Penile cancer is

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

that develops in the skin or tissues of the

penis A penis (plural ''penises'' or ''penes'' () is the primary sexual organ that male animals use to inseminate females (or hermaphrodites) during copulation. Such organs occur in many animals, both vertebrate and invertebrate, but males do n ...

. Symptoms may include abnormal growth, an

ulcer An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...

or sore on the skin of the penis, and bleeding or foul smelling discharge. Risk factors include

phimosis Phimosis (from Greek φίμωσις ''phimōsis'' 'muzzling'.) is a condition in which the foreskin of the penis cannot stretch to allow it to be pulled back past the glans. A balloon-like swelling under the foreskin may occur with urination. In ...

(inability to retract

foreskin In male human anatomy, the foreskin, also known as the prepuce, is the double-layered fold of skin, mucosal and muscular tissue at the distal end of the human penis that covers the glans and the urinary meatus. The foreskin is attached to the g ...

of the penis), chronic

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

, smoking,

HPV infection Human papillomavirus infection (HPV 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 res ...

, condylomata acuminate, having multiple sexual partners, and early age of sexual intercourse. Around 95% of penile cancers are squamous cell carcinomas. Other types of penile cancer such as

Merkel cell carcinoma Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer occurring in about 3 people per 1,000,000 members of the population. It is also known as cutaneous APUDoma, primary neuroendocrine carcinoma of the skin, primary small cell carcin ...

small cell carcinoma Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell c ...

, and

melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...

are generally rare. In 2020, it occurred in 36,000 men and caused 13,000 deaths.

Signs and symptoms

Penile cancer can present as redness and irritation on the penis with a skin thickening on the glans or inner foreskin or an ulcerative, outward growing
exophytic
or “finger-like” (papillary) growth. Penile cancer may accompany penile discharge with or without difficulty or burning or tingling while urinating (

dysuria Dysuria refers to painful or uncomfortable urination. It is one of a constellation of ''irritative'' bladder symptoms (also sometimes referred to as lower urinary tract symptoms), which includes nocturia and urinary frequency. Diagnosis The c ...

) and bleeding from the penis.

Risk factors

Infections

HIV infection Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ma ...

—HIV-positive men have eight-fold increased risk of developing penile cancer than HIV-negative men. *

Human papillomavirus Human papillomavirus infection (HPV 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 res ...

—HPV is a risk factor in the development of penile cancer. According to the

Center for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...

(CDC), HPV is responsible for about 800 (about 40%) of 1,570 cases of penile cancer diagnosed annually in the United States. There are more than 120 types of HPV. *

Genital warts Genital warts are a sexually transmitted infection caused by certain types of human papillomavirus (HPV). They are generally pink in color and project out from the surface of the skin. Usually they cause few symptoms, but can occasionally be pai ...

—Genital or perianal warts increase the risk of invasive penile cancer by about 3.7 times if they occurred more than two years before the reference date. About half of men with penile cancer also have

genital warts Genital warts are a sexually transmitted infection caused by certain types of human papillomavirus (HPV). They are generally pink in color and project out from the surface of the skin. Usually they cause few symptoms, but can occasionally be pai ...

, which are caused by HPV.

Hygiene and injury

* Poor

hygiene Hygiene is a series of practices performed to preserve health. According to the World Health Organization (WHO), "Hygiene refers to conditions and practices that help to maintain health and prevent the spread of diseases." Personal hygiene refer ...

—Poor hygiene can increase a man's risk of penile cancer. *

Smegma Smegma (Ancient Greek σμῆγμα : ''smēgma'') is a combination of shed skin cells, skin oils, and moisture. It occurs in both male and female mammalian genitalia. In females, it collects around the clitoris and in the folds of the labia ...

