Oropharyngeal squamous cell carcinoma: p16/p53 immunohistochemistry as a strong predictor of HPV tumour status.

AIMS: Oropharyngeal squamous cell carcinomas (OPSCC) related to human papillomavirus (HPV) infection have a better prognosis than those without HPV infection. Although p16INK4a overexpression is used as a surrogate marker for HPV infection, 5-20% of p16-positive OPSCC are described as being unrelated to HPV infection, with worse overall survival compared to OPSCC-related HPV. There is therefore a risk of undertreating a proportion of OPSCC patients falsely considered to be HPV-driven because of p16 positivity. TP53 mutations are highly prevalent in OPSCC driven by mutagens in tobacco and alcohol. We describe herein a combined p16/p53 algorithm to predict HPV tumour status in OPSCC. METHODS AND RESULTS: A total of 110 OPSCC were identified in the database of the pathology department and were studied using p16 and p53 immunohistochemistry. For p16-positive or p16-negative/wild-type patterns-p53 (WT-p53) cases (n = 63), DNA in-situ hybridisation for high-risk HPV was performed, and if negative the HPV status was controlled by HPV DNA polymerase chain reaction (PCR) (n = 19). A significant association between TP53 mutation and pattern of p53 expression was found (WT-p53, seven of 16, P < 0.001). The p16-positive/WT-p53 was significantly associated with HPV+ tumour status (p16-positive/WT-p53, 50 of 110, P < 0.001). Interestingly, a subset of p16-positive OPSCC was unrelated to HPV (13.5%, eight of 59), and showed mutant-type staining of p53 expression. CONCLUSIONS: The p16 protein immunopositivity in conjunction with the mutant-type pattern of p53 staining helped to reclassify a subset of p16-positive OPSCC as OPSCC-unrelated HPV. This approach could be routinely applied by pathologists involved in the management of OPSCC, because of their potential therapeutic implications.

Role of gene signatures combined with pathology in classification of oropharynx head and neck cancer.

Treatment personalisation remains an unmet need in oropharynx cancer (OPC). We aimed to determine whether gene expression signatures improved upon clinico-pathological predictors of outcome in OPC. The clinico-pathological predictors, AJCC version 7 (AJCC 7), AJCC 8, and a clinical algorithm, were assessed in 4 public series of OPC (n = 235). Literature review identified 16 mRNA gene expression signatures of radiosensitivity, HPV status, tumour hypoxia, and microsatellite instability. We quality tested signatures using a novel sigQC methodology, and added signatures to clinico-pathological variables as predictors of survival, in univariate and multivariate analyses. AJCC 7 Stage was not predictive of recurrence-free survival (RFS) or overall survival (OS). AJCC 8 significantly predicted RFS and OS. Gene signature quality was highly variable. Among HPV-positive cases, signatures for radiosensitivity, hypoxia, and microsatellite instability revealed significant underlying inter-tumour biological heterogeneity, but did not show prognostic significance when adjusted for clinical covariates. Surprisingly, among HPV-negative cases, a gene signature for HPV status was predictive of survival, even after adjustment for clinical covariates. Across the whole series, several gene signatures representing HPV and microsatellite instability remained significant in multivariate analysis. However, quality control and independent validation remain to be performed to add prognostic information above recently improved clinico-pathological variables.

[Treatment de-intensification strategies for HPV-driven oropharyngeal cancer: A short review]. / Désescalade thérapeutique dans les cancers de l'oropharynx induit par les HPV : mise au point.

The incidence of oropharyngeal cancer induced by human papillomavirus (HPV) infection is steadily increasing in developed countries. These tumors are more chemoradiosensitive and have a better prognosis than HPV-negative one. In addition, they occur in younger and better-off patients with longer life expectancy. Current radiotherapy and chemotherapy protocols are currently being questioned as they may expose HPV-positive patients to excessive treatment and unnecessary toxic effects. Less intensive treatment regimens could possibly achieve similar efficacy with lower toxicity and improved quality of life. The aim of this work was to summarize the knowledge on these tumors and their implications for radiation oncologists. In this update, we will discuss ongoing de-escalation trials and highlight the issues raised by these studies. We will also comment on the results of recently published de-intensification studies. Three main strategies are analyzed in the present article: the de-escalation of the drug associated with radiotherapy, the de-escalation of the radiotherapy dose (in concomitant chemoradiotherapy, after induction chemotherapy, in a postoperative setting) and de-escalation of radiation target volumes. Our findings ultimately indicate that clinicians should not change the management of oropharyngeal cancer patients outside of clinical trials.

