Head and neck cancer is a general term encompassing multiple

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

s that can develop in the head and neck region. These include cancers of the mouth, tongue, gums and lips (

oral cancer 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. In the mouth, it most commonly starts as a painless red or white patch, that thickens, gets ulcerated ...

), voice box ( laryngeal), throat (

nasopharyngeal The pharynx (: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the esophagus and trachea (the tubes going down to the stomach and the lungs respectively). It is found in vertebrates and invertebrates, though its ...

, oropharyngeal, hypopharyngeal),

salivary glands The salivary glands in many vertebrates including mammals are exocrine glands that produce saliva through a system of Duct (anatomy), ducts. Humans have three paired major salivary glands (Parotid gland, parotid, Submandibular gland, submandibula ...

, nose and sinuses. Head and neck cancer can present a wide range of symptoms depending on where the cancer developed. These can include an ulcer in the mouth that does not heal, changes in the voice,

difficulty swallowing Dysphagia is difficulty in swallowing. Although classified under " symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or li ...

, red or white patches in the mouth, and a neck lump. The majority of head and neck cancer is caused by the use of

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

tobacco Tobacco is the common name of several plants in the genus '' Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the ...

(including

smokeless tobacco Smokeless tobacco is a tobacco product that is used by means other than smoking. Their use involves chewing, sniffing, or placing the product between gum and the cheek or lip. Smokeless tobacco products are produced in various forms, such as ...

). An increasing number of cases are caused by the

human papillomavirus Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and r ...

(HPV). Other risk factors include the

Epstein–Barr virus The Epstein–Barr virus (EBV), also known as human herpesvirus 4 (HHV-4), is one of the nine known Herpesviridae#Human herpesvirus types, human herpesvirus types in the Herpesviridae, herpes family, and is one of the most common viruses in ...

, chewing betel quid (paan),

radiation exposure Radiation exposure is a measure of the ionization of air due to ionizing radiation from photons. It is defined as the electric charge freed by such radiation in a specified volume of air divided by the mass of that air. As of 2007, "medical radia ...

, poor nutrition and workplace exposure to certain toxic substances. About 90% are pathologically classified as squamous cell cancers. The diagnosis is confirmed by a

tissue biopsy A biopsy is a medical test commonly performed by a surgeon, an interventional radiologist, or an interventional cardiologist. The process involves the extraction of sample cells or tissues for examination to determine the presence or extent o ...

. The degree of surrounding tissue invasion and distant spread may be determined by

medical imaging Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to revea ...

and

blood test A blood test is a medical laboratory, laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose ...

s. Not using tobacco or alcohol can reduce the risk of head and neck cancer. Regular dental examinations may help to identify signs before the cancer develops. The

HPV vaccine Human papillomavirus (HPV) vaccines are vaccines intended to provide acquired immunity against infection by certain types of human papillomavirus. The first HPV vaccine became available in 2006. Currently there are six licensed HPV vaccines: ...

helps to prevent HPV-related oropharyngeal cancer. Treatment may include a combination of surgery,

radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

, and

targeted therapy Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy (oncology), hormonal therapy and cytotoxic chemotherapy. As a form of molecular medici ...

. In the early stage head and neck cancers are often curable but 50% of people see their doctor when they already have an advanced disease. Globally, head and neck cancer accounts for 650,000 new cases of cancer and 330,000 deaths annually on average. In 2018, it was the seventh most common cancer worldwide, with 890,000 new cases documented and 450,000 people dying from the disease. The usual age at diagnosis is between 55 and 65 years old. The average

5-year survival The five-year survival rate is a type of survival rate for estimating the prognosis of a particular disease, normally calculated from the point of diagnosis. Lead time bias from earlier diagnosis can affect interpretation of the five-year surviva ...

following diagnosis in the

developed world A developed country, or advanced country, is a sovereign state that has a high quality of life, developed economy, and advanced technological infrastructure relative to other less industrialized nations. Most commonly, the criteria for eval ...

is 42–64%.

Signs and symptoms

Head and neck cancers can cause a broad range of symptoms, many of which occur together. These can be categorised local (head and neck cancer-specific), general and

gastrointestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. ...

symptoms. Local symptoms include changes in taste and voice, inflammation of the mouth or throat (

mucositis Mucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tract, usually as an adverse effect of chemotherapy and radiotherapy treatment for cancer. Mucositis can occur anywhere along the gastrointestinal (G ...

), dry mouth (

xerostomia Xerostomia, also known as dry mouth, is a subjective complaint of dryness in the mouth, which may be associated with a change in the composition of saliva, reduced salivary flow, or have no identifiable cause. This symptom is very common and is o ...

), and difficulty swallowing (

dysphagia Dysphagia is difficulty in swallowing. Although classified under " symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or l ...

). General symptoms include difficulty sleeping, tiredness, depression, nerve damage (

peripheral neuropathy Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropa ...

). Gastrointestinal symptoms are typically nausea and vomiting. Symptoms predominantly include a sore on the face or oral cavity that does not heal, trouble swallowing, or a change in voice. In those with advanced disease, there may be unusual bleeding, facial pain, numbness or swelling, and visible lumps on the outside of the neck or oral cavity. Head and neck cancer often begins with benign signs and symptoms of the disease, like an enlarged

lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...

on the outside of the neck, a hoarse-sounding voice, or a progressive worsening cough or sore throat. In the case of head and neck cancer, these symptoms will be notably persistent and become chronic. There may be a lump or a sore in the throat or neck that does not heal or go away. There may be difficulty or pain in swallowing. Speaking may become difficult. There may also be a persistent earache. Other symptoms can include: a lump in the lip, mouth, or gums; ulcers or mouth sores that do not heal; bleeding from the mouth or numbness; bad breath; discolored patches that persist in the mouth; a sore tongue; and slurring of speech if the cancer is affecting the tongue. There may also be congested sinuses, weight loss, and some numbness or paralysis of

facial muscles The facial muscles are a group of striated skeletal muscles supplied by the facial nerve (cranial nerve VII) that, among other things, control facial expression. These muscles are also called mimetic muscles. They are only found in mammals, alth ...

Mouth

Oral cancer affects the areas of the mouth, including the inner lip,

tongue The tongue is a Muscle, muscular organ (anatomy), organ in the mouth of a typical tetrapod. It manipulates food for chewing and swallowing as part of the digestive system, digestive process, and is the primary organ of taste. The tongue's upper s ...

floor of the mouth In human anatomy, the mouth is the first portion of the alimentary canal that receives food and produces saliva. The oral mucosa is the mucous membrane epithelium lining the inside of the mouth. In addition to its primary role as the beginning ...

gums The gums or gingiva (: gingivae) consist of the mucosal tissue that lies over the mandible and maxilla inside the mouth. Gum health and disease can have an effect on general health. Structure The gums are part of the soft tissue lining of the ...

, and

hard palate The hard palate is a thin horizontal bony plate made up of two bones of the facial skeleton, located in the roof of the mouth. The bones are the palatine process of the maxilla and the horizontal plate of palatine bone. The hard palate spans ...

