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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Esophageal cancer may be due to either squamous cell carcinoma (ESCC) or adenocarcinoma (EAC). SCCs tend to occur closer to the mouth, while adenocarcinomas occur closer to the stomach. Dysphagia (difficulty swallowing, solids worse than liquids) and painful swallowing are common initial symptoms. If the disease is localized, surgical removal of the affected esophagus may offer the possibility of a cure. If the disease has spread, chemotherapy and radiotherapy are commonly used.
Ninety percent of cases of head and neck cancer (cancer of the mouth, nasal cavity, nasopharynx, throat and associated structures) are due to squamous cell carcinoma.
MCC usually presents as a firm, painless, nodule (up to 2 cm diameter) or mass (>2 cm diameter). These flesh-colored, red, or blue tumors typically vary in size from 0.5 cm (less than one-quarter of an inch) to more than 5 cm (2 inches) in diameter, and usually enlarge rapidly. Although MCC's may arise almost anywhere on the body, about half originate on sun-exposed areas of the head and neck, one-third on the legs, and about one-sixth on the arms. In about 12% of cases, no obvious anatomical site of origin ("primary site") can be identified.
Merkel-cell cancers tend to invade locally, infiltrating the underlying subcutaneous fat, fascia, and muscle, and typically metastasize early in their natural history, most often to the regional lymph nodes. MCCs also spread aggressively through the blood vessels, particularly to liver, lung, brain, and bone.
The early lesions are usually asymptomatic. The patients presenting with an advanced stage of the disease comprises around 66-77% of the cases.
The most important signs include a lump in the neck when palpated and weight loss.
People may also present with fatigue as a symptom.
The primary tumor does not have readily discernible signs or symptoms as they grow within the tonsillar capsule. It is difficult to notice anything suspicious on examination of the tonsil other than slight enlargement or the development of firmness around the area.
The carcinoma may occur in one or more sites deep within the tonsillar crypts. It may be accompanied by the enlargement of the tonsil. The affected tonsil grows into the oropharyngeal space making it noticeable by the patient in the form of a neck mass mostly in the jugulodiagastric region.
As the tonsils consist of a rich network of lymphatics, the carcinoma may metastasise to the neck lymph nodes which many are cystic.
Extension of tumor to skull or mediastinum can occur.
The additional symptoms include a painful throat, dysphagia, otalgia (due to cranial nerve involvement), foreign body sensation, bleeding, fixation of tongue (infiltration of deep muscles) and trismus (if the pterygoid muscle is involved in the parapharyngeal space).
On the other hand, the tumor may also present as a deep red or white fungating wound growing outwards, breaking the skin surface with a central ulceration. This wound-like ulcer fails to heal (non-healing) leading to bleeding and throat pain and other associated symptoms.
During biopsy, the lesion may show three signs: Gritty texture, Firmness and cystification owing to keratinization, fribrosis and necrosis respectively.
Cervical lymphydenopathy may be present.
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. The tumors frequently present at advanced stages, and around 70% of patients present with metastasis to the cervical lymph nodes.
The most common site for the incidence of the tumor is: the lateral wall of oropharynx 45%; base of the tongue 40%; posterior wall 10% and soft palate 5%. 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.
Main risk factors of developing carcinoma tonsil include tobacco smoking and regular intake of high amount of alcohol. It has also been linked to a virus called Human Papilloma Virus (HPV type HPV16). Other risk factors include poor maintenance of oral hygiene, a genetic predisposition leading to inclination towards development of throat cancer, immunocompromised states (such as post solid-organ transplant), and chronic exposure to agents such as asbestos and perchloroethylene in certain occupations, radiation therapy and dietary factors.
In its early stages, it can go unnoticed. It can be painless with slight physical changes. But the precursor tissue changes, can be noticed by the doctors.
Early stage symptoms can include persistent red or white patches, a non-healing ulcer, progressive swelling or enlargement, unusual surface changes, sudden tooth mobility without apparent cause, unusual oral bleeding or epitaxis and prolonged hoarseness.
