Periodontitis is associated with decreased experimental pressure pain tolerance: The Tromsø Study 2015-2016.

AIM: To assess the relationship between periodontitis and experimental pain tolerance. MATERIALS AND METHODS: Participants from the population-based seventh survey of the Tromsø Study with data on periodontitis were included (n = 3666, 40-84 years old, 51.6% women). Pain tolerance was assessed through (i) pressure pain tolerance (PPT) test with a computerized cuff pressure algometry on the leg, and (ii) cold-pressor tolerance (CPT) test where one hand was placed in circulating 3°C water. Cox proportional hazard regression was used to assess the association between periodontitis and pain tolerance adjusted for age, sex, education, smoking and obesity. RESULTS: In the fully adjusted model using the 2012 Centers for Disease Control/American Academy of Periodntology case definitions for surveillance of periodontitis, moderate (hazard ratio [HR] = 1.09; 95% confidence interval [CI]: 1.01, 1.18) and severe (HR = 1.25, 95% CI: 1.11, 1.42) periodontitis were associated with decreased PPT. Using the 2018 classification of periodontitis, having Stage II/III/IV periodontitis was significantly associated with decreased PPT (HR = 1.09; 95% CI: 1.01, 1.18) compared with having no or stage I periodontitis. There were no significant associations between periodontitis and CPT in fully adjusted models. CONCLUSIONS: Moderate and severe periodontitis was associated with experimental PPT.

Are dental visiting patterns and oral pain associated with dental disease among Norwegian adults? A cross-sectional study based on the Tromsø study.

OBJECTIVES: The present study aims to describe the dental visiting patterns in a Norwegian adult population and their associations with sociodemographic and oral health variables, including oral pain. We further explore if the utilization of dental health services and oral pain predicts caries and periodontitis, the most common oral diseases. MATERIALS AND METHODS: We use data from the seventh wave of the Tromsø study performed in 2015-2016. In this cross-sectional survey, all residents 40 years or older in Tromsø municipality in Norway were invited, of whom 21,083 (65%) participated. All participants answered questionnaires assessing sociodemographic characteristics, use of health services, and self-reported health measures, including pain. Almost 4000 participants underwent a dental examination with registration of caries and periodontitis. Associations of dental visiting patterns and utilization of dental services the past 12 months with sociodemographic-, self-reported-, and clinical oral health measures were analyzed by cross-tabulation and Pearson's χ2 tests, as well as with logistic regression analyses with caries and periodontitis as outcomes. RESULTS: A regular, annual dental visiting pattern was the most common, but among respondents with severe dental anxiety and poor dental health, visiting for acute problems only or never (symptomatic visiting) was the most common. Intervals of more than 24 months between visits and a symptomatic visiting pattern were associated with caries, whereas shorter than 12-month intervals and a symptomatic visiting pattern were associated with periodontitis. Many characteristics were shared among respondents with the lowest and the highest utilization of dental services, including oral pain, a difficult financial situation and poorer self-reported and clinical dental health. CONCLUSIONS: Regular dental visits at 12-24 month intervals were associated with beneficial oral health parameters, compared with more frequent, rarer, and symptomatic dental visiting patterns. Oral pain was an unreliable predictor of caries and periodontitis.

Polymorphism in epigenetic regulating genes in relation to periodontitis, number of teeth, and levels of high-sensitivity C-reactive protein and glycated hemoglobin: The Tromsø Study 2015-2016.

