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Purpose: To study the 10-year overall survival predictions, and mechanisms behind, of head and neck (HN) quality of life (QoL) scores obtained at diagnosis and 6, 9, and 12 months following diagnosis in a cohort of HN squamous cell carcinoma (HNSCC) patients., Methods: Consecutive HNSCC patients (N = 109) subjected to standard workup and treatment self-reported their QoL measured by the EORTC Quality of Life Questionnaire (QLQ) H&N-35 between November 2002 and June 2005. Each QoL index was calculated and additionally aggregated to one sum score. The included patients were at diagnosis younger than 78 years, judged adequately cognitive functioning, and scheduled for curative treatment. Self-reported smoking, alcohol consumption, and socio-demographic information were registered. Twenty-two patients were high-risk (hr)-HPV DNA tumor positive. If the treatment goal was changed to palliative, no new QoL information was collected. All living patients were followed until 10 years after diagnosis., Results: Median survival was 105 months. Significant overall survival predictions were found from the EORTC H&N-35 QLQ sum scores continuously measured at diagnosis (p = 0.006) and obtained at 6 (p = 0.02), 9 (p = 0.002) and 12 (p = 0.05) months. Lower QoL predicted lower overall survival. These sum score survival predictions were in part independent of TNM stage, hr-HPV status, gender, age, alcohol and smoking status. The indices "pain", "swallowing", "social eating", and "feeling ill" were predictive of survival at 3 out of 4 measuring points (diagnosis, 6, 9 and 12 months) in univariate analyses., Conclusion: EORTC H&N-35 QLQ scores at diagnosis and throughout the first year thereafter harbor prognostic power.

Background: The aim of this study was to examine periodontal status with a time-efficient screening method from a cohort of newly diagnosed oropharynx squamous cell carcinoma (OPSCC) patients and to study to what extent dental disease level predicted survival. Aims/objective: Can measuring level of dental pathology based on a blind investigation of a routine orthopantogram (OPG) obtained during diagnostic workup reveal prognostic information?, Materials and Methods: We included 97 patients diagnosed between 2003 and 2010. Radiographic alveolar bone loss was measured. At least 4 mm bone loss from cement-enamel junction on at least two teeth was registered as periodontal pathology. The number of missing and filled teeth (MFT), residual roots and apical radiolucencies were noted. Clinical data were determined through hospital patient records., Results: The horizontal bone loss discriminated between hr-HPV(+) versus hr-HPV(-) status, but secondary to age and smoking history at diagnosis. Vertical and horizontal bone loss predicted survival directly, and adjusted by gender, patient, smoking history, TN stage and hr-HPV tumor infection at diagnosis., Conclusions: Degree of periodontal OPG pathology at the time of OPSCC diagnosis to some extent predicted hr-HPV infection, but predicted non-disease-specific long-term survival., Significance: Degree of periodontal OPG pathology at diagnosis predicts prognosis.

Background: Oropharyngeal squamous cell carcinoma (OPSCC) positive for human papillomavirus (HPV) increases wolrd wide., Aims/objectives: The objective for this study has been to evaluate tumor phenotypes and tumor host responses with respect to five-year disease-specific survival (DSS) in HPV(+) and HPV(-) patients., Material and Methods: Two hundred patients with OPSCC have been treated between 1992 and 2010. Histopathology slides from these patients have been morphologically evaluated in formalin-fixed, paraffin-embedded (FFPE) stained with hematoxylin-eosin (HE). From HE-stained sections tumor phenotype (keratinization, fraction of mature cancer cells and pattern of invasion) and tumor host responses (inflammation and stromal desmoplasia) were evaluated with respect to five years DSS., Results: High tumor inflammatory response and low stromal desmoplasia had an independent effect predicting better five-year DSS among all patients and when analyzed separately in the HPV(-) and HPV(+) cohort of patients using a Cox regression survival analysis that also included standard clinical prognostic variables among OPSCC patients., Conclusion: Tumor host responses, inflammation and stromal desmoplasia may become part of routine work-up in OPSCC patients due to prognostic value., Significance: We present a method, accessible in most clinical locations and would give important additional information about prognosis in OPSCC patients.

Objectives: To evaluate the 5- and 10-year survival prediction of health-related quality of life (HRQoL) scores obtained at diagnosis and at 6, 9 and 12 months after diagnosis in a cohort of curable head and neck squamous cell carcinoma (HNSCC) patients., Materials and Methods: HNSCC patients (n = 109) reported their HRQoL measured by the EORTC Quality of Life Questionnaire (QLQ) general (C30) questionnaire. At diagnosis, the included patients were below 78 years of age and at diagnosis planned treated with curative intent. Clinical variables and self-reported smoking, alcohol consumption and socio-demographic information were registered. From diagnostic blocks, we found 22 patients to be human papillomavirus (HPV) positive. New HRQoL scores were not obtained if the patient treatment changed from curative to palliative throughout the HRQoL data acquisition. Survival was determined from the National Population Register of Norway., Results: Decreased survival with low HRQoL scores from EORTC QLQ scores was demonstrated with HRQoL scores obtained from different time points of the four time points studied. These survival predictions were mostly independent of HPV status, gender, age, TNM stage, tumor site, alcohol consumption, present smoking status and whether comorbidities were present at diagnosis; as well as to some extent with an adjustment of the same HRQoL score/index obtained at diagnosis. The specific indices "physical function", "general pain" and "sleep disturbance" were in particular predictive of survival., Conclusion: HRQoL scores obtained throughout the first year after diagnosis contained prognostic power to overall survival when measured both at 5 and 10 years of observation.

