Penile warts are the most common sexually transmitted disease in men, caused by the human papillomavirus (HPV). Penile warts typically appear as soft, flesh-colored or brown plaques on the glans and shaft of the penis.
To update the current understanding, diagnosis, and treatment of penile warts, we conducted a review using key terms and terms 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. HPV infection does not mean that a person will develop genital warts. An estimated 0. 5% to 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 that belongs to the genus Papillomavirus in the family Papillomaviridae and infects only humans. The 8-kilobase circular genome of the virus encodes eight genes, including two encapsulating structural proteins, namely the genes for L1 and L2. The virus-like particle containing L1 is used to make HPV vaccines. L1 and L2 mediate HPV infection.
You can be infected with different types of HPV at the same time. In adults, genital HPV infection spreads mainly through sexual contact, less often through oral sex, skin-to-skin and fomites. In children, HPV infection can occur as a result of sexual abuse, vertical transmission, self-infection, close household contact, and infection through fomites. HPV penetrates the cells of the basal layer of the epidermis through microtraumas on the skin or mucous membrane.
The incubation period of the infection lasts from 3 weeks to 8 months, on average 2-4 months. The disease occurs more often in people with the following predisposing factors: immunodeficiency, unprotected sex, multiple sexual partners, sexual partners with multiple sexual partners, history of sexually transmitted infections, early sexual activity, shorter time between encountersnew partner and sexual intercourse, living with him, uncircumcision and smoking. Other predisposing factors are moisture, maceration, trauma and epithelial defects in the penile region.
Fabricated
Histologic examination reveals papillomatosis, focal parakeratosis, severe acanthosis, multiple vacuolated koilocytes, vascular dilatation, and large keratohyaline granules.
Clinical manifestations
Penile warts are usually asymptomatic and may occasionally itch or cause pain. Genital warts are usually found on the frenulum, the glans penis, the inner surface of the foreskin, and the coronal sulcus. At the onset of the disease, penile warts typically appear as small, discrete, soft, smooth, pearl-like, dome-shaped papules.
Lesions can occur individually or in groups (clustered). They can be pedunculated or broad-based (sediate). Over time, papules can coalesce into plaques. Warts can be filiform, exophytic, papillomatous, verrucous, hyperkeratotic, cerebriform, mushroom-shaped, or cauliflower-shaped. The color can be flesh-colored, pink, erythematous, brown, violet, or hyperpigmented.
Diagnosis
The diagnosis is made clinically, usually based on history and examination. Dermoscopy and in vivo confocal microscopy improve diagnostic accuracy. Morphologically, warts can vary from finger-shaped and conical to mosaic. Features of vascularization include glomerular, hairpin, and punctate vessels. Papillomatosis is an organic feature of warts. Some authors recommend the use of the acetic acid test (whitening of the surface of the 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 is considered low for other types of penile warts and subclinical infected areas. Skin biopsy is rarely warranted, but should be considered in the presence of atypical symptoms (eg, atypical pigmentation, induration, attachment to underlying structures, hard consistency, ulceration, or bleeding), when the diagnosis is uncertain, or in warts that are refractory to treatment. various treatments. Although some authors recommend PCR diagnostics, among other things, to determine the HPV type that determines the risk of developing malignant tumors, HPV typing is not recommended in routine practice.
Differential diagnosis
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 post-syphilis, sc. , schwannoma, bowenoid papulosis and squamous cell carcinoma.
Pearly penile papulesAsymptomatic, in the form of small, smooth, soft, yellowish, pearly white or flesh-colored, conical or dome-shaped papules 1-4 mm in diameter. Lesions are usually uniform in size and shape and symmetrically distributed. The papules are usually located in one, two or more rows in a circle around the crown and sulcus of the glans. Papules are usually more noticeable on the back of the crown and less noticeable towards the frenulum.
Fordyce granules- these are enlarged sebaceous glands. On the glans and shaft of the penis, Fordyce granules appear asymptomatically, isolated or in groups, as discrete, cream-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 pulled. Sometimes a thick, chalky or cheese-like substance can be squeezed out of these grains.