Late stage symptoms can include an indurated area, paresthesia or dysesthesia of the tongue or lips, airway obstruction, chronic serous otitis media, otalgia, trismus, dysphagia, cervical lymphadenopathy, persistent pain or referred pain and altered vision.
The symptoms of laryngeal cancer depend on the size and location of the tumour. Symptoms may include the following:
- Hoarseness or other voice changes
- A lump in the neck
- A sore throat or feeling that something is stuck in the throat
- Persistent cough
- Stridor - a high-pitched wheezing sound indicative of a narrowed or obstructed airway
- Bad breath
- Earache (""referred"")
- Difficulty swallowing
Treatment effects can include post-operative changes in appearance, difficulty eating, or loss of voice that may require learning alternate methods of speaking.
Swelling of the lymph nodes in the neck is the initial presentation in many people, and the diagnosis of NPC is often made by lymph node biopsy. Signs and symptoms related to the primary tumor include trismus, pain, otitis media, nasal regurgitation due to paresis (loss of or impaired movement) of the soft palate, hearing loss and cranial nerve palsy (paralysis). Larger growths may produce nasal obstruction or bleeding and a "nasal twang". Metastatic spread may result in bone pain or organ dysfunction. Rarely, a paraneoplastic syndrome of osteoarthropathy (diseases of joints and bones) may occur with widespread disease.
Merkel-cell carcinoma (MCC) is a rare and highly aggressive skin cancer, which, in most cases, is caused by the Merkel cell polyomavirus (MCV) discovered by scientists at the University of Pittsburgh in 2008. It is also known as cutaneous APUDoma, primary neuroendocrine carcinoma of the skin, primary small cell carcinoma of the skin, and trabecular carcinoma of the skin.
Approximately 80% of Merkel-cell carcinomas are caused by MCV. The virus is clonally integrated into the cancerous Merkel cells. In addition, the virus has a particular mutation only when found in cancer cells, but not when it is detected in healthy skin cells. Direct evidence for this oncogenetic mechanism comes from research showing that inhibition of production of MCV proteins causes MCV-infected Merkel carcinoma cells to die but has no effect on malignant Merkel cells that are not infected with this virus. MCV-uninfected tumors, which account for approximately 20% of Merkel-cell carcinomas, appear to have a separate and as-yet unknown cause. These tumors tend to have extremely high genome mutation rates, due to ultraviolet light exposure, whereas MCV-infected Merkel cell carcinomas have low rates of genome mutation. No other cancers have been confirmed so far to be caused by this virus. Because of the viral origin for this cancer, immunotherapies are a promising avenue for research to treat virus-positive Merkel-cell carcinoma.
This cancer is considered to be a form of neuroendocrine tumor. While patients with a small tumor (less than 2 cm) that has not yet metastasized to regional lymph nodes have an expected 5-year survival rate of more than 80 percent, once a lesion has metastasized regionally, the rate drops to about 50 percent. Up to half of patients that have been seemingly treated successfully (i.e. that initially appear cancer-free) subsequently suffer a recurrence of their disease. Recent reviews cite an overall 5-year survival rate of about 60% for all MCC combined.
Merkel-cell carcinoma occurs most often on the sun-exposed face, head, and neck.
SCC of the skin begins as a small nodule and as it enlarges the center becomes necrotic and sloughs and the nodule turns into an ulcer.
- The lesion caused by SCC is often asymptomatic
- Ulcer or reddish skin plaque that is slow growing
- Intermittent bleeding from the tumor, especially on the lip
- The clinical appearance is highly variable
- Usually the tumor presents as an ulcerated lesion with hard, raised edges
- The tumor may be in the form of a hard plaque or a papule, often with an opalescent quality, with tiny blood vessels
- The tumor can lie below the level of the surrounding skin, and eventually ulcerates and invades the underlying tissue
- The tumor commonly presents on sun-exposed areas (e.g. back of the hand, scalp, lip, and superior surface of pinna)
- On the lip, the tumor forms a small ulcer, which fails to heal and bleeds intermittently
- Evidence of chronic skin photodamage, such as multiple actinic keratoses (solar keratoses)
- The tumor grows relatively slowly
Laryngeal cancer, also known as cancer of the larynx or laryngeal carcinoma, are mostly squamous cell carcinomas, reflecting their origin from the skin of the larynx.
