Head and neck cancer

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Head and neck cancer
Diagram showing the parts of the pharynx CRUK 334.svg
Parts of the head and neck that can be affected by cancer.
Specialty Oncology, oral and maxillofacial surgery
Symptoms Lump or sore that does not heal, sore throat that does not go away, trouble swallowing, change in voice [1]
Risk factors Alcohol, tobacco, betel quid, human papillomavirus, radiation exposure, certain workplace exposures, Epstein–Barr virus [1] [2]
Diagnostic method Tissue biopsy [1]
PreventionNot using tobacco or alcohol [2]
TreatmentSurgery, radiation therapy, chemotherapy, targeted therapy [1]
Frequency5.5 million (affected during 2015) [3]
Deaths379,000 (2015) [4]

Head and neck cancer develops from tissues in the lip and oral cavity (mouth), larynx (throat), salivary glands, nose, sinuses, or skin of the face. [5] The most common types of head and neck cancer occur in the lips, mouth, and larynx. [5] Symptoms predominantly include a sore that does not heal or a change in the voice. [1] 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, it is possible for an afflicted individual to experience difficulty breathing. [6]

Contents

The majority of head and neck cancer is caused by the use of alcohol or tobacco, including smokeless tobacco, with increasing cases linked to the human papillomavirus (HPV). [6] [2] Other risk factors include the Epstein–Barr virus, betel quid, radiation exposure, and certain workplace exposures. [6] About 90% are pathologically classified as squamous cell cancers. [7] [2] The diagnosis is confirmed by a tissue biopsy. [6] The degree of surrounding tissue invasion and distant spread may be determined by medical imaging and blood tests. [6]

Not using tobacco or alcohol can reduce the risk of head and neck cancer. [2] 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. [8] This is because oropharyngeal cancer typically presents in the 4th–6th decade of life, and this is a relatively new vaccine. While screening in the general population does not appear to be useful, screening high-risk groups by examination of the throat might be useful. [2] Head and neck cancer is often curable if it is diagnosed early; however, outcomes are typically poor if it is diagnosed late. [2] Treatment may include a combination of surgery, radiation therapy, chemotherapy, and targeted therapy. [6] Previous diagnosis and treatment of a head and neck cancer confer a higher risk of developing a second head and neck cancer or recurrence. [6]

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. [8] 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. [9] The 2017 worldwide figure cites head and neck cancers as representing 5.3% of all cancers (not including non-melanoma skin cancers). [10] [5] Notably, head and neck cancer secondary to chronic alcohol or tobacco use has been steadily declining as less of the population chronically smokes tobacco. [8] 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. [5] [8] This increase since the 1970s has mostly affected wealthier nations and male populations. [11] [12] [5] 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. [5] [13]

The usual age at diagnosis is between 55 and 65 years old. [14] The average 5-year survival following diagnosis in the developed world is 42–64%. [14] [15]

Signs and symptoms

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. [16] Head and neck cancer often begins with benign signs and symptoms of the disease, like an enlarged lymph node 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. [17]

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.

Mouth

Squamous cell carcinoma of the mouth Oral cancer (1) squamous cell carcinoma histopathology.jpg
Squamous cell carcinoma of the mouth

Squamous cell cancers are common in areas of the mouth, including the inner lip, tongue, floor of the mouth, gums, and hard palate. Cancers of the mouth are strongly associated with tobacco use, especially the use of chewing tobacco or dipping tobacco, as well as heavy alcohol use. Cancers of this region, particularly the tongue, are more frequently treated with surgery than other head and neck cancers. Lip and oral cavity cancers are the most commonly encountered types of head and neck cancer. [5]

Surgeries for oral cancers include:

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

Nose

Paranasal sinus and nasal cavity cancer affects the nasal cavity and the paranasal sinuses. Most of these cancers are squamous cell carcinomas. [18]

Nasopharynx

Nasopharyngeal cancer arises in the nasopharynx, the region in which the nasal cavities 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, which is distinct in its epidemiology, biology, clinical behavior, and treatment and is treated as a separate disease by many experts.

Throat

Most oropharyngeal cancers are squamous cell carcinomas that begin in the oropharynx (throat), the middle part of the throat that includes the soft palate, the base of the tongue, and the tonsils. [1] Squamous cell cancers of the tonsils are more strongly associated with human papillomavirus 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, [19] but this advantage for HPV-associated cancer applies only to oropharyngeal cancers. [20]

People with oropharyngeal carcinomas are at high risk of developing a second primary head and neck cancer. [21]

Hypopharynx

The hypopharynx 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 early due to the extensive lymphatic network around the larynx.

Larynx

Laryngeal cancer begins in the larynx, or "voice box", and is the second most common type of head and neck cancer encountered. [5] Cancer may occur on the vocal folds 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.

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. [22]

Most tumors of the salivary glands differ from the common squamous cell carcinomas of the head and neck in cause, histopathology, clinical presentation, and therapy. Other uncommon tumors arising in the head and neck include teratomas, adenocarcinomas, adenoid cystic carcinomas, and mucoepidermoid carcinomas. [23] Rarer still are melanomas and lymphomas of the upper aerodigestive tract.

Causes

Alcohol and tobacco

When DNA undergoes oxidative damage, two of the most common damages change guanine to 8-hydroxyguanine or to 2,6-diamino-4-hydroxy-5-formamidopyrimidine. Guanine and 2 oxidative products.svg
When DNA undergoes oxidative damage, two of the most common damages change guanine to 8-hydroxyguanine or to 2,6-diamino-4-hydroxy-5-formamidopyrimidine.

