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

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%.

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.

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

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.

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.

Squamous cell cancers are common in the mouth, including the inner lip, tongue, floor of mouth, gingivae, and hard palate. Cancers of the mouth are strongly associated with tobacco use, especially use of chewing tobacco or "dip", as well as heavy alcohol use. Cancers of this region, particularly the tongue, are more frequently treated with surgery than are other head and neck cancers.

Surgeries for oral cancers include

- Maxillectomy (can be done with or without orbital exenteration)

- Mandibulectomy (removal of the mandible or lower jaw or part of it)

- Glossectomy (tongue removal, can be total, hemi or partial)

- Radical neck dissection

- Mohs procedure

- Combinational e.g., glossectomy and laryngectomy done together.

The defect is typically covered/improved by using another part of the body and/or skin grafts and/or wearing a prosthesis.

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.

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.

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.

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.

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.

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.

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.

Nasopharynx cancer or nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx, most commonly in the postero-lateral nasopharynx or pharyngeal recess or 'Fossa of Rosenmüller' accounting for 50% cases. NPC occurs in children and adults. NPC differs significantly from other cancers of the head and neck in its occurrence, causes, clinical behavior, and treatment. It is vastly more common in certain regions of East Asia and Africa than elsewhere, with viral, dietary and genetic factors implicated in its causation. It is most common in males. It is a squamous cell carcinoma or an undifferentiated type. Squamous epithelial cells are a flat type of cell found in the skin and the membranes that line some body cavities. Differentiation means how different the cancer cells are from normal cells. "Undifferentiated cells" are cells that do not have their mature features or functions.

Florid cutaneous papillomatosis (also known as the Schwartz-Burgess syndrome) is an obligate paraneoplastic syndrome.

FCP begins as the sudden onset of numerous cutaneous papillomas that are clinically indistinguishable from viral warts. The papillomas range from 1 to 3 mm in diameter may spread to involve the entire body, including the face. Pruritus, which may sometimes precede the onset of FCP, is evident in the affected regions in about half of patients. Evaluation of a skin biopsy clearly distinguishes FCP from viral warts.

FCP is associated with underlying cancer of the breast, bladder, ovary, uterus, prostate, and lung. Other associated underlying malignancies include squamous cell carcinomas and lymphomas such as non-Hodgkin's lymphoma.

FCP is sometimes seen together with other signs of internal cancer, especially malignant acanthosis nigricans, tripe palms, Leser–Trélat sign, and hypertrichosis lanuginosa acquisita. FCP tends to improve in association with surgical or chemotherapeutic therapy of the underlying internal cancer. A recurrence or exacerbation of FCP may be linked with tumor regrowth or metastatic spread.

The characteristic eruption is of multiple warty papules and nodules beginning on acral skin, especially the hands and wrists, and disseminating onto the skin of the entire body. These skin lesions develop on the trunk, extremities, and face, and are almost twice as common in men than in women, especially individuals aged 53–72 years. Pruritus is also associated.

Vaginal bleeding or spotting in women after menopause occurs in 90% of endometrial cancer. Bleeding is especially common with adenocarcinoma, occurring in two-thirds of all cases. Abnormal menstrual cycles or extremely long, heavy, or frequent episodes of bleeding in women before menopause may also be a sign of endometrial cancer.

Symptoms other than bleeding are not common. Other symptoms include thin white or clear vaginal discharge in postmenopausal women. More advanced disease shows more obvious symptoms or signs that can be detected on a physical examination. The uterus may become enlarged or the cancer may spread, causing lower abdominal pain or pelvic cramping. Painful sexual intercourse or painful or difficult urination are less common signs of endometrial cancer. The uterus may also fill with pus (pyometrea). Of women with these less common symptoms (vaginal discharge, pelvic pain, and pus), 10–15% have cancer.

Leukoplakia could be classified as mucosal disease, and also as a premalignant condition. Although the white color in leukoplakia is a result of hyperkeratosis (or acanthosis), similarly appearing white lesions that are caused by reactive keratosis (smoker's keratosis or frictional keratoses e.g. morsicatio buccarum) are not considered to be leukoplakias. Leukoplakia could also be considered according to the affected site, e.g. oral leukoplakia, leukoplakia of the urinary tract, including bladder leukoplakia or leukoplakia of the penis, vulvae, cervix or vagina. Leukoplakia may also occur in the larynx, possibly in association with gastro-esophageal reflux disease. Oropharyngeal leukoplakia is linked to the development of esophageal squamous cell carcinoma, and sometimes this is associated with tylosis, which is thickening of the skin on the palms and soles of the feet (see: Leukoplakia with tylosis and esophageal carcinoma). Dyskeratosis congenita may be associated with leukoplakia of the oral mucosa and of the anal mucosa.

In the context of lesions of the mucous membrane lining of the bladder, leukoplakia is a historic term used to describe a visualized white patch which histologically represents keratinization in an area of squamous metaplasia. The symptoms may include frequency, suprapubic pain (pain felt above the pubis), hematuria (blood in the urine), dysuria (difficult urination or pain during urination), urgency, and urge incontinence. The white lesion may be seen during cystoscopy, where it appears as a whitish-gray or yellow lesion, on a background of inflamed urothelium and there may be floating debris in the bladder. Leukoplakia of the bladder may undergo cancerous changes, so biopsy and long term follow up are usually indicated.

Cancer patients undergoing chemotherapy usually become symptomatic four to five days after beginning treatment, reaching a peak at around day 10, and then slowly improving over the course of a few weeks. Mucositis associated with radiotherapy usually appears at the end of the second week of treatment and may last for six to eight weeks.

As a result of cell death in reaction to chemo- or radio-therapy, the mucosal lining of the mouth becomes thin, may slough off and then become red, inflamed and ulcerated. The ulcers may become covered by a yellowish white fibrin clot called a pseudomembrane. Peripheral erythema is usually present. Ulcers may range from 0.5 cm to greater than 4 cm. Oral mucositis can be severely painful. The degree of pain is usually related to the extent of the tissue damage. Pain is often described as a burning sensation accompanied by reddening. Due to pain, the patient may experience trouble speaking, eating, or even opening the mouth.

Dysgeusia, or an alteration in taste perception, is common, especially for those who are receiving concomitant radiation therapy to the neck and mouth area. "Taste blindness", or an altered sense of taste, is a temporary condition that occurs because of effects on taste buds that are mostly located in the tongue. Sometimes, only partial recovery of taste occurs. Common complaints are of food tasting too sweet or too bitter or of a continuous metallic taste.

In the initial phase of the disease, the mucosa feels leathery with palpable fibrotic bands. In the advanced stage the oral mucosa loses its resiliency and becomes blanched and stiff. The disease is believed to begin in the posterior part of the oral cavity and gradually spread outward.

Other features of the disease include:

- Xerostomia

- Recurrent ulceration

- Pain in the ear or deafness

- Nasal intonation of voice

- Restriction of the movement of the soft palate

- A budlike shrunken uvula

- Thinning and stiffening of the lips

- Pigmentation of the oral mucosa

- Dryness of the mouth and burning sensation

- Decreased mouth opening and tongue protrusion

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.