Acrochordons, also known as skin tags ("skin tags"), soft, flesh-colored to dark brown, pedunculated or broad-based skin growths with a smooth outline. They can sometimes be hyperkeratotic or warty in appearance. Most acrochordons are between 2 and 5 mm in diameter, although they can sometimes be larger, especially in the groin. Acrochordons can appear almost anywhere on the body, but are most commonly seen on the neck and intertriginal areas. When they appear in the penile area, they can mimic penile warts.
Condylomas lata- These are skin lesions caused by the spirochete Treponema pallidum in secondary syphilis. Clinically, condylomas lata appear as moist, grayish-white, velvety, flat or cauliflower-like, broad 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 may appear on the oral mucosa, as well as alopecia and generalized lymphadenopathy.
Granuloma annularebenign, self-limiting inflammatory disease of the dermis and subcutaneous tissue. The pathology is characterized by asymptomatic, hard, brownish-purple, red or flesh-colored papules, which are usually arranged in a ring. As the condition progresses, central involution is observed. The ring of papules often grows together to form a ring-shaped plaque. The granuloma is usually found on the extensor surface of the distal limbs, but can also be detected on the shaft and glans of the penis.
Lichen planus of the skina chronic inflammatory dermatosis that manifests as flat, polygonal, purple, pruritic papules and plaques. Most often, the rash appears on the hands, back, trunk, legs, ankles, and the flexor surface of the penis. About 25% of lesions occur on the genitals.
Epidermal nevusHamartoma 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 that follows Blaschko's lines. The disease usually begins in the first year of life. Its color varies from flesh to yellow and brown. Over time, the lesion may thicken and become a wart.
Capillary varicose lymphangioma is a benign saccular expansion of the skin and subcutaneous lymph nodes. The condition is characterized by clusters of blisters resembling frog spawn. The color depends on the content: the whitish, yellowish or light brown color is due to the color of the lymph fluid, and the reddish or bluish color is due to the presence of red blood cells in the lymph fluid due to bleeding. The blisters may change and take on a warty appearance. It is most often found on the limbs, less often in the area of the genitals.
Lymphogranuloma venereuma sexually transmitted disease caused by Chlamydia trachomatis. The disease is characterized by transient, painless genital papules and, less commonly, erosions, ulcers, or pustules, followed by inguinal and/or femoral lymphadenopathy known as buboes.
In general,syringomasasymptomatic, small, soft or dense, flesh-colored or brown papules with a diameter of 1-3 mm. They are usually found in the periorbital areas and on the cheeks. However, syringomas can appear on the penis and buttocks. Penile syringomas can be confused with penile warts.
Schwannoma- These are neoplasms from Schwann cells. Penile Schwannoma usually presents as a single, asymptomatic, slow-growing nodule on the back of the shaft of the penis.
Bowenoid papulosisa precancerous focal intraepidermal dysplasia that usually appears as multiple red-brown papules or plaques in the anogenital area, especially in the penis. The pathology is consistent with squamous cell carcinoma in situ. In 2-3% of cases, progression to invasive squamous cell carcinoma occurs.
In general,squamous cell carcinomathe penis manifests itself in the form of a lump, ulcer or redness. The rash can be warty, leukoplakia or sclerosis. The most popular place is the glans penis, followed by the foreskin and 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 contagiousness, stigma, concerns about future fertility and cancer risk, and their association with other sexually transmitted diseases. An estimated 20-34% of affected patients have a sexually transmitted disease. Patients often experience 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 negatively affect 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 anogenital cancer, head cancer, and neck cancer due to co-infection with high-risk HPV.
Forecast
If left untreated, genital warts may go away on their own, remain the same, or increase in size and number. About a third of penile warts will regress 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. Although the warts disappear, the HPV infection may remain, which can lead to recurrence. The relapse rate ranges from 25-67% within 6 months of treatment. Relapses occur in a higher percentage in cases of subclinical infection, repeated infection after sexual contact (reinfection), and immunodeficiency conditions.
Treatment
Active treatment of penile warts is more beneficial than follow-up because it leads to faster healing of lesions, reduces fear of partner infection, relieves emotional stress, improves cosmetic appearance, reduces social stigma associated with penile lesions, and relieves symptoms (e. g. itching, pain or bleeding). Penile warts that have been present for more than 2 years are much less likely to heal on their own, so active treatment should be recommended first. Counseling of sexual partners is mandatory. Screening for sexually transmitted diseases is also recommended.
