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.

People with HPV-mediated oropharyngeal cancer tend to have higher survival rates. The prognosis for people with oropharyngeal cancer depends on the age and health of the person and the stage of the disease. It is important for people with oropharyngeal cancer to have follow-up exams for the rest of their lives, as cancer can occur in nearby areas. In addition, it is important to eliminate risk factors such as smoking and drinking alcohol, which increase the risk for second cancers.

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.

The risk factors that can increase the risk of developing oropharyngeal cancer are:

- Smoking and chewing tobacco

- Heavy alcohol use

- A diet low in fruits and vegetables

- Chewing betel quid, a stimulant commonly used in parts of Asia

- Mucosal infection with human papilloma virus (HPV) (HPV-mediated oropharyngeal cancer)

- HPV infection

- Plummer-Vinson syndrome

- Poor nutrition

- Asbestos exposure

Certain genetic changes including: P53 mutation and CDKN2A (p16) mutations.

High-risk lesions:

- Erythroplakia

- Speckled erythroplakia

- Chronic hyperplastic candidiasis

Medium-risk lesions:

- Oral submucosal fibrosis

- Syphilitic glossitis

- Sideropenic dysphagia (or Paterson-Kelly-Brown syndrome)

Low-risk lesions:

- Oral lichen planus

- Discoid lupus erythematosus

- Discoid keratosis congenita

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.

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

Tobacco smoke is one of the main risk factors for head and neck cancer and one of the most carcinogenic compounds in tobacco smoke is acrylonitrile. (See Tobacco smoking). 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 mutagenic. DNA glycosylase NEIL1 prevents mutagenesis by 8-oxo-dG and removes formamidopyrimidines from DNA.

However, cigarette smokers have a lifetime increased risk for head and neck cancers that is 5- to 25-fold increased over the general population.

The ex-smoker's risk for squamous cell cancer of the head and neck begins to approach the risk in the general population twenty years after smoking cessation. The high prevalence of tobacco and alcohol use worldwide and the high association of these cancers with these substances makes them ideal targets for enhanced cancer prevention.

Smokeless tobacco is cause of oral and pharyngeal cancers (oropharyngeal cancer). Cigar smoking is an important risk factor for oral cancers as well.

Other environmental carcinogens suspected of being potential causes of head and neck cancer include occupational exposures such as nickel refining, exposure to textile fibers, and woodworking. Use of marijuana, especially while younger, is linked to an increase in squamous-cell carcinoma cases while other studies suggest use is not shown to be associated with oral squamous cell carcinoma, or associated with decreased squamous cell carcinoma.

Excessive consumption of processed meats and red meat were associated with increased rates of cancer of the head and neck in one study, while consumption of raw and cooked vegetables seemed to be protective.

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.

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 the vitamin users.

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.

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.

Since many, if not most, anal cancers derive from HPV infections, and since the HPV vaccine before exposure to HPV prevents infection by some strains of the virus and has been shown to reduce the incidence of potentially precancerous lesions, scientists surmise that HPV vaccination may reduce the incidence of anal cancer.

On 22 December 2010, the U.S. Food and Drug Administration approved Gardasil vaccine to prevent anal cancer and pre-cancerous lesions in males and females aged 9 to 26 years. The vaccine has been used before to help prevent cervical, vulvar, and vaginal cancer, and associated lesions caused by HPV types 6, 11, 16, and 18 in women.

Most mucosal squamous cell head and neck cancers, including oropharyngeal cancer (OPC), have historically been attributed to tobacco and alcohol use. However this pattern has changed considerably since the 1980s. It was realised that some cancers occur in the absence of these risk factors and

an association between human papilloma virus (HPV) and various squamous cell cancers, including OPC, was first described in 1983. Since then both molecular and epidemiological evidence has been accumulating, with the International Agency for Research on Cancer (IARC) stating that high-risk HPV types 16 and 18 are carcinogenic in humans, in 1995, and In 2007 that HPV was a cause for oral cancers. Human papillomavirus (HPV)-positive cancer (HPV+OPC) incidence has been increasing while HPV-negative (HPV-OPC) cancer incidence is declining, a trend that is estimated to increase further in coming years. Since there are marked differences in clinical presentation and treatment relative to HPV status, HPV+OPC is now viewed as a distinct biologic and clinical condition.

Human HPV has long been implicated in the pathogenesis of several anogenital cancers including those of the anus, vulva, vagina, cervix, and penis. In 2007 it was also implicated by both molecular and epidemiological evidence in cancers arising outside of the anogenital tract, namely oral cancers. HPV infection is common among healthy individuals, and is acquired largely through sexual contact. Although less data is available, prevalence of HPV infection is at least as common among men as among women, with 2004 estimates of about 27% among US women aged 14–59.