—Smegma, a whitish substance that can accumulate beneath the foreskin, is associated with greater risk of penile cancer. The American Cancer Society suggests that smegma may not be carcinogenic, but may increase the risk by causing irritation and inflammation of the penis. *

Balanitis Balanitis is inflammation of the glans penis. When the foreskin is also affected, the proper term is balanoposthitis. Balanitis on boys still in diapers must be distinguished from redness caused by ammoniacal dermatitis. The word ''balanitis'' ...

and penile injury—Inflammation of the

and/or the

glans penis In male human anatomy, the glans penis, commonly referred to as the glans, is the bulbous structure at the distal end of the human penis that is the human male's most sensitive erogenous zone and their primary anatomical source of sexual p ...

(balanitis) is associated with about 3.1 times increased risk of penile cancer. It is usually caused by poor hygiene,

allergic reactions Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...

to certain

soaps Soap is a surfactant cleaning compound used for personal or other cleaning. Soap may also refer to: Education * Supplemental Offer and Acceptance Program, for medical students who were not initially matched with U.S. residencies by the National ...

, or an underlying health condition such as

reactive arthritis Reactive arthritis, also known as Reiter's syndrome, is a form of inflammatory arthritis that develops in response to an infection in another part of the body (cross-reactivity). Coming into contact with bacteria and developing an infection can ...

, infection, or

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

.PubMed Health

PubMed PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine (NLM) at the National Institutes of Health maintain the ...

, Last Reviewed: September 16, 2011 Small tears and abrasions of the penis are associated with about 3.9 times increased risk of cancer. *

Phimosis Phimosis (from Greek φίμωσις ''phimōsis'' 'muzzling'.) is a condition in which the foreskin of the penis cannot stretch to allow it to be pulled back past the glans. A balloon-like swelling under the foreskin may occur with urination. In ...

—Phimosis is a medical condition where the foreskin cannot be fully retracted over the glans. It is considered a significant risk factor in the development of penile cancer (

odds ratio An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of A in the presence of B and the odds of A in the absence of B, or equivalently (due ...

of 38–65). Phimosis may also be a symptom of penile cancer. *

Paraphimosis Paraphimosis is an uncommon medical condition in which the foreskin of a penis becomes trapped behind the glans penis, and cannot be ''reduced'' (pulled back to its normal flaccid position covering the glans). If this condition persists for several ...

—Paraphimosis is a medical condition where the foreskin becomes trapped behind the

glans The glans (, plural "glandes" ; from the Latin word for "acorn") is a vascular structure located at the tip of the penis in male mammals or a homologous genital structure of the clitoris in female mammals. Structure The exterior structure ...

. It is considered a risk factor for the development of penile cancer. *

Circumcision Circumcision is a surgical procedure, procedure that removes the foreskin from the human penis. In the most common form of the operation, the foreskin is extended with forceps, then a circumcision device may be placed, after which the foreskin ...

—Some studies show that circumcision during infancy or in childhood may provide partial protection against penile cancer, but this is not the case when performed in adulthood. It has been suggested that the reduction in risk may be due to reduced risk of

; other possible mechanisms include reduction in risk of

smegma Smegma (Ancient Greek σμῆγμα : ''smēgma'') is a combination of shed skin cells, skin oils, and moisture. It occurs in both male and female mammalian genitalia. In females, it collects around the clitoris and in the folds of the labia ...

and

HPV Human papillomavirus infection (HPV 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 re ...

infection.

Other

* Age—Penile cancer is rarely seen in men under the age of 50. About 4 out of 5 men diagnosed with penile cancer are over the age of 55. *

Lichen sclerosus Lichen sclerosus (LS) is a chronic, inflammatory skin disease of unknown cause which can affect any body part of any person but has a strong preference for the genitals (penis, vulva) and is also known as balanitis xerotica obliterans (BXO) when ...

—Lichen sclerosus is a disease causing white patches on the skin. Lichen sclerosus increases the risk of penile cancer. As the exact cause of lichen sclerosus is unknown, there is no known way to prevent it. *

Tobacco Tobacco is the common name of several plants in the genus '' Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the ...