. Cancers of the mouth are strongly associated with

use, especially the use of

chewing tobacco Chewing tobacco is a type of smokeless tobacco, smokeless tobacco product that is placed between the cheek and lower Gums, gum to draw out its flavor. It consists of coarsely chopped aged tobacco that is flavored and often sweetened; it is not gr ...

dipping tobacco Dipping tobacco is a type of finely ground or shredded, moistened smokeless tobacco product. It is commonly and idiomatically known as ''dip''. Dipping tobacco is used by placing a pinch, or "dip", of tobacco between the lip and the gum (subla ...

, as well as heavy

use. Cancers of this region, particularly the tongue, are more frequently treated with

surgery Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery s ...

than other head and neck cancers. Lip and oral cavity cancers are the most commonly encountered types of head and neck cancer. Surgeries for oral cancers include: * Maxillectomy (can be done with or without orbital exenteration) * Mandibulectomy (removal of the lower jaw or part of it) *

Glossectomy A glossectomy is the surgical removal of all or part of the tongue. It is performed in order to curtail malignant growth such as oral cancer. Often only a portion of the tongue needs to be removed, in which case the procedure is called a partia ...

(tongue removal; can be total, hemi, or partial) * Radical neck dissection * Combinational (e.g., glossectomy and

laryngectomy Laryngectomy is the removal of the larynx. In a total laryngectomy, the entire larynx is removed (including the vocal folds, hyoid bone, epiglottis, thyroid and cricoid cartilage and a few tracheal cartilage rings) with the separation of the a ...

done together). The defect is typically covered or improved by using another part of the body and/or skin grafts and/or wearing a

prosthesis In medicine, a prosthesis (: prostheses; from ), or a prosthetic implant, is an artificial device that replaces a missing body part, which may be lost through physical trauma, disease, or a condition present at birth (Congenital, congenital disord ...

Nose

Paranasal sinus and nasal cavity cancer affects the

nasal cavity The nasal cavity is a large, air-filled space above and behind the nose in the middle of the face. The nasal septum divides the cavity into two cavities, also known as fossae. Each cavity is the continuation of one of the two nostrils. The nas ...

and the

paranasal sinuses Paranasal sinuses are a group of four paired air-filled spaces that surround the nasal cavity. The maxillary sinuses are located under the eyes; the frontal sinuses are above the eyes; the ethmoidal sinuses are between the eyes and the sphe ...

. Most of these cancers are squamous cell carcinomas.

Nasopharynx

Nasopharyngeal cancer arises in the

nasopharynx The pharynx (: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the esophagus and trachea (the tubes going down to the stomach and the lungs respectively). It is found in vertebrates and invertebrates, though its ...

, the region in which the nasal cavities and the

Eustachian tube The Eustachian tube (), also called the auditory tube or pharyngotympanic tube, is a tube that links the nasopharynx to the middle ear, of which it is also a part. In adult humans, the Eustachian tube is approximately long and in diameter. It ...

s connect with the upper part of the throat. While some nasopharyngeal cancers are biologically similar to the common head and neck cancers, "poorly differentiated" nasopharyngeal carcinoma is lymphoepithelioma, which is distinct in its

epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and Risk factor (epidemiology), determinants of health and disease conditions in a defined population, and application of this knowledge to prevent dise ...

, biology, clinical behavior, and treatment and is treated as a separate disease by many experts.

Throat

Most

oropharyngeal cancer Oropharyngeal cancer, also known as oropharyngeal squamous cell carcinoma and tonsil cancer, 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 t ...

s begin in the

oropharynx The pharynx (: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the esophagus and trachea (the tubes going down to the stomach and the lungs respectively). It is found in vertebrates and invertebrates, though its ...

(throat), the middle part of the throat that includes the

soft palate The soft palate (also known as the velum, palatal velum, or muscular palate) is, in mammals, the soft biological tissue, tissue constituting the back of the roof of the mouth. The soft palate is part of the palate of the mouth; the other part is ...

, the base of the

, and the

tonsil The tonsils ( ) are a set of lymphoid organs facing into the aerodigestive tract, which is known as Waldeyer's tonsillar ring and consists of the adenoid tonsil (or pharyngeal tonsil), two tubal tonsils, two palatine tonsils, and the lingual t ...

s. Cancers of the tonsils are more strongly associated with

infection than are cancers of other regions of the head and neck. HPV-positive oropharyngeal cancer generally has a better outcome than HPV-negative disease, with a 54% better survival rate, but this advantage for HPV-associated cancer applies only to oropharyngeal cancers. People with oropharyngeal carcinomas are at high risk of developing a second primary head and neck cancer.

Hypopharynx

The

hypopharynx The pharynx (: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the esophagus and trachea (the tubes going down to the stomach and the lungs respectively). It is found in vertebrates and invertebrates, though its ...

includes the pyriform sinuses, the posterior pharyngeal wall, and the postcricoid area. Tumors of the hypopharynx frequently have an advanced stage at diagnosis and have the most adverse prognoses of pharyngeal tumors. They tend to

metastasize Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

early due to the extensive lymphatic network around the

larynx The larynx (), commonly called the voice box, is an organ (anatomy), organ in the top of the neck involved in breathing, producing sound and protecting the trachea against food aspiration. The opening of larynx into pharynx known as the laryngeal ...

Larynx

Laryngeal cancer begins in the

, or "voice box", and is the second most common type of head and neck cancer encountered. Cancer may occur on the

vocal folds In humans, the vocal cords, also known as vocal folds, are folds of throat tissues that are key in creating sounds through Speech, vocalization. The length of the vocal cords affects the pitch of voice, similar to a violin string. Open when brea ...

themselves ("glottic" cancer) or on tissues above and below the true cords ("supraglottic" and "subglottic" cancers, respectively). Laryngeal cancer is strongly associated with

tobacco smoking Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or released from the mouth, as is generally done with pipes and cigars. The practice is believed to hav ...

. Surgery can include laser excision of small vocal cord lesions, partial laryngectomy (removal of part of the larynx), or total laryngectomy (removal of the whole larynx). If the whole larynx has been removed, the person is left with a permanent tracheostomy. Voice rehabilitation in such patients can be achieved in three important ways: esophageal speech, tracheoesophageal puncture, or electrolarynx. One would likely require intensive teaching, speech therapy, and/or an electronic device.

Trachea and salivary glands

Cancer of the trachea is a rare cancer usually classified as a

lung cancer Lung cancer, also known as lung carcinoma, is a malignant tumor that begins in the lung. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged ...

. Most tumors of the salivary glands differ from the common head and neck cancers in cause,

histopathology Histopathology (compound of three Greek words: 'tissue', 'suffering', and '' -logia'' 'study of') is the microscopic examination of tissue in order to study the manifestations of disease. Specifically, in clinical medicine, histopatholog ...

, clinical presentation, and therapy. Other uncommon tumors arising in the head and neck include

teratoma A teratoma is a neoplasia, tumor made up of several types of biological tissue, tissue, such as hair, muscle, Human tooth, teeth, or bone. Teratomata typically form in the tailbone (where it is known as a sacrococcygeal teratoma), ovary, or test ...

adenocarcinomas Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ; AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, o ...

adenoid cystic carcinoma Adenoid cystic carcinoma is a rare type of cancer that can exist in many different body sites. This tumor most often occurs in the salivary glands, but it can also be found in many anatomic sites, including the breast, lacrimal gland, human lung, ...

s, and mucoepidermoid carcinomas. Rarer still are

melanomas Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...

and

lymphomas Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...

of the upper aerodigestive tract.

