Head And Neck Squamous Cell Carcinoma
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Head and neck cancer develops from tissues in the lip and oral cavity (mouth),
larynx The larynx (), commonly called the voice box, is an 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 inlet is about ...
(throat),
salivary gland The salivary glands in 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 minor salivary glands. Salivary gla ...
s, nose, sinuses or the skin of the face. The most common types of head and neck cancers occur in the lip, mouth, and larynx. Symptoms predominantly include a sore that does not heal or a change in the voice. Some may experience a sore throat that does not go away. 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. Given the location of these cancers, trouble breathing may also be present. The majority of head and neck cancer is caused by the use of alcohol or
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 che ...
, with increasing cases linked to 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 res ...
(HPV). Other risk factors include Epstein-Barr virus,
betel quid Betel nut chewing, also called betel quid chewing or areca nut chewing, is a practice in which areca nuts (also called "betel nuts") are chewed together with slaked lime and betel leaves for their stimulant and narcotic effects. The practice ...
, radiation exposure, certain workplace exposures. About 90% are pathologically classified as squamous cell cancers. The diagnosis is confirmed by
tissue biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a disea ...
. 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 rev ...
and blood tests. Not using tobacco or alcohol can reduce the risk for head and neck cancer. The HPV vaccine may reduce the lifetime risk of oral cancer if taken prior to the onset of sexual activity, but confirmation will likely not be known until around 2060. This is because oropharyngeal cancer typical presents in the 4th – 6th decade of life, and this is a relatively new vaccine. While
screening Screening may refer to: * Screening cultures, a type a medical test that is done to find an infection * Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees) * Screening (environmental), a ...
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 often is curable if it is diagnosed early; however, outcomes are typically poor if it is diagnosed late. Treatment may include a combination of surgery,
radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
,
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
, 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 and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks ...
. Previous diagnosis and treatment of one head and neck cancer confers higher risk of developing a second head and neck cancer or recurrence. 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 dying from the disease. 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 men to women, as women often have a higher immune response to infection. The usual age at diagnosis is between 55 and 65 years old. The average 5-year survival following diagnosis in the
developed world A developed country (or industrialized country, high-income country, more economically developed country (MEDC), advanced country) is a sovereign state that has a high quality of life, developed economy and advanced technological infrastruct ...
is 42–64%.


Signs and symptoms

Symptoms predominantly include a sore of the face or oral cavity that does not heal, trouble swallowing, or a change in the 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 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 inclu ...
on the outside of the neck, a hoarse-sounding voice or 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 difficult or painful swallowing. Speaking may become difficult. There may also be a persistent
earache Ear pain, also known as earache or otalgia, is pain in the ear. Primary ear pain is pain that originates from the ear. Secondary ear pain is a type of referred pain, meaning that the source of the pain differs from the location where the pain i ...
. 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 muscle 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 ...
s.


Mouth

Squamous cell cancer Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise 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 ...
s are common in areas of the mouth, including the inner lip,
tongue The tongue is a muscular organ (anatomy), organ in the mouth of a typical tetrapod. It manipulates food for mastication and swallowing as part of the digestive system, digestive process, and is the primary organ of taste. The tongue's upper surfa ...
,
floor of 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 (plural: ''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 lin ...
, 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
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 ...
use, especially use of
chewing tobacco Chewing tobacco is a type of smokeless tobacco product that is placed between the cheek and lower gum to draw out its flavor. Some users chew it, others do not. It consists of coarsely chopped aged tobacco that is flavored and often sweetened; ...
or
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 ( sublab ...
, as well as heavy alcohol use. Cancers of this region, particularly the tongue, are more frequently treated with
surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...
than are other head and neck cancers. Lip and oral cavity cancers are the most typically encountered type of head and neck cancers. Surgeries for oral cancers include: * Maxillectomy (can be done with or without
orbital exenteration An evisceration is the removal of the eye's contents, leaving the scleral shell and extraocular muscles intact.Cassin, B. and Solomon, S. ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishing Company, 1990.Zein W"Evisceration ...
) * 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 partial ...
(tongue removal, can be total, hemi or partial) * Radical
neck dissection The neck dissection is a surgical procedure for control of neck lymph node metastasis from squamous cell carcinoma (SCC) of the head and neck. The aim of the procedure is to remove lymph nodes from one side of the neck into which cancer cells may ...
* Combinational e.g., glossectomy and
laryngectomy Laryngectomy is the removal of the larynx and separation of the airway from the mouth, nose and esophagus. In a total laryngectomy, the entire larynx is removed (including the vocal folds, hyoid bone, epiglottis, Thyroid cartilage, thyroid and cr ...
done together. The defect is typically covered/improved by using another part of the body and/or skin grafts and/or wearing a
prosthesis In medicine, a prosthesis (plural: prostheses; from grc, πρόσθεσις, prósthesis, addition, application, attachment), or a prosthetic implant, is an artificial device that replaces a missing body part, which may be lost through trau ...
.


