Immunohistochemical and molecular imaging biomarker signature for the prediction of failure site after chemoradiation for head and neck squamous cell carcinoma.

OBJECTIVE: To identify a failure site-specific prognostic model by combining immunohistochemistry (IHC) and molecular imaging information to predict long-term failure type in squamous cell carcinoma of the head and neck. PATIENT AND METHODS: Tissue microarray blocks of 196 head and neck squamous cell carcinoma cases were stained for a panel of biomarkers using IHC. Gross tumor volume (GTV) from the PET/CT radiation treatment planning CT scan, maximal Standard Uptake Value (SUVmax) of fludeoxyglucose (FDG) and clinical information were included in the model building using Cox proportional hazards models, stratified for p16 status in oropharyngeal carcinomas. Separate models were built for time to locoregional failure and time to distant metastasis. RESULTS: Higher than median p53 expression on IHC tended toward a risk factor for locoregional failure but was protective for distant metastasis, χ2 for difference p = .003. The final model for locoregional failure included p53 (HR: 1.9; p: .055), concomitant cisplatin (HR: 0.41; p: .008), ß-tubulin-1 (HR: 1.8; p: .08), ß-tubulin-2 (HR: 0.49; p: .057) and SUVmax (HR: 2.1; p: .046). The final model for distant metastasis included p53 (HR: 0.23; p: .025), Bcl-2 (HR: 2.6; p: .08), SUVmax (HR: 3.5; p: .095) and GTV (HR: 1.7; p: .063). CONCLUSIONS: The models successfully distinguished between risk of locoregional failure and risk of distant metastasis, which is important information for clinical decision-making. High p53 expression has opposite prognostic effects for the two endpoints; increasing risk of locoregional failure, but decreasing the risk of metastatic failure, but external validation of this finding is needed.

Correlation between HPV status at T and N sites of oropharyngeal squamous cell carcinomas.

OBJECTIVES: Human papilloma virus (HPV) is known to be associated with oropharyngeal squamous cell carcinomas (OPSCC) and may potentially play a vital role in tumor metastasis. The purpose of this study was to correlate HPV status of cervical lymph node metastases with their respective primary OPSCC tumor. METHODS: Formalin-fixed, paraffin-embedded (FFPE) tissue samples obtained from 34 patients with cervical lymph node metastases were analyzed with HPV 16 DNA polymerase chain reaction (PCR), p16 immunohistochemistry and HPV typing. The results were correlated with the HPV status and type found in the primary tumors of OPSCC. RESULTS: Comparing HPV DNA status with p16 we found that 21 primary tumors and lymph node metastases were HPV positive (61.8%) and seven primary tumors and lymph node metastases were HPV negative (20.6%). Six patient samples differed when correlating the primary tumor and lymph node metastasis (17.6%). CONCLUSIONS: In this study, HPV status in OPSCCs and their cervical lymph node metastases correlated in the vast majority of cases. However, HPV detection methods may have certain limitations resulting in varying degree of non-correlation. This should be taken into account when stratifying treatment in regard to HPV status.

Double positivity for HPV DNA/p16 in tonsillar and base of tongue cancer improves prognostication: Insights from a large population-based study.

