Penile cancer
Penile cancer is 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. Risk factors include phimosis (inability to retract foreskin of the penis), chronic inflammation, smoking, HPV infection, 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, small cell carcinoma, and melanoma 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) and bleeding from the penis. Pathogenesis. Penile cancer arises from precursor lesions, which generally progress from low-grade to high-grade lesions. For HPV related penile cancers this sequence is as follows: 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 HPV negative cancers the most common precursor lesion is lichen sclerosus (LS). Diagnosis. The International Society of Urological Pathology (ISUP) recommends the use of p16 immunostaining 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: 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. Staging. 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. The T portion of the AJCC TNM staging guidelines are for the primary tumor as follows: Anatomic Stage or Prognostic Groups of penile cancer are as follows: HPV positive tumors. 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%. 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, radiation therapy, chemotherapy, and biological therapy. The most common treatment is one of five types of surgery: 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 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. However, in the developing world penile cancer is much more common. For instance, in Paraguay, Uruguay, Uganda and Brazil 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 has been estimated as 1 in 1,437 in the United States and 1 in 1,694  in Denmark.