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Role of infectious agents in the carcinogenesis of brain and head and neck cancers  [cached]
Alibek Kenneth,Kakpenova Ainur,Baiken Yeldar
Infectious Agents and Cancer , 2013, DOI: 10.1186/1750-9378-8-7
Abstract: This review concentrates on tumours that are anatomically localised in head and neck regions. Brain cancers and head and neck cancers together account for more than 873,000 cases annually worldwide, with an increasing incidence each year. With poor survival rates at late stages, brain and head and neck cancers represent serious conditions. Carcinogenesis is a multi-step process and the role of infectious agents in this progression has not been fully identified. A major problem with such research is that the role of many infectious agents may be underestimated due to the lack of or inconsistency in experimental data obtained globally. In the case of brain cancer, no infection has been accepted as directly oncogenic, although a number of viruses and parasites are associated with the malignancy. Our analysis of the literature showed the presence of human cytomegalovirus (HCMV) in distinct types of brain tumour, namely glioblastoma multiforme (GBM) and medulloblastoma. In particular, there are reports of viral protein in up to 100% of GBM specimens. Several epidemiological studies reported associations of brain cancer and toxoplasmosis seropositivity. In head and neck cancers, there is a distinct correlation between Epstein-Barr virus (EBV) and nasopharyngeal carcinoma (NPC). Considering that almost every undifferentiated NPC is EBV-positive, virus titer levels can be measured to screen high-risk populations. In addition there is an apparent association between human papilloma virus (HPV) and head and neck squamous cell carcinoma (HNSCC); specifically, 26% of HNSCCs are positive for HPV. HPV type 16 was the most common type detected in HNSCCs (90%) and its dominance is even greater than that reported in cervical carcinoma. Although there are many studies showing an association of infectious agents with cancer, with various levels of involvement and either a direct or indirect causative effect, there is a scarcity of articles covering the role of infection in carcinogenesis of brain and head and neck cancers. We review recent studies on the infectious origin of these cancers and present our current understanding of carcinogenic mechanisms, thereby providing possible novel approaches to cancer treatment.
MicroRNAs in Head and Neck Cancer  [PDF]
Keziah John,Jennifer Wu,Bing-Wei Lee,Camile S. Farah
International Journal of Dentistry , 2013, DOI: 10.1155/2013/650218
Abstract: microRNAs (miRs) are small noncoding single-stranded RNAs, about 19–25 nucleotides long. They have been shown to be capable of altering mRNA expression; thus some are oncogenic or tumour suppressive in nature and are regulated by cellular and epigenetic factors. The molecular pathogenic pathway of many cancers has been modified since the discovery of miRs. Head and neck squamous cell carcinoma (HNSCC), the sixth most common cancer in the world, has recently been associated with infection by the human papillomavirus (HPV). miR expression profiles are altered in the transition from dysplasia to carcinoma, with some changes being specific to the underlying risk factor. This difference is particularly significant in HPV-positive HNSCC where host miRs are modulated by the virus, creating a different profile to HPV-negative HNSCC. Saliva, as an easily collected proximal biofluid containing numerous miRs, presents an attractive noninvasive diagnostic tool in detecting HNSCC and determining prognosis. Furthermore, miRs may play a role in the analysis of surgical margins for residual tumour extension and in the development of novel miR-based therapeutic targets and agents. 1. Introduction Head and neck cancer (HNC) is the 6th most common cancer in the world [1], referring to cancers of the aerodigestive tract, including lip, oral cavity, nasal cavity, paranasal sinuses, pharynx, larynx, oropharynx, hypopharynx, salivary glands, and local lymph nodes [2]. 90% of all HNCs are squamous cell carcinomas (HNSCCs), arising from the mucosal lining in these regions [2]. 