Around 75% of cases are caused by alcohol and tobacco use. [1]

Tobacco smoking is one of the main risk factors for head and neck cancer. A major carcinogenic compound in tobacco smoke is acrylonitrile. [24] Acrylonitrile appears to indirectly cause DNA damage by increasing oxidative stress, leading to increased levels of 8-oxo-2'-deoxyguanosine (8-oxo-dG) and formamidopyrimidine in DNA. [25] (see image). Both 8-oxo-dG and formamidopyrimidine are mutagenic. [26] [27] DNA glycosylase NEIL1 prevents mutagenesis by 8-oxo-dG [28] and removes formamidopyrimidines from DNA. [29]

However, cigarette smokers have a lifetime increased risk for head and neck cancer that is 5 to 25 times higher than the general population. [30] 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. [31]

Smokeless tobacco is a cause of oral cancer and oropharyngeal cancer. [32] Smokeless tobacco (including products where tobacco is chewed) is associated with a higher risk of developing head and neck cancer; this link has been established in the United States as well as in East Asian countries. [5] [33] [34] Cigar smoking is also an important risk factor for oral cancer. [35] The use of electronic cigarettes may also lead to the development of head and neck cancers due to the substances like propylene glycol, glycerol, nitrosamines, and metals contained therein, which can cause damage to the airways. [36] [5] This area of study requires more research to prove correlation and/or causation, however. [36] [5]

Diet

In one study, excessive consumption of eggs, processed meats, and red meat was associated with increased rates of cancer of the head and neck, while consumption of raw and cooked vegetables seemed to be protective. [37]

Vitamin E was not found to prevent the development of leukoplakia, the white plaques that are the precursor for carcinomas of the mucosal surfaces, in adult smokers. [38] Another study examined a combination of vitamin E and beta carotene in smokers with early-stage cancer of the oropharynx and found a worse prognosis in vitamin E users. [39]

Betel nut

Betel nut chewing is associated with an increased risk of squamous cell carcinoma of the head and neck. [1] [40]

Infection

Human papillomavirus

Some head and neck cancers are caused by the human papillomavirus (HPV). [1] In particular, HPV16 is a causal factor for some head and neck squamous-cell carcinomas (HNSCCs). [41] [42] Approximately 15–25% of HNSCC contain genomic DNA from HPV, [43] and the association varies based on the site of the tumor, [44] especially HPV-positive oropharyngeal cancer, with the highest distribution in the tonsils, where HPV DNA is found in 45–67% of the cases, [45] less often in the hypopharynx (13–25%), and least often in the oral cavity (12–18%) and larynx (3–7%). [46] [47]

Some experts estimate that while up to 50% of tonsil cancers may be infected with HPV, only 50% of these are likely to be caused by HPV (as opposed to the usual tobacco and alcohol causes). The role of HPV in the remaining 25–30% is not yet clear. [48] Oral sex is not risk-free and results in a significant proportion of HPV-related head and neck cancer. [49]

Positive HPV16 status is associated with an improved prognosis over HPV-negative OSCC. [50]

HPV can induce tumors by several mechanisms: [51]

  1. E6 and E7 oncogenic proteins.
  2. Disruption of tumor suppressor genes.
  3. High-level DNA amplifications, for example, oncogenes.
  4. Generating alternative nonfunctional transcripts.
  5. interchromosomal rearrangements.
  6. Distinct host genome methylation and expression patterns, produced even when the virus is not integrated into the host genome.

Induction of cancer can be associated with the expression of viral oncoproteins, the most important E6 and E7, or other mechanisms, many of which run through 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 of which can be found even when the virus is identified in episomes. [52] [44] 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 and Cdk4, thereby avoiding pRb phosphorylation and thereby preventing the release of E2F, is a transcription factor required for the activation of genes involved in cell proliferation. pRb remains bound to E2F while this action is phosphorylated, preventing the 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.[ citation needed ]

Viral integration tends to occur in or near oncogenes or tumor suppressor genes, and it is for this reason that the integration of the virus can greatly contribute to the development of tumor characteristics. [52]

Epstein–Barr virus

Epstein–Barr virus (EBV) infection is associated with nasopharyngeal cancer. 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 the consumption of salted fish, which may contain high levels of nitrites. [53]

Gastroesophageal reflux disease

The presence of gastroesophageal reflux disease (GERD) or laryngeal reflux disease can also be a major factor. Stomach acids that flow up through the esophagus can damage its lining and raise susceptibility to throat cancer.

Hematopoietic stem cell transplantation

People after hematopoietic stem cell transplantation (HSCT) are at a higher risk for oral squamous cell carcinoma. Post-HSCT oral cancer may have more aggressive behavior and a poorer prognosis when compared to oral cancer in non-HSCT patients. [54] This effect is supposed to be due to continuous, lifelong immune suppression and chronic oral graft-versus-host disease. [54]

Other possible causes

There are several risk factors for developing head and neck cancer. These include a poor diet resulting in vitamin deficiencies (worse if this is caused by heavy alcohol intake); a weakened immune system; asbestos exposure; prolonged exposure to wood dust or paint fumes; exposure to petroleum industry chemicals; and being over the age of 55 years. Other risk factors include the appearance of white patches or spots in the mouth, known as leukoplakia, [23] which in about 13 of cases develops into cancer, and breathing or inhaling silica from cutting concrete, stone, or cinderblocks, especially in enclosed areas such as a warehouse, garage, or basement.

Other environmental carcinogens 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, especially when younger, has been linked to an increase in squamous-cell carcinoma cases in at least one study, [55] while other studies suggest use is not shown to be associated with oral squamous cell carcinoma or decreased squamous cell carcinoma. [56] [57]

Diagnosis

PET-CT scanning of lymph node metastases in cancer 2.jpg
PET-CT scanning of lymph node metastases in cancer.jpg
Left inferior internal jugular node metastases with extranodal invasion, two years after brachytherapy for tongue cancer. PET-CT scanning of a male in his 30s, 64 minutes after fludeoxyglucose (18F) was administered, shows some fluff around the tumor.

