The person typically already has a history of  atopy  and an atopic family history. Eczema, otolaryngeal symptoms of hay fever or asthma will often dominate leading to the food allergy being unsuspected. Often well-cooked, canned, pasteurized, or frozen food offenders cause little to no reaction due to  denaturation  of the cross-reacting proteins, [ 9 ]  causing delay and confusion in diagnosis as the symptoms are elicited only to the raw or fully ripened fresh foods. Correct diagnosis of the allergen types involved is critical. Those with OAS may be allergic to more than just pollen. Oral reactions to food are often mistakenly self-diagnosed by patients as caused by pesticides or other contaminants. Other reactions to food—such as  lactose intolerance  and intolerances which result from a patient being unable to metabolize naturally occurring chemicals (e.g., salicylates and proteins) in food—need to be distinguished from the systemic symptoms of OAS. [ citation needed ]


Many people are unaware that they have OAS. However, if  swelling ,  tingling  or pain develops while eating certain foods, it is wise to see an allergy specialist. Before a diagnosis can be made, it is best to keep a food diary. This is important as the  physician  can then perform an allergy test. A comprehensive history is obtained so that random testing is avoided. The diagnosis of OAS may involve skin prick tests, blood tests, patch tests or oral challenges. [ citation needed ]


To confirm OAS, the suspected food is consumed in a normal way. The period of observation after ingestion and symptoms are recorded. If other factors such as combined foods are required, this is also replicated in the test. For example, if the individual always develops symptoms after eating followed by exercise, then this is replicated in the laboratory. [ citation needed ]


OAS must be managed in conjunction with the patient's other allergies, primarily the allergy to pollen.  The symptom severity may wax and wane with the pollen levels. Published pollen counts and seasonal charts are useful but may be ineffective in cases of high wind or unusual weather, as pollen can travel hundreds of kilometers from other areas. In addition, patients are advised to avoid the triggering foods, particularly nuts. Peeling or cooking the foods has been shown to eliminate the effects of some allergens such as  mal d 1  (apple), but not others such as celery or strawberry.  In the case of foods such as hazelnut, which have more than one allergen, cooking may eliminate one allergen but not the other. [ citation needed ]


Antihistamines  may also relieve the symptoms of the allergy by blocking the immune pathway.  Persons with a history of severe anaphylactic reaction may carry an injectable emergency dose of  epinephrine  (such as an EpiPen).  Oral steroids may also be helpful.  Allergy immunotherapy  has been reported to improve or cure OAS in some patients.  Immunotherapy with extracts containing birch pollen may benefit those with apple or hazelnut related to birch pollen-allergens. Even so, the increase in the amount of apple/hazelnut tolerated was small (from 12.6 to 32.6 g apple), and as a result, a patient's management of OAS would be limited. [ 16 ]


Oropharyngeal cancer , [ 1 ] [ 2 ] [ 3 ]  also known as  oropharyngeal squamous cell carcinoma  and  tonsil cancer , [ 1 ]  is a disease in which abnormal cells with the potential to both grow locally and spread to other parts of the body are found in the  oral cavity , in the tissue of the part of the throat ( oropharynx ) that includes the  base of the tongue , the  tonsils , the soft  palate , and the walls of the  pharynx . [ 1 ] [ 2 ] [ 3 ] [ 5 ]


The two types of oropharyngeal cancers are  HPV-positive oropharyngeal cancer , which is caused by an oral  human papillomavirus infection ; [ 1 ] [ 2 ] [ 3 ] [ 4 ]  and HPV-negative oropharyngeal cancer, which is linked to  use of alcohol ,  tobacco , or both. [ 1 ] [ 6 ]


Oropharyngeal cancer is diagnosed by  biopsy  of observed abnormal tissue in the throat. Oropharyngeal cancer  is staged according to the appearance of the abnormal cells on the biopsy coupled with the dimensions and the extent of the abnormal cells found. Treatment is with surgery, chemotherapy, or radiation therapy; or some combination of those treatments.


The signs and symptoms of oropharyngeal cancer may include: [ 5 ] [ 7 ] [ 8 ]


The risk factors that can increase the risk of developing oropharyngeal cancer are: [ 1 ] [ 7 ]


The cancer can spread three ways: [ 7 ]


Diagnosis is by  biopsy  of observed abnormal tissue in the oropharynx.


The  National Cancer Institute  (2016) provides the following definition: [ 14 ]


Abnormal cells are found in the lining of the  oropharynx . These may become cancer and spread into nearby normal tissue.


Cancer has formed and is 20 mm or smaller and has not spread outside the oropharynx.


Cancer has formed and is larger than 20 mm, but not larger than 40 mm. Also, it has not yet spread outside the oropharynx.


Cancer has spread to other parts of the body; the  tumor  may be any size and may have spread to lymph nodes.


Regarding the primary prevention of  HPV-positive oropharyngeal cancer ,  HPV vaccines  show more than 90% efficacy in preventing vaccine-type HPV infections and their correlated anogenital  precancerous lesions . [ 1 ]  A research conducted in 2017 demonstrated that HPV vaccination induces HPV antibodies levels at the  oral cavity  that correlate with circulating levels. [ 1 ]


Regarding the primary prevention of HPV-positive oropharyngeal cancer,  safe oral sex habits  should be advised [ 1 ]  (see  Sex education ). Regarding the primary prevention of HPV-negative oropharyngeal cancer, educating people on the risks of chewing  betel quid ,  alcohol use , and  tobacco smoking  is of the prime importance in the control and prevention of oropharyngeal cancers. [ 1 ]


People with  HPV-positive oropharyngeal cancer  tend to have higher survival rates. [ 1 ] [ 6 ]  However, HPV is tested for by the presence of the  biomarker   p16 , which normally increases in the presence of HPV. Some people can have elevated levels of p16 but test negative for HPV and vice versa. This is known as discordant cancer. The five-year survival for people who test positive for HPV and p16 is 81%, for discordant cancer it is 53 – 55%, and 40% for those who test negative for p16 and HPV. [ 15 ] [ 16 ]  The  prognosis  for people with oropharyngeal cancer depends on the age and health of the person and the stage of the disease. [ 1 ]  It is important for people with oropharyngeal cancer to have follow-up exams for the rest of their lives, as cancer can occur in nearby areas. In addition, it is important to eliminate risk factors such as smoking and drinking alcohol, which increase the risk for second cancers. [ 5 ]


Traditionally, oropharyngeal cancer has been managed through combination of surgery and radiotherapy. Other treatments have been developed including a combination of surgery, radiotherapy, chemotherapy and immunotherapy, but with limited improvement in survival rates. [ 17 ]  Studies comparing different combinations of treatment on patient outcomes have shown insufficient evidence that any treatment combination is superior to others. [ 17 ]


Oral cancer , also known as  oral cavity cancer ,  tongue cancer  or  mouth cancer , is a  cancer  of the lining of the lips, mouth, or upper throat. [ 6 ]  In the mouth, it most commonly starts as a painless  red  or  white patch , that thickens, gets ulcerated and continues to grow. When on the lips, it commonly looks like a persistent crusting ulcer that does not heal, and slowly grows. [ 7 ]  Other symptoms may include difficult or painful swallowing, new lumps or bumps in the neck, a swelling in the mouth, or a feeling of numbness in the mouth or lips. [ 8 ]


Risk factors include  tobacco  and  alcohol use . [ 9 ] [ 10 ]  Those who use both alcohol and tobacco have a 15 times greater risk of oral cancer than those who use neither. [ 11 ]  Other risk factors include  betel nut chewing [ 12 ]  and  sun exposure  on the lip. [ 13 ]   HPV  infection may play a limited role in some oral cavity cancers. [ 14 ]  Oral cancer is a subgroup of  head and neck cancers . [ 6 ]  Diagnosis is made by sampling ( biopsy ) of the lesion, followed by an imaging workup (called staging) which can include  CT scan ,  MRI ,  PET scan  to determine the local extension of the tumor, and if the disease has spread to distant parts of the body.


Oral cancer can be prevented by avoiding tobacco products, limiting alcohol use, sun protection on the lip, HPV vaccination, and avoidance of  betel nut chewing . Treatments used for oral cancer can include a combination of  surgery  (to remove the tumor and  regional lymph nodes ),  radiation therapy ,  chemotherapy , or  targeted therapy . The types of treatments will depend on the size, locations, and spread of the cancer taken into consideration with the general health of the person. [ 7 ]


In 2018, oral cancer occurred globally in about 355,000 people, and resulted in 177,000 deaths. [ 5 ]  Between 1999 and 2015 in the United States, the rate of oral cancer increased 6% (from 10.9 to 11.6 per 100,000). Deaths from oral cancer during this time decreased 7% (from 2.7 to 2.5 per 100,000). [ 15 ]  Oral cancer has an overall 5 year survival rate of 65% in the United States as of 2015. [ 4 ]  This varies from 84% if diagnosed when localized, compared to 66% if it has spread to the lymph nodes in the neck, and 39% if it has spread to distant parts of the body. [ 4 ]  Survival rates also are dependent on the location of the disease in the mouth. [ 16 ]


The signs and symptoms of oral cancer depend on the location of the  tumor  but are generally thin, irregular, red and/or white patches in the mouth. The classic warning sign is a persistent rough patch with  ulceration , and a raised border that is minimally painful. On the lip, the ulcer is more commonly crusting and dry, and in the  pharynx  it is more commonly a mass. It can also be associated with loose teeth, bleeding gums, persistent  ear ache , a feeling of numbness in the lip and chin, or swelling. [ 17 ]  When the cancer extends to the  oropharynx  (back of the throat), there can also be  difficulty swallowing .