80–90% of these are related to prolonged alcohol and tobacco use, while 30–50% have been associated with the human papillomavirus (HPV) [3], with type 16 being the most common type detected in HNSCC [2]. There is significant geographic variation in its incidence, with South-East Asia, the Pacific regions, Latin America, and parts of Central and Eastern Europe presenting a higher incidence than other regions; for instance, HNSCC is the most common cancer type in India, accounting for 40% of all malignancies [4, 5]. The 5-year survival rate of smoking associated with HNSCC is still 30–50%, with survivors experiencing poor quality of life [3]. Furthermore, HNSCC is usually not detected in the early stages of the disease as they may not display clinical symptoms [3, 6]. Hence methods for early detection and diagnosis of lesions with malignant potential [7–9], measures for prevention, and novel treatment methods are instrumental for improving treatment outcomes and patients’ quality of life. miRs are small,
Clinico-pathological profile of head and neck malignancies at University College Hospital, Ibadan, Nigeria
Akinyele O Adisa, Bukola F Adeyemi, Abideen O Oluwasola, Bamidele Kolude, Effiong EU Akang, Jonathan O Lawoyin
Head & Face Medicine , 2011, DOI: 10.1186/1746-160x-7-9
Abstract: One thousand, one hundred and ninety two patients with head and neck malignancies were analysed according to age, gender, topography and histology.There was an annual hospital frequency of 62 cases per year. The overall mean age for these malignancies was 43.9 (SD ± 19.3) years. The lesions from the respiratory tract were the most frequent (43.2%) of all cases. The palate was the most frequent intra-oral site (13.8%). Epithelial malignancies constituted 73.4% of all cases with a male: female ratio of 2:1, a mean age of 48.1 (SD ± 17.5) years and were mostly located in the larynx (19.7%). Lymphomas constituted 17.5% of all head and neck cancers with a male: female ratio of 1.6:1, a mean age of 35.1 (SD ± 20.6) years and nodal involvement (39.7%) was most common. Sarcomas constituted 8.9% of all malignancies with a male: female ratio of 1.5:1, mean age of 27.1 (SD ± 16.7) years and the maxillofacial bones (42.5%) were most commonly involved. Neuroendocrine malignancies accounted for 0.2% of head and neck malignancies with a male: female ratio of 1:1, a mean age of 28.5 (SD ± 6.4) years and both cases involved the nose.This study has further confirmed that carcinomas remain the most frequent cancers of the head and neck region in south-western Nigeria.Head and neck cancers are malignant neoplasms occurring in the nasal cavities, paranasal sinuses, nasopharynx, hypopharnyx, oropharynx, ear, scalp, oral cavity and salivary glands [1]. These malignancies are associated with various aetiological factors such as tobacco and alcohol use [2], infection by oncogenic viruses, genetic factors and nutritional deficiency [3].Head and neck cancer is the tenth most common cancer in the world [4] and is an important cause of morbidity and mortality [5]. Patients with head and neck cancer have specific requirements that are beyond the needs of most other patients diagnosed with other types of cancer [6]. Several assorted histological types of tumours are found in the head and neck reg
Biomarkers for Cancers of the Head and Neck
Viviana P. Lutzky, Denis J. Moss, David Chin, William B. Coman, Peter G. Parsons and Glen M. Boyle
Clinical Medicine Insights: Ear, Nose and Throat , 2012,
Abstract: Head and neck cancer is a broad term used to describe malignancies that arise in the nasal and oral cavities, pharynx and larynx, as well as the paranasal sinuses. Head and neck squamous cell carcinoma (HNSCC) affects the squamous epithelium of the oral cavity, tongue and oropharynx, excluding the nasopharynx. Recent advances in molecular technology, including gene expression and proteomic profiling appear to offer the potential for the development of specific biomarkers including diagnostic tools which may act as an aid to guide therapy for this malignancy. The other human head and neck cancer included in this review, nasopharyngeal carcinoma (NPC) is a malignancy derived from the undifferentiated epithelium of the nasopharyngeal cavity, and is considered here as a separate entity because its strong association with Epstein-Barr virus (EBV) presents the opportunity for the development of virus related and unrelated biomarkers. In particular, IgA antibodies to EBV and high levels of EBV DNA in serum samples of NPC patients have been recorded. This review aims to summarize some current and also potential new biomarkers that could be used for screening, diagnosis, monitoring and prognostic prediction for cancers of the head and neck, including NPC and HNSCC.
