Penile warts are the most common sexually transmitted disease in men and are caused by the human papillomavirus (HPV). Penile warts usually present as soft, flesh-colored and brown plaques on the glans and shaft of the penis.
A review was conducted using key terms and phrases such as "penile warts" and "genital warts" to provide an update on the current understanding, diagnosis, and treatment of penile warts. The search strategy included meta-analysis, randomized controlled trials, clinical trials, observational studies and reviews.
Epidemiology
HPV infection is the most common sexually transmitted disease in the world. HPV infection 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 peak age of the disease is 25-29 years.
Etiopathogenesis
HPV is a non-enveloped capsid double-stranded DNA virus belonging to the Papillomavirus genus of the Papillomaviridae family that infects only humans. The virus has a circular genome, 8 kilobases long, that encodes eight genes, including the genes for two encapsulating structural proteins, L1 and L2. The virus-like particle containing L1 is used in the production of HPV vaccines. L1 and L2 mediate HPV infection.
At the same time, it is possible to be infected with different types of HPV. In adults, genital HPV infection is mainly transmitted through sexual intercourse and, less commonly, through oral sex, skin-to-skin contact, and fomites. HPV infection in children can occur through sexual abuse, vertical transmission, self-infection, close household contact, and transmission through fomites. HPV penetrates the cells of the basal layer of the epidermis through microtraumas in the skin or mucous membrane.
The incubation period of infection is from 3 weeks to 8 months, on average 2 - 4 months. The disease is more common in people with the following predisposing factors: immunodeficiency, unprotected sex, multiple sexual partners, sexual partner with multiple sexual partners, history of sexually transmitted infections, early sexual activity, shorter time between meetings. having and having sex with a new partner, not being circumcised and not smoking. Other predisposing factors are moisture, maceration, trauma and epithelial defects in the penile area.
Histopathology
Histological examination reveals papillomatosis, focal parakeratosis, severe acanthosis, numerous vacuolated koilocytes, vascular narrowing and large keratohyaline granules.
Clinical manifestations
Penile warts are usually asymptomatic and can sometimes itch or cause pain. Genital warts are usually located on the frenulum, glans penis, inner surface of the foreskin and coronal sulcus. At the onset of the disease, penile warts usually appear as small, discrete, soft, smooth, pearly, dome-shaped papules.
Lesions can occur individually or in groups (clusters). They can be pedunculated or broad-based (sessile). Over time, papules can coalesce and become plaques. Warts can be filiform, exophytic, papillomatous, verrucous, hyperkeratotic, cerebriform, mushroom-shaped, or cauliflower-shaped. The color may be flesh-colored, pink, erythematous, brown, purple, or hyperpigmented.
Diagnosis
Diagnosis is made clinically, usually based on history and examination. Dermoscopy and in vivo confocal microscopy help improve diagnostic accuracy. Morphologically, warts can vary from finger-shaped and epiphyseal to mosaic. Among the features of vascularization can be found glomerular, hairpin and punctate vessels. Papillomatosis is an integral feature of warts. Some authors suggest using the acetic acid test (whitening of the surface of warts 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 for other penile warts and subclinically infected areas is considered low. A skin biopsy is rarely warranted, but should be considered when there are atypical features (eg, atypical pigmentation, induration, adhesions to underlying structures, hard consistency, ulceration or bleeding), the diagnosis is uncertain, or there are warts resistant to treatment. different treatments. Although some authors suggest PCR diagnostics to determine, among other things, the type of HPV that determines the risk of malignancy, HPV typing is not recommended in routine practice.
Differential diagnosis
Differential diagnosis includes pearly papules of the penis, Fordyce granules, acrochordons, condylomas in syphilis, molluscum contagiosum, granuloma annulare, lichen planus, lichen planus, seborrheic keratosis, epidermal nevus, capillary vemalioma, capillary veteria, violins. syringoma, post-traumatic neuroma, schwannoma, bowenoid papulosis and squamous cell carcinoma.
Pearly papules of the penisIt presents as asymptomatic, small, smooth, soft, yellowish, pearl white or flesh-colored, conical or dome-shaped papules with a diameter of 1-4 mm. 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 crown and groove of the head of the penis. Papules are more prominent posterior to the crown and less prominent 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 clustered, discrete, creamy yellow smooth papules 1-2 mm in diameter. These papules are more noticeable on the shaft of the penis during erection or when the foreskin is retracted. Sometimes a dense chalky or cheese-like material can be squeezed out of these pellets.
Acrochordons, also known as skin tags ("skin tags"), are soft, flesh-colored to dark brown, smooth-contoured, pedunculated or broad-based skin growths. Sometimes they can be hyperkeratotic or have a warty appearance. Most acrochordons are between 2 and 5 mm in diameter, although they can sometimes be larger, especially in the groin. Acrochordons can appear on almost any part of the body, but are most often seen in the neck and intertriginous regions. When they appear 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 appear as moist, gray-white, velvety, flat or cauliflower-like, large 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. An erythematous or whitish rash may occur on the oral mucosa, as well as alopecia and generalized lymphadenopathy.
