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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)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
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.
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.
Vaginal squamous cell carcinoma spreads slowly and usually stays near the vagina, but may spread to the lungs and liver. This is the most common type of vaginal cancer.
Penile cancer arises from precursor lesions, which generally progress from low-grade to high-grade lesions. For HPV related penile cancers this sequence is as follows:
- A. Squamous hyperplasia;
- B. Low-grade penile intraepithelial neoplasia (PIN);
- C. High-grade PIN (carcinoma in situ—Bowen's disease, Erythroplasia of Queyrat and bowenoid papulosis (BP));
- D. Invasive Carcinoma of the Penis.
However, in some cases non-dysplastic or mildly dysplastic lesions may progress directly into cancer. Examples include flat penile lesions (FPL) and condylomata acuminata.
In HPV negative cancers the most common precursor lesion is lichen sclerosus (LS).
Like many malignancies, penile cancer can spread to other parts of the body. It is usually a primary malignancy, the initial place from which a cancer spreads in the body. Much less often it is a secondary malignancy, one in which the cancer has spread to the penis from elsewhere. The staging of penile cancer is determined by the extent of tumor invasion, nodal metastasis, and distant metastasis.
The T portion of the AJCC TNM staging guidelines are for the primary tumor as follows:
- TX: Primary tumor cannot be assessed.
- T0: No evidence of primary tumor.
- Tis: Carcinoma "in situ".
- Ta: Noninvasive verrucous carcinoma.
- T1a: Tumor invades subepithelial connective tissue without lymph vascular invasion and is not poorly differentiated (i.e., grade 3–4).
- T1b: Tumor invades subepithelial connective tissue with lymph vascular invasion or is poorly differentiated.
- T2: Tumor invades the corpus spongiosum or cavernosum.
- T3: Tumor invades the urethra or prostate.
- T4: Tumor invades other adjacent structures.
Anatomic Stage or Prognostic Groups of penile cancer are as follows:
- Stage 0—Carcinoma "in situ".
- Stage I—The cancer is moderately or well differentiated and only affects the subepithelial connective tissue.
- Stage II—The cancer is poorly differentiated, affects lymphatics, or invades the corpora or urethra.
- Stage IIIa—There is deep invasion into the penis and metastasis in one lymph node.
- Stage IIIb—There is deep invasion into the penis and metastasis into multiple inguinal lymph nodes.
- Stage IV—The cancer has invaded into structures adjacent to the penis, metastasized to pelvic nodes, or distant metastasis is 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.
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.
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 possible signs of oropharyngeal cancer are:
- A sore throat that persists
- Pain or difficulty with swallowing
- Unexplained weight loss
- Voice changes
- Ear pain
- A lump in the back of the throat or mouth
- A lump in the neck
- A dull pain behind the sternum
- Cough
Many malignancies can develop in vulvar structures. The signs and symptoms can include:
- Itching, burn, or bleeding on the vulva that does not go away.
- Changes in the color of the skin of the vulva, so that it looks redder or whiter than is normal.
- Skin changes in the vulva, including what looks like a rash or warts.
- Sores, lumps, or ulcers on the vulva that do not go away.
- Pain in the pelvis, especially during urination or sex.
Typically, a lesion presents in the form of a lump or ulcer on the labia majora and may be associated with itching, irritation, local bleeding or discharge, in addition to pain with urination or pain during sexual intercourse. The labia minora, clitoris, perineum and mons are less commonly involved. Due to modesty or embarrassment, patients may put off seeing a doctor.
Melanomas tend to display the typical asymmetry, uneven borders and dark discoloration as do melanomas in other parts of the body.
Adenocarcinoma can arise from the Bartholin gland and present with a painful lump.
Basal cell carcinoma makes up about 1–2% of vulvar cancer. These tend to be slow-growing lesions on the labia majora but can occur anywhere on the vulva. Their behavior is similar to basal cell cancers in other locations. They often grow locally and have low risk for deep invasion or metastasis.
