The Role of HPV in Determining Treatment, Survival, and Prognosis of Head and Neck Squamous Cell Carcinoma.

Human papillomavirus (HPV) infection has been identified as a significant etiological agent in the development of head and neck squamous cell carcinoma (HNSCC). HPV's involvement has alluded to better survival and prognosis in patients and suggests that different treatment strategies may be appropriate for them. Only some data on the epidemiology of HPV infection in the oropharyngeal, oral cavity, and laryngeal SCC exists in Europe. Thus, this study was carried out to investigate HPV's impact on HNSCC patient outcomes in the Irish population, one of the largest studies of its kind using consistent HPV testing techniques. A total of 861 primary oropharyngeal, oral cavity, and laryngeal SCC (OPSCC, OSCC, LSCC) cases diagnosed between 1994 and 2013, identified through the National Cancer Registry of Ireland (NCRI), were obtained from hospitals across Ireland and tested for HPV DNA using Multiplex PCR Luminex technology based in and sanctioned by the International Agency for Research on Cancer (IARC). Both overall and cancer-specific survival were significantly improved amongst all HPV-positive patients together, though HPV status was only a significant predictor of survival in the oropharynx. Amongst HPV-positive patients in the oropharynx, surgery alone was associated with prolonged survival, alluding to the potential for de-escalation of treatment in HPV-related OPSCC in particular. Cumulatively, these findings highlight the need for continued investigation into treatment pathways for HPV-related OPSCC, the relevance of introducing boys into national HPV vaccination programs, and the relevance of the nona-valent Gardasil-9 vaccine to HNSCC prevention.

A common complaint a rare disease!

A 2-year-old previously well child presented to the emergency department with temperatures and lethargy. He was pale and looked unwell. He received a fluid bolus and was commenced on intravenous ceftriaxone. Pus was discharging from his left ear with postauricular swelling and erythema. Given clinical concerns, urgent neuroimaging was arranged.

Osteosarcoma (osteogenic sarcoma) of the jaws presenting in general dental practice - a series of four cases.

Introduction Osteosarcoma is the most common primary malignant bone tumour, usually arising in the long bones, with occurrence in the head and neck accounting for 8% of all osteosarcomas. Clinical features include swelling, pain, facial dysesthesia and abnormal mobility of teeth. Treatment consists of a combination of surgery, radiotherapy and chemotherapy.Case series Here, we present four cases of osteosarcoma of the jaws - two maxillary and two mandibular. All cases were initially assessed in the dental primary care setting before being referred for specialist opinion.Discussion The purpose of this paper is to present an overview of an uncommon but serious disease which can mimic common life-threatening dento-facial conditions. We discuss the diagnostic features, with an overview of clinical, histopathological and radiographic features.Conclusion These cases are important reminders of the potential clinical and radiographic appearance of a rare cause of facial swelling, and highlight the role of the general dental practitioner in early diagnosis and referral.

The Potential of Raman Spectroscopy in the Diagnosis of Dysplastic and Malignant Oral Lesions.

Early diagnosis, treatment and/or surveillance of oral premalignant lesions are important in preventing progression to oral squamous cell carcinoma (OSCC). The current gold standard is through histopathological diagnosis, which is limited by inter- and intra-observer errors and sampling errors. The objective of this work was to use Raman spectroscopy to discriminate between benign, mild, moderate and severe dysplasia and OSCC in formalin fixed paraffin preserved (FFPP) tissues. The study included 72 different pathologies from which 17 were benign lesions, 20 mildly dysplastic, 20 moderately dysplastic, 10 severely dysplastic and 5 invasive OSCC. The glass substrate and paraffin wax background were digitally removed and PLSDA with LOPO cross-validation was used to differentiate the pathologies. OSCC could be differentiated from the other pathologies with an accuracy of 70%, while the accuracy of the classifier for benign, moderate and severe dysplasia was ~60%. The accuracy of the classifier was lowest for mild dysplasia (~46%). The main discriminating features were increased nucleic acid contributions and decreased protein and lipid contributions in the epithelium and decreased collagen contributions in the connective tissue. Smoking and the presence of inflammation were found to significantly influence the Raman classification with respective accuracies of 76% and 94%.