Typically, the lesions cause very little pain until they become larger and then are associated with a local pain, burning sensation or ear ache (referred otalgia). [ 18 ]  As the lesion spreads to the  lymph nodes  of the neck, a painless, hard mass will develop. If it spreads elsewhere in the body, general aches can develop, most often due to  bone metastasis . [ 18 ]


The main causes of oral cancer are alcohol and tobacco (smoked or  chewed ). The risk is especially high when a person regularly uses both. The more is consumed of either the higher the risk of developing oral cancer. Like all environmental factors, the rate at which cancer will develop is dependent on the dose, frequency and method of application of the  carcinogen  (the substance that is causing the cancer). [ 19 ] [ 20 ]  Aside from tobacco and alcohol, other carcinogens for oral cancer include viruses (particularly  HPV  16 and 18),  radiation , and  UV light . [ 7 ]


Tobacco  is the greatest single cause of oral and pharyngeal cancer. Using tobacco increases the risk of oral cancer by 3 to 6 times [ 20 ] [ 9 ]  and is responsible for around 40% of all oral cancers. [ 21 ]   Smokeless tobacco  (including  chewing tobacco ,  snuff ,  snus ) also causes oral cancer. [ 22 ] [ 23 ] [ 24 ]   Cigar  and  pipe smoking  are also important risk factors. [ 25 ]


The use of  electronic cigarettes  may also lead to the development of head and neck cancers due to the substances like  propylene glycol ,  glycerol ,  nitrosamines , and metals contained therein, which can cause damage to the airways. [ 26 ]


Use of  marijuana  has currently not been shown to be associated with head and neck cancer risk. [ 27 ]


Drinking  alcohol  is a major cause of oral cancer. [ 28 ] [ 29 ]  It was responsible for 20% of global oral cancer cases in 2020. [ 30 ]  The more alcohol is consumed regularly the higher the risk, but light to moderate drinking still somewhat increases the chances of getting oral cancer. [ 31 ]  The risk is especially high when both alcohol and tobacco are used. [ 32 ]


It has been controversial if the use of alcohol-based  mouthwashes  increases oral cancer risk. [ 33 ]  As of 2024, there is some limited evidence supporting that the use of mouthwashes containing alcohol can increase the occurrence of oral cancer in some cases. [ 34 ]  There are complex interactions between alcohol content, usage patterns, reduction of oral pathogens, poor oral hygiene, smoking, and drinking which make any broad conclusion very tenuous in the absence of rigorously controlled studies. [ 35 ] [ 34 ]  In subgroup analyses, various combinations of smoking, drinking alcohol, poor oral hygiene, and using mouthwash several times a day for 35 years or more significantly increased risk. [ 36 ]  Although alcohol is necessary to dissolve some active antimicrobial agents, Rao et al. advise reducing the alcohol content of mouthwashes if possible. [ 34 ]
According to a 2024 IARC report, drinking alcohol is the primary cause of around 20% of the nearly 75,000 lip and mouth cancers diagnosed worldwide annually. [ 37 ]


Infection with  human papillomavirus  (HPV), particularly type 16, is a cause of oropharyngeal cancer (tonsils, base of tongue). [ 38 ]  However, its role in the genesis of oral cavity cancers is a matter of debate. [ 14 ]  A 2023 meta-analysis observed that the HPV was present 6% of all oral cavity cancer cases, however without establishing a role of this virus in the oncogenesis of these tumors. The authors even reported that some base of tongue tumors may have been misclassified as oral cavity tumors, therefore mistakenly increasing the rate of HPV-positive oral cavity cancers. [ 39 ]


Chewing  betel quid  (paan) and  Areca nut -based products is known to be a strong risk factor for developing oral cancer even in the absence of tobacco. It doubles the risk of oral cancer 2.1 times [ 20 ]  and when chewed with additional tobacco in its preparation (like in  gutka ), there is an even higher risk. [ 40 ]


In  India  where such practices are common, oral cancer represents up to 40% of all cancers, compared to just 4% in the  UK .


People after  hematopoietic stem cell transplantation  (HSCT) are at a higher risk for oral cancer. Post-HSCT oral cancer may have more aggressive behavior with poorer prognosis, when compared to oral cancer in people not treated with HSCT. [ 41 ]  This effect is supposed to be owing to the continuous lifelong  immune  suppression and chronic oral  graft-versus-host disease . [ 41 ]


This HPV16 (along with HPV18) is the same virus responsible for the vast majority of all  cervical cancers  and is the most common sexually transmitted infection. Risk factors for developing HPV-positive oropharyngeal cancer include multiple sexual partners, anal and oral sex and a weak immune system. [ 42 ]


A  premalignant  (or precancerous) lesion is defined as "a benign, morphologically altered tissue that has a greater than normal risk of malignant transformation." There are several different types of premalignant lesion that occur in the mouth. Some oral cancers begin as white patches ( leukoplakia ), red patches ( erythroplakia ) or mixed red and white patches (erythroleukoplakia or "speckled leukoplakia"). Other common premalignant lesions include  oral submucous fibrosis  and  actinic cheilitis . [ 43 ]  In the Indian subcontinent oral submucous fibrosis is very common due to  betel nut  chewing. This condition is characterized by limited opening of mouth and burning sensation on eating of spicy food. This is a progressive lesion in which the opening of the mouth becomes progressively limited, and later on even normal eating becomes difficult.


Oral  squamous cell carcinoma  is the end product of an unregulated proliferation of mucous basal cells. A single precursor cell is transformed into a clone consisting of many daughter cells with an accumulation of altered genes called  oncogenes . What characterizes a malignant tumor over a benign one is its ability to metastasize. This ability is independent of the size or grade of the tumor (often seemingly slow growing cancers like the adenoid cystic carcinoma can metastasis widely). It is not just rapid growth that characterizes a  cancer , but their ability to secrete enzymes, angiogeneic factors, invasion factors, growth factors and many other factors that allow it to spread. [ 7 ]


The full causal relation between alcohol consumption and the elevated risk of cancer remains unclear, but  acetaldehyde  plays a major role. [ 44 ]  Immediately after alcohol consumption, there are elevated levels of acetaldehyde in saliva, peaking after about 2 minutes. Acetaldehyde is produced by the oral microbiome, and also by enzymes in the oral mucosa, saliva glands, and liver. It is also naturally present in alcoholic beverages. Of these, the microbiome is the major contributor, accounting for at least half of the acetaldehyde present. Poor oral hygiene, smoking, and heavy drinking induce an increase in acetaldehyde-producing bacteria in the mouth. Many species of bacteria contribute to acetaldehyde production and their epidemiological significance is not known. The acetaldehyde reacts with oral epithelial cells, inducing DNA modifications, which can lead to mutations and cancer development. The ability to metabolize acetaldehyde in the mouth is limited, so it may remain in the saliva for hours. L-cysteine tablets may be used to decrease acetaldehyde exposure in the oral cavity. [ 45 ]


Diagnosis of oral cancer is completed for (1) initial diagnosis, (2)  staging , and (3) treatment planning. A complete history, and clinical examination is first completed, then a  wedge of tissue  is cut from the suspicious lesion for  tissue diagnosis . This might be done with scalpel biopsy,  punch biopsy ,  fine or core needle biopsy . In this procedure, the  surgeon  cuts all, or a piece of the tissue, to have it examined under a microscope by a  pathologist . [ 46 ]  Brush biopsies are not considered accurate for the diagnosis of oral cancer. [ 47 ]  Salivary biomarkers are also being under investigation with emerging outcomes and could potentially be used as a non-invasive diagnostic tool in the future. [ 48 ]


With the first biopsy, the  pathologist  will provide a  tissue diagnosis  (e.g.  squamous cell carcinoma ), and  classify  the cell structure. They may add additional information that can be used in staging, and treatment planning, such as the  mitotic rate , the  depth of invasion , and the  HPV  status of the tissue.


After the tissue is confirmed cancerous, other tests will be completed to:


Other, more invasive tests, may also be completed such as  fine needle aspiration ,  biopsy  of  lymph nodes , and  sentinel node biopsy . When the cancer has spread to lymph nodes, their exact location, size, and spread beyond the capsule (of the lymph nodes) needs to be determined, as each can have a significant impact on treatment and prognosis. Small differences in the pattern of lymph node spread, can have a significant impact on treatment and prognosis. Panendoscopy may be recommended, because the tissues of the entire upper  aerodigestive tract  are generally affected by the same  carcinogens , so other primary cancers are a common occurrence. [ 49 ] [ 50 ]


From these collective findings, taken in consideration with the health and desires of the person, the cancer team develops a plan for treatment. Since most oral cancers require surgical removal, a second set of  histopathologic  tests will be completed on any tumor removed to determine the prognosis, need for additional surgery, chemotherapy, radiation, immunotherapy, or other interventions.


Oral cancer is a subgroup of  head and neck cancers  which includes those of the  oropharynx ,  larynx ,  nasal cavity  and  paranasal sinuses ,   salivary glands , and  thyroid gland . Oral  melanoma , while part of head and neck cancers is considered separately. [ 6 ]  Other cancers can occur in the mouth (such as  bone cancer ,  lymphoma , or  metastatic cancers  from distant sites) but are also considered separately from oral cancers. [ 6 ]


Oral  cancer staging  is an assessment of the degree of spread of the cancer from its original source. [ 51 ]  It is one of the factors affecting both the  prognosis  and the potential treatment of oral cancer. [ 51 ]


The evaluation of squamous cell carcinoma of the mouth and pharynx staging uses the  TNM classification  (tumor, node, metastasis). This is based on the size of the primary tumor, lymph node involvement, and distant metastasis. [ 52 ]


TMN evaluation allows the person to be classified into a prognostic staging group; [ 52 ]


The  US Preventive Services Task Force  (USPSTF) in 2013 stated evidence was insufficient to determine the balance of benefits and harms of screening for oral cancer in adults without symptoms by primary care providers. [ 53 ]  The  American Academy of Family Physicians  comes to similar conclusions while the  American Cancer Society  recommends that adults over 20 years who have periodic health examinations should have the oral cavity examined for cancer. [ 53 ]  The  American Dental Association  recommends that providers remain alert for signs of cancer during routine examinations. [ 53 ]


There are a variety of screening devices such as  toluidine blue , brush biopsy, or  fluorescence imaging , however, there is no evidence that routine use of these devices in general dental practice is helpful. [ 54 ]  Potential risks of using screening devices include false positives, unnecessary surgical biopsies, and a financial burden. [ 54 ]  Micronuclei assays can help in early detection of pre-malignant and malignant lesions, thereby improving survival and reducing morbidity associated with treatment. [ medical citation needed ]


There has also been research showing potential in using oral cytology as a diagnostic test for oral cancer instead of traditional biopsy techniques. In oral cytology, a brush is used to take some cells from the suspected lesion/area and these are sent to a laboratory for examination. [ 55 ]  This can be much less invasive and painful than a scalpel biopsy for the patient, however, there needs to be further research before oral cytology can be considered as an effective routine screening tool when compared to biopsies. [ 55 ]


Oral cancer (squamous cell carcinoma) is usually treated with surgery alone, or in combination with adjunctive therapy, including radiation, with or without chemotherapy. [ 46 ] : 602   With small lesions (T1), surgery or radiation have similar control rates, so the decision about which to use is based on functional outcome, and complication rates. [ 46 ]


In most centres, removal of  squamous cell carcinoma  from the oral cavity and neck is achieved primarily through surgery. This also allows a detailed examination of the tissue for  histopathologic  characteristics, such as depth, and spread to lymph nodes that might require radiation or chemotherapy. For small lesions (T1–2), access to the oral cavity is through the mouth. When the lesion is larger, involves the bone of the  maxilla  or  mandible , or access is limited due to mouth opening, the upper or lower lip is split, and the cheek pulled back to give greater access to the mouth. [ 46 ]  When the tumor involves the jaw bone, or when surgery or radiation will cause severe limited mouth opening, part of the bone is also removed with the tumor.


Spread of cancer from the oral cavity to the  lymph nodes  of the neck has a significant effect on  survival . Between 60 and 70% of people with early stage oral cancer will have no lymph node involvement of the neck  clinically , but 20–30% of those people (or up to 20% of all those affected) will have clinically undetectable spread of cancer to the lymph nodes of the neck (called occult disease).


