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It has been shown that podoplanin expression is associated with carcinoma of the aerodigestive tract. Recent studies indicate that podoplanin may serve as a prognostic biomarker in oral carcinoma. In order to provide evidence on the role of podoplanin in oropharyngeal squamous cell carcinoma, we evaluated the prognostic impact of podoplanin in these patients. We analyzed formalin-fixed tissue samples from 107 consecutive patients with oropharyngeal squamous cell carcinoma. HPV typing and immunohistochemical staining for both p16 and podoplanin were performed. Expression of podoplanin was seen in 38.3% of all cases. We found no correlation of the podoplanin scores with either p16 expression or with HPV status. There was no significant correlation of podoplanin expression with the staging variables T, N, M, and tumor grading. Podoplanin expression did neither influence the 5-year overall survival nor the 5-year disease-free survival. Concluding, we could not find a prognostic role of podoplanin expression neither in the HPV-positive cases nor in the HPV-negative cases. It appears that podoplanin is not expressed as often in oropharyngeal cancer compared to oral cancer. We could not show any relation of lymph node metastases and podoplanin expression in this homogenous cohort of tumors.

Background: Carcinoma of unknown primary (CUP) of the neck are heterogeneous tumors in their clinical and biological characteristics, and a preoperative prognostic marker is desirable to optimize staging and therapy and to improve outcome and survival. For CUP syndrome, no optimized diagnostic and treatment strategy or biomarker have yet been determined., Methods: Forty-seven patients presenting with CUP syndrome were analyzed after thorough standard diagnostic staging procedures. All patients were surgically treated with tonsillectomy, neck dissection of the diseased neck, as well as adjuvant chemoradiation. The tissue of lymph node metastases (and, if found, of the primary tumor) was analyzed regarding expression of p16, epidermal growth factor receptor (EGFR), and presence of human papillomavirus (HPV) DNA., Results: In 39% of all cases (20 of 47), the primary cancer was found during diagnostic workup. If HPV DNA was detected in the neck lymph node metastasis, the primary cancer was significantly more frequently found in the oropharynx (p = .002). Patients with a p16-positive tumor had a significantly higher 5-year overall survival (OS; 33% vs 69%; p = .045, disease-free survival [DSF] 77% vs 89%; p = not significant [NS]). Patients with p16-positive neck metastasis and no detectable primary cancer had a better prognosis. Expression of EGFR in this series did not have a significant effect on prognosis., Conclusion: In patients presenting with CUP syndrome, p16 immunohistochemistry can serve to locate the primary cancer in the oropharynx. It is a positive prognostic indicator in patients with those heterogeneous cancers., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: The influence of human papillomavirus (HPV) status on survival for patients with very advanced inoperable oropharyngeal SCC treated with radiochemotherapy (RCT) was studied., Methods: Patients received either 69.2 Gy with concomitant boost (ccb) or 70 Gy conventionally fractionated (cf), weekly paclitaxel 40 mg/m(2), and carboplatin area under the concentration-time curve (AUC) 1. Tumor was analyzed for the presence of high-risk HPV-DNA using polymerase chain reaction (PCR) and direct DNA sequencing. p16-expression, survivin, and epidermal growth factor receptor (EGFR) expression were evaluated by immunohistochemistry and influence on survival was calculated., Results: Of 52 patients, 25.0% were HPV positive and 75.0% HPV negative. The 2-year progression-free survival (PFS) was 70.1% for p16-positive patients and 37.1% for p16-negative patients (p = .005). The 3-year overall survival (OS) rate was 43.9% for all patients and did not significantly differ between the groups. Neither survivin nor EGFR expression influenced PFS or OS significantly., Conclusions: HPV status influences PFS in patients with advanced, nonresectable tumor stages but not OS. Additional risk factors seem to have a stronger influence on survival than HPV status., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: To report outcome and toxicity of concurrent radiochemotherapy with carboplatin and paclitaxel in advanced squamous cell carcinomas of the oropharynx and hypopharynx., Patients and Methods: Advanced inoperable carcinomas of the oropharynx and hypopharynx were treated with either hyper-fractionated, accelerated radiotherapy (50.0 Gy/2.0 with concomitant boost to 69.2 Gy/1.6) or conventional fractionated radiotherapy (70.2-72 Gy/1.8) concurrent with paclitaxel 40 mg/m2 and carboplatin AUC 1 weekly for 6 weeks. Acute and long-term toxicity was measured according to WHO- and CTC-criteria., Results: A total of 84 patients were included between 2000 and 2008. Median follow-up time of patients alive was 36 months. Conventionally fractionated radiotherapy was given to 16 patients, while 68 patients were treated with concomitant boost. Finally, 88.1% of patients received full dose paclitaxel. Acute mucositis ≥ grade 3 was present in 51.2% of patients, while 6% of patients experienced ≥ grade 3 leucopenia and thrombopenia. A supportive gastric feeding tube was implanted in 89.1% of patients. Overall survival after 2 years was 46.3%, progression-free survival after 2 years was 41.0%. There was no significant survival difference between the different radiotherapy protocols., Conclusion: Concomitant carboplatin and paclitaxel is feasible and effective in advanced carcinomas of the head and neck.