The aim was to explore the overall survival (OS) for palatine tonsillar squamous cell carcinoma (TSCC), subdivided, according to certainty of tonsillar tumour origin, into specified tonsillar squamous cell carcinomas (STSCCs) and nonspecified tonsillar squamous cell carcinomas (NSTSCCs), and base of tongue squamous cell carcinoma (BSCC) when stratifying for HPV DNA status, p16 expression and combined HPV/p16 status. We included all patients (n = 797) diagnosed with TSCCs and BSCCs in Eastern Denmark as registered in the Danish Head and Neck Cancer Group (DAHANCA) database and the Danish Pathology Databank, 2000-2010. Patients were treated according to national guidelines (radiotherapy +/- concomitant cisplatin). All specimens were analysed using HPV DNA PCR and p16 immunohistochemistry. Clinical information was retrieved from the DAHANCA database and the Danish National Patient Registry. Information on vital status was obtained from the Danish Civil Registration System. We observed improved OS for HPV+/p16+ BSCCs compared to HPV-/p16- (hazard ratio for death [HR], 0.15; 95% CI, 0.09-0.24). Among STSCCs, HPV+/p16+ showed the lowest HR (0.19, 95% CI, 0.13-0.29); whereas, HPV-/p16+ showed an intermediate HR (0.39; 95% CI, 0.22-0.70). For NSTSCCs, HPV+/p16+ and HPV-/p16+ showed similar OS (HRs, 0.39; 95% CI, 0.26-0.59; and 0.48; 95% CI, 0.24-0.95, respectively). Combined HPV+/p16+ was a significantly better prognostic marker in BSCCs and STSCCs than HPV DNA and p16, alone (all p-values < 0.05). Whereas, combined testing in NSTSCC was not better than p16 (p = 0.53), alone. In conclusion, double positivity for HPV/p16 in conjunction with the certainty of tumour site improved prognosis.

Stationary facial nerve paresis after surgery for recurrent parotid pleomorphic adenoma: a follow-up study of 219 cases in Denmark in the period 1985-2012.

The purpose was to assess degree of permanent facial nerve dysfunction after surgery for recurrent pleomorphic adenoma (RPA) of the parotid gland, including variables that might influence re-operation outcomes. Nationwide retrospective longitudinal cohort study including a questionnaire survey of patients undergoing surgery for RPA. Of 219 living patients, 198 (92 %) responded and 127 (63 %) reported no facial dysfunction. Statistically significant associations were found between number of surgeries and permanent facial nerve dysfunction of all degrees (OR 1.43, 95 % CI 1.16-1.78, p = 0.001). A not significant tendency for females to be associated with worse outcome was found (p = 0.073). Risks of different degrees of paresis after the second-fourth surgeries were found (OR 1.86-2.19, p < 0.05). Our study demonstrates a significant correlation between number of surgeries for RPA of the parotid and severity of facial nerve paresis. This is important when informing and planning treatment of these patients.

Does age affect prognosis in salivary gland carcinoma patients? A national Danish study.

AIM: To compare incidence, histology, treatment modalities, disease stages, and outcome in elderly patients (≥70 years) compared to younger (<70 years). METHODS: From the national Danish salivary gland carcinoma database, 871 patients diagnosed with a primary salivary gland carcinoma from January 1990 to December 2005 were identified. Variables necessary for statistical analyses were extracted from the database. RESULTS: The younger patients have a significantly better crude, disease-specific and recurrence-free survival than the elderly ones. In univariate analysis, significantly more patients in the young group were WHO performance status 0 and in disease stage I + II, and they presented with significantly more histological low grade tumors. In multivariate analysis, chronological age seemed to be of no prognostic significance to salivary gland carcinoma patients as opposed to performance status, disease stage and histological grade. CONCLUSIONS: Salivary gland carcinoma patients over the age of 70 years have a poor prognosis compared to younger patients, which can be explained by higher disease stages, more histological high grade subtypes and a poorer performance status at the time of diagnosis.

Pleomorphic adenoma of the parotid gland 1985-2010: A Danish nationwide study of incidence, recurrence rate, and malignant transformation.

BACKGROUND: Pleomorphic adenoma is the most frequent salivary gland tumor and is known for its tendency to recur and for its ability to transform to carcinoma ex pleomorphic adenoma (Ca-ex-PA). Along with pleomorphic adenoma demographics, we present the first nationwide study with long-term follow-up on these topics. METHODS: The Danish Pathology Data Bank was searched for parotid pleomorphic adenoma and Ca-ex-PA in the period 1985 to 2010 and all pathology descriptions were reviewed. Ca-ex-PA specimens were reviewed by a pathologist. RESULTS: A total of 5.497 patients were identified and 2.86% had at least one recurrence. An incidence of 4.29/100,000/year was found. The rate of malignant transformation in recurrent pleomorphic adenoma was 3.3%. CONCLUSION: We report an up-to-date assessment of the epidemiology of pleomorphic adenoma. We found an increasing incidence and low recurrence rate compared with previous studies. The risk of Ca-ex-PA for patients with recurrent pleomorphic adenoma was low compared to the literature. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1364-E1369, 2016.

