Penile warts are the most common sexually transmitted disease in men and are caused by the human papillomavirus (HPV). Penile warts typically appear as soft, flesh-colored to brown plaques on the glans and shaft of the penis.
To provide an up-to-date overview of the current understanding, diagnosis and treatment of penile warts, a review was carried out using key terms and phrases such as "penile warts" and "genital warts". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies and reviews.
Epidemiology
HPV infection is the most common sexually transmitted disease worldwide. Infection with HPV does not mean that a person will develop genital warts. It is estimated that 0. 5–5% of sexually active young adult men have genital warts on physical examination. The disease peaks at 25 – 29 years.
etiopathogenesis
HPV is a non-enveloped double-stranded capsid DNA virus that belongs to the genus Papillomavirus of the family Papillomaviridae and only infects humans. The virus has a circular genome of 8 kilobases in length that encodes eight genes, including the genes for two encapsidating structural proteins, namely L1 and L2. The virus-like particle containing L1 is used in the production of HPV vaccines. L1 and L2 mediate HPV infection.
It is also possible to become infected with different types of HPV at the same time. In adults, genital HPV infection is transmitted primarily through sexual contact and less commonly through oral sex, skin-to-skin sex, and fomites. In children, HPV infection can occur as a result of sexual abuse, vertical transmission, self-infection, infection through close household contact and from fomites. HPV penetrates the cells of the basal layer of the epidermis through microtrauma on the skin or mucous membrane.
The incubation period of an infection is 3 weeks to 8 months, with an average of 2 to 4 months. The disease occurs more often in people with the following predisposing factors: immunodeficiency, unprotected sexual intercourse, multiple sexual partners, a sexual partner with multiple sexual partners, a history of sexually transmitted infections, early sexual activity, a shorter period of time between meeting new partners and sexual intercourse, living with him, not be circumcised and smoke. Other predisposing factors include moisture, maceration, trauma and epithelial defects in the penile area.
Histopathology
Histological examination shows papillomatosis, focal parakeratosis, severe acanthosis, multiple vacuolated koilocytes, vascular distention, and large keratohyaline granules.
Clinical manifestations
Penile warts are usually asymptomatic and may occasionally cause itching or pain. Genital warts are usually located on the frenulum, glans, inside of the foreskin, and coronal sulcus. At the onset of the disease, penile warts typically appear as small, discrete, soft, smooth, pearly, dome-shaped papules.
Lesions can occur singly or in clusters (grouped). They can be stalked or broad-based (sessile). Over time, papules can merge into plaques. Warts can be filiform, exophytic, papillomatous, warty, hyperkeratotic, cerebriform, fungal, or cauliflower-shaped. The color can be flesh-colored, pink, flushed, brown, purple or hyperpigmented.
diagnosis
The diagnosis is made clinically, usually on the basis of history and examination. Dermoscopy and in vivo confocal microscopy help improve diagnostic accuracy. Morphologically, warts can vary from finger-shaped to pineal-shaped to mosaic-like. Features of vascularization include glomerular, hairpin, and punctate vessels. Papillomatosis is a key feature of warts. Some authors suggest the use of the acetic acid test (whitening of the surface of the wart when acetic acid is applied) to facilitate the diagnosis of penile warts.
The sensitivity of this test is high for hyperplastic penile warts, but the sensitivity is considered low for other types of penile warts and subclinically infected areas. A skin biopsy is rarely warranted but should be considered when atypical features are present (e. g. atypical pigmentation, induration, adherence to underlying structures, hard consistency, ulcers or bleeding), when the diagnosis is uncertain, or in the case of warts, who do not respond to various treatments. Although some authors propose PCR diagnostics to determine, among other things, the HPV type that determines the risk of malignancy, HPV typing is not recommended in routine practice.
Differential diagnosis
The differential diagnosis includes pearly penile papules, Fordyce granules, acrochordons, condylomas lata in syphilis, molluscum contagiosum, granuloma annulare, lichen planus, lichen planus, seborrheic keratosis, epidermal nevus, capillary varicose lymphangioma, lymphogranuloma venereum, scabies, syringoma, post-traumatic neuroma , schwannoma, bowenoid papulosis and squamous cell carcinoma.