The management of the neck is crucial, since spread to it reduces the chance of survival by 50%. [ 56 ]  If there is evidence of lymph node involvement of the neck, during the diagnostic phase, then a modified radical  neck dissection  is generally performed. Where the neck lymph nodes have no evidence of involvement clinically, but the oral cavity lesion is high risk for spread (e.g. T2 or above lesions), then a neck dissection of the lymph nodes above the level of the  omohyoid muscle  may be completed. T1 lesions that are 4 mm or greater in thickness have a significant risk of spread to neck nodes. When disease if found in the nodes after removal (but not seen clinically) the recurrence rates is 10–24%. If post-operative radiation is added, the failure rate is 0–15%. When lymph nodes are clinically found during the diagnosis phase, and radiation is added post-operative, disease control is >80%. [ 57 ]


Chemotherapy and  radiotherapy  are most often used, as an adjunct to surgery, to control oral cancer that is greater than stage 1, or has spread to either regional lymph nodes or other parts of the body. [ 46 ]  Radiotherapy alone can be used instead of surgery, for very small lesions, but is generally used as an adjunct when lesions are large, cannot be completely removed, or have spread to the lymph nodes of the neck.  Chemotherapy  is useful in oral cancers when used in combination with other treatment modalities such as radiation therapy but it is not used alone as a monotherapy. When a cure is unlikely, it can also be used to extend life and can be considered palliative but not  curative care . [ 58 ]


Monoclonal antibody therapy  (with agents such as  cetuximab ) have been shown to be effective in the treatment of squamous cell head and neck cancers, and are likely to have an increasing role in the future management of this condition when used in conjunction with other established treatment modalities, although it is not a replacement for chemotherapy in head and neck cancers. [ 59 ] [ 58 ]  Likewise, molecularly targeted therapies and immunotherapies may be effective for the treatment of oral and oropharyngeal cancers. Adding epidermal growth factor receptor monoclonal antibody (EGFR mAb) to standard treatment may increase survival, keeping the cancer limited to that area of the body and may decrease reappearance of the cancer. [ 59 ]


Following treatment,  rehabilitation  may be necessary to improve movement, chewing, swallowing, and speech.  Speech and language pathologists  may be involved at this stage. Treatment of oral cancer will usually be by a multidisciplinary team, with treatment professionals from the realms of radiation, surgery, chemotherapy, nutrition, dentistry, and even psychology all possibly involved with diagnosis, treatment, rehabilitation, and care. Due to the location of oral cancer, there may be a period where the person requires a  tracheotomy  and  feeding tube .


Survival rates for oral cancer depend on the precise site and the stage of the cancer at diagnosis. Overall, 2011 data from the SEER database shows that survival is around 57% at five years when all stages of initial diagnosis, all genders, all ethnicities, all age groups, and all treatment modalities are considered. Survival rates for stage 1 cancers are approximately 90%, hence the emphasis on early detection to increase survival outcome for people. Similar survival rates are reported from other countries, such as Germany. [ 60 ]


Globally, it newly occurred in about 355,000 people and resulted in 177,000 deaths in 2018. [ 5 ]  Of these 355,000, about 246,000 are males and 108,000 are females. [ 5 ]


In 2013, oral cancer resulted in 135,000 deaths, up from 84,000 deaths in 1990. [ 61 ]  Oral cancer occurs more often in people from lower and middle income countries. [ 62 ]


Europe places second-highest after Southeast Asia among all continents for age-standardised rate (ASR) specific to oral and oropharyngeal cancer. It is estimated that there were 61,400 cases of oral and lip cancer within Europe in 2012. Hungary recorded the highest number of mortality and morbidity due to oral and pharyngeal cancer among all European countries while Cyprus reported the lowest numbers  [ 63 ]


British Cancer Research found 2,386 deaths due to oral cancer in 2014; while most oral cancer cases are diagnosed in older adults between 50 and 74 years old, this condition can affect the young as well; [ 64 ]  6% of people affected by oral cancer are under 45 years of age. [ 65 ]  The United Kingdom is 16th-lowest for males and 11th-highest for females for oral cancer incidence among Europe. Additionally, there is a regional variability within the United Kingdom, with Scotland and northern England having higher rates than southern England. The same analysis applies to lifetime risk of developing oral cancer, as in Scotland it is 1.84% in males and 0.74% in females, higher than the rest of the UK, being 1.06% and 0.48%, respectively.


Oral cancer is the sixteenth most-common cancer in the United Kingdom (around 6,800 people were diagnosed with oral cancer in the United Kingdom in 2011), and it is the 19th most-common cause of cancer death (around 2,100 people died from the disease in 2012). [ 65 ]


The highest incidence of oral and pharyngeal cancer was recorded in Denmark, with age-standardised rates per 100,000 of 13.0, followed by Lithuania (9.9) and the United Kingdom (9.8). [ 63 ]  Lithuania reported the highest incidence in men while Denmark reported the highest in women. The highest rates for mortality in 2012 were reported in Lithuania (7.5), Estonia (6.0), and Latvia (5.4). [ 63 ]  Incidence of oral cancer in young adults (ages 20–39 years old) in Scandinavia has reportedly risen approximately 6-fold between 1960 and 1994 [ 66 ]  The high incidence rate of oral and pharyngeal cancer in Denmark could be attributed to their higher alcohol intake than citizens of other Scandinavian countries and low intake of fruits and vegetables in general.


Hungary (23.3), Slovakia (16.4), and Romania (15.5) reported the highest incidences of oral and pharyngeal cancer. [ 63 ]  Hungary also recorded the highest incidence in both genders as well as the highest mortality rates in Europe. [ 63 ]  It is ranked third globally for cancer mortality rates. [ 67 ]  Cigarette smoking, excessive alcohol consumption, inequalities in the care received by people with cancer, and gender-specific systemic risk factors have been determined as the leading causes for the high morbidity and mortality rates in Hungary. [ 68 ] [ 69 ] [ 70 ] [ 71 ]


The incidence rates of oral cancer in western Europe found France, Germany and Belgium to be highest. The ASRs (per 100,000) were 15.0, 14.6, and 14.1, respectively. When filtered by gender category, the same countries rank top 3 for male, however, in different order of Belgium (21.9), Germany (23.1), and France (23.1). France, Belgium, and the Netherlands rank highest for females, with ASRs 7.6, 7.0, and 7.0, respectively. [ 63 ]


Incidence of oral and oropharyngeal cancers were recorded, finding Portugal, Croatia and Serbia to have highest rates (ASR per 100,000). These values are 15.4, 12, and 11.7, respectively.


It is the eleventh-most-common cancer in the United States among males while in Canada and Mexico it is the twelfth and thirteenth-most-common cancer respectively. The ASIR for lip and oral cavity cancer among men in Canada and Mexico is 4.2 and 3.1, respectively. [ 72 ]


Of all the cancers, oral cancer attributes to 3% in males, opposed to 2% in women. New cases of oral cancer in US as of 2013, approximated almost 66,000 with almost 14000 attributed from tongue cancer, and nearly 12000 from the mouth, and the remainder from the oral cavity and pharynx. In the previous year, 1.6% of lip and oral cavity cancers were diagnosed, where the age-standardised incidence rate (ASIR) across all geographic regions of United States of America estimates at 5.2 per 100,000 population. [ 72 ]


In 2022, close to 54,000 Americans are projected to be diagnosed with oral or oropharyngeal cancer. 66% of the time, these will be found as late stage three and four disease. It will cause over 8,000 deaths. Of those newly diagnosed, only slightly more than half will be alive in five years. Similar survival estimates are reported from other countries. For example, five-year relative survival for oral cavity cancer in Germany is about 55%. [ 60 ]  In the US oral cancer accounts for about 8 percent of all malignant growths.


Oral cancers overall risk higher in black males opposed to white males, however specific oral cancers-such as of the lip, have a higher risk in white males opposed to black males. Overall, rates of oral cancer between gender groups (male and female) seem to be decreasing, according to data from 3 studies. [ 73 ]


The ASIR across all geographic regions of South America as of 2012 sits at 3.8 per 100,000 population where approximately 6,046 deaths have occurred due to lip and oral cavity cancer, where the age-standardized mortality rate remains at 1.4. [ 74 ]


In Brazil, however, lip and oral cavity cancer is the 7th most common cancer, with an estimated 6,930 new cases diagnosed in the year 2012. This number is rising and has an overall higher ASIR at 7.2 per 100,000 population whereby an approx 3000 deaths have occurred  [ 74 ]


Rates are increasing across both males and females. As of 2017, almost 50000 new cases of oropharyngeal cancers will be diagnosed, with incidence rates being more than twice as high in men than women. [ 74 ]


Oral cancer is one of the most-common types of cancer in Asia due to its association with smoking (tobacco, bidi), betel quid and alcohol consumption. Regionally incidence varies with highest rates in South Asia, particularly India, Bangladesh, Sri Lanka, Pakistan, and Afghanistan. [ 75 ]  In South East Asia and Arab countries, although the prevalence is not as high, estimated incidences of oral cancer ranged from 1.6 to 8.6/ 100,000 and 1.8 to 2.13/ 100,000 respectively. [ 76 ] [ 77 ]  According to GLOBOCAN 2012, the estimated age-standardised rates of cancer incidence and mortality was higher in males than females. However, in some areas, specifically South East Asia, similar rates were recorded for both genders. [ 76 ]  The average age of those diagnosed with oral squamous cell carcinoma is approximately 51–55. [ 75 ]  In 2012, there were 97,400 deaths recorded due to oral cancer. [ 78 ]


Oral cancer is the third-most-common form of cancer in India with over 77 000 new cases diagnosed in 2012 (2.3:1 male to female ratio). [ 79 ]  Studies estimate over five deaths per hour. [ 80 ]  One of the reasons behind such high incidence might be popularity of betel and areca nuts, which are considered to be risk factors for development of oral cavity cancers. [ 81 ]


There is limited data for the prevalence of oral cancer in Africa. The following rates describe the number of new cases (for incidence rates) or deaths (for mortality rates) per 100 000 individuals per year. [ 78 ]


The incidence rate of oral cancer is 2.6 for both sexes. The rate is higher in males at 3.3 and lower in females at 2.0. [ 78 ]


The mortality rate is lower than the incidence rate at 1.6 for both sexes. The rate is again higher for males at 2.1 and lower for females at 1.3. [ 78 ]


The following rates describe the number of new cases or deaths per 100 000 individuals per year. The incidence rate of oral cancer is 6.3 for both sexes; this is higher in males at 6.8–8.8 and lower in females at 3.7–3.9. [ 82 ]  The mortality rate is significantly lower than the incidence rate at 1.0 for both sexes. The rate is higher in males at 1.4 and lower in females at 0.6. [ 83 ]  Table 1 provides age-standardised incidence and mortality rates for oral cancer based on the location in the mouth. The location 'other mouth' refers to the buccal mucosa, the vestibule and other unspecified parts of the mouth. The data suggests lip cancer has the highest incidence rate while gingival cancer has the lowest rate overall. In terms of mortality rates, oropharyngeal cancer has the highest rate in males and tongue cancer has the highest rate in females. Lip, palatal and gingival cancer have the lowest mortality rates overall. [ 83 ]


Oral cancers are the fourth most common type seen in other animals in veterinary medicine, with older animals having higher chances of developing it. [ 84 ]


Dogs that are a breed that is at higher risk of developing oral cancer are more susceptible. Tumors that are found early in development can be removed by surgery, however some cases involve removing a part of the jaw. Chemotherapy is used following surgeries or to remove a tumor that cannot be accessed. Tumors that are caught when the cancer has already spread to other places of the body will result in the dog living for only 6-12 more months. [ 85 ]


The most common type of oral cancer seen in cats is squamous cell carcinoma. Due to tumors developing in hidden spots such as beneath the tongue, when the tumors in the cats mouth are caught it is often untreatable. [ 86 ]  Risk factors include secondhand smoke, as the smoke settles on the fur which is ingested when cats groom, and potentially the over consumption of canned food and use of flea collars. [ 87 ]


In  anatomy , the  orbit [ a ]  is the  cavity  or socket/hole of the  skull  in which the  eye  and  its appendages  are situated. "Orbit" can refer to the bony socket, [ 1 ]  or it can also be used to imply the contents. [ 2 ]  In the adult human, the volume of the orbit is about 28 millilitres (0.99 imp fl oz; 0.95 US fl oz), [ 3 ]  of which the eye occupies 6.5 ml (0.23 imp fl oz; 0.22 US fl oz). [ 4 ]  The orbital contents comprise the eye, the  orbital  and  retrobulbar  fascia,  extraocular muscles ,  cranial nerves   II ,  III ,  IV ,  V , and  VI , blood vessels, fat, the  lacrimal gland  with its  sac  and  duct , the  eyelids ,  medial  and  lateral palpebral ligaments , cheek ligaments, the  suspensory ligament ,  septum ,  ciliary ganglion  and  short ciliary nerves .


