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Head and neck cancer is a general term encompassing multiple that can develop in the head and neck region. These include cancers of the mouth, tongue, gums and lips (oral cancer), voice box (Laryngeal cancer), throat (nasopharyngeal, oropharyngeal, hypopharyngeal), salivary glands, nose and sinuses.
Head and neck cancer can present a wide range of symptoms depending on where the cancer developed. These can include an Mouth ulcer that does not heal, Hoarse voice, Dysphagia, Leukoplakia, and a Neck mass.
The majority of head and neck cancer is caused by the use of alcohol or tobacco (including smokeless tobacco). An increasing number of cases are caused by the human papillomavirus (HPV). Other risk factors include the Epstein–Barr virus, chewing betel quid (paan), radiation exposure, poor nutrition and workplace exposure to certain toxic substances. About 90% are pathologically classified as squamous cell cancers. (2025). 9789283204299, World Health Organization. ISBN 9789283204299 The diagnosis is confirmed by a Biopsy. The degree of surrounding tissue invasion and distant spread may be determined by medical imaging and .
Not using tobacco or alcohol can reduce the risk of head and neck cancer. Regular dental examinations may help to identify signs before the cancer develops. The HPV vaccine helps to prevent HPV-related oropharyngeal cancer. Treatment may include a combination of surgery, radiation therapy, chemotherapy, and targeted therapy. In the early stage head and neck cancers are often curable but 50% of people see their doctor when they already have an advanced disease.
Globally, head and neck cancer accounts for 650,000 new cases of cancer and 330,000 deaths annually on average. In 2018, it was the seventh most common cancer worldwide, with 890,000 new cases documented and 450,000 people dying from the disease. The usual age at diagnosis is between 55 and 65 years old. The average 5-year survival following diagnosis in the developed world is 42–64%.
Symptoms predominantly include a sore on the face or oral cavity that does not heal, trouble swallowing, or a change in voice. In those with advanced disease, there may be unusual bleeding, facial pain, numbness or swelling, and visible lumps on the outside of the neck or oral cavity. Head and neck cancer often begins with benign signs and symptoms of the disease, like an enlarged lymph node on the outside of the neck, a Hoarse 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 Ear pain. (2025). 9780080533841, Academic Press. ISBN 9780080533841
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.
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.
People with oropharyngeal carcinomas are at high risk of developing a second primary head and neck cancer.
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.
Most tumors of the salivary glands differ from the common head and neck cancers in cause, histopathology, clinical presentation, and therapy. Other uncommon tumors arising in the head and neck include , adenocarcinomas, adenoid cystic carcinomas, and mucoepidermoid carcinomas. (2025). 9781891483622, Cmp United Business Media. ISBN 9781891483622 Rarer still are melanomas and lymphomas of the upper aerodigestive tract.
There is thought to be a dose-dependent relationship between alcohol use and development of head and neck cancer where higher rates of alcohol consumption contribute to an increased risk of developing head and neck cancer. Alcohol use following a diagnosis of head and neck cancer also contributes to other negative outcomes. These include physical effects such as an increased risk of developing a second primary cancer or other malignancies, cancer recurrence, and worse prognosis in addition to an increased chance of having a future feeding tube placed and osteoradionecrosis of the jaw. Negative social factors are also increased with sustained alcohol use after diagnosis including unemployment and work disability.
The way in which alcohol contributes to cancer development is not fully understood. It is thought to be related to permanent damage of DNA strands by a metabolite of alcohol called acetaldehyde. Other suggested mechanisms include nutritional deficiencies and genetic variations.
Tobacco smoking is one of the main risk factors for head and neck cancer. Cigarette smokers have a lifetime increased risk for head and neck cancer that is 5 to 25 times higher than the general population. The ex-smoker's risk of developing head and neck cancer begins to approach the risk in the general population 15 years after smoking cessation. In addition, people who smoke have a worse prognosis than those who have never smoked. Furthermore, people who continue to smoke after diagnosis of head and neck cancer have the highest probability of dying compared to those who have never smoked. This effect is seen in patients with HPV-positive head and neck cancer as well. It has also been demonstrated that passive smoking, both at work and at home, increases the risk of head and neck cancer.
