Detection of antibody subclasses IgA, IgM and IgG against HPV L1 in HPV-positive oropharyngeal squamous cell carcinoma patients: a pilot study.

PURPOSE: Despite prognostic superiority of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), up to 25% of patients will suffer from recurrence within the first 5 years. Therefore, it is of great scientific interest to find relevant biomarkers to identify patients at risk. In this prospective observational study, we aimed to investigate the dynamics of HPV-L1 capsid protein specific antibody (AB) subclasses IgA, IgM, and IgG in HPV-positive OPSCC patients under therapy. METHODS: Serum samples from HPV-positive OPSCC patients, identified by positive p16-immunohistochemistry, were collected before and during tumor-specific therapy and 3-6 months during follow-up. They were analyzed for the presence of HPV-L1 AB subclasses IgA, IgM, and IgG using an HPV-L1-specific immuno-assay. Additionally, a PCR-based HPV-DNA detection from the tumor tissue was performed. RESULTS: Altogether, 33 patients with a mean follow-up of 55 months were included. Analysis of a total of 226 serum samples revealed that the most common L1-AB-subclass pattern was characterized by IgG > > IgA > IgM without significant fluctuation during the course of disease. Patients with excessive IgG levels tended to higher tumor stages and three out of three patients with disease recurrence showed increasing IgG AB titers beforehand. Seven patients showed an IgA dominance at diagnosis, which was associated with a better disease-free survival. CONCLUSION: Despite limited cases, our prospective pilot study revealed promising trends in HPV L1 AB subclasses and may contribute useful information for future risk stratification and post-treatment monitoring in HPV-positive OPSCC patients.

Endoscopic trans-sphenoidal pituitary surgery does not impact postoperative nasal quality of life.

PURPOSE: The aim of this prospective longitudinal study was to assess both subjective quality of life using questionnaires and objective examination of nasal function with regard to olfaction, nasal air flow and mucociliary clearance in patients after minimally invasive, turbinate-preserving endoscopic transnasal trans-sphenoidal pituitary surgery. METHODS: Patients undergoing endoscopic transnasal pituitary surgery were recruited prospectively and examined during three study visits, preoperatively and 3 and 6 months postoperatively. We examined nasal function using sniffin' sticks test, rhinomanometry, saccharin transit time test, and endoscopic and radiological scores. In addition, the influence on subjective quality of life and mental health was recorded using the Sinonasal-Outcome-Test-20 (SNOT-20) and the Hospital-Anxiety-and-Depression-Scale (HADS). RESULTS: 20 patients undergoing endoscopic pituitary tumor resections were included. No significant changes in olfaction or mucociliary clearance were noted. Nasal air flow showed a tendency to increase in the postoperative course lacking significance. Both the endoscopy and the radiological scores showed a significant deterioration, especially after 3 months, with a trend towards improvement over time. However, neither the SNOT-20 nor the HADS showed significant changes compared to baseline. CONCLUSIONS: Our concept of minimally invasive endoscopic tumor resections on the pituitary gland with preservation of nasal turbinates shows low morbidity for the patient. Despite objectifiable surgery-associated changes in the nose, nasal physiology in terms of smell, airflow and mucociliary clearance can be preserved and the subjective quality of life of our patients remains stable.

Trichoblastic carcinosarcoma of the neck: Case report and molecular analysis of a seldom, relapsing entity and a review of the literature.

Trichoblastic carcinosarcoma is a seldom biphasic adnexal tumor with malignant epithelial and mesenchymal components. The authors report the first tumor on the neck developed from preexistent trichoblastoma showing aggressive, recurrent behavior. An 82-year-old man presented with a solitary 3-cm exophytic lesion. Histology verified the diagnosis of trichoblastic carcinosarcoma. Four years earlier, a trichoblastic carcinoma arising in a preexisting trichoblastoma was excised at the same location. Despite successful surgical treatments, three local recurrences within 4 years were diagnosed. After the second relapse, the patient agreed on adjuvant radiation. Twelve months later, another relapse was excised in toto. In the last surgical specimen, only the mesenchymal component was found. Copy number variation analysis of the preexisting tumor and two recurrences revealed the same entity and additional chromosomal aberrations in the recurrences. Adnexal carcinosarcomas are seldom, yet presumably underdiagnosed biphasic tumors with aggressive growth potential. They should have adequate preoperative clarification with wide tumor excision, as radiosensitivity seems to be of limited effect.