—Chewing or

smoking Smoking is a practice in which a substance is burned and the resulting smoke is typically breathed in to be tasted and absorbed into the bloodstream. Most commonly, the substance used is the dried leaves of the tobacco plant, which have bee ...

tobacco increases the risk of penile cancer by 1.5–6 times depending on the duration smoking and daily number of cigarettes. *

Ultraviolet light Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nanometer, nm (with a corresponding frequency around 30 Hertz, PHz) to 400 nm (750 Hertz, THz), shorter than that of visible light, but longer than ...

—Men with

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...

who have been treated using UV light and a drug known as

psoralen Psoralen (also called psoralene) is the parent compound in a family of naturally occurring organic compounds known as the linear furanocoumarins. It is structurally related to coumarin by the addition of a fused furan ring, and may be considered ...

have an increased risk of penile cancer.

Pathogenesis

Penile cancer arises from

precursor Precursor or Precursors may refer to: * Precursor (religion), a forerunner, predecessor ** The Precursor, John the Baptist Science and technology * Precursor (bird), a hypothesized genus of fossil birds that was composed of fossilized parts of u ...

lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...

s, which generally progress from low-grade to high-grade lesions. For HPV related penile cancers this sequence is as follows: #

Squamous Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

hyperplasia; # Low-grade penile intraepithelial neoplasia (PIN); # High-grade PIN (carcinoma in situ—

Bowen's disease Squamous-cell skin cancer, also known as cutaneous squamous-cell carcinoma (cSCC), is one of the main types of skin cancer along with basal cell cancer and melanoma. It usually presents as a hard lump with a scaly top but can also form an ulcer. ...

, Erythroplasia of Queyrat and

bowenoid papulosis Bowenoid papulosis is a cutaneous condition characterized by the presence of pigmented verrucous papules on the body of the penis.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. . They are assoc ...

(BP)); # Invasive carcinoma of the penis. However, in some cases non- dysplastic or mildly dysplastic lesions may progress directly into cancer. Examples include flat penile lesions (FPL) and '' condylomata acuminata''. In

negative cancers the most common precursor lesion is

lichen sclerosus Lichen sclerosus (LS) is a chronic, inflammatory skin disease of unknown cause which can affect any body part of any person but has a strong preference for the genitals (penis, vulva) and is also known as balanitis xerotica obliterans (BXO) when ...

(LS).

Diagnosis

The International Society of Urological Pathology (ISUP) recommends the use of

p16 p16 (also known as p16INK4a, cyclin-dependent kinase inhibitor 2A, CDKN2A, multiple tumor suppressor 1 and numerous other synonyms), is a protein that slows cell division by slowing the progression of the cell cycle from the G1 phase to the S p ...

^INK4A

immunostaining In biochemistry, immunostaining is any use of an antibody-based method to detect a specific protein in a sample. The term "immunostaining" was originally used to refer to the immunohistochemical staining of tissue sections, as first described by A ...

for the diagnosis and classification of HPV-related penile cancer.

Classification

Around 95% of penile cancers are squamous cell carcinomas. They are classified into the following types: * basaloid (4%) * warty (6%) * mixed warty-basaloid (17%) * verrucous (8%) * papillary (7%) * other SCC mixed (7%) * sarcomatoid carcinomas (1%) * not otherwise specified (49%) Other types of carcinomas are rare and may include

small cell Small cells are low-powered cellular radio access nodes that operate in licensed and unlicensed spectrum that have a range of 10 meters to a few kilometers. In other words, they are base stations with low power consumption and cheap cost that ...

Merkel cell Merkel cells, also known as Merkel-Ranvier cells or tactile epithelial cells, are oval-shaped mechanoreceptors essential for light touch sensation and found in the skin of vertebrates. They are abundant in highly sensitive skin like that of the f ...

clear cell In histology, a clear cell is a cell that shows a clear cytoplasm when stained with hematoxylin and eosin (H&E). Normal histology In the skin, some secretory cells in the epithelium appear as clear cells, and are one of the components of eccrine ...

