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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." Chewing betel nuts is an additional risk factor commonly seen in Taiwan.
Some studies in Australia, Brazil and Germany pointed to alcohol-containing mouthwashes as also being potential causes. The claim was that constant exposure to these alcohol-containing rinses, even in the absence of smoking and drinking, leads to significant increases in the development of oral cancer. However, studies conducted in 1985, 1995, and 2003 summarize that alcohol-containing mouth rinses are not associated with oral cancer. In a March 2009 brief, the American Dental Association said "the available evidence does not support a connection between oral cancer and alcohol-containing mouthrinse". A 2008 study suggests that acetaldehyde (a breakdown product of alcohol) is implicated in oral cancer, but this study specifically focused on abusers of alcohol and made no reference to mouthwash. Any connection between oral cancer and mouthwash is tenuous without further investigation.
In a study of Europeans, smoking and other tobacco use was associated with about 75 percent of oral cancer cases, caused by irritation of the mucous membranes of the mouth from smoke and heat of cigarettes, cigars, and pipes. Tobacco contains over 60 known carcinogens, and the combustion of it, and by-products from this process, is the primary mode of involvement. Use of chewing tobacco or snuff causes irritation from direct contact with the mucous membranes.
Tobacco use in any form by itself, and even more so in combination with heavy alcohol consumption, continues to be an important risk factor for oral cancer. However, due to the current trends in the spread of HPV16, as of early 2011 the virus is now considered the primary causative factor in 63% of newly diagnosed patients.
When associated with the lung, it is typically a centrally located large cell cancer (non-small cell lung cancer or NSCLC). It often has a paraneoplastic syndrome causing ectopic production of parathyroid hormone-related protein (PTHrP), resulting in hypercalcemia, however paraneoplastic syndrome is more commonly associated with small cell lung cancer.
It is primarily due to smoking.
Human papillomavirus infection (HPV) has been associated with SCC of the oropharynx, lung, fingers and anogenital region.
Smoking and alcohol abuse as the major risk factors. Viral causes has recently been taken under consideration as one of the risk factors. Viruses such as Epstein-Barr virus (EBV) (majorly involved in causing nasopharyngeal carcinoma) and human papilloma virus are included in this category. Chewing of betel nut ("Areca catechu") quid has been directly associated to cause oral cancers. It has also been stated under the FDA poisonous plant data base by the U.S Food and Drug Administration
An unbalanced diet, deficit in fruits and vegetables has shown to increase the risk of cancer.
Prognosis can range considerably for patients, depending where on the scale they have been staged. Generally speaking, the earlier the cancer is diagnosed, the better the prognosis. The overall 5-year survival rate for all stages of penile cancer is about 50%.
Compared to other breeds of dog, Scottish terriers have a much increased risk of developing transitional cell carcinoma.
Penile cancer is a rare cancer in developed nations with annual incidence varying from 0.3 to 1 per 100,000 per year accounting for around 0.4–0.6% of all malignancies. The annual incidence is approximately 1 in 100,000 men in the United States, 1 in 250,000 in Australia, and 0.82 per 100,000 in Denmark. In the United Kingdom, fewer than 500 men are diagnosed with penile cancer every year.
However, in the developing world penile cancer is much more common. For instance, in Paraguay, Uruguay, Uganda and Brazil the incidence is 4.2, 4.4, 2.8 and 1.5–3.7 per 100,000, respectively. In some South American countries, Africa, and Asia, this cancer type constitutes up to 10% of malignant diseases in men.
The lifetime risk has been estimated as 1 in 1,437 in the United States and 1 in 1,694 in Denmark.
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.
The long-term outcome of squamous cell carcinomas is dependent upon several factors: the sub-type of the carcinoma, available treatments, location(s) and severity, and various patient health-related variables (accompanying diseases, age, etc.). Generally, the long-term outcome is positive, as less than 4% of Squamous cell carcinoma cases are at risk of metastasis. Some particular forms of squamous cell carcinomas have a higher mortality rate. One study found squamous cell carcinoma of the penis had a much greater rate of mortality than some other forms of squamous cell carcinoma, that is, about 23%, although this relatively high mortality rate may be associated with possibly latent diagnosis of the disease due to patients avoiding genital exams until the symptoms are debilitating, or refusal to submit to a possibly scarring operation upon the genitalia. Squamous cell carcinoma occurring in the organ transplant population is also associated with a higher risk of mortality.
The incidence of squamous cell carcinoma continues to rise around the world. A recent study estimated that there are between 180,000 and 400,000 cases of SCC in the United States in 2013. Risk factors for squamous cell carcinoma varies with age, gender, race, geography, and genetics. The incidence of SCC increases with age and the peak incidence is usually around 60 years old. Males are affected with SCC at a ratio of 2:1 in comparison to females. Caucasians are more likely to be affected, especially those with fair Celtic skin and chronically exposed to UV radiation. Squamous cell carcinoma of the skin is the most common among all sites of the body. Solid organ transplant recipients (heart, lung, liver, pancreas, among others) are also at a heightened risk of developing aggressive, high-risk SCC. There are also a few rare congenital diseases predisposed to cutaneous malignancy. In certain geographic locations, exposure to arsenic in well water or from industrial sources may significantly increase the risk of SCC.