Nose

Paranasal sinus and nasal cavity cancer 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 occur ...
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 nasal c ...
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 sphenoi ...
. Most of these cancers are squamous cell carcinomas.


Nasopharynx

Nasopharyngeal cancer arises in the
nasopharynx The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struct ...
, the region in which the
nasal cavities 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 nasal c ...
and the Eustachian tubes connect with the upper part of the throat. While some nasopharyngeal cancers are biologically similar to the common head and neck squamous cell carcinomas (HNSCCs), "poorly differentiated" nasopharyngeal carcinoma is
lymphoepithelioma Lymphoepithelioma is a type of poorly differentiated nasopharyngeal carcinoma characterized by prominent infiltration of lymphocytes in the area involved by tumor. Lymphoepithelioma is also known as "class III nasopharyngeal carcinoma" in the Wo ...
, which is distinct in its
epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population. It is a cornerstone of public health, and shapes policy decisions and evidenc ...
, biology, clinical behavior, and treatment, and is treated as a separate disease by many experts.


Throat

Most
oropharyngeal cancer Oropharyngeal cancer (OPC), also known as oropharyngeal squamous cell carcinoma (OPSCC) 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 ca ...
s are squamous cell carcinomas that begin in the
oropharynx The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struc ...
(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 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 hard palate. ...
, the base of the
tongue The tongue is a muscular organ (anatomy), organ in the mouth of a typical tetrapod. It manipulates food for mastication and swallowing as part of the digestive system, digestive process, and is the primary organ of taste. The tongue's upper surfa ...
, 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, two tubal tonsils, two palatine tonsils, and the lingual tonsils. These organs play ...
s. Squamous cell cancers of the tonsils are more strongly associated with
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 res ...
infection than are cancers of other regions of the head and neck.
HPV-positive oropharyngeal cancer Human papillomavirus-positive oropharyngeal cancer (HPV-positive OPC or HPV+OPC), is a cancer ( squamous cell carcinoma) of the throat caused by the human papillomavirus type 16 virus (HPV16). In the past, cancer of the oropharynx (throat) was as ...
generally has a better outcomes than HPV-negative disease with a 54% better survival, but this advantage for HPV associated cancer applies only to oropharyngeal cancers. People with oropharyngeal carcinomas are at high risk of developing second primary head and neck cancer.


Hypopharynx

The
hypopharynx The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struct ...
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 spread 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, then, ...
early due to the extensive lymphatic network around the
larynx The larynx (), commonly called the voice box, is an 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 inlet is about ...
.


Larynx

Laryngeal cancer begins in the
larynx The larynx (), commonly called the voice box, is an 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 inlet is about ...
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, vocal cords, also known as vocal folds or voice reeds, are folds of throat tissues that are key in creating sounds through vocalization. The size of vocal cords affects the pitch of voice. Open when breathing and vibrating for speech ...
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 simply released from the mouth, as is generally done with pipes and cigars. The practice is believed ...
. 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 through three important ways – esophageal speech, tracheoesophageal puncture, or electrolarynx. One would likely require the help of intensive teaching and speech therapy and/or an electronic device.


