 9.9 per cent and 18.5 per cent, respectively. The incidence in patients aged over 40 years (18.5 per cent) was statistically significant (p = 0.003). CONCLUSION: The incidence of cystic squamous cell carcinoma metastases in lateral cervical cysts in patients aged over 40 years is high enough to call for excisional biopsy with frozen section, panendoscopy with direct biopsies, tonsillectomy and even neck dissection in cases of histologically confirmed carcinoma.

Human papillomavirus detection in matched oral rinses, oropharyngeal and oral brushings of cancer-free high-risk individuals.

OBJECTIVES: The detection of oral Human Papillomavirus (HPV) may be of clinical utility because of the major role HPV plays in the etiology of oropharyngeal cancer. However, oral HPV testing is not standardized and the best sampling method has yet to be identified. We aimed to compare HPV findings in matched oral rinse-and-gargles (rinses), oropharyngeal brushings and oral brushings. MATERIALS AND METHODS: HPV-DNA was investigated using Linear Array in samples collected from cancer-free individuals at increased risk for oral HPV. RESULTS: 163 oral rinses already tested for HPV were selected. The matched oropharyngeal (n = 163) and oral brushings (n = 100) were analyzed. The detection rate for any HPV, high-risk (HR)-HPVs and HPV16 was significantly higher in rinses than brushings. The overall agreement for any HPV between rinses and oropharyngeal brushings was 51.2% (Cohen K: 0.14, 95% CI: 0.07-0.21). The proportion of positive agreement was 16.8%. The overall agreement for HR-HPVs was 74.1% (Cohen K: 0.20, 95% CI: 0.07-0.33). The genotype-specific profile of rinses and brushings which were concomitantly HPV-positive only partially overlapped in cases with multiple infections, with more genotypes detected in the rinse, which were not isolated in the corresponding brushings. CONCLUSION: The agreement for HPV status between rinses and brushings is poor, particularly for the HPV-positive findings. Despite the fact that the origin of the HPV-infected cells present in the oral rinse is unclear, since they could not be traced back to the oropharynx or oral cavity, oral rinses provided the highest detection rate for HR-HPVs and HPV16.

Cytology and direct human papillomavirus testing on fine needle aspirates from cervical lymph node metastases of patients with oropharyngeal squamous cell carcinoma or occult primary.

OBJECTIVE: Cervical lymph node fine needle aspirates (FNAs) may represent the only specimens available for an initial characterisation of patients with lymphadenopathy. Morphology and human papillomavirus (HPV) DNA presence were evaluated in FNAs collected from patients with oropharyngeal squamous cell carcinoma (OPSCC) or cancer of unknown primary (CUP). FNA HPV results were compared with those of the respective formalin-fixed paraffin-embedded (FFPE) primary cancer. METHODS: Liquid-based cytology was performed on FNAs collected in PreservCyt. HPV-DNA was analysed by the INNO-LiPA HPV genotyping Extra II on both cytological and FFPE samples. The CINtec® Histology Kit was used to assess p16 expression in cancer tissues. RESULTS: Forty-seven FNAs were collected from OPSCC and 16 from CUP patients. Cancer cells were found in 35/47 cases (74.5%), while 11 (23.4%) showed only necrosis and one (2.1%) was negative for malignancy. HPV-DNA was detected in 30/47 FNAs (63.8%), mostly harbouring HPV16 (90.0%). An excellent agreement was observed between the FNA and corresponding FFPE HPV status (raw agreement: 97.5%; Cohen κ: 0.94). The HPV test result on the necrotic FNAs completely matched that of the respective primary cancer. FNA HPV testing correctly identified 26/27 HPV-driven OPSCCs (96.3%). HPV was detected in nine of 16 FNAs (56.2%) from CUP patients. CONCLUSIONS: HPV status of metastatic cervical lymph node FNAs reflects that of the corresponding primary OPSCCs even when cell integrity in the FNA is not preserved and only necrotic debris are present. In patients with initial CUP, HPV-positivity on the FNA may guide the diagnostic workup and therapeutic management, since it suggests an oropharyngeal origin.

Mouse double minute 4 variants modify susceptibility to risk of recurrence in patients with squamous cell carcinoma of the oropharynx.

