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Immunotherapy and penis cancer

Abstract
Penis cancer, a cancerous disease in which malignant cells appear in the tissues of the penis. It occurs in the uncircumcised older men. It is recognized by at least two independent carcinogenic routes: virus and non-virus induced. The penis cancer is also very rare in Europe and North America. In the United States, penis cancer generally occurs in less than 1 man in 100,000 and accounts for less than 1% of cancer in men. Around half of the cancers are mainly caused by an infection with high risk human papilloma virus (hrHPV), and its main type is HPV-16. The other types of penis cancer arise, independent of hrHPV infection. The most common symptoms of penis cancer are irregular swelling at the end of the penis, a growth or sore on the penis, skin thickening on the penis, changes in the color of the penis, small and crusty bumps beneath the foreskin, reddish and velvety rash beneath the foreskin, and pain in the shaft or tip of the penis. Squamous cell or epidermoid carcinomas, basal cell carcinoma, melanoma and sarcoma are different types of penis cancers which are usually rare. The immunotherapy is a good alternative of chemotherapy for the treatment of penis cancer, but maximum drugs and therapies are under the clinical trials for FDA approval.
Keywords: penis cancer, merkel cell carcinoma, squamous cell or epidermoid carcinomas, basal cell carcinoma, melanoma and sarcoma, genitalwarts, penile injury, and psoralen high risk human papilloma virus (hrHPV)

Volume 7 Issue 1 – 2019
Timothy Allen, Shoja E Razavi, Naveed Basha Court
Global Allied Pharmaceuticals, Center for Excellence in Research and Development, USA
Correspondence: Timothy Allen, Global Allied Pharmaceuticals, Center for Excellence in Research and Development, 160 Vista Oak Dr. Longwood, FL 32779, USA, Email
Received: December 14, 2018 | Published: January 10, 2019

Abbreviations: AIN, anal intraepithelial neoplasias; CR, complete response; HIV, human immunodeficiency virus; HPV, human papilloma virus; hrHPV, high risk human papilloma virus; PIN, penis intraepithelial neoplasias; RCT, randomized controlled trials; RR, recurrence rates; VIN, vulvar intraepithelial neoplasias
Introduction/Epidemiology
Penis cancer is when the malignant cells appear in the tissues of the penis. Approximately 95% of penile cancers are squamous cell carcinoma. Othertypes; of penis cancer like melanoma, small cell carcinoma, Merkel cell carcinoma are usually rare.1 The penis cancer is also very rare in Europe and North America. In the United States, penis cancer generally occurs in less than 1 man in 100,000 and accounts for less than 1% of cancer in men. However, penis cancer is much more common in some regions of South America, Africa, and Asia, where it holds for up to 10% of cancers in men.2 According to the National Cancer Institute, in the year 2014 in United States, 1,640 new cases were estimated. Additionally, in the same year, 320 death cases were also estimated.3 As per the statistical analysis, the age-standardized incidence of penis cancer is much higher in non-Western world. It signifies 10-20% of cancerous disease in men, ranging from 0.7 to 3 per 100,000 persons in India to 8.3 per 100,000 men in Brazil, and even higher in Uganda, where it is usually diagnosed. The penis cancer is a very rare cancer among all the male cancers, with higher incidences observed in between the age of 75-84 years.2,4
Etiology/Predisposing Factors
Generally, penis cancer occurs in the uncircumcised men. Circumcision is the elimination of the foreskin,and may decrease the chances of penis cancer.5 The different types of penis cancer are as follows:5
a.
Epidermoid/squamous cell carcinoma: About 95% of the penile cancers are squamous cell or epidermoid carcinomas. The epidermoid carcinoma can initiate anywhere on the penis; though, it normally develops on or under the foreskin.

b.
Basal cell carcinoma: Below the squamous cells in the lower epidermis, are round cells, known as basal cells and occasionally, these can transform into malignancy. It is a type of non-melanoma skin cancer, which represents less than 2% of penis cancer.
c.
Melanoma: Although, this type is the rarest subtype of penile cancer, it is the one with the worst prognosis.
d.
Sarcoma: Sarcoma accounts for about 1% of penis cancer. These are the cancers that develop in connective tissues, such as fat, muscles, and blood vessels.
The most common symptoms of penis cancer are irregular swelling at the end of the penis, a growth or sore on the penis, skin thickening on the penis, changes in the color of the penis, small and crusty bumps beneath the foreskin, reddish and velvety rash beneath the foreskin, and pain in the shaft or tip of the penis.5 There are common risk factors of penis cancer, such as age, smoking, HPV infection, phimosis, HIV infection, genital warts, penile injury, and psoralen –UV-A chemotherapy.2
Pathophysiology/Molecular basis
In the molecular concept, the penis cancer is recognized by at least two independent carcinogenic routes: virus and non-virus induced. Around half of the cancers are mainly caused by an infection with high risk human papilloma virus (hrHPV), and its main type is HPV-16.6–11 The other types of penis cancer arise, independent of hrHPV infection.12 However, the molecular routes of disruption vary in many ways, which is particularly related to the early genetic events and the activity of the known viral oncogenes, E6 and E7. The various common cellular pathways are disrupted at the earlier and later stages during the penis cancer , in both the virus and non-virus induced types of cancer . The penis cancer is likely to be initiated through the interference with the cellular p16INK4a/cyclin D/Rb pathways or p14AER/MDM2/p53, either by viral (HPV) or non-viral (mutation) mechanism. This might result in an uncontrolled division of cells, and may also trigger a state of chromosomal instability, which further drives the carcinogenic process. The metastasis, angiogenesis,

Immunotherapy and penis cancer