, sebaceous cell or basal cell tumors. Non-epithelial malignancies such as

s and

sarcoma A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal ( connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sar ...

s are even more rare.

Staging

Like many

malignancies Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...

, penile cancer can spread to other parts of the body. It is usually a primary malignancy, the initial place from which cancer spreads in the body. Much less often it is a secondary malignancy, one in which the cancer has spread to the penis from elsewhere. The staging of penile cancer is determined by the extent of tumor invasion, nodal metastasis, and distant metastasis. The T portion of the

AJCC {{Short description, Organization standardising cancer staging The American Joint Committee on Cancer (AJCC) is an organization best known for defining and popularizing cancer staging standards, officially the AJCC staging system. The American Joi ...

TNM staging The TNM Classification of Malignant Tumors (TNM) is a globally recognised standard for classifying the extent of spread of cancer. It is a classification system of the anatomical extent of tumor cancers. It has gained wide international acceptance ...

guidelines are for the primary tumor as follows: * TX: Primary tumor cannot be assessed. * T0: No evidence of primary tumor. * Tis: Carcinoma ''in situ''. * Ta: Noninvasive verrucous carcinoma. * T1a: Tumor invades subepithelial connective tissue without lymph vascular invasion and is not poorly differentiated (i.e., grade 3–4). * T1b: Tumor invades subepithelial connective tissue with lymph vascular invasion or is poorly differentiated. * T2: Tumor invades the corpus spongiosum or cavernosum. * T3: Tumor invades the urethra or prostate. * T4: Tumor invades other adjacent structures. Anatomic Stage or Prognostic Groups of penile cancer are as follows: * Stage 0—Carcinoma ''in situ''. * Stage I—The cancer is moderately or well-differentiated and only affects the subepithelial connective tissue. * Stage II—The cancer is poorly differentiated, affects lymphatics, or invades the corpora or urethra. * Stage IIIa—There is deep invasion into the penis and metastasis in one lymph node. * Stage IIIb—There is deep invasion into the penis and metastasis into multiple inguinal lymph nodes. * Stage IV—The cancer has invaded into structures adjacent to the penis, metastasized to pelvic nodes, or distant metastasis is present.

HPV positive tumors

prevalence in penile cancers is high at about 40%.

HPV16 ''Papillomaviridae'' is a family of non- enveloped DNA viruses whose members are known as papillomaviruses. Several hundred species of papillomaviruses, traditionally referred to as "types", have been identified infecting all carefully inspected ...

is the predominant genotype accounting for approximately 63% of HPV-positive tumors. Among warty/basaloid cancers the HPV prevalence is 70–100% while in other types it is around 30%.

Prevention

HPV vaccine Human papillomavirus (HPV) vaccines are vaccines that prevent infection by certain types of human papillomavirus (HPV). Available HPV vaccines protect against either two, four, or nine types of HPV. All HPV vaccines protect against at least HP ...

s such as

Gardasil Gardasil is an HPV vaccine for use in the prevention of certain strains of human papillomavirus (HPV). Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledge ...

Cervarix Cervarix is a vaccine against certain types of cancer-causing human papillomavirus (HPV). Cervarix is designed to prevent infection from HPV types 16 and 18, that cause about 70% of cervical cancer cases. These types also cause most HPV-induced ...

may reduce the risk of HPV and, consequently, penile cancer. * The use of condoms is thought to be protective against HPV-associated penile cancer. * Good genital hygiene, which involves washing the penis, the scrotum, and the foreskin daily with water, may prevent balanitis and penile cancer. However, soaps with harsh ingredients should be avoided. * Cessation of smoking may reduce the risk of penile cancer. * Circumcision during infancy or in childhood may provide partial protection against penile cancer. Several authors have proposed circumcision as a possible strategy for penile cancer prevention; however, the American Cancer Society points to the rarity of the disease and notes that neither the American Academy of Pediatrics nor the Canadian Academy of Pediatrics recommend routine neonatal circumcision. * Phimosis can be prevented by practising proper hygiene and by retracting the foreskin on a regular basis. * Paraphimosis can be prevented by not leaving the foreskin retracted for prolonged periods of time.