BACKGROUND: The aim of this study was to investigate the association between periodontitis and four single nucleotide polymorphisms (SNPs) in genes involved in epigenetic regulation of DNA, and between these same SNPs and tooth loss, high-sensitivity C-reactive protein (hs-CRP), and glycated hemoglobin (HbA1c) levels. METHODS: We included participants with periodontal examination (n = 3633, aged: 40-93 years) from the Tromsø Study seventh survey (2015-2016), Norway. Periodontitis was defined according to the 2017 AAP/EFP classification system as no periodontitis, grades A, B, or C. Salivary DNA was extracted and genotyping was performed to investigate four SNPs (rs2288349, rs35474715, rs34023346, and rs10010325) in the sequence of the genes DNMT1, IDH2, TET1, and TET2. Association between SNPs and periodontitis was analyzed by logistic regression adjusted for age, sex, and smoking. Subgroup analyses on participants aged 40-49 years were performed. RESULTS: In participants aged 40-49 years, homozygous carriage of minor A-allele of rs2288349 (DNMT1) was associated with decreased susceptibility to periodontitis (grade A: odds ratio [OR] 0.55; p = 0.014: grade B/C OR 0.48; p = 0.004). The minor A-allele of rs10010325 (TET2) was associated with increased susceptibility to periodontitis (grade A OR 1.69; p = 0.035: grade B/C OR 1.90; p = 0.014). In the entire sample, homozygous carriage of the G-allele of rs35474715 (IDH2) was associated with having ≤24 teeth (OR 1.31; p = 0.018). Homozygous carriage of the A-allele of TET2 was associated with hs-CRP≥3 mg/L (OR 1.37; p = 0.025) and HbA1c≥6.5% (OR 1.62; p = 0.028). CONCLUSIONS: In this Norwegian population, there were associations between polymorphism in genes related to DNA methylation and periodontitis, tooth loss, low-grade inflammation, and hyperglycemia.

Eating and speech problems in oral and pharyngeal cancer survivors - Associations with treatment-related side-effects and time since diagnosis.

AIMS: The aim of this cross-sectional study was to find factors associated with problems with the ability to eat and speak in oral and pharyngeal cancer (OPC) survivors and to evaluate if the panorama of oral problems varied with time since diagnosis. METHODS AND RESULTS: A questionnaire assessing cancer diagnosis and treatment, oral health-related quality of life, and presence of treatment-related side-effects was sent to members of the Norwegian Head and Neck Cancer Association. Three-quarters (n = 117) of the respondents experienced xerostomia, and 51% (n = 79) had dysphagia. Prevalence of dysphagia, trismus, and dysphonia was lowest among respondents diagnosed within the last 5-10 years prior to the study. Eating problems were reported by 75% (n = 121) of the OPC survivors and were associated with xerostomia, dysphagia, trismus, having removed part of the tongue, cancer diagnosis within 5 years prior to the study and having little problems with caries and tooth fracture. Speaking problems were experienced by 60% (n = 93) of the OPC survivors, and were associated with dysphonia, dysphagia, and trismus. CONCLUSION: Our study shows a high prevalence of oral problems among OPC survivors and points to targets for interventions for eating and speech impairments that may improve oral health-related quality of life.

Pain, discomfort, and functional impairment after extraction of primary teeth in children with palatally displaced canines - a randomized control trial comparing extraction of the primary canine versus extraction of the primary canine and the primary first molar.

CONCLUSION: Primary canines and first molars can be extracted in a way that is associated with relatively low levels of pain and discomfort during and after the procedures. Double extractions induced more pain and discomfort than single extractions, which should be accounted for in the treatment planning. MATERIAL AND METHODS: Twenty-eight children, aged 9.5-14 years with displaced permanent maxillary canines were randomly assigned for extraction of the primary canine only or the primary canine and the primary first molar. Pain and discomfort were rated on visual analogue scales, and influence on daily activities was assessed by a questionnaire that has been previously tested for reliability and validity. Differences between groups were assessed by independent samples t-tests, Mann-Whitney U-tests or the Fisher's exact test. OBJECTIVE: To assess pain, discomfort, and functional impairment in children experiencing extraction of primary canine or primary canine and primary first molar as an interceptive treatment for palatally displaced permanent canines. RESULTS: Tooth extraction was associated with low levels of pain and discomfort on a group level. Extraction of both the canine and the first molar was associated with significantly more pain and discomfort than was the extraction of the canine only. Extractions were associated with chewing problems among one-third to half of the children, otherwise, few children reported any jaw impairment after extraction.