A major carcinogenic compound in tobacco smoke is acrylonitrile. Acrylonitrile appears to indirectly cause DNA damage by increasing oxidative stress, leading to increased levels of 8-oxo-2'-deoxyguanosine (8-oxo-dG) and formamidopyrimidine in DNA. (see image). Both 8-oxo-dG and formamidopyrimidine are . DNA glycosylase NEIL1 prevents mutagenesis by 8-oxo-dG and removes formamidopyrimidines from DNA.
Smokeless tobacco (including products where tobacco is Chewing tobacco) is a cause of oral cancer. Increased risk of oral cancer caused by smokeless tobacco is present in countries such as the United States but particularly prevalent in Southeast Asia where the use of smokeless tobacco is common. Smokeless tobacco is associated with a higher risk of developing head and neck cancer due to the presence of the tobacco-specific carcinogen N'-nitrosonornicotine.
Cigar and pipe smoking are also important risk factors for oral cancer. They have a dose dependent relationship with more consumption leading to higher chances of developing cancer. The use of electronic cigarettes may also lead to the development of head and neck cancers due to the substances like propylene glycol, glycerol, , and metals contained therein, which can cause damage to the airways. Exposure to e-vapour has been shown to reduce cell viability and increase the rate of cell death via apoptosis or necrosis with or without nicotine. This area of study requires more research, however. Similarly, additional research is needed to understand how marijuana possibly promotes head and neck cancers. A 2019 meta-analysis did not conclude that marijuana was associated with head and neck cancer risk. Yet individuals with cannabis use disorder were more likely to be diagnosed with such cancers in a large study published 2024.
In terms of nutritional supplements, antioxidants such as vitamin E and beta-carotene might reduce the toxic effect of radiotherapy in people with head and neck cancer but they can also increase recurrence rates, especially in smokers.
The incidence of HPV-related head and neck cancer is increasing, especially in the Western world. In the United States, the incidence of HPV-positive oropharyngeal cancer has overtaken HPV-positive cervical cancer as the leading HPV related cancer type. An increased incidence has particularly affected males. As a result, recent changes have resulted in the HPV vaccine being offered to adolescent boys between 12 and 13 (previously only offered to girls between this age due to cervical cancer risks) and men under 45 who have sex with men in the UK.
Over 20 different high-risk HPV subtypes have been implicated in causing head and neck cancer. In particular, HPV-16 is responsible for up to 90% of oropharyngeal cancer in North America. Approximately 15–25% of head and neck cancers contain genomic DNA from HPV, and the association varies based on the site of the tumor. In the case of HPV-positive oropharyngeal cancer, the highest distribution is in the tonsils, where HPV DNA is found in 45–67% of the cases, and it is less often in the hypopharynx (13–25%), and least often in the oral cavity (12–18%) and larynx (3–7%).
Positive HPV16 status is associated with an improved prognosis over HPV-negative oropharyngeal cancer due to better response to radiotherapy and chemotherapy.
HPV can induce tumors by several mechanisms:
There are observed biological differences between HPV-positive and HPV-negative head and neck cancer, for example in terms of mutation patterns. In HPV-negative disease, genes frequently mutated include TP53, CDKN2A and PIK3CA. In HPV-positive disease, these genes are less frequently mutated, and the tumour suppressor gene p53 and pRb (protein retinoblastoma) are commonly inactivated by HPV oncoproteins E6 and E7 respectively. In addition, viral infections such as HPV can cause aberrant DNA methylation during cancer development. HPV-positive head and neck cancers demonstrate higher levels of such DNA methylation compared to HPV-negative disease.
E6 sequesters p53 to promote p53 degradation, while E7 inhibits pRb. Degradation of p53 results in cells being unable to respond to checkpoint signals that are normally present to activate apoptosis when DNA damage is signalled. Loss of pRb leads to deregulation of cell proliferation and apoptosis. Both mechanisms therefore leave cell proliferation unchecked and increase the chance of carcinogenesis.