Trachea

Cancer of the
trachea The trachea, also known as the windpipe, is a Cartilage, cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all air-breathing animals with lungs. The trachea extends ...
is a rare cancer usually classed as a
lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...
. Most tumors of the
salivary glands The salivary glands in 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 minor salivary glands. Salivary gla ...
differ from the common squamous cell carcinomas of the head and neck in cause,
histopathology Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία '' -logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spe ...
, clinical presentation, and therapy. Other uncommon tumors arising in the head and neck include
teratoma A teratoma is a tumor made up of several different types of tissue, such as hair, muscle, teeth, or bone. Teratomata typically form in the ovary, testicle, or coccyx. Symptoms Symptoms may be minimal if the tumor is small. A testicular ter ...
s,
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, or ...
,
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, lung, brain ...
s, and
mucoepidermoid carcinoma Mucoepidermoid carcinoma (MEC) is the most common type of minor salivary gland malignancy in adults. Mucoepidermoid carcinoma can also be found in other organs, such as bronchi, lacrimal sac, and thyroid gland. Mucicarmine staining is one stain us ...
s. Rarer still are
melanomas Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye (u ...
and
lymphomas Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enla ...
of the upper aerodigestive tract.


Causes


Alcohol and tobacco

Around 75% of cases are caused by alcohol and
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 ...
use.
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 simply released from the mouth, as is generally done with pipes and cigars. The practice is believed ...
is one of the main risk factors for 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 tobacco smoking, smoking of cigarettes and other tobacco products. Temperatures in burning cigarettes range from about 400 °C between puffs to abo ...
is
acrylonitrile Acrylonitrile is an organic compound with the formula and the structure . It is a colorless, volatile liquid although commercial samples can be yellow due to impurities. It has a pungent odor of garlic or onions. In terms of its molecular ...
. 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. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
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 Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...
, 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 leve ...
(8-oxo-dG) and formamidopyrimidine in DNA. (see image). Both 8-oxo-dG and formamidopyrimidine are mutagenic.
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 st ...
NEIL1 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. However, cigarette smokers have a lifetime increased risk for head and neck cancers that is 5- to 25-fold increased over the general population. The ex-smoker's risk for developing a head and neck cancer begins to approach the risk in the general population 15 years after smoking cessation. The high prevalence of tobacco and alcohol use worldwide and the high association of these cancers with these substances makes them ideal targets for enhanced cancer prevention. Smokeless tobacco is a cause of
oral cancer Oral cancer, also known as mouth cancer, is cancer of the lining of the lips, mouth, or upper throat. In the mouth, it most commonly starts as a painless white patch, that thickens, develops red patches, an ulcer, and continues to grow. When on ...
and
oropharyngeal cancer Oropharyngeal cancer (OPC), also known as oropharyngeal squamous cell carcinoma (OPSCC) 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 ca ...
. Smokeless tobacco (including products where tobacco is chewed) is associated with a risk of developing head and neck cancers; this link has been established in the United States as well as in East Asian countries.
Cigar A cigar is a rolled bundle of dried and fermented tobacco leaves made to be smoked. Cigars are produced in a variety of sizes and shapes. Since the 20th century, almost all cigars are made of three distinct components: the filler, the binder l ...
smoking is also an important risk factor for oral cancer. It should also be noted that 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 there in; which can cause damage to airways. This area of study requires more research to prove correlation and/or causation, however. Other environmental
carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive subs ...
s suspected of being potential causes of head and neck cancer include occupational exposures such as nickel ore refining, exposure to textile fibers, and woodworking. Use of
marijuana Cannabis, also known as marijuana among other names, is a psychoactive drug from the cannabis plant. Native to Central or South Asia, the cannabis plant has been used as a drug for both recreational and entheogenic purposes and in various tra ...
, especially when younger, has been linked to an increase in squamous-cell carcinoma cases in at least one study, while other studies suggest use is not shown to be associated with oral squamous cell carcinoma, or associated with decreased squamous cell carcinoma.