Causes

Alcohol and tobacco

Alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

and

use are major risk factors for head and neck cancer. 72% of head and neck cancer cases are caused by using both alcohol and tobacco. This rises to 89% when looking specifically at laryngeal cancer. There is thought to be a dose-dependent relationship between alcohol use and development of head and neck cancer where higher rates of alcohol consumption contribute to an increased risk of developing head and neck cancer. Alcohol use following a diagnosis of head and neck cancer also contributes to other negative outcomes. These include physical effects such as an increased risk of developing a second primary cancer or other malignancies, cancer recurrence, and worse prognosis in addition to an increased chance of having a future

feeding tube A feeding tube is a medical device used to provide nutrition to people who cannot obtain nutrition by mouth, are unable to swallow safely, or need nutritional supplementation. The state of being fed by a feeding tube is called gavage, enteral f ...

placed and osteoradionecrosis of the jaw. Negative social factors are also increased with sustained alcohol use after diagnosis including unemployment and work disability. The way in which alcohol contributes to cancer development is not fully understood. It is thought to be related to permanent damage of DNA strands by a metabolite of alcohol called

acetaldehyde Acetaldehyde (IUPAC systematic name ethanal) is an organic compound, organic chemical compound with the chemical formula, formula , sometimes abbreviated as . It is a colorless liquid or gas, boiling near room temperature. It is one of the most ...

. Other suggested mechanisms include nutritional deficiencies and genetic variations.

Tobacco smoking Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or released from the mouth, as is generally done with pipes and cigars. The practice is believed to hav ...

is one of the main risk factors for head and neck cancer. Cigarette smokers have a lifetime increased risk for head and neck cancer that is 5 to 25 times higher than the general population. The ex-smoker's risk of developing head and neck cancer begins to approach the risk in the general population 15 years after

smoking cessation Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is Addiction, addictive and can cause Substance dependence, dependence. As a resu ...

. In addition, people who smoke have a worse prognosis than those who have never smoked. Furthermore, people who continue to smoke after diagnosis of head and neck cancer have the highest probability of dying compared to those who have never smoked. This effect is seen in patients with HPV-positive head and neck cancer as well. It has also been demonstrated that

passive smoking Passive smoking is the inhalation of tobacco smoke, called passive smoke, secondhand smoke (SHS) or environmental tobacco smoke (ETS), by individuals other than the active Tobacco smoking, smoker. It occurs when tobacco smoke diffuses into the ...

, both at work and at home, increases the risk of head and neck cancer. A major carcinogenic compound in

tobacco smoke Tobacco smoke is a sooty aerosol produced by the incomplete combustion of tobacco during the smoking of cigarettes and other tobacco products. Temperatures in burning cigarettes range from about 400 °C between puffs to about 900 °C ...

acrylonitrile Acrylonitrile is an organic compound with the formula and the structure . It is a colorless, volatile liquid. It has a pungent odor of garlic or onions. Its molecular structure consists of a vinyl group () linked to a nitrile (). It is an im ...

. Acrylonitrile appears to indirectly cause

DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified ...

by increasing

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

, leading to increased levels of

8-oxo-2'-deoxyguanosine 8-Oxo-2'-deoxyguanosine (8-oxo-dG) is an oxidized derivative of deoxyguanosine. 8-Oxo-dG is one of the major products of DNA oxidation. Concentrations of 8-oxo-dG within a cell are a measurement of oxidative stress. In DNA Steady-state levels ...

(8-oxo-dG) and formamidopyrimidine in DNA. (see image). Both 8-oxo-dG and formamidopyrimidine are

mutagen In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in ...

ic.

DNA glycosylase DNA glycosylases are a family of enzymes involved in base excision repair, classified under EC number EC 3.2.2. Base excision repair is the mechanism by which damaged bases in DNA are removed and replaced. DNA glycosylases catalyze the first ste ...

NEIL1 Endonuclease VIII-like 1 is an enzyme that in humans is encoded by the ''NEIL1'' gene. NEIL1 belongs to a class of DNA glycosylases homologous to the bacterial Fpg/Nei family. These glycosylases initiate the first step in base excision repair by ...

prevents

mutagenesis Mutagenesis () is a process by which the genetic information of an organism is changed by the production of a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using lab ...

by 8-oxo-dG and removes formamidopyrimidines from DNA.

Smokeless tobacco Smokeless tobacco is a tobacco product that is used by means other than smoking. Their use involves chewing, sniffing, or placing the product between gum and the cheek or lip. Smokeless tobacco products are produced in various forms, such as ...

(including products where tobacco is chewed) is a cause of

. Increased risk of oral cancer caused by smokeless tobacco is present in countries such as the United States but particularly prevalent in Southeast Asian countries where the use of smokeless tobacco is common. Smokeless tobacco is associated with a higher risk of developing head and neck cancer due to the presence of the tobacco-specific carcinogen N'-nitrosonornicotine.

Cigar A cigar is a rolled bundle of dried and Fermentation, fermented tobacco leaves made to be Tobacco smoking, smoked. Cigars are produced in a variety of sizes and shapes. Since the 20th century, almost all cigars are made of three distinct comp ...

and

pipe smoking Pipe smoking is the practice of tasting (or, less commonly, inhaling) the smoke produced by burning a substance, most commonly tobacco or cannabis, in a pipe. It is the oldest traditional form of smoking. Regular pipe smoking is known to carry s ...

are also important risk factors for oral cancer. They have a dose dependent relationship with more consumption leading to higher chances of developing cancer. The use of

electronic cigarette An electronic cigarette (e-cigarette), or vape, is a device that simulates smoking. It consists of an atomizer, a power source such as a battery, and a container such as a cartridge or tank. Instead of smoke, the user inhales vapor. As such ...

s may also lead to the development of head and neck cancers due to the substances like

propylene glycol Propylene glycol ( IUPAC name: propane-1,2-diol) is a viscous, colorless liquid. It is almost odorless and has a faintly sweet taste. Its chemical formula is CH3CH(OH)CH2OH. As it contains two alcohol groups, it is classified as a diol. An al ...

glycerol Glycerol () is a simple triol compound. It is a colorless, odorless, sweet-tasting, viscous liquid. The glycerol backbone is found in lipids known as glycerides. It is also widely used as a sweetener in the food industry and as a humectant in pha ...

nitrosamine Nitrosamines (or more formally ''N''-nitrosamines) are organic compounds produced by industrial processes. The chemical structure is , where R is usually an alkyl group. Nitrosamines have a nitroso group () that are "probable human carcinogens", ...

s, and metals contained therein, which can cause damage to the airways. Exposure to e-vapour has been shown to reduce cell viability and increase the rate of

cell death Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as di ...

via

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who i ...

with or without nicotine. This area of study requires more research, however. Similarly, additional research is needed to understand how

marijuana Cannabis (), commonly known as marijuana (), weed, pot, and ganja, List of slang names for cannabis, among other names, is a non-chemically uniform psychoactive drug from the ''Cannabis'' plant. Native to Central or South Asia, cannabis has ...

possibly promotes head and neck cancers. A 2019 meta-analysis did not conclude that marijuana was associated with head and neck cancer risk. Yet individuals with cannabis use disorder were more likely to be diagnosed with such cancers in a large study published 2024.

