Anal cancer

Last updated
Anal cancer
Diagram showing stage 1 anal cancer CRUK 189.svg
Diagram showing stage 1 anal cancer
Specialty Oncology
Symptoms Anal bleeding or lump [1]
Usual onsetAge over 45 years [2]
Types Squamous cell carcinoma, adenocarcinoma, small cell carcinoma, melanoma [3]
Risk factors Human papillomavirus (HPV), HIV/AIDS, receptive anal sex, smoking, many sexual partners [1] [4]
Diagnostic method Physical examination, tissue biopsy [1]
Differential diagnosis Anal warts, hemorrhoids, anal fissure [5]
Prevention HPV vaccination, avoiding risk factors [6]
Treatment Radiation therapy, chemotherapy, surgery [1]
Prognosis Five year survival ~68% (US 2015) [2]
Frequency8,300 (US 2019) [2]
Deaths1,280 (US 2019) [2]

Anal cancer is a cancer which arises from the anus, the distal opening of the gastrointestinal tract. [1] Symptoms may include bleeding from the anus or a lump near the anus. [1] Other symptoms may include pain, itchiness, or discharge from the anus. [1] A change in bowel movements may also occur. [1]

Contents

Risk factors include human papillomavirus (HPV), HIV/AIDS, receptive anal sex, [4] smoking, and many sexual partners. [1] Anal cancer is typically a squamous cell carcinoma. [3] Other types include adenocarcinoma, small cell carcinoma, and melanoma. [3] Diagnosis is suspected based on physical examination and confirmed by tissue biopsy. [1]

Prevention includes avoiding risk factors and HPV vaccination. [6] Standard treatment may include radiation therapy, chemotherapy, and surgery. [1] About 8,300 people are diagnosed a year in the United States, representing about 0.5% of new cancers. [2] Onset is typically after the age of 45. [2] Women are affected more often than men. [2] The number of cases has increased since the 1990s. [3] The five-year survival rate in the United States is 68%. [2]

Signs and symptoms

A squamous cell carcinoma of the anus visible Squamous cell carcinoma of anal rim 01.jpg
A squamous cell carcinoma of the anus visible

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. [7] [8]

Risk factors

Pathology

Most anal cancers are squamous cell carcinomas (epidermoid carcinomas), that arises near the squamocolumnar junction. It may be keratinizing (basaloid) or non-keratinizing (cloacogenic). [17]

Other types of anal cancer are adenocarcinoma, lymphoma, sarcoma or melanoma.

Staging

Pathologic TNM staging of anal carcinomas: [18] [19]

Primary tumor (pT)

Regional lymph nodes (pN)

Distant metastasis (pM)

Prevention

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, [20] scientists surmise that HPV vaccination may reduce the incidence of anal cancer. [21] The efficacy of the vaccine against HPV types 16 and 18 in naive women ≤26 years old has been shown to be between 91-100% but is lower when individuals are vaccinated irrespective of baseline HPV infection at 76%. [22]

In 2010, Gardasil was approved in the US 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. [23]

Screening

As the incidence of anal cancer has increased in recent years, screening and early detection of anal intraepithelial neoplasia (AIN) has become a necessity in patients at risk. This screening detects premalignant lesions, which are highly prevalents, and improves the staging of lesions after treatment. [24]

Anal Pap smears similar to those used in cervical cancer screening have been studied for early detection of anal cancer in high-risk individuals. [25] In 2011, an HIV clinic implemented a program to enhance access to anal cancer screening for HIV-positive men. Nurse practitioners perform anal Papanicolaou screening, and men with abnormal results receive further evaluation with high-resolution anoscopy. The program has helped identify many precancerous growths, allowing them to be safely removed. [26] A similar study was performed in women with a history of cervical cancer or high-grade cervical intraepithelial neoplasia. More than 30% had abnormal anal Pap smears and one third of those already had anal intraepithelial neoplasia. [27]

Treatment

Localised disease

Localised disease (carcinoma-in-situ) and the precursor condition, anal intraepithelial neoplasia (anal dysplasia or AIN) can be ablated with minimally invasive methods such as infrared photocoagulation. [28]