Salivary adenoid cystic carcinoma in Denmark 1990-2005: Outcome and independent prognostic factors including the benefit of radiotherapy. Results of the Danish Head and Neck Cancer Group (DAHANCA).

AIM: To describe outcome and prognostic factors, including the effect of radiotherapy, in a consecutive national series of salivary gland adenoid cystic carcinomas. METHODS: From the national Danish salivary gland carcinoma database in the structure of DAHANCA, 201 patients diagnosed with adenoid cystic carcinoma, and treated with a curative intent, were identified in the period between 1990 and 2005. Variables necessary for statistical analyses were extracted from the database. RESULTS: The 10-year crude survival and disease specific survival rates were 58% and 75%, respectively. The 10-year locoregional control rate was 70%, and 36% of patients experienced a recurrence during follow-up (median 7.5 years); 18% developed distant metastases (most commonly to the lungs). In multivariate analysis, stage and margin status were both important factors with regards to survival and locoregional control. Radiotherapy did not improve survival, but it did improve the locoregional control rate. CONCLUSIONS: The treatment of choice is surgery with as wide margins as possible including elective, selective neck dissection. Adjuvant radiotherapy should be considered in patients with incomplete tumor resection, high disease stages, and tumors with a solid growth pattern.

Immunohistochemical biomarkers and FDG uptake on PET/CT in head and neck squamous cell carcinoma.

BACKGROUND: There is an exciting complementarity between the spatial resolution provided by molecular imaging of a single, often unspecific, biomarker on one hand and the more detailed biological profile achievable from a diagnostic biopsy using a panel of immunohistochemical (IHC) markers on the other. A number of previous studies have shown a relationship between glucose transport protein expression and 18F-Fludeoxyglucose (FDG) PET uptake. Here, FDG uptake is analyzed in relation to expression of a selected panel of IHC cancer biomarkers in head and neck squamous cell carcinomas (HNSCC). MATERIAL AND METHODS: IHC staining for Bcl-2, ß-tubulin-1 and 2, p53, EGFR, Ki-67, glutathione-S-transferase-π and p16 was performed on formalin-fixed paraffin embedded diagnostic biopsies from 102 HNSCC cases treated at Rigshospitalet during 2005-2009. The proportion of positive cells was used for analyses, except p16, which was scored according to EORTC guidelines. In all cases, maximal FDG standardized uptake value (SUV) metrics were extracted for the primary tumor, TSUVmax. Univariate linear regression and multiple linear regression of TSUVmax versus IHC markers were performed. RESULTS: In univariate analyses, TSUVmax showed negative associations with Bcl-2 (p = 0.002) and p16 (p = 0.005) indices and positive association with ß-tubulin-1 index (p = 0.003). On multivariate analysis, TSUVmax remained associated with ß-tubulin-1 (p = 0.009), Bcl-2 (p = 0.03) and p16 (p = 0.03). All correlations had r-squared < 0.3. CONCLUSION: Statistically significant correlations were observed between the expression of IHC biomarkers and maximum FDG uptake in the primary tumor.

Activation of the interleukin-6/Janus kinase/STAT3 pathway in pleomorphic adenoma of the parotid gland.

The interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway is of crucial importance in promoting tumorigenesis in several malignant tumors but may also be active in benign tumors, e.g., of pleomorphic adenoma (PA). In this study we characterize the expression of the pathway components with immunohistochemistry and selected mRNAs and microRNAs (miRNAs) regulated by this pathway in isolated duct- and myoepithelial cells in PA. 46 PAs were immunostained and 10 of these were used for in situ hybridization (ISH). Six frozen specimens were analyzed using reverse transcription-polymerase chain reaction (RT-PCR). Using immunohistochemistry, IL-6, JAK1, JAK2 and STAT3 were detected significantly more frequently in PA cells than in cells from normal salivary gland tissue. Using RT-PCR cyclin D1, fibroblast growth factor 2, and p21 were found to be overexpressed while matrix metallopeptidase 9 was detected at low levels in PA compared to normal salivary gland. ISH showed significant overexpression of miR-181b in PA, while miR-21 was undetectable in PA and normal tissue. Overexpression of the pathway components and its mRNA and miRNA products provide important clues regarding the growth of PAs. Our findings brings us one step closer to targeted treatment of this tumor entity, although in vitro studies are warranted to confirm this.

A reverse Warburg metabolism in oral squamous cell carcinoma is not dependent upon myofibroblasts.

BACKGROUND: The reverse Warburg effect describes the phenomenon that epithelial cancer cells take advantage of the metabolic machinery from nearby cancer-associated fibroblast, inducing them to produce lactate and ketones to fuel the high metabolic demands of the epithelial tumour tissues. This is in breast cancer observed as a lack of stromal caveolin-1 (CAV-1) and an increased expression of monocarboxylate transporter 4 (MCT-4) in the tumour stroma, with a concomitant increase in the expression of monocarboxylate transporter 1 (MCT-1) in the epithelial, tumour compartment. The lack of CAV-1 and increased expression of MCT-4 have been shown to have prognostic importance, primarily in patients with breast cancer. However, this phenomenon has only scarcely been described in oral squamous cell carcinoma (OSCC). Given the prognostic importance of myofibroblasts in OSCC, we also examined a potential relationship between the expression of MCT-4 and the presence of myofibroblasts. METHODS: Paraffin-embedded tissues from 30 patients with OSCC were immunostained with antibodies towards MCT-1, MCT-4, Cav-1, GLUT-1, α-SMA, TOMM20 and KI-67, and evaluated for their specific epithelial and stromal expression. RESULTS AND CONCLUSIONS: In patients with OSCC, we find an increased expression of MCT-1 and MCT-4 in both the epithelial and stromal compartment, with almost no overlap in their spatial expression. We found a large spatial overlap between α-SMA and MCT-1 in the stroma compartment, but no relationship between MCT-4 and myofibroblasts. Interestingly, we did not observe any relationship between the absence of CAV-1 and the presence of MCT-4 as has been shown in breast carcinomas.

A high and increasing HPV prevalence in tonsillar cancers in Eastern Denmark, 2000-2010: the largest registry-based study to date.

The aim was to explore whether the incidence of tonsillar squamous cell carcinomas (TSCCs) increased in Eastern Denmark, 2000-2010, and whether human papillomavirus (HPV) could explain the increase, and to assess the association of HPV prevalence with gender, age, and origin (i.e., the certainty of tonsillar tumor origin). We applied HPV DNA PCR and p16 immunohistochemistry to all TSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and in the Danish Pathology Data Bank (n = 632). Pathologists reviewed and subdivided the tumors into two groups: specified and nonspecified TSCCs. Approximately 10% of HPV-positive tumors was genotyped by amplicon next-generation sequencing. The overall crude incidence of TSCCs increased significantly (2.7% per year) and was explained by an increasing incidence of HPV-positive TSCCs (4.9% per year). The overall HPV prevalence was 58%, with HPV16 being the predominant HPV type. In multivariate analysis, the HPV prevalence was associated with age (<55 vs. >60 years) (OR, 1.72; 95% CI 1.13-2.63) and origin (nonspecified vs. specified TSCCs) (OR, 0.15; 95% CI 0.11-0.22). The association of HPV prevalence with origin increased over time in specified TSCCs (OR per year, 1.10; 95% CI 1.01-1.19), whereas no change over time was observed among nonspecified TSCCs (OR per year, 0.99; 95% CI 0.90-1.08). In conclusion, the observed increase in the number of HPV-positive TSCCs can explain the increasing number of TSCCs in Eastern Denmark, 2000-2010. HPV prevalence was associated with younger age (<55 years) and a high certainty of tonsillar tumor origin.