Cancer can develop in any part of the larynx, but the cure rate is affected by the location of the tumour. For the purposes of tumour staging, the larynx is divided into three anatomical regions: the glottis (true vocal cords, anterior and posterior commissures); the supraglottis (epiglottis, arytenoids and aryepiglottic folds, and false cords); and the subglottis.
Most laryngeal cancers originate in the glottis. Supraglottic cancers are less common, and subglottic tumours are least frequent.
Laryngeal cancer may spread by direct extension to adjacent structures, by metastasis to regional cervical lymph nodes, or more distantly, through the blood stream. Distant metastases to the lung are most common. In 2013 it resulted in 88,000 deaths up from 76,000 deaths in 1990. Five year survival rates in the United States are 60%.
Nasopharyngeal carcinoma, commonly known as nasopharyngeal cancer, is classified as a malignant neoplasm, or cancer, arising from the mucosal epithelium of the nasopharynx, most often within the "lateral nasopharyngeal recess" or "fossa of Rosenmüller" (a recess behind the entrance of the eustachian tube opening). The World Health Organization classifies nasopharyngeal carcinoma in three types. Type 1 (I) is keratinizing squamous cell carcinoma. Type 2a (II) is non-keratinizing squamous cell carcinoma. Type 2b (III) is undifferentiated carcinoma. Type 2b (III) nonkeratinizing undifferentiated form also known as lymphoepithelioma is most common, and is most strongly associated with Epstein-Barr virus infection of the cancerous cells.
Individuals with a basal-cell carcinoma typically present with a shiny, pearly skin nodule. However, superficial basal-cell cancer can present as a red patch similar to eczema. Infiltrative or morpheaform basal-cell cancers can present as a skin thickening or scar tissue – making diagnosis difficult without using tactile sensation and a skin biopsy. It is often difficult to visually distinguish basal-cell cancer from acne scar, actinic elastosis, and recent cryodestruction inflammation.
Head and neck cancers are malignant neoplasms that arise in the head and region which comprises nasal cavity, paranasal sinuses, oral cavity, salivary glands, pharynx, and larynx. Majority of head and neck cancers histologically belong to squamous cell type and hence they are categorized as Head and Neck Squamous Cell Carcinoma (abbreviated as HNSCC)[Forastiere AA, 2003]. HNSCC are the 6th most common cancers worldwide and 3rd most common cancers in developing world. They account for ~ 5% of all malignancies worldwide (Ferlay J, 2010) and 3% of all malignancies in the United States (Siegel R, 2014).
Risk factors include tobacco consumption (chewing or smoking), alcohol consumption, Epstein-Barr virus (EBV) infection, human papilloma virus (HPV; esp. HPV 16, 18) infection, betel nut chewing, wood dust exposures, consumption of certain salted fish and others (NCI Factsheet, 2013). EBV infection has been specifically associated with nasopharyngeal cancer. Reverse smoking was considered as a risk factor for oral cancer. Interestingly, "Cis-retinoic acid" (i.e. supplements of retinoic acid) intake may increase the risk of HNSCC in active smokers. Low consumption of fruits and vegetables was associated with higher incidence of HNSCC.
HNSCC classification: Based on the HPV infection status, head and neck cancers are classified into HPV-positive and HPV-negative categories. So far, this is the only available molecular classification. Majority (>50%) of oral cancers are HPV-positive in the U.S. HPV-positive oral cancers are widely prevalent in younger patients and are associated with multiple sexual partners and oral sexual practices. HPV-positive cancers have better prognosis, especially for nonsmokers as compared to HPV-negative cancers.
