Penile intraepithelial neoplasia (PIN or PeIN) is a treatable rare condition of precancerous lesion that affects the epidermal layer of the penis. Around 45-50% of penile malignancies are caused due to viral infection by Human Papillomavirus (HPV), of which HPV16 and HPV18 are major tumor causing agents. Non-HPV factors such as chronic inflammatory disease and lichen sclerosus can also cause penile cancers.

Symptoms

The factors causing PeIN lead to symptomatic and asymptomatic conditions such as inflammatory and papulosquamous lesions, infectious lesions, and neoplastic lesions.

Inflammatory and papulosquamous lesions

• Lichen sclerosus produces symptoms such as pain, phimosis, obstructive voiding, and pruritus. Clinically, it may appear as phimotic prepuce, bleeding in hypopigmented areas and with cellophane texture.
• Lichen planus presents with symptoms such as itching and soreness. It appears as polygonal, flat-topped, violaceous sores which are often seen in the extragenital areas.
• Angiokeratomas is an asymptomatic condition of inflammatory and papulosquamous lesion and this type of lesion appear as blue or red sores on the glans of the penis.
• Lichen nitidus is also an asymptomatic condition that occurs in the hypopigmented areas which are in the form of pinhead-sized papules.
• Psoriasis is a symptomatic condition that has itching of the penile surface with some clinical appearance such as salmon or red colored, papulosquamous, and circinate plaques with silvery or white scales on skin.

Infectious lesions

There are some symptoms associated with infectious lesions such as genital herpes, and HPV lesions of the PeIN.

• Genital herpes is a primary disease that characterizes the symptoms of genital vesicles such as prodermal local paresthesias, burning sensation, itching, and hypersensitivity. The clinical appearance of genital herpes includes scarring, formation of pustule from vesicles located on the base of erythematous skin and an isolated dermatome.
• HPV lesions are asymptomatic penile condition which appears as irregular or lobulated surface on perianal and perineum regions with exophytic warts.    

Neoplastic lesions

• Carcinoma in situ is a symptomatic condition of PeIN with symptoms like pain and pruritus. The clinical appearance varies with the development of ulcers on the foreskin of the penile region.
• Invasive squamous cell carcinoma is a symptomatic penile tumor with clinical symptoms of delayed exophytic appearance generally painless. This type of tumor can be local or metastasis.

Causes

The abnormal cell growth on the epidermal layer of the penis is caused by the following factors such as HPV infection, chronic skin disease, exposure to ultraviolet rays, and formation of smegma.

HPV infection: HPV plays a major role in causing penile cancer by interacting with tumor suppressor genes such as Rb (Retinoblastoma) genes, tumor protein p53, and oncogenes. It has been found that the DNA of HPV is present in about 70 to 100% of intraepithelial neoplasia of the penis. Generally, people who undergo multiple sexual contacts have a greater risk of HPV infection that results in the development of penile lesions.

Chronic skin disease: The chronic skin disease that causes intraepithelial neoplasia includes lichen sclerosus, and lichen planus. In lichen sclerosus, the region of genetalia and the anus become weak and cause irritation, excoriation, and fissuring which leads to premalignant condition of penis. Lichen planus is an inflammatory condition that develops itchy and flat-topped bumps resulting in PeIN.

Exposure to ultraviolet rays: The exposure to ultraviolet rays comprising psoralen and ultraviolet on a surface of the skin can lead to DNA damage causing abnormal cell growth in the regions of glans and shaft of the penis.

Smegma: Smegma is a white-colored substance accumulated below the glans which has an elevated risk of causing penile tumors. This substance is not carcinogenic but enhances the risk of penile lesion by causing inflammation and pain in the penis.

Balanitis: Balanitis is a common condition that occurs in uncircumcised males, causing PeIN. This condition occurs due to some factors such as infection of the skin surface, poor hygiene, usage of rough soaps, and uncontrolled diabetes.

Human immunodeficiency virus (HIV): HIV is a subgroup of retrovirus that causes HIV infection, resulting in the damage of the immune system of the body. Males testing HIV positive have an eight times greater risk of premalignant lesions than males testing HIV negative.

Phimosis: Phimosis is a medical condition that is considered as a significant cause for penile cancer. It is an inability to redevelop the prepuce enveloping the glans of the penis.

Paraphimosis: Paraphimosis is also found in uncircumcised males in which the foreskin is struck behind the glans and cannot be further pulled to the tip of penis. This condition is a risk factor for the growth of PeIN.  

Smoking and tobacco chewing: Cigarette smoking and tobacco chewing are also considered as the high-risk factors of causing penile malignancy depending on the number of cigarettes and amount of tobacco utilized by an individual.