Head and Neck Melanoma  [PDF]
R. Shashanka,B. R. Smitha
ISRN Surgery , 2012, DOI: 10.5402/2012/948302
Abstract: The incidence of malignant melanoma appears to be increasing at an alarming rate throughout the world over the past 30–40 years and continues to increase in the United States, Canada, Australia, Asia, and Europe. The behavior of head and neck melanoma is aggressive, and it has an overall poorer prognosis than that of other skin sites. The authors review the published literature and text books, intending to give an overall picture of malignant melanomas of the head and neck and a special emphasis on treatment considerations with controversies in treatment including biopsy, radiation therapy, sentinel node biopsy, and nodal dissection. 1. Background Melanoma is a malignancy of pigment-producing cells (melanocytes) located predominantly in the skin but also found in the eyes, ears, GI tract, leptomeninges, and oral and genital mucous membranes. The incidence of malignant melanoma appears to be increasing at an alarming rate throughout the world over the past 30–40 years and continues to increase in the United States, Canada, Australia, Asia, and Europe [1–3]. Melanoma accounts for 65% of all deaths from skin cancer, reflecting its lethal nature. Most head andneck melanomas (70–90%) occur on the face [4], with the cheek the most common site [5]. Malignant melanomas of the neck (7%) and scalp (3%) are much less frequent [6, 7]. Melanomas of the external ear constitute 7% of the head and neck melanomas [8]. Although malignant melanomas of all cutaneous sites are slightly more common in women, melanomas of the head and neck are twice as common in men [7, 9]. Head and neck melanoma also tends to affect a slightly older aged group than melanomas in other sites [10]. Head and neck melanoma in children is a very rare and is usually associated with giant congenital nevus [11]. Melanoma that does not originate in the skin is a very rare tumor and is considered as one of the most deadly of all human neoplasms [12, 13]. Primary mucosal melanomas represent only 1.7–3% of all primary melanomas [1, 14]. Generally, survival from head and neck melanoma is reported as 17% at 5 years and the 10-year survival rate is 5% [15]. We have reviewed the published reports and text-books, intending to give an overall picture of malignant melanomas of the head and neck. 2. Pathophysiology The sequence of events in which normal melanocytes transform into melanoma cells, referred to as melanoma genesis, is poorly understood. It likely involves a multistep process of progressive genetic mutations that (1) alter cell proliferation, differentiation, and death and (2) impact susceptibility
The Professional Medical Journal , 2011,
Abstract: The pectoralis major myocutaneous pedicle flap (PMMPF) has been considered to be the "workhorse" ofpedicled flaps in head and neck reconstruction. Despite the use of free flaps, this flap is still considered the mainstay of head and neckreconstruction. The flap is usually associated with a high incidence of complications compared with the free fasciocutaneous flaps yet its size,viability, and versatility make it a valuable tool for extending the limits of resectability and reconstruction. It is type V muscle flap with thedominant vascular supply from the pectoral branch of thoracoacromial artery. Objective: To share our experience of pectoralis majormyocutaneous pedicle flap in selected cases of head and neck reconstruction. The indications, type of reconstruction and complications of theflap utilization were evaluated. Patients and Methods: Between March 2005 and August 2010, a 37 head and neck reconstructive proceduresusing the PMMPF were carried out. The indications for the flap use were defects due to resection of stage II-IV cancer in the head and neckregion. The site, stage of the disease and the postoperative complications were all documented. Results: Pectoralis major myocutaneouspedicled flap reconstructions were used to reconstruct defects in the following sites: oral cavity (25 patients); oropharynx/ hypopharynx, (7patients); and neck or face (5 patients). Of the 37 PMMPF reconstructions, 30 flaps were carried out as primary reconstructive procedures,whereas 7 flaps were "salvage" procedures. Twentyfive patients (67.59%) had complications. A higher complication rates were associated withthe utilization of the flap as a salvage procedure, number of co- morbidities, and in oral cavity reconstructions. Conclusions: The pectoralismajor myocutaneous pedicled flap is still an acceptable method of head and neck reconstruction. It is fast, reliable, provides safe repair and isindicated especially where bulk is needed.