A person usually presents to the physician complaining of one or more of the above symptoms. The person will typically undergo a needle biopsy of this lesion, and if histopathologic information is available, a multidisciplinary discussion of the optimal treatment strategy will be undertaken between the radiation oncologist, surgical oncologist, and medical oncologist.[ medical citation needed ] Most (90%) cancers of the head and neck are squamous cell-derived, termed "head-and-neck squamous-cell carcinomas". [7]

Histopathology

Throat cancers are classified according to their histology 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. [58]

Squamous-cell carcinoma

Squamous-cell carcinoma is a cancer of the squamous cell, a kind of epithelial cell found in both the skin and mucous membranes. It accounts for over 90% of all head and neck cancers, [59] including more than 90% of throat cancer. [23] 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 and neck (SCCHN). [60]

Adenocarcinoma

Adenocarcinoma is a cancer of the epithelial tissue that has glandular characteristics. Several head and neck cancers are adenocarcinomas (either of intestinal or non-intestinal cell types). [59]

Prevention

Avoidance of recognized 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. [1]

When diagnosed early, oral, head, and neck cancers can be treated more easily, and the chances of survival increase tremendously. [1] As of 2017, it was not known if existing HPV vaccines can help prevent head and neck cancer. [1]

Management

Improvements in diagnosis and local management, as well as targeted therapy, have led to improvements in quality of life and survival for people with head and neck cancer. [61]

After a histologic diagnosis has been established and tumor extent determined, such as with the use of PET-CT, [62] 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. [ citation needed ]

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 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 larynx 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 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. [63] This technique helps give the person as much speech and swallowing function as possible after surgery. [64]

Radiation therapy

Radiation mask used in the treatment of throat cancer Radiation-mask.jpg
Radiation mask used in the treatment of throat cancer

Radiation therapy 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 dysfunction and pituitary axis dysfunction. [65] 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. [66]

Chemotherapy

Chemotherapy 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 and carboplatin. Cetuximab is also used in the treatment of throat cancer.

Docetaxel-based chemotherapy has shown a very good response in locally advanced head and neck cancer. Docetaxel is the only taxane approved by the 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. [67]

While not specifically a chemotherapy, amifostine is often administered intravenously by a chemotherapy clinic prior to IMRT radiotherapy sessions. Amifostine protects the gums and salivary glands from the effects of radiation.[ citation needed ]

There is no evidence that erythropoietin should be routinely given with radiotherapy. [68]

Photodynamic therapy

Photodynamic therapy may have promise for treating mucosal dysplasia and small head and neck tumors. [23] Amphinex is showing good results in early clinical trials for the treatment of advanced head and neck cancer. [69]

Targeted therapy

Targeted therapy, according to the National Cancer Institute, 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 squamous cell carcinomas of the head and neck include cetuximab, bevacizumab, and erlotinib.

Cetuximab is used for treating people with advanced-stage cancer who cannot be treated with conventional chemotherapy (cisplatin). [70] [71] However, cetuximab's efficacy is still under investigation by researchers. [72]

Gendicine is a gene therapy that employs an adenovirus to deliver the tumor suppressor gene p53 to cells. It was approved in China in 2003 for the treatment of head and neck squamous cell carcinoma. [73]

The mutational profiles of HPV+ and HPV- head and neck cancer have been reported, further demonstrating that they are fundamentally distinct diseases. [74] [ non-primary source needed ]

Immunotherapy

Immunotherapy 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 HNSCC with disease progression on or after platinum-containing chemotherapy. [75] Later that year, the FDA approved nivolumab for the treatment of recurrent or metastatic HNSCC with disease progression on or after platinum-based chemotherapy. [76] In 2019, the FDA approved pembrolizumab for the first-line treatment of metastatic or unresectable recurrent HNSCC. [77]

Treatment side effects

Depending on the treatment used, people with head and neck cancer may experience the following symptoms and treatment side effects: [23] [66]

Psychosocial

Programs to support the emotional and social well-being of people who have been diagnosed with head and neck cancer may be offered. [78] 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. [78]

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. [79] 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. [ citation needed ] 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. [8]

Consensus panels in America (AJCC) 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 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. [80]

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 tumors. The incidence of second primary tumors ranges in studies from 9% [81] to 23% [82] at 20 years. Second primary tumors are the major threat to long-term survival after successful therapy of early-stage HNSCC. [83] 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 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 esophagus 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 and vomiting, 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 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. [84] 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. [84]

Mental health

Cancer in the head or neck may impact a person's mental well-being and can sometimes lead to social isolation. [78] 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. [78] Some people may also have a changed physical appearance, differences in swallowing or breathing, and residual pain to manage. [78]

Caregiver stress

Caregivers for people with head and neck cancer show higher rates of caregiver stress and poorer mental health compared to both the general population and those caring for non-head and neck cancer patients. [85] 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. [86] 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. [86]

Others

Like any cancer, metastasis 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, it will prevent the body from producing enough red blood cells and affect the proper functioning of the white blood cells and the body's immune system; spreading to the circulatory system will prevent oxygen from being transported to all the cells of the body; and throat cancer can throw the nervous system into chaos, making it unable to properly regulate and control the body.

Epidemiology

Age-standardized death from oro-pharyngeal cancer per 100,000 inhabitants in 2004
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no data
less than 2
2-4
4-6
6-8
8-10
10-12
12-14
14-16
16-18
18-20
20-25
more than 25 Mouth and oropharynx cancers world map - Death - WHO2004.svg
Age-standardized death from oro-pharyngeal cancer per 100,000 inhabitants in 2004
  no data
  less than 2
  2-4
  4-6
  6-8
  8-10
  10-12
  12-14
  14-16
  16-18
  18-20
  20-25
  more than 25

The number of new cases of head and neck cancer 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. [88] 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, is the most common cause of death in young men. [89]

Research

Immunotherapy with immune checkpoint inhibitors is being investigated in head and neck cancers. [93]

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Oral cancer, also known as 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 white patch, that thickens, develops red patches, an ulcer, and continues to grow. When on the lips, it commonly looks like a persistent crusting ulcer that does not heal, and slowly grows. Other symptoms may include difficult or painful swallowing, new lumps or bumps in the neck, a swelling in the mouth, or a feeling of numbness in the mouth or lips.

<span class="mw-page-title-main">Anal cancer</span> Medical condition

Anal cancer is a cancer which arises from the anus, the distal opening of the gastrointestinal tract. Symptoms may include bleeding from the anus or a lump near the anus. Other symptoms may include pain, itchiness, or discharge from the anus. A change in bowel movements may also occur.