Diet

Many dietary nutrients are associated with cancer protection and its development. Generally, foods with a protective effect with respect to oral cancer demonstrate

antioxidant Antioxidants are Chemical compound, compounds that inhibit Redox, oxidation, a chemical reaction that can produce Radical (chemistry), free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants ...

and anti-inflammatory effects such as fruits, vegetables,

curcumin Curcumin is a bright yellow chemical produced by plants of the ''Curcuma longa'' species. It is the principal curcuminoid of turmeric (''Curcuma longa''), a member of the ginger family, Zingiberaceae. It is sold as a herbal supplement, cosmetic ...

and

green tea Green tea is a type of tea made from the leaves and buds of the '' Camellia sinensis'' that have not undergone the withering and oxidation process that creates oolong teas and black teas. Green tea originated in China in the late 1st millenn ...

. Conversely, pro-inflammatory food substances such as

red meat In gastronomy, red meat is commonly red when raw (and a dark color after it is cooked), in contrast to white meat, which is pale in color before (and after) cooking. In culinary terms, only flesh from mammals or fowl (not fish) is classified ...

processed meat Processed meat is considered to be any meat that has been modified in order to either improve its taste or to extend its shelf life. Methods of meat processing include salting, curing, fermentation, smoking, and the addition of chemical prese ...

and fried food can increase the risk of developing head and neck cancer. An increased adherence to the

Mediterranean diet The Mediterranean diet is a concept first proposed in 1975 by the American biologist Ancel Keys and chemist Margaret Keys. The diet took inspiration from the eating habits and traditional food typical of Crete, much of the rest of Greece, and s ...

is also related to a lower risk of cancer mortality and a reduced risk of developing multiple cancers including head and neck cancer. Elevated levels of

nitrite The nitrite polyatomic ion, ion has the chemical formula . Nitrite (mostly sodium nitrite) is widely used throughout chemical and pharmaceutical industries. The nitrite anion is a pervasive intermediate in the nitrogen cycle in nature. The name ...

s in preserved meats and salted fish have been shown to increase the risk of nasopharyngeal cancer. Overall, a poor nutritional intake (often associated with alcoholism) with subsequent

vitamin deficiencies Vitamin deficiency is the condition of a long-term lack of a vitamin. When caused by not enough vitamin intake it is classified as a ''primary deficiency'', whereas when due to an underlying disorder such as malabsorption it is called a ''seconda ...

is a risk factor for head and neck cancer. In terms of nutritional supplements, antioxidants such as

vitamin E Vitamin E is a group of eight compounds related in molecular structure that includes four tocopherols and four tocotrienols. The tocopherols function as fat-soluble antioxidants which may help protect cell membranes from reactive oxygen speci ...

and beta-carotene might reduce the toxic effect of radiotherapy in people with head and neck cancer but they can also increase recurrence rates, especially in smokers.

Betel nut

Betel nut chewing is associated with an increased risk of head and neck cancer. When chewed with additional tobacco in its preparation (like in

gutka Gutka, ghutka, or guṭkha () is a type of betel quid and chewing tobacco preparation made of crushed areca nut (also called betel nut), tobacco, catechu, paraffin wax, slaked lime (calcium hydroxide) and sweet or savory flavourings, in India ...

), there is an even higher risk, especially for oral and oropharyngeal cancers.

Genetics

People who develop head and neck cancer may have a

genetic predisposition Genetic predisposition refers to a genetic characteristic which influences the possible phenotypic development of an individual organism within a species or population under the influence of environmental conditions. The term genetic susceptibil ...

for the condition. There are seven known genetic variations ( loci) which specifically increase the chances of developing oral and pharyngeal cancer. Family history, that is having a first-degree relative with head and neck cancer, is also a risk factor. In addition, genetic variations in pathways involved in

alcohol metabolism The pharmacology of ethanol involves both pharmacodynamics (how it affects the body) and pharmacokinetics (how the body processes it). In the body, ethanol primarily affects the central nervous system, acting as a depressant and causing sedatio ...

(for example

alcohol dehydrogenase Alcohol dehydrogenases (ADH) () are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to N ...

) have been associated with an increased head and neck cancer risk.

Radiation

It is known that prior exposure to

radiation In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or a material medium. This includes: * ''electromagnetic radiation'' consisting of photons, such as radio waves, microwaves, infr ...

of the head and neck is associated with an increased risk of cancer, particularly thyroid, salivary gland and squamous cell carcinomas, although there is a time-delay of many years and the overall risk is still low.

Infection

Human papillomavirus

Some head and neck cancers, and in particular oropharyngeal cancer, are caused by the

(HPV), and 70% of all head and neck cancer cases are related to HPV. Risk factors for HPV-positive oropharyngeal cancer include multiple sexual partners, anal and oral sex and a weak immune system. The incidence of HPV-related head and neck cancer is increasing, especially in the Western world. In the United States, the incidence of HPV-positive oropharyngeal cancer has overtaken HPV-positive

cervical cancer Cervical cancer is a cancer arising from the cervix or in any layer of the wall of the cervix. It is due to the abnormal growth of cells that can invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later sympt ...

as the leading HPV related cancer type. An increased incidence has particularly affected males. As a result, recent changes have resulted in the

being offered to adolescent boys between 12-13 (previously only offered to girls between this age due to cervical cancer risks) and men under 45 who have sex with men in the UK. Over 20 different high-risk HPV subtypes have been implicated in causing head and neck cancer. In particular, HPV-16 is responsible for up to 90% of oropharyngeal cancer in North America. Approximately 15–25% of head and neck cancers contain genomic DNA from HPV, and the association varies based on the site of the tumor. In the case of HPV-positive oropharyngeal cancer, the highest distribution is in the

tonsils The tonsils ( ) are a set of lymphoid organs facing into the aerodigestive tract, which is known as Waldeyer's tonsillar ring and consists of the adenoid tonsil (or pharyngeal tonsil), two tubal tonsils, two palatine tonsils, and the lingual ...

, where HPV DNA is found in 45–67% of the cases, and it is less often in the hypopharynx (13–25%), and least often in the oral cavity (12–18%) and larynx (3–7%). Positive HPV16 status is associated with a improved prognosis over HPV-negative oropharyngeal cancer due to better response to

radiotherapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...

and

. HPV can induce tumors by several mechanisms: # E6 and E7 oncogenic proteins. # Disruption of

tumor suppressor gene A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell (biology), cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results ...

s. # High-level DNA amplifications, for example,

oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

s. # Generating alternative nonfunctional transcripts. # Interchromosomal rearrangements. # Distinct host genome methylation and expression patterns, produced even when the virus is not integrated into the host genome. There are observed biological differences between HPV-positive and HPV-negative head and neck cancer, for example in terms of

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

patterns. In HPV-negative disease, genes frequently mutated include ''

TP53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

CDKN2A ''CDKN2A'', also known as cyclin-dependent kinase inhibitor 2A, is a gene which in humans is located at chromosome 9, band p21.3. It is ubiquitously expressed in many tissues and cell types. The gene codes for two proteins, including the INK4 f ...