The orbits are conical or four-sided pyramidal cavities, which open into the midline of the face and point back into the head. Each consists of a base, an apex and four walls. [ 5 ]


There are two important  foramina , or windows, two important  fissures , or grooves, and one  canal  surrounding the  globe  in the orbit. There is a  supraorbital foramen , an  infraorbital foramen , a  superior orbital fissure , an  inferior orbital fissure  and the  optic canal , each of which contains structures that are crucial to normal eye functioning. The supraorbital foramen contains the supraorbital nerve, the first division of the  trigeminal nerve  or V1 and lies just lateral to the  frontal sinus . The infraorbital foramen contains the second division of the trigeminal nerve, the  infraorbital nerve  or V2, and sits on the anterior wall of the  maxillary sinus . Both foramina are crucial as potential pathways for cancer and infections of the orbit to spread  into the brain  or other deep facial structures.


The  optic canal  contains the ( cranial nerve II ) and the  ophthalmic artery , and sits at the junction of the sphenoid sinus with the  ethmoid air cells , superomedial and  posterior  to structures at the orbital apex. It provides a pathway between the orbital contents and the  middle cranial fossa . The superior orbital fissure lies just  lateral  and  inferior  to the optic canal, and is formed at the junction of the  lesser  and  greater wing  of the  sphenoid bone . It is a major pathway for intracranial communication, containing cranial nerves  III ,  IV ,  VI  which control eye movement via the  extraocular muscles , and the ophthalmic branches of  cranial nerve V , or V1. The second division of the trigeminal nerve enters the skull base at the  foramen rotundum , or V2. The inferior orbital fissure lies inferior and lateral to the ocular globe at the lateral wall of the maxillary sinus. It is not as important in function, though it does contain a few branches of the maxillary nerve and the infraorbital artery and vein. [ 6 ]  Other minor structures in the orbit include the  anterior  and  posterior ethmoidal foramen  and  zygomatic orbital foramen .


The bony walls of the orbital canal in humans do not derive from a single bone, but a mosaic of seven  embryologically  distinct structures: the  zygomatic bone   laterally , the  sphenoid bone , with its lesser wing forming the optic canal and its greater wing forming the lateral posterior portion of the bony orbital process, the  maxillary bone   inferiorly  and  medially  which, along with the  lacrimal  and  ethmoid bones , forms the medial wall of the  orbital canal . The ethmoid air cells are extremely thin, and form a structure known as the  lamina papyracea , the most delicate bony structure in the skull, and one of the most commonly fractured bones in orbital trauma. The lacrimal bone also contains the  nasolacrimal duct . The superior bony margin of the orbital rim, otherwise known as the  orbital process , is formed by the frontal bone. [ 7 ]


The roof (superior wall) is formed primarily by the orbital plate  frontal bone , and also the lesser wing of  sphenoid  near the apex of the orbit. The orbital surface presents medially by trochlear fovea and laterally by lacrimal fossa. [ 8 ]


The floor (inferior wall) is formed by the orbital surface of  maxilla , the orbital surface of  zygomatic bone  and the minute orbital process of  palatine bone . Medially, near the orbital margin, is located the groove for  nasolacrimal duct . Near the middle of the floor, located infraorbital groove, which leads to the infraorbital foramen. The floor is separated from the lateral wall by  inferior orbital fissure , which connects the orbit to  pterygopalatine  and  infratemporal fossa .


The medial wall is formed primarily by the orbital plate of  ethmoid , as well as contributions from the frontal process of maxilla, the  lacrimal bone , and a small part of the body of the sphenoid. It is the thinnest wall of the orbit, evidenced by pneumatized ethmoidal cells. [ 8 ]


The lateral wall is formed by the frontal process of zygomatic and more posteriorly by the orbital plate of the greater wing of sphenoid. The bones meet at the zygomaticosphenoid suture. The lateral wall is the thickest wall of the orbit, important because it is the most exposed surface, highly vulnerable to blunt force trauma.


The base, orbital margin, which opens in the face, has four borders. The following bones take part in their formation:


The orbit holds and protects the  eyes .


The movement of the eye is controlled by six distinct extraocular muscles, a  superior , an  inferior , a  medial  and a  lateral  rectus, as well as a  superior  and an  inferior oblique . The superior ophthalmic vein is a sigmoidal vessel along the superior margin of the orbital canal that drains deoxygenated blood from surrounding musculature. The  ophthalmic artery  is a crucial structure in the orbit, as it is often the only source of collateral blood to the brain in cases of large  internal carotid   infarcts , as it is a collateral pathway to the  circle of Willis . In addition, there is the  optic canal , which contains the optic nerve, or cranial nerve II, and is formed entirely by the lesser wing of the sphenoid, separated from the supraorbital fissure by the  optic strut . Injury to any one of these structures by infection, trauma or neoplasm can cause temporary or permanent visual dysfunction, and even blindness if not promptly corrected. [ 9 ]  The orbits also protect the eye from mechanical injury. [ 5 ]


In the orbit, the surrounding fascia allows for smooth rotation and protects the orbital contents. If excessive tissue accumulates behind the ocular globe, the eye can protrude, or become  exophthalmic . [ 5 ]


Enlargement of the  lacrimal gland , located superotemporally within the orbit, produces protrusion of the eye inferiorly and medially (away from the location of the lacrimal gland). Lacrimal gland may be enlarged from  inflammation  (e.g.  sarcoid ) or  neoplasm  (e.g.  lymphoma  or  adenoid cystic carcinoma ). [ 10 ]


Tumors (e.g.  glioma  and  meningioma  of the  optic nerve ) within the cone formed by the horizontal rectus muscles produce axial protrusion (bulging forward) of the eye.


Graves disease  may also cause axial protrusion of the eye, known as  Graves' ophthalmopathy , due to buildup of  extracellular matrix   proteins  and  fibrosis  in the rectus muscles. Development of Graves' ophthalmopathy may be independent of thyroid function. [ 11 ]


The  ossicles  (also called  auditory ossicles ) are three  irregular bones  in the  middle ear  of  humans  and other  mammals , and are among the smallest  bones  in the human body. Although the term "ossicle" literally means "tiny bone" (from  Latin   ossiculum ) and may refer to any small bone throughout the body, it typically refers specifically to the  malleus ,  incus  and  stapes  ("hammer, anvil, and stirrup") of the middle ear.


The auditory ossicles serve as a  kinematic chain  to transmit and amplify ( intensify )  sound  vibrations collected from the air by the  ear drum  to the fluid-filled  labyrinth  ( cochlea ). The absence or pathology of the auditory ossicles would constitute a moderate-to-severe  conductive hearing loss .


The ossicles are, in order from the eardrum to the inner ear (from superficial to deep): the  malleus ,  incus , and  stapes , terms that in  Latin  are translated as "the  hammer ,  anvil , and  stirrup ". [ 1 ]


Studies have shown that ear bones in mammal embryos are attached to the  dentary , which is part of the lower  jaw . These are ossified portions of  cartilage —called  Meckel's cartilage —that are attached to the jaw. As the embryo develops, the cartilage hardens to form bone. Later in development, the bone structure breaks loose from the jaw and migrates to the inner ear area. The structure is known as the middle ear, and is made up of the  stapes ,  incus ,  malleus , and  tympanic membrane . These correspond to the  columella ,  quadrate ,  articular , and  angular  structures in the amphibian, bird or reptile jaw. [ 3 ]


As sound waves vibrate the tympanic membrane (eardrum), it in turn moves the nearest ossicle, the malleus, to which it is attached. The malleus then transmits the vibrations, via the incus, to the stapes, and so ultimately to the membrane of the fenestra ovalis (oval window), the opening to the vestibule of the inner ear.


Sound traveling through the air is mostly reflected when it comes into contact with a liquid medium; only about 1/30 of the sound energy moving through the air would be transferred into the liquid. [ 4 ]  This is observed from the abrupt cessation of sound that occurs when the head is submerged underwater. This is because the relative incompressibility of a liquid presents resistance to the force of the sound waves traveling through the air. The ossicles give the eardrum a  mechanical advantage  via lever action and a reduction in the area of force distribution; the resulting vibrations are stronger but don't move as far. This allows more efficient coupling than if the sound waves were transmitted directly from the outer ear to the oval window. This reduction in the area of force application allows a large enough increase in  pressure  to transfer most of the sound energy into the liquid. The increased pressure will compress the fluid found in the cochlea and transmit the stimulus. Thus, the lever action of the ossicles changes the vibrations so as to improve the transfer and reception of sound, and is a form of  impedance matching .


However, the extent of the movements of the ossicles is controlled (and constricted) by two muscles attached to them (the  tensor tympani  and the  stapedius ). It is believed that these muscles can contract to dampen the vibration of the ossicles, in order to protect the inner ear from excessively loud noise (theory 1) and that they give better frequency resolution at higher frequencies by reducing the transmission of low frequencies (theory 2) (see  acoustic reflex ). These muscles are more highly developed in  bats  and serve to block outgoing cries of the bats during  echolocation  (SONAR).