<span class="mw-page-title-main">Verrucous carcinoma</span> Medical condition

Verrucous carcinoma (VC) is an uncommon variant of squamous cell carcinoma. This form of cancer is often seen in those who chew tobacco or use snuff orally, so much so that it is sometimes referred to as "Snuff dipper's cancer".

p16 Mammalian protein found in Homo sapiens

p16, is a protein that slows cell division by slowing the progression of the cell cycle from the G1 phase to the S phase, thereby acting as a tumor suppressor. It is encoded by the CDKN2A gene. A deletion in this gene can result in insufficient or non-functional p16, accelerating the cell cycle and resulting in many types of cancer.

<span class="mw-page-title-main">Nasopharyngeal carcinoma</span> Type of throat cancer; most common to occur in the nasopharynx

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, accounting for 50% of cases. NPC occurs in children and adults. NPC differs significantly from other cancers of the head and neck in its occurrence, causes, clinical behavior, and treatment. It is vastly more common in certain regions of East Asia and Africa than elsewhere, with viral, dietary and genetic factors implicated in its causation. It is most common in males. It is a squamous cell carcinoma of an undifferentiated type. Squamous epithelial cells are a flat type of cell found in the skin and the membranes that line some body cavities. Undifferentiated cells are cells that do not have their mature features or functions.

The Danish Head and Neck Cancer (DAHANCA) group was established in 1976 as a working group by the Danish Society for Head and Neck Oncology with the primary aim to develop national guidelines for the treatment of head and neck cancer in Denmark.

<span class="mw-page-title-main">Squamous cell papilloma</span> Medical condition

A squamous cell papilloma is a generally benign papilloma that arises from the stratified squamous epithelium of the skin, lip, oral cavity, tongue, pharynx, larynx, esophagus, cervix, vagina or anal canal. Squamous cell papillomas are typically associated with human papillomavirus (HPV) while sometimes the cause is unknown.

HspE7 is an investigational therapeutic vaccine candidate being developed by Nventa Biopharmaceuticals for the treatment of precancerous and cancerous lesions caused by the human papillomavirus (HPV). HspE7 uses recombinant DNA technology to covalently fuse a heat shock protein (Hsp) to a target antigen, thereby stimulating cellular immune system responses to specific diseases. HspE7 is a patented construct consisting of the HPV Type 16 E7 protein and heat shock protein 65 (Hsp65) and is currently the only candidate using Hsp technology to target the over 20 million Americans already infected with HPV.

The Head and Neck Cancer Alliance (HNCA) is a non-profit organization that works with health professionals and organizations, celebrities and survivors to enhance the overall effort in prevention, treatment, and detection of cancers of the head and neck region.

<span class="mw-page-title-main">Oropharyngeal cancer</span> Pharynx cancer that is located in the oropharynx

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 tissue of the part of the throat (oropharynx) that includes the base of the tongue, the tonsils, the soft palate, and the walls of the pharynx.

<span class="mw-page-title-main">HPV-positive oropharyngeal cancer</span> Cancer of the throat

Human papillomavirus-positive oropharyngeal cancer, is a cancer of the throat caused by the human papillomavirus type 16 virus (HPV16). In the past, cancer of the oropharynx (throat) was associated with the use of alcohol or tobacco or both, but the majority of cases are now associated with the HPV virus, acquired by having oral contact with the genitals of a person who has a genital HPV infection. Risk factors include having a large number of sexual partners, a history of oral-genital sex or anal–oral sex, having a female partner with a history of either an abnormal Pap smear or cervical dysplasia, having chronic periodontitis, and, among men, younger age at first intercourse and a history of genital warts. HPV-positive OPC is considered a separate disease from HPV-negative oropharyngeal cancer.

Carcinoma of the tonsil is a type of squamous cell carcinoma. The tonsil is the most common site of squamous cell carcinoma in the oropharynx. It comprises 23.1% of all malignancies of the oropharynx. The tumors frequently present at advanced stages, and around 70% of patients present with metastasis to the cervical lymph nodes. . The most reported complaints include sore throat, otalgia or dysphagia. Some patients may complain of feeling the presence of a lump in the throat. Approximately 20% patients present with a node in the neck as the only symptom.

Human papillomavirus (HPV)-associated oropharyngeal cancer awareness and prevention is a vital concept from a public and community health perspective.

<span class="mw-page-title-main">Squamous-cell carcinoma</span> Carcinoma that derives from squamous epithelial cells

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 lining of the respiratory and digestive tracts.