'' and '' PIK3CA''. In HPV-positive disease, these genes are less frequently mutated, and the tumour suppressor gene p53 and

pRb PRB may refer to: Companies and organizations * Periodic Review Board * Population Reference Bureau * Poudreries Réunies de Belgique, former Belgium armaments manufacturer * PRB (company), Australian Automotive Manufacturer * PRB, French Coatings ...

(protein retinoblastoma) are commonly inactivated by HPV oncoproteins E6 and E7 respectively. In addition, viral infections such as HPV can cause aberrant

DNA methylation DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter (genetics), promoter, DNA methylati ...

during cancer development. HPV-positive head and neck cancers demonstrate higher levels of such DNA methylation compared to HPV-negative disease. E6 sequesters p53 to promote p53 degradation, while E7 inhibits pRb. Degradation of p53 results in cells being unable to respond to checkpoint signals that are normally present to activate

when DNA damage is signalled. Loss of pRb leads to deregulation of

cell proliferation Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation ...

and apoptosis. Both mechanisms therefore leave cell proliferation unchecked and increase the chance of

carcinogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cell (biology), cells are malignant transformation, transformed into cancer cells. The process is characterized by changes at the cellular, G ...

Epstein–Barr virus

(EBV) infection is associated with nasopharyngeal cancer. Nasopharyngeal cancer caused by EBV commonly occurs in some countries of the Mediterranean and Asia, where EBV

antibody titer Titer (American English) or titre (British English) is a way of expressing concentration. Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure that inherently only evaluates as positi ...

s can be measured to screen high-risk populations.

Gastroesophageal reflux disease

The presence of

gastroesophageal reflux disease Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is a chronic upper gastrointestinal disease in which stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/or ...

(GERD) or laryngeal reflux disease can also be a major factor.

Stomach acid Gastric acid or stomach acid is the acidic component – hydrochloric acid – of gastric juice, produced by parietal cells in the gastric glands of the stomach lining. In humans, the pH is between one and three, much lower than most other an ...

s that flow up through the

esophagus The esophagus (American English), oesophagus (British English), or œsophagus (Œ, archaic spelling) (American and British English spelling differences#ae and oe, see spelling difference) all ; : ((o)e)(œ)sophagi or ((o)e)(œ)sophaguses), c ...

can damage its lining and raise susceptibility to throat cancer.

Hematopoietic stem cell transplantation

People after

hematopoietic stem cell transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce ...

(HSCT) are at a higher risk for oral cancer. Post-HSCT oral cancer may have more aggressive behavior and a poorer prognosis when compared to oral cancer in non-HSCT patients. This effect is supposed to be due to continuous, lifelong

immune In biology, immunity is the state of being insusceptible or resistant to a noxious agent or process, especially a pathogen or infectious disease. Immunity may occur naturally or be produced by prior exposure or immunization. Innate and adaptive ...

suppression and chronic oral

graft-versus-host disease Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants. White blood cells of the donor's immune system which rema ...

Other risk factors

Several other risk factors have been identified in the development of head and neck cancer. These include occupational environmental

carcinogen A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...

exposure such as

asbestos Asbestos ( ) is a group of naturally occurring, Toxicity, toxic, carcinogenic and fibrous silicate minerals. There are six types, all of which are composed of long and thin fibrous Crystal habit, crystals, each fibre (particulate with length su ...

, wood dust,

mineral acid A mineral acid (or inorganic acid) is an acid derived from one or more inorganic compounds, as opposed to organic acids which are acidic, organic compounds. All mineral acids form hydrogen ions and the conjugate base when dissolved in water. Ch ...

, sulfuric acid mists and metal dusts. In addition, weakened immune systems, age greater than 55 years, poor socioeconomic factors such as lower incomes and occupational status, and low

body mass index Body mass index (BMI) is a value derived from the mass (Mass versus weight, weight) and height of a person. The BMI is defined as the human body weight, body mass divided by the square (algebra), square of the human height, body height, and is ...

(<18.5 kg/m2) are also risk factors. Poor

oral hygiene Oral hygiene is the practice of keeping one's oral cavity clean and free of disease and other problems (e.g. bad breath) by regular brushing of the teeth (dental hygiene) and adopting good hygiene habits. It is important that oral hygiene be carr ...

and chronic oral cavity inflammation (for example secondary to chronic gum inflammation) are also linked to an increased head and neck cancer risk. The presence of

leukoplakia Oral leukoplakia is a potentially malignant disorder affecting the oral mucosa. It is defined as "essentially an oral mucosal white/gray lesion that cannot be considered as any other definable lesion." Oral leukoplakia is a gray patch or plaque th ...

, which is the appearance of white patches or spots in the mouth, can develop into cancer in about 1⁄3 of cases.

Diagnosis

A significant proportion of people with head and neck cancer will present to their physicians with an already advanced stage disease. This can either be down to patient factors (delays in seeking medical attention), or physician factors (such as delays in referral from primary care, or non-diagnostic investigation results). A person usually presents to the physician complaining of one or more of the typical symptoms. These symptoms may be site specific (such as a laryngeal cancer causing hoarse voice), or not site specific (earache can be caused by multiple types of head and neck cancers). The physician will undertake a thorough history to determine the nature of the symptoms and the presence or absence of any risk factors. The physician will also ask about other illnesses such as heart or lung diseases as they may impact their fitness for potentially curative treatment. Clinical examination will involve examination of the neck for any masses, examining inside the mouth for any abnormalities and assessing the rest of the pharynx and larynx with a nasendoscope. Further investigations will be directed by the symptoms discussed and any abnormalities identified during the exam. Neck masses typically undergo assessment with

ultrasound Ultrasound is sound with frequency, frequencies greater than 20 Hertz, kilohertz. This frequency is the approximate upper audible hearing range, limit of human hearing in healthy young adults. The physical principles of acoustic waves apply ...

and a

fine-needle aspiration Fine-needle aspiration (FNA) is a diagnostic procedure used to investigate lumps or masses. In this technique, a thin (23–25 gauge (0.52 to 0.64 mm outer diameter)), hollow needle is inserted into the mass for sampling of cells that, a ...

(FNA, a type of needle biopsy). Concerning

lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by injury or diseases. The term ''Lesion'' is derived from the Latin meaning "injury". Lesions may occur in both plants and animals. Types There is no de ...

s that are readily accessible (such as in the mouth) can be biopsied with a

local anaesthetic A local anesthetic (LA) is a medication that causes absence of all sense, sensation (including pain) in a specific body part without loss of consciousness, providing local anesthesia, as opposed to a general anesthetic, which eliminates all sen ...

. Lesions less readily available can be biopsied either with the patient awake or under a

general anaesthetic General anaesthetics (or anesthetics) are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced coma that causes lack of awaren ...

depending on local expertise and availability of specialist equipment. The cancer will also need to be staged (accurately determine its size, association with nearby structures, and spread to distant sites). This is typically done by scanning the patient with a combination of

magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...

(MRI),

computed tomography A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...

(CT) and/or

positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, r ...