Previously, anal cancer was treated with surgery, and in early-stage disease (i.e., localised cancer of the anus without metastasis to the inguinal lymph nodes), surgery is often curative. The difficulty with surgery has been the necessity of removing the internal and external anal sphincter, with concomitant fecal incontinence. For this reason, many patients with anal cancer have required permanent colostomies. [17]

Current gold-standard therapy is the combination of chemotherapy and radiation treatment to reduce the necessity of debilitating surgery. [29] This "combined modality" approach has led to the increased preservation of an intact anal sphincter, and therefore improved quality of life after definitive treatment. Survival and cure rates are excellent, and many patients are left with a functional sphincter. Some patients have fecal incontinence after combined chemotherapy and radiation. Biopsies to document disease regression after chemotherapy and radiation were commonly advised, but are not as frequent any longer. Current chemotherapy consists of continuous infusion 5-FU over four days with bolus mitomycin given concurrently with radiation. 5-FU and cisplatin are recommended for metastatic anal cancer. [30] For stages I to III anal squamous cell carcinoma, using cisplatin instead of mitomycin C (MMC) in chemoradiation therapy doesn't improve overall survival or slow down the cancer compared to the standard treatment of 5-FU plus MMC. Although cisplatin might cause fewer blood-related side effects, 5-FU combined with MMC is still the preferred treatment for nonmetastatic anal cancer. [31] A 2024 systematic review found that chemoradiation therapy (CRT) with 5-FU and Mitomycin C improves locoregional control and colostomy-free survival compared to radiation alone, though with increased acute hematologic toxicity. [32]

Metastatic or recurrent disease

10 to 20% of patients treated for anal cancer will develop distant metastatic disease following treatment. [33] Metastatic or recurrent anal cancer is difficult to treat, and usually requires chemotherapy. Radiation is also employed to palliate specific locations of disease that may be causing symptoms. Chemotherapy commonly used is similar to other squamous cell epithelial neoplasms, such as platinum analogues, anthracyclines such as doxorubicin, and antimetabolites such as 5-FU and capecitabine. JD Hainsworth developed a protocol that includes Taxol and Carboplatinum along with 5-FU. [34]

Prognosis

Median survival rates for people with distant metastases range from 8 to 34 months. [33] Surgical resection with permanent colostomies was the standard treatment until the 1970s, yielding 5-year overall survival of approximately 50%. The best overall survival rates are seen after combined radiation therapy combined with chemotherapy (5-FU + Mitomycin) in people with T2N0 and T3N0 categories of disease (5-y overall survival: 82%). The 5-year overall survival rates of patients with T4 with no involved lymph nodes, T3 with involved lymph nodes, and T4 with involved lymph nodes disease after the combined treatment is 57%, 57%, and 42%, respectively. [35] [36]

Radiation therapy side effects (and occurrence rates) include acute (27%) and late (17%) dermatological toxicities, acute (14%) and late (27%) gastrointestinal toxicities, [37] and chronic pelvic radiation disease (1-10%), e.g., irreversible lumbosacral plexopathy. [38]

Epidemiology

Worldwide in 2002 there were an estimated 30,400 new cases of anal cancer. [11] With approximately equal fractions in the developing (15,900) and developed (14,500) countries. [11] An estimated 90% (27,400) were attributable to human papillomavirus (HPV). [11]

United States

In 2014 about 7,060 new cases of anal cancer were diagnosed in the United States (4,430 in women and 2,630 in men). [39] It is typically found in adults, average age early 60s. [39] In 2019, an estimated 8,300 adults will be diagnosed with anal cancer. [40]

In the United States, an estimated 800 to 900 people die of anal cancer annually. [39]

United Kingdom

Anal cancer accounts for less than 1% of all cancer cases and deaths in the United Kingdom. Around 1,200 people were diagnosed with the disease in 2011, and around 310 people died in 2012. [41]

Related Research Articles

<span class="mw-page-title-main">Cervical cancer</span> Cancer arising from the cervix

Cervical cancer is a cancer arising from the cervix or in any layer of the wall of the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal vaginal bleeding, pelvic pain or pain during sexual intercourse. While bleeding after sex may not be serious, it may also indicate the presence of cervical cancer.