mTOR Pathway and mTOR Inhibitors in Head and Neck Cancer  [PDF]
Wei Gao,John Zeng Hong Li,Jimmy Yu Wai Chan,Wai Kuen Ho,Thian-Sze Wong
ISRN Otolaryngology , 2012, DOI: 10.5402/2012/953089
Abstract: Head and neck cancer is the sixth most common type of Cancer worldwide. Since conventional treatment regimens are nonselective and are associated with systemic toxicities, intense investigations focus on molecular targeted therapy with high selectivity and low adverse effects. mTOR signaling pathway has been found to be activated in head and neck cancer, making it attractive for targeted therapy. In addition, expression levels of mTOR and downstream targets eIF4E, 4EBP1, S6K1, and S6 are potential diagnostic and prognostic biomarkers for head and neck cancer. mTOR inhibitors, such as rapamycin and its derivatives temsirolimus and everolimus, exhibit inhibitory effects on head and neck cancer in both in vitro cell line model and in vivo xenograft model. A large number of clinical trials have been initiated to evaluate the therapeutic effects of mTOR inhibitors on patients with head and neck cancer. mTOR inhibitor has potential as a single therapeutic agent or in combination with radiation, chemotherapeutic agents, or other targeted therapeutic agents to obtain synergistic repression on head and neck cancer. 1. Introduction Head and neck cancer is the sixth most common type of cancer worldwide, with about 650,000 new cases in the world every year [1]. Tobacco and alcohol consumption is a main risk factor for head and neck cancer [1]. In addition, accumulating evidence has shown that human papillomavirus and Epstein-Barr virus are associated with carcinogenesis in oropharyngeal cancers and nasopharyngeal cancers, respectively [2, 3]. The treatment methods for head and neck cancer include surgery, radiotherapy, and chemotherapy [4]. Patients with early stages of disease are treated by surgery and radiotherapy, while patients with advanced stages of disease are administrated by surgery and chemoradiotherapy [4]. Platinum-based agents (cisplatin/carboplatin), taxane agents (docetaxel/paclitaxel), and 5-fluorouracil are the most common chemotherapeutic agents for head and neck cancer [4–7] (Table 1). Table 1: Chemotherapeutic model for head and neck cancer. Despite advances in treatment methods for head and neck cancer, the survival rate has not been largely improved [4]. The major reason is that conventional treatment regimens are nonselective and are related with systemic toxicities [8, 9]. Therefore, intense investigations focus on alternative treatment strategies with less systemic toxicities for head and neck cancer. Since molecular targeted therapy has high selectivity and low adverse effects, it exhibits promise as an alternative treatment strategy for
The Use of Epidermal Growth Factor Receptor Monoclonal Antibodies in Squamous Cell Carcinoma of the Head and Neck  [PDF]
Jeffery S. Russell,A. Dimitrios Colevas
Chemotherapy Research and Practice , 2012, DOI: 10.1155/2012/761518
Abstract: Targeting of the EGF receptor (EGFR) has become a standard of care in several tumor types. In squamous cell carcinoma of the head and neck, monoclonal antibodies directed against EGFR have become a regular component of therapy for curative as well as palliative treatment strategies. These agents have anti-tumor efficacy as a single modality and have demonstrated synergistic tumor killing when combined with radiation and/or chemotherapy. While cetuximab has been the primary anti-EGFR monoclonal antibody used in the US, variant anti-EGFR monoclonal antibodies have been used in several clinical studies and shown benefit with improved toxicity profiles. Next generation anti-EGFR monoclonal antibodies may demonstrate multi-target epitope recognition, enhanced immune cell stimulation, or conjugation with radioisotopes in order to improve clinical outcomes. Identification of the specific patient subset that would optimally benefit from anti-EGFR monoclonal antibodies remains an elusive goal. 1. Introduction In 2012, head and neck cancers of the oral cavity and pharynx will make up an estimated 2.5% of cancer diagnoses in the United States and for the 40,250 new cases diagnosed, there will be an estimated 7,850 deaths [1]. Worldwide, head and neck cancers are approximately 5% of all new cancer diagnoses, with a large proportion of these cases originating in developing countries [2]. Locally advanced squamous cell carcinoma of the head and neck (SCCHN) has cure rates of only 30–60%, even with combined therapeutic approaches [3]. Local recurrence rates of 30–50% and distant metastasis rates of 13–22% illustrate the need for more effective therapies [4, 5]. Towards this end, molecular analysis of SCCHN has