Endoscopic management of sinonasal tumours in the Nordic university hospitals: a survey.

PURPOSE: The Nordic countries (27 M) all have comparable, publicly funded healthcare systems, and the management of sinonasal tumours is centralised to the 21 university hospitals. We sought to assess and compare the treatment practice of sinonasal tumours across the Nordic countries. METHODS: A web-based questionnaire was sent to all university hospital departments of otorhinolaryngology-head and neck surgery in the Nordic countries. RESULTS: Answers were obtained from all 21 Nordic university hospitals. The endoscopic approach was widely utilised by all, with most (62%) centres reporting 3-4 surgeons performing endoscopic sinonasal tumour surgery. Finland reported the lowest rates of centralisation among university hospitals despite having the highest number of 0.1-1 M catchment population hospitals. Most centres (88%) opted for the endoscopic approach in a patient case warranting medial maxillectomy. In a case of a Kadish C esthesioneuroblastoma, most (52%) of the centres preferred an endoscopic approach. Most centres (62%) reported favouring the endoscopic approach in a case describing a juvenile angiofibroma. Regarding a case describing a sinonasal undifferentiated carcinoma, consensus was tied (38% vs. 38%) between endoscopic resection followed by postoperative (chemo)radiotherapy (RT/CRT) and induction chemotherapy followed by RT/CRT or surgery followed by RT/CRT. CONCLUSION: Endoscopic approach was widely utilised in the Nordic countries. The case-based replies showed differences in treatment practice, both internationally and nationally. The rate of centralisation among university hospitals remains relatively low, despite the rarity of these tumours.

Occupational risk variation of nasopharyngeal cancer in the Nordic countries.

BACKGROUND: The aim of this study was to estimate occupational risk variation in the incidence of nasopharyngeal cancer (NPC) in a large population-based cohort of the Nordic Occupational Cancer (NOCCA) study. METHODS: This study is based on a cohort of almost 15 million persons from Denmark, Finland, Iceland, Norway and Sweden, with 2898 nasopharyngeal cancer cases diagnosed in 1961-2005. The data on occupations were gathered from population censuses and cancer data from the national cancer registries. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were estimated using the national NPC incidence rates as the reference. RESULTS: There were 1980 male and 918 female NPC patients. The highest SIRs of NPC were observed among male waiters (SIR 3.69, 95% CI 1.91-6.45) and cooks and stewards (SIR 2.24, 95% CI 1.16-3.91). Among women, launderers had the highest SIR of NPC (2.04, 95% CI 1.02-3.65). Significantly decreased SIRs were found among male farmers (SIR 0.79, 95% CI 0.68-0.92) and male textile workers (SIR 0.49, 95% CI 0.22-0.93). CONCLUSIONS: This study suggests that NPC may be associated with several work-related exposure agents such as smoking, kitchen air pollution and solvents. In future, occupational exposure-risk relations should be studied to understand more about causality and to assess effective prevention strategies.

Base of tongue squamous cell carcinomas, outcome depending on treatment strategy and p16 status. A population-based study from the Swedish Head and Neck Cancer Register.