Stratification of HPV-associated and HPV-negative oropharyngeal squamous cell carcinomas based on DNA methylation epigenotypes.

While the incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing in these two decades, primarily due to human papillomavirus (HPV), stratification of OPSCC into molecular subgroups showing different clinicopathological features has not been fully investigated. We performed DNA methylome analysis using Infinium 450k for 170 OPSCC cases, including 89 cases in our cohort and 81 cases reported by The Cancer Genome Atlas, together with targeted exon sequencing analysis. We stratified OPSCC by hierarchical clustering analysis using methylome data. Methylation levels of classifier markers were validated quantitatively using pyrosequencing, and area under the curve (AUC) values of receiver operating characteristics (ROC) curves were calculated. OPSCC was stratified into four epigenotypes: HPV(+) high-methylation (OP1), HPV(+) intermediate-methylation (OP2), HPV(-) intermediate-methylation (OP3) and HPV(-) low-methylation (OP4). Ten methylation marker genes were generated: five to classify HPV(+) cases into OP1 and OP2, and five to classify HPV(-) cases into OP3 and OP4. AUC values of ROC curves were 0.969 and 0.952 for the two marker panels, respectively. While significantly higher TP53 mutation and CCND1 copy number gains were observed in HPV(-) than in HPV(+) groups (p < 0.01), no significant difference of genomic aberrations was observed between OP1 and OP2, or OP3 and OP4. The four epigenotypes showed significantly different prognosis (p = 0.0006), distinguishing the most favorable OPSCC subgroup (OP1) among generally favorable HPV(+) cases, and the most unfavorable OPSCC subgroup (OP3) among generally unfavorable HPV(-) cases. HPV(+) and HPV(-) OPSCC are further divided into distinct DNA methylation epigenotypes, showing significantly different prognosis.

[A comparison of the 7th and 8th edition of the AJCC TNM staging systems for predicting survival in oropharyngeal cancer].

Objective:The aim of this study is to evaluate the prognostic value of the 8th edition of AJCC TNM classification in comparison with the 7th edition for oropharyngeal cancer. Method: The clinical and pathological data of 142 patients with oropharyngeal squamous cell carcinoma were retrospectively analyzed. The p16 protein was detected by immunohistochemical staining. Survival and survival analysis were performed using the Kaplan-Meier method and the Log-rank test. Result:The 5-year disease-specific survival（DSS）,the 5-year overall survival (OS) and the median survival time for patients with oropharyngeal cancer were 55.4%,50.4% and 60.3 months, respectively. P16-immunostaining was scored positive in 39 samples (27.5%,39/142).Based on the seventh edition of AJCC staging, there were 4 patients in stage Ⅰ,17 patients in stage Ⅱ,27 patients in stage Ⅲ and 94 patients in stage Ⅳ,respectively.However, there was no significant difference in survival between the patients with stage Ⅰ-Ⅱ and those with Ⅲ-Ⅳ(5-year DSS:75.9% of stage Ⅰ-Ⅱ patients vs. 52.2% of stage Ⅲ-Ⅳ patients;P=0.109).In comparison, 22 patients were diagnosed as stage Ⅰ,24 were stage Ⅱ,27 were stage Ⅲ and 69 were stage Ⅳ using the eighth edition. The 5-year DSS for patients with stage Ⅰ,Ⅱ,Ⅲ and Ⅳ was 88.4%, 80.5%, 73.2% and 29.1%, respectively. The overall difference was statistically significant (P=0.000). Conclusion:Compared with the seventh edition staging, the eighth edition of the AJCC oropharyngeal cancer staging system considers the prognosis of patients with different causes of oropharyngeal cancer, and can more accurately predict the prognosis of patients.

HPV Status Improves Classification of Head and Neck Gray Zone Cancers.