Pearly penile papulesPresented as asymptomatic, small, smooth, soft, yellowish, pearly white or flesh-colored, conical or dome-shaped papules with a diameter of 1 – 4 mm. The lesions are usually uniform in size and shape and symmetrically distributed. Typically, papules are located in single, double, or multiple rows in a circle around the apex and groove of the glans. Papules tend to be more visible on the crown ridge and less noticeable toward the frenulum.
Fordyce granules- these are enlarged sebaceous glands. On the glans and shaft of the penis, Fordyce granules appear as asymptomatic, isolated or grouped, discrete, creamy yellow, smooth papules 1–2 mm in diameter. These papules are more visible on the shaft of the penis during erection or when the foreskin is pulled. Sometimes a dense, chalky or cheese-like material can be squeezed out of these granules.
Acrochordons, also called skin tags, are soft, flesh-colored to dark brown, stalked or broad-based skin growths with a smooth outline. Sometimes they can be hyperkeratotic or have a warty appearance. Most acrochordons are between 2 and 5 mm in diameter, althoughThey can sometimes be larger, especially in the groin area. Acrochordons can appear on almost any part of the body, but are most commonly seen on the neck and intertriginous area. When they occur in the penile area, they can mimic penile warts.
Condylomas lata- These are skin lesions in secondary syphilis caused by the spirochete Treponema pallidum. Clinically, condylomas lata appear as moist, grayish-white, velvety, flat or cauliflower-like, wide papules or plaques. They tend to develop in warm, moist areas of the genitals and perineum. Secondary syphilis is characterized by a nonpruritic, diffuse, symmetrical maculopapular rash on the trunk, palms, and soles. Systemic manifestations include headache, fatigue, pharyngitis, myalgia, and arthralgia. Erythematous or whitish rashes on the oral mucosa, as well as alopecia and generalized lymphadenopathy, may occur.
Granuloma annulareis a benign, self-limiting inflammatory disease of the dermis and subcutaneous tissue. The pathology is characterized by asymptomatic, solid, brownish-purple, erythematous or flesh-colored papules, usually arranged in a ring shape. As the disease progresses, central regression can be noted. A ring of papules often grows together to form a ring-shaped plaque. Granulomas are usually located on the extensor surfaces of the distal extremities, but can also be found on the shaft and glans.
Lichen planus of the skinis a chronic inflammatory dermatosis that manifests as flat, polygonal, purple, itchy papules and plaques. Most often, the rash occurs on the flexural surfaces of the hands, back, trunk, legs, ankles and glans. Approximately 25% of lesions occur on the genitals.
Epidermal nevusis a hamartoma that arises from embryonic ectoderm and differentiates into keratinocytes, apocrine glands, eccrine glands, hair follicles, and sebaceous glands. The classic lesion is a solitary, asymptomatic, well-circumscribed plaque that follows Blaschko's lines. The onset of the disease usually occurs in the first year of life. The color varies from fleshy to yellow and brown. Over time, the lesion may thicken and become warty.
Capillary varicose lymphangioma is a benign sac-shaped enlargement of the cutaneous and subcutaneous lymph nodes. The condition is characterized by clusters of bubbles resembling frog spawn. The color depends on the content: a whitish, yellow or light brown color is due to the color of the lymph fluid, a reddish or bluish color is due to the presence of red blood cells in the lymph fluid as a result of bleeding. The blisters may change and take on a warty appearance. Most often on the extremities, less often in the genital area.
Lymphogranuloma venereumis a sexually transmitted disease caused by Chlamydia trachomatis. The disease is characterized by a transient, painless genital papule and, more rarely, an erosion, ulcer or pustule, followed by inguinal and/or femoral lymphadenopathy called buboes.
Generally,Syringomasare asymptomatic, small, soft or dense, flesh-colored or brown papules with a diameter of 1–3 mm. They are mostly found in the periorbital area and on the cheeks. However, syringomas can occur on the penis and buttocks. When syringomas are located on the penis, they can be confused with penile warts.
Schwannomas- These are neoplasms that originate from Schwann cells. A penile schwannoma usually presents as a single, asymptomatic, slow-growing lump on the back of the penile shaft.