BACKGROUND: The base of tongue squamous cell carcinoma (BOTSCC) is mainly an HPV-related tumor. Radiotherapy (EBRT) ± concomitant chemotherapy (CT) is the backbone of the curatively intended treatment, with brachytherapy (BT) boost as an option. With four different treatment strategies in Sweden, a retrospective study based on the population-based Swedish Head and Neck Cancer Register (SweHNCR) was initiated. MATERIAL AND METHODS: Data on tumors, treatment and outcomes in patients with BOTSCC treated between 2008 and 2014 were validated through medical records and updated as needed. Data on p16 status were updated or completed with immunohistochemical analysis of archived tumor material. Tumors were reclassified according to the UICC 8th edition. RESULTS: Treatment was EBRT, EBRT + CT, EBRT + BT or EBRT + CT + BT in 151, 145, 82 and 167 patients respectively (n = 545). A p16 analysis was available in 414 cases; 338 were p16+ and 76 p16-. 5-year overall survival (OS) was 68% (95% CI: 64-72%), with76% and 37% for p16+ patients and p16- patients, respectively. An increase in OS was found with the addition of CT to EBRT for patients with p16+ tumors, stages II-III, but for patients with tumor stage I, p16+ (UICC 8) none of the treatment strategies was superior to EBRT alone. CONCLUSION: In the present retrospective population-based study of BOTSCC brachytherapy was found to be of no beneficial value in curatively intended treatment. An increase in survival was found for EBRT + CT compared to EBRT alone in patients with advanced cases, stages II and III (UICC 8), but none of the regimes was significantly superior to EBRT as a single treatment modality for stage I (UICC 8), provided there was p16 positivity in the tumor. In the small group of patients with p16- tumors, a poorer prognosis was found, but the small sample size did not allow any comparisons between different treatment strategies.

Enteral tube feeding of head and neck cancer patients undergoing definitive chemoradiotherapy in the Nordic Countries: Survey of the Scandinavian Society for Head and Neck Oncology.

PURPOSE: We assessed current policies and perceptions of enteral tube feeding in head and neck cancer (HNC) patients undergoing chemoradiotherapy (CRT). A web-based survey was used to compare the timing and method of tube feeding within and between the five Nordic countries, covering a population of 27 million. METHODS: From each of the 21 Nordic university hospitals, one oncologist and one otorhinolaryngology-head and neck (ORL-HN) surgeon responded to a survey. The respondents were asked whether tube insertion before the onset of CRT, or during CRT as required (prophylactic vs. reactive) was preferred. The use of a pretreatment nutritional screening tool and the choice of feeding route (nasogastric vs. gastrostomy tube) were assessed. In total, we analyzed responses from 21 oncologists and 21 ORL-HN surgeons. RESULTS: A tendency was observed towards decreasing the use of a PEG tube. Of the 21 university hospitals, only 2 (10%) reported using a prophylactic PEG tube in over half of HNC patients undergoing definitive CRT. The preferred method for reactive tube feeding was by a NG tube in 14 of 21 (67%), and by a PEG in 7 of 21 (33%). In general, both oncologists and ORL-HN surgeons were content with their current policy. CONCLUSIONS: The practices for enteral tube feeding in HNC management vary within and between the Nordic countries. We suggest that unified protocols for tube feeding should be developed for this patient population.

Incidence of IP and risk of malignant transformation in the Swedish population 1960-2010.

The true incidence of inverted papilloma (IP) is not yet known. From hospital-based studies, its incidence has been estimated to approximately 0.5/100,000 person years. Earlier hospital case studies have shown that IP can undergo a malignant transformation in 1-53 %. The frequency of its malignant transformation on a population basis is unknown. To our knowledge, no standardised incidence ratio (SIR) has been reported for malignancies among IPs. This study aims to investigate these incidences on a population basis. Using the data from the Swedish Cancer Registry (SCR), we have identified patients with IP and patients with Squamous Cell Carcinoma (SCC) diagnosed between 1960 and 2010 in Sweden. Incidence of IP and incidence of SCC among patients with IP and SIR were analyzed. Eight hundred and fourteen patients with IP were identified. The incidence of IPs reported to the SCR increased from 1960 to 2010. In this cohort, SCC was overrepresented, as compared with the general population. The incidence of IP in the Swedish population seems to have increased.

Cancer of the gingiva.

Cancer of the gingiva is a rare disease in the Western World. It most commonly affects elderly population. Because of its rarity, the reporting on the disease is sparse and often grouped with other subsites of oral cancer, which makes conclusions difficult to interpret. The aim of this paper is to review the literature on gingival cancer as a specific subsite of oral cancer and report on published prognostic factors as well as treatment of local and regional disease. We also present differences between gingival cancer subgroups, mandibular and maxillary gingival cancer. In addition, both surgical and oncological treatments are reviewed. It seems that surgery is the preferred initial treatment approach for the majority of patients with gingival cancer, although adjuvant radiation, with or without chemotherapy, is commonly recommended to increase locoregional control.