Occasionally the joints between the ossicles become rigid. One condition,  otosclerosis , results in the fusing of the stapes to the oval window. This reduces  hearing  and may be treated surgically using a passive  middle ear implant . [ further explanation needed ]


There is some doubt as to the discoverers of the auditory ossicles and several anatomists from the early 16th century have the discovery attributed to them with the two earliest being  Alessandro Achillini  and  Jacopo Berengario da Carpi . [ 5 ]  Several sources, including  Eustachi  and  Casseri , [ 6 ]  attribute the discovery of the malleus and incus to the anatomist and philosopher  Achillini . [ 7 ]  The first written description of the malleus and incus was by  Berengario da Carpi  in his  Commentaria super anatomia Mundini  (1521), [ 8 ]  although he only briefly described two bones and noted their theoretical association with the transmission of sound. [ 9 ]   Niccolo Massa 's  Liber introductorius anatomiae [ 10 ]  described the same bones in slightly more detail and likened them both to little hammers. [ 9 ]  A much more detailed description of the first two ossicles followed in  Andreas Vesalius '  De humani corporis fabrica [ 11 ]  in which he devoted a chapter to them. Vesalius was the first to compare the second element of the ossicles to an anvil although he offered the molar as an alternative comparison for its shape. [ 12 ]  The first published description of the stapes came in  Pedro Jimeno 's  Dialogus de re medica  (1549) [ 13 ]  although it had been previously described in public lectures by  Giovanni Filippo Ingrassia  at the  University of Naples  as early as 1546. [ 14 ]


The term  ossicle  derives from  ossiculum , a  diminutive  of "bone" ( Latin :  os ;  genitive   ossis ). [ 15 ]  The malleus gets its name from Latin  malleus , meaning "hammer", [ 16 ]  the incus gets its name from Latin  incus  meaning "anvil" from incudere meaning "to forge with a hammer", [ 17 ]  and the stapes gets its name from Modern Latin "stirrup", probably an alteration of Late Latin  stapia  related to stare "to stand" and pedem, an accusative of pes "foot", so called because the bone is shaped like a stirrup – this was an invented Modern Latin word for "stirrup", for which there was no classical Latin word, as the ancients did not use stirrups. [ 18 ]


The  otic ganglion  is a small   parasympathetic ganglion  located immediately below the  foramen ovale  in the  infratemporal fossa  and on the medial surface of the  mandibular nerve . It is functionally associated with the  glossopharyngeal nerve  and innervates the  parotid gland  for salivation.


It is one of four parasympathetic ganglia of the head and neck. The others are the  ciliary ganglion , the  submandibular ganglion  and the  pterygopalatine ganglion .


The otic ganglion is a small (2–3 mm), oval shaped, flattened  parasympathetic ganglion  of a reddish-grey color, located immediately below the  foramen ovale  in the  infratemporal fossa  and on the medial surface of the  mandibular nerve .


It is in relation, laterally, with the trunk of the mandibular nerve at the point where the motor and sensory roots join; medially, with the cartilaginous part of the  auditory tube , and the origin of the  tensor veli palatini ; posteriorly, with the  middle meningeal artery . It surrounds the origin of the nerve to the  medial pterygoid .


The preganglionic  parasympathetic  fibres originate in the  inferior salivatory nucleus  of the  glossopharyngeal nerve . They leave the glossopharyngeal nerve by its  tympanic  branch and then pass via the  tympanic plexus  and the  lesser petrosal nerve  to the otic ganglion.  Here, the fibers synapse and the postganglionic fibers pass by communicating branches to the  auriculotemporal nerve , which conveys them to the  parotid gland . They produce vasodilator and secretomotor effects.


Its sympathetic root is derived from the plexus on the  middle meningeal artery . It contains post-ganglionic fibers arising in the  superior cervical ganglion . The fibers pass through the ganglion without relay and reach the  parotid gland  via the  auriculotemporal nerve . They are vasomotor in function.


The sensory root comes from the  auriculotemporal nerve  and is sensory to the  parotid gland .


The motor fibers supplying the  medial pterygoid  and the  tensor veli palatini  and the  tensor tympani  pass through the ganglion without relay.


Frey's syndrome  is caused by re-routing of parasympathetic and sympathetic fibres of the auriculotemporal nerve (V3) within the otic ganglion. It is a complication of surgery involving the parotid gland whereby injury to these branches, which innervate the parotid gland and sweat glands of the face respectively, form abnormal connections. Salivation leads to perspiration and flushing of the pre-auricular region and is called 'gustatory sweating'.


This article incorporates text in the  public domain  from  page 897  of the 20th edition of   Gray's Anatomy   (1918)


Otitis media  is a group of  inflammatory  diseases of the  middle ear . [ 2 ]  One of the two main types is  acute otitis media  ( AOM ), [ 3 ]  an  infection  of rapid onset that usually presents with ear pain. [ 1 ]  In young children this may result in pulling at the ear, increased crying, and poor sleep. [ 1 ]  Decreased eating and a  fever  may also be present. [ 1 ]


The other main type is  otitis media with effusion  ( OME ), typically not associated with symptoms, [ 1 ]  although  occasionally a feeling of fullness is described; [ 4 ]  it is defined as the presence of non-infectious fluid in the middle ear which may persist for weeks or months often after an episode of acute otitis media. [ 4 ]   Chronic suppurative otitis media  ( CSOM ) is middle ear inflammation that results in a perforated tympanic membrane with discharge from the ear for more than six weeks. [ 7 ]  It may be a complication of acute otitis media. [ 4 ]  Pain is rarely present. [ 4 ]


All three types of otitis media may be associated with  hearing loss . [ 2 ] [ 3 ]  If children with hearing loss due to OME do not learn  sign language , it may affect their ability to learn. [ 8 ]


The cause of AOM is related to childhood  anatomy  and  immune function . [ 4 ]  Either bacteria or viruses may be involved. [ 4 ]  Risk factors include exposure to smoke, use of  pacifiers , and attending  daycare . [ 4 ]  It occurs more commonly among  indigenous Australians  and those who have  cleft lip and palate  or  Down syndrome . [ 4 ] [ 9 ]  OME frequently occurs following AOM and may be related to  viral upper respiratory infections , irritants such as smoke, or  allergies . [ 3 ] [ 4 ]  Looking at the eardrum is important for making the correct diagnosis. [ 10 ]  Signs of AOM include bulging or a lack of movement of the  tympanic membrane  from a puff of air. [ 1 ] [ 11 ]  New discharge not related to  otitis externa  also indicates the diagnosis. [ 1 ]


A number of measures decrease the risk of otitis media including  pneumococcal  and  influenza vaccination ,  breastfeeding , and avoiding tobacco smoke. [ 1 ]  The use of  pain medications  for AOM is important. [ 1 ]  This may include  paracetamol  (acetaminophen),  ibuprofen ,  benzocaine  ear drops, or  opioids . [ 1 ]  In AOM, antibiotics may speed recovery but may result in side effects. [ 12 ]  Antibiotics are often recommended in those with severe disease or under two years old. [ 11 ]  In those with less severe disease they may only be recommended in those who do not improve after two or three days. [ 11 ]  The initial antibiotic of choice is typically  amoxicillin . [ 1 ]  In those with frequent infections, surgical placement of  tympanostomy tubes  may decrease recurrence. [ 1 ]  In children with otitis media with effusion  antibiotics  may increase resolution of symptoms, but may cause diarrhoea, vomiting and skin rash. [ 13 ]


Worldwide AOM affects about 11% of people a year (about 325 to 710 million cases). [ 14 ] [ 15 ]  Half the cases involve children less than five years of age and it is more common among males. [ 4 ] [ 14 ]  Of those affected about 4.8% or 31 million develop chronic suppurative otitis media. [ 14 ]  The total number of people with CSOM is estimated at 65–330 million people. [ 16 ]  Before the age of ten OME affects about 80% of children at some point. [ 4 ]  Otitis media resulted in 3,200 deaths in 2015 – down from 4,900 deaths in 1990. [ 6 ] [ 17 ]


The primary symptom of acute otitis media is  ear pain ; other possible symptoms include  fever , reduced hearing during periods of illness, tenderness on touch of the skin above the ear, purulent discharge from the ears,  irritability , ear blocking sensation and diarrhea (in infants). Since an episode of otitis media is usually precipitated by an  upper respiratory tract infection  (URTI), there are often accompanying symptoms like a  cough  and  nasal discharge . [ 1 ]   One might also experience a feeling of fullness in the ear.


Discharge from the ear can be caused by acute otitis media with perforation of the eardrum, chronic suppurative otitis media, tympanostomy tube otorrhea, or acute otitis externa. Trauma, such as a  basilar skull fracture , can also lead to cerebrospinal fluid otorrhea (discharge of CSF from the ear) due to cerebral spinal drainage from the brain and its covering (meninges). [ citation needed ]


The common cause of all forms of otitis media is dysfunction of the  Eustachian tube . [ 18 ]  This is usually due to inflammation of the  mucous membranes  in the  nasopharynx , which can be caused by a viral  upper respiratory tract infection  (URTI),  strep throat , or possibly by  allergies . [ 19 ]


By reflux or aspiration of unwanted secretions from the nasopharynx into the normally sterile middle-ear space, the fluid may then become infected – usually with  bacteria . The virus that caused the initial upper respiratory infection can itself be identified as the  pathogen  causing the infection. [ 19 ]


As its typical symptoms overlap with other conditions, such as acute external otitis, symptoms alone are not sufficient to predict whether acute otitis media is present; it has to be complemented by visualization of the  tympanic membrane . [ 20 ] [ 21 ]  Examiners may use a pneumatic  otoscope  with a rubber bulb attached to assess the mobility of the tympanic membrane. Other methods to diagnose otitis media is with a  tympanometry ,  reflectometry , or hearing test.


In more severe cases, such as those with associated hearing loss or high  fever ,  audiometry ,  tympanogram ,  temporal bone   CT  and  MRI  can be used to assess for associated complications, such as  mastoid effusion ,  subperiosteal   abscess  formation,  bony destruction ,  venous thrombosis  or  meningitis . [ 22 ]


Acute otitis media in children with moderate to severe bulging of the tympanic membrane or new onset of otorrhea (drainage) is not due to external otitis. Also, the diagnosis may be made in children who have mild bulging of the ear drum and recent onset of ear pain (less than 48 hours) or intense erythema (redness) of the ear drum. To confirm the diagnosis, middle-ear effusion and inflammation of the eardrum (called  myringitis  or tympanitis) have to be identified; signs of these are fullness, bulging, cloudiness and redness of the eardrum. [ 1 ]  It is important to attempt to differentiate between acute otitis media and otitis media with effusion (OME), as antibiotics are not recommended for OME. [ 1 ]  It has been suggested that bulging of the tympanic membrane is the best sign to differentiate AOM from OME, with a bulging of the membrane suggesting AOM rather than OME. [ 23 ]


Viral otitis may result in blisters on the external side of the tympanic membrane, which is called  bullous myringitis  ( myringa  being Latin for "eardrum"). [ 24 ]  However, sometimes even examination of the eardrum may not be able to confirm the diagnosis, especially if the canal is small. If wax in the ear canal obscures a clear view of the eardrum it should be removed using a blunt cerumen curette or a wire loop. An upset young child's crying can cause the eardrum to look inflamed due to distension of the small blood vessels on it, mimicking the redness associated with otitis media. [ 25 ]


The most common bacteria isolated from the middle ear in AOM are  Streptococcus pneumoniae ,  Haemophilus influenzae ,  Moraxella catarrhalis , [ 1 ]  and  Staphylococcus aureus . [ 26 ]


Otitis media with  effusion  (OME), also known as serous otitis media (SOM) or secretory otitis media (SOM), and colloquially referred to as 'glue ear', [ 27 ]  is fluid accumulation that can occur in the  middle ear  and  mastoid air cells  due to negative pressure produced by dysfunction of the Eustachian tube. This can be associated with a viral upper respiratory infection (URI) or bacterial infection such as otitis media. [ 28 ]  An effusion can cause  conductive hearing loss  if it interferes with the transmission of vibrations of  middle ear bones  to the  vestibulocochlear nerve complex  that are created by  sound waves . [ 29 ]


Early-onset OME is associated with feeding of infants while lying down, early entry into group  child care , parental  smoking , lack or too short a period of  breastfeeding , and greater amounts of time spent in group child care, particularly those with a large number of children. These risk factors increase the incidence and duration of OME during the first two years of life. [ 30 ]


Chronic suppurative otitis media (CSOM) is a long-term middle ear inflammation causing persistent ear discharge due to a perforated eardrum. It often follows an unresolved upper respiratory infection leading to acute otitis media. Prolonged inflammation leads to middle ear swelling, ulceration, perforation, and attempts at repair with granulation tissue and polyps. This can worsen discharge and inflammation, potentially developing into CSOM, often associated with cholesteatoma. Symptoms may include ear discharge or pus seen only on examination. Hearing loss is common. Risk factors include poor eustachian tube function, recurrent ear infections, crowded living, daycare attendance, and certain craniofacial malformations. [ citation needed ]


Worldwide approximately 11% of the human population is affected by AOM every year, or 709 million cases. [ 14 ] [ 15 ]  About 4.4% of the population develop CSOM. [ 15 ]


According to the  World Health Organization , CSOM is a primary cause of hearing loss in children. [ 31 ]  Adults with recurrent episodes of CSOM have a higher risk of developing permanent conductive and sensorineural hearing loss.