Granuloma annulareis a benign, self-limiting inflammatory disease of the dermis and subcutaneous tissue. The pathology is characterized by asymptomatic, firm, brown-purple, erythematous or flesh-colored papules, usually arranged in a ring. As the condition progresses, central involution may be noted. A ring of papules often grow 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 of the penis and the glans.
Lichen planus of the skinis a chronic inflammatory dermatosis that manifests as flat, polygonal, purple, itchy papules and plaques. Most often, the rash appears on the curved surfaces of the hands, back, trunk, feet, ankles and the head of the penis. About 25% of lesions occur in the genitals.
Epidermal nevusis a hamartoma arising from embryonic ectoderm that differentiates into keratinocytes, apocrine glands, eccrine glands, hair follicles, and sebaceous glands. The classic lesion is a solitary, asymptomatic, well-circumscribed plaque following Blaschko's lines. The onset of the disease usually occurs in the first year of life. The color varies from flesh to yellow to brown. Over time, the lesion may thicken and turn into a wart.
Capillary varicose lymphangioma is a benign follicular enlargement of the skin and subcutaneous lymph nodes. The condition is characterized by multiple blisters that look like frog spawn. Its color depends on its composition: whitish, yellow or light brown color is due to the color of the lymph fluid, and red or blue color is due to the presence of red blood cells in the lymph fluid due to bleeding. Blisters can undergo changes and take on a warty appearance. It occurs most often in the extremities, less often in the genital area.
Lymphogranuloma venereumChlamydia trachomatis is a sexually transmitted disease. The disease is characterized by a transient painless genital papule and, less commonly, an erosion, ulcer or pustule, followed by inguinal and/or femoral lymphadenopathy known as bubular.
Usually,syringomasare asymptomatic, small, soft or firm, flesh-colored or brown papules 1-3 mm in diameter. They are usually found in the periorbital areas and cheeks. However, syringomas can be seen on the penis and buttocks. When located on the penis, syringomas can be mistaken for penile warts.
Schwannomas- These are neoplasms arising from Schwann cells. Penile schwannoma usually presents as a single, asymptomatic, slow-growing nodule on the dorsal aspect of the penile shaft.
Bowenoid papulosisis a precancerous focal intraepidermal dysplasia that usually appears as multiple reddish-brown papules or plaques in the anogenital area, especially on the penis. The pathology is consistent with squamous cell carcinoma in situ. Progression to invasive squamous cell carcinoma occurs in 2-3% of cases.
Usually,squamous cell carcinomamanifests itself as a penile nodule, ulcer, or erythematous lesion. The rash may appear as a wart, leukoplakia, or sclerosis. The most favored site is the head of the penis, followed by the foreskin and shaft of the penis.
Complications
Penile warts can be a cause of significant concern or anxiety for the patient and their sexual partner due to their cosmetic appearance and their contagiousness, stigma, 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 sexually transmitted diseases. Patients often experience feelings of guilt, shame, low self-esteem and fear. People with penile warts have higher rates of sexual dysfunction, depression, and anxiety than the healthy population. This condition can have a negative psychosocial impact on the patient and can have a negative impact on the quality of life. Large exophytic lesions may cause bleeding, urethral obstruction, and interfere with intercourse. Malignant transformation is rare, except in immunocompromised individuals. Patients with penile warts have an increased risk of developing anogenital cancer, head cancer, and neck cancer as a result of co-infection with high-risk HPV.
Forecast
If left untreated, genital warts may go away on their own, remain unchanged, or increase in size and number. About one-third of penile warts go away without treatment, and the average time it takes for them to disappear is about 9 months. With proper treatment, 35-100% of warts disappear within 3-16 weeks. Even if the warts go away, the HPV infection may remain, causing recurrence. Relapse rates within 6 months of treatment range from 25-67%. A higher percentage of relapses occurs in patients with subclinical infection, recurrent infection after sexual intercourse (reinfection), and immunodeficiencies.
Treatment
Active treatment of penile warts is preferable to continuation because it leads to faster resolution of lesions, reduces fear of partner infection, relieves emotional stress, improves cosmetic appearance, reduces social stigma associated with penile lesions, and relieves symptoms (eg, itching, painor bleeding). Penile warts lasting more than 2 years are unlikely to resolve 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. There are very few detailed comparisons of different treatment methods. Effectiveness varies depending on the treatment method. To date, no treatment has been shown to be consistently superior to other treatments. The choice of treatment should depend on the skill level of the doctor, the patient's preferences and tolerance to treatment, as well as the number of warts and the severity of the disease. Comparative effectiveness, ease of administration, side effects, cost, and availability of treatment should also be considered. In general, self-administered treatment is considered less effective than self-administered treatment.