Quantification of Trapezius Muscle Innervation During Neck Dissections: Cervical Plexus Versus the Spinal Accessory Nerve.

OBJECTIVES: Despite increasing use of selective, nerve-sparing surgical techniques during neck dissections, the reported rate of postoperative paralysis of the trapezius muscle is still high. The aim of the study is to measure and compare motor inflow to the trapezius muscle, in order to better understand the peripheral neuroanatomy. METHODS: Intraoperative nerve monitoring (electroneurography) in patients undergoing routine neck dissection (n=18). The innervation of the 3 functional parts of the trapezius muscle was mapped and quantified through compound muscle action potentials. RESULTS: In 18/18 (100%) of the patients, the spinal accessory nerve (SAN) innervated all parts of the trapezius muscle. In 7/18 (39%) of the patients, an active motor branch from the cervical plexus was detected, equally distributed to all functional parts of the trapezius muscle, at levels comparable to the SAN. CONCLUSIONS: Compared to the SAN, branches from cervical plexus provide a significant amount of neural input to all parts of the trapezius muscle. Intraoperative nerve monitoring can be used in routine neck dissections to detect these branches, which may be important following surgical injury to the SAN.

Sinonasal malignancies in Sweden 1960-2010; a nationwide study of the Swedish population.

INTRODUCTION: Sinonasal malignancies (SNM) are rare and the prognosis is generally poor. Recently, a change in incidence for SNM has been reported. In this study, we investigated population-based trends for SNM in Sweden. METHODS: We identified 3,221 patients from the Swedish National Cancer Registry diagnosed with primary malignancies arising from the nasal cavity, paranasal sinuses, or both, during the period 1960 through 2010. Incidence, gender and age, anatomical sites and relative survival were investigated. RESULTS: The incidence for SNM decreased except for sinonasal malignant melanoma (SNMM) and adenoid cystic cancer (even though a very small group) during the study period. More than 50 % of the malignancies involved the nasal cavity. The five-year relative survival was highest for adenoid cystic cancer followed by adenocarcinoma. SNMM and undifferentiated carcinoma had the poorest prognosis. CONCLUSION: We found that the incidence for SNM has decreased during the study period 1960 through 2010, except for SNMM that has increased.

The human carotid body releases acetylcholine, ATP and cytokines during hypoxia.

Studies on experimental animals established that the carotid bodies are sensory organs for detecting arterial blood O2 levels and that the ensuing chemosensory reflex is a major regulator of cardiorespiratory functions during hypoxia. However, little information is available on the human carotid body responses to hypoxia. The present study was performed on human carotid bodies obtained from surgical patients undergoing elective head and neck cancer surgery. Our results show that exposing carotid body slices to hypoxia for a period as brief as 5 min markedly facilitates the release of ACh and ATP. Furthermore, prolonged hypoxia for 1 h induces an increased release of interleukin (IL)-1ß, IL-4, IL-6, IL-8 and IL-10. Immunohistochemical analysis revealed that type 1 cells of the human carotid body express an array of cytokine receptors as well as hypoxia-inducible factor-1α and hypoxia-inducible factor-2α. Taken together, these results demonstrate that ACh and ATP are released from the human carotid body in response to hypoxia, suggesting that these neurotransmitters, as in several experimental animal models, play a role in hypoxic signalling also in the human carotid body. The finding that the human carotid body releases cytokines in response to hypoxia adds to the growing body of information suggesting that the carotid body may play a role in detecting inflammation, providing a link between the immune system and the nervous system.

Distribution of sentinel nodes from parotid tumors-A feasibility study.