Diet

Excessive consumption of eggs, processed meats, and red meat were associated with increased rates of cancer of the head and neck in one study, while consumption of raw and cooked vegetables seemed to be protective.
Vitamin E Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four tocotrienols. Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vi ...
was not found to prevent the development of
leukoplakia Oral leukoplakia is a ''potentially malignant disorder'' affecting the oral mucosa. It is defined as "essentially an oral mucosal white lesion that cannot be considered as any other definable lesion." Oral leukoplakia is a white patch or plaque th ...
, the white plaques that are the precursor for carcinomas of the mucosal surfaces, in adult smokers. Another study examined a combination of Vitamin E and
beta carotene Beta (, ; uppercase , lowercase , or cursive ; grc, βῆτα, bē̂ta or ell, βήτα, víta) is the second letter of the Greek alphabet. In the system of Greek numerals, it has a value of 2. In Modern Greek, it represents the voiced labio ...
in smokers with early-stage cancer of the oropharynx, and found a worse
prognosis Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stabl ...
in the vitamin users.


Betel nut

Betel nut The betel (''Piper betle'') is a vine of the family Piperaceae, which includes pepper and kava. The betel plant is native to Southeast Asia. It is an evergreen, dioecious perennial, with glossy heart-shaped leaves and white catkins. Betel p ...
chewing is associated with an increased risk of squamous cell cancer of the head and neck.


Infection


Human papillomavirus

Some head and neck cancers are caused by
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 res ...
(HPV). In particular, HPV16 is a causal factor for some head and neck squamous-cell carcinomas (HNSCCs). Approximately 15–25% of HNSCC contain genomic DNA from HPV, and the association varies based on the site of the tumor, especially
HPV-positive oropharyngeal cancer Human papillomavirus-positive oropharyngeal cancer (HPV-positive OPC or HPV+OPC), is a cancer ( squamous cell carcinoma) of the throat caused by the human papillomavirus type 16 virus (HPV16). In the past, cancer of the oropharynx (throat) was as ...
, with highest distribution 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, two tubal tonsils, two palatine tonsils, and the lingual tonsils. These organs play a ...
, where HPV DNA is found in (45 to 67%) of the cases, less often in the hypopharynx (13–25%), and least often in the oral cavity (12–18%) and larynx (3–7%). Some experts estimate that while up to 50% of cancers of the tonsil may be infected with HPV, only 50% of these are likely to be caused by HPV (as opposed to the usual
tobacco 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 ...
and alcohol causes). The role of HPV in the remaining 25–30% is not yet clear. Oral sex is not risk free and results in a significant proportion of HPV-related head and neck cancer. Positive HPV16 status is associated with improved prognosis over HPV-negative OSCC. HPV can induce tumor by several mechanisms: # E6 and E7 oncogenic proteins. # Disruption of
tumor suppressor gene A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a 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 in a loss or red ...
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 virus isn't integrated into the host genome. Induction of cancer can be associated for the expression of viral oncoproteins, the most important E6 and E7, or other mechanisms many of them run by the integration such as the generation of altered transcripts, disruption of tumor suppressors, high levels of DNA amplifications, interchromosomial rearrangements, or changes in DNA methylation patterns, the latter being able to find even when the virus is identified in episomes. E6 sequesters p53 to promote p53 degradation while E7 inhibits pRb. p53 prevents cell growth when DNA is damaged by activating apoptosis and p21, a kinase that blocks the formation of cyclin D / Cdk4 avoiding pRb phosphorylation and thereby prevents release of E2F is a transcription factor required for activation of genes involved in cell proliferation. pRb remains bound to E2F while this action phosphorylated preventing activation of proliferation. Therefore, E6 and E7 act synergistically in triggering cell cycle progression and therefore uncontrolled proliferation by inactivating the p53 and Rb tumor suppressors. Viral integration tends to occur in or near oncogenes or
tumor suppressor gene A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a 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 in a loss or red ...
s and it is for this reason that the integration of the virus can greatly contribute to the development of tumor characteristics.