Given the crucial role of Mouse double minute 4 (MDM4) oncoprotein in p53 pathway, single nucleotide polymorphisms (SNPs) could serve as such biomarkers for prediction of SCCOP recurrence. Thus, we investigated associations between three tagging putatively functional variants of MDM4, two in the 3' untranslated region of 3' UTR [rs11801299 (NC_000001.10:g.204529084G>A) and rs10900598(NC_000001.10:g.204525568G>T)] and one in intron 1 [rs1380576(NC_000001.10:g.204488278G>C)], and recurrence risk of SCCOP in 1,008 incident patients. A log-rank test and multivariable Cox models were used to assess associations. Patients with MDM4-rs10900598 GT/TT had a worse disease-free survival (DFS) compared with corresponding GG genotype, while those with rs11801299 AG/AA genotypes had a lower recurrence risk than the cases with rs11801299 GG genotype (both log-rank, P < 0.001). Multivariable analysis showed that significantly different recurrence risk were found among patients with MDM4-rs10900598 GT/TT and rs11801299 AG/AA variant genotypes (HR, 2.0, 95% CI, 1.4-2.9 and HR, 0.4, 95% CI, 0.3-0.6, respectively) compared with their corresponding common homozygous genotypes. Furthermore, after combining the risk genotypes of the three SNPs, patients among low-risk group had a significantly lower risk of SCCOP recurrence than those in high-risk group (HR, 0.2, 95% CI, 0.1-0.3). The risk for both individual SNPs or combined risk genotypes was restricted to HPV-positive SCCOP patients. Our findings suggest that the MDM4 polymorphisms may, individually or in combination, confer an independent risk of SCCOP recurrence, particularly in HPV-positive SCCOP patients. However, larger studies are needed to validate our findings.

Treatment selection in oropharyngeal cancer: a surveillance, epidemiology, and end results (SEER) patterns of care analysis.

PURPOSE: Treatment for oropharyngeal cancer (OPC) has changed over the past two decades under multiple influences. We provide a population-based description of the application of radiotherapy, surgery, and chemotherapy to OPC in 1997, 2004, and 2009. METHODS: The National Cancer Institute's Patterns of Care study for OPC included multiple variables not available in the public-use dataset. We identified factors correlating with selection of primary surgery versus radiotherapy with or without chemotherapy (RTC) and analyzed predictors of all-cause mortality. We estimated the frequency of human papillomavirus (HPV) testing. RESULTS: RTC was more common in 2009 than in 1997, and was more commonly applied to Stage IV cases. However, RTC was not an independent risk factor for mortality compared with surgery. HPV status was known in 14% of patients in 2009. CONCLUSIONS: RTC is the most common treatment for OPC, but it may not provide the best outcomes. HPV testing was uncommon in 2009.

Minimizing adjuvant treatment after transoral robotic surgery through surgical margin revision and exclusion of radiographic extracapsular extension: A Prospective observational cohort study.

BACKGROUND: We investigated in a prospective cohort of patients treated with trans-oral robotic surgery (TORS) for oropharyngeal cancer (OPC), who were selected for the absence of radiographic extra-capsular extension (ECS) and surgically revised for inadequate margins, the possibility of reducing adjuvant radiation (RT)/chemo-radiation therapy (CRT) without jeopardizing tumor control and functional outcome. METHODS: We conducted a prospective observational cohort of patients treated with TORS for oropharyngeal cancer. RESULTS: Twenty-nine patients with T1/2N0 to N2B stage cancers were treated with TORS. Forty-five percent of them were treated for secondary primaries. Nine of 29 patients (31%) were revised for close/positive margins. Adjuvant RT was prescribed for 2 of 19 patients with early squamous cell carcinoma (SCCs) and CRT for 1 of 10 patients with advanced oropharyngeal SCCs. Overall survival (OS), disease-specific survival (DSS), and locoregional control at 2 years were 85%, 96%, and 93%, respectively. Posttreatment Functional Outcome Swallowing Scale (FOSS) scores worsened with prior or adjuvant RT, local recurrence, site, and revision for margins. CONCLUSION: Patients with early and moderately advanced oropharyngeal SCC selected for radiographic ECS and revised for inadequate margins have excellent tumor control and favorable functional recovery. © 2017 Wiley Periodicals, Inc. Head Neck 39: 965-973, 2017.

A functional variant at the miRNA binding site in E2F1 gene is associated with risk and tumor HPV16 status of oropharynx squamous cell carcinoma.