In Britain, 0.9% of children and 0.5% of adults have CSOM, with no difference between the sexes. [ 31 ]  The incidence of CSOM across the world varies dramatically where high income countries have a relatively low prevalence while in low income countries the prevalence may be up to three times as great. [ 14 ]  Each year 21,000 people worldwide die due to complications of CSOM. [ 31 ]


Adhesive otitis media occurs when a thin  retracted ear drum  becomes sucked into the middle-ear space and stuck (i.e., adherent) to the  ossicles  and other bones of the middle ear.


AOM is far less common in breastfed infants than in formula-fed infants, [ 32 ]  and the greatest protection is associated with exclusive breastfeeding (no formula use) for the first six months of life. [ 1 ]  A longer duration of breastfeeding is correlated with a longer protective effect. [ 32 ]


Pneumococcal conjugate vaccines  (PCV) in early infancy decrease the risk of acute otitis media in healthy infants. [ 33 ]  PCV is recommended for all children, and, if implemented broadly, PCV would have a significant  public health  benefit. [ 1 ]   Influenza vaccination  in children appears to reduce rates of AOM by 4% and the use of antibiotics by 11% over 6 months. [ 34 ]  However, the vaccine resulted in increased adverse-effects such as fever and runny nose. [ 34 ]  The small reduction in AOM may not justify the side effects and inconvenience of influenza vaccination every year for this purpose alone. [ 34 ]  PCV does not appear to decrease the risk of otitis media when given to high-risk infants or for older children who have previously experienced otitis media. [ 33 ]


Risk factors such as season, allergy predisposition and presence of older siblings are known to be determinants of recurrent otitis media and persistent middle-ear effusions (MEE). [ 35 ]  History of recurrence, environmental exposure to tobacco smoke, use of daycare, and lack of breastfeeding have all been associated with increased risk of development, recurrence, and persistent MEE. [ 36 ] [ 37 ]  Pacifier use has been associated with more frequent episodes of AOM. [ 38 ]


Long-term antibiotics, while they decrease rates of infection during treatment, have an unknown effect on long-term outcomes such as  hearing loss . [ 39 ]  This method of prevention has been associated with emergence of undesirable  antibiotic-resistant otitic bacteria . [ 1 ]


There is moderate evidence that the sugar substitute  xylitol  may reduce infection rates in healthy children who go to daycare. [ 40 ]


Evidence does not support  zinc  supplementation as an effort to reduce otitis rates except maybe in those with severe  malnutrition  such as  marasmus . [ 41 ]


Probiotics  do not show evidence of preventing acute otitis media in children. [ 42 ]


Oral and topical  pain killers  are the mainstay for the treatment of pain caused by otitis media. Oral agents include  ibuprofen ,  paracetamol  (acetaminophen), and  opiates . A 2023 review found evidence for the effectiveness of single or combinations of oral pain relief in acute otitis media is limited. [ 43 ]  Topical agents shown to be effective include  antipyrine and benzocaine ear drops . [ 44 ]


A 2008 review found reason to not recommend  decongestants  and  antihistamines , either nasal or oral, due to the lack of benefit and concerns regarding side effects, but this review was withdrawn from publication for being outdated. [ 45 ]  Half of cases of  ear pain  in children resolve without treatment in three days and 90% resolve in seven or eight days. [ 46 ]  The use of steroids is not supported by the evidence for acute otitis media. [ 47 ] [ 48 ]


Use of antibiotics for acute otitis media has benefits and harms. As over 82% of acute episodes settle without treatment, about 20 children must be treated to prevent one case of ear pain, 33 children to prevent one  perforation , and 11 children to prevent one opposite-side ear infection. For every 14 children treated with antibiotics, one child has an episode of vomiting, diarrhea or a rash. [ 49 ]   Analgesics  may relieve pain, if present. For people requiring surgery to treat otitis media with effusion, preventative antibiotics may not help reduce the risk of post-surgical complications. [ 50 ]


For bilateral acute otitis media in infants younger than 24 months, there is evidence that the benefits of antibiotics outweigh the harms. [ 12 ]  A 2015 Cochrane review concluded that watchful waiting is the preferred approach for children over six months with non severe acute otitis media. [ 12 ]


Most children older than 6 months of age who have acute otitis media do not benefit from treatment with antibiotics. If antibiotics are used, a  narrow-spectrum antibiotic  like  amoxicillin  is generally recommended, as  broad-spectrum antibiotics  may be associated with more adverse events. [ 1 ] [ 51 ]  If there is  resistance  or use of amoxicillin in the last 30 days then  amoxicillin-clavulanate  or another penicillin derivative plus beta lactamase inhibitor is recommended. [ 1 ]  Taking amoxicillin once a day may be as effective as twice [ 52 ]  or three times a day. While less than 7 days of antibiotics have fewer side effects, more than seven days appear to be more effective. [ 53 ]  If there is no improvement after 2–3 days of treatment a change in therapy may be considered. [ 1 ]  Azithromycin appears to have less side effects than either high dose amoxicillin or amoxicillin/clavulanate. [ 54 ]


Tympanostomy tubes  (also called "grommets") are recommended with three or more episodes of acute otitis media in 6 months or four or more in a year, with at least one episode or more attacks in the preceding 6 months. [ 1 ]  There is tentative evidence that children with recurrent acute otitis media (AOM) who receive tubes have a modest improvement in the number of further AOM episodes (around one fewer episode at six months and less of an improvement at 12 months following the tubes being inserted). [ 55 ] [ 56 ]


Evidence does not support an effect on long-term hearing or language development. [ 56 ] [ 57 ]  A common complication of having a tympanostomy tube is otorrhea, which is a discharge from the ear. [ 58 ]  The risk of persistent  tympanic membrane perforation  after children have grommets inserted may be low. [ 55 ]  It is still uncertain whether or not grommets are more effective than a course of antibiotics. [ 55 ]


Oral antibiotics should not be used to treat uncomplicated acute tympanostomy tube otorrhea. [ 58 ]  They are not sufficient for the bacteria that cause this condition and have side effects including increased risk of opportunistic infection. [ 58 ]  In contrast, topical antibiotic eardrops are useful. [ 58 ]


The decision to treat is usually made after a combination of physical exam and laboratory diagnosis, with additional testing including  audiometry ,  tympanogram ,  temporal bone   CT  and  MRI . [ 59 ] [ 60 ] [ 61 ]  Decongestants, [ 62 ]  glucocorticoids, [ 63 ]  and topical antibiotics are generally not effective as treatment for non-infectious, or  serous , causes of mastoid effusion. [ 59 ]  Moreover, it is recommended against using  antihistamines  and decongestants in children with OME. [ 62 ]  In less severe cases or those without significant hearing impairment, the effusion can resolve spontaneously or with more conservative measures such as  autoinflation . [ 64 ] [ 65 ]  In more severe cases,  tympanostomy tubes  can be inserted, [ 57 ]  possibly with  adjuvant   adenoidectomy [ 59 ]  as it shows a significant benefit as far as the resolution of middle ear effusion in children with OME is concerned. [ 66 ]


Topical antibiotics are of uncertain benefit as of 2020. [ 67 ]  Some evidence suggests that topical antibiotics may be useful either alone or with antibiotics by mouth. [ 67 ]  Antiseptics are of unclear effect. [ 68 ]  Topical antibiotics (quinolones) are probably better at resolving ear discharge than antiseptics. [ 69 ]


Complementary and alternative medicine  is not recommended for otitis media with effusion because there is no evidence of benefit. [ 28 ]   Homeopathic  treatments have not been proven to be effective for acute otitis media in a study with children. [ 70 ]   An  osteopathic manipulation technique  called the Galbreath technique [ 71 ]  was evaluated in one randomized controlled clinical trial; one reviewer concluded that it was promising, but a 2010 evidence report found the evidence inconclusive. [ 72 ]


Complications of acute otitis media consists of perforation of the ear drum, infection of the mastoid space behind the ear ( mastoiditis ), and more rarely intracranial complications can occur, such as  bacterial meningitis ,  brain abscess , or  dural sinus thrombosis . [ 73 ]  It is estimated that each year 21,000 people die due to complications of otitis media. [ 14 ]


In severe or untreated cases, the tympanic membrane may  perforate , allowing the  pus  in the middle-ear space to drain into the  ear canal . If there is enough, this drainage may be obvious. Even though the perforation of the tympanic membrane suggests a highly painful and traumatic process, it is almost always associated with a dramatic relief of pressure and pain. In a simple case of acute otitis media in an otherwise healthy person, the body's defenses are likely to resolve the  infection  and the ear drum nearly always heals.
An option for severe acute otitis media in which analgesics are not controlling ear pain is to perform a tympanocentesis, i.e., needle aspiration through the tympanic membrane to relieve the ear pain and to identify the causative organism(s).