Oral health related quality of life in long-term survivors of head and neck cancer compared to a general population from the seventh Tromsø study.

BACKGROUND: Both the incidence and survival rate of head and neck cancer (HNC) is increasing, making quality of life of HNC survivors an important issue. METHODS: In this cross-sectional study we compared the oral health related quality of life (OHRQoL) of long-term HNC survivors to that of a general population cohort from the seventh survey of the Tromsø study with the Oral Impact on Daily Performances questionnaire. Comparisons were done with frequency analyses and cross tabulation. We also assessed OHRQoL's association to sociodemographic and oral health related variables in both cohorts as well as with cancer related variables in the HNC cohort with regression analyses. RESULTS: The HNC survivors had four times the risk of reporting problems with daily performances compared with the general population cohort. The ability to eat and enjoy food was most frequently affected in both cohorts. Moderate-poor self-rated dental health and general health as well as high frequency of dental visits were significantly associated with poorer OHRQoL. To have a history of oral or pharyngeal cancer was associated with more problems than having a history of laryngeal cancer. CONCLUSIONS: Our study shows that HNC treatment is associated with a strong and lasting impairment of OHRQoL, highlighting the need to find less toxic, yet effective ways to treat the disease, and to provide easy access to expert dental care at all stages of the disease to minimize morbidity. Given the widespread side effects of cancer treatment, a multidisciplinary approach might be required to improve the OHRQoL of HNC survivors.

Bisphenol A replacement chemicals, BPF and BPS, induce protumorigenic changes in human mammary gland organoid morphology and proteome.

SignificanceBisphenol A (BPA), found in many plastic products, has weak estrogenic effects that can be harmful to human health. Thus, structurally related replacements-bisphenol S (BPS) and bisphenol F (BPF)-are coming into wider use with very few data about their biological activities. Here, we compared the effects of BPA, BPS, and BPF on human mammary organoids established from normal breast tissue. BPS disrupted organoid architecture and induced supernumerary branching. At a proteomic level, the bisphenols altered the abundance of common targets and those that were unique to each compound. The latter included proteins linked to tumor-promoting processes. These data highlighted the importance of testing the human health effects of replacements that are structurally related to chemicals of concern.

Validation of Selected Head and Neck Cancer Prognostic Markers from the Pathology Atlas in an Oral Tongue Cancer Cohort.

The Pathology Atlas is an open-access database that reports the prognostic value of protein-coding transcripts in 17 cancers, including head and neck cancer. However, cancers of the various head and neck anatomical sites are specific biological entities. Thus, the aim of the present study was to validate promising prognostic markers for head and neck cancer reported in the Pathology Atlas in oral tongue squamous cell carcinoma (OTSCC). We selected three promising markers from the Pathology Atlas (CALML5, CD59, LIMA1), and analyzed their prognostic value in a Norwegian OTSCC cohort comprising 121 patients. We correlated target protein and mRNA expression in formalin-fixed, paraffin-embedded cancer tissue to five-year disease-specific survival (DSS) in univariate and multivariate analyses. Protein expression of CALML5 and LIMA1 were significantly associated with five-year DSS in the OTSCC cohort in univariate analyses (p = 0.016 and p = 0.043, respectively). In multivariate analyses, lymph node metastases, tumor differentiation, and CALML5 were independent prognosticators. The prognostic role of the other selected markers for head and neck cancer patients identified through unbiased approaches could not be validated in our OTSCC cohort. This underlines the need for subsite-specific analyses for head and neck cancer.

Temporomandibular disorders in an adult population in northern Norway: A cross-sectional study.