Bowenoid papulosisis a precancerous focal intraepidermal dysplasia that usually presents as multiple reddish-brown papules or plaques in the anogenital area, particularly in the penis. The pathology is consistent with squamous cell carcinoma in situ. Invasive squamous cell carcinoma progresses in 2 to 3% of cases.
Generally,Squamous cell carcinomaPenis manifests itself in the form of a lump, ulcer or erythematous lesion. The rash may be warty, leukoplakic, or sclerotic. The preferred location is the glans, followed by the foreskin and the shaft of the penis.
Complications
Penile warts can cause significant concern or distress to the patient and their sexual partner due to their cosmetic appearance and their contagiousness, stigmatization, concerns about future fertility and cancer risk, and their association with other sexually transmitted diseases. It is estimated that 20-34% of affected patients have underlying sexually transmitted diseases. Patients often experience feelings of guilt, shame, low self-esteem and anxiety. People with penile warts are more likely to suffer from sexual dysfunction, depression and anxiety compared to the healthy population. This condition can have negative psychosocial effects on the patient and negatively impact their quality of life. Large exophytic lesions may bleed, cause urethral obstruction, and interfere with sexual intercourse. Malignant transformation is rare, except in immunocompromised individuals. Patients with penile warts are at increased risk of developing genital cancer, head cancer, and neck cancer due to co-infection with high-risk HPV.
forecast
If no treatment is given, genital warts may resolve on their own, remain unchanged, or increase in size and number. Approximately one-third of penile warts resolve without treatment and the average time to disappear is about 9 months. With proper treatment, 35 to 100% of warts disappear within 3 to 16 weeks. Although the warts disappear, the HPV infection may persist and cause a recurrence. Relapse rates range from 25 to 67% within 6 months of treatment. A higher percentage of relapses occurs in patients with subclinical infection, recurrent infection (reinfection) after sexual intercourse and in the presence of immunodeficiencies.
Treatment
Active treatment of penile warts is preferable to follow-up care because it results in faster resolution of lesions, reduces fear of partner infection, relieves emotional distress, improves cosmetic appearance, reduces social stigma associated with penile lesions, and relieves symptoms (e. g. , e. g. itching, pain or bleeding). Penile warts that have persisted for more than two years are significantly less likely to disappear on their own, so active treatment should be offered first. Counseling of sexual partners is mandatory. Screening for sexually transmitted diseases is also recommended.
Active treatments can be divided into mechanical, chemical, immunomodulatory and antiviral treatments. There are very few detailed comparisons of different treatment methods with each other. The effectiveness varies depending on the treatment method. To date, no one treatment has been proven to be consistently superior to other treatments. The choice of treatment should depend on the doctor's skills, the patient's preference and tolerance to the treatment, as well as the number of warts and the severity of the disease. The comparative effectiveness, ease of administration, side effects, cost and availability of the treatment should also be considered. In general, self-administered treatment is considered less effective than self-administered treatment.
The patient carries out the treatment at home (according to the doctor's prescription)
Treatment methods in the clinic
Methods used in the clinic include podophyllin, liquid nitrogen cryotherapy, bichloroacetic acid or trichloroacetic acid, oral cimetidine, surgical excision, electrocautery, and carbon dioxide laser therapy.
Liquid podophyllin 25%, derived from podophyllotoxin, stops mitosis and causes tissue necrosis. The medication is applied directly to the penile wart once a week for 6 weeks (maximum 0. 5 ml per treatment). Podophyllin should be washed off 1 to 4 hours after treatment and should not be applied to areas of high skin moisture. The effectiveness of wart removal reaches 62%. Due to reports of toxicity, including deaths, associated with the use of podophyllin, podofilox, which has a much better safety profile, is considered preferred.
Liquid nitrogen, the treatment of choice for penile warts, can be applied directly to the wart and 2 mm around it using a spray bottle or cotton-tipped applicator. Liquid nitrogen causes tissue damage and cell death by rapidly freezing into ice crystals. The minimum temperature required to destroy warts is -50 °C, although some authors believe that -20 °C is also effective.