Sinonasal mucosal melanoma: treatment strategies and survival rates for a rare disease entity : A single center experience and review of literature.

BACKGROUND: Sinonasal mucosal melanoma (SNMM) is a rare disease entity comprising 0.4-1.3% of all melanomas. Surgery with free margins has been the primary treatment over decades. Neither the addition of radiotherapy nor chemotherapy could significantly improve outcome rates of this devastating malignancy. This study presents our clinical experience with SNMM over a 19-year period and summarizes the current body of literature on SNMM. METHODS: This retrospective analysis included 12 patients with SNMM treated from 2001 to 2019 at an academic center. Additionally, a literature review of the last 29 years on treatment and survival data of SNMM was conducted. RESULTS: Main initial symptoms were epistaxis and nasal obstruction. Of the patients 9 underwent endoscopic surgery, 6 received adjuvant therapy. 3 patients who did not undergo surgery, received chemoradiotherapy, radiotherapy alone, and chemotherapy alone, respectively. At the time of diagnosis 2 patients had distant metastases and 4 patients developed distant metastases during the course of the disease. Mean overall survival (OS) was 30.6 months, 3­year and 5­year OS were 25%, and 18.2%, respectively. CONCLUSION: Unspecific symptoms and hidden anatomic locations lead to delayed diagnosis and increased rates of metastatic dissemination. Distant metastasis is the main treatment failure in SNMM. Surgery with free margins remains the primary treatment for SNMM. Adjuvant radiotherapy might improve local control in individual cases but efficient systemic therapy is needed to improve outcome rates. To evaluate and define more effective targeted treatment options and improve outcome rates, homogeneous data and prospective multicentric analysis are needed.

Preliminary insights into the impact of primary radiochemotherapy on the salivary microbiome in head and neck squamous cell carcinoma.

Squamous cell carcinoma is the most common type of throat cancer. Treatment options comprise surgery, radiotherapy, and/or chemo(immuno)therapy. The salivary microbiome is shaped by the disease, and likely by the treatment, resulting in side effects caused by chemoradiation that severely impair patients' well-being. High-throughput amplicon sequencing of the 16S rRNA gene provides an opportunity to investigate changes in the salivary microbiome in health and disease. In this preliminary study, we investigated alterations in the bacterial, fungal, and archaeal components of the salivary microbiome between healthy subjects and patients with head and neck squamous cell carcinoma before and close to the end point of chemoradiation ("after"). We enrolled 31 patients and 11 healthy controls, with 11 patients providing samples both before and after chemoradiation. Analysis revealed an effect on the bacterial and fungal microbiome, with a partial antagonistic reaction but no effects on the archaeal microbial community. Specifically, we observed an individual increase in Candida signatures following chemoradiation, whereas the overall diversity of the microbial and fungal signatures decreased significantly after therapy. Thus, our study indicates that the patient microbiome reacts individually to chemoradiation but has potential for future optimization of disease diagnostics and personalized treatments.

DRH1 - a novel blood-based HPV tumour marker.

BACKGROUND: To date, no studies have successfully shown that a highly specific, blood-based tumour marker to detect clinically relevant HPV-induced disease could be used for screening, monitoring therapy response or early detection of recurrence. This study aims to assess the clinical performance of a newly developed HPV16-L1 DRH1 epitope-specific serological assay. METHODS: In a multi-centre study sera of 1486 patients (301 Head and Neck Squamous Cell Carcinoma (HNSCC) patients, 12 HIV+ anal cancer patients, 80 HIV-positive patients, 29 Gardasil-9-vaccinees, 1064 healthy controls) were tested for human HPV16-L1 DRH1 antibodies. Analytical specificity was determined using WHO reference-sera for HPV16/18 and 29 pre- and post-immune sera of Gardasil-9-vaccinees. Tumour-tissue was immunochemically stained for HPV-L1-capsidprotein-expression. FINDINGS: The DRH1-competitive-serological-assay showed a sensitivity of 95% (95% CI, 77.2-99.9%) for HPV16-driven HNSCC, and 90% (95% CI, 55.5-99.7%) for HPV16-induced anal cancer in HIV-positives. Overall diagnostic specificity was 99.46% for men and 99.29% for women ≥ 30 years. After vaccination, antibody level increased from average 364 ng/ml to 37,500 ng/ml. During post-therapy-monitoring, HNSCC patients showing an antibody decrease in the range of 30-100% lived disease free over a period of up to 26 months. The increase of antibodies from 2750 to 12,000 ng/ml mirrored recurrent disease. We can also show that the L1-capsidprotein is expressed in HPV16-DNA positive tumour-tissue. INTERPRETATION: HPV16-L1 DRH1 epitope-specific antibodies are linked to HPV16-induced malignant disease. As post-treatment biomarker, the assay allows independent post-therapy monitoring as well as early diagnosis of tumour recurrence. An AUC of 0.96 indicates high sensitivity and specificity for early detection of HPV16-induced disease. FUNDING: The manufacturer provided assays free of charge.