Biomedical applications of vibrational spectroscopy: Oral cancer diagnostics.

Vibrational spectroscopy, based on either infrared absorption or Raman scattering, has attracted increasing attention for biomedical applications. Proof of concept explorations for diagnosis of oral potentially malignant disorders and cancer are reviewed, and recent advances critically appraised. Specific examples of applications of Raman microspectroscopy for analysis of histological, cytological and saliva samples are presented for illustrative purposes, and the future prospects, ultimately for routine, chairside in vivo screening are discussed.

Small and Thin Oral Squamous Cell Carcinomas may Exhibit Adverse Pathologic Prognostic Features.

We set out to record the frequency of recognised adverse pathologic features in early oral squamous cell carcinoma (OSCC) and correlate with neck disease, in particular in small and thin carcinomas, a group that might be assumed to behave less aggressively. We also examined the possibility of a biopsy site interfering with assessment of WPOI5 in small tumors. We reviewed all OSCCs ≤ 20 mm size and ≤ 10 mm depth reported at our institution over a 5-year period. Tumor maximum dimension, depth, perineural invasion (PNI), lymphovascular invasion (LVI), worst pattern of invasion (WPOI), and nodal status were recorded. Out of 95 cases, there were 44 (46.3%) small and 78 (82.1%) thin OSCCs. Depth and WPOI were significant factors in predicting nodal disease. There were 41 (43.2%) OSCC that were small and thin, of which 9.8% had PNI, none had LVI, and 61% had WPOI 4 or 5. Their rate of PNI and of nodal disease was similar to the other early OSCC. Assessment of WPOI5 at a biopsy site was only a problem in 2/38 cases. In early OSCC, depth and WPOI are important factors in predicting nodal disease. The very earliest OSCC (small and thin) have a similar rate of PNI and of nodal disease to other early OSCC, suggesting that while there may be a tendency to de-escalate treatment, these small tumours should be managed in the same way as for all early OSCC. In addition, the presence of scarring due to a biopsy in very small carcinomas rarely affects assessment of WPOI5.

The detection of oral cancer and potentially malignant disorders in Ireland: An observational study of 100 cases.

OBJECTIVE: To describe the diagnostic details of a sample of histologically diagnosed malignant and potentially malignant oral lesions from Ireland; to examine how these lesions were first detected, and by whom; and to determine whether factors influenced how these lesions were detected, who detected them, and the type of lesion diagnosed. METHODS: A retrospective review was carried out of the clinical notes relating to oral lesions histologically diagnosed as squamous cell carcinoma (SCC), carcinoma in-situ, or epithelial dysplasia from biopsies performed in hospital-based specialist units and submitted to a diagnostic pathology service based in Dublin, Ireland, between June and December 2015. In addition to sex, age, and smoking status, details were collected relating to the diagnosis, how the lesion was detected, and by whom. RESULTS: There were 100 cases reviewed: SCC (29), carcinoma in-situ (5), and epithelial dysplasia (66). There were 49 opportunistic findings: dentists detected 47 (94 percent), and 51 presenting complaints: primary care physicians (PCPs) detected 30 (60 percent). There was a lower likelihood of opportunistic findings among males (odds ratio 0.41; 95 percent CI 0.18, 0.91). CONCLUSIONS: Dentists in Ireland detected significant proportions of malignant and potentially malignant oral lesions as opportunistic findings, although opportunistic findings were less likely to occur among male patients.

Pathology in Irish medical education.

Pathology is the study of disease and is an important component in medical education. However, with medical curriculum reform, its role and contribution to medical courses is under potential threat. We surveyed the status of pathology in all six Irish medical schools. Information was received from five direct undergraduate and four graduate entry programmes. Pathology was recognisable as a core subject in all but one of the medical schools, was generally taught in years two or three, and the greatest contact hours were for histopathology (44-102 hours). Lectures were the most common teaching modality, and all used single best or extended matching answer multiple-choice questions as part of assessments. Currently, pathology is very visible in Irish medical education but needs to remain relevant with the move to theme and case-based teaching. There is heavy reliance on lectures and on non-academic/full-time hospital staff to deliver teaching, which may not be sustainable.