found the overexpression of the epidermal growth factor receptor (EGFR) at rates of up to 90% in tumors and EGFR overexpression has been associated with a poor prognosis [6–11]. The deregulation or inappropriate activation of the EGFR family members has been shown to drive oncogenic transformation, tumor cell proliferation, and cell survival pathways in a variety of malignancies [12–14]. Ligand binding or mutations within the EGF receptor cause activation of downstream signaling pathways, such as Ras/Raf/MAPK and PI3?K/Akt [15–17]. Thus, agents that specifically target EGFR and consequently its downstream signaling pathways are appealing candidates to enhance tumor cell killing, especially in high-expressing tumors such as SCCHN. Currently, therapy for targeting EGFR can be divided between small molecule tyrosine kinase inhibitors and monoclonal antibodies. In
Receptor-Tyrosine-Kinase-Targeted Therapies for Head and Neck Cancer  [PDF]
Lisa A. Elferink,Vicente A. Resto
Journal of Signal Transduction , 2011, DOI: 10.1155/2011/982879
Abstract: Molecular therapeutics for treating epidermal growth factor receptor-(EGFR-) expressing cancers are a specific method for treating cancers compared to general cell loss with standard cytotoxic therapeutics. However, the finding that resistance to such therapy is common in clinical trials now dampens the initial enthusiasm over this targeted treatment. Yet an improved molecular understanding of other receptor tyrosine kinases known to be active in cancer has revealed a rich network of cross-talk between receptor pathways with a key finding of common downstream signaling pathways. Such cross talk may represent a key mechanism for resistance to EGFR-directed therapy. Here we review the interplay between EGFR and Met and the type 1 insulin-like growth factor receptor (IGF-1R) tyrosine kinases, as well as their contribution to anti-EGFR therapeutic resistance in the context of squamous cell cancer of the head and neck, a tumor known to be primarily driven by EGFR-related oncogenic signals. 1. Introduction Squamous cell carcinoma of the head and neck (HNSCC) is a heterogeneous disease that includes tumors arising from the mucosal epithelial surface of the oral cavity, oropharynx, hypopharynx, and larynx. Although these tumors originate within different anatomic sites within the upper aerodigestive tract, they are histologically identical (95% of HNSCC are squamous cell carcinomas), share common etiologic risk factors and overlapping metastatic target site profiles (reviewed in [1–3]). Recent genetic analysis of human head and neck tumors has revealed common molecular alterations including p53 mutation, p14ARF, and p16 methylation, as well as Cyclin D and EGFR amplification [3–6]. Despite these similarities, the distinct anatomic subsites are associated with differing rates of regional metastasis—for example, vocal cord lesions tend to metastasize less frequently than oropharyngeal or hypopharyngeal lesions. This variation may be attributed to differing densities of lymph draining vessels within each of the relevant subsites. Patients who exhibit metastases into the regional nodal basin exhibit a 50% decrease in survival irrespective of treatment [7–15]. The incidence of HNSCC has continued to increase over the last 3 decades. Currently, it is the 5th leading cause of cancer by incidence and the 6th leading cause of cancer mortality in the world [16, 17]. Recurrent and/or metastatic HNSCC patients have a poor prognosis, with a median survival of less than 1-2 years [18, 19]. Several lines of evidence indicate that cancer is a disease resulting from dynamic
Role of Met Axis in Head and Neck Cancer  [PDF]
Yiru Xu,Gary J. Fisher
Cancers , 2013, DOI: 10.3390/cancers5041601
Abstract: Head and neck cancer is the sixth most common type of cancer worldwide. Despite advances in aggressive multidisciplinary treatments, the 5-year survival rate for this dreadful disease is only 50%, mostly due to high rate of recurrence and early involvement of regional lymph nodes and subsequent metastasis. Understanding the molecular mechanisms responsible for invasion and metastasis is one of the most pressing goals in the field of head and neck cancer. Met, also known as hepatocyte growth factor receptor (HGFR), is a member of the receptor protein tyrosine kinase (RPTK) family. There is compelling evidence that Met axis is dysregulated and plays important roles in tumorigenesis, progression, metastasis, angiogenesis, and drug resistance in head and neck cancer. We describe in this review current understanding of Met axis in head and neck cancer biology and development of therapeutic inhibitors targeting Met axis.
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