Staging and grading of HNSCC: HNSCC are classified according to the tumor-node-metastasis (TNM) system of American Joint Committee on cancer. TNM staging system for HNSCC are discussed else where.
Symptoms include lump or sore, sore throat, hoarse of voice, difficulty in swallowing etc (NCI Factsheet, 2013).
Treatment for HNSCC is predominantly based on the stage of the disease. Factors such as patient fitness, baseline swallow, airway functional status, and others are considered before determining the treatment plan. Standard of care for HNSCC includes one or combination of the following: surgery, radiation, chemotherapeutic agents such as Cisplatin, 5-Flurouracil (5-FU) etc. Molecularly targeted therapies were developed since the discovery of role of epidermal growth factor receptor (EGFR) signaling in HNSCC development, progression and prognosis. These targeted therapies include monoclonal antibodies (such as cetuximab, panitumumab etc.) and tyrosine kinase inhibitors (such as erlotinib, gefitinib, etc.). Among these EGFR-targeting agents, only cetuximab has been approved by FDA in 2006 for HNSCC treatment.
Ninety percent (MacMillan, 2015) of cases of head and neck cancer (cancer of the mouth, nasal cavity, nasopharynx, throat and associated structures) are due to squamous cell carcinoma. Symptoms may include a poorly healing mouth ulcer, a hoarse voice or other persistent problems in the area. Treatment is usually with surgery (which may be extensive) and radiotherapy. Risk factors include smoking, alcohol consumption and hematopoietic stem cell transplantation (Elad S, Zadik Y, Zeevi I, et al., 2010, pp. 1243–1244). In addition, recent studies show that about 25% of mouth and 35% of throat cancers are associated with HPV. The 5 year disease free survival rate for HPV positive cancer is significantly higher when appropriately treated with surgery, radiation and chemotherapy as compared to non-HPV positive cancer, substantiated by multiple studies including research conducted by Maura Gillison, "et al." of Johns Hopkins Sidney Kimmel Cancer Center.
Basal cell carcinoma can be divided into three groups, based on the growth patterns.
1. Superficial basal cell carcinoma, formerly referred to in-situ basal cell carcinoma, is characterized by a superficial proliferation of neoplastic basal cells. This tumor is generally responsive to topic chemotherapy, such as Aldara (Imiquimod), or Fluorouracil.
2. Infiltrative basal cell carcinoma, that also encompasses morpheaform and micronodular basal cell cancer, is more difficult to treat with conservative methods, given its tendency to penetrate into deeper layers of the skin.
3. Nodular basal cell carcinoma includes most of the remaining categories of basal-cell cancer. It is not unusual to encounter heterogeneous morphologic features within the same tumor.
Throat cancer usually begins with symptoms that seem harmless enough, like an enlarged lymph node on the outside of the neck, a sore throat or a hoarse sounding voice. However, in the case of throat cancer, these conditions may persist 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 be a persistent earache. Other possible but less common symptoms include some numbness or paralysis of the face muscles.
Presenting symptoms include :
- Mass in the neck
- Neck pain
- Bleeding from the mouth
- Sinus congestion, especially with nasopharyngeal carcinoma
- Bad breath
- Sore tongue
- Painless ulcer or sores in the mouth that do not heal
- White, red or dark patches in the mouth that will not go away
- Earache
- Unusual bleeding or numbness in the mouth
- Lump in the lip, mouth or gums
- Enlarged lymph glands in the neck
- Slurring of speech (if the cancer is affecting the tongue)
- Hoarse voice which persists for more than six weeks
- Sore throat which persists for more than six weeks
- Difficulty swallowing food
- Change in diet or weight loss
Like other cancers arising in the head and neck region, HPV+OPC may be an asymptomatic incidental finding of an abnormality in the mouth, by the patient or a health professional, present with local symptoms such as difficulties with speech, swallowing, and breathing as well as pain and infection, or as a swelling in the neck if the cancer has spread to lymph nodes there. These may be accompanied by more general symptoms such as loss of appetite, weight loss and weakness.
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."