BACKGROUND: Optimum management of the N0 neck is unresolved in parotid salivary gland cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis and its´ clinical use is increasing for head and neck tumors. The object of this study was to establish whether the technique is applicable to detect distribution of sentinel nodes for parotid tumors. MATERIALS AND METHODS: Prosepective observational study in 30 patients with benign or low-grade T1-T2N0 malignant tumors in the parotid gland planned for surgical treatment. Distribution of SN was detected with a preoperative ultrasound-guided peritumoral injection with a technetium-99 (Tc-99 m) laballed tracer followed by a SPECT-CT and intraoperative measurement in the neck and parotidal tissue. In patients with cytologically suspected malignant tumor or highly unclerar cytology, SNB was also performed. RESULTS: Sentinel nodes (SNs) were detected in 26/30 cases. Out of these, 7 presented with only one SN, whereas multiple sentinel nodes where detected in 19 cases. No SNs were found in neck level 1. SN was detected in level 5 independent of tumor location within the parotid gland. An intraparotidal distribution of SNs was more frequent in larger tumors. CONCLUSIONS: The use of SN-technique in the planning of surgical treatment of parotid tumors seems feasible. It may be of clinical value for patients with parotid cancer to enable a more accurate staging and to detect occult metastasis in the SNs within the parotid as well as in the neck, enabaling the possibility to surgically remove all positive SNs at primary surgery and with reduced surgical morbidity.

Treatment and outcome among patients with laryngeal squamous cell carcinoma in Stockholm-A population-based study.

Objective: Survival of patients with advanced laryngeal squamous cell carcinoma (LSCC) remains poor and management protocols warrant further development. We thus investigated treatment and outcome-related factors for LSCC in Stockholm, Sweden. Methods: In a retrospective setting, 520 patients with LSCC diagnosed during 2000-2014, were included. Data on stage, treatment, and outcome were correlated with recurrence-free and overall survival (RFS and OS, respectively). Results: Five-year OS for all patients was 65%. Five-year RFS for T1a, T1b, T2, T3, and T4 glottic LSCC was 90%, 91%, 77%, 47%, and 80%, respectively. The corresponding figures for T1, T2, T3, and T4 supraglottic LSCC were 64%, 66%, 64%, and 86%. Conclusion: Patients with a T3 glottic LSCC had unexpectedly poor survival, especially when compared with patients with a T4 tumor. Patients with T4 disease were primarily treated with laryngectomy and postoperative radiotherapy (RT)/chemoradiotherapy (CRT), while most patients with T3 LSCC were treated with RT/CRT.

Radiotherapy-Dose Escalated for Large Volume Primary Tumors-And Cetuximab with or without Induction Chemotherapy for HPV Associated Squamous Cell Carcinoma of the Head and Neck-A Randomized Phase II Trial.

The leading cause of death for patients with HPV associated squamous cell carcinoma of the head and neck (SCCHN) after treatment with chemoradiotherapy (CRT) nowadays is peripheral metastasis. This study investigated whether induction chemotherapy (IC) could improve progression free survival (PFS) and impact on relapse pattern after CRT. METHODS: Eligible patients in this multicenter, randomized, controlled, phase 2 trial had p16-positive locoregionally advanced SCCHN. Patients were randomized in a 1:1 ratio to either RT with cetuximab (arm B) versus the same regimen preceded by two cycles of taxotere/cisplatin/5-FU (arm A). The RT dose was escalated to 74.8 Gy for large volume primary tumors. Eligibility criteria included patients of 18-75 years, an ECOG performance status 0-1, and adequate organ functions. RESULTS: From January 2011 to February 2016, 152 patients, all with oropharyngeal tumors were enrolled, 77 in arm A and 75 in arm B. Two patients, one in each group, withdrew their consent after randomization, leaving 150 patients for the ITT analysis. PFS at 2 years was 84.2% (95% CI 76.4-92.8) in arm A and 78.4% (95% CI 69.5-88.3) in arm B (HR 1.39, 95% CI 0.69-2.79, p = 0.40). At the time of analysis, there were 26 disease failures, 9 in arm A and 17 in arm B. In arm A, 3 patients had local, 2 regional, and 4 distant relapses as first sites of recurrence, and in arm B, 4, 4, and 9 relapses in corresponding sites. Eight out of 26 patients with disease progression had salvage therapy and 7 were alive NED (no evidence of disease), at 2 years. Locoregional control was 96% in arm A and 97.3% in arm B and OS 93% and 90.5%, respectively. Local failure as first site of recurrence was low, in 4.6% of patients and was similar for T1/T2 and T3/T4 tumors (n.s). Nevertheless, out of 7 patients with primary local failures, 4 were treated with the escalated RT dose. Toxicity was low and similar in the treatment arms. There was one fatal event in arm A where the combined effects of the drugs used in chemotherapy and cetuximab could not be ruled out. CONCLUSIONS: PFS, locoregional control and toxicity did not differ between the two arms, OS was high, and there were few local relapses. In arm B, more than twice as many patients had distant metastasis as the first site of relapse compared to arm A. The response to IC was found to define 29% of patients in arm A who did not have a tumor relapse during follow-up. An escalated dose of 74.8 Gy could mitigate the negative impact of large tumor volume but for some patients, even this intensified treatment was insufficient.