Sex-specific differences in patients with nonmelanoma skin cancer of the pinna.

BACKGROUND: Generally, it is known that men are affected more frequently by nonmelanoma skin cancer (NMSC) than women. The aim of our study was to investigate the effect of sex on the characteristics of NMSCs of the pinna at the population that our center serves and to compare it with the international data. METHODS: We analyzed retrospectively the data of 225 patients with NMSC of the pinna. Sex-specific differences were investigated for basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) subgroups. RESULTS: The ratio of BCC to cSCC was determined in male patients at 1:1.3, in contrast in females it was identified at 4:1 (P = .001). CONCLUSION: In our study, a new aspect of the sex-dependent distribution of cSCC and BCC of the pinna was demonstrated. Women are affected four times more frequently by BCC than by cSCC, whereas in men this ratio is approximately equal.

Early effects of cigarette smoke extract on human oral keratinocytes and carcinogenesis in head and neck squamous cell carcinoma.

BACKGROUND: Cigarette smoking is a major risk factor for head and neck squamous cell carcinoma. Still, the effect of cigarette smoke on the molecular level is unclear. The aim of the present study was to investigate the early effects of cigarette smoke on carcinogenesis of head and neck squamous cell carcinoma. METHODS: Human oral keratinocytes were exposed for 1 week to standardized cigarette smoke extract, and subsequently RT-quantitative PCR array was performed. Protein expression of dysregulated genes was determined by immunohistochemistry in tissue samples of oral squamous cell carcinoma, oral leukoplakia, and tonsil mucosa. RESULTS: RT-PCR revealed upregulation of ITGA-2 and MMP-1, whereas TEK receptor tyrosine kinase was downregulated in human oral keratinocytes. ITGA-2 and MMP-1 were significantly overexpressed in tissue samples of oral squamous cell carcinoma in comparison to normal mucosa (P <.01 in all experiments). CONCLUSION: Upregulation of ITGA-2 and MMP-1 induced by cigarette smoke contributes significantly to oral carcinogenesis.

Concordance of tumor infiltrating lymphocytes, PD-L1 and p16 expression in small biopsies, resection and lymph node metastases of oropharyngeal squamous cell carcinoma.

OBJECTIVE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC), especially human papillomavirus (HPV)-associated, is increasing worldwide. Immunotherapy become available for patients with carcinomas in the head and neck region, however without ideal biomarker. Markers like PD-L1 vary in the clone of the antibody used, and the method of evaluation. Adequate and reliable immune cells characterization and evaluation is still not found. Furthermore, studies analyzing representativeness of different tissue samples are scarce. We analyzed small biopsy, lymph node (LN) metastasis and resected OPSCC, in regards of tumor infiltrating lymphocyte (TIL) density, PD-L1 and p16 expression. MATERIAL AND METHODS: Patients with OPSCC diagnosed from 2000 to 2016, with small biopsy, resection specimen and LN metastasis samples were selected. We analyzed TILs on hematoxylin-eosin stain, and PD-L1 and p16 expression in tumor cells. Concordance between different tumor locations was evaluated. RESULTS: 93 patients, with 65 small biopsies, 72 resection specimens, and 70 LN metastases were included. TILs, p16 and PD-L1 demonstrated very high concordance. Additionally, PD-L1 expression in the small biopsies was more representative of the PD-L1 expression in the resection specimens, than the LN samples. CONCLUSION: TILs density can be reliably assessed using hematoxylin-eosin stain with high concordance between the small biopsy, resection specimen and LN metastasis. Evaluation of concordance of p16 expression is very high, nevertheless some cases might be misdiagnosed on a small biopsy or lymph node metastasis. Evaluation of PD-L1 expression is very reliable on the biopsy specimen. Different PD-L1 clones and methods of evaluation still remain to be addressed.