Human papillomavirus in head and neck squamous cell carcinoma of unknown primary is a common event and a strong predictor of survival.

BACKGROUND: The purpose of this study was to examine the prevalence of human papillomavirus (HPV) in patients with head and neck squamous cell carcinoma of unknown primary (CUP). METHODS: All patients diagnosed with and treated for CUP between January 1, 2000, and June 1, 2011, at two Danish medical centers were included. All patients received a thorough diagnostic work-up, including FDG-PET, before being diagnosed as CUP. We determined the HPV status in all patients using a combination of HPV DNA PCR and p16 stain. In addition, clinical information on the study patients was retrieved from clinical records. RESULTS: Of the identified 60 patients with CUP, 13 were shown to be positive for HPV DNA, amounting to 22% of the study population. In addition, we were able to show a clear disease-free and overall-survival benefit in the HPV-positive group, with a hazard ratio of 0.16 (95% CI: 0.038-0.67) for over-all survival. This survival benefit was also apparent when adjusted for advanced age in a multivariate Cox regression analysis. CONCLUSION: A fairly large percentage of CUP cases are HPV-related, and because this is related to both the location and prognosis, we recommend HPV testing as part of the diagnostic work-up.

MiR-21 expression in the tumor stroma of oral squamous cell carcinoma: an independent biomarker of disease free survival.

Oral squamous cell carcinoma (OSCC) patients have a high mortality rate; thus, new clinical biomarkers and therapeutic options are needed. MicroRNAs (miRNAs) are short noncoding RNAs that regulate posttranscriptional gene expression and are commonly deregulated in OSCC and other cancers. MicroRNA-21 (miR-21) is the most consistently overexpressed miRNA in several types of cancer, and it might be a useful clinical biomarker and therapeutic target. To better understand the role of miR-21 in OSCC, paraffin-embedded tumor tissue samples from 86 patients with primary OSCC were analyzed by in situ hybridization. We found that miR-21 was primarily expressed in the tumor stroma and in some tumor-associated blood vessels with no expression in the adjacent normal epithelia or stroma. Using image analysis, we quantitatively estimated miR-21 expression levels specifically in the stroma of a cohort of OSCC samples. These miR-21 levels significantly correlated with disease free survival with the highest levels being located in the stroma. Stromal miR-21 expression was independently associated with a poorer prognosis, even after adjusting for clinical parameters (perineural invasion and N-stage) in a multivariate analysis. In summary, we have shown that miR-21 is located in the carcinoma cells, stroma and blood vessels of tumors, and its expression specifically in the stromal compartment has a negative prognostic value in OSCC.

Staging of cervical lymph nodes in oral squamous cell carcinoma: adding ultrasound in clinically lymph node negative patients may improve diagnostic work-up.

INTRODUCTION: Clinical staging of patients with oral squamous cell carcinoma (OSCC) is crucial for the choice of treatment. Computed tomography (CT) and/or magnetic resonance imaging (MRI) are typically recommended and used for staging of the cervical lymph nodes (LNs). Although ultrasonography (US) is a non-expensive, accessible and non-ionising imaging modality this method is not consistently used. This study aimed to investigate if addition of US of patients classified as clinically LN negative (cN0) by CT and/or MRI, increases the detection of LN metastases. Also, we aimed to identify which of the sonographic characteristics: echogenicity, border, shape, appearance of hilum and nodal blood-flow pattern best detect metastases in this patient group. METHOD: Fifty-one patients with OSCC classified as cN0 by CT/MRI were consecutively included and prospectively examined with US prior to sentinel node biopsy or selective neck dissection. Localisation, size and sonographic characteristics were registered for each LN and compared with the pathological findings. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for different size measurements and sonographic characteristics. RESULTS: We found that short axial diameter was the best size criterion for detection of metastases. However, the sonographic characteristics were better predictors than size and the presence at least four of the sonographic characteristics: hypo-echoic or heterogeneous appearance; irregular border; spherical shape; absence of nodal hilum; and peripheral nodal blood-flow resulted in a sensitivity of 43.8; specificity 91.4; PPV 70.0; and NPV 78.0. The number of patients with occult metastases decreased from 16 out of 51 (31%) to nine out of 51 (18%). Three patients (6%) were over-staged by US. CONCLUSION: The addition of US to the clinical work-up of patients with cN0 OSCC increases the detection of metastases, thus US potentially reduces the number of patients requiring a secondary neck surgery after sentinel node biopsy.

