Head and neck cancers are a group of cancers; all of biologically similar origin that affect portions of the upper aerodigestive tract. About 90% of the head and neck cancers are squamous cell carcinomas, originating from keratinizing or malpighian epithelial cells, giving the name Squamous Cell Carcinoma of the Head and Neck (HNSCC). Typical of all squamous cell carcinomas, HNSCC begin as surface lesions which may be erythoplasia or lekoplakia. Most commonly affected sites are the lip, floor of the mouth, tongue, soft palate, salivary gland, nasal cavity, paranasal sinuses, tonsilar pillar, larynx, and the pharynx. Symptoms differ according to the exact place of origin of the carcinoma. For example, carcinomas of the oral cavity present with a white or red patch on the gums, tongue, or lining of the mouth, or a swelling of the jaw, while carcinomas of the nasal cavity may present with blocked sinuses, and chronic sinus infection. Incidentally, males are more frequently affected than females. Environmental factors play a major role in the development of HNSCC. Known risk factors include tobacco smoking, alcohol consumption, sun exposure, and infection by Human Papillomavirus (HPV) or Epstein Barr Virus (EBV). Internationally, an estimated 17 people in every 100,000 are affected by HNSCC.
Suspected lesions in the head and neck area need to be biopsied. Other modes of confirming the diagnosis of HNSCC include direct laryngoscopy, endoscopy, X-ray, MRI, PET, and/or CT scans. Biopsies are used to confirm and stage and grade the cancer. Therapies of treatment differ according to the stage and site of cancer. Radiation therapy is used for carcinomas of the tongue, and the floor of the mouth, while carcinomas of the tonsil and larynx are controlled by a combination of surgery and radiotherapy. Metastasis to lymph nodes and systemic involvement necessitate chemotherapy. Post treatment, regular follow-up is necessary to detect any recurrence of the cancer. Five-year survival rates vary from 90% for lower lip carcinoma to 17% for tonsilar carcinoma involving the lymph nodes.
[See: Morocco > Laantri et al., 2011].
In an attempt to develop molecular assay for the early detection of premalignant lesions, Abou-Elhamd et al. (2008) investigated six microsatellite markers in 170 individuals from Egypt having precancerous lesions and SCC of the head and neck. The study also included 50 control individuals. The six markers were located on chromosomes 3p, 9p, 17p, and 5q, and were known for showing loss of homozygosity (LOH) in HNSCCs and precancerous lesions. The most informative of these markers were found to be CFS1-R, D3S1286, and D9S171. The least frequent marker for LOH detection was D17S654, and it failed to amplify premalignant DNA. The results showed that the regions 9p21.1-22.3 and 17p13 were prone to genetic instability in HNSCC tumors, and that LOH at these loci could be of particular value in early detection or prognosis.
Laantri et al. (2011) analyzed single nucleotide polymorphisms (SNPs) in the XRCC1 and OGG1 genes in 598 nasopharyngeal carcinoma (NPC) cases from Morocco, Algeria, and Tunisia and 545 controls frequency matched by recruitment center, age, sex, and urban/rural household. They foudn out that the XRCC1 and OGG1 genes are unlikely to play a role in the susceptibility to NPC in North Africans.