The Oral Cancer Foundation, sometimes abbreviated to OCF, is an American, IRS-registered, 501(c)(3) non-profit organization, which focuses on oral and oropharyngeal cancer related issues and public awareness of the disease.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 "Oropharyngeal Cancer Treatment (Adult) (PDQ®)–Patient Version". National Cancer Institute. 22 November 2019. Retrieved 28 November 2019.
  2. 1 2 3 4 5 6 7 World Cancer Report 2014. World Health Organization. 2014. pp. Chapter 5.8. ISBN   978-9283204299.
  3. Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, et al. (GBD 2015 Disease and Injury Incidence and Prevalence Collaborators) (October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC   5055577 . PMID   27733282.
  4. Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, et al. (GBD 2015 Mortality and Causes of Death Collaborators) (October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1459–1544. doi:10.1016/s0140-6736(16)31012-1. PMC   5388903 . PMID   27733281.
  5. 1 2 3 4 5 6 7 8 9 10 11 Aupérin A (May 2020). "Epidemiology of head and neck cancers: an update". Current Opinion in Oncology. 32 (3): 178–186. doi:10.1097/CCO.0000000000000629. PMID   32209823. S2CID   214644380.
  6. 1 2 3 4 5 6 7 "Head and Neck Cancers". NCI . 29 March 2017. Retrieved 7 February 2021.
  7. 1 2 Vigneswaran N, Williams MD (May 2014). "Epidemiologic trends in head and neck cancer and aids in diagnosis". Oral and Maxillofacial Surgery Clinics of North America. 26 (2): 123–141. doi:10.1016/j.coms.2014.01.001. PMC   4040236 . PMID   24794262.
  8. 1 2 3 4 5 Chow LQ (January 2020). "Head and Neck Cancer". The New England Journal of Medicine. 382 (1): 60–72. doi:10.1056/nejmra1715715. PMID   31893516. S2CID   209482428.
  9. Siegel RL, Miller KD, Jemal A (January 2020). "Cancer statistics, 2020". CA: A Cancer Journal for Clinicians. 70 (1): 7–30. doi: 10.3322/caac.21590 . PMID   31912902.
  10. Fitzmaurice C, Abate D, Abbasi N, Abbastabar H, Abd-Allah F, Abdel-Rahman O, et al. (Global Burden of Disease Cancer Collaboration) (December 2019). "Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study". JAMA Oncology. 5 (12): 1749–1768. doi:10.1001/jamaoncol.2019.2996. PMC   6777271 . PMID   31560378.
  11. Gillison ML, Castellsagué X, Chaturvedi A, Goodman MT, Snijders P, Tommasino M, et al. (February 2014). "Eurogin Roadmap: comparative epidemiology of HPV infection and associated cancers of the head and neck and cervix". International Journal of Cancer. 134 (3): 497–507. doi:10.1002/ijc.28201. PMID   23568556. S2CID   37877664.
  12. Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C (October 2015). "Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma". Journal of Clinical Oncology. 33 (29): 3235–3242. doi:10.1200/JCO.2015.61.6995. PMC   4979086 . PMID   26351338.
  13. Giuliano AR, Nyitray AG, Kreimer AR, Pierce Campbell CM, Goodman MT, Sudenga SL, et al. (June 2015). "EUROGIN 2014 roadmap: differences in human papillomavirus infection natural history, transmission and human papillomavirus-related cancer incidence by gender and anatomic site of infection". International Journal of Cancer. 136 (12): 2752–2760. doi:10.1002/ijc.29082. PMC   4297584 . PMID   25043222.
  14. 1 2 "SEER Stat Fact Sheets: Oral Cavity and Pharynx Cancer". SEER. April 2016. Archived from the original on 15 November 2016. Retrieved 29 September 2016.
  15. Beyzadeoglu M, Ozyigit G, Selek U (2014). Radiation Therapy for Head and Neck Cancers: A Case-Based Review. Springer. p. 18. ISBN   9783319104133. Archived from the original on 2017-09-10.
  16. McIlwain WR, Sood AJ, Nguyen SA, Day TA (May 2014). "Initial symptoms in patients with HPV-positive and HPV-negative oropharyngeal cancer". JAMA Otolaryngology–Head & Neck Surgery. 140 (5): 441–447. doi: 10.1001/jamaoto.2014.141 . PMID   24652023.
  17. Ensley JF (2003). Head and neck cancer : emerging perspectives. Amsterdam: Academic Press. ISBN   978-0-08-053384-1. OCLC   180905431.
  18. "Paranasal Sinus and Nasal Cavity Cancer Treatment (Adult) (PDQ®)–Patient Version". National Cancer Institute. 8 November 2019. Retrieved 4 December 2019.
  19. O'Rorke MA, Ellison MV, Murray LJ, Moran M, James J, Anderson LA (December 2012). "Human papillomavirus related head and neck cancer survival: a systematic review and meta-analysis". Oral Oncology. 48 (12): 1191–1201. doi:10.1016/j.oraloncology.2012.06.019. PMID   22841677. Archived (PDF) from the original on 2017-09-10.
  20. Ragin CC, Taioli E (October 2007). "Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis". International Journal of Cancer. 121 (8): 1813–1820. doi: 10.1002/ijc.22851 . PMID   17546592.
  21. Krishnatreya M, Rahman T, Kataki AC, Das A, Das AK, Lahkar K (2013). "Synchronous primary cancers of the head and neck region and upper aero digestive tract: defining high-risk patients". Indian Journal of Cancer. 50 (4): 322–326. doi: 10.4103/0019-509x.123610 . PMID   24369209.
  22. "Throat cancer | Head and neck cancers | Cancer Research UK". www.cancerresearchuk.org. Retrieved 28 November 2019.
  23. 1 2 3 4 5 6 7 8 Ridge JA, Glisson BS, Lango MN, Feigenberg S, Horwitz EM (2008). "Head and neck tumors." (PDF). In Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (eds.). Cancer management: a multidisciplinary approach (11th ed.). pp. 39–86.
  24. Cunningham FH, Fiebelkorn S, Johnson M, Meredith C (November 2011). "A novel application of the Margin of Exposure approach: segregation of tobacco smoke toxicants". Food and Chemical Toxicology. 49 (11): 2921–2933. doi:10.1016/j.fct.2011.07.019. PMID   21802474.