Epstein–Barr virus

Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is b ...
(EBV) infection is associated with
nasopharyngeal cancer 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 ...
. Nasopharyngeal cancer occurs endemically in some countries of the Mediterranean and Asia, where EBV antibody titers can be measured to screen high-risk populations. Nasopharyngeal cancer has also been associated with consumption of salted fish, which may contain high levels of
nitrites The nitrite 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 nitrite also r ...
.


Gastroesophageal reflux disease

The presence of acid reflux disease (gastroesophageal reflux disease
ERD ERD may refer to: * Érd, a city in Hungary * Berdyansk Airport, in Ukraine * Economic Relations Division (Bangladesh), of the Bangladeshi Ministry of Finance * Elastic recoil detection Elastic recoil detection analysis (ERDA), also referred ...
or larynx reflux disease can also be a major factor.
Stomach acid Gastric acid, gastric juice, or stomach acid is a digestive fluid formed within the stomach lining. With a pH between 1 and 3, gastric acid plays a key role in digestion of proteins by activating digestive enzymes, which together break down the ...
s that flow up through the
esophagus The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to the ...
can damage its lining and raise susceptibility to throat cancer.


Hematopoietic stem cell transplantation

Patients 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 of a patient and to produce ...
(HSCT) are at a higher risk for oral squamous cell carcinoma. Post-HSCT oral cancer may have more aggressive behavior with poorer prognosis, when compared to oral cancer in non-HSCT patients. This effect is supposed to be owing to the continuous lifelong
immune In biology, immunity is the capability of multicellular organisms to resist harmful microorganisms. Immunity involves both specific and nonspecific components. The nonspecific components act as barriers or eliminators of a wide range of pathogens ...
suppression and chronic oral graft-versus-host disease.


Other possible causes

There are several risk factors for developing throat cancer. These include
smoking Smoking is a practice in which a substance is burned and the resulting smoke is typically breathed in to be tasted and absorbed into the bloodstream. Most commonly, the substance used is the dried leaves of the tobacco plant, which have bee ...
or
chewing tobacco Chewing tobacco is a type of smokeless tobacco product that is placed between the cheek and lower gum to draw out its flavor. Some users chew it, others do not. It consists of coarsely chopped aged tobacco that is flavored and often sweetened; ...
or other things, such as
gutkha Gutka, ghutka, guṭkha or betel quid is a chewing tobacco preparation made of crushed areca nut (also called betel nut), tobacco, catechu, paraffin wax, Calcium hydroxide, slaked lime (Calcium hydroxide) and sweet or savory flavourings, in Ind ...
, or
paan Betel nut chewing, also called betel quid chewing or areca nut chewing, is a practice in which areca nuts (also called "betel nuts") are chewed together with slaked lime and betel leaves for their stimulant and narcotic effects. The practice ...
, heavy alcohol consumption, poor diet resulting in
vitamin A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an Nutrient#Essential nutrients, essential micronutrient that an organism needs in small quantities for the proper functioning of its ...
deficiencies (worse if this is caused by heavy alcohol intake), weakened
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
,
asbestos Asbestos () is a naturally occurring fibrous silicate mineral. There are six types, all of which are composed of long and thin fibrous crystals, each fibre being composed of many microscopic "fibrils" that can be released into the atmosphere b ...
exposure, prolonged exposure to wood dust or paint fumes, exposure to
petroleum Petroleum, also known as crude oil, or simply oil, is a naturally occurring yellowish-black liquid mixture of mainly hydrocarbons, and is found in geological formations. The name ''petroleum'' covers both naturally occurring unprocessed crud ...
industry chemicals, and being over the age of 55 years. Other risk factors include the appearance of white patches or spots in the mouth, known as
leukoplakia Oral leukoplakia is a ''potentially malignant disorder'' affecting the oral mucosa. It is defined as "essentially an oral mucosal white lesion that cannot be considered as any other definable lesion." Oral leukoplakia is a white patch or plaque th ...
, which in about of cases develops into cancer, and breathing or inhaling silica from cutting concrete, stone or cinder-blocks, especially in enclosed areas such as a warehouse, garage or basement.