Active treatments can be divided into mechanical, chemical, immunomodulating and antiviral treatments. 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 level of training of the doctor, the patient's preferences and tolerance for 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 must also be taken into account. In general, self-medication is less effective than self-medication.
The patient performs 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.
25% liquid podophyllin from podophyllotoxin causes mitosis arrest and tissue necrosis. The drug should be applied directly to the penile wart once a week for 6 weeks (up to 0. 5 ml per treatment). Podophyllin should be washed off 1-4 hours after treatment and should not be applied to areas with high skin moisture content. The wart removal efficiency reaches 62%. For toxicity, including death, associated with the use of podophyllin, podofilox is preferred, which has a much better safety profile.
Liquid nitrogen, the treatment of choice for penile warts, can be applied directly to the wart and 2mm around it using a spray bottle or cotton-tipped applicator. Liquid nitrogen causes tissue damage and cell death by rapidly freezing to form ice crystals. The minimum temperature required to kill warts is -50°C, although some authors believe that -20°C is also effective.
The wart removal efficiency reaches 75%. Side effects include pain during treatment, redness, peeling, blistering, erosion, ulceration and dispigmentation at the application site. A recently graduated II. A phase II parallel randomized trial in 16 Iranian men with genital warts showed that cryotherapy using a Wartner preparation containing 75% dimethyl ether and 25% propane was also effective. More research is needed to confirm or refute this conclusion. It must be said that cryotherapy using the Wartner preparation is less effective than cryotherapy using liquid nitrogen.
Bichloroacetic acid and trichloroacetic acid can be used to treat small penile warts because their penetration through the skin is limited. Each of these acids works by coagulating the protein, followed by cell destruction, and consequently removes the penile wart. A burning sensation may occur at the site of application. Relapses after using bichloroacetic acid or trichloroacetic acid occur as often as with other methods. Medicines can be used up to three times a week. Wart removal efficiency ranges from 64 to 88%.
Electrocoagulation, laser therapy, carbon dioxide laser or surgical excision are performed by mechanical destruction of the wart and can be used in cases where there is a rather large wart or a group of warts that are difficult to remove with conservative treatment methods. Mechanical treatment methods have the highest percentage of efficiency, but their use carries a greater risk of scarring the skin. Local anesthesia applied 20 minutes before the procedure to non-occluded lesions or a mixture of local anesthetics applied to occluded lesions one hour before the procedure is considered a measure to reduce discomfort and pain during the procedure. General anesthesia can be used for surgical removal of large lesions.
Alternative treatments
Patients who do not respond to first-line 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.
Antiviral therapy with cidofovir may be considered in immunocompromised patients with unresponsive warts. 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, 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 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 the transmission of HPV when used consistently and correctly. Sexual partners with anogenital warts should be treated.
HPV vaccines before sexual activity are effective in the primary prevention of infection. This is because the vaccines do not protect against HPV vaccine-related diseases that the individual 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 Medicine, and the International Human Papillomavirus Society recommend routine vaccination for girls and boys with the disease. the 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 the HPV vaccine must be administered in month 0, in months 1–2. month (usually 2) and in the 6th month. Catch-up vaccination is recommended for men under 21 and women under 26 if they were not vaccinated at the target age. Vaccination is also recommended for gay or immunocompetent men under the age of 26 if they have not been vaccinated before. Vaccination reduces the likelihood of HPV infection and the subsequent development of 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 incidence of anogenital warts decreased significantly from 2008 to 2014 due to the introduction of the HPV vaccine.
Conclusion
Penile warts are a sexually transmitted disease caused by HPV. This pathology can have a negative psychosocial impact on the patient and negatively affect their quality of life. Although about one-third of penile warts resolve without treatment, active treatment is preferred to speed resolution of warts, 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 often combined. So far, no treatment has been proven to be better than the others. The choice of treatment method depends on the level of expertise of the doctor in this method, the patient's preferences and the tolerability 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 must also be taken into account. HPV vaccinations before sexual intercourse are effective in the primary prevention of infection. The target age for vaccination is 11-12 years for both girls and boys.