OBJECTIVES: The aim of the study was to assess the prevalence of symptoms indicative of temporomandibular disorders (TMD) in an adult population in Troms County in Northern Norway, as well as the associations between TMD and socio-demographic factors, dental status, self-reported general, and oral health as well as oral health related quality of life (OHQoL). METHODS: Data were collected from a structured questionnaire and a clinical examination of a random sample of almost 2000 adults, 20-79-year-old, in Troms County in Northern Norway. RESULTS: Women had a higher prevalence of all self-reported and clinical signs of pain and dysfunction in the temporomandibular complex compared to men. For both genders, sounds from the temporomandibular joint (TMJ) upon clinical examination was the most common symptom, followed by pain to palpation of jaw muscles. Headache was the most common of the self-reported symptoms and sounds from the TMJ the second most common. Young women had a higher prevalence of self-reported headache and jaw- and face pain compared to middle-aged and elderly women. TMD-related symptoms of pain were significantly associated with poor self-reported general health and correlated with OHQoL as assessed by the oral health impact profile 14 questionnaire. CONCLUSION: Being women and having moderate to poor self-reported general health were associated with clinical signs and self-reported symptoms of pain in the jaw, face and head region. Self-reported symptoms of TMD correlated more strongly with OHQoL than clinical signs.

Oral health and use of dental services in different stages of adulthood in Norway: a cross sectional study.

BACKGROUND: Socioeconomic status and oral health care habits may change throughout adult life. This calls for age-stratified analyses of oral health in the adult population to uncover differences that could be of importance for organizing adequate oral health care services. The aim of the present study was to describe self-reported oral health in different age groups in a general adult population in Norway, and to explore associations between self-reported oral health and age groups, sociodemographic factors, use of dental services, number of teeth and dental caries. METHODS: We used data from a cross-sectional study of almost 2000 Norwegian adults, 20-79 years old. The study included both a structured questionnaire and a clinical examination to assess sociodemographic variables, use of dental services, self-reported oral and general health as well as dental caries and number of teeth. For analysis, the participants were divided into three age groups: young adults (20-29 years), middle-aged adults (30-59 years), and senior adults (60 years and older). Differences among groups were analyzed by cross-tabulation, and logistic regression analyses were used to assess associations between variables. RESULTS: Forty-eight percent of the participants rated their oral health as good. Almost half of the participants had at least one carious tooth, with the highest caries prevalence among the young adults. To be caries free was strongly associated with reporting good oral health among the young and middle-aged adults. One third of the senior adults had fewer than 20 teeth, which was associated with reporting moderate or poor oral health. Less than half of the young adults reported regular use of dental services, and 40% of them had postponed dental visits for financial reasons during the past 2 years. Regardless of age group, having to postpone dental visits for financial reasons or having poor-to-moderate general health were associated with high odds for reporting moderate or poor oral health. CONCLUSIONS: That there were important age-group differences in self-reported and clinical measures of oral health and in the use of dental health services demonstrates the importance of age-stratified analyses in oral health research. Many adults, especially among the young, faced financial barriers for receiving dental health services, which was associated with poorer self-reported oral health. This argues for a need to revisit the financing of oral health care for adults in Norway.

Nephronectin as a Matrix Effector in Cancer.

The extracellular matrix protein nephronectin plays an important regulatory role during embryonic development, controlling renal organogenesis through integrin α8ß1 association. Nephronectin has three main domains: five N-terminal epidermal growth factor-like domains, a linker region harbouring two integrin-binding motifs (RGD and LFEIFEIER), and a C-terminal MAM domain. In this review, we look into the domain-related functions of nephronectin, and tissue distribution and expression. During the last two decades it has become evident that nephronectin also plays a role during cancer progression and in particular metastasis. Nephronectin is overexpressed in both human and mouse breast cancer compared to normal breast tissue where the protein is absent. Cancer cells expressing elevated levels of nephronectin acquire increased ability to colonise distant organs. In particular, the enhancer-motif (LFEIFEIER) which is specific to the integrin α8ß1 association induces viability via p38 MAPK and plays a role in colonization. Integrins have long been desired as therapeutic targets, where low efficiency and receptor redundancy have been major issues. Based on the summarised publications, the enhancer-motif of nephronectin could present a novel therapeutic target.

The effect of interleukin-17F on vasculogenic mimicry in oral tongue squamous cell carcinoma.