(PET). Exactly which investigations are required will depend on a variety of factors such as the site of concern and the size of the tumour. Some people will present with a neck lump containing cancer cells (identified by FNA) that have spread from elsewhere, but with no identifiable primary site on initial assessment. In such cases people will undergo additional testing to attempt to find the initial site of cancer, as this has significant implications for their treatment. These patients undergo MRI scanning, PET-CT and then panendoscopy and biopsies of any abnormal areas. If the scans and panendoscopy still do not identify a primary site for the cancer, affected people will undergo a bilateral

tonsillectomy Tonsillectomy is a surgical procedure in which both palatine tonsils are fully removed from the back of the throat. The procedure is mainly performed for recurrent tonsillitis, throat infections and obstructive sleep apnea (OSA). For those wit ...

and tongue base mucosectomy (as these are the most common subsites of cancer that spread to the neck). This procedure can be done with or without robotic assistance. Once a diagnosis is confirmed, a multidisciplinary discussion of the optimal treatment strategy will be undertaken between the radiation oncologist, surgical oncologist, and medical oncologist. A histopathologist and a

radiologist Radiology ( ) is the medical specialty that uses medical imaging to diagnose diseases and guide treatment within the bodies of humans and other animals. It began with radiography (which is why its name has a root referring to radiation), but tod ...

will also be present to discuss the biopsy and imaging findings. Most (90%) cancers of the head and neck are

squamous cell Epithelium or epithelial tissue is a thin, continuous, protective layer of Cell (biology), cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial (Mesothelium, mesothelial) tissues line ...

-derived, termed "head-and-neck squamous-cell carcinomas".

Histopathology

Throat cancers are classified according to their

histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...

or cell structure and are commonly referred to by their location in the oral cavity and neck. This is because where the cancer appears in the throat affects the prognosis; some throat cancers are more aggressive than others, depending on their location. The stage at which the cancer is diagnosed is also a critical factor in the prognosis of throat cancer. Treatment guidelines recommend routine testing for the presence of HPV for all oropharyngeal squamous cell carcinoma tumors. Accurate prognostic stratification as well as segmentation of Head-and-Neck Squamous-Cell-Carcinoma (HNSCC) patients can be an important clinical reference when designing therapeutic strategies. Study developed a deep learning framework combining PET/CT fusion imaging with Hybrid Machine Learning Systems (HMLS) for automated tumor segmentation and recurrence-free survival prediction in HNSCC patients. They set to enable automated segmentation of tumors and prediction of recurrence-free survival (RFS) using advanced deep learning techniques and Hybrid Machine Learning Systems (HMLSs).

Squamous-cell carcinoma

Squamous-cell carcinoma Squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...

is a

of the

, a kind of

epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

cell found in both the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

and

mucous membrane A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...

s. It accounts for over 90% of all head and neck cancers, including more than 90% of throat cancer. Squamous cell carcinoma is most likely to appear in males over 40 years of age with a history of heavy alcohol use coupled with smoking. All squamous cell carcinomas arising from the oropharynx, and all neck node

metastases Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

of unknown primary should undergo testing for HPV status. This is essential to adequately stage the tumour and adequately plan treatment. Due to the different biology of HPV positive and negative cancers, differentiating HPV status is also important for ongoing research to determine the best treatments.

Nasopharyngeal carcinoma Nasopharyngeal carcinoma (NPC), or nasopharynx cancer, is the most common cancer originating in the nasopharynx, most commonly in the postero-lateral nasopharynx or pharyngeal recess (fossa of Rosenmüller), accounting for 50% of cases. NPC occurs ...

s, or neck node metastases possibly arising from the nasopharynx will also be tested for Ebstein Barr virus. The tumor marker Cyfra 21-1 may be useful in diagnosing squamous cell carcinoma of the head and neck (SCCHN).

Adenocarcinoma

Adenocarcinoma Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ; AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or ...

is a cancer of the epithelial tissue that has

gland A gland is a Cell (biology), cell or an Organ (biology), organ in an animal's body that produces and secretes different substances that the organism needs, either into the bloodstream or into a body cavity or outer surface. A gland may also funct ...

ular characteristics. Several head and neck cancers are adenocarcinomas (either of intestinal or non-intestinal cell types).

Prevention

Avoidance of risk factors (such as smoking and alcohol) is the single most effective form of prevention. Regular dental examinations may identify pre-cancerous lesions in the oral cavity. While screening in the general population does not appear to be useful, screening high-risk groups by examination of the throat might be useful. Head and neck cancer is often curable if it is diagnosed early; however, outcomes are typically poor if it is diagnosed late. When diagnosed early, oral, head, and neck cancers can be treated more easily, and the chances of survival increase tremendously. The

helps to prevent the development of HPV-related oropharyngeal cancer.

Management

Improvements in diagnosis and local management, as well as

, have led to improvements in quality of life and survival for people with head and neck cancer. After a histologic diagnosis has been established and tumor extent determined, such as with the use of PET-CT, the selection of appropriate treatment for a specific cancer depends on a complex array of variables, including tumor site, relative morbidity of various treatment options, concomitant health problems, social and logistic factors, previous primary tumors, and the person's preference. Treatment planning generally requires a multidisciplinary approach involving specialist surgeons, medical oncologists, and radiation oncologists. Surgical resection and radiation therapy are the mainstays of treatment for most head and neck cancers and remain the standard of care in most cases. For small primary cancers without regional metastases (stage I or II), wide surgical excision alone or curative radiation therapy alone is used. For more extensive primary tumors or those with regional metastases (stage III or IV), planned combinations of pre- or postoperative radiation and complete surgical excision are generally used. More recently, as historical survival and control rates have been recognized as less than satisfactory, there has been an emphasis on the use of various induction or concomitant chemotherapy regimens.

Surgery

Surgery Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery s ...

as a treatment is frequently used for most types of head and neck cancer. Usually, the goal is to remove the cancerous cells entirely. This can be particularly tricky if the cancer is near the

and can result in the person being unable to speak. Surgery is also commonly used to resect (remove) some or all of the cervical lymph nodes to prevent further spread of the disease. Transoral robotic surgery (TORS) is gaining popularity worldwide as the technology and training become more accessible. It now has an established role in the treatment of early stage oropharyngeal cancer. There is also a growing trend worldwide towards TORS for the surgical treatment of laryngeal and hypopharyngeal tumours. CO₂ laser surgery is also another form of treatment. Transoral laser microsurgery allows surgeons to remove tumors from the voice box with no external incisions. It also allows access to tumors that are not reachable with robotic surgery. During the surgery, the surgeon and pathologist work together to assess the adequacy of excision ("margin status"), minimizing the amount of normal tissue removed or damaged. This technique helps give the person as much speech and swallowing function as possible after surgery.

Radiation therapy

Radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

is the most common form of treatment. There are different forms of radiation therapy, including 3D conformal radiation therapy, intensity-modulated radiation therapy, particle beam therapy, and brachytherapy, which are commonly used in the treatment of cancers of the head and neck. Most people with head and neck cancer who are treated in the United States and Europe are treated with intensity-modulated radiation therapy using high-energy photons. At higher doses, head and neck radiation is associated with

thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by ...

dysfunction and

pituitary The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus control much of th ...

axis dysfunction. Radiation therapy for head and neck cancers can also cause acute skin reactions of varying severity, which can be treated and managed with topically applied creams or specialist films.