HPV oral infection precedes the development of HPV+OPC. Slight injuries in the mucous membrane serve as an entry gate for HPV, which thus works into the basal layer of the epithelium. People testing positive for HPV type 16 virus (HPV16) oral infection have a 14 times increased risk of developing HPV+OPC. Immunosuppression seems to be an increased risk factor for HPV+OPC. Individuals with TGF-β1 genetic variations, specially T869C, are more likely to have HPV16+OPC. TGF-β1 plays an important role in controlling the immune system. In 1993 it was noted that patients with human papillomavirus (HPV)-associated anogenital cancers had a 4-fold increased risk of tonsillar squamous-cell carcinoma. Although evidence suggests that HPV16 is the main cause of OPC in humans not exposed to smoking and alcohol, the degree to which tobacco and/or alcohol use may contribute to increase the risk of HPV+OPC has not always been clear but it appears that both smoking and HPV infection are independent and additive risk factors for developing OPC. Human herpesvirus-8 infection can potentiate the effects of HPV-16.

Risk factors include a high number of sexual partners (25% increase >= 6 partners), a history of oral-genital sex (125% >= 4 partners), or anal–oral sex, a female partner with a history of either an abnormal Pap smear or cervical dysplasia, chronic periodontitis, and, among men, decreasing age at first intercourse and history of genital warts.

Tobacco smoking or chewing is the most common causative factor, with more than 80% of persons with leukoplakia having a positive smoking history. Smokers are much more likely to suffer from leukoplakia than non-smokers. The size and number of leukoplakia lesions in an individual is also correlated with the level of smoking and how long the habit has lasted for. Other sources argue that there is no evidence for a direct causative link between smoking and oral leukoplakia. Cigarette smoking may produce a diffuse leukoplakia of the buccal mucosa, lips, tongue and rarely the floor of mouth. Reverse smoking, where the lit end of the cigarette is held in the mouth is also associated with mucosal changes. Tobacco chewing, e.g. betel leaf and areca nut, called paan, tends to produce a distinctive white patch in a buccal sulcus termed "tobacco pouch keratosis". In the majority of persons, cessation triggers shrinkage or disappearance of the lesion, usually within the first year after stopping.

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.

Although the synergistic effect of alcohol with smoking in the development of oral cancer is beyond doubt, there is no clear evidence that alcohol is involved in the development of leukoplakia, but it does appear to have some influence. Excessive use of a high alcohol containing mouth wash (> 25%) may cause a grey plaque to form on the buccal mucosa, but these lesions are not considered true leukoplakia.

A precancerous condition or premalignant condition, sometimes called a potentially precancerous condition or potentially premalignant condition, is a state of disordered morphology of cells that is associated with an increased risk of cancer. If left untreated, these conditions may lead to cancer. Such conditions are usually either dysplasia or benign neoplasia (and the dividing line between those is sometimes blurry). Sometimes the term "precancer" is used to describe carcinoma in situ, which is a noninvasive cancer that has not progressed to an aggressive, invasive stage. Not all carcinoma in situ will progress to invasive disease.

Premalignant lesions are morphologically atypical tissue which appears abnormal under microscopic examination, and in which cancer is more likely to occur than in its apparently normal counterpart.

Examples of premalignant conditions include:

- actinic keratosis

- Barrett's esophagus

- atrophic gastritis

- ductal carcinoma in situ

- dyskeratosis congenita

- sideropenic dysphagia

- lichen planus

- oral submucous fibrosis

- solar elastosis

- cervical dysplasia

- leukoplakia

- erythroplakia

The term was coined in 1875 by Romanian physician Victor Babeş.

The American Cancer Society estimated that in 2014 about 7,060 new cases of anal cancer would be diagnosed in the United States (4,430 in women and 2,630 in men) . It is typically found in adults, average age early 60s.

In the United States, an estimated 800 to 900 people die of anal cancer annually.

The etiology of florid cutaneous papillomatosis is unknown. It is likely directly induced by an underlying neoplasm secreting a growth factor. One candidate may be alpha-transforming growth factor, structurally related to epidermal growth factor, but antigenically distinct from it. The underlying cancer is most often gastric adenocarcinoma but also with breast cancer, bladder cancer, hepatobiliary cancer, ovarian cancer, uterine cancer, prostate cancer, lung cancer and cervical cancer. Other associated underlying malignancies include squamous cell carcinomas and lymphomas.