Lacrimal gland pleomorphic adenoma and carcinoma ex pleomorphic adenoma: genomic profiles, gene fusions, and clinical characteristics.

PURPOSE: To study genetic alterations in lacrimal gland pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma (Ca-ex-PA) with focus on copy number changes and expression patterns of the translocation target genes PLAG1, HMGA2, and CRTC1-MAML2 in relation to clinical data. DESIGN: Experimental study. PARTICIPANTS: A total of 36 tumors from 32 patients with lacrimal gland PA or Ca-ex-PA were included in the study. METHODS: Genome wide, high-resolution array-based comparative genomic hybridization (arrayCGH) and immunohistochemistry were used to study the genomic profiles and expression patterns of the translocation targets PLAG1, HMGA2, and CRTC1-MAML2. MAIN OUTCOME MEASURES: Copy number alterations (gains/losses) and protein expression of PLAG1, HMGA2, and CRTC1-MAML2. RESULTS: Genome-wide arrayCGH analysis revealed normal genomic profiles in 10 of 17 PA samples. The average number of genomic imbalances per tumor was 3.25 (range, 1-7) in primary and recurrent PAs with alterations compared with 7.7 (range, 4-12) in Ca-ex-PAs. Five recurrent copy number alterations were identified in PAs, including losses of 1pter-p31.3, 6q22.1-q24.3, 8q24.22-q24.3, and 13q21.31-q21.33, and gain of 9p23-p22.3. Gain of 9p23-p22.3 also was seen in a Ca-ex-PA. In Ca-ex-PA, gain of 22q12.3-qter was the only recurrent alteration. Detailed analysis of the array data identified NFIB and PDGFB as the 2 major candidate target oncogenes that may be activated as a result of copy number gains involving 9p and 22q. Both genes have been implicated in the pathogenesis of PA and other types of salivary gland tumors. Immunohistochemical analysis revealed frequent overexpression of the translocation target gene PLAG1 in PAs and in 1 Ca-ex-PA. In contrast, overexpression of HMGA2 was observed in only a small subset of PAs. The CRTC1-MAML2 fusion oncoprotein was overexpressed in 2 mucoepidermoid Ca-ex-PAs. CONCLUSIONS: Lacrimal and salivary gland PAs and Ca-ex-PAs have similar genomic profiles and frequently overexpress the PLAG1 oncoprotein. Copy number gains involving 9p23-p22.3 (NFIB) and 22q12-qter (PDGFB) may be of importance for disease progression in a subset of lacrimal gland PAs.

Three-year follow-up of sentinel node-negative patients with early oral cavity squamous cell carcinoma.

BACKGROUND: Resection of the primary tumor followed by sentinel node biopsy (SNB) for the clinically N0 patient has been implemented in our Head and Neck University Center. The purpose of this study was to report on the outcome for patients with negative SNB. METHODS: From April 2007 to October 2009, 53 consecutive SNB-negative patients with oral cavity squamous cell carcinoma (SCC) T1 to T2 were accrued. Follow-up was done continuously with the most recent examination in October 2011. The location of the sentinel lymph nodes was determined using dynamic and planar lymphoscintigraphy and single photon emission CT (SPECT)-CT. Intraoperatively, a hand-held gamma probe was applied. The harvested sentinel lymph nodes underwent histopathologic examination using step-serial sectioning at 150-µm intervals and immunohistochemistry. In the follow-up period, we observed and examined the SNB-negative patients for recurrence, morbidity, and mortality. RESULTS: Fifty-three SNB-negative patients were identified. Eight patients received adjuvant radiotherapy (RT) because of incomplete excision on the T site after the primary operation. An additional 2 patients received RT because of recurrences on the T site and N site. One patient died of recurrence on the T site and N site without having received additional treatment. Six patients died of nonrelated causes. During follow-up, 3 patients with both T-site and N-site recurrence were found. No case of isolated recurrence on the N site only was found. Thirty-six SNB-negative patients treated only surgically with a median follow-up of 37 months (range, 25-52 months) and no recurrence remain under active review. CONCLUSION: Only 3 of the SNB-negative patients subsequently developed recurrence in the T site and N site. The remaining 36 patients had no N-site recurrence at median follow-up of 37 months.