Human papillomavirus (HPV) activates E2F1-driven transcription via the E7-RB1-E2F pathway. Genetic polymorphisms in the 3' untranslated region (UTR) targeted by miRNAs can affect the regulation of target genes and individual cancer risk. Thus, we hypothesized that a polymorphism at the 3'UTR miRNA binding site of E2F1 gene (rs3213180) was associated with risk of oral squamous cell carcinoma (OSCC) and tumor HPV status of oropharynx squamous cell carcinoma (OPSCC). We determined the E2F1rs3213180 polymorphism and HPV16 L1 serology of 325 OSCC patients and 335 controls, and tumor HPV16 status of 552 OPSCC. Logistic regression models were used to calculate associations of E2F1rs3213180 polymorphism with risk of HPV-associated OSCC and tumor HPV status of OPSCC. The risk of HPV-associated OSCC was modified by the E2F1rs3213180 polymorphism. Patients with both HPV seropositivity and the Ins/Del or Ins/Ins genotype of E2F1rs3213180 had the highest risk of OSCC, while the lowest risk was detected in patients with HPV seronegativity and the Del/Del genotype. A similar and more prominent effect was detected in OPSCC, but not in oral cavity squamous cell carcinoma (OCSCC) patients. Notably, that effect trend was pronounced in never-smokers and never-drinkers. Furthermore, the patients with the E2F1rs3213180 Ins/Del or Ins/Ins genotype were 2.9 times more likely to have HPV-positive tumors than those with the Del/Del genotype. Our results suggest that the E2F1rs3213180 polymorphism may influence susceptibility to HPV-associated OSCC, particularly for OPSCC, never-smokers and never-drinkers, but not for patients with OCSCC. Additional larger population and functional studies are warranted to confirm our findings. © 2016 Wiley Periodicals, Inc.

Meta-analysis on survival of patients treated with transoral surgery versus radiotherapy for early-stage squamous cell carcinoma of the oropharynx.

BACKGROUND: Transoral surgery (TOS) for patients with early stage oropharyngeal squamous cell carcinoma (SCC) is increasingly used, however, criticized, because of less optimal access to the tumor than open techniques and thus potentially jeopardizing tumor control in comparison with radiotherapy (RT). Therefore, we compared the currently available data on survival provided by TOS versus RT. METHODS: Survival data were extracted after a MEDLINE, Web of Science, and Google Scholar search followed by a meta-analysis. RESULTS: The analysis was based on 729 patients in the RT group versus 276 in the TOS group with similar quality of studies in both groups. The 5-year disease-specific survival (DSS)/overall survival (OS) was 90.4% (95% confidence interval [CI], 85.6% to 95.2%/58.8%; 95% CI, 52.8% to 64.7%) in the RT group versus 89.6% (95% CI, 81.8% to 97.3%/78.1%; 95% CI, 71.2% to 85.1%) in the TOS group. CONCLUSION: The data suggest equivalent efficacy of both treatments in terms of disease control for early stage oropharyngeal SCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: 2143-2150.

Oncologic safety of the submental flap for reconstruction in oral cavity malignancies.

OBJECTIVES: To evaluate the oncologic safety of the submental flap regarding potential transposition of involved nodes to the reconstruction site and recognize the submental flap as an excellent option for oral cavity reconstruction. STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic referral center. SUBJECTS AND METHODS: All patients undergoing reconstruction with submental flaps following the resection of primary and recurrent malignancies of the oral cavity between 2002 and 2012 were reviewed. Analysis included tumor location, staging, reconstructive details, postoperative course, and outcomes. RESULTS: Fifty patients were identified having undergone submental flap reconstruction of defects following resection for oral cavity malignancies. No patient had identifiable clinical or radiographic level I nodal involvement preoperatively. Patients' ages ranged from 35 to 88 years (mean, 70 years). American Joint Committee on Cancer staging of patients included stage II (n = 16, 32%), stage III (n = 10, 20%), and stage IVa disease (n = 28, 48%). All patients underwent a level 1A and 1B dissection with removal of the nodal basin and submandibular gland. The prevalence of occult lymph node metastasis involving level 1 was 10%. On follow-up, there were no local recurrences associated with submental flap transposition to the oral cavity. One patient with multifocal oral disease had a tongue recurrence geographically separate from the submental flap reconstruction. There was 100% flap survival. CONCLUSIONS: The submental flap provides a rapid and reliable option for oral cavity defect reconstruction. With appropriate management of the level 1 nodal compartment, oncologic outcomes are not compromised.