The Pre-Treatment C-Reactive Protein Represents a Prognostic Factor in Patients with Oral and Oropharyngeal Cancer Treated with Radiotherapy.

The purpose of the present study was to evaluate the prognostic significance of the pre- treatment C-reactive protein (CRP) level in a cohort of 503 patients with oral and oropharyngeal cancer treated at a tertiary academic center between 2000 and 2017. Cancer-specific survival (CSS), overall survival (OS) and loco-regional control (LC) were calculated using Kaplan-Meier analysis. To evaluate the prognostic value of the CRP level for the clinical endpoints, univariate and multivariate Cox regression models were applied. The median follow-up period was 61 months. Patients were divided into elevated CRP (≥5 mg/L) and normal CRP groups, according to pre-treatment plasma levels. An increased CRP level was significantly associated with shorter CSS (p < 0.001, log-rank test), as well as with shorter OS (p < 0.001, log-rank test) and loco-regional control (p = 0.001, log-rank test). In addition, multivariate analysis identified CRP as an independent predictor for CSS (hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.08-2.35; p = 0.020) as well as for OS (HR 1.62, 95%CI 1.17-2.24; p = 0.004) and LC (HR 1.50, 95%CI 1.06-2.14; p = 0.023). In subgroup analysis, Kaplan Meier curves revealed that an elevated pre-treatment CRP level was a consistent prognostic factor for poor CSS (p = 0.003, log-rank test), OS (p = 0.001, log-rank test), and LC (p = 0.028, log-rank test) in patients treated with definitive (chemo-) radiotherapy, whereas a significant association in patients undergoing surgery and postoperative radiotherapy was not detected. The pre-treatment CRP level seems to represent a prognostic factor for CSS, OS, and LC in patients with oral and oropharyngeal cancer, particularly in those treated with definitive (chemo-) radiotherapy. Additional large-scale prospective studies are warranted to confirm and extend our findings.

Head and neck cancer in Styria : An epidemiologic and clinical audit.

BACKGROUND: The outcome of patients with cancer of the head and neck is significantly improved by increased interdisciplinary cooperation. The main focus of this study was a comparison of epidemiologic factors (age, sex, origin, staging) of patients with head and neck cancer in Styria, with those for patients throughout Austria. METHODS: A retrospective data analysis of collected archived tumor board protocols of the Comprehensive Cancer Center (CCC) Graz included the patient's age, sex, area of residence, TNM stage, reasons for inoperability, comorbidities and performance status by ECOG (Eastern Cooperative Oncology Group), was performed. This study focuses on 340 patients who presented with a head and neck malignancy for the first time. RESULTS: In the period from January 2014 to December 2015 a total of 252 men (74.1%) and 88 women (25.9%) with malignant head and neck tumors, were presented in the tumor board for the first time. The mean age at diagnosis was 63.4 years. In 45.5% the patients already demonstrated advanced tumor stages (T4 = 27.9%, T3 = 17.6%). Most newly diagnosed neoplasms were cancers of the oropharynx (24.1%), larynx (19.4%) and oral cavity (18.8%) and 36.5% were considered to be inoperable. Curative and palliative treatments were initiated in 83.2% and 16.9%, respectively. CONCLUSION: The region of south Styria showed a higher incidence of T3 and T4 tumors of the oropharynx than the average Austrian population. Measures to increase awareness of this problem should be initiated to support general otorhinolaryngologists and general practitioners in detecting oropharyngeal cancers at an earlier stage.

Interposition of Retrosternal Pedicled Jejunum After Hypopharyngolaryngo-Esophagogastrectomy.

Reconstruction of the upper gastrointestinal tract presents a surgical challenge after esophagogastrectomy, especially when it includes hypopharyngolaryngectomy. Reconstruction is generally undertaken with interposed colon as a substitute conduit, but it carries several risks. Alternative reconstruction of the foregut with pedicled retrosternal jejunum anastomosed at the level of the base of the tongue is described.

Surgical quality assurance in head and neck cancer trials: an EORTC Head and Neck Cancer Group position paper based on the EORTC 1420 'Best of' and 24954 'larynx preservation' study.

