Alcohol and tobacco When DNA undergoes oxidative damage, two of the most common damages change guanine to 8-hydroxyguanine or to 2,6-diamino-4-hydroxy-5-formamidopyrimidine. Around 75% of cases are caused by alcohol and tobacco use. Tobacco smoking is one of the main risk factors for<unk> . A major carcinogenic compound in tobacco smoke is acrylonitrile. Acrylonitrile appears to indirectly cause DNA damage by increasing oxidative stress, leading to increased levels of 8-oxo-2'-deoxyguanosine (8-oxo-dG) and formamidopyrimidine in DNA. (see image). Both 8-oxo-dG and formamidopyrimidine are mutagenic. DNA glycosylase NEIL1 prevents mutagenesis by 8-oxo-dG and removes formamidopyrimidines from DNA. However, cigarette smokers have a lifetime increased risk for<unk> s that is 5- to 25-fold increased over the general population. The ex-smoker's risk for developing a<unk>  begins to approach the risk in the general population 15 years after smoking cessation. The high prevalence of tobacco and alcohol use worldwide and the high association of these<unk> s with these substances makes them ideal targets for enhanced<unk>  prevention. Smokeless tobacco is a cause of oral<unk>  and oropharyngeal<unk> . Smokeless tobacco (including products where tobacco is chewed) is associated with a risk of developing<unk> s; this link has been established in the United States as well as in East Asian countries.Cigar smoking is also an important risk factor for oral<unk> . It should also be noted that the use of electronic cigarettes may also lead to the development of<unk> s due to the substances like propylene glycol, glycerol, nitrosamines and metals contained there in; which can cause damage to airways. This area of study requires more research to prove correlation and/or causation, however. Other environmental carcinogens suspected of being potential causes of<unk>  include occupational exposures such as nickel ore refining, exposure to textile fibers, and woodworking. Use of marijuana, especially when younger, has been linked to an increase in squamous-cell carcinoma cases in at least one study, while other studies suggest use is not shown to be associated with oral squamous cell carcinoma, or associated with decreased squamous cell carcinoma. Diet Excessive consumption of eggs, processed meats, and red meat were associated with increased rates of<unk>  of the<unk>  and<unk>  in one study, while consumption of raw and cooked vegetables seemed to be protective. Vitamin E was not found to prevent the development of leukoplakia, the white plaques that are the precursor for carcinomas of the mucosal surfaces, in adult smokers. Another study examined a combination of Vitamin E and beta carotene in smokers with early-stage<unk>  of the oropharynx, and found a worse prognosis in the vitamin users. Betel nut Betel nut chewing is associated with an increased risk of squamous cell<unk>  of the<unk>  and<unk> . Infection Human papillomavirus Some<unk> s are caused by human papillomavirus (HPV). In particular, HPV16 is a causal factor for some<unk>  and<unk>  squamous-cell carcinomas (HNSCCs). Approximately 15–25% of HNSCC contain genomic DNA from HPV, and the association varies based on the site of the tumor, especially HPV-positive oropharyngeal<unk> , with highest distribution in the tonsils, where HPV DNA is found in (45 to 67%) of the cases, less often in the hypopharynx (13–25%), and least often in the oral cavity (12–18%) and larynx (3–7%). Some experts estimate that while up to 50% of<unk> s of the tonsil may be infected with HPV, only 50% of these are likely to be caused by HPV (as opposed to the usual tobacco and alcohol causes). The role of HPV in the remaining 25–30% is not yet clear. Oral sex is not risk free and results in a significant proportion of HPV-related<unk> . Positive HPV16 status is associated with improved prognosis over HPV-negative OSCC. HPV can induce tumor by several mechanisms: # E6 and E7 oncogenic proteins. # Disruption of tumor suppressor genes. # High-level DNA amplifications, for example, oncogenes. # Generating alternative nonfunctional transcripts . # interchromosomal rearrangements. # Distinct host genome methylation and expression patterns, produced even when virus isn't integrated into the host genome. Induction of<unk>  can be associated for the expression of viral oncoproteins, the most important E6 and E7, or other mechanisms many of them run by the integration such as the generation of altered transcripts, disruption of tumor suppressors, high levels of DNA amplifications, interchromosomial rearrangements, or changes in DNA methylation patterns, the latter being able to find even when the virus is identified in episomes. E6 sequesters p53 to promote p53 degradation while E7 inhibits pRb. p53 prevents cell growth when DNA is damaged by activating apoptosis and p21, a kinase that blocks the formation of cyclin D / Cdk4 avoiding pRb phosphorylation and thereby prevents release of E2F is a transcription factor required for activation of genes involved in cell proliferation. pRb remains bound to E2F while this action phosphorylated preventing activation of proliferation. Therefore, E6 and E7 act synergistically in triggering cell cycle progression and therefore uncontrolled proliferation by inactivating the p53 and Rb tumor suppressors. Viral integration tends to occur in or near oncogenes or tumor suppressor genes and it is for this reason that the integration of the virus can greatly contribute to the development of tumor characteristics. Epstein–Barr virus Epstein–Barr virus (EBV) infection is associated with nasopharyngeal<unk> . Nasopharyngeal<unk>  occurs endemically in some countries of the Mediterranean and Asia, where EBV antibody titers can be measured to screen high-risk populations. Nasopharyngeal<unk>  has also been associated with consumption of salted fish, which may contain high levels of nitrites. Gastroesophageal reflux disease The presence of acid reflux disease (gastroesophageal reflux disease GERD) or larynx reflux disease can also be a major factor. Stomach acids that flow up through the esophagus can damage its lining and raise susceptibility to throat<unk> . Hematopoietic stem cell transplantation Patients after hematopoietic stem cell transplantation (HSCT) are at a higher risk for oral squamous cell carcinoma. Post-HSCT oral<unk>  may have more aggressive behavior with poorer prognosis, when compared to oral<unk>  in non-HSCT patients. This effect is supposed to be owing to the continuous lifelong immune suppression and chronic oral graft-versus-host disease. Other possible causes There are several risk factors for developing throat<unk> . These include smoking or chewing tobacco or other things, such as gutkha, or paan, heavy alcohol consumption, poor diet resulting in vitamin deficiencies (worse if this is caused by heavy alcohol intake), weakened immune system, asbestos exposure, prolonged exposure to wood dust or paint fumes, exposure to petroleum industry chemicals, and being over the age of 55 years. Other risk factors include the appearance of white patches or spots in the mouth, known as leukoplakia, which in about ⅓ of cases develops into<unk> , and breathing or inhaling silica from cutting concrete, stone or cinder-blocks, especially in enclosed areas such as a warehouse, garage or basement.
Head and neck cancer
Laryngeal cancer
Oral cancer
Paranasal sinus and nasal cavity cancer
Oropharyngeal cancer
Hypopharyngeal cancer
Nasal polyp
Nasal glioma