Human papillomavirus and oropharyngeal cancer in Greenland in 1994-2010.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is associated with the sexually transmitted human papillomavirus (HPV), smoking and alcohol. In Greenland, a high rate of HPV-induced cervical cancer and venereal diseases are found, which exposes the population for high risk of HPV infection. In Greenland, only girls are included in the mandatory HPV vaccination program. OBJECTIVE: To investigate the annual incidence of OPSCC and the proportion of HPV-associated OPSCC (HPV+ OPSCC) in Greenland in 1994-2010. DESIGN: At Rigshospitalet, University of Copenhagen, we identified all Greenlandic patients diagnosed and treated for OPSCC from 1994 to 2010. Sections were cut from the patient's paraffin-embedded tissue blocks and investigated for p16 expression by immunohistochemistry. HPV analyses were performed with 2 sets of general HPV primers and 1 set of HPV16-specific primer. HPV+ OPSCC was defined as both >75% p16+ cells and PCR positive for HPV. RESULTS: Of 26 Greenlandic patients diagnosed with OPSCC, 17 were males and 9 were females. The proportion of HPV+ OPSCC in the total study period was 22%, without significant changes in the population in Greenland. We found an increase in the proportion of HPV+ OPSCC from 14% in 1994-2001 to 25% in 2002-2010 (p=0.51). Among males from 20 to 27% (p=0.63) and in females from 0 to 20% (p=0.71). The annual OPSCC incidence increased from 2.3/100,000 (CI=1.2-4.2) in 1994-2001 to 3.8/100,000 (CI=2.4-6.2) in 2002-2010: among males from 2.4/100,000 (CI=1.0-5.7) to 5.0/100,000 (CI=2.9-8.9). CONCLUSION: Even though the population is at high risk of HPV infection, the proportion of 22% HPV+ OPSCC in the total study period is low compared to Europe and the United States. This might be explained by our small study size and/or by ethnic, geographical, sexual and cultural differences. Continuing observations of the OPSCC incidence and the proportion of HPV+ OPSCC in Greenland are needed.

Nodal yield in selective neck dissection.

CONCLUSION: The total lymph node yield in neck dissection is highly variable and depends on anatomical, surgical and pathological parameters. A minimum yield of six lymph nodes for a selective neck dissection (SND) as recommended in guidelines lies in the lower range of the reported clinical nodal yields. A future application of a lymph node ratio may improve the risk stratification of head and neck cancer patients. However, this will require a higher number of retrieved lymph nodes. OBJECTIVES: To compare the clinical guideline recommendations for nodal yield in SND with the number of lymph nodes obtained from cadavers and the clinical nodal yield reported in the literature. METHODS: Lymph nodes retrieved from SND specimens from nine fresh cadavers were quantified histopathologically. The literature on nodal yields reportedly obtained by clinicians performing neck dissections was reviewed. Finally, the discussion makes reference to the six lymph nodes currently recommended in international clinical guidelines. RESULTS: For clinical SNDs (I-III) the lowest mean nodal yield was 19.4, for SNDs (II-IV) it was 26.4. The cadaver SNDs (I-III and II-IV) yielded 8.8 (range 1-15) and 10.4 nodes (range 1-19), respectively.