Diagnosis

A person usually presents to the physician complaining of The person will typically undergo a
needle biopsy 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, aft ...
of this lesion, and a
histopathologic Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία ''-logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spec ...
information is available, a multidisciplinary discussion of the optimal treatment strategy will be undertaken between the
radiation oncologist A radiation oncologist is a specialist physician who uses ionizing radiation (such as megavoltage X-rays or radionuclides) in the treatment of cancer. Radiation oncology is one of the three primary specialties, the other two being surgical and ...
, surgical oncologist, and medical oncologist. Most (90%) cancers of the head and neck are
squamous cell Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
-derived termed as "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 which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
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 upon 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 tumours.


Squamous-cell carcinoma

Squamous-cell carcinoma Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise 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 th ...
is a
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
of the
squamous cell Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
– a kind of
epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
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 cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...
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 is ...
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. The tumor marker Cyfra 21-1 may be useful in diagnosing squamous cell carcinoma of the head/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 epithelial tissue that has
gland In animals, a gland is a group of cells in an animal's body that synthesizes substances (such as hormones) for release into the bloodstream (endocrine gland) or into cavities inside the body or its outer surface (exocrine gland). Structure De ...
ular characteristics. Several head and neck cancers are adenocarcinomas (either of intestinal or non-intestinal cell-type).


Prevention

Avoidance of recognised risk factors (as described above) is the single most effective form of prevention. Regular dental examinations may identify pre-cancerous lesions in the oral cavity. When diagnosed early, oral, head and neck cancers can be treated more easily and the chances of survival increase tremendously. As of 2017 it was not known if existing HPV vaccines can help prevent head and neck cancer.


Management

Improvements in diagnosis and local management, as well as
targeted therapy Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks ...
, 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, 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 and medical 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. 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 are recognized as less than satisfactory, there has been an emphasis on the use of various induction or concomitant chemotherapy regimens.


Surgery

Surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...
as a treatment is frequently used in 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
larynx The larynx (), commonly called the voice box, is an 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 inlet is about ...
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. CO2 laser surgery is also another form of treatment.
Transoral laser microsurgery Transoral laser microsurgery is a form of minimally invasive surgery used by several medical centers, including the Advent Health Cancer Institute, Orlando Florida (Advent Health Celebration) and Mayo Clinic to remove small and medium tumors thro ...
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, 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, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
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 treatments 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 in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...
dysfunction and
pituitary In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The hypop ...
axis dysfunction. Radiation therapy of head and neck cancers can also cause acute skin reactions of varying levels of severity, which can be treated and managed with topically applied creams or specialist films.