A person usually presents to the physician complaining of one or more of the typical symptoms. These symptoms may be site specific (such as a laryngeal cancer causing hoarse voice), or not site specific (earache can be caused by multiple types of head and neck cancers).
The physician will undertake a thorough history to determine the nature of the symptoms and the presence or absence of any risk factors. The physician will also ask about other illnesses such as heart or lung diseases as they may impact their fitness for potentially curative treatment. Clinical examination will involve examination of the neck for any masses, examining inside the mouth for any abnormalities and assessing the rest of the pharynx and larynx with a Nasoendoscopy.
Further investigations will be directed by the symptoms discussed and any abnormalities identified during the exam.
typically undergo assessment with ultrasound and a fine-needle aspiration (FNA, a type of needle biopsy). Concerning that are readily accessible (such as in the mouth) can be biopsied with a Local anesthetic. Lesions less readily available can be biopsied either with the patient awake or under a general anaesthetic depending on local expertise and availability of specialist equipment.
The cancer will also need to be Cancer staging (accurately determine its size, association with nearby structures, and spread to distant sites). This is typically done by scanning the patient with a combination of magnetic resonance imaging (MRI), CT scan (CT) and/or positron emission tomography (PET). Exactly which investigations are required will depend on a variety of factors such as the site of concern and the size of the tumour.
Some people will present with a neck lump containing cancer cells (identified by FNA) that have spread from elsewhere, but with no identifiable primary site on initial assessment. In such cases people will undergo additional testing to attempt to find the initial site of cancer, as this has significant implications for their treatment. These patients undergo MRI scanning, PET-CT and then Endoscopy and Biopsy of any abnormal areas. If the scans and panendoscopy still do not identify a primary site for the cancer, affected people will undergo a bilateral tonsillectomy and tongue base mucosectomy (as these are the most common subsites of cancer that spread to the neck). This procedure can be done with or without robotic assistance.
Once a diagnosis is confirmed, a multidisciplinary discussion of the optimal treatment strategy will be undertaken between the radiation oncologist, surgical oncologist, and medical oncology. A Histopathology and a Radiology will also be present to discuss the biopsy and imaging findings. Most (90%) cancers of the head and neck are squamous cell-derived, termed "head-and-neck squamous-cell carcinomas".
All squamous cell carcinomas arising from the oropharynx, and all neck node Metastasis of unknown primary should undergo testing for HPV status. This is essential to adequately stage the tumour and adequately plan treatment. Due to the different biology of HPV positive and negative cancers, differentiating HPV status is also important for ongoing research to determine the best treatments.
Nasopharyngeal carcinomas, or neck node metastases possibly arising from the nasopharynx will also be tested for Ebstein Barr virus.
The tumor marker Cyfra 21-1 may be useful in diagnosing squamous cell carcinoma of the head and neck (SCCHN).
Regular dental examinations may identify pre-cancerous lesions in the oral cavity. While Cancer screening in the general population does not appear to be useful, screening high-risk groups by examination of the throat might be useful. Head and neck cancer is often curable if it is diagnosed early; however, outcomes are typically poor if it is diagnosed late.
When diagnosed early, oral, head, and neck cancers can be treated more easily, and the chances of survival increase tremendously. The HPV vaccine helps to prevent the development of HPV-related oropharyngeal cancer.
After a histologic diagnosis has been established and tumor extent determined, such as with the use of PET-CT, the selection of appropriate treatment for a specific cancer depends on a complex array of variables, including tumor site, relative morbidity of various treatment options, concomitant health problems, social and logistic factors, previous primary tumors, and the person's preference. Treatment planning generally requires a multidisciplinary approach involving specialist surgeons, medical oncologists, and radiation oncologists.