Data Set for the Reporting of Carcinomas of the Nasal Cavity and Paranasal Sinuses: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

The International Collaboration on Cancer Reporting was established to internationally unify and standardize the pathologic reporting of cancers based on collected evidence, as well as to allow systematic multi-institutional intercountry data collection to guide cancer care in the future. This data set has been developed by the collaborative efforts of an international multidisciplinary panel of experts involved in the care of patients with carcinomas of the nasal cavity and paranasal sinuses (sinonasal tract). The nasal cavity and paranasal sinuses (including frontal, sphenoid, ethmoid, and maxillary sinuses) comprise a very complex anatomic area of the head and neck, affected by a sometimes bewildering array of neoplasms. Management of malignancies in this anatomic region involves complex surgery because of the anatomic confines and close proximity to many vital structures. Given a multidisciplinary approach, the standardized reporting of the carcinomas that develop in this anatomic region include both required (core) and recommended (noncore) elements in pathology reporting in order to be able to identify critical prognostic factors, often requiring clinical and radiologic correlation. A summary of the International Collaboration on Cancer Reporting guidelines and clinically relevant elements, along with additional explanatory notes, are provided, based on evidentiary support from the literature, set in the context of practical application.

Oral lymphangiectasias and Crohn's disease: two case reports.

Lymphangiectasias, or acquired lymphangiomas, are rare in the oral cavity, more typically occurring on the skin or the genital area and, to our knowledge, have not been reported previously in association with Crohn's disease. Lymphangiectasias can occur at any age and develop secondary to chronic obstruction of the lymphatics. This differentiates them from congenital lymphangiomas, which are congenital malformations of the lymphatic system. We present 2 cases of oral lymphangiectasias associated with Crohn's disease, one of which was treated successfully with cryotherapy.

The influence of smoking, age and stage at diagnosis on the survival after larynx, hypopharynx and oral cavity cancers in Europe: The ARCAGE study.

Head and neck cancer (HNC) is a preventable malignancy that continues to cause substantial morbidity and mortality worldwide. Using data from the ARCAGE and Rome studies, we investigated the main predictors of survival after larynx, hypopharynx and oral cavity (OC) cancers. We used the Kaplan-Meier method to estimate overall survival, and Cox proportional models to examine the relationship between survival and sociodemographic and clinical characteristics. 604 larynx, 146 hypopharynx and 460 OC cancer cases were included in this study. Over a median follow-up time of 4.6 years, nearly 50% (n = 586) of patients died. Five-year survival was 65% for larynx, 55% for OC and 35% for hypopharynx cancers. In a multivariable analysis, we observed an increased mortality risk among older (≥71 years) versus younger (≤50 years) patients with larynx/hypopharynx combined (LH) and OC cancers [HR = 1.61, 95% CI 1.09-2.38 (LH) and HR = 2.12, 95% CI 1.35-3.33 (OC)], current versus never smokers [HR = 2.67, 95% CI 1.40-5.08 (LH) and HR = 2.16, 95% CI 1.32-3.54 (OC)] and advanced versus early stage disease at diagnosis [IV versus I, HR = 2.60, 95% CI 1.78-3.79 (LH) and HR = 3.17, 95% CI 2.05-4.89 (OC)]. Survival was not associated with sex, alcohol consumption, education, oral health, p16 expression, presence of HPV infection or body mass index 2 years before cancer diagnosis. Despite advances in diagnosis and therapeutic modalities, survival after HNC remains low in Europe. In addition to the recognized prognostic effect of stage at diagnosis, smoking history and older age at diagnosis are important prognostic indicators for HNC.

Cytokeratin 7 in Oropharyngeal Squamous Cell Carcinoma: A Junctional Biomarker for Human Papillomavirus-Related Tumors.

