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.

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.

Factors that contribute to the development of hypopharyngeal cancer include:

- Smoking

- Chewing tobacco

- Heavy alcohol use

- Poor diet

Smoking, like lung cancer, can cause hypopharyngeal cancer because it contains carcinogens that alter the DNA or RNA in a dividing cell. These alterations may change a normal DNA sequence to an oncogene, a gene that causes cancer after exposure to a carcinogen.

Squamous cells, a type of cell that lines hollow organs like the throat, mouth, lungs, and outer layer of skin, are particularly vulnerable when exposed to cigarette smoke.

Chewing tobacco can have the same effects as smoking and is also linked to hypopharyngeal cancer. The chewing tobacco is placed into the mouth, leaving it exposed to enzymes, like amylase, which partly digests the carcinogenic material. Saliva is swallowed, along with the cancer-promoting material, which passes through the hypopharynx on its way to the esophagus.

Heavy alcohol use is linked to Hypopharyngeal Cancer as well. Alcohol damages the lining of the hypopharynx, increasing the amount of chemicals that are allowed to seep into the underlying membranes. Heavy alcohol use is also associated with nutritional deficiencies.

A disease called Plummer-Vinson syndrome, a genetic disorder that causes a long-term iron deficiency, may also lead to Hypopharyngeal Cancer. Other factors like a deficiency in certain vitamins also appear to contribute to this type of cancer.

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.

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

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.

Tobacco smoking is the main known contributor to urinary bladder cancer; in most populations, smoking is associated with over half of bladder cancer cases in men and one-third of cases among women, however these proportions have reduced over recent years since there are fewer smokers in Europe and North America. There is an almost linear relationship between smoking duration (in years), pack years and bladder cancer risk. A risk plateau at smoking about 15 cigarettes a day can be observed (meaning that those who smoke 15 cigarettes a day are approximately at the same risk as those smoking 30 cigarettes a day). Quitting smoking reduces the risk, however former smokers will most likely always be at a higher risk of bladder cancer compared to never smokers. Passive smoking has not been proven to be involved.

Thirty percent of bladder tumors probably result from occupational exposure in the workplace to carcinogens such as benzidine. 2-Naphthylamine, which is found in cigarette smoke, has also been shown to increase bladder cancer risk. Occupations at risk are bus drivers, rubber workers, motor mechanics, leather (including shoe) workers, blacksmiths, machine setters, and mechanics. Hairdressers are thought to be at risk as well because of their frequent exposure to permanent hair dyes.

In addition to these major risk factors there are also numerous other modifiable factors that are less strongly (i.e. 10–20% risk increase) associated with bladder cancer, for example, obesity. Although these could be considered as minor effects, risk reduction in the general population could still be achieved by reducing the prevalence of a number of smaller risk factor together.

It has been suggested that mutations at HRAS, KRAS2, RB1, and FGFR3 may be associated in some cases.

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.

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.

A 2008 study commissioned by the World Health Organisation concluded that "specific fruit and vegetables may act to reduce the risk of bladder cancer." Fruit and yellow-orange vegetables, particularly carrots and those containing selenium, are probably associated with a moderately reduced risk of bladder cancer. Citrus fruits and cruciferous vegetables were also identified as having a possibly protective effect. However an analysis of 47,909 men in the Health Professionals Follow-Up Study showed little correlation between cancer reduction and high consumption of fruits and vegetables overall, or yellow or green leafy vegetables specifically, compared to the statistically significant reduction among those men who consumed large amounts of cruciferous vegetables.

In a 10-year study involving almost 49,000 men, researchers found that men who drank at least 1,44 L of water (around 6 cups) per day had a significantly reduced incidence of bladder cancer when compared with men who drank less. It was also found that: "the risk of bladder cancer decreased by 7% for every 240 mL of fluid added". The authors proposed that bladder cancer might partly be caused by the bladder directly contacting carcinogens that are excreted in urine, although this has not yet been confirmed in other studies.

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

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.

Symptoms of Hypopharyngeal Cancer include:

- Swollen lymph nodes in the neck (first sign of a problem in half of all patients)

- Sore throat in one location that persists after treatment

- Pain that radiates from the throat to the ears

- Difficult or painful swallowing (often leads to malnutrition and weight loss because of a refusal to eat)

- Voice changes (late stage cancer)

Tobacco smoking is associated with an increased risk of ureteral cancer.

Human papillomavirus infection (HPV) has been associated with SCC of the oropharynx, lung, fingers and anogenital region.

Cigarette smoking, both active and passive, increases the risk of cervical cancer. Among HPV-infected women, current and former smokers have roughly two to three times the incidence of invasive cancer. Passive smoking is also associated with increased risk, but to a lesser extent.

Smoking has also been linked to the development of cervical cancer. Smoking can increase the risk in women a few different ways, which can be by direct and indirect methods of inducing cervical cancer. A direct way of contracting this cancer is a smoker has a higher chance of CIN3 occurring which has the potential of forming cervical cancer. When CIN3 lesions lead to cancer, most of them have the assistance of the HPV virus, but that is not always the case, which is why it can be considered a direct link to cervical cancer. Heavy smoking and long-term smoking seem to have more of a risk of getting the CIN3 lesions than lighter smoking or not smoking at all. Although smoking has been linked to cervical cancer, it aids in the development of HPV which is the leading cause of this type of cancer. Also, not only does it aid in the development of HPV, but also if the woman is already HPV-positive, she is at an even greater likelihood of contracting cervical cancer.

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.

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.

Long-term use of oral contraceptives is associated with increased risk of cervical cancer. Women who have used oral contraceptives for 5 to 9 years have about three times the incidence of invasive cancer, and those who used them for 10 years or longer have about four times the risk.

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%.

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.

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.”

There are two primary types of vaginal cancer: squamous-cell carcinoma and adenocarcinoma.

- Vaginal squamous-cell carcinoma arises from the squamous cells (epithelium) that line the vagina. This is the most common type of vaginal cancer. It is found most often in women aged 60 or older.

- Vaginal adenocarcinoma arises from the glandular (secretory) cells in the lining of the vagina that produce some vaginal fluids. Adenocarcinoma is more likely to spread to the lungs and lymph nodes.

- Clear cell adenocarcinoma occurs in a small percentage of women (termed "DES-Daughters") born between 1938 and 1973 (later outside the United States) that were exposed to the drug diethylstilbestrol (DES) in utero. DES was prescribed to 5 to 10 million mothers period to prevent possible miscarriages and premature births. Typically, women develop DES-related adenocarcinoma before age 30, but increasing evidence suggests possible effects or cancers (including other forms of vaginal glandular tumors) at a later age. DES-exposure in women is also linked to various infertility and pregnancy complications. Daughters exposed to DES in utero may also have an increased risk of moderate/severe cervical squamous cell dysplasia and an increased risk of breast cancer. Approximately one in 1,000 (0.1%) DES Daughters will be diagnosed with clear cell adenocarcinoma. The risk is virtually non-existent among premenopausal women not exposed to DES.

- Vaginal germ cell tumors (primarily teratoma and endodermal sinus tumor) are rare. They are found most often in infants and children.

- Sarcoma botryoides, a rhabdomyosarcoma also is found most often in infants and children.

- Vaginal melanoma, a melanoma that appears in the vagina.

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.