Surgical resection and radiation therapy are the mainstays of treatment for most head and neck cancers and remain the standard of care in most cases. For small primary cancers without regional metastases (stage I or II), wide surgical excision alone or curative radiation therapy alone is used. For more extensive primary tumors or those with regional metastases (stage III or IV), planned combinations of pre- or postoperative radiation and complete surgical excision are generally used. More recently, as historical survival and control rates have been recognized as less than satisfactory, there has been an emphasis on the use of various induction or concomitant chemotherapy regimens.
CO2 laser surgery is also another form of treatment. Transoral laser microsurgery allows surgeons to remove tumors from the voice box with no external incisions. It also allows access to tumors that are not reachable with robotic surgery. During the surgery, the surgeon and pathologist work together to assess the adequacy of excision ("margin status"), minimizing the amount of normal tissue removed or damaged. This technique helps give the person as much speech and swallowing function as possible after surgery.[1]
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 head and neck cancer.
While not specifically a chemotherapy, amifostine is often administered intravenously by a chemotherapy clinic prior to IMRT radiotherapy sessions. Amifostine protects the gums and from the effects of radiation.
There is no evidence that erythropoietin should be routinely given with radiotherapy.
Cetuximab is used for treating people with advanced-stage cancer who cannot be treated with conventional chemotherapy (cisplatin). However, cetuximab's efficacy is still under investigation by researchers.
Gendicine is a gene therapy that employs an Adenoviridae to deliver the tumor suppressor gene p53 to cells. It was approved in China in 2003 for the treatment of head and neck cancer.
The mutational profiles of HPV+ and HPV- head and neck cancer have been reported, further demonstrating that they are fundamentally distinct diseases.
In 2016, the FDA granted accelerated approval to pembrolizumab for the treatment of people with recurrent or metastatic head and neck cancer with disease progression on or after platinum-containing chemotherapy. Later that year, the FDA approved nivolumab for the treatment of recurrent or metastatic head and neck cancer with disease progression on or after platinum-based chemotherapy. In 2019, the FDA approved pembrolizumab for the first-line treatment of metastatic or unresectable recurrent head and neck cancer.
Consensus panels in America (AJCC) and Europe (UICC) have established staging systems for head and neck cancers. These staging systems attempt to standardize clinical trial criteria for research studies and define prognostic categories of disease. Head and neck cancers are staged according to the TNM classification system, where T is the size and configuration of the tumor, N is the presence or absence of lymph node metastases, and M is the presence or absence of distant metastases. The T, N, and M characteristics are combined to produce a "stage" of the cancer, from I to IVB.
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. 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.
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. The high symptom burden patients' experience necessitates complex caregiver roles, often requiring hospital staff training, which caregivers can find distressing when asked to do so for the first time. It is becoming increasingly apparent that caregivers (most often spouses, children, or close family members) might not be adequately informed about, prepared for, or trained for the tasks and roles they will encounter during the treatment and recovery phases of this unique patient population, which span both technical and emotional support. Of note, caregivers of patients who report lower quality of life demonstrate increased burden and fatigue that extend beyond the treatment phase.
Examples of technically difficult caregiver duties include tube feeding, oral suctioning, wound maintenance, medication delivery safe for tube feeding, and troubleshooting home medical equipment. If the cancer affects the mouth or larynx, caregivers must also find a way to effectively communicate among themselves and with their healthcare team. This is in addition to providing emotional support for the person undergoing cancer therapy.
]] Globally, head and neck cancer accounts for 650,000 new cases of cancer and 330,000 deaths annually on average. In 2018, it was the seventh most common cancer worldwide, with 890,000 new cases documented and 450,000 people dying from the disease. The risk of developing head and neck cancer increases with age, especially after 50 years. Most people who do so are between 50 and 70 years old.
In North America and Europe, the tumors usually arise from the oral cavity, oropharynx, or larynx, whereas nasopharyngeal cancer is more common in the Mediterranean countries and in the Far East. In Southeast China and Taiwan, head and neck cancer, specifically nasopharyngeal cancer, is the most common cause of death in young men.
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