Post-Treatment Neck Dissection of Tonsillar and Base of Tongue Squamous Cell Carcinoma in the Era of PET-CT, HPV, and p16.

Human-papillomavirus (HPV)-positive tonsillar and base of tongue carcinomas (TSCC/BOTSCC) are rising in incidence and treatments with radiotherapy, chemoradiotherapy (RT/CRT), and neck dissections (NDs) have several side effects. Therefore, an improved selection of patients needing salvage NDs would be beneficial. We examined the prevalence and localisations of viable tumour cells in neck lymph nodes in patients post-RT/CRT, identified by fluorodeoxyglucose positron-emission tomography with computer-tomography (FDG PET-CT), with a focus on HPV-associated tumours. Patients with 217 TSCC/BOTSCC with tumours assessed for HPV-DNA and p16INK4a undergoing FDG PET-CT 12 weeks after treatment and/or an ND were included. The FDG PET-CT data were compared with the findings in the pathology report after the ND. In total, 36/217 (17%) patients were selected for an ND due to positive findings in post-treatment FDG PET-CT. Of these, 35/36 were HPV-associated, 10/36 (28%) had viable tumour cells in the pathology reports of the neck specimen, and 8/10 (80%) were consistent with the FDG PET-CT findings, while 2/36 (5%) were missed by FDG PET-CT. We conclude that FDG PET-CT 12 weeks after RT/CRT is useful, but not completely reliable for finding all the metastases of HPV-associated TSCC/BOTSCC. Nonetheless, our data indicate that an ND could be more selectively guided by FDG PET-CT.

Prevalence of cystic metastases in a consecutive cohort of surgically removed branchial cleft cysts.

BACKGROUND: Solitary cystic lesion of the neck may often be the only initial presenting symptom for branchial cleft cysts and cystic metastases. AIMS/OBJECTIVES: To analyse the malignancy rate detected in patients undergoing surgical treatment for lateral branchial cleft cyst. MATERIAL AND METHODS: The records of all patients with surgical procedure code ENB40 (Excision of lateral branchial cleft cyst- or fistula) between 2003 and 2019 were reviewed. After excluding 150 patients, 436 patients were included for final analysis. Re-evaluation of the cytology including HPV-analysis was performed in those who had a malignant cyst. RESULTS: Cystic metastases were demonstrated histologically after surgical excision in 13 patients (3%). In patients over 18 years of age, the prevalence of cystic metastasis regardless of the primary tumour type was 3.3%. CONCLUSION AND SIGNIFICANCE: When the investigation protocol for solitary cystic lesions of the neck is followed, the negative predictive value for malignancy is 97%. All adult patients with a cytologic verified diagnosis of branchial cyst should be examined with HPV-analysis of the cystic sample before excision of the cyst. Failure of predicting a malignancy is often associated with cytology of poor cellularity which may be improved by more frequent use of ultrasound guided fine-needle aspiration cytology (FNAC).