Oral tongue squamous cell carcinoma (OTSCC) is one of the most common cancers worldwide and is characterized by early metastasis and poor prognosis. Recently, we reported that extracellular interleukin-17F (IL-17F) correlates with better disease-specific survival in OTSCC patients and has promising anticancer effects in vitro. Vasculogenic mimicry (VM) is the formation of an alternative vasculogenic system by aggressive tumor cells, which is implicated in treatment failure and poor survival of cancer patients. We sought to confirm the formation of VM in OTSCC and to investigate the effect of IL-17F on VM formation. Here, we showed that highly invasive OTSCC cells (HSC-3 and SAS) form tube-like VM on Matrigel similar to those formed by human umbilical vein endothelial cells. Interestingly, the less invasive cells (SCC-25) did not form any VM structures. Droplet-digital PCR, FACS, and immunofluorescence staining revealed the presence of CD31 mRNA and protein in OTSCC cells. Additionally, in a mouse orthotopic model, HSC-3 cells expressed VE-cadherin (CD144) but lacked Von Willebrand Factor. We identified different patterns of VM structures in patient samples and in an orthotopic OTSCC mouse model. Similar to the effect produced by the antiangiogenic drug sorafenib, IL-17F inhibited the formation of VM structures in vitro by HSC-3 and reduced almost all VM-related parameters. In conclusion, our findings indicate the presence of VM in OTSCC and the antitumorigenic effect of IL-17F through its effect on the VM. Therefore, targeting IL-17F or its regulatory pathways may lead to promising therapeutic strategies in patients with OTSCC.

Tumour cells express functional lymphatic endothelium-specific hyaluronan receptor in vitro and in vivo: Lymphatic mimicry promotes oral oncogenesis?

Lymphatic metastasis represents the main route of tumour cell dissemination in oral squamous cell carcinoma (OSCC). Yet, there are no FDA-approved therapeutics targeting cancer-related lymphangiogenesis to date. The lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE-1), a specific lymphatic marker, is associated with poor survival in OSCC patients. In this study, we present a potential novel mechanism of lymphatic metastasis in OSCC-lymphatic mimicry (LM), a process whereby tumour cells form cytokeratin+/LYVE-1+, but podoplanin-negative, mosaic endothelial-like vessels. LM was detected in one-third (20/57; 35.08%) of randomly selected OSCC patients. The LM-positive patients had shorter overall survival (OS) compared to LM-negative group albeit not statistically significant. Highly-metastatic tumour cells formed distinct LM structures in vitro and in vivo. Importantly, the siRNA-mediated knockdown of LYVE-1 not only impaired tumour cell migration but also blunted their capacity to form LM-vessels in vitro and reduced tumour metastasis in vivo. Together, our findings uncovered, to our knowledge, a previously unknown expression and function of LYVE-1 in OSCC, whereby tumour cells could induce LM formation and promote lymphatic metastasis. Finally, more detailed studies on LM are warranted to better define this phenomenon in the future. These studies could benefit the development of targeted therapeutics for blocking tumour-related lymphangiogenesis.

Evaluation Challenges in the Validation of B7-H3 as Oral Tongue Cancer Prognosticator.

B7-H3 was the only molecule identified with prognostic potential from a recent systematic review of the prognostic value of immune checkpoints in oral cancer. We aimed to validate this finding in a multicenter international cohort. We retrospectively retrieved 323 oral tongue squamous cell carcinoma (OTSCC) samples from three different countries (Brazil, Finland, and Norway) for immunostaining and scoring for B7-H3. We evaluated tumor immunogenicity by analyzing the amount of tumor-infiltrating lymphocytes and divided the tumors into immune hot and cold. To increase the reliability of the results, both digital and manual visual scoring were used. Survival curves were constructed based on the Kaplan-Meier method, and the Cox proportional hazard model was utilized for univariate and multivariate survival analysis. B7-H3 expression was not significantly associated with overall or disease-specific survival in the whole OTSCC cohort. When divided into immune hot and cold tumors, high B7-H3 expression was significantly associated with poor disease-specific and overall survival in the immune hot group, depending on the scoring method and the country of the cohort. This was achieved only in the univariate analysis. In conclusion, B7-H3 was a negative prognosticator for OTSCC patient survival in the subgroup of immune hot tumors, and was not validated as a prognosticator in the full cohort. Our findings suggest that the immune activity of the tumor should be considered when testing immune checkpoints as biomarkers.