Most patients with verrucous carcinoma have a good prognosis. Local recurrence is not uncommon, but metastasis to distant parts of the body is rare. Patients with oral verrucous carcinoma may be at greater risk of a second oral squamous cell carcinoma, for which the prognosis is worse.
Verrucous carcinoma may occur in various head and neck locations, as well as in the genitalia. The oral cavity is the most common site of this tumor. The ages range from 50 to 80 years with a male predominance and a median age of 67 years. VC may grow large in size, resulting in the destruction of adjacent tissue, such as bone and cartilage.
The diagnosis of VC is established by close communication between surgeons and pathologists.
Surgeons must provide adequate specimens including the full thickness of the tumors and adjacent uninvolved mucosa for correct diagnoses.
Surgery is considered as the treatment of choice, but the extent of surgical margin and the adjuvant radiotherapy are still controversial.
The major risk factors are cigarette smoking and alcohol consumption, while betel nut is an additional factor in Taiwan. Different gene mutation sites in head and neck cancer between western countries and Taiwan have been reported. The presentation of VC originated from exposure to different carcinogens may not be the same.
Oral cancer, also known as mouth cancer, is a type of head and neck cancer and is any cancerous tissue growth located in the oral cavity.
It may arise as a primary lesion originating in any of the tissues in the mouth, by metastasis from a distant site of origin, or by extension from a neighboring anatomic structure, such as the nasal cavity. Alternatively, the oral cancers may originate in any of the tissues of the mouth, and may be of varied histologic types: teratoma, adenocarcinoma derived from a major or minor salivary gland, lymphoma from tonsillar or other lymphoid tissue, or melanoma from the pigment-producing cells of the oral mucosa. There are several types of oral cancers, but around 90% are squamous cell carcinomas, originating in the tissues that line the mouth and lips. Oral or mouth cancer most commonly involves the tongue. It may also occur on the floor of the mouth, cheek lining, gingiva (gums), lips, or palate (roof of the mouth). Most oral cancers look very similar under the microscope and are called squamous cell carcinoma, but less commonly other types of oral cancer occur, such as Kaposi's sarcoma.
In 2013 oral cancer resulted in 135,000 deaths up from 84,000 deaths in 1990. Five-year survival rates in the United States are 63%.
Salivary gland–like carcinomas of the lung generally refers a class of rare cancers that arise from the uncontrolled cell division (mitosis) of mutated cancer stem cells in lung tissue. They take their name partly from the appearance of their abnormal cells, whose structure and features closely resemble those of cancers that form in the major salivary glands (parotid glands, submandibular glands and sublingual glands) of the head and neck. Carcinoma is a term for malignant neoplasms derived from cells of epithelial lineage, and/or that exhibit cytological or tissue architectural features characteristically found in epithelial cells.
This class of primary lung cancers contains several histological variants, including mucoepidermoid carcinoma of the lung, adenoid cystic carcinoma of the lung, epithelial-myoepithelial carcinoma of the lung, and other (even more rare) variants. .
Most cases (80%) of squamous cell carcinoma attributed to ultraviolet radiation present in areas of the skin that are usually more exposed to sunlight (e.g., head, face, neck). Although a particular form of squamous cell carcinoma, Kangri cancer is more often associated with the abdomen, thigh, and leg regions due to the usage and positioning of kangri pots, which come in close contact with these anatomical features.
Over time, the use of Kangri pots to keep warm results in erythema ab igne, a precancerous keratotic growth that “take the shape of superficial, serpegenous, reticular blackish brown colored lesions.” Eventually, the cells at the lesion site become more irregular in shape and form; the lesions “ulcerate” and may become itchy and bloody. The resulting irregular growth is the presentation of Kangri cancer.