Khalifa and Al-Khabouri (2004) were the first to conduct a prospective single arm study to determine the safety and efficacy of neoadjuvant chemotherapy in treating patients with locally advanced non-metastatic head and neck cancer in Oman in a period of three years (1998-2001). The study group included newly diagnosed untreated patients with locally advanced non metastatic tumor with inclusion criteria of good general condition. Patients with uncontrolled angina, active infection or other malignancies were excluded. All patients were clinically examined, and investigated with pre-treatment endoscopy (for tumor staging and measurement), CT scans of the head and neck and chest X-ray. Out of 73 eligible patients (28 females, 45 males; median age: 52 years), 60% had stage III and 40% had stage IV non metastatic disease, and 75% had performance status of 0 to 1. The majority (30%) had nasopharyngeal cancer, while oral cavity cancer affected only 12% of the study group, while other cancers in the group were that of the larynx (21%), oropharynx (21%), and hypopharynx (16%). The treatment regimen used in this study was three cycles of chemotherapy (cisplatin and 5-fluorouracil), followed by local radiotherapy. Megavoltage radiation was used for all patients who received dental checks before it. The intended three cycles of neoadjuvant chemotherapy were completed in 68% of the patients and all patients completed their radiotherapy sessions. The reported toxicity to chemotherapy were nausea and vomiting (7%), diarrhea (4%), neutropenia (4%), and mucositis (7%). Due to reversible toxicities, 14% had cycle delays of less than a week while 5% had more than a week. Unlike chemotherapy, there was no interruption of radiotherapy but two patients had elective tracheostomy and four had percutaneous endoscopic gastrostomy along the radiotherapy course. The overall response was seen in 68% (45% with complete and 23% with partial response) after chemotherapy, which increased to 80% (55% with complete and 25% with partial response) after radiotherapy, while the rate of stable and progressive disease (SD and PD, respectively) decreased from 22% and 10%, respectively, after chemotherapy to 12% and 8% after radiotherapy. The median DFP was calculated to be 11 months and was affected by the stage and the site of the primary tumor. According to the univariate analysis, the DFP and OS were affected by the tumor primary site, age, stage of the disease and the performance status, while the multivariate analysis showed that both the initial response to chemotherapy and primary nasopharyngeal carcinoma were significantly related to OS. The median follow up period was found to be 16 months and so was the median survival for the whole group. About 20% of the patients were alive at the end of the study, of which 60% with nasopharygeal, two had hypo-pharyngeal and four had primary laryngeal carcinoma.
Alsbeih et al. (2008) studied the association between two SNPs, XRCC1 p.Arg399Gln and XRCC3 p.Thr241Met and late reactions to radiotherapy in 50 Saudi patients with head and neck cancer. There were 43 males and seven females, with a median of 49 years. The appearance and the intensification of subcutaneous and deep tissues fibrosis were measured in the patients following radiotherapy. A significant association was found between the presence of XRCC1 p.Arg399Gln SNP and risk of late normal tissue complication following radiotherapy. However, this association was not found for the XRCC3 p.Thr241Met SNP.
Al-Hadyan et al. (2012) conducted an investigation to identify SNPs associated with the risk of head and neck cancer. Ten SNPs in genes affecting cell cycle control and DNA repair were selected for this study. DNA was extracted from the blood samples of 156 Saudi individuals affected with head and neck cancer, as well as 251 healthy Saudi controls. SNPs were genotyped by direct sequencing. Three SNPs were found to have a statistically significant allelic association with head and neck cancer. These included C31A in the gene p21 [p=0.04, OR=1.44 (1.02-2.03)], A2790G in the gene Ku80 [p=0.04, OR=1.5 (1.01-2.23)] and T309G in the gene MDM2 [(p=0.0003, OR=0.58 (0.43-0.78)]. While the first two variants were associated with a higher risk of cancer, the T309G variant was found to have a protective affect against the disease. Cancer cases and controls were found to be in Hardy-Weinberg equilibrium.
Dysvik et al., (2006) studied gene expression profiles in head and neck squamous cell carcinomas (HNSCC) and pairwised normal controls from Sudanese (n = 72) and Norwegian (n = 45) patients using a 15K cDNA microarray. Samples from Sudan were grouped according to anatomic location/patients' habit of toombak (snuff) use, and 37 pools of 2 to 11 tumors matched to 37 pools of their normal controls from the same patients, respectively, were prepared. For controls, 33 of the pools were hybridized against Human Reference RNA. Dysvik et al., (2006) identified 136 genes from Sudan and 154 from Norway as differentially expressed between tumors and controls. Changes of the genes found were confirmed in >70% of the pools by hybridization against Reference RNA. Seventy-three genes and three main pathways (signal transduction, cell communication, and ligand-receptor interaction) were of relevance to the HNSCCs from both countries. Hierarchical clustering of the 73 genes identified subclasses of mixed tumors from the two populations, two independent subgroups for Norwegian tumors by their anatomic sites, and five subgroups for Sudanese tumors by their toombak habits. These results are indicative that the development of HNSCCs is mediated by similar biological pathways regardless of differences related to race, ethnicity, lifestyle, and/or exposure to environmental carcinogens. Of particular interest, however, is the valuable association of gene expression signature found with toombak use and anatomic site of the tumors.