Tumor budding score predicts lymph node status in oral tongue squamous cell carcinoma and should be included in the pathology report.

BACKGROUND: The majority of oral cavity cancers arise in the oral tongue. The aim of this study was to evaluate the prognostic value of tumor budding in oral tongue squamous cell carcinoma, both as a separate variable and in combination with depth of invasion. We also assessed the prognostic impact of the 8th edition of the American Joint Committee on Cancer's TNM classification (TNM8), where depth of invasion (DOI) supplements diameter in the tumor size (T) categorization. METHODS: Patients diagnosed with primary oral tongue squamous cell carcinoma were evaluated retrospectively. Spearman bivariate correlation analyses with bootstrapping were used to identify correlation between variables. Prognostic value of clinical and histopathological variables was assessed by Log rank and Cox regression analyses with bootstrapping using 5-year disease specific survival as outcome. The significance level for the hypothesis test was 0.05. RESULTS: One-hundred and fifty patients had available material for microscopic evaluation on Hematoxylin and Eosin-stained slides and were included in the analyses. Reclassification of tumors according to TNM8 caused a shift towards a higher T status compared to the previous classification. The tumor budding score was associated with lymph node metastases where 23% of the patients with low-budding tumors had lymph node metastases, compared with 43% of those with high-budding tumors. T-status, lymph node status, tumor budding, depth of invasion, and the combined tumor budding/depth of invasion score were all significantly associated with survival in univariate analyses. In multivariate analyses only N-status was an independent prognosticator of survival. CONCLUSION: Reclassification according to TNM8 shifted many tumors to a higher T-status, and also increased the prognostic value of the T-status. This supports the implementation of depth of invasion to the T-categorization in TNM8. Tumor budding correlated with lymph node metastases and survival. Therefore, information on tumor budding can aid clinicians in treatment planning and should be included in pathology reports of oral tongue squamous cell carcinomas.

A combined histo-score based on tumor differentiation and lymphocytic infiltrate is a robust prognostic marker for mobile tongue cancer.

We wanted to evaluate the prognostic value of common histopathological variables in a large cohort of patients with cancer in the mobile tongue as such information can be important for treatment stratification of the individual patient, especially for patients with low-stage disease. In addition, we wanted to investigate whether an alternative scoring model with fewer options would compromise the prognostic value. One hundred fifty patients with oral tongue squamous cell carcinomas that were treated in curative intent and with available HE-stained tumor sections were included. We reclassified all tumors and performed univariate and multivariate survival analyses of histopathological and clinical variables. For the complete cohort, lymph node status, grade of differentiation, perineural infiltration, and lymphocytic infiltration were independent prognosticators. In the low-stage disease group, independent prognostic factors were tumor size, grade of differentiation, and lymphocytic infiltrate. For patients with low-stage disease, a histo-score combining the scores for tumor differentiation and lymphocytic infiltrate identified a group of patients with particularly low survival, as patients with moderately or poorly differentiated tumors and little lymphocytic infiltrate had a less favorable 5-year survival outcome than patients in the high-stage disease group. This study shows that a histo-score combining tumor differentiation and lymphocytic infiltration should be given special consideration in treatment planning. Our results also illustrate that many variables can be scored with fewer options than previously suggested to increase their reproducibility, and still maintain their prognostic value.

Nephronectin promotes breast cancer brain metastatic colonization via its integrin-binding domains.