Treatment

Treatment of penile cancer will vary depending on the clinical stage of the tumor at the time of diagnosis. There are several treatment options for penile cancer, depending on staging. They include

surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...

radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radi ...

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

, and biological therapy. The most common treatment is one of five types of surgery: *

Wide local excision A wide local excision (WLE) is a surgical procedure to remove a small area of diseased or problematic tissue with a margin of normal tissue. This procedure is commonly performed on the breast and to skin lesions, but can be used on any area of the ...

—the tumor and some surrounding healthy tissue are removed *

Microsurgery Microsurgery is a general term for surgery requiring an operating microscope. The most obvious developments have been procedures developed to allow anastomosis of successively smaller blood vessels and nerves (typically 1 mm in diameter) whic ...

—surgery performed with a microscope is used to remove the tumor and as little healthy tissue as possible *

Laser surgery Laser surgery is a type of surgery that uses a laser (in contrast to using a scalpel) to cut tissue. Examples include the use of a laser scalpel in otherwise conventional surgery, and soft-tissue laser surgery, in which the laser beam vapor ...

—laser light is used to burn or cut away cancerous cells *

—cancerous foreskin is removed * Amputation (

penectomy Penectomy is penis removal through surgery, generally for medical or personal reasons. Medical reasons for penectomy Cancer, for example, sometimes necessitates removal of part or all of the penis. The amount of penis removed depends on the se ...

)—a partial or total removal of the penis, and possibly the associated

lymph nodes A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...

. The role of radiation therapy includes an organ-sparing approach for early-stage penile cancer at specialized centres. Furthermore, adjuvant therapy is used for patients with locally advanced disease or for symptom management.

Prognosis

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%.

Epidemiology

Penile cancer is a rare cancer in

developed nations A developed country (or industrialized country, high-income country, more economically developed country (MEDC), advanced country) is a sovereign state that has a high quality of life, developed economy and advanced technological infrastruct ...

, with annual incidence varying from 0.3 to 1 per 100,000 per year, accounting for around 0.4–0.6% of all malignancies. The annual incidence is approximately 1 in 100,000 men in the United States, 1 in 250,000 in Australia, and 0.82 per 100,000 in Denmark. In the United Kingdom, fewer than 500 men are diagnosed with penile cancer every year. In the

developing world A developing country is a sovereign state with a lesser developed industrial base and a lower Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is also no clear agreem ...

, penile cancer is much more common. For instance, in

Paraguay Paraguay (; ), officially the Republic of Paraguay ( es, República del Paraguay, links=no; gn, Tavakuairetã Paraguái, links=si), is a landlocked country in South America. It is bordered by Argentina to the south and southwest, Brazil to th ...

Uruguay Uruguay (; ), officially the Oriental Republic of Uruguay ( es, República Oriental del Uruguay), is a country in South America. It shares borders with Argentina to its west and southwest and Brazil to its north and northeast; while bordering ...

Uganda }), is a landlocked country in East Africa East Africa, Eastern Africa, or East of Africa, is the eastern subregion of the African continent. In the United Nations Statistics Division scheme of geographic regions, 10-11-(16*) territor ...

and

Brazil Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...

the incidence is 4.2, 4.4, 2.8 and 1.5–3.7 per 100,000, respectively. In some South American countries, Africa, and Asia, this cancer type constitutes up to 10% of malignant diseases in men. The

lifetime risk In epidemiology, incidence is a measure of the probability of occurrence of a given medical condition in a population within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time peri ...

has been estimated as 1 in 1,437 in the United States and 1 in 1,694 in Denmark.

References

External links

{{DEFAULTSORT:Penile cancer Male genital neoplasia Rare cancers

Papillomavirus-associated diseases