  25. Pu X, Kamendulis LM, Klaunig JE (September 2009). "Acrylonitrile-induced oxidative stress and oxidative DNA damage in male Sprague-Dawley rats". Toxicological Sciences. 111 (1): 64–71. doi:10.1093/toxsci/kfp133. PMC   2726299 . PMID   19546159.
  26. Kalam MA, Haraguchi K, Chandani S, Loechler EL, Moriya M, Greenberg MM, Basu AK (2006). "Genetic effects of oxidative DNA damages: comparative mutagenesis of the imidazole ring-opened formamidopyrimidines (Fapy lesions) and 8-oxo-purines in simian kidney cells". Nucleic Acids Research. 34 (8): 2305–2315. doi:10.1093/nar/gkl099. PMC   1458282 . PMID   16679449.
  27. Jena NR, Mishra PC (October 2013). "Is FapyG mutagenic?: Evidence from the DFT study". ChemPhysChem. 14 (14): 3263–3270. doi:10.1002/cphc.201300535. PMID   23934915.
  28. Suzuki T, Harashima H, Kamiya H (May 2010). "Effects of base excision repair proteins on mutagenesis by 8-oxo-7,8-dihydroguanine (8-hydroxyguanine) paired with cytosine and adenine". DNA Repair. 9 (5): 542–550. doi:10.1016/j.dnarep.2010.02.004. hdl: 2115/43021 . PMID   20197241. S2CID   207147128.
  29. Nemec AA, Wallace SS, Sweasy JB (October 2010). "Variant base excision repair proteins: contributors to genomic instability". Seminars in Cancer Biology. 20 (5): 320–328. doi:10.1016/j.semcancer.2010.10.010. PMC   3254599 . PMID   20955798.
  30. Andre K, Schraub S, Mercier M, Bontemps P (September 1995). "Role of alcohol and tobacco in the aetiology of head and neck cancer: a case-control study in the Doubs region of France". European Journal of Cancer, Part B. 31B (5): 301–309. doi:10.1016/0964-1955(95)00041-0. PMID   8704646.
  31. La Vecchia C, Franceschi S, Bosetti C, Levi F, Talamini R, Negri E (April 1999). "Time since stopping smoking and the risk of oral and pharyngeal cancers". Journal of the National Cancer Institute. 91 (8): 726–728. doi:10.1093/jnci/91.8.726a. hdl: 2434/520105 . PMID   10218516.
  32. Winn D (1992). "Smokeless Tobacco and Aerodigestive Tract Cancers: Recent Research Directions". The Biology and Prevention of Aerodigestive Tract Cancers. Advances in Experimental Medicine and Biology. Vol. 320. pp. 39–46. doi:10.1007/978-1-4615-3468-6_6. ISBN   978-0-306-44244-5. PMID   1442283.
  33. Wyss AB, Hashibe M, Lee YA, Chuang SC, Muscat J, Chen C, et al. (November 2016). "Smokeless Tobacco Use and the Risk of Head and Neck Cancer: Pooled Analysis of US Studies in the INHANCE Consortium". American Journal of Epidemiology. 184 (10): 703–716. doi:10.1093/aje/kww075. PMC   5141945 . PMID   27744388.
  34. Lee YA, Li S, Chen Y, Li Q, Chen CJ, Hsu WL, et al. (January 2019). "Tobacco smoking, alcohol drinking, betel quid chewing, and the risk of head and neck cancer in an East Asian population". Head & Neck. 41 (1): 92–102. doi:10.1002/hed.25383. PMID   30552826. S2CID   54632009.
  35. Iribarren C, Tekawa IS, Sidney S, Friedman GD (June 1999). "Effect of cigar smoking on the risk of cardiovascular disease, chronic obstructive pulmonary disease, and cancer in men". The New England Journal of Medicine. 340 (23): 1773–1780. CiteSeerX   10.1.1.460.1056 . doi:10.1056/NEJM199906103402301. PMID   10362820.
  36. 1 2 Ralho A, Coelho A, Ribeiro M, Paula A, Amaro I, Sousa J, et al. (December 2019). "Effects of Electronic Cigarettes on Oral Cavity: A Systematic Review". The Journal of Evidence-Based Dental Practice. 19 (4): 101318. doi:10.1016/j.jebdp.2019.04.002. PMID   31843181. S2CID   145920823.
  37. Levi F, Pasche C, La Vecchia C, Lucchini F, Franceschi S, Monnier P (August 1998). "Food groups and risk of oral and pharyngeal cancer". International Journal of Cancer. 77 (5): 705–709. doi: 10.1002/(SICI)1097-0215(19980831)77:5<705::AID-IJC8>3.0.CO;2-Z . PMID   9688303.
  38. Liede K, Hietanen J, Saxen L, Haukka J, Timonen T, Häyrinen-Immonen R, Heinonen OP (June 1998). "Long-term supplementation with alpha-tocopherol and beta-carotene and prevalence of oral mucosal lesions in smokers". Oral Diseases. 4 (2): 78–83. doi:10.1111/j.1601-0825.1998.tb00261.x. PMID   9680894.
  39. Bairati I, Meyer F, Gélinas M, Fortin A, Nabid A, Brochet F, et al. (April 2005). "A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients". Journal of the National Cancer Institute. 97 (7): 481–488. doi: 10.1093/jnci/dji095 . PMID   15812073.
  40. Jeng JH, Chang MC, Hahn LJ (September 2001). "Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives". Oral Oncology. 37 (6): 477–492. doi:10.1016/S1368-8375(01)00003-3. PMID   11435174.
  41. "Biomarkers for Cancers of the Head and Neck" . Retrieved 2014-08-07.
  42. D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, et al. (May 2007). "Case-control study of human papillomavirus and oropharyngeal cancer". The New England Journal of Medicine. 356 (19): 1944–1956. doi: 10.1056/NEJMoa065497 . PMID   17494927. S2CID   18819678.
  43. Kreimer AR, Clifford GM, Boyle P, Franceschi S (February 2005). "Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review". Cancer Epidemiology, Biomarkers & Prevention. 14 (2): 467–475. doi: 10.1158/1055-9965.EPI-04-0551 . PMID   15734974.
  44. 1 2 Joseph AW, D'Souza G (August 2012). "Epidemiology of human papillomavirus-related head and neck cancer". Otolaryngologic Clinics of North America. 45 (4): 739–764. doi:10.1016/j.otc.2012.04.003. PMID   22793850.
  45. Perez-Ordoñez B, Beauchemin M, Jordan RC (May 2006). "Molecular biology of squamous cell carcinoma of the head and neck". Journal of Clinical Pathology. 59 (5): 445–453. doi:10.1136/jcp.2003.007641. PMC   1860277 . PMID   16644882.