Quality improvement of care for patients with head and neck cancer remains a constant objective for the multidisciplinary team of physicians managing these patients. The purpose of quality assurance (QA) for head and neck surgical oncology and surgical trials however differs. While QA for the general head and neck patient aims to improve global outcome through structural changes of health-care systems, QA for surgical trials pursues the goal to help providing meaningful results from a clinical trial through the definition of structure, process and outcome measures within the trial. Establishing a QA program for surgical trials is challenging largely due to the variation in the execution of surgical techniques. Within this article, we describe the surgical QA program, which was developed for the phase III European Organisation for Research and Treatment of Cancer (EORTC) 1420 study, a trial assessing swallowing function after transoral surgery compared with radiation therapy. We propose based on our experience to further develop surgical QA for surgical clinical trials by introducing two separate components, one adaptable and one non-adaptable. The adaptable is tailored to the scientific question and specific procedure; the non-adaptable consists of minimal structural requirements of the clinical unit to participate in surgical trials at EORTC as well as guidelines and incentives for protocol adherence based on our experience in EORTC 24954. Finally, we strongly believe that surgical QA designed for clinical trials may serve as a basis for the development of QA surgical guidelines in clinical practice.

Comparative Analysis of Clinical and Pathological Lymph Node Staging Data in Head and Neck Squamous Cell Carcinoma Patients Treated at the General Hospital Vienna.

BACKGROUND: Results from publications evaluating discrepancies between clinical staging data in relation to pathological findings demonstrate that a significant number of head and neck squamous cell carcinoma (HNSCC) patients are not correctly staged. The aim of this retrospective study was to analyze potential discrepancies of radiological assessment versus pathological data of regional lymph node involvement and to compare the results with data published in the literature. PATIENTS AND METHODS: In a retrospective analysis we focused on patients with HNSCC routinely treated by surgery plus postoperative radiotherapy between 2002 and 2012. For inclusion, complete pre-operative clinical staging information with lymph node status and patho-histological information on involved lymph node regions as well as survival outcome data were mandatory. We included 87 patients (UICC stage III-IV 90.8%) for which the aforementioned data obtained by CT or MRI were available. Overall survival rates were estimated by the Kaplan-Meier method. The Pearson correlation coefficient and Spearman's rank correlation coefficient (non-linear relationship) was calculated. RESULTS: Discrepancies at the level of overall tumour stage assessment were noticed in 27.5% of all cases. Thereof, 5.7% were assigned to patho-histological up-staging or down-staging of the primary tumour. At the lymph node level, 11.5% of the patients were downstaged, and 10.3% were upstaged. CONCLUSIONS: The study showed that in approximately one-fifth (21.8%) of the patients, lymph node assessment by CT or MRI differs from the pathologic staging, an outcome that corresponds well with those published by several other groups in this field.

6-shogaol induces apoptosis and enhances radiosensitivity in head and neck squamous cell carcinoma cell lines.

Ginger (Zingiber officinale Roscoe) is used for a wide array of conditions in traditional medicine in Asia, but little is known about the effect on head and neck cancer. In this study, the effect of two major pharmacologically active compounds of ginger, 6-gingerol and 6-shogaol, were studied on head and neck cancer cell lines. Furthermore, experiments in combination with established treatment methods for head and neck cancer were performed. Proliferation assays showed a dose-dependent reduction of cell viability. Flow cytometry analysis revealed the induction of apoptosis. Western blot analysis indicated that the antiapoptotic protein survivin was suppressed after treatment. Although a combination of 6-shogaol with cisplatin exhibited no synergistic effect, the combination with irradiation showed a synergistic reduction of clonogenic survival. In conclusion, ginger compounds have many noteworthy effects on head and neck cancer cell lines. In particular, the enhancement of radiosensitivity is remarkable.

The salivary microbiome as an indicator of carcinogenesis in patients with oropharyngeal squamous cell carcinoma: A pilot study.

This study aimed to undertake an initial, comparative analysis of the oral salivary microbiome of patients with oral and oropharyngeal squamous cell carcinoma versus healthy controls. This project, conceived as a pilot study, included 11 patients (1 female, 10 male, mean age 61.6 yrs., SD = 8.2 yrs.) and 11 healthy controls (1 female, 10 male, mean age 46.7 yrs., SD = 15.1 yrs.). Samples of saliva were analysed by high-throughput sequencing of the 16S rRNA gene using the MiSeq platform. Sequence data revealed microbial changes that may mirror disease progression and reflect clinical preconditions such as age, alcohol consumption, tumour size, lymph node status, smoking habit, and tumour HPV-positivity. Consequently, mapping microbial changes in patients with oral and oropharyngeal squamous cell carcinomas might improve our understanding of the pathobiology of the disease, and help in the design of novel diagnostic and treatment strategies.