Background: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) represents a distinct subgroup of head and neck tumors. We analyze the expression of cytokeratin 7, a junctional biomarker with a SEQIKA fragment, which stabilizes HPV-16 E7 transcripts, in oropharyngeal SCCs.Methods: Archived tumor specimens and epidemiologic data were collected from patients with oropharyngeal SCCs over 10 years. Briefly, DNA was extracted from tissue blocks, and HPV testing was carried out using SPF10 HPV PCR and INNO-LiPA HPV Genotyping. Immunohistochemical staining for CK7 and p16ink4a was performed on the Ventana BenchMark Ultra Immunostainer. Analysis was by light microscopy using the H-score. CK7 expression was correlated with epidemiologic data, p16ink4a positivity, and HPV status using SPSS.Results: CK7 expression was observed specifically and uniformly in the tonsillar crypt epithelium of normal tonsils and tumor specimens. There were 226 cases of oropharyngeal SCCs, with 70 demonstrating both HPV and p16 positivity. Of 216 cases evaluated for CK7, 106 demonstrated some positivity, whereas H-score > 60 was seen in 55 of these. CK7 H-score > 60 was significantly associated with tonsillar subsite and HPV and p16 positivity.Conclusions: An association between CK7 and HPV has been demonstrated. CK7-expressing tonsillar crypt cells potentially represent an oropharyngeal subsite susceptible to HPV-related SCC.Impact: Along with the cervix and anorectum, specific oropharyngeal expression of CK7 in a site predisposed to HPV-related tumors may suggest a role for CK7 in the pathogenesis of this subgroup of tumors. Further research is warranted to characterize the association between CK7 and HPV-related head and neck SCC. Cancer Epidemiol Biomarkers Prev; 26(5); 702-10. ©2017 AACR.

Anaplastic thyroid carcinoma: Failure of conventional therapy but hope of targeted therapy.

BACKGROUND: Anaplastic thyroid cancer has a median survival between 1.2 and 10 months. The purpose of our study was to evaluate the outcomes of patients with anaplastic thyroid cancer in Ireland. METHODS: We carried out a retrospective analysis of the Irish National Cancer Database for patients with anaplastic thyroid cancer between 2000 and 2010. RESULTS: Of a total of 64 patients (40 women, 24 men), the median age was 69 years, and 29.7% of the patients had distant metastases. The overall median survival was 2.3 months and the 1, 2, and 5-year survival was 12.5%, 6.25%, and 4.69%, respectively. On univariate analysis age, sex, metastases at diagnosis, and multimodality treatment were statistically significant indicators of prognosis, and metastases at diagnosis remained statistically significant on multivariate analysis. CONCLUSION: These results correlate with the American Thyroid Association (ATA) guidelines, in which, when possible, multimodality therapy offers a survival advantage to a select group of patients. Novel therapies may offer the greatest hope for these patients. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1122-E1129, 2016.

Aggressive giant cell lesion of the jaws: a review of management options and report of a mandibular lesion treated with denosumab.

Giant cell lesions (GCLs), previously referred to as giant cell granulomas, are benign tumors of the jaws of unknown etiology. Surgical management of aggressive GCLs is challenging, as these lesions demonstrate a tendency to recur following surgical removal. In addition, surgical treatment can be associated with significant morbidity. In an attempt to reduce both the extent of morbidity and the recurrence rate following surgery, a number of pharmacologic therapies have been advocated on the basis of assumptions about the predominant cell types and receptors, for the management of these lesions. This report describes the use of denosumab, an agent originally used for its anti-resorptive effects, in the management of an aggressive GCL of the mandible in an older patient, who was unsuitable for extensive surgery and in whom treatment with intralesional triamcinolone had proved unsuccessful. Denosumab may be a viable alternative or adjunct to surgery in the management of GCLs of the jaws.

Neoadjuvant crizotinib in advanced inflammatory myofibroblastic tumour with ALK gene rearrangement.

BACKGROUND: Inflammatory myofibroblastic tumours (IMTs) are rare sarcomas that were first described in the lung. They are composed of myofibroblastic mesenchymal spindle cells accompanied by an inflammatory infiltrate of plasma cells. Complete resection is the treatment of choice. There is currently no standard treatment for inoperable or recurrent disease. Expression of ALK protein triggered by ALK gene rearrangement at chromosome 2p23 has been found in 36%-60% of IMTs. CASE REPORT: We report a rapid early response to crizotinib as neoadjuvant therapy, enabling surgical excision of a large ALK-translocated IMT, which resulted in complete disease clearance. To the best of our knowledge, this is the first case in the literature of a patient with IMT in whom crizotinib was used successfully in the neoadjuvant or curative setting.

Dynamic modulation of shared sensory and motor cortical rhythms mediates speech and non-speech discrimination performance.