Long-Term Survival and Recurrence in Oropharyngeal Squamous Cell Carcinoma in Relation to Subsites, HPV, and p16-Status.

Long-term survival data in relation to sub-sites, human papillomavirus (HPV), and p16INK4a (p16) for patients with oropharyngeal squamous cell carcinoma (OPSCC) is still sparse. Furthermore, reports have indicated atypical and late recurrences for patients with HPV and p16 positive OPSCC. Therefore, we assessed long-term survival and recurrence in relation to oropharyngeal subsite and HPV/p16 status. A total of 529 patients with OPSCC, diagnosed in the period 2000-2010, with known HPVDNA and p16-status, were included. HPV/p16 status and sub-sites were correlated to disease-free and overall survival (DFS and OS respectively). The overexpression of p16 (p16+) is associated with significantly better long-term OS and DFS in tonsillar and base of tongue carcinomas (TSCC/BOTSCC), but not in patients with other OPSCC. Patients with HPVDNA+/p16+ TSCC/BOTSCC presented better OS and DFS compared to those with HPVDNA-/p16- tumors, while those with HPVDNA-/p16+ cancer had an intermediate survival. Late recurrences were rare, and significantly more frequent in patients with p16- tumors, while the prognosis after relapse was poor independent of HPVDNA+/-/p16+/- status. In conclusion, patients with p16+ OPSCC do not have more late recurrences than p16-, and a clear prognostic value of p16+ was only observed in TSCC/BOTSCC. Finally, the combination of HPVDNA and p16 provided superior prognostic information compared to p16 alone in TSCC/BOTSCC.

Tonsillar Microbiota: a Cross-Sectional Study of Patients with Chronic Tonsillitis or Tonsillar Hypertrophy.

Chronic tonsillitis (CT) and tonsillar hypertrophy (TH) are common tonsillar diseases that are related to infection and inflammation. Little is known about tonsillar microbiota and its role in CT and TH. This study aims to identify palatine tonsillar microbiota both on the surface and in the core tissues of CT and TH patients. In total, 22 palatine tonsils were removed and collected from CT and TH patients who underwent surgery. The surface and core microbiota in the tonsils of CT and TH patients were compared using 16S rRNA gene sequencing of V3-V4 regions. Differential tonsillar microbiotas were found in the CT versus TH patients and surface versus core tissues. Further, a higher relative abundance of bacterial genera, including Haemophilus, Streptococcus, Neisseria, Capnocytophaga, Kingella, Moraxella, and Lachnospiraceae [G-2] in patients with TH and Dialister, Parvimonas, Bacteroidales [G-2], Aggregatibacter, and Atopobium in patients with CT, was observed. Of these, the differential genera of Dialister, Parvimonas, and Neisseria served as key factors in the tonsillar microbiota network. Notably, four representable tonsillar microbial types were identified, with one, consisting of a higher abundance of Haemophilus and Neisseria, exclusively detected in the TH patients. This study analyzed the different tonsillar microbiota from the surface and core tissues of CT and TH patients. Several bacteria and various microbial types related to CT and TH were identified, along with potential bacterial networks and related immune pathways.IMPORTANCE The human microbiota has been shown to be functionally connected to infectious and inflammation-related diseases. So far, only limited studies had been performed on tonsillar microbiota, although tonsils play an essential role in the human immune defense system and encountered numerous microorganisms. Our work presented different tonsillar microbiota from surface and core tissues of chronic tonsillitis (CT) and tonsillar hypertrophy (TH) patients. Notably, one tonsillar microbiota type, which contains a higher abundance of Haemophilus and Neisseria, was only detected in the TH patients. Furthermore, certain bacteria, such as Haemophilus, Neisseria, Dialister, and Parvimonas, may serve as microbial biomarkers to discriminate CT patients from TH patients. These data provide important microbiota data in the tonsillar research area and are highly useful for researchers both in the oral microbiome field and clinical field.