<span class="mw-page-title-main">Human papillomavirus infection</span> Human disease

Human papillomavirus infection is caused by a DNA virus from the Papillomaviridae family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and results in either warts or precancerous lesions. These lesions, depending on the site affected, increase the risk of cancer of the cervix, vulva, vagina, penis, anus, mouth, tonsils, or throat. Nearly all cervical cancer is due to HPV, and two strains – HPV16 and HPV18 – account for 70% of all cases. HPV16 is responsible for almost 90% of HPV-positive oropharyngeal cancers. Between 60% and 90% of the other cancers listed above are also linked to HPV. HPV6 and HPV11 are common causes of genital warts and laryngeal papillomatosis.

<span class="mw-page-title-main">Bladder cancer</span> Urinary system cancer that begins in the urinary bladder

Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become malignant.

Penile cancer, or penile carcinoma, is a cancer that develops in the skin or tissues of the penis. Symptoms may include abnormal growth, an ulcer or sore on the skin of the penis, and bleeding or foul smelling discharge.

<span class="mw-page-title-main">Oral cancer</span> Cancer of the lining of the lips, mouth, or upper throat

Oral cancer, also known as oral cavity cancer, tongue cancer or mouth cancer, is a cancer of the lining of the lips, mouth, or upper throat. In the mouth, it most commonly starts as a painless red or white patch, that thickens, gets ulcerated and continues to grow. When on the lips, it commonly looks like a persistent crusting ulcer that does not heal, and slowly grows. Other symptoms may include difficult or painful swallowing, new lumps or bumps in the neck, a swelling in the mouth, or a feeling of numbness in the mouth or lips.

This is a list of terms related to oncology. The original source for this list was the US National Cancer Institute's public domain Dictionary of Cancer Terms.

<span class="mw-page-title-main">Cervical intraepithelial neoplasia</span> Medical condition

Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia, is the abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer. More specifically, CIN refers to the potentially precancerous transformation of cells of the cervix.

<span class="mw-page-title-main">Koilocyte</span> Type of cell that has been changed by HPV

A koilocyte is a squamous epithelial cell that has undergone a number of structural changes, which occur as a result of infection of the cell by human papillomavirus (HPV). Identification of these cells by pathologists can be useful in diagnosing various HPV-associated lesions.

<span class="mw-page-title-main">Vulvar cancer</span> Cancer involving the vulva

Vulvar cancer is a cancer of the vulva, the outer portion of the female genitals. It most commonly affects the labia majora. Less often, the labia minora, clitoris, or Bartholin's glands are affected. Symptoms include a lump, itchiness, changes in the skin, or bleeding from the vulva.

<span class="mw-page-title-main">Nasopharyngeal carcinoma</span> Type of throat cancer; most common to occur in the nasopharynx

Nasopharyngeal carcinoma (NPC), or nasopharynx cancer, is the most common cancer originating in the nasopharynx, most commonly in the postero-lateral nasopharynx or pharyngeal recess, accounting for 50% of 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 of an undifferentiated type. Squamous epithelial cells are a flat type of cell found in the skin and the membranes that line some body cavities. Undifferentiated cells are cells that do not have their mature features or functions.

Vaginal cancer is an extraordinarily rare form of cancer that develops in the tissue of the vagina. Primary vaginal cancer originates from the vaginal tissue – most frequently squamous cell carcinoma, but primary vaginal adenocarcinoma, sarcoma, and melanoma have also been reported – while secondary vaginal cancer involves the metastasis of a cancer that originated in a different part of the body. Secondary vaginal cancer is more common. Signs of vaginal cancer may include abnormal vaginal bleeding, dysuria, tenesmus, or pelvic pain, though as many as 20% of women diagnosed with vaginal cancer are asymptomatic at the time of diagnosis. Vaginal cancer occurs more frequently in women over age 50, and the mean age of diagnosis of vaginal cancer is 60 years. It often can be cured if found and treated in early stages. Surgery alone or surgery combined with pelvic radiation is typically used to treat vaginal cancer.

HspE7 is an investigational therapeutic vaccine candidate being developed by Nventa Biopharmaceuticals for the treatment of precancerous and cancerous lesions caused by the human papillomavirus (HPV). HspE7 uses recombinant DNA technology to covalently fuse a heat shock protein (Hsp) to a target antigen, thereby stimulating cellular immune system responses to specific diseases. HspE7 is a patented construct consisting of the HPV Type 16 E7 protein and heat shock protein 65 (Hsp65) and is currently the only candidate using Hsp technology to target the over 20 million Americans already infected with HPV.