The presence of HPV within the tumour has been realised to be an important factor for predicting survival since the 1990s. Tumor HPV status is strongly associated with positive therapeutic response and survival compared with HPV-negative cancer, independent of the treatment modality chosen and even after adjustment for stage. While HPV+OPC patients have a number of favourable demographic features compared to HPV-OPC patients, such differences account for only about ten per cent of the survival difference seen between the two groups. Response rates of over 80% are reported in HPV+ cancer and three-year progression free survival has been reported as 75–82% and 45–57%, respectively, for HPV+ and HPV- cancer, and improving over increasing time. It is likely that HPV+OPC is inherently less maligant than HPV-OPC, since patients treated by surgery alone have a better survival after adjustment for stage. In one study, less than 50% of patients with HPV-OPC were still alive after five years, compared to more than 70% with HPV+OPC and an equivalent stage and disease burden.

In RTOG clinical trial 0129, in which all patients with advanced disease received radiation and chemotherapy, a retrospective analysis (recursive-partitioning analysis, or RPA) at three years identified three risk groups for survival (low, intermediate, and high) based on HPV status, smoking, T stage and N stage ("see" Ang et al., Fig. 2). HPV status was the major determinant of survival, followed by smoking history and stage. 64% were HPV+ and all were in the low and intermediate risk group, with all non-smoking HPV+ patients in the low risk group. 82% of the HPV+ patients were alive at three years compared to 57% of the HPV- patients, a 58% reduction in the risk of death. Locoregional failure is also lower in HPV+, being 14% compared to 35% for HPV-. HPV positivity confers a 50–60% lower risk of disease progression and death, but the use of tobacco is an independently negative prognostic factor. A pooled analysis of HPV+OPC and HPV-OPC patients with disease progression in RTOG trials 0129 and 0522 showed that although less HPV+OPC experienced disease progression (23 v. 40%), the median time to disease progression following treatment was similar (8 months). The majority (65%) of recurrences in both groups occurred within the first year after treatment and were locoregional. HPV+ did not reduce the rate of metastases (about 45% of patients experiencing progression), which are predominantly to the lungs (70%), although some studies have reported a lower rate. with 3-year distant recurrence rates of about 10% for patients treated with primary radiation or chemoradiation. Even if recurrence or metastases occur, HPV positivity still confers an advantage.

By contrast tobacco usage is an independently negative prognostic factor, with decreased response to therapy, increased disease recurrence rates and decreased survival. The negative effects of smoking, increases with amount smoked, particularly

if greater than 10 pack-years. For patients such as those treated on RTOG 0129 with primary chemoradiation, detailed nomograms have been derived from that dataset combined with RTOG 0522, enabling prediction of outcome based on a large number of variables. For instance, a 71 year old married non-smoking high school graduate with a performance status (PS) of 0, and no weight loss or anaemia and a T3N1 HPV+OPC would expect to have a progression-free survival of 92% at 2 years and 88% at 5 years. A 60 year old unmarried nonsmoking high school graduate with a PS of 1, weight loss and anaemia and a T4N2 HPV+OPC would expect to have a survival of 70% at two years and 48% at five years. Less detailed information is available for those treated primarily with surgery, for whom less patients are available, as well as low rates of recurrence (7–10%), but features that have traditionally been useful in predicting prognosis in other head and neck cancers, appear to be less useful in HPV+OPC. These patients are frequently stratified into three risk groups:

- Low risk: No adverse pathological features

- Intermediate risk: T3–T4 primary, perineural or lymphovascular invasion, N2 (AJCC 7)

- High risk: Positive margins, ECE

HPV+OPC patients are less likely to develop other cancers, compared to other head and neck cancer patients. A possible explanation for the favourable impact of HPV+ is "the lower probability of occurrence of 11q13 gene amplification, which is considered to be a factor underlying faster and more frequent recurrence of the disease" Presence of TP53 mutations, a marker for HPV- OPC, is associated with worse prognosis. High grade of p16 staining is thought to be better than HPV PCR analysis in predicting radiotherapy response.

Florid cutaneous papillomatosis is almost twice as common in men than in women, and is usually diagnosed in individuals aged 53–72 years (mean patient age, 58.5 years).

Nasopharynx cancer as of 2010 resulted in 65,000 deaths globally up from 45,000 in 1990.

NPC is uncommon in the United States and most other nations, representing less than 1 case per 100,000 in most populations. but is extremely common in southern regions of China, particularly in Guangdong, accounting for 18% of all cancers in China. It is sometimes referred to as "Cantonese cancer" because it occurs in about 25 cases per 100,000 people in this region, 25 times higher than the rest of the world. It is also quite common in Taiwan. This could be due to the South East Asian diet which typically includes consumption of salted vegetables, fish and meat. While NPC is seen primarily in middle-aged persons in Asia, a high proportion of African cases appear in children. The cause of increased risk for NPC in these endemic regions is not clear. In low-risk populations, such as in the United States, a bimodal peak is observed. The first peak occurs in late adolescence/early adulthood (ages 15–24 years), followed by a second peak later in life (ages 65–79 years).