In epidemiologic studies, patients with head and neck squamous cell carcinoma (HNSCC) are classified mainly by the International Classification of Diseases (ICD) codes. However, some patients are of an unclear subsite, the "gray zone" cases, which could reflect ICD coding error, absence of primary subsite, or extensive primary tumors that cross over multiple subsites of the oral cavity and oropharynx. Patients with gray zone squamous cell carcinomas were compared with patients with oral cavity squamous cell carcinoma (OSCC) or oropharyngeal squamous cell carcinoma (OPSCC) and stratified by human papillomavirus (HPV) status that was determined by p16 immunostaining or HPV serology. Comparisons consisted of clinicodemographic features and prognostic outcomes presented by Kaplan-Meier curves and Cox proportional hazards regression models, reported as hazard ratios. There were 158 consecutive patients with gray zone HNSCC diagnosed at the Princess Margaret Cancer Center between 2006 and 2017: 66 had subsite coding discrepancies against the clinician's documentation ("discrepant" cases; e.g., the diagnosis by the clinician was OSCC, while the classification by ICD coding was OPSCC), while 92 were squamous cell carcinoma of unknown primary of the head and neck (SCCUPHN) after complete diagnostic workup. Comparators included 721 consecutive OSCC and 938 OPSCC adult cases. All HPV-positive cohorts (OPSCC, discrepant, and SCCUPHN) had similar clinicodemographic characteristics and better 3- and 5-y overall survival and disease-free survival than their HPV-negative counterparts. In contrast, HPV-negative discrepant cases had prognostic outcomes most similar to HPV-negative OPSCC cases, while HPV-negative SCCUPHN had survival outcomes most similar to those of patients with OSCC in this study. HPV-positive status can improve the classification of patients with unclear or discrepant oral/oropharyngeal subsite, an improvement over classification systems that are solely clinician defined or conducted through ICD coding. However, due to clinical practice, we could not make definitive reclassification for patients with HPV-negative gray zone HNSCC.

HPV detection and genotyping of head and neck cancer biopsies by molecular testing with regard to the new oropharyngeal squamous cell carcinoma classification based on HPV status.

Recently, both the World Health Organization/International Agency for Research on Cancer (WHO/IARC) and the American Joint Committee on Cancer (AJCC) have classified oropharyngeal squamous cell carcinoma (OPSCC) on the basis of HPV status. For this purpose, the WHO/IARC recommended direct molecular HPV testing. In practice, formalin-fixed, paraffin-embedded (FFPE) biopsy specimens are frequently the only available samples. We herein compared in parallel two commercially available molecular assays that were first designed for cervical HPV detection and genotyping: Inno-Lipa HPV Genotyping Extra II (IL) and Anyplex II HPV28 (AP28). A total of 55 samples were tested. By IL assay, chosen as reference assay, 27 (49.1%) biopsies were positive for HPV16, 10 (18.2%) were positive for HPV but negative for HPV16, and 18 (32.7%) were negative for HPV. A valid result with AP28 was obtained for 51 biopsy samples (92.7%). Among 37 HPV positive samples by IL, 33 (89.2%) were positive by AP28. The agreement between both assays was good (Cohen's κ = 0.78). Among the six discrepancies between assays, always associated with low HPV16 viral load, four biopsies positive for HPV16 by IL could not be detected by AP28. Taken together, these observations demonstrate that both assays could be used in routine HPV detection and genotyping on FFPE biopsy samples of head and neck tumours.

[WHO classification of head and neck tumours 2017: Main novelties and update of diagnostic methods]. / Classification de l'OMS 2017 des tumeurs de la tête et du cou : principales nouveautés et mise à jour des méthodes diagnostiques.

The publication of the new WHO classification of head and neck tumours in 2017 brought major modifications. Especially, a new chapter is dedicated to the oropharynx, focusing on the description of squamous cell carcinoma induced by the virus Human Papilloma Virus (HPV), and new entities of tumors are described in nasal cavities and sinuses. In this article are presented the novelties and main changes of this new classification, as well as the updates of the diagnostic methods (immunohistochemistry, cytogenetics or molecular biology).

HPV-relatedness definitions for classifying HPV-related oropharyngeal cancer patient do impact on TNM classification and patients' survival.