An anal Pap smear is the anal counterpart of the cervical Pap smear. It is used for the early detection of anal cancer. Some types of human papillomavirus (HPV) can cause anal cancer. Other HPV types cause anogenital warts. Cigarette smokers, men who have sex with men, individuals with a history of immunosuppression and women with a history of cervical, vaginal and vulval cancer are at increased risk of getting anal cancer. Vaccination against HPV before initial sexual exposure can reduce the risk of anal cancer.

<span class="mw-page-title-main">Sebaceous carcinoma</span> Malignant tumor of oil glands in the skin

Sebaceous carcinoma, also known as sebaceous gland carcinoma (SGc), sebaceous cell carcinoma, and meibomian gland carcinoma, is an uncommon malignant cutaneous (skin) tumor. Most are typically about 1.4 cm at presentation. SGc originates from sebaceous glands in the skin and, therefore, may originate anywhere in the body where these glands are found. SGc can be divided into 2 types: periocular and extraocular. The periocular region is rich in sebaceous glands making it a common site of origin. The cause of these lesions in the vast majority of cases is unknown. Occasional cases may be associated with Muir-Torre syndrome. SGc accounts for approximately 0.7% of all skin cancers, and the incidence of SGc is highest in Caucasian, Asian, and Indian populations. Due to the rarity of this tumor and variability in clinical and histological presentation, SGc is often misdiagnosed as an inflammatory condition or a more common neoplasm. SGc is commonly treated with wide local excision or Mohs micrographic surgery, and the relative survival rates at 5 and 10 years are 92.72 and 86.98%, respectively.

<span class="mw-page-title-main">Oropharyngeal cancer</span> Pharynx cancer that is located in the oropharynx

Oropharyngeal cancer, also known as oropharyngeal squamous cell carcinoma and tonsil cancer, is a disease in which abnormal cells with the potential to both grow locally and spread to other parts of the body are found in the oral cavity, in the tissue of the part of the throat (oropharynx) that includes the base of the tongue, the tonsils, the soft palate, and the walls of the pharynx.

<span class="mw-page-title-main">HPV-positive oropharyngeal cancer</span> Cancer of the throat

Human papillomavirus-positive oropharyngeal cancer, is a cancer of the throat caused by the human papillomavirus type 16 virus (HPV16). In the past, cancer of the oropharynx (throat) was associated with the use of alcohol or tobacco or both, but the majority of cases are now associated with the HPV virus, acquired by having oral contact with the genitals of a person who has a genital HPV infection. Risk factors include having a large number of sexual partners, a history of oral-genital sex or anal–oral sex, having a female partner with a history of either an abnormal Pap smear or cervical dysplasia, having chronic periodontitis, and, among men, younger age at first intercourse and a history of genital warts. HPV-positive OPC is considered a separate disease from HPV-negative oropharyngeal cancer.

Neuroendocrine carcinoma of the cervix is best defined separately:Neuroendocrine: Of, relating to, or involving the interaction between the nervous system and the hormones of the endocrine glands.Carcinoma: An invasive malignant tumor derived from epithelial tissue that tends to metastasize to other areas of the body.

<span class="mw-page-title-main">Cervical cancer staging</span> Medical condition

Cervical cancer staging is the assessment of cervical cancer to determine the extent of the spread of cancer beyond the cervix. This is important for determining how serious the cancer is and to create the best treatment plan.

Conjunctival squamous cell carcinoma and corneal intraepithelial neoplasia comprise ocular surface squamous neoplasia (OSSN). SCC is the most common malignancy of the conjunctiva in the US, with a yearly incidence of 1–2.8 per 100,000. Risk factors for the disease are exposure to sun, exposure to UVB, and light-colored skin. Other risk factors include radiation, smoking, HPV, arsenic, and exposure to polycyclic hydrocarbons.

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. It comprises 23.1% of all malignancies of the oropharynx. The tumors frequently present at advanced stages, and around 70% of patients present with metastasis to the cervical lymph nodes. . 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.

References

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