Chemotherapy

Chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
in 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 in other parts of the body. Typical chemotherapy agents are a combination of
paclitaxel Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer ...
and
carboplatin Carboplatin, sold under the trade 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 used b ...
.
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 an ...
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-ce ...
-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 ap ...
approved by US FDA for head and neck cancer, in combination with cisplatin and fluorouracil for the induction treatment of inoperable, locally advanced squamous cell carcinoma of the head and neck. While not specifically a chemotherapy,
amifostine Amifostine (ethiofos) is a cytoprotective adjuvant used in cancer chemotherapy and radiotherapy involving DNA-binding chemotherapeutic agents. It is marketed by Clinigen Group under the trade name Ethyol. Indications Amifostine is used therapeu ...
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 nutrie ...
by a chemotherapy clinic prior to
IMRT Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
radiotherapy sessions. Amifostine protects the gums and
salivary glands The salivary glands in 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 minor salivary glands. Salivary gla ...
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 the bo ...
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 popularly used in treating acne. It is used cl ...
may have promise in treating mucosal dysplasia and small head and neck tumors. Amphinex is giving good results in early clinical trials for 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 and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks ...
, 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 therapy Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks ...
used in squamous cell cancers of the head and neck 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 an ...
, bevacizumab and
erlotinib Erlotinib, sold under the brand name Tarceva among others, is a medication used to treat non-small cell lung cancer (NSCLC) and pancreatic cancer. Specifically it is used for NSCLC with mutations in the epidermal growth factor receptor (EGFR) ...
. The best quality data are available for
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 an ...
since the 2006 publication of a randomized clinical trial comparing radiation treatment plus cetuximab versus radiation treatment alone. This study found that concurrent
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 an ...
and radiotherapy improves survival and locoregional disease control compared to radiotherapy alone, without a substantial increase in
side effects In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
, as would be expected with the concurrent chemoradiotherapy, which is the current gold standard treatment for advanced head and neck cancer. Whilst this study is of pivotal significance, interpretation is difficult since cetuximab-radiotherapy was not directly compared to chemoradiotherapy. The results of ongoing studies to clarify the role of
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 an ...
in this disease are awaited with interest. Another study evaluated the impact of adding
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 an ...
to conventional chemotherapy (
cisplatin Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, br ...
) versus
cisplatin Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, br ...
alone. This study found no improvement in survival or disease-free survival with the addition of
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 an ...
to the conventional chemotherapy. However, another study which completed in March 2007 found that there was an improvement in survival. A 2010 review concluded that the combination of cetuximab and platin/5-fluorouracil should be considered the current standard first-line regimen.
Gendicine Gendicine is a recombinant adenovirus engineered to express wildtype-p53 (rAd-p53). This virus is designed to treat patients with tumors which have mutated p53 genes. __TOC__ History Gendicine is the first gene therapy product approved for clin ...
is a
gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...
that employs an adenovirus to deliver the
tumor suppressor gene A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a 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 in a loss or red ...
p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
to cells. It was approved in China in 2003 for the treatment of head and neck squamous cell carcinoma. The mutational profile of
HPV 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 re ...
+ and HPV- head and neck cancer has 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 Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast canc ...
for the treatment of people with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy. Later that year, the FDA approved
nivolumab Nivolumab, sold under the brand name Opdivo, is a medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urotheli ...
for the treatment of recurrent or metastatic HNSCC with disease progression on or after platinum-based chemotherapy. In 2019, the FDA approved
pembrolizumab Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast canc ...
for the first-line treatment of metastatic or unresectable recurrent HNSCC.


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 ( ...
*
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 temporary, ...
*
Xerostomia Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause. This symptom is very common and is often seen as a side ef ...
*
Gastroesophageal reflux Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is one of the upper gastrointestinal chronic diseases where stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/ ...
*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 the 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, a better prognosis, compared to non-associated HPV head and neck cancer. Consensus panels in America (
AJCC {{Short description, Organization standardising cancer staging The American Joint Committee on Cancer (AJCC) is an organization best known for defining and popularizing cancer staging standards, officially the AJCC staging system. The American Joi ...
) and Europe ( UICC) have established staging systems for head and neck squamous-cell cancers. These staging systems attempt to standardize clinical trial criteria for research studies, and attempt to define prognostic categories of disease. Squamous cell cancers of the head and neck 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 squamous cell carcinoma (HNSCC) 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 cancers develop at their primary site but then go on to metastasize or spread to other parts of the body. These fur ...
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 HNSCC. Their high incidence results from the same carcinogenic exposure responsible for the initial primary process, called
field cancerization Field cancerization or field effect (also termed field change, field change cancerization, field carcinogenesis, cancer field effect or premalignant field defect) is a biological process in which large areas of cells at a tissue surface or within ...
.