Treatment involves excision, but these lesions have a tendency to recur if not completely removed.
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.
Symptoms of anal cancer can include pain or pressure in the anus or rectum, a change in bowel habits, a lump near the anus, rectal bleeding, itching or discharge. Bleeding may be severe.
Cytologic features of serous carcinoma are:
- Marked intragroup nuclear pleomorphism.
- Macronucleoli.
- "Knobby" group borders (in large groups).
- Hydropic vacuoles.
Symptoms of serous carcinoma may include:
- Discomfort/pain or bloating in abdomen
- Frequent urination
- Weight loss
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.
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.
Oropharyngeal cancer is a disease in which cancer form in the tissues of the throat (oropharynx). The oropharynx is the middle part of the throat that includes the base of the tongue, the tonsils, the soft palate, and the walls of the pharynx. Oropharyngeal cancers can be divided into two types, HPV-positive, which are related to human papillomavirus infection, and HPV-negative cancers, which are usually linked to alcohol or tobacco use.
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%.
These terms are related since they represent the steps of the progression toward cancer:
- Dysplasia is the earliest form of precancerous lesion recognizable in a biopsy. Dysplasia can be low-grade or high-grade. High-grade dysplasia may also be referred to as carcinoma "in situ".
- Invasive carcinoma, usually simply called cancer, has the potential to invade and spread to surrounding tissues and structures, and may eventually be lethal.
Most anal cancers are squamous cell carcinomas (epidermoid carcinomas), that arises near the squamocolumnar junction. It may be keratinizing (basaloid) or non-keratinizing (cloacogenic).
Other types of anal cancer are adenocarcinoma, lymphoma, sarcoma or melanoma.
Cancer can be considered a very large and exceptionally heterogeneous family of malignant diseases, with squamous cell carcinomas comprising one of the largest subsets.
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
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.
Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or both. Adenocarcinomas are part of the larger grouping of carcinomas, but are also sometimes called by more precise terms omitting the word, where these exist. Thus invasive ductal carcinoma, the most common form of breast cancer, is adenocarcinoma but does not use the term in its name—however, esophageal adenocarcinoma does to distinguish it from the other common type of esophageal cancer, esophageal squamous cell carcinoma. Several of the most common forms of cancer are adenocarcinomas, and the various sorts of adenocarcinoma vary greatly in all their aspects, so that few useful generalizations can be made about them.
In the most specific usage (narrowest sense), the glandular origin or traits are exocrine; endocrine gland tumors, such as a VIPoma, an insulinoma, or a pheochromocytoma, are typically not referred to as adenocarcinomas but rather are often called neuroendocrine tumors. Epithelial tissue sometimes includes, but is not limited to, the surface layer of skin, glands, and a variety of other tissue that lines the cavities and organs of the body. Epithelial tissue can be derived embryologically from any of the germ layers (ectoderm, endoderm, or mesoderm). To be classified as adenocarcinoma, the cells do not necessarily need to be part of a gland, as long as they have secretory properties. Adenocarcinoma is the malignant counterpart to adenoma, which is the benign form of such tumors. Sometimes adenomas transform into adenocarcinomas, but most do not.
Well differentiated adenocarcinomas tend to resemble the glandular tissue that they are derived from, while poorly differentiated adenocarcinomas may not. By staining the cells from a biopsy, a pathologist can determine whether the tumor is an adenocarcinoma or some other type of cancer. Adenocarcinomas can arise in many tissues of the body owing to the ubiquitous nature of glands within the body, and, more fundamentally, to the potency of epithelial cells. While each gland may not be secreting the same substance, as long as there is an exocrine function to the cell, it is considered glandular and its malignant form is therefore named adenocarcinoma.
The signs and symptoms are similar to other cervical cancers and may include post-coital bleeding and/or pain during intercourse (dyspareunia). Early lesions may be completely asymptomatic.