Children with recurrent episodes of acute otitis media and those with otitis media with effusion or chronic suppurative otitis media have higher risks of developing  conductive  and  sensorineural hearing loss . Globally approximately 141 million people have mild hearing loss due to otitis media (2.1% of the population). [ 74 ]  This is more common in males (2.3%) than females (1.8%). [ 74 ]


This hearing loss is mainly due to fluid in the middle ear or rupture of the tympanic membrane. Prolonged duration of otitis media is associated with ossicular complications and, together with persistent tympanic membrane perforation, contributes to the severity of the disease and hearing loss. When a cholesteatoma or granulation tissue is present in the middle ear, the degree of hearing loss and ossicular destruction is even greater. [ 75 ]


Periods of conductive hearing loss from otitis media may have a detrimental effect on speech development in children. [ 76 ] [ 77 ] [ 78 ]  Some studies have linked otitis media to learning problems, attention disorders, and problems with social adaptation. [ 79 ]  Furthermore, it has been demonstrated that individuals with otitis media have more depression/anxiety-related disorders compared to individuals with normal hearing. [ 80 ]  Once the infections resolve and hearing thresholds return to normal, childhood otitis media may still cause minor and irreversible damage to the middle ear and cochlea. [ 81 ]  More research on the importance of screening all children under 4 years old for otitis media with effusion needs to be performed. [ 77 ]


Acute otitis media is very common in childhood. It is the most common condition for which medical care is provided in children under five years of age in the US. [ 19 ]  Acute otitis media affects 11% of people each year (709 million cases) with half occurring in those below five years. [ 14 ]  Chronic suppurative otitis media affects about 5% or 31 million of these cases with 22.6% of cases occurring annually under the age of five years. [ 14 ]  Otitis media resulted in 2,400 deaths in 2013 – down from 4,900 deaths in 1990. [ 17 ]


Australian Aboriginals  experience a high level of  conductive hearing loss  largely due to the massive incidence of middle ear disease among the young  in Aboriginal communities . Aboriginal children experience middle ear disease for two and a half years on average during childhood compared with three months for non indigenous children. If untreated it can leave a permanent legacy of hearing loss. [ 82 ]  The higher incidence of deafness in turn contributes to poor social, educational and emotional outcomes for the children concerned. Such children as they grow into adults are also more likely to experience employment difficulties and find themselves caught up in the criminal justice system. Research in 2012 revealed that nine out of ten Aboriginal prison inmates in the  Northern Territory  suffer from significant hearing loss. [ 83 ]
Andrew Butcher speculates that the lack of  fricatives  and the unusual  segmental  inventories of  Australian languages  may be due to the very high presence of otitis media ear infections and resulting hearing loss in their populations. People with hearing loss often have trouble distinguishing different vowels and hearing fricatives and  voicing  contrasts. Australian Aboriginal languages thus seem to show similarities to the speech of people with hearing loss, and avoid those sounds and distinctions which are difficult for people with early childhood hearing loss to perceive. At the same time, Australian languages make full use of those distinctions, namely place of articulation distinctions, which people with otitis media-caused hearing loss can perceive more easily. [ 84 ]  This hypothesis has been challenged on historical, comparative, statistical, and medical grounds. [ 85 ]


The term  otitis media  is composed of  otitis ,  Ancient Greek  for "inflammation of the ear", and  media ,  Latin  for "middle".


Oxybuprocaine  ( INN ), also known as  benoxinate  or  BNX , is an ester-type  local anesthetic , which is used especially in  ophthalmology  and  otolaryngology . Oxybuprocaine is sold by  Novartis  under the brand names  Novesine  or  Novesin .


Safety for use in pregnancy and lactation has not been established.


Anaesthesia starts with a latency of 30 to 50 seconds and lasts for about 10 to 30 minutes, depending on  perfusion . The drug is metabolised by  esterases  in blood plasma and liver. [ 3 ]


When used excessively, oxybuprocaine like any other topical anesthetic used in the eye and on mucous membranes (like for example  tetracaine ,  proxymetacaine  and  proparacaine ) can cause irritation,  hypersensitivity ,  anaphylaxis , irreversible corneal damage and even complete destruction of the cornea. [ 2 ] [ 4 ]  (Excessive use means several times a day during several days or even weeks.)


Oxybuprocaine is incompatible with  silver  and  mercury  salts, as well as  alkaline  substances. It also reduces the antimicrobial action of  sulfonamides . [ 3 ]


The nitration of 3-hydroxybenzoic acid [99-06-9] (0) gives 3-hydroxy-4-nitrobenzoic acid [619-14-7] ( 1 ).  Fischer esterification with ethanol gives ethyl 3-hydroxy-4-nitrobenzoate [717-01-1] ( 2 ). The phenoxide ion was then prepared from potash ( 3 ). Alkylation with  1-bromobutane   supplied ethyl 3-butoxy-4-nitrobenzoate,  CID:13346201  ( 4 ). The product is crystallized from hydrochloric acid, and then halogenation with thionyl chloride gives 3-butoxy-4-nitrobenzoyl chloride [23442-21-9] ( 5 ). Esterification with diethylaminoethanol [100-37-8] ( 6 ) gives 2-(diethylamino)ethyl 3-butoxy-4-nitrobenzoate,  CID:13346204  ( 7 ) Lastly, catalytic hydrogenation over Raney-Nickel completes the synthesis of Oxybuprocaine ( 8 ).


The  palate  ( / ˈ p æ l ɪ t / ) is the roof of the  mouth  in humans and other  mammals . It separates the  oral cavity  from the  nasal cavity . [ 1 ]  A similar structure is found in  crocodilians , but in most other  tetrapods , the oral and nasal cavities are not truly separated. The palate is divided into two parts, the anterior, bony  hard palate  and the posterior, fleshy  soft palate  (or velum). [ 2 ] [ 3 ]


The  maxillary nerve  branch of the  trigeminal nerve  supplies  sensory innervation  to the palate.


The hard palate forms before birth.


If the fusion is incomplete,  a  cleft palate  results.


When functioning in conjunction with other parts of the mouth, the palate produces certain sounds, particularly  velar ,  palatal ,  palatalized ,  postalveolar ,  alveolopalatal , and  uvular   consonants . [ 4 ]


The  English   synonyms  palate and palatum, and also the related adjective palatine (as in  palatine bone ), are all from the  Latin   palatum  via  Old French   palat , words that like their English  derivatives , refer to the "roof" of the mouth. [ 5 ]


The Latin word  palatum  is of unknown (possibly  Etruscan ) ultimate origin and served also as a source to the Latin word meaning palace,  palatium , from which other senses of  palatine  and the English word palace derive, and not the other way round. [ 6 ]


As the roof of the mouth was once considered the seat of the sense of  taste , palate can also refer to this sense itself, as in the phrase "a discriminating palate". By further extension, the flavor of a food (particularly beer or wine) may be called its palate, as when a wine is said to have an  oaky  palate.


In  anatomy , the  palatine bones  ( / ˈ p æ l ə t aɪ n / ; [ 1 ] [ 2 ]  derived from the Latin  palatum ) are two  irregular bones  of the  facial skeleton  in many animal species, located above the  uvula  in the  throat . Together with the  maxilla , they comprise the  hard palate .


The palatine bones are situated at the back of the  nasal cavity  between the  maxilla  and the  pterygoid process of the sphenoid bone .


They contribute to the walls of three cavities: the floor and lateral walls of the nasal cavity, the roof of the mouth, and the floor of the orbits. They help to form the  pterygopalatine  and  pterygoid fossae , and the  inferior orbital fissures .


Each palatine bone somewhat resembles the letter L, and consists of a  horizontal plate , a  perpendicular plate , and three projecting processes—the  pyramidal process , which is directed backward and lateral from the junction of the two parts, and the  orbital  and  sphenoidal processes , which surmount the vertical part, and are separated by a deep notch, the sphenopalatine notch. The two plates form the posterior part of the hard palate and the floor of the nasal cavity; anteriorly, they join with the maxillae. The two horizontal plates articulate with each other at the posterior part of the median palatine suture and more anteriorly with the maxillae at the transverse palatine suture. [ 3 ]


The human palatine articulates with six bones: the  sphenoid ,  ethmoid ,  maxilla ,  inferior nasal concha ,  vomer  and opposite palatine.


There are two important foramina in the palatine bones that transmit nerves and blood vessels to this region: the greater and lesser palatine. The larger  greater palatine foramen  is located in the posterolateral region of each of the palatine bones, usually at the apex of the maxillary third molar. The greater palatine foramen transmits the greater palatine nerve and blood vessels. A smaller opening nearby, the  lesser palatine foramen , transmits the lesser palatine nerve and blood vessels to the soft palate and tonsils. Both foramina are openings of the pterygopalatine canal that carries the descending palatine nerves and blood vessels from the pterygopalatine fossa to the palate. [ 3 ]


The  sphenopalatine foramen  is the opening between the sphenoid bone and orbital processes of the palatine bone; it opens into the nasal cavity and gives passage to branches from the pterygopalatine ganglion and the  sphenopalatine artery  from the maxillary artery. [ 3 ]


In  bony fish , the palatine bone consists of the perpendicular plate only, lying on the inner edge of the maxilla. The lower surface of the bone may bear several teeth, forming a second row behind those of the maxilla; in many cases, these are actually larger than the maxillary teeth. Although a similar pattern was present in primitive  tetrapods , the palatine bone is reduced in most living  amphibians , forming, in  frogs  and  salamanders , only a narrow bar between the vomer and maxilla. [ 4 ]


Early fossil  reptiles  retained the arrangement seen in more primitive vertebrates, but in  mammals , the lower surface of the palatine became folded over during evolution, forming the horizontal plate, and meeting in the midline of the mouth. This forms the rear of the  hard palate , separating the oral and nasal cavities, and making it easier to breathe while eating. A  parallel  development has occurred to varying degrees in many living reptiles, reaching its greatest extent in  crocodilians . In  birds , the palatine bones remain separate, long the sides of the rear part of the upper jaw, and typically have a mobile articulation with the  cranium . [ 4 ]


There are numerous variations amongst mammals, amphibians and other species. For example, the palatine bone in many amphibians such as the  rough-skinned newt  manifests as a distinct V-shaped structure. [ 5 ]  In the case of cat species, the horizontal and a vertical elements join at a 45-degree angle. [ 6 ]


This article incorporates text in the  public domain  from  page 166  of the 20th edition of   Gray's Anatomy   (1918)


The  palatine glands  form a continuous layer on the posterior surface of the  mucous membrane  of the  soft palate  and around the  uvula . They are pure mucous glands.


This article incorporates text in the  public domain  from  page 1141  of the 20th edition of   Gray's Anatomy   (1918)


Palatine tonsils , commonly called the  tonsils  and occasionally called the  faucial tonsils , [ 1 ]  are  tonsils  located on the left and right sides at the back of the  throat  in humans and other mammals, which can often be seen as flesh-colored, pinkish lumps. Tonsils only present as "white lumps" if they are inflamed or infected with symptoms of exudates (pus drainage) and severe swelling.


Tonsillitis  is an  inflammation  of the tonsils and will often, but not necessarily, cause a sore throat and  fever . [ 2 ]  In  chronic  cases,  tonsillectomy  may be indicated. [ 3 ]


The palatine tonsils are located in the  isthmus of the fauces , between the  palatoglossal arch  and the  palatopharyngeal arch  of the  soft palate .


The palatine tonsil is one of the  mucosa-associated lymphoid tissues  (MALT), located at the entrance to the upper respiratory and  gastrointestinal  tracts to protect the body from the entry of exogenous material through mucosal sites. [ 4 ] [ 5 ]  In consequence it is a site of, and potential focus for, infections, and is one of the chief immunocompetent tissues in the  oropharynx . It forms part of the  Waldeyer's ring , which comprises the  adenoid , the paired  tubal tonsils , the paired palatine tonsils and the  lingual tonsils . [ 6 ]  From the pharyngeal side, they are covered with a  stratified squamous epithelium , whereas a fibrous capsule links them to the wall of the pharynx. Through the capsule pass trabecules that contain small blood vessels, nerves and lymphatic vessels. These trabecules divide the tonsil into lobules.