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 lead to a person to choke on their food in the early stages of digestion and interfere with the food's smooth travels down into the
esophagus The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to 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. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
and
vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...
, which can deprive a 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 Enteral administration is food or drug administration via the human gastrointestinal tract. This contrasts with parenteral nutrition or drug administration (Greek ''para'', "besides" + ''enteros''), which occurs from routes outside the GI tract ...
, 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.


Respiratory system

In the cases of some throat cancers, the air passages in the
mouth In animal anatomy, the mouth, also known as the oral cavity, or in Latin cavum oris, is the opening through which many animals take in food and issue vocal sounds. It is also the cavity lying at the upper end of the alimentary canal, bounded on ...
and behind the
nose A nose is a protuberance in vertebrates that houses the nostrils, or nares, which receive and expel air for respiration alongside the mouth. Behind the nose are the olfactory mucosa and the sinuses. Behind the nasal cavity, air next passes th ...
may become blocked from lumps or the swelling from the open sores. If the throat cancer is near the bottom of the throat, it has a high likelihood of spreading to the
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
s and interfering with the person's ability to
breath Breathing (or ventilation) is the process of moving air into and from the lungs to facilitate gas exchange with the internal environment, mostly to flush out carbon dioxide and bring in oxygen. All aerobic creatures need oxygen for cellular ...
e; this is even more likely if the person is a smoker, because they are highly susceptible to
lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...
.


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 decreased ability or inability to eat, speak or effectively communicate. Physical appearance is often altered by both the cancer itself 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.


Patient Experience

Increased Caregiver Distress Unique to care for Head and Neck Cancer Patients Multiple studies have shown caregivers for head and neck cancer patients show higher rates of distress and poorer mental health compared to both the general population as well as those caring for non-head-and-neck cancer patients. The high symptom burden patients' experience necessitate 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 caregivers (most often spouses, children or close family members) might not be adequately informed about, nor prepared or trained for the tasks and roles he/she will encounter during the treatment and recovery phase for this unique patient population, which span both technical and emotional support. Of note, caregivers of patient's who report lower quality of life, demonstrate increased burden and fatigue that extents beyond the treatment phase. Examples of technically difficult caregiver duties include: tube feeding, oral suctioning, wound maintenance, medication delivery safe for tube feeding, and trouble shooting at home medical equipment. If the cancer affect the mouth or larynx, caregivers must also find a way to effectively communicate amongst themselves and with their healthcare team. This is in addition to providing emotional support for the person undergoing cancer therapy.


Others

Like any
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
, metastasization affects many areas of the body, as the cancer spreads from cell to cell and organ to organ. For example, if it spreads to the
bone marrow Bone marrow is a semi-solid tissue found within the 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 is composed of hematopoietic ce ...
, it will prevent the body from producing enough
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s and affects the proper functioning of the
white blood cell White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...
s and the body's
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
; spreading to the
circulatory system The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
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 highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
into chaos, making it unable to properly regulate and control the body.


Epidemiology

The number of new cases of head and neck cancers in the United States was 40,490 in 2006, accounting for about 3% of adult malignancies. A total of 11,170 people died of their disease in 2006. The worldwide incidence exceeds half a million cases annually. 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 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 ...
, is the most-common cause of death in young men. * 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, and are almost twice as likely to die of these cancers. * 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. * Smoking and tobacco use are directly related to oropharyngeal (throat) cancer deaths.''Reducing the Health Consequences of Smoking: 25 Years of Progress. A Report of the Surgeon General'', U. S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, 1989. * The risk of developing head and neck cancers increases with age, especially after 50 years. Most people who do so are between 50 and 70 years old.


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 t ...
(National Library of Medicine)
Head and Neck Cancer Treatment
at RadiologyInfo
Head and Neck Cancer
at Cancer.net ( American Society of Clinical Oncology) {{Authority control Otorhinolaryngology Health effects of tobacco Wikipedia medicine articles ready to translate