BACKGROUND: Given the different nature and better outcomes of oropharyngeal carcinoma (OPC) associated with human papillomavirus (HPV) infection, a novel clinical stage classification for HPV-related OPC has been accepted for the 8th edition AJCC TNM (ICON-S model). However, it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. MATERIAL AND METHODS: The aim of this study was to compare different staging system models proposed for HPV-related OPC patients: 7th edition AJCC TNM, RPA stage with non-anatomic factors (Princess Margaret), RPA with N categories for nasopharyngeal cancer (MD-Anderson) and AHR-new (ICON-S), according to different HPV-relatedness definitions: HPV-DNA detection plus an additional positive marker (p16INK4a or HPV-mRNA), p16INK4a positivity alone or the combination of HPV-DNA/p16INK4a positivity as diagnostic tests. RESULTS: A total of 788 consecutive OPC cases diagnosed from 1991 to 2013 were considered eligible for the analysis. Of these samples, 66 (8.4%) were positive for HPV-DNA and (p16INK4a or HPV-mRNA), 83 (10.5%) were p16INK4a positive and 58 (7.4%) were double positive for HPV-DNA/p16INK4a. ICON-S model was the staging system, which performed better in our series when using at least two biomarkers to define HPV-causality. When the same analysis was performed considering only p16INK4a-positivity, RPA stage with non-anatomic factors (Princess Margaret) has the best classification based on AIC criteria. CONCLUSION: HPV-relatedness definition for classifying HPV-related OPC patient do impact on TNM classification and patients' survival. Further studies assessing HPV-relatedness definitions are warranted to better classify HPV-related OPC patients in the era of de-escalation clinical trials.

What should we expect from robotic surgery for second primary oropharyngeal cancer?

The outcomes of second primary oropharyngeal cancer (SPOPC) may not be determined by oropharyngeal cancer but from the other index cancer as well. The management of (SPOPC) remains inconclusive and limited. Transoral robotic surgery (TORS) to maximize the functional outcomes without reducing oncologic effect is suggested as the primary treatment for selected oropharyngeal cancer. This study aimed to evaluate the feasibility and outcomes of TORS for the management of SPOPC. Patients who underwent TORS from January 2011 to June 2015 at a tertian referral center in Taiwan were recruited. Loco-regional status, overall survival (OS), disease-specific survival (DSS), and postoperative functional status were evaluated. Fifteen patients received TORS for SPOPC with curative intent, including eleven with tongue-base carcinomas, and four with tonsil carcinomas. One case was terminated because of inadequate exposure and the other 14 cases were completed with negative pathologic margins. Two-year OS and DSS were 53 and 77%, respectively. Patients with SPOPC occurring within 6 months had poorer outcomes (p = 0.044). The median time to feeding-tube removal was 5 days, and one patient had long-term gastric-tube dependence. Patients of age <65 years with synchronous SPOPC and esophageal cancer as the other index cancer were significant worse in oncologic outcomes. We concluded that TORS is a feasible alternative treatment in selected patients with SPOPC. Patients with metachronous T1-2 SPOPC without an esophageal primary can achieve excellent survival after TORS, while TORS can maximize functional preservation with limited destruction in patients with low life expectancy.

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Oropharynx.

The changes for oropharyngeal lesions in the 2017 edition of the WHO/IARC Classification of Head and Neck Tumours reference book are dramatic and significant, largely due to the growing impact of high risk human papillomavirus (HPV). The upcoming edition divides tumours of the oral cavity and oropharynx into separate chapters, classifies squamous cell carcinomas (SCC) of the oropharynx on the basis of HPV status, abandons the practice of histologic grading for oropharyngeal SCCs that are HPV positive, recognizes small cell carcinoma of the oropharynx, and combines polymorphous low grade adenocarcinoma and cribriform adenocarcinoma of tongue and minor salivary glands under the single term "polymorphous adenocarcinoma." This review not only calls attention to these changes, but describes the rationale driving these changes and highlights their implications for routine clinical practice.

Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study.