The nerves supplying the palatine tonsils come from the  maxillary division  of the  trigeminal nerve  via the lesser palatine nerves, and from the tonsillar branches of the  glossopharyngeal nerve . The glossopharyngeal nerve continues past the palatine tonsil and innervates the posterior 1/3 of the tongue to provide general and taste sensation. [ 6 ]  This nerve is most likely to be damaged during a  tonsillectomy , which leads to reduced or lost general sensation and taste sensation to the posterior third of the tongue. [ 7 ] [ 8 ]


Blood supply is provided by tonsillar branches of five arteries: the  dorsal lingual artery  (of the  lingual artery ),  ascending palatine artery  (of the  facial artery ), tonsillar branch (of the facial artery),  ascending pharyngeal artery  (of the  external carotid artery ), and the  lesser palatine artery  (a branch of the  descending palatine artery , itself a branch of the  maxillary artery ).
The tonsils venous drainage is by the  peritonsillar plexus , which drain into the lingual and pharyngeal veins, which in turn drain into the  internal jugular vein . [ 6 ]


Palatine tonsils consist of approximately 15 crypts, which result in a large internal surface. The tonsils contain four lymphoid compartments that influence immune functions, namely the reticular crypt  epithelium , the  extrafollicular  area, the mantle zones of  lymphoid  follicles, and the follicular germinal centers. In human palatine tonsils, the very first part exposed to the outside environment is tonsillar epithelium. [ 9 ]


Tonsillar (relating to palatine tonsil) B cells can mature to produce all the five major  immunoglobulin  (Ig, aka antibody) classes. [ 5 ]  Furthermore, when incubated in vitro with either  mitogens  or specific  antigens , they produce specific antibodies against  diphtheria toxoid ,  poliovirus ,  Streptococcus pneumoniae ,  Haemophilus influenzae ,  Staphylococcus aureus , and the  lipopolysaccharide  of  E. coli . Most  Immunoglobulin A  produced by tonsillar B cells in vitro appears to be 7S monomers, although a significant proportion may be l0S dimeric IgA.


In addition to humoral immunity elicited by tonsillar and  adenoidal  B cells following antigenic stimulation, there is considerable T-cell response in palatine tonsils. [ 5 ]  Thus, natural infection or intranasal immunization with live,  attenuated   rubella  virus vaccine has been reported to prime tonsillar  lymphocytes  much better than  subcutaneous  vaccination. Also, natural infection with  varicella zoster virus  has been found to stimulate tonsillar lymphocytes better than lymphocytes from  peripheral blood .


Cytokines  are humoral  immunomodulatory  proteins or  glycoproteins  which control or modulate the activities of target cells, resulting in gene activation, leading to mitotic division, growth and differentiation, migration, or  apoptosis . They are produced by wide range of cell types upon antigen-specific and non-antigen specific stimuli. It has been reported by many studies that the clinic outcome of many infectious,  autoimmune , or malignant diseases appears to be influenced by the overall balance of production (profiles) of pro-inflammatory and anti-inflammatory cytokines. Therefore, determination of cytokine profiles in tonsil study will provide key information for further in-depth analysis of the cause and underlying mechanisms of these disorders, as well as the role and possible interactions between the T- and B-lymphocytes and other immunocompetent cells. [ 10 ]


The cytokine network represents a very sophisticated and versatile regulatory system that is essential to the immune system for overcoming the various defense strategies of microorganisms. Through several studies, the  Th1  and  Th2  cytokines and cytokine mRNA are both detectable in tonsillar hypertrophy (or  obstructive sleep apnea , OSA) and recurrent  tonsillitis  groups. It showed that human palatine tonsil is an active immunological organ containing a wide range of cytokine-producing cells. Both Th1 and Th2 cells are involved in the  pathophysiology  of TH and RT conditions. Indeed, human tonsils persistently harbor  microbial  antigens even when the subject is asymptomatic of ongoing infection. It could also be an effect of ontogeny of the immune system.


The pathogenesis of infectious/inflammatory disease in the tonsils most likely has its basis in their anatomic location and their inherent function as organ of immunity, processing infectious material, and other antigens and then becoming, paradoxically, a focus of infection/inflammation. No single theory of pathogenesis has yet been accepted, however. Viral infection with secondary bacterial invasion may be one mechanism of the initiation of chronic disease, [ 11 ]  but the effects of the environment, host factors, the widespread use of antibiotics, ecological considerations, and diet all may play a role. [ 12 ]  A recent cross-sectional study revealed a high rate of prevalent virus infections in non-acutely ill patients undergoing routine tonsillectomy. However, none of the 27 detected viruses showed positive association to the tonsillar disease. [ 13 ]


In children, the tonsils are common sites of infections that may give rise to acute or chronic tonsillitis. However, it is still an open question whether tonsillar hypertrophy is also caused by a persistent infection. Tonsillectomy is one of the most common major operations performed on children. The indications for the operation have been complicated by the controversy over the benefits of removing a chronically infected tissue and the possible harm caused by eliminating an important immune inductive tissue. [ 14 ] [ 15 ]


The information that is necessary to make a rational decision to resolve this controversy can be obtained by understanding the immunological potential of the normal palatine tonsils and comparing these functions with the changes that occur in the chronically diseased counterparts.


Tonsillitis  is the inflammation of tonsils. Acute tonsillitis is the most common manifestation of tonsillar disease. It is associated with sore throat, fever and  difficulty swallowing . [ 16 ]  The tonsils may appear normal sized or enlarged but are usually erythematous. Often, but not always,  exudates  can be seen. Not all these signs and symptoms are present in every patient.


Recurrent infection has been variably defined as from four to seven episodes of acute tonsillitis in one year, five episodes for two consecutive years or three episodes per year for 3 consecutive years. [ 17 ] [ 18 ]


Tonsillar hypertrophy is the enlargement of the tonsils, but without the history of inflammation. Obstructive tonsillar hypertrophy is currently the most common reason for tonsillectomy. [ 14 ]  These patients present with varying degrees of disturbed sleep which may include symptoms of loud snoring, irregular breathing, nocturnal choking and coughing, frequent awakenings,  sleep apnea ,  dysphagia  and/or daytime hypersomnolence. These may lead to behavioral/mood changes in patients and facilitate the need for a  polysomnography  in order to determine the degree to which these symptoms are disrupting their sleep. [ 19 ] [ 20 ]


The  palatopharyngeus  ( palatopharyngeal  or  pharyngopalatinus )  muscle  is a small  muscle  in the  roof of the mouth .


It is a long, fleshy fasciculus, narrower in the middle than at either end, forming, with the mucous membrane covering its surface, the  palatopharyngeal arch .


It is separated from the  palatoglossus muscle  by an angular interval, in which the  palatine tonsil  is lodged. It arises from the soft palate, where it is divided into two fasciculi by the  levator veli palatini  and  musculus uvulae .


Passing laterally and downward behind the palatine tonsil, the palatopharyngeus joins the  stylopharyngeus  and is inserted with that muscle into the posterior border of the thyroid cartilage, some of its fibers being lost on the side of the  pharynx  and others passing across the middle line posteriorly to decussate with the muscle of the opposite side.


Motor innervation of this muscle is provided through the pharyngeal plexus of the CN X (vagal nerve), SVE (special visceral efferent) fibers.


The  palatine velum  is slightly raised by the  levator veli palatini  and made tense by the  tensor veli palatini ; the palatopharyngeus muscles, by their contraction, pull the  pharynx  upward over the  bolus  of food and nearly come together, the  uvula  filling up the slight interval between them.


By these means the bolus is prevented from passing into the  nasopharynx ; at the same time, the palatopharyngeus muscles form an inclined plane, directed obliquely downward and backward, along the under surface of which the bolus descends into the lower part of the pharynx.


This article incorporates text in the  public domain  from  page 1140  of the 20th edition of   Gray's Anatomy   (1918)


Paranasal sinus and nasal cavity cancer  is a type of  cancer  that is caused by the appearance and spread of malignant cells into the  paranasal sinus  and  nasal cavity . The cancer most commonly occurs in people between 50 and 70 years old, and occurs twice as often in males as in females. [ 3 ]  During early phases of the cancer, symptoms may include  nasal obstruction  and  hyposmia , as well as other symptoms. [ 3 ]  More symptoms may develop as  malignant cells  further grow and spread into other nearby tissue such as the  palate  or orbital floor.  X-rays  of the head and  MRI  can aid in diagnosis of the cancer while tumor resection surgery,  radiation therapy  and  chemotherapy  can be used for treatment of the cancer.


People with early stage nasal cavity or paranasal sinus cancer often do not show any symptoms, therefore, these types of cancer are usually diagnosed in the later stages. Nasal cavity or paranasal sinus cancer is often discovered when a person is being treated for a seemingly benign, inflammatory disease of the sinuses, such as  sinusitis . [ 4 ]  The signs and symptoms of later stage cancer are generally caused by the spread of malignant cells into the neighbouring structures of the paranasal sinus and nasal cavity. [ 5 ]  There are often no obvious signs and symptoms before tumor cells spread into bone tissue. During the progress of the cancer, the overall signs and symptoms may include sinus pressure and pain, blocked sinus, headaches, nosebleeds, pain and pressure in the ears, among other symptoms. [ 1 ]  Different symptoms may appear as the tumor starts to spread into other body structures. Symptoms such as  proptosis ,  diplopia  and other eye problems may appear if the tumor spreads into the  orbit . [ 5 ]  Symptoms such as  trismus  (lockjaw), facial swelling,  toothache , mid-face or jaw numbness may occur if the tumor spreads into the  infratemporal fossa ,  pterygopalatine fossae  or masseteric space. [ 5 ]  The spread of the cancer into the cranial cavity may lead to  headaches ,  nerve damage , and  cerebrospinal fluid leak .


Cigarette smoking is strongly related to the risk of developing nasal cancer. Smokers have an excess 20% risk of developing nasal cancer.[2] There is a positive relationship between the quantity of cigarettes smoked and time period of smoking, and an increased risk of developing nasal cancer. Quitting smoking decreases the risk. There is also a positive relationship between having a spouse that smokes and developing nasal cancer.[2]


Direct contact of tobacco powder with the gums and the mucous membranes of the mouth can largely increase the risk of developing nasal or paranasal sinus cancer. [ 6 ]


Environmental factors are likely one of the main causes of paranasal sinus and nasal cavity cancer.[2] Exposure to wood dust and nickel dust may cause paranasal sinus and nasal cavity tumors. [ 3 ]  Exposure to radium fumes,  formaldehyde  fumes and other substances used in the production of leather and other textiles may also increase the risk. [ 7 ]  Exposure to air pollution may also increase the risk of getting the cancer. [ 7 ]


Alcohol consumption  may increase the risk  of cancer.[2] There is no evidence that alcohol increases the risk of any specific histological type of paranasal sinus and nasal cavity cancer. [ 6 ]  Consumption of large amounts of salted and smoked food may also increase the risk of developing paranasal sinus and nasal cavity cancer.[2]  Human papillomavirus infection  is likely a major cause of paranasal sinus and nasal cavity cancer. [ 1 ]  Other chronic nasal conditions may also increase the risk. [ 6 ]


Physical examination can performed to find physical signs of cancer such as swollen lymph nodes, lumps, or other abnormalities. [ 1 ]  Past medical records can also provide essential information for diagnosis. [ 1 ]  There are no blood or urine tests that can diagnose paranasal sinus and nasal cavity cancer. [ 7 ]