The effectiveness of wart removal reaches 75%. Side effects include pain during treatment, erythema, desquamation, blistering, erosion, ulceration, and dyspigmentation at the application site. A recent parallel phase II randomized trial in 16 Iranian men with genital warts showed that cryotherapy with Wartner's formulation, which contained a mixture of 75% dimethyl ether and 25% propane, was also effective. Further research is needed to confirm or refute this conclusion. It must be said that cryotherapy with the composition of Wartner is less effective than cryotherapy with liquid nitrogen.
Bichloroacetic acid and trichloroacetic acid can be used to treat small penile warts because their ability to penetrate the skin is limited. Each of these acids works by coagulating proteins, followed by cell destruction and subsequent removal of the penile wart. A burning sensation may occur at the application site. Relapses occur just as often after using bichloroacetic acid or trichloroacetic acid as with other methods. The medication can be used up to three times a week. The effectiveness of wart removal is between 64 and 88%.
Electrocoagulation, laser therapy, carbon dioxide laser, or surgical excision through mechanical destruction of the wart can be used for larger warts or clusters of warts that are difficult to remove using conservative treatment methods. Mechanical treatment methods are most effective, but their use carries a higher risk of scarring the skin. Local anesthesia applied to non-occluded lesions 20 minutes before the procedure or a mixture of local anesthetics applied to occluded lesions one hour before the procedure should be considered as measures to relieve discomfort and pain during the procedure. General anesthesia may be used to surgically remove large lesions.
Alternative treatments
Patients who do not respond to initial treatments may respond to other treatments or a combination of treatments. Second-line therapy includes topical, intralesional, or intravenous cidofovir, topical 5-fluorouracil, and topical ingenol mebutate.
In immunocompromised patients with refractory warts, antiviral therapy with cidofovir may be considered. Cidofovir is an acyclic nucleoside phosphonate that competitively inhibits viral DNA polymerase, thereby preventing viral replication.
Side effects of topical (intralesional) cidofovir include irritation, erosion, postinflammatory pigmentary changes, and superficial scarring at the application site. The main side effect of intravenous cidofovir is nephrotoxicity, which can be prevented by hydration with saline and probenecid.
prevention
Genital warts can be prevented to some extent by delaying sexual activity and limiting the number of sexual partners. Latex condoms reduce HPV transmission when used consistently and correctly. Sexual partners with anogenital warts should be treated.
HPV vaccines are effective before sexual activity and are used for primary infection prevention. This is because vaccines do not provide protection against diseases caused by vaccinated types of HPV that a person acquired through previous sexual activity. The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention, the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, the American Academy of Family Practice, and the International Human Papillomavirus Society recommend routine vaccination of girls and boys with HPV-Vaccine.
The target age for vaccination for girls and boys is 11 – 12 years. The vaccine can be administered as early as 9 years of age. Three doses of the HPV vaccine should be given at month 0, months 1 to 2 (usually 2), and month 6. A catch-up vaccination is indicated for men under 21 years of age and women under 26 years of age if they have not yet been vaccinated at the target age. The vaccination is also recommended for gay or immunocompetent men under the age of 26 if they have not yet been vaccinated. Vaccination reduces the likelihood of becoming infected with HPV and subsequently developing penile warts and penile cancer. Vaccinating both men and women reduces the risk of genital warts on the penis better than vaccinating men only, because men can get HPV infection from their sexual partners. The prevalence of anogenital warts decreased significantly from 2008 to 2014 due to the introduction of HPV vaccination.
Diploma
Penile warts are a sexually transmitted disease caused by HPV. This pathology can have negative psychosocial effects on the patient and negatively affect his quality of life. Although about a third of penile warts disappear without treatment, active treatment is preferred to accelerate wart resolution, reduce fear of infection, reduce emotional stress, improve cosmetic appearance, and reduce the social stigma associated with penile lesionsreduce and relieve symptoms.
Active treatment methods can be mechanical, chemical, immunomodulatory and antiviral and are often combined. To date, no treatment has been proven to be superior to the others. The choice of treatment method should depend on the doctor's competence in this method, the patient's preference and tolerance of the treatment, as well as the number of warts and the severity of the disease. The comparative effectiveness, ease of use, side effects, cost and availability of the treatment should also be taken into account. HPV vaccines before sexual activity are effective in primary prevention of infections. The target age for vaccination is 11 to 12 years for both girls and boys.