This study demonstrates a role for the extracellular matrix protein nephronectin (NPNT) in promoting experimental breast cancer brain metastasis, possibly through enhanced binding to- and migration through brain endothelial cells. With the introduction of more targeted breast cancer treatments, a prolonged survival has resulted during the last decade. Consequently, an increased number of patients develop metastasis in the brain, a challenging organ to treat. We recently reported that NPNT was highly expressed in primary breast cancer and associated with unfavourable prognosis. The current study addresses our hypothesis that NPNT promotes brain metastases through its integrin-binding motifs. SAGE-sequencing revealed that NPNT was significantly up-regulated in human breast cancer tissue compared to pair-matched normal breast tissue. Human brain metastatic breast cancers expressed both NPNT and its receptor, integrin α8ß1. Using an open access repository; BreastMark, we found a correlation between high NPNT mRNA levels and poor prognosis for patients with the luminal B subtype. The 66cl4 mouse cell line was used for expression of wild-type and mutant NPNT, which is unable to bind α8ß1. Using an in vivo model of brain metastatic colonization, 66cl4-NPNT cells showed an increased ability to form metastatic lesions compared to cells with mutant NPNT, possibly through reduced endothelial adhesion and transmigration.

Characteristics and prognosis of primary treatment-naïve oral cavity squamous cell carcinoma in Norway, a descriptive retrospective study.

OBJECTIVES: Incidence of oral cavity squamous cell carcinomas is rising worldwide, and population characterization is important to follow for future trends. The aim of this retrospective study was to present a large cohort of primary oral cavity squamous cell carcinoma from all four health regions of Norway, with descriptive clinicopathological characteristics and five-year survival outcomes. MATERIALS AND METHODS: Patients diagnosed with primary treatment-naïve oral cavity squamous cell carcinomas at all four university hospitals in Norway between 2005-2009 were retrospectively included in this study. Clinicopathological data from the electronic health records were compared to survival data. RESULTS: A total of 535 patients with primary treatment-naïve oral cavity squamous cell carcinomas were identified. The median survival follow-up time was 48 months (range 0-125 months) after treatment. The median five-year overall survival was found to be 47%. Median five-year disease-specific survival was 52%, ranging from 80% for stage I to 33% for stage IV patients. For patients given treatment with curative intent, the overall survival was found to be 56% and disease-specific survival 62%. Median age at diagnosis was 67 years (range 24-101 years), 64 years for men and 72 years for women. The male: female ratio was 1.2. No gender difference was found in neither tumor status (p = 0.180) nor node status (p = 0.266), but both factors influenced significantly on survival (p<0.001 for both). CONCLUSIONS: We present a large cohort of primary treatment-naïve oral cavity squamous cell carcinomas in Norway. Five-year disease-specific survival was 52%, and patients eligible for curative treatment had a five-year disease-specific survival up to 62%.

Grading of oral squamous cell carcinomas - Intra and interrater agreeability: Simpler is better?

BACKGROUND: Numerous studies have been presented on histological grading of oral squamous cell carcinomas (OSCC) for predicting survival, but uncertainty of their usefulness rises due to discordances of results. A scoring system should be robust and well validated, and intra- and interrater agreement can be used as a tool to visualize the strength of reproducibility. METHODS: Here, we present an intra- and inter-observer study on evaluation of OSCC using some of the most common histopathological parameters. The observers were from different Norwegian university hospitals, and calibration to ensure accuracy was first performed. Percentage of the agreement was calculated for the score made by the individual observer at different times, as well as between pairs of observers. RESULTS: The evaluation made by the same observer at two different time points (intrarater) correlated better than observations made by different participants (interrater). In an attempt to increase the rate of agreement, many of the parameters were either dichotomized into simply low- and high grade, or to a three-tier system when more than three options in the original design. This increased the concurrence with 15.4% for the intrarater and with 23% for the interrater comparisons. CONCLUSION: High agreement for histopathological parameters can be difficult to obtain on hematoxylin and eosin staining in scoring systems with many options. A simpler system might be more advantageous to achieve higher degree of reproducibility.