  46. Paz IB, Cook N, Odom-Maryon T, Xie Y, Wilczynski SP (February 1997). "Human papillomavirus (HPV) in head and neck cancer. An association of HPV 16 with squamous cell carcinoma of Waldeyer's tonsillar ring". Cancer. 79 (3): 595–604. doi: 10.1002/(SICI)1097-0142(19970201)79:3<595::AID-CNCR24>3.0.CO;2-Y . PMID   9028373.
  47. Hobbs CG, Sterne JA, Bailey M, Heyderman RS, Birchall MA, Thomas SJ (August 2006). "Human papillomavirus and head and neck cancer: a systematic review and meta-analysis" (PDF). Clinical Otolaryngology. 31 (4): 259–266. doi:10.1111/j.1749-4486.2006.01246.x. PMID   16911640. S2CID   2502403. Archived (PDF) from the original on 2017-08-11.
  48. Weinberger PM, Yu Z, Haffty BG, Kowalski D, Harigopal M, Brandsma J, et al. (February 2006). "Molecular classification identifies a subset of human papillomavirus--associated oropharyngeal cancers with favorable prognosis". Journal of Clinical Oncology. 24 (5): 736–747. doi:10.1200/JCO.2004.00.3335. PMID   16401683. Archived from the original on 2009-01-20.
  49. Haddad RI (2007). "Human Papillomavirus Infection and Oropharyngeal Cancer" (PDF). Archived from the original (PDF) on 2012-05-13. Retrieved 2012-09-26.
  50. Tahtali A, Hey C, Geissler C, Filman N, Diensthuber M, Leinung M, et al. (August 2013). "HPV status and overall survival of patients with oropharyngeal squamous cell carcinoma--a retrospective study of a German head and neck cancer center". Anticancer Research. 33 (8): 3481–3485. PMID   23898123. Archived from the original on 2016-01-07.
  51. Schmitz M, Driesch C, Beer-Grondke K, Jansen L, Runnebaum IB, Dürst M (September 2012). "Loss of gene function as a consequence of human papillomavirus DNA integration". International Journal of Cancer. 131 (5): E593–E602. doi:10.1002/ijc.27433. PMID   22262398. S2CID   21515048.
  52. 1 2 Parfenov M, Pedamallu CS, Gehlenborg N, Freeman SS, Danilova L, Bristow CA, et al. (October 2014). "Characterization of HPV and host genome interactions in primary head and neck cancers". Proceedings of the National Academy of Sciences of the United States of America. 111 (43): 15544–15549. Bibcode:2014PNAS..11115544P. doi: 10.1073/pnas.1416074111 . PMC   4217452 . PMID   25313082.
  53. "Risks and causes | Nasopharyngeal cancer | Cancer Research UK". www.cancerresearchuk.org. Retrieved 4 December 2019.
  54. 1 2 Elad S, Zadik Y, Zeevi I, Miyazaki A, de Figueiredo MA, Or R (December 2010). "Oral cancer in patients after hematopoietic stem-cell transplantation: long-term follow-up suggests an increased risk for recurrence". Transplantation. 90 (11): 1243–1244. doi: 10.1097/TP.0b013e3181f9caaa . PMID   21119507.
  55. Zhang ZF, Morgenstern H, Spitz MR, Tashkin DP, Yu GP, Marshall JR, et al. (December 1999). "Marijuana use and increased risk of squamous cell carcinoma of the head and neck". Cancer Epidemiology, Biomarkers & Prevention. 8 (12): 1071–1078. PMID   10613339.
  56. Rosenblatt KA, Daling JR, Chen C, Sherman KJ, Schwartz SM (June 2004). "Marijuana use and risk of oral squamous cell carcinoma". Cancer Research. 64 (11): 4049–4054. doi: 10.1158/0008-5472.CAN-03-3425 . PMID   15173020.
  57. Liang C, McClean MD, Marsit C, Christensen B, Peters E, Nelson HH, Kelsey KT (August 2009). "A population-based case-control study of marijuana use and head and neck squamous cell carcinoma". Cancer Prevention Research. 2 (8): 759–768. doi:10.1158/1940-6207.CAPR-09-0048. PMC   2812803 . PMID   19638490.
  58. "Routine HPV Testing in Head and Neck Squamous Cell Carcinoma. EBS 5-9". May 2013. Archived from the original on 30 September 2016. Retrieved 22 May 2017.
  59. 1 2 Haines III GK (24 May 2013). "Pathology of Head and Neck Cancers I: Epithelial and Related Tumors". In Radosevich JA (ed.). Head & Neck Cancer: Current Perspectives, Advances, and Challenges. Springer Science & Business Media. pp. 257–87. ISBN   978-94-007-5827-8. Archived from the original on 7 January 2016.
  60. Wang YX, Hu D, Yan X (September 2013). "Diagnostic accuracy of Cyfra 21-1 for head and neck squamous cell carcinoma: a meta-analysis". European Review for Medical and Pharmacological Sciences. 17 (17): 2383–2389. PMID   24065233.
  61. Al-Sarraf M (2002). "Treatment of locally advanced head and neck cancer: historical and critical review". Cancer Control. 9 (5): 387–399. doi: 10.1177/107327480200900504 . PMID   12410178.
  62. Eyassu E, Young M (2023), "Nuclear Medicine PET/CT Head and Neck Cancer Assessment, Protocols, and Interpretation", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   34424632 , retrieved 2023-11-24
  63. Maxwell JH, Thompson LD, Brandwein-Gensler MS, Weiss BG, Canis M, Purgina B, et al. (December 2015). "Early Oral Tongue Squamous Cell Carcinoma: Sampling of Margins From Tumor Bed and Worse Local Control". JAMA Otolaryngology–Head & Neck Surgery. 141 (12): 1104–1110. doi:10.1001/jamaoto.2015.1351. PMC   5242089 . PMID   26225798.
  64. Archived March 5, 2012, at the Wayback Machine
  65. Mahmood SS, Nohria A (July 2016). "Cardiovascular Complications of Cranial and Neck Radiation". Current Treatment Options in Cardiovascular Medicine. 18 (7): 45. doi:10.1007/s11936-016-0468-4. PMID   27181400. S2CID   23888595.
  66. 1 2 Yan J, Yuan L, Wang J, Li S, Yao M, Wang K, Herst PM (September 2020). "Mepitel Film is superior to Biafine cream in managing acute radiation-induced skin reactions in head and neck cancer patients: a randomised intra-patient controlled clinical trial". Journal of Medical Radiation Sciences. 67 (3): 208–216. doi: 10.1002/jmrs.397 . PMC   7476193 . PMID   32475079.
  67. "FDA Approval for Docetaxel - National Cancer Institute". Cancer.gov. Archived from the original on 2014-09-01. Retrieved 2014-08-07.