Oscillatory models of speech processing have proposed that rhythmic cortical oscillations in sensory and motor regions modulate speech sound processing from the bottom-up via phase reset at low frequencies (3-10 Hz) and from the top-down via the disinhibition of alpha/beta rhythms (8-30 Hz). To investigate how the proposed rhythms mediate perceptual performance, electroencephalographic (EEG) was recorded while participants passively listened to or actively identified speech and tone-sweeps in a two-force choice in noise discrimination task presented at high and low signal-to-noise ratios. EEG data were decomposed using independent component analysis and clustered across participants using principle component methods in EEGLAB. Left and right hemisphere sensorimotor and posterior temporal lobe clusters were identified. Alpha and beta suppression was associated with active tasks only in sensorimotor and temporal clusters. In posterior temporal clusters, increases in phase reset at low frequencies were driven by the quality of bottom-up acoustic information for speech and non-speech stimuli, whereas phase reset in sensorimotor clusters was associated with top-down active task demands. A comparison of correct discrimination trials to those identified at chance showed an earlier performance related effect for the left sensorimotor cluster relative to the left-temporal lobe cluster during the syllable discrimination task only. The right sensorimotor cluster was associated with performance related differences for tone-sweep stimuli only. Findings are consistent with internal model accounts suggesting that early efferent sensorimotor models transmitted along alpha and beta channels reflect a release from inhibition related to active attention to auditory discrimination. Results are discussed in the broader context of dynamic, oscillatory models of cognition proposing that top-down internally generated states interact with bottom-up sensory processing to enhance task performance.

Laryngotracheal presentation of anaplastic thyroid carcinoma with squamous differentiation: seven cases demonstrating an under-recognized diagnostic pitfall.

AIMS: To describe a series of anaplastic thyroid carcinomas that mimicked primary head and neck squamous cell carcinoma (HNSCC) by virtue of both morphology and clinical presentation. METHODS AND RESULTS: Seven cases were identified in a 15-year period where a biopsy of an airway lesion that appeared to be squamous cell carcinoma was, in fact, anaplastic thyroid carcinoma. The tumours had squamous and/or spindle cell morphology, with only the squamous component being apparent in the airway biopsy. Some tumours arose within metaplastic (n = 3) or atypical (n = 3) epithelium, supporting the diagnosis of a primary mucosal tumour. Positive PAX8 (n = 5) and TTF-1 (n = 4) staining was identified. CONCLUSIONS: An endotracheal presentation of anaplastic thyroid carcinoma with squamous morphology may be misdiagnosed as a primary head and neck squamous cell carcinoma. PAX8 and TTF-1 expression are helpful in making the distinction, but the problem lies in suspecting a thyroid carcinoma in what appears to be a straightforward diagnosis of HNSCC.

Altering the architecture of tissue engineered hypertrophic cartilaginous grafts facilitates vascularisation and accelerates mineralisation.

Cartilaginous tissues engineered using mesenchymal stem cells (MSCs) can be leveraged to generate bone in vivo by executing an endochondral program, leading to increased interest in the use of such hypertrophic grafts for the regeneration of osseous defects. During normal skeletogenesis, canals within the developing hypertrophic cartilage play a key role in facilitating endochondral ossification. Inspired by this developmental feature, the objective of this study was to promote endochondral ossification of an engineered cartilaginous construct through modification of scaffold architecture. Our hypothesis was that the introduction of channels into MSC-seeded hydrogels would firstly facilitate the in vitro development of scaled-up hypertrophic cartilaginous tissues, and secondly would accelerate vascularisation and mineralisation of the graft in vivo. MSCs were encapsulated into hydrogels containing either an array of micro-channels, or into non-channelled 'solid' controls, and maintained in culture conditions known to promote a hypertrophic cartilaginous phenotype. Solid constructs accumulated significantly more sGAG and collagen in vitro, while channelled constructs accumulated significantly more calcium. In vivo, the channels acted as conduits for vascularisation and accelerated mineralisation of the engineered graft. Cartilaginous tissue within the channels underwent endochondral ossification, producing lamellar bone surrounding a hematopoietic marrow component. This study highlights the potential of utilising engineering methodologies, inspired by developmental skeletal processes, in order to enhance endochondral bone regeneration strategies.