The patient is receiving treatment at home (as prescribed by the doctor)
Treatment methods used 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, works by mitosis arrest and tissue necrosis. The drug is applied directly to the wart of the penis once a week for 6 weeks (maximum 0. 5 ml for treatment). Podophyllin should be washed off 1-4 hours after treatment and should not be applied to areas with high moisture of the skin. The effectiveness of removing warts reaches 62%. Due to reports of toxicity, including death, associated with the use of podophyllin, podofilox, which has a better safety profile, is preferred.
Liquid nitrogen, the treatment of choice for penile warts, can be applied 2 mm directly onto and around the wart using a spray bottle or cotton-tipped applicator. Liquid nitrogen freezes rapidly to form ice crystals, causing tissue damage and cell death. The minimum temperature required to destroy warts is -50 ° C, although some authors believe that -20 ° C is also effective.
The effectiveness of removing warts reaches 75%. Side effects include pain, erythema, desquamation, blistering, erosion, ulceration, and application site dyspigmentation during treatment. A recent phase II parallel randomized trial in 16 Iranian men with genital warts showed that cryotherapy containing Wartner's mixture of 75% dimethyl ether and 25% propane was also effective. Further studies are needed to confirm or refute this conclusion. It should be noted that cryotherapy using Wartner composition is less effective than cryotherapy using liquid nitrogen.
Dichloroacetic 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 work by coagulating the protein, then destroying the cell and eventually removing the penile wart. A burning sensation may occur at the application site. After using bichloroacetic or trichloroacetic acid, relapses occur as often as with other methods. Medicines can be used up to three times a week. The effectiveness of removing warts ranges from 64 to 88%.
Electrocoagulation, laser therapy, carbon dioxide laser, or surgical excision work by mechanically destroying warts and can be used in cases where there is a large enough wart or a cluster of warts that are difficult to remove with conservative treatments. Mechanical treatment methods have the highest efficiency, but their use has a higher risk of scarring the skin. Local anesthetic applied to non-occluded lesions 20 minutes prior to the procedure or local anesthetic mixture applied to occluded lesions one hour prior to the procedure should be considered as measures to reduce discomfort and pain during the procedure. General anesthesia may be used to surgically remove large lesions.
Alternative treatment methods
Patients who do not respond to first-line therapies may respond to other therapies or a combination of therapies. Second-line therapy includes topical, intralesional, or intravenous cidofovir, topical 5-fluorouracil, and topical ingenol mebutate.
Antiviral therapy with cidofovir may be considered in immunocompromised patients with refractory warts. Cidofovir is an acyclic nucleoside phosphonate that competitively inhibits viral DNA polymerase, thereby preventing viral replication.
Side effects of topical (internal) cidofovir include irritation, erosion, post-inflammatory pigmentary changes, and superficial scarring at the application site. The main side effect of intravenous cidofovir is nephrotoxicity, which can be prevented with saline hydration and probenecid.
Prevention
Genital warts can be prevented to some extent by delaying intercourse and limiting the number of sexual partners. Latex condoms, when used consistently and correctly, reduce HPV transmission. Sexual partners with anogenital warts should be treated.
HPV vaccines are effective in preventing infection prior to sexual activity. This is because vaccines do not provide protection against diseases caused by HPV vaccine types that individuals have 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 recommends routine vaccination of girls and boys. HPV vaccine.
The target age for vaccination is 11-12 years for girls and boys. The vaccine can be administered from the age of 9. Three doses of HPV vaccine should be given at month 0, months 1-2 (usually 2) and month 6. A catch-up vaccine is indicated for males younger than 21 years and females younger than 26 years if not vaccinated at the target age. Vaccination is also recommended for homosexual or immunocompetent men under 26 years of age if not previously vaccinated. The vaccine reduces the chance of contracting HPV and subsequently developing penile warts and penile cancer. Vaccinating both men and women is more beneficial in reducing the risk of penile genital warts than vaccinating only men because men can acquire HPV infection from their sexual partners. The prevalence of anogenital warts decreased significantly between 2008 and 2014 due to the introduction of the HPV vaccine.
The result
Penile warts are a sexually transmitted disease caused by HPV. This pathology can have a negative psychosocial impact on the patient and negatively affect his quality of life. Although approximately one-third of penile warts go away without treatment, active treatment is preferred to speed wart resolution, reduce fear of infection, reduce emotional distress, improve cosmetic appearance, reduce social stigma associated with penile lesions, and relieve symptoms.
Active treatment methods can be mechanical, chemical, immunomodulatory and antiviral and are often combined. So far, no treatment has been proven to be superior to the others. The choice of treatment method should depend on the level of skill of the doctor in this method, the preference and tolerance of the patient, as well as the number of warts and the severity of the disease. Comparative effectiveness, ease of use, side effects, cost, and availability of treatment should also be considered. HPV vaccines before sex are effective in preventing infection in the first place. The target age for vaccination is 11-12 years for both girls and boys.