ARTSCAN III: A Randomized Phase III Study Comparing Chemoradiotherapy With Cisplatin Versus Cetuximab in Patients With Locoregionally Advanced Head and Neck Squamous Cell Cancer.

PURPOSE: We performed an open-label randomized controlled phase III study comparing treatment outcome and toxicity between radiotherapy (RT) with concomitant cisplatin versus concomitant cetuximab in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC; stage III-IV according to the Union for International Cancer Control TNM classification, 7th edition). MATERIALS AND METHODS: Eligible patients were randomly assigned 1:1 to receive either intravenous cetuximab 400 mg/m2 1 week before start of RT followed by 250 mg/m2/wk, or weekly intravenous cisplatin 40 mg/m2, during RT. RT was conventionally fractionated. Patients with T3-T4 tumors underwent a second random assignment 1:1 between standard RT dose 68.0 Gy to the primary tumor or dose escalation to 73.1 Gy. Primary end point was overall survival (OS) evaluated using adjusted Cox regression analysis. Secondary end points were locoregional control, local control with dose-escalated RT, pattern of failure, and adverse effects. RESULTS: Study inclusion was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. At 3 years, OS was 88% (95% CI, 83% to 94%) and 78% (95% CI, 71% to 85%) in the cisplatin and cetuximab groups, respectively (adjusted hazard ratio, 1.63; 95% CI, 0.93 to 2.86; P = .086). The cumulative incidence of locoregional failures at 3 years was 23% (95% CI, 16% to 31%) compared with 9% (95% CI, 4% to 14%) in the cetuximab versus the cisplatin group (Gray's test P = .0036). The cumulative incidence of distant failures did not differ between the treatment groups. Dose escalation in T3-T4 tumors did not increase local control. CONCLUSION: Cetuximab is inferior to cisplatin regarding locoregional control for concomitant treatment with RT in patients with locoregionally advanced HNSCC. Additional studies are needed to identify possible subgroups that still may benefit from concomitant cetuximab treatment.

Survival of patients with oropharyngeal squamous cell carcinomas (OPSCC) in relation to TNM 8 - Risk of incorrect downstaging of HPV-mediated non-tonsillar, non-base of tongue carcinomas.

BACKGROUND: TNM-8 staging separates oropharyngeal squamous cell carcinomas (OPSCC) into human papillomavirus (HPV)-mediated and -unrelated OPSCC based on p16INK4a overexpression (p16+), as surrogate marker for HPV. However, OPSCC is histologically and clinically heterogenous including tonsillar and base of tongue squamous cell carcinomas (TSCC and BOTSCC respectively), and carcinomas of soft palate and walls (otherOPSCC). The significance of HPV is established in TSCC/BOTSCC, while its role in otherOPSCC is unclear, which is not considered in TNM-8. Here, p16+ was therefore evaluated in relation to overall survival (OS) and tumor stage per OPSCC subsite. PATIENTS AND METHODS: All 932 patients, treated with curative intent in Stockholm 2000-2016 with OPSCC, previously analyzed for p16 expression, were included. Clinical data, including stage and OS, was collected retrospectively. RESULTS: Patients with p16+ otherOPSCC had significantly poorer OS compared to patients with p16+ TSCC/BOTSCC (p = 0.005) and their survival was similar to that of patients with p16-otherOPSCC/TSCC/BOTSCC. Moreover, patients with TNM-8 stage I-II and p16+ otherOPSCC had a significant poorer OS compared to patients with p16+ TSCC/BOTSCC and similar stage (p = 0.02). Lastly, patients with otherOPSCC and low TNM-7 stage had a significant better OS, as compared to those with a high stage (p = 0.019) while no hazard discrimination was observed with TNM-7 in TSCC/BOTSCC. CONCLUSION: Our results indicate a risk of misclassification of patients with otherOPSCC and low TNM-8 stage. We suggest that p16 should only be evaluated in TSCC/BOTSCC and that patients with otherOPSCC should all be staged as patients with HPV-unrelated (p16-) OPSCC.