BACKGROUND: Human papillomavirus-related (HPV+) oropharyngeal cancer is a rapidly emerging disease with generally good prognosis. Many prognostic algorithms for oropharyngeal cancer incorporate HPV status as a stratification factor, rather than recognising the uniqueness of HPV+ disease. The International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) aimed to develop a TNM classification specific to HPV+ oropharyngeal cancer. METHODS: The ICON-S study included patients with non-metastatic oropharyngeal cancer from seven cancer centres located across Europe and North America; one centre comprised the training cohort and six formed the validation cohorts. We ascertained patients' HPV status with p16 staining or in-situ hybridisation. We compared overall survival at 5 years between training and validation cohorts according to 7th edition TNM classifications and HPV status. We used recursive partitioning analysis (RPA) and adjusted hazard ratio (AHR) modelling methods to derive new staging classifications for HPV+ oropharyngeal cancer. Recent hypotheses concerning the effect of lower neck lymph nodes and number of lymph nodes were also investigated in an exploratory training cohort to assess relevance within the ICON-S classification. FINDINGS: Of 1907 patients with HPV+ oropharyngeal cancer, 661 (35%) were recruited at the training centre and 1246 (65%) were enrolled at the validation centres. 5-year overall survival was similar for 7th edition TNM stage I, II, III, and IVA (respectively; 88% [95% CI 74-100]; 82% [71-95]; 84% [79-89]; and 81% [79-83]; global p=0·25) but was lower for stage IVB (60% [53-68]; p<0·0001). 5-year overall survival did not differ among N0 (80% [95% CI 73-87]), N1-N2a (87% [83-90]), and N2b (83% [80-86]) subsets, but was significantly lower for those with N3 disease (59% [51-69]; p<0·0001). Stage classifications derived by RPA and AHR models were ranked according to survival performance, and AHR-New was ranked first, followed by AHR-Orig, RPA, and 7th edition TNM. AHR-New was selected as the proposed ICON-S stage classification. Because 5-year overall survival was similar for patients classed as T4a and T4b, T4 is no longer subdivided in the re-termed ICON-S T categories. Since 5-year overall survival was similar among N1, N2a, and N2b, we re-termed the 7th edition N categories as follows: ICON-S N0, no lymph nodes; ICON-S N1, ipsilateral lymph nodes; ICON-S N2, bilateral or contralateral lymph nodes; and ICON-S N3, lymph nodes larger than 6 cm. This resembles the N classification of nasopharyngeal carcinoma but without a lower neck lymph node variable. The proposed ICON-S classification is stage I (T1-T2N0-N1), stage II (T1-T2N2 or T3N0-N2), and stage III (T4 or N3). Metastatic disease (M1) is classified as ICON-S stage IV. In an exploratory training cohort (n=702), lower lymph node neck involvement had a significant effect on survival in ICON-S stage III but had no effect in ICON-S stage I and II and was not significant as an independent factor. Overall survival was similar for patients with fewer than five lymph nodes and those with five or more lymph nodes, within all ICON-S stages. INTERPRETATION: Our proposed ICON-S staging system for HPV+ oropharyngeal cancer is suitable for the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer TNM classification. Future work is needed to ascertain whether T and N categories should be further refined and whether non-anatomical factors might augment the full classification. FUNDING: None.

TNM classification of the oral cavity carcinomas: some suggested modifications.

TNM system is a universally recognized cancer classification. It's based on the assessment of anatomical extent of tumor (T), nodal (N) and distant metastases (M). The first edition of TNM was published in 1968 and has since been updated several times. Relevant characteristics that affect prognosis prognosis, such as depth of invasion, tumor volume, surgical margin infiltration, and the number of involved nodes as well as the presence of extracapsular spread (such data should be determined by the pathologist and included in pTNM staging ­ ed. note) are not included in the TNM classification. Following a discussion on most recent classification updates we will discuss the factors, which in our opinion and in concordance with the most recent literature, deserve special consideration and influence management of oral carcinomas.

MRI texture analysis predicts p53 status in head and neck squamous cell carcinoma.

BACKGROUND AND PURPOSE: Head and neck cancer is common, and understanding the prognosis is an important part of patient management. In addition to the Tumor, Node, Metastasis staging system, tumor biomarkers are becoming more useful in understanding prognosis and directing treatment. We assessed whether MR imaging texture analysis would correctly classify oropharyngeal squamous cell carcinoma according to p53 status. MATERIALS AND METHODS: A cohort of 16 patients with oropharyngeal squamous cell carcinoma was prospectively evaluated by using standard clinical, histopathologic, and imaging techniques. Tumors were stained for p53 and scored by an anatomic pathologist. Regions of interest on MR imaging were selected by a neuroradiologist and then analyzed by using our 2D fast time-frequency transform tool. The quantified textures were assessed by using the subset-size forward-selection algorithm in the Waikato Environment for Knowledge Analysis. Features found to be significant were used to create a statistical model to predict p53 status. The model was tested by using a Bayesian network classifier with 10-fold stratified cross-validation. RESULTS: Feature selection identified 7 significant texture variables that were used in a predictive model. The resulting model predicted p53 status with 81.3% accuracy (P < .05). Cross-validation showed a moderate level of agreement (κ = 0.625). CONCLUSIONS: This study shows that MR imaging texture analysis correctly predicts p53 status in oropharyngeal squamous cell carcinoma with ∼80% accuracy. As our knowledge of and dependence on tumor biomarkers expand, MR imaging texture analysis warrants further study in oropharyngeal squamous cell carcinoma and other head and neck tumors.