Background: Cancer-associated fibroblasts (CAFs) were shown to be important for tumour progression in head and neck squamous cell carcinomas (HNSCCs). Their heterogeneity and lack of specific markers is increasingly recognized. Integrin α11 was recently shown to be expressed by CAFs and might serve as a specific CAF marker., Aim: To investigate integrin α11 expression and its correlation with the expression of a well-known marker of CAF, alpha smooth muscle actin (α-SMA), in HNSCC., Methods: Fresh frozen (FF) and formalin-fixed paraffin-embedded (FFPE) samples from healthy volunteers (n = 24), oral lichen planus (OLP) (n = 32) and HNSCC (n = 106) were collected together with clinical data after ethical approval. Immunohistochemistry to detect integrin α11 and α-SMA was performed on FF and FFPE samples. qPCR for integrin α11 (ITGA11) and α-SMA (ACTA2) was performed on FF samples. Data were analysed using chi-square test and Kaplan-Meier survival analysis., Results: Significantly higher levels of integrin α11 and α-SMA at both protein and mRNA levels were found in HNSCC vs. normal controls and OLP. A strong correlation was found between integrin α11 and α-SMA expression, and double staining showed their colocalization. Both integrin α11 and α-SMA were detected surrounding metastatic islands. Expression of α-SMA at tumour front but not tumour centre correlated with patient survival., Conclusion: Integrin α11 was overexpressed in HNSCC stroma and colocalized with α-SMA. Expression of α-SMA at tumour front but not tumour centre had prognostic value for survival, pinpointing the importance of assessing tumour front when evaluating stromal molecules as prognostic biomarkers., (© 2016 The Authors. Journal of Oral Pathology & Medicine Published by John Wiley & Sons Ltd.)

We changed the primary oropharynx squamous cell carcinoma (OPSCC) treatment recommendation from primary radiation therapy (RT) to tumor surgery and neck dissection, followed by RT around the year 2000 with apparently improved survival. However, high-risk human papilloma virus (hr-HPV)-16-caused OPSCCs have increased during this period. Furthermore, hr-HPV+ OPSCC carry a better prognosis than hr-HPV-negative patients. We have, therefore, evaluated the 5-year survival in the period from 1992 to 1999 versus 2000 to 2008 stratified by hr-HPV tumor infection status. Ninety-six OPSCC patients were treated from 1992 to 1999 compared with 136 patients from 2000 to 2008. The 5-year disease-specific survival (DDS) and overall survival (OS) were recorded, while the health-related quality of life (HRQoL) scores were obtained from some of the cured patients. Thirty-eight (40 %) in the first period and 86 OPSCCs (63 %) in the second period were hr-HPV+. In the first period, 16 versus 62 patients in the last period were treated by neck dissection, primary tumor surgery, and RT. DSS among all the hr-HPV-negative patients in the first period was 51 versus 55 % in the second period, and the corresponding OS was 33 versus 31 %, respectively. The DSS among all the hr-HPV+ patients was 78 % in the first period versus 77 % in the second period, while the OS was 71 versus 69 %, respectively. The HRQoL scores among successfully treated patients were worse following surgery, plus RT than RT only. The hr-HPV-adjusted 5-year survival in OPSCC patients was similar between the two time periods. A decreased HRQoL was associated with surgical therapy, which indicates that hr-HPV+ OPSCC patients may be treated by primary RT followed by major surgery only if RT treatment fails.