Background: The epidermal growth factor receptor (EGFR) and the inhibitor of apoptosis protein survivin play important roles in the regulation of cellular proliferation and survival in squamous cell carcinomas. Their correlation in oropharyngeal squamous cell carcinoma (OSCC) has not been evaluated yet., Methods: In this multicenter study, we analyzed the expression of survivin and EGFR in tissue specimens from 73 selected patients with OSCC using immunohistochemistry., Results: Higher cytoplasmic survivin scores were significantly correlated with high scores of EGFR expression (p=.013). Nuclear survivin expression was associated with a poor overall survival rate with an estimated 3-year overall survival probability of 17.3% versus 87.4% for non-nuclear expression of survivin (p<.001). Multivariate analysis revealed that nuclear survivin expression was an independent negative prognostic factor (p=.008)., Conclusion: Considering the strong impact of nuclear survivin expression on survival, the survivin expression should be prospectively evaluated to select patients with an increased risk for disease recurrence., (Copyright (c) 2008 Wiley Periodicals, Inc. Head Neck 2008.)

The clinical management of patients with primary oropharyngeal squamous cell carcinoma remains controversial. The results of a combined approach involving surgery for the primary tumor, neck dissection, and postoperative radiotherapy were reviewed. A retrospective review was carried out for 211 patients meeting the inclusion criteria of resectable squamous cell carcinoma of the oropharynx. Overall survival and disease-free survival rates were calculated using the Kaplan-Meier method. Univariate (Log-rank test) and multivariate (Cox proportional hazards models) statistical analyses were carried out to investigate the role of clinical factors as significant prognostic markers. The 2- and 5-year disease-free survival rates were 79.8% and 68.8%, respectively. In univariate and multivariate analyses, positive resection margins were the only and independent significant prognostic markers for impaired disease-free survival (Log-rank: p=0.0238; Cox model: p=0.045; hazard ratio 2.48 [95% confidence interval 1.02-6.05]). In univariate analysis, male sex was the only significant negative prognostic factor for overall survival (Log-rank: p=0.0453), whereas Cox multivariate analysis identified extracapsular spread as an independent prognostics marker (p=0.049; hazard ratio 1.86 [95% confidence interval 1.00-3.43]). We conclude that the presented multimodal approach of surgery for the primary tumor and the neck followed by postoperative radio(chemo)therapy seems to be superior to non-surgical treatment protocols, as it results in better disease-free and overall survival. To assess this multimodal treatment approach, morbidity and economic considerations need to be further analyzed.

Objective/hypothesis: Tumor control and survival are considered the most important measures of treatment efficacy for patients with primary oropharyngeal squamous cell carcinoma. Furthermore, multimodal treatment protocols should be judged by their complication rates, morbidity, and therapy costs., Study Design: The results of a combined approach of primary surgery and neck dissection with postoperative radio(chemo)therapy were analyzed in retrospective chart review., Methods: Two hundred eleven patients' records were analyzed for surgical complications, therapeutic morbidity, and treatment costs., Results: The rate of postoperative hemorrhage was 4.7%. We observed no fatal complications. Ten percent of our patients required nutrition through percutaneous endoscopic gastrostomy (PEG). Twelve percent of all patients required long-term tracheostomy. The rates of PEG and tracheostomy were significantly higher in patients operated by the transcervical approach. The costs for the combined approach ranged from 10,587 euros (13,377 dollars) to 24,531 euros (30,996 dollars)., Conclusions: The presented multimodal approach provides a low rate of surgical complications and a tolerable morbidity. Considering the excellent oncologic results, this extensive and more cost-intensive multimodal approach is justified for patients with oropharyngeal cancer.

Purpose: To prove an expected benefit of concurrent radiochemotherapy (RCT), a two-arm randomized multicentric study was performed. In a subgroup analysis the influence of pretherapeutical hemoglobin level (p-Hb) on survival under locoregional control (SLC) was tested., Patients and Methods: The study included primarily untreated Stage III/IV (International Union Against Cancer [UICC]) oropharyngeal and hypopharyngeal carcinomas. Patients were randomized to receive either hyperfractionated (hf) and accelerated (acc) RCT with two cycles 5-fluorouracil (600 mg/m(2)/day) and carboplatin (70 mg/m(2)/day) on Days 1-5 and 29-33 or hf-acc radiotherapy (RT) alone. Total RT dose in both arms was 69.9 Gy in 38 days in concomitant boost technique., Results: After a median follow-up time of 57 months, SLC is significantly better in RCT than in RT (p = 0.01), with median SLC of 17 months and 11 months, respectively. Also overall survival (OS) shows a benefit for RCT (p = 0.016), with a median survival of 23 months for RCT and 16 months for RT. However, the benefit in SLC and OS is not seen in hypopharyngeal carcinomas. In a multivariate analysis of oropharyngeal cancer patients, p-Hb levels lower than 12.7 g/dL resulted in lower SLC compared with higher p-Hb levels up to 13.8 g/dL. P-Hb levels >13.8 g/dL did not further improve SLC., Conclusions: Hyperfractionated-accelerated RCT is superior to hf-acc RT in oropharyngeal carcinomas. P-Hb levels >13.8 g/dL do not further improve SLC.