Squamous cell carcinoma of eye tissues is one of the most frequent neoplasms of cattle.
Although the exact cause of vulvar cancer isn't known, certain factors appear to increase your risk of the disease.
- Increasing age
- Exposure to human papillomavirus
- Smoking
- Being infected with the human immunodeficiency virus (HIV)
- Having a history of precancerous conditions of the vulva
- Having a skin condition involving the vulva
Use of the kangri pot has been correlated with the risk of Kangri cancer. The pot holds hot wood and charcoal, and as a unit, the pot is put in direct contact with the skin of the abdomen and the thigh areas as a way to keep warm during winters in north India. Elements that are believed to contribute to the development of Kangri cancer are heat, burning wood particles, smoke, soot, and tar of burnt chinar leaves that could also be used as a fuel source for burning in the production of heat.
In one study, researchers noted kangri pot usage patterns and found that Kangri cancer “patients gave the history of using the Kangri especially for 3-4 winter months [...] every year for 5-6 hours daily.”
Beyond the behavioral risk factor of prolonged usage of Kangri pots, researchers have begun to look at genetic mutations that may make some people more predisposed to develop Kangri cancer.
- In one study, compared to a control group, people with Kangri cancer were found to be approximately twice as likely to have a mutation in the TP53 gene (codon 72 polymorphism). Patients with higher grade tumors exhibited more proline amino acid mutations at this site.
- Another study confirmed this association of Kangri Cancer and TP53 mutations, specifically substitutions and insertions, in 40% of the Kangri cancer patients who were studied. The researchers observed a significant correlation with mutation status and age as well as with the presence of lymph nodes in patients. TP53 may, in the future, serve as “potential molecular marker and prognostic tool” for Kangri cancer. Furthermore, PTEN mutations were found in two of thirty patients studied; though due to the small sample size, no useful conclusions could be postulated.
- Two polymorphisms of the HSP70 gene were discovered to be correlated with “poor prognosis” of Kangri cancer; the “Hsp70-2 A/G or G/G and Hsp70homC/C genotypes” could potentially be utilized to measure risk of Kangri cancer development as well as to predict prognosis.
Some conditions such as lichen sclerosus, squamous dysplasia or chronic vulvar itching may precede cancer. In younger women affected with vulvar cancer, risk factors include low socioeconomic status, multiple sexual partners, cigarette use and cervical cancer. Patients that are infected with HIV tend to be more susceptible to vulvar cancer as well. Human papillomavirus (HPV) infection is associated with vulvar cancer.
Clear-cell adenocarcinoma is a type of adenocarcinoma that shows clear cells.
Types include:
- Clear-cell adenocarcinoma of the vagina
- Clear-cell ovarian carcinoma
- Uterine clear-cell carcinoma
- Clear-cell adenocarcinoma of the lung (which is a type of Clear-cell carcinoma of the lung)
See also:
- Clear-cell squamous cell carcinoma of the lung
Between 250,000 and 1 million American women are diagnosed with CIN annually. Women can develop CIN at any age, however women generally develop it between the ages of 25 to 35.
Tonsillar carcinoma can be either HPV related or HPV unrelated. It is shown that cases which are HPV positive have a better prognosis than those with HPV negative oropharyngeal cancer.
In most series, LCLC's comprise between 5% and 10% of all lung cancers.
According to the Nurses' Health Study, the risk of large cell lung carcinoma increases with a previous history of tobacco smoking, with a previous smoking duration of 30 to 40 years giving a relative risk of approximately 2.3 compared to never-smokers, and a duration of more than 40 years giving a relative risk of approximately 3.6.
Another study concluded that cigarette smoking is the predominant cause of large cell lung cancer. It estimated that the odds ratio associated with smoking two or more packs/day for current smokers is 37.0 in men and 72.9 in women.
EMECL is extremely rare, with only a handful of cases reported in the literature.
In the lung, two salivary gland-like carcinomas, mucoepidermoid carcinoma and adenoid cystic carcinoma, while extremely uncommon, occur far more often than does EMECL.
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.
It used to be thought that cases of CIN progressed through these stages toward cancer in a linear fashion.
However most CIN spontaneously regress. Left untreated, about 70% of CIN-1 will regress within one year, and 90% will regress within two years. About 50% of CIN 2 will regress within 2 years without treatment.
Progression to cervical carcinoma in situ (CIS) occurs in approximately 11% of CIN1 and 22% of CIN2. Progression to invasive cancer occurs in approximately 1% of CIN1, 5% in CIN2 and at least 12% in CIN3.
Progression to cancer typically takes 15 (3 to 40) years. Also, evidence suggests that cancer can occur without first detectably progressing through these stages and that a high grade intraepithelial neoplasia can occur without first existing as a lower grade.
It is thought that the higher risk HPV infections, have the ability to inactivate tumor suppressor genes such as the p53 gene and the RB gene, thus allowing the infected cells to grow unchecked and accumulate successive mutations, eventually leading to cancer.
Treatment does not affect the chances of getting pregnant but does increase the risk of second trimester miscarriages.
The prognosis of EMECL is relatively good, and considerably better than most other forms of NSCLC. The skull and dura are possible sites for metastasis from pulmonary EMC. The MIB-1 index is a predictive marker of malignant potential.