Some therapies for other forms of cancer increase the lifetime risk of endometrial cancer, which is a baseline 2–3%. Tamoxifen, a drug used to treat estrogen-positive breast cancers, has been associated with endometrial cancer in approximately 0.1% of users, particularly older women, but the benefits for survival from tamoxifen generally outweigh the risk of endometrial cancer. A one to two-year course of tamoxifen approximately doubles the risk of endometrial cancer, and a five-year course of therapy quadruples that risk. Raloxifene, a similar drug, did not raise the risk of endometrial cancer. Previously having ovarian cancer is a risk factor for endometrial cancer, as is having had previous radiotherapy to the pelvis. Specifically, ovarian granulosa cell tumors and thecomas are tumors associated with endometrial cancer.

Low immune function has also been implicated in endometrial cancer. High blood pressure is also a risk factor, but this may be because of its association with obesity. Sitting regularly for prolonged periods is associated with higher mortality from endometrial cancer. The risk is not negated by regular exercise, though it is lowered.

Nasopharyngeal carcinoma (NPC) is caused by a combination of factors: viral, environmental influences, and heredity. The viral influence is associated with infection with Epstein-Barr virus (EBV). The Epstein-Barr virus is one of the most common viruses. 95 percent of all people in the U.S. are exposed to this virus by the time they are 30–40 years old. The World Health Organization does not have set preventative measures for this virus because it is so easily spread and is worldwide. Very rarely does Epstein-Barr virus lead to cancer, which suggests a variety of influencing factors. Other likely causes include genetic susceptibility, consumption of food (in particular salted fish) containing carcinogenic volatile nitrosamines. Various mutations that activate NF-κB signalling have been reported in almost half of NPC cases investigated.

The association between Epstein-Barr virus and nasopharyngeal carcinoma is unequivocal in World Health Organization (WHO) types II and III tumors but less well-established for WHO type I (WHO-I) NPC, where preliminary evaluation has suggested that human papillomavirus HPV may be associated. EBV DNA was detectable in the blood plasma samples of 96% of patients with non-keratinizing NPC, compared with only 7% in controls. The detection of nuclear antigen associated with Epstein-Barr virus (EBNA) and viral DNA in NPC type 2 and 3, has revealed that EBV can infect epithelial cells and is associated with their transformation. The cause of NPC (particularly the endemic form) seems to follow a multi-step process, in which EBV, ethnic background, and environmental carcinogens all seem to play an important role. More importantly, EBV DNA levels appear to correlate with treatment response and may predict disease recurrence, suggesting that they may be an independent indicator of prognosis. The mechanism by which EBV alters nasopharyngeal cells is being elucidated to provide a rational therapeutic target.

Smoking and the use of progestin are both protective against endometrial cancer. Smoking provides protection by altering the metabolism of estrogen and promoting weight loss and early menopause. This protective effect lasts long after smoking is stopped. Progestin is present in the combined oral contraceptive pill and the hormonal intrauterine device (IUD). Combined oral contraceptives reduce risk more the longer they are taken: by 56% after four years, 67% after eight years, and 72% after twelve years. This risk reduction continues for at least fifteen years after contraceptive use has been stopped. Obese women may need higher doses of progestin to be protected. Having had more than five infants (grand multiparity) is also a protective factor, and having at least one child reduces the risk by 35%. Breastfeeding for more than 18 months reduces risk by 23%. Increased physical activity reduces an individual's risk by 38–46%. There is preliminary evidence that consumption of soy is protective.

Most patients will develop flat, brownish spots (melanotic macules) on the skin, especially on the lips and oral mucosa, during the first year of life, and a patient’s first bowel obstruction due to intussusception usually occurs between the ages of six and 18 years. The cumulative lifetime cancer risk begins to rise in middle age. Cumulative risks by age 70 for all cancers, gastrointestinal (GI) cancers, and pancreatic cancer are 85%, 57%, and 11%, respectively.

A 2011 Dutch study followed 133 patients for 14 years. The cumulative risk for cancer was 40% and 76% at ages 40 and 70, respectively. 42 (32%) of the patients died during the study, of which 28 (67%) were cancer related. They died at a median age of 45. Mortality was increased compared with the general population.

A family with sinonasal polyposis were followed up for 28 years. Two cases of sinonasal type adenocarcinoma developed. This is a rare cancer. This report suggested that follow up of sinus polyps in this syndrome may be indicated.