Chemotherapy

Chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

for throat cancer is not generally used to ''cure'' the cancer as such. Instead, it is used to provide an inhospitable environment for metastases so that they will not establish themselves in other parts of the body. Typical chemotherapy agents are a combination of

paclitaxel Paclitaxel, sold under the brand name Taxol among others, is a chemotherapy medication used to treat ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer, and pancreatic cancer. It is administered b ...

and

carboplatin Carboplatin, sold under the brand name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is a ...

Cetuximab Cetuximab, sold under the brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor medication used for the treatment of metastatic colorectal cancer and head and neck cancer. Cetuximab is a chimeric (mouse/human) monoclonal a ...

is also used in the treatment of throat cancer.

Docetaxel Docetaxel (DTX or DXL), sold under the brand name Taxotere among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-cel ...

-based chemotherapy has shown a very good response in locally advanced head and neck cancer. Docetaxel is the only

taxane Taxanes are a class of diterpenes. They were originally identified from plants of the genus ''Taxus'' (yews), and feature a taxadiene core. Paclitaxel (Taxol) and docetaxel (Taxotere) are widely used as chemotherapy agents. Cabazitaxel was FDA app ...

approved by the FDA for head and neck cancer, in combination with cisplatin and fluorouracil for the induction treatment of inoperable, locally advanced head and neck cancer. While not specifically a chemotherapy, amifostine is often administered

intravenously Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

by a chemotherapy clinic prior to IMRT radiotherapy sessions. Amifostine protects the gums and

salivary gland The salivary glands in many vertebrates including mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands ( parotid, submandibular, and sublingual), as well as hundreds of min ...

s from the effects of radiation. There is no evidence that

erythropoietin Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production ( erythropoiesis) in th ...

should be routinely given with radiotherapy.

Photodynamic therapy

Photodynamic therapy Photodynamic therapy (PDT) is a form of phototherapy involving light and a photosensitizing chemical substance used in conjunction with molecular oxygen to elicit cell death ( phototoxicity). PDT is used in treating acne, wet age-related macula ...

may have promise for treating mucosal dysplasia and small head and neck tumors. Amphinex is showing good results in early clinical trials for the treatment of advanced head and neck cancer.

Targeted therapy

Targeted therapy Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy (oncology), hormonal therapy and cytotoxic chemotherapy. As a form of molecular medici ...

, according to the

National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...

, is "a type of treatment that uses drugs or other substances, such as monoclonal antibodies, to identify and attack specific cancer cells without harming normal cells." Some targeted therapies used in head and neck cancers include

cetuximab Cetuximab, sold under the brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor medication used for the treatment of metastatic colorectal cancer and head and neck cancer. Cetuximab is a chimeric (mouse/human) monoclonal a ...

bevacizumab Bevacizumab, sold under the brand name Avastin among others, is a monoclonal antibody medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and use ...

, and erlotinib.

is used for treating people with advanced-stage cancer who cannot be treated with conventional chemotherapy (

cisplatin Cisplatin is a chemical compound with chemical formula, formula ''cis''-. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, c ...

). However, cetuximab's efficacy is still under investigation by researchers. Gendicine is a

gene therapy Gene therapy is Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells. The first attempt at modifying human DNA ...

that employs an

adenovirus Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from t ...

to deliver the

p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

to cells. It was approved in China in 2003 for the treatment of head and neck cancer. The mutational profiles of HPV+ and HPV- head and neck cancer have been reported, further demonstrating that they are fundamentally distinct diseases.

Immunotherapy

Immunotherapy Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...

is a type of treatment that activates the immune system to fight cancer. One type of immunotherapy, immune checkpoint blockade, binds to and blocks inhibitory signals on immune cells to release their anti-cancer activities. In 2016, the FDA granted accelerated approval to pembrolizumab for the treatment of people with recurrent or metastatic head and neck cancer with disease progression on or after platinum-containing chemotherapy. Later that year, the FDA approved

nivolumab Nivolumab, sold under the brand name Opdivo, is an anti-cancer medication in the class of immune checkpoint inhibitors. It selectively binds and blocks the programmed death-1 (PD-1) receptor on T cells, thereby facilitating their activation ...

for the treatment of recurrent or metastatic head and neck cancer with disease progression on or after platinum-based chemotherapy. In 2019, the FDA approved pembrolizumab for the first-line treatment of metastatic or unresectable recurrent head and neck cancer.

Treatment side effects

Depending on the treatment used, people with head and neck cancer may experience the following symptoms and treatment side effects: * Eating problems * Pain associated with lesions *

Mucositis Mucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tract, usually as an adverse effect of chemotherapy and radiotherapy treatment for cancer. Mucositis can occur anywhere along the gastrointestinal (G ...

Nephrotoxicity Nephrotoxicity is toxicity in the kidneys. It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function. There are various forms, and some drugs may affect kidney function in more than one way. Nephrotoxin ...

and

ototoxicity Ototoxicity is the property of being toxic to the ear (''oto-''), specifically the cochlea or auditory nerve and sometimes the vestibular system, for example, as a side effect of a drug. The effects of ototoxicity can be reversible and tempora ...

Xerostomia Xerostomia, also known as dry mouth, is a subjective complaint of dryness in the mouth, which may be associated with a change in the composition of saliva, reduced salivary flow, or have no identifiable cause. This symptom is very common and is o ...

* Gastroesophageal reflux * Radiation-induced

osteonecrosis of the jaw Osteonecrosis of the jaw (ONJ) is a severe bone disease (osteonecrosis) that affects the jaws (the maxilla and the mandible). Various forms of ONJ have been described since 1861, and a number of causes have been suggested in the literature. Osteo ...

* Radiation-induced acute skin reactions

Psychosocial

Programs to support the emotional and social well-being of people who have been diagnosed with head and neck cancer may be offered. There is no clear evidence on the effectiveness of these interventions or any particular type of psychosocial program or length of time that is most helpful for those with head and neck cancer.

Prognosis

Although early-stage head and neck cancers (especially laryngeal and oral cavity) have high cure rates, up to 50% of people with head and neck cancer present with advanced disease. Cure rates decrease in locally advanced cases, whose probability of cure is inversely related to tumor size and even more so to the extent of regional node involvement. HPV-associated oropharyngeal cancer has been shown to respond better to chemoradiation and, subsequently, have a better prognosis compared to non-associated HPV head and neck cancer. Consensus panels in America ( AJCC) and Europe ( UICC) have established staging systems for head and neck cancers. These staging systems attempt to standardize clinical trial criteria for research studies and define prognostic categories of disease. Head and neck cancers are staged according to the TNM classification system, where T is the size and configuration of the tumor, N is the presence or absence of lymph node metastases, and M is the presence or absence of distant metastases. The T, N, and M characteristics are combined to produce a "stage" of the cancer, from I to IVB.

Problem of second primaries

Survival advantages provided by new treatment modalities have been undermined by the significant percentage of people cured of head and neck cancer who subsequently develop second

primary tumor A primary tumor is a tumor growing at the anatomical site where tumor progression began and proceeded to yield a cancerous mass. Most solid cancers develop at their primary site but may then go on to metastasize or spread to other parts of the b ...

s. The incidence of second primary tumors ranges in studies from 9% to 23% at 20 years. Second primary tumors are the major threat to long-term survival after successful therapy of early-stage head and neck cancer. Their high incidence results from the same carcinogenic exposure responsible for the initial primary process, called field cancerization.

