Penile cancer

• HIV infection—HIV-positive men have eight-fold increased risk of developing penile cancer than HIV-negative men.[7][8]
• Human papillomavirus—HPV is a risk factor in the development of penile cancer.[9] According to the Center for Disease Control and Prevention (CDC), HPV is responsible for about 800 (about 40%) of 1,570 cases of penile cancer diagnosed annually in the United States.[10][11] There are more than 120 types of HPV.[12]
• Genital warts—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.[9] About half of men with penile cancer also have genital warts, which are caused by HPV.[13]

• Poor hygiene—Poor hygiene can increase a man's risk of penile cancer.[14][15]
• Smegma—Smegma, a whitish substance that can accumulate beneath the foreskin, is associated with greater risk of penile cancer.[7][16] The American Cancer Society suggests that smegma may not be carcinogenic, but may increase the risk by causing irritation and inflammation of the penis.[7]
• Balanitis and penile injury—Inflammation of the foreskin and/or the glans penis (balanitis) is associated with about 3.1 times increased risk of penile cancer.[9] It is usually caused by poor hygiene, allergic reactions to certain soaps, or an underlying health condition such as reactive arthritis, infection, or diabetes.[17] Small tears and abrasions of the penis are associated with about 3.9 times increased risk of cancer.
• Phimosis—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 of 38–65).[9] Phimosis may also be a symptom of penile cancer.[18]
• Paraphimosis—Paraphimosis is a medical condition where the foreskin becomes trapped behind the glans. It is considered a risk factor for the development of penile cancer.[7]
• Circumcision—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.[19] It has been suggested that the reduction in risk may be due to reduced risk of phimosis;[7][19] other possible mechanisms include reduction in risk of smegma and HPV infection.[7]

• 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.[7]
• Lichen sclerosus—Lichen sclerosus is a disease causing white patches on the skin. Lichen sclerosus increases the risk of penile cancer.[14][20] As the exact cause of lichen sclerosus is unknown, there is no known way to prevent it.[14]
• Tobacco—Chewing or smoking tobacco increases the risk of penile cancer by 1.5–6 times depending on the duration smoking and daily number of cigarettes.[4][9][14]
• Ultraviolet light—Men with psoriasis who have been treated using UV light and a drug known as psoralen have an increased risk of penile cancer.[7][14]

Around 95% of penile cancers are squamous cell carcinomas. They are classified into the following types:[22]

• 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, Merkel cell, clear cell, sebaceous cell or basal cell tumors. Non-epithelial malignancies such as melanomas and sarcomas are even more rare.[4]

Like many malignancies, 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.[23]

The T portion of the AJCC TNM staging guidelines are for the primary tumor as follows:[23]

• 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:[23]

• 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.

Human papillomavirus prevalence in penile cancers is high at about 40%. HPV16 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%.[4]