Human papillomavirus-positive oropharyngeal cancer (HPV+OPC) is a subtype of oropharyngeal squamous cell carcinomas (OSCC), associated with the human papillomavirus type 16 virus (HPV16). Historically, cancer of the throat oropharynx (throat) was associated with the use of alcohol and tobacco, but the majority of cases are now associated with the HPV virus. HPV+OPC differs in a number of respects from OPC not associated with HPV (HPV-OPC), and is considered a separate disease. HPV has long been associated with cancers in the anogenital region, but in 2007 it was also recognized as a cause of oropharyngeal cancer. HPV is common among healthy adults and is largely transmitted through sexual contact, but tobacco use increases the risk of cancer.
Detection of a tumour suppressor protein, known as p16, is commonly used to diagnose an HPV associated OPC. The extent of disease is described in the standard cancer staging system, using the AJCC TNM system, based on the T stage (size and extent of tumour), N stage (extent of involvement of regional lymph nodes) and M stage (whether there is spread of the disease outside the region or not), and combined into an overall stage from I–IV. In 2016, a separate staging system was developed for HPV+OPC, distinct from HPV-OPC.
The historical treatment of OPC was surgical, with an approach through the neck and splitting of the jaw bone, which resulted in a considerable risk of death. Later, radiotherapy with or without the addition of chemotherapy, provided a less invasive alternative, and the results in terms of treating the cancer, were comparable. Newer minimally invasive surgical techniques through the mouth have improved outcomes, and surgery is often followed by radiation and or chemotherapy in high risk cases. In the absence of high quality evidence, management decisions are often based on technical factors, likely functional loss and the persons preferences. Some HPV+OPC may first appear in lymph nodes in the neck, without an obvious source (cancer of unknown primary origin) but removal of tonsil tissue from the oropharynx will often show hidden disease. The presence of HPV in the tumour is associated with a better response to treatment and a better outcome, independent of the treatment methods used and a nearly 60% reduced risk of dying from the cancer. Most recurrence occurs locally and within the first year after treatment. The use of tobacco decreases the chances of survival. While most head and neck cancer has been declining with reduced smoking rates, HPV+OPC has been increasing. Compared to HPV-OPC patients, HPV+OPC patients tend to be younger, have a higher socioeconomic status and are less likely to smoke. In addition they tend to have smaller tumours, but are more likely to have involvement of the cervical lymph nodes. In the United States and other countries, the number of cases of oropharyngeal cancer has been increasing steadily, with the incidence of HPV+OPC increasing faster than the decline in HPV-OPC. The increase is seen particularly in young men in developed countries, and HPV+OPC now accounts for the majority of all OPC cases.
Attempts are being made to reduce the incidence of HPV+OPC by introducing vaccination that includes HPV types 16 and 18, found in 95% of these cancers, prior to exposure to the virus. Early data suggest a reduction in infection rates.
Lung cancer is a large and exceptionally heterogeneous family of malignancies. Over 50 different histological variants are explicitly recognized within the 2004 revision of the World Health Organization (WHO) typing system ("WHO-2004"), currently the most widely used lung cancer classification scheme. Many of these entities are rare, recently described, and poorly understood. However, since different forms of malignant tumors generally exhibit diverse genetic, biological, and clinical properties — including response to treatment — accurate classification of lung cancer cases are critical to assuring that patients with lung cancer receive optimum management.
Under WHO-2004, lung carcinomas are divided into 8 major taxa:
- Squamous cell carcinoma
- Small cell carcinoma
- Adenocarcinoma
- Large cell carcinoma
- Adenosquamous carcinoma
- Sarcomatoid carcinoma
- Carcinoid tumor
- Salivary gland-like carcinoma
In the United States, about 20-30 cases are reported each year. This may be a gross underestimate of the total number of cases as few laboratories have the reagents and expertise to make the diagnosis. The symptoms are similar to other forms of cancer and dependent on the stage. While generalized symptoms (weight loss and fatigue) may be seen, site specific symptoms are also present. If the tumor involves the head and neck region (in about 35%), then pain, a mass, obstructive symptoms, among others, may be experienced. NUT midline carcinomas are not specific to any tissue type or organ.
Common sites include the head, neck and mediastinum. The median age at diagnosis is 17 years, but older patients may be affected.
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.