Histological subtypes and characteristic structures of HPV-associated oropharyngeal carcinoma: study with Japanese cases.

BACKGROUND: Human papillomavirus-associated oropharyngeal carcinoma (HPV-OPC) is clinicopathologically distinct entity from the HPV-unassociated one (nHPV-OPC). This study aimed to determine the relationship between histological subtypes of OPC and HPV status for Japanese cases and to identify histological structures of HPV-OPC. METHODS: 66 OPC cases were categorized into conventional squamous cell carcinoma (SCC) and the variants. Conventional SCC was subcategorized into keratinizing (KSCC), non-keratinizing (NKSCC), and hybrid SCC (HSCC). HPV status of all cases was determined using p16-immunohistochemistry and HPV-DNA ISH. RESULTS: Two histological subtypes, NKSCC and HSCC, tended to be HPV-OPC and KSCC tended to be nHPV-OPC with statistical significance. Two histological structures, abrupt keratinization, defined in the text, and comedo-necrosis among non-maturing tumor island, were observed for 58.1% and 38.7% of HPV-OPC, and tended to exist for HPV-OPC with statistical significance. CONCLUSIONS: This study showed the association of NKSCC/HSCC with HPV-OPC in Japanese cases, and two histological structures, abrupt keratinization and comedo-necrosis among non-maturing island, were considered characteristic histological features of HPV-OPC. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1816432541113073.

Morphologic features of conventional squamous cell carcinoma of the oropharynx: 'keratinizing' and 'nonkeratinizing' histologic types as the basis for a consistent classification system.

Morphologic assessment is one of the most basic tools that pathologists use to classify tumors. Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx has unique morphologic features that can be readily recognized under the microscope. Yet, these features are not widely recognized or uniformly reported. In our practice, we group oropharyngeal squamous cell carcinomas into 'nonkeratinizing', 'nonkeratinizing with maturation', and 'keratinizing' histologic types. The 'nonkeratinizing' type has a very strong association with HPV, while the 'keratinizing' type has a weaker association with the virus. 'Nonkeratinizing with maturation' is intermediate but much more closely related to the 'nonkeratinizing' type. This classification system parallels that of sinonasal and nasopharyngeal squamous cell carcinomas where nonkeratinizing squamous cell carcinomas are widely recognized histologic variants. This review will discuss this classification system and its utility in routine clinical practice.

Recognition of nonkeratinizing morphology in oropharyngeal squamous cell carcinoma - a prospective cohort and interobserver variability study.

AIMS: Nonkeratinizing morphology in oropharyngeal squamous cell carcinoma (NKSCC) strongly correlates with human papillomavirus and p16 status, but as a unique diagnostic entity is not widely recognized by pathologists. We sought to prospectively examine the performance of a new histological typing system during 1 year of routine clinical practice (Aim 1) and also its reproducibility amongst six head and neck pathologists using a 40 case test set (Aim 2). METHODS AND RESULTS: The three histological types were: Type 1 (keratinizing), Type 2 (nonkeratinizing with maturation) and Type 3 (nonkeratinizing). For Aim 1, there were 85 cases. p16 immunohistochemistry was positive in five of the 18 (27.8%) cases classified as Type 1, 18 of the 19 (94.7%) as Type 2, and 47 of the 48 (97.9%) as Type 3. For Aim 2, agreement among pathologists on the test cases was best for types 1 and 3 (kappa values 0.62 and 0.56; P < 0.0001) and lowest for type 2 (kappa 0.35; P < 0.0001). All 21 cases classified as NK SCC (type 3) by any of the reviewers was p16 positive. CONCLUSIONS: Pathologists can recognize NK SCC with good agreement, and when a pathologist classifies a tumour as NK SCC, this reliably predicts p16 positivity.

Magnetic resonance imaging of oropharyngeal cancer.

Magnetic resonance imaging (MRI) is a powerful tool for cross-sectional analysis of head and neck anatomy and pathology. This is especially true with regard to oropharyngeal neoplasms, where soft tissue spread, nodal disease, perineural extension, and osseous involvement may significantly alter therapy and prognosis. In this article, we will provide a background on oropharyngeal cancers and MRI techniques and strategies, describing potential advantages of MRI with regard to particular anatomic subsites of the oropharynx. Future imaging trends in perfusion and diffusion MRI of such cancers are also discussed.