Digestive system

Many people with head and neck cancer are also not able to eat sufficiently. A tumor may impair a person's ability to swallow and eat, and throat cancer may affect the

digestive system The human digestive system consists of the gastrointestinal tract plus the accessory organs of digestion (the tongue, salivary glands, pancreas, liver, and gallbladder). Digestion involves the breakdown of food into smaller and smaller compone ...

. The difficulty in swallowing can cause a person to choke on their food in the early stages of digestion and interfere with the food's smooth travel down into the

and beyond. The treatments for throat cancer can also be harmful to the digestive system as well as other body systems. Radiation therapy can lead to

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

and

vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...

, which can deprive the body of vital fluids (although these may be obtained through intravenous fluids if necessary). Frequent vomiting can lead to an electrolyte imbalance, which has serious consequences for the proper functioning of the heart. Frequent vomiting can also upset the balance of stomach acids, which has a negative impact on the digestive system, especially the lining of the stomach and esophagus.

Enteral feeding A feeding tube is a medical device used to provide nutrition to people who cannot obtain nutrition by mouth, are unable to swallow safely, or need nutritional supplementation. The state of being fed by a feeding tube is called gavage, enteral fee ...

, a method that adds nutrients directly into a person's stomach using a nasogastric feeding tube or a gastrostomy tube, may be necessary for some people. Further research is required to determine the most effective method of enteral feeding to ensure that people undergoing radiotherapy or chemoradiation treatment are able to stay nourished during their treatment.

Mental health

Cancer in the head or neck may impact a person's mental well-being and can sometimes lead to social isolation. This largely results from a decreased ability or inability to eat, speak, or effectively communicate. Physical appearance is often altered by the cancer itself and/or as a consequence of treatment side effects. Psychological distress may occur, and feelings such as uncertainty and fear may arise. Some people may also have a changed physical appearance, differences in swallowing or breathing, and residual pain to manage. Caregiver stress Caregivers for people with head and neck cancer show higher rates of

caregiver stress Caregiver syndrome or caregiver stress is a condition that strongly manifests exhaustion, anger, rage, or guilt resulting from unrelieved caring for a chronically ill patient. This condition is not listed in the United States' ''Diagnostic and S ...

and poorer mental health compared to both the general population and those caring for non-head and neck cancer patients. The high symptom burden patients' experience necessitates complex caregiver roles, often requiring hospital staff training, which caregivers can find distressing when asked to do so for the first time. It is becoming increasingly apparent that caregivers (most often spouses, children, or close family members) might not be adequately informed about, prepared for, or trained for the tasks and roles they will encounter during the treatment and recovery phases of this unique patient population, which span both technical and emotional support. Of note, caregivers of patients who report lower quality of life demonstrate increased burden and fatigue that extend beyond the treatment phase. Examples of technically difficult caregiver duties include tube feeding, oral suctioning, wound maintenance, medication delivery safe for tube feeding, and troubleshooting home medical equipment. If the cancer affects the mouth or larynx, caregivers must also find a way to effectively communicate among themselves and with their healthcare team. This is in addition to providing emotional support for the person undergoing cancer therapy.

Others

Like any

metastasis Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

affects many areas of the body as the cancer spreads from cell to cell and

organ Organ and organs may refer to: Biology * Organ (biology), a group of tissues organized to serve a common function * Organ system, a collection of organs that function together to carry out specific functions within the body. Musical instruments ...

to organ. For example, if it spreads to the

bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...

, it will prevent the body from producing enough

red blood cell Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...

s and affect the proper functioning of the

white blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

s and the body's

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

; spreading to the

circulatory system In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart ...

will prevent oxygen from being transported to all the cells of the body; and throat cancer can throw the

nervous system In biology, the nervous system is the complex system, highly complex part of an animal that coordinates its behavior, actions and sense, sensory information by transmitting action potential, signals to and from different parts of its body. Th ...

into chaos, making it unable to properly regulate and control the body.

Epidemiology

Mouth and oropharynx cancers world map - Death - WHO2004

Globally, head and neck cancer accounts for 650,000 new cases of cancer and 330,000 deaths annually on average. In 2018, it was the seventh most common cancer worldwide, with 890,000 new cases documented and 450,000 people dying from the disease. The risk of developing head and neck cancer increases with age, especially after 50 years. Most people who do so are between 50 and 70 years old. In North America and Europe, the tumors usually arise from the oral cavity, oropharynx, or larynx, whereas nasopharyngeal cancer is more common in the Mediterranean countries and in the Far East. In Southeast China and Taiwan, head and neck cancer, specifically nasopharyngeal cancer, is the most common cause of death in young men.

United States

In the United States, head and neck cancer makes up 3% of all cancer cases (averaging 53,000 new diagnoses per year) and 1.5% of cancer deaths. The 2017 worldwide figure cites head and neck cancers as representing 5.3% of all cancers (not including non-melanoma skin cancers). Notably, head and neck cancer secondary to chronic alcohol or tobacco use has been steadily declining as less of the population chronically smokes tobacco. However, HPV-associated oropharyngeal cancer is rising, particularly in younger people in westernized nations, which is thought to be reflective of changes in oral sexual practices, specifically with regard to the number of oral sexual partners. This increase since the 1970s has mostly affected wealthier nations and male populations. This is due to evidence suggesting that transmission rates of HPV from women to men are higher than from men to women, as women often have a higher immune response to infection. * In 2008, there were 22,900 cases of oral cavity cancer, 12,250 cases of laryngeal cancer, and 12,410 cases of pharyngeal cancer in the United States. * In 2002, 7,400 Americans were projected to die of these cancers.Cancer Facts and Figures

, American Cancer Society 2002. * More than 70% of throat cancers are at an advanced stage when discovered. * Men are 89% more likely than women to be diagnosed with these cancers and are almost twice as likely to die of them. * African Americans are disproportionately affected by head and neck cancer, with younger ages of incidence, increased mortality, and more advanced disease at presentation. Laryngeal cancer incidence is higher in African Americans relative to white, Asian, and Hispanic populations. There is a lower survival rate for similar tumor states in African Americans with head and neck cancer.

Research

Immunotherapy with immune checkpoint inhibitors is being investigated in head and neck cancers.

References

External links

Head and Neck Cancer
at

MedlinePlus MedlinePlus is an online information service produced by the United States National Library of Medicine. The service provides curated consumer health information in English and Spanish with select content in additional languages. The site brings ...

(National Library of Medicine)
Head and neck cancer
at

Macmillan Cancer Support Macmillan Cancer Support is one of the largest British charities and provides specialist health care, information and financial support to people affected by cancer. It also looks at the social, emotional and practical impact cancer can have, an ...

(UK)
Head and Neck Cancer Treatment
at

RadiologyInfo The Radiological Society of North America (RSNA) is a Nonprofit organization, non-profit organization and an international society of radiologists, medical physicists and other medical imaging professionals representing 31 radiologic subspecialt ...

Head and Neck Cancer
at Cancer.net (

American Society of Clinical Oncology The American Society of Clinical Oncology (ASCO) is a professional organization representing physicians of all oncology sub-specialties who care for people with cancer. Founded in 1964 by Fred Ansfield, Harry Bisel, Herman Freckman, Arnoldus G ...

)
Head and Neck Cancer UK
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