Effect of thymoquinone on head and neck squamous cell carcinoma cells in vitro: Synergism with radiation.

Thymoquinone (TQ) is the main bioactive constituent present in black seed oil (Nigella sativa); it has shown anti-inflammatory and anti-neoplastic effects in various cancer cell types. The aim of the present study was to investigate the effects of TQ on head and neck squamous cell carcinoma (HNSCC) cell lines, on its own and in combination with radiation and cisplatin, respectively. The SCC25 and CAL27 HNSCC cell lines were treated with TQ alone and in combination with cisplatin or radiation, respectively. Proliferation assays and clonogenic assays were performed. Apoptosis was detected by flow cytometry. TQ exhibited dose-dependent cytotoxicity via apoptosis in the investigated cell lines. In combination with cisplatin, TQ resulted in no significant increase in cytotoxicity. Combined with radiation, TQ significantly reduced clonogenic survival compared with each treatment method alone. TQ is a promising agent in the treatment of head and neck cancer due to its anti-proliferative and radiosensitizing properties. However, the combination of TQ with cisplatin showed no therapeutic benefit in vitro.

Role of cancer stem-cell marker doublecortin-like kinase 1 in head and neck squamous cell carcinoma.

BACKGROUND: So far, no data is available on the role of the tumor stem cell marker doublecortin-like kinase 1 (DCLK1) in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to evaluate DCLK1 expression in HNSCC patients that underwent surgery and postoperative radiotherapy, and to assess its potential as a therapeutic target in vitro. METHODS: We immunohistochemically stained for DCLK1 in 127 sections of HNSCC samples obtained during surgery of HNSCC patients and correlated the expression to patients' overall- and disease-free survival, as well as human papilloma virus (HPV) status. Additionally, we compared our survival data with data obtained from The Cancer Genome Atlas (TCGA). The effects of the DCLK1 inhibitor LRRK-2-in-1 on HNSCC cell lines alone and in combination with irradiation. RESULTS: Expression of DCLK1 in 127 patients was associated with poor survival. In particular, DCLK1 expression had a significant impact on survival of oropharyngeal carcinoma patients. Specifically, DCLK1+/HPV- patients had the worst prognosis after simultaneous assessment of DCLK1 and HPV status in comparison to the other three possible DCLK1/HPV constellations. Higher levels of DCLK1 mRNA were also associated with poor clinical outcome. Inhibition of DCLK1 in our HNSCC cell lines led to growth arrest and induction of apoptosis. The combination of DCLK1 inhibition with irradiation had a synergistic effect. CONCLUSION: Firstly, DCLK1 is a prognostic biomarker for shortened survival. Secondly, through inhibition of DCLK1, it may serve as a therapeutic target as well.

A 5­year update of patients with HPV positive versus negative oropharyngeal cancer after radiochemotherapy in Austria.

BACKGROUND: After publishing promising results for the treatment of patients with human papilloma virus (HPV) positive oropharyngeal cancer with radiochemotherapy regarding 2­year survival, we present an update of the disease-specific and disease-free survival after 5 years. PATIENTS AND METHODS: A total of 29 patients of which 18 were HPV negative and 11 HPV positive with squamous cell carcinoma of the oropharynx received radiation therapy with or without chemotherapy (cisplatin) or immunotherapy (cetuximab) between 2007 and 2009. At time of the present analysis, six patients are still alive including four with HPV positive and two with HPV negative oropharyngeal carcinoma, while 15 out of 16 patients with HPV negative tumors died and 1 died of another cause with evidence of disease. RESULTS: Since the 2­year disease-specific survival of patients with HPV positive cancer of the oropharynx was published with 100% versus 30.4% in HPV negative tumors, we now present the 5­year disease-specific survival after treatment, which was 85.7% in HPV positive versus 11.1% in HPV negative patients. CONCLUSION: We present the results of patients receiving radiochemo(immuno)therapy for oropharyngeal cancer regarding the HPV status, which is still promising.