Background: Although several approaches for identification and isolation of carcinoma cells with tumour initiating properties have been established, enrichment of a population of pure and viable tumour-initiating cells (TICs) is still problematic. This study investigated possibilities to isolate a population of cancer cells with tumour initiating properties based on their adherence properties, rather than expression of defined markers or clonogenicity., Methods: Several human cell lines derived from oral dysplasia and oral squamous cell carcinoma (OSCC), as well as primary cells derived from patients with OSCC were allowed to adhere to collagen IV-coated dishes sequentially. Rapid adherent cells (RAC), middle adherent cells (MAC) and late adherent cells (LAC) were then harvested and further investigated for their morphology, stem cell-like properties and molecular profile while grown in vitro and tongue xenotransplantation in NOD-SCID mice at serial dilutions., Results: RAC showed significantly higher colony forming efficiency (p<0.05), sphere forming ability, greater migration ability (p<0.05), exhibited longer G2 phase and displayed higher expression of integrin β1 and other stem-cell related molecules as compared to MAC and LAC. RAC induced tongue tumours in NOD-SCID mice with the highest incidence. These tumours were also bigger and metastasised more frequently in loco-regional lymph nodes than MAC and LAC., Conclusions: These findings prove for the first time that OSCC cells with tumour initiating properties can be enriched based on their rapid adhesiveness to collagen IV. This separation procedure provides a potentially useful tool for isolating TICs in OSCC for further studies on understanding their characteristics and drug-resistant behaviour., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Conclusions: Patients with human papillomavirus (HPV)-positive tumours had better 5-year disease-specific survival (DSS) than HPV-negative patients. TNM score only predicted prognosis among HPV-negative patients. A previous history of smoking and age at diagnosis predicted DSS among HPV-positive patients whereas operability at diagnosis predicted DSS among both HPV-positive and HPV-negative patients., Objectives: HPV is a risk factor for oropharyngeal squamous cell carcinoma (OPSCC). The extent to which smoking, age and operability could play a role in HPV-positive surgically treated head and neck SCCs has not been extensively addressed previously and this study aimed to evaluate these factors., Methods: We identified 232 patients with OPSCC, of which 186 from the tonsil or base of the tongue region were treated in the period 1992-2008 in Western Norway. The 5-year DSS was recorded. Details on smoking history and whether the lesion was operable or not, as well as clinical information, were obtained retrospectively from the hospital records., Results: TNM stage predicted survival only among HPV-negative patients. A previous smoking affected prognosis only among HPV-positive patients (relative risk (RR) = 2.5; confidence interval (CI) = 1.0-6.2; p = 0.05). Increasing age of the patient had a negative effect on survival in HPV-positive patients only, especially among the oldest quartile (RR = 4.4; CI = 2.0-9.0; p < 0.001). Whether the tumour was operable or not uniquely predicted DSS both among HPV-positive (RR = 0.34; CI = 0.13-0.93; p < 0.05) and HPV-negative (RR = 0.25; CI = 0.10-0.66; p < 0.01) patients with tonsil/base of the tongue SCC.

Conclusions: We determined that 55% of the patients with oropharynx squamous cell carcinoma (OPSCC) had human papilloma virus (HPV)-positive tumors. We demonstrated that HPV-positive patients had better 5-year disease-specific survival (DSS) than the HPV-negative counterparts. This was also primarily true for cancers originating in the tonsil or base of the tongue with T3 and/or N2 tumors., Objective: Urogenital high risk (hr) HPV is an important risk factor, and probably causative agent, for OPSCC. The study investigated these factors., Methods: We identified 232 patients with OPSCC, of which 186 lesions were from the tonsil or base of the tongue region, treated in the period 1992-2008 in Western Norway. Five-year DSS was recorded for all patients., Results: In all, 124 of 226 patients had HPV-positive tumors. All except five HPV-positive patients had HPV-16-positive tumors; 69% of the patients with tonsil or base of the tongue SCC had HPV-positive tumors, whereas 14% of remaining OPSCC patients had HPV-positive tumors. Five-year DSS with HPV-positive tumor was 77% compared with 53% with an HPV-negative tumor (p < 0.001), also valid with adjustment for age, gender, and TNM stage, but primarily determined with patients with the specific tumor sites tonsils and base of the tongue with TNM stages T3 or N2.

Since 1992 we have prospectively included all head and neck cancer patients in our health region in a departmental based register. Our hospital takes care of all head and neck cancer patients in our health region consisting of approximately 1 million people. In 1997, we evaluated the results of the treatment of oropharyngeal cancer in the 1992-1997 period. On the basis of this evaluation, we changed our treatment policy for tonsillar and base of tongue carcinoma. We first changed the treatment for the lesions with worst prognosis, i.e., those with T3-T4 carcinomas, from radiotherapy only, to radical surgery and postoperative radiotherapy. We have since that time increasingly also operated the smaller oropharyngeal carcinomas. The 2 years' overall survival and disease-specific survival for all patients diagnosed in the 1992-1997 period was 56 and 63%, respectively. The results from a similar group of patients in the 6 years' period from 2000 to 2005, after the change in treatment, have increased to 83 and 88%. When we looked at the subgroup of patients in the 2000-2005 period treated with surgery and postoperative radiotherapy, 45 out of 69 patients (65%) presenting with an oropharyngeal cancer were fit for operation. With radical surgery and postoperative radiation therapy, the 2 years overall survival is now 91%. The 2-year disease-specific survival is 96% and the locoregional control is 98%. This is a marked improvement as compared to radiotherapy alone and definitely competitive with modern radiochemotherapy.

In this prospective study, the patients with head and neck cancer admitted to the Department of Otolaryngology and Head and Neck Surgery, Haukeland University Hospital, underwent examination with ultrasound of the abdomen (112 patients) and total bone scintigraphy (118 patients) in the primary staging of the disease and before the start of treatment. In only one patient did we find metastases of head and neck cancer in the liver by these additional investigations, and one patient was found to have bone metastases. No second primary cancers were found by these extra examinations. One patient was found to have an asymptomatic aorta aneurysm and was in need of urgent surgical treatment. Based on these findings, we nowadays only use ultrasound of the abdomen and total bone scintigraphy as part of the general examination of new head and neck patients in selected cases.