Prevalence and predictive role of p16 and epidermal growth factor receptor in surgically treated oropharyngeal and oral cavity cancer.

BACKGROUND: The purpose of this study was to describe the relationship of p16 and epidermal growth factor receptor (EGFR) expression with survival in surgically treated patients who had oropharyngeal or oral cavity squamous cell carcinoma (SCC). METHODS: Tissue from 36 patients with oropharyngeal SCC and 49 patients with oral cavity SCC treated between 1997 and 2001 was imbedded and immunostained using a tissue microarray. RESULTS: The p16 was positive in 57% and 13% of patients with oropharyngeal SCC and oral cavity SCC, respectively. EGFR was positive in 60% and 63% of patients with oropharyngeal SCC and oral cavity SCC, respectively. In patients with oropharyngeal SCC, p16 expression was associated with improved disease-specific survival (DSS), overall survival (OS), and time to recurrence (TTR) (p < .01, < .01, and <.01, respectively). EGFR expression was associated with poorer DSS, OS, and TTR (p < .01, = .01, and < .01, respectively). For oropharyngeal SCC, when examining both p16 and EGFR expression as combined biomarkers, high p16 expression coupled with low EGFR expression was associated with improved DSS (p p16 = .01; p EGFR = .01). Patients with oral cavity SCC showed no association between biomarker and outcome. CONCLUSIONS: For patients with oropharyngeal SCC, high p16 and low EGFR were associated with improved outcome, suggesting a predictive role in surgically treated patients.

A Case of Bronchogenic Cyst in the Retropharyngeal Space / 대한이비인후과학회지

The bronchogenic cyst is an uncommon benign congenital anomaly of the primitive ventral foregut. They usually occur in the mediastinum and intrapulmonary regions. Localization in the cervical area is unusual and the majority of cases reported have been found in the pediatric population. Radiologically, it can not be differentiated from other cystic lesions. Therefore, it is pa-thologically confirmed only when there are bronchial tissues such as pseudostratified ciliated columnar epithelium, smooth muscle, mucous gland or cartilage. Since this cyst has potential for complication, a complete excision is mandatory. We recently experienced a case of retropharyngeal bronchogenic cyst presenting as a lump sensation in 32-year-old male. In this article, we reviewed the etiology, the diagnosis, and the treatment of this case with a review of the literatures.

Clinical efficacy of primary tumor volume measurements: comparison of different primary sites.

OBJECTIVES: The purpose of study was to determine the clinical efficacy of primary tumor volume measurements of different primary sites in the oropharynx compared to the oral cavity. METHODS: A retrospective analysis of 85 patients with oral cavity or oropharynx cancer. The tumor area was manually outlined from axial magnetic resonance (MR) series. The software calculated the tumor volumes, automatically. The values of the primary tumor volumes were then subdivided into separate groups (3,500 mm(3)). RESULTS: The prognostic indicators were the cT and cN (oral cavity); age, primary site, cT, cN, and primary tumor volume (oropharynx) on the univariate analysis. There was no significant prognostic factor for oral cavity cancer on the multivariate analysis. Primary site, cN, and primary tumor volume were independent prognostic indicators for oropharynx cancer by multivariate analysis. CONCLUSION: Primary tumor volume measurement is a reliable way to stratify outcome, and make up for the weak points in the American Joint Committee on Cancer staging system with oropharynx cancer.

Clinical Efficacy of Primary Tumor Volume Measurements: Comparison of Different Primary Sites

OBJECTIVES: The purpose of study was to determine the clinical efficacy of primary tumor volume measurements of different primary sites in the oropharynx compared to the oral cavity. METHODS: A retrospective analysis of 85 patients with oral cavity or oropharynx cancer. The tumor area was manually outlined from axial magnetic resonance (MR) series. The software calculated the tumor volumes, automatically. The values of the primary tumor volumes were then subdivided into separate groups (3,500 mm3). RESULTS: The prognostic indicators were the cT and cN (oral cavity); age, primary site, cT, cN, and primary tumor volume (oropharynx) on the univariate analysis. There was no significant prognostic factor for oral cavity cancer on the multivariate analysis. Primary site, cN, and primary tumor volume were independent prognostic indicators for oropharynx cancer by multivariate analysis. CONCLUSION: Primary tumor volume measurement is a reliable way to stratify outcome, and make up for the weak points in the American Joint Committee on Cancer staging system with oropharynx cancer.