  68. Lambin P, Ramaekers BL, van Mastrigt GA, Van den Ende P, de Jong J, De Ruysscher DK, Pijls-Johannesma M (July 2009). "Erythropoietin as an adjuvant treatment with (chemo) radiation therapy for head and neck cancer". The Cochrane Database of Systematic Reviews (3): CD006158. doi:10.1002/14651858.CD006158.pub2. PMID   19588382.
  69. "Inoperable cancers killed by new laser surgery" The Times. UK. 3-April-2010 p15
  70. Blick SK, Scott LJ (2007). "Cetuximab: A Review of its Use in Squamous Cell Carcinoma of the Head and Neck and Metastatic Colorectal Cancer". Drugs. 67 (17): 2585–2607. doi:10.2165/00003495-200767170-00008. ISSN   0012-6667. PMID   18034592. S2CID   195690071.
  71. Cantwell LA, Fahy E, Walters ER, Patterson JM (26 November 2020). "Nutritional prehabilitation in head and neck cancer: a systematic review". Supportive Care in Cancer. 30 (11): 8831–8843. doi:10.1007/s00520-022-07239-4. ISSN   0941-4355. PMID   35913625. S2CID   251221072.
  72. Muraro E, Fanetti G, Lupato V, Giacomarra V, Steffan A, Gobitti C, Vaccher E, Franchin G (10 July 2021). "Cetuximab in locally advanced head and neck squamous cell carcinoma: Biological mechanisms involved in efficacy, toxicity and resistance". Critical Reviews in Oncology/Hematology. 164: 103424. doi:10.1016/j.critrevonc.2021.103424. PMID   34245856. S2CID   235791305.
  73. Pearson S, Jia H, Kandachi K (January 2004). "China approves first gene therapy". Nature Biotechnology. 22 (1): 3–4. doi:10.1038/nbt0104-3. PMC   7097065 . PMID   14704685.
  74. Lechner M, Frampton GM, Fenton T, Feber A, Palmer G, Jay A, et al. (2013). "Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors". Genome Medicine. 5 (5): 49. doi: 10.1186/gm453 . PMC   4064312 . PMID   23718828.
  75. Center for Drug Evaluation and Research (2019-02-09). "pembrolizumab (KEYTRUDA)". FDA.
  76. Center for Drug Evaluation and Research (2018-11-03). "Nivolumab for SCCHN". FDA.
  77. Center for Drug Evaluation and Research (2019-06-11). "FDA approves pembrolizumab for first-line treatment of head and neck squamous cell carcinoma". FDA.
  78. 1 2 3 4 5 Semple C, Parahoo K, Norman A, McCaughan E, Humphris G, Mills M (July 2013). "Psychosocial interventions for patients with head and neck cancer". The Cochrane Database of Systematic Reviews (7): CD009441. doi:10.1002/14651858.CD009441.pub2. hdl: 10026.1/3146 . PMID   23857592. S2CID   42090352.
  79. 1 2 Gourin CG, Podolsky RH (July 2006). "Racial disparities in patients with head and neck squamous cell carcinoma". The Laryngoscope. 116 (7): 1093–1106. doi:10.1097/01.mlg.0000224939.61503.83. PMID   16826042. S2CID   11140152.
  80. Iro H, Waldfahrer F (November 1998). "Evaluation of the newly updated TNM classification of head and neck carcinoma with data from 3247 patients". Cancer. 83 (10): 2201–2207. doi: 10.1002/(SICI)1097-0142(19981115)83:10<2201::AID-CNCR20>3.0.CO;2-7 . PMID   9827726.
  81. Jones AS, Morar P, Phillips DE, Field JK, Husband D, Helliwell TR (March 1995). "Second primary tumors in patients with head and neck squamous cell carcinoma". Cancer. 75 (6): 1343–1353. doi: 10.1002/1097-0142(19950315)75:6<1343::AID-CNCR2820750617>3.0.CO;2-T . PMID   7882285.
  82. Cooper JS, Pajak TF, Rubin P, Tupchong L, Brady LW, Leibel SA, et al. (September 1989). "Second malignancies in patients who have head and neck cancer: incidence, effect on survival and implications based on the RTOG experience". International Journal of Radiation Oncology, Biology, Physics. 17 (3): 449–456. doi:10.1016/0360-3016(89)90094-1. PMID   2674073.
  83. Priante AV, Castilho EC, Kowalski LP (April 2011). "Second primary tumors in patients with head and neck cancer". Current Oncology Reports. 13 (2): 132–137. doi:10.1007/s11912-010-0147-7. PMID   21234721. S2CID   207335139.
  84. 1 2 Nugent B, Lewis S, O'Sullivan JM (January 2013). "Enteral feeding methods for nutritional management in patients with head and neck cancers being treated with radiotherapy and/or chemotherapy". The Cochrane Database of Systematic Reviews. 2013 (1): CD007904. doi:10.1002/14651858.CD007904.pub3. PMC   6769131 . PMID   23440820.
  85. Longacre ML, Ridge JA, Burtness BA, Galloway TJ, Fang CY (January 2012). "Psychological functioning of caregivers for head and neck cancer patients". Oral Oncology. 48 (1): 18–25. doi:10.1016/j.oraloncology.2011.11.012. PMC   3357183 . PMID   22154127.
  86. 1 2 Sherrod AM, Murphy BA, Wells NL, Bond SM, Hertzog M, Gilbert J, et al. (2014-05-20). "Caregiving burden in head and neck cancer". Journal of Clinical Oncology. 32 (15_suppl): e20678. doi:10.1200/jco.2014.32.15_suppl.e20678. ISSN   0732-183X.
  87. "WHO Disease and injury country estimates". World Health Organization. 2009. Archived from the original on 2009-11-11. Retrieved Nov 11, 2009.
  88. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ (2006). "Cancer statistics, 2006". CA: A Cancer Journal for Clinicians. 56 (2): 106–130. doi: 10.3322/canjclin.56.2.106 . PMID   16514137. S2CID   21618776.
  89. Titcomb CP (2001). "High incidence of nasopharyngeal carcinoma in Asia". Journal of Insurance Medicine. 33 (3): 235–238. PMID   11558403.
  90. 1 2 Cancer Facts and Figures, Archived 2007-09-29 at the Wayback Machine , American Cancer Society 2002.
  91. "Throat Cancer". Patient information web page. NCH Healthcare Systems. 1999. Archived from the original on 2007-07-01. Retrieved 2007-06-17.
  92. 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.
  93. Syn NL, Teng MW, Mok TS, Soo RA (December 2017). "De-novo and acquired resistance to immune checkpoint targeting". The Lancet. Oncology. 18 (12): e731–e741. doi:10.1016/s1470-2045(17)30607-1. PMID   29208439.