Penile warts are the most common sexually transmitted disease in men and are caused by the human papillomavirus (HPV). Penile warts usually appear as soft, flesh-colored to brown plaques on the glans and shaft of the penis.
To provide an update on the current understanding, diagnosis, and treatment of penile warts, a review was conducted using key terms and phrases such as "penile warts" and "genital 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 worldwide. HPV infection does not mean that a person will develop genital warts. It is estimated that 0. 5 - 5% of young sexually active men have genital warts on physical examination. The peak age of the disease is 25 - 29 years.
Etiopathogenesis
HPV is a non-enveloped double-stranded DNA virus that belongs to the genus Papillomavirus of the family Papillomaviridae and infects only humans. The virus has a circular genome of 8 kilobases in length, which encodes eight genes, including genes for two structural encapsulating proteins, 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 be infected with different types of HPV at the same time. In adults, genital HPV infection is mainly transmitted through sexual contact and, less commonly, through oral sex, skin-to-skin and fomites. In children, HPV infection can occur as a result of sexual abuse, vertical transmission, self-infection, infection through close family contact and through fomites. HPV penetrates the cells of the basal layer of the epidermis through microtraumas in the skin or mucosa.
The incubation period of infection varies from 3 weeks to 8 months, with an average of 2 - 4 months. The disease is more common in individuals 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 period ofshort period of time between meeting the new partner and having sex while living with him, not being circumcised and smoking. Other predisposing factors are moisture, maceration, trauma and epithelial defects in the penile region.
Histopathology
Histologic examination reveals papillomatosis, focal parakeratosis, severe acanthosis, multiple vacuolated koilocytes, vascular distension, and large keratohyalin granules.
Clinical manifestations
Penile warts are usually asymptomatic and may occasionally itch or cause pain. Genital warts are usually located on the frenulum, on the penis, on the inner surface of the foreskin, and in the coronal sulcus. Early in the disease, penile warts usually appear as small, discrete, soft, smooth, pearly, dome-shaped papules.
Lesions can occur individually or in groups (clustered). They can be pedunculated or broad-based (sexual). Over time, the papules can coalesce into plaques. Warts can be filiform, exophytic, papillomatous, verrucous, hyperkeratotic, cerebriform, fungal, or cauliflower-shaped. The color may be flesh-colored, pink, erythematous, brown, purple, or hyperpigmented.
diagnostic
Diagnosis is made clinically, usually based on history and examination. In vivo dermoscopy and confocal microscopy help improve diagnostic accuracy. Morphologically, warts can vary from spindle-shaped and pineal-shaped to mosaic. Among the features of vascularization, glomerular, flomerular and punctate vessels can be distinguished. Papillomatosis is an integral feature of warts. Some authors suggest the use of the acetic acid test (whitening of the wart surface when acetic acid is applied) to facilitate the diagnosis of penile warts.
The sensitivity of this test is high for hyperplastic penile warts, but for other types of penile warts and subclinical infected areas the sensitivity is considered low. Skin biopsy is rarely warranted but should be considered in the presence of atypical features (eg, atypical pigmentation, induration, adhesions to underlying structures, firm consistency, ulceration, or bleeding), when the diagnosis is uncertain, or forwarts that are refractory to various treatments. Although some authors propose 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 penile papules, Fordyce granules, acrochordons, condyloma lata in syphilis, molluscum contagiosum, granuloma annulare, lichen planus, lichen planus, seborrheic keratosis, epidermal nevus, capillary varicosities, lymphangioma, lymphangioma-granuloma. matic neuroma, schwannoma, bowenoid papulosis and squamous carcinoma.
Pearly penile papulesThey appear as asymptomatic, small, smooth, soft, yellow, white to curtain 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, the papules are located in single, double or multiple rows in a circle around the crown and groove of the glans penis. Papules tend to be 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 grouped, discrete, creamy yellow, smooth papules 1 - 2 mm in diameter. These papules are most visible on the shaft of the penis during erection or when the foreskin is retracted. Sometimes a dense foamy or cheese-like material can be squeezed out of these grains.
Acrochordons, also known as skin tags ("skin tags"), are soft, flesh-colored to dark brown, pedunculated or broad-based skin growths with a smooth outline. Sometimes they may 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 almost anywhere on the body, but are most commonly seen on the neck and intertriginous areas. When they appear in the penile area, they can mimic penile warts.
Condyloma lata- These are skin lesions in secondary syphilis caused by the spirochete, Treponema pallidum. Clinically, condylomas lata appear as broad, moist, gray-white, velvety, flat, or cauliflower-like 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 white rashes on the oral mucosa may appear, 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, purple-brown, erythematous or flesh-colored papules, usually located in a ring. As the condition progresses, central involution may be seen. A ring of papules often grows together to form a ring-shaped plaque. The granuloma is usually found on the extensor surfaces of the distal extremities, but may also be found on the shaft and penis.
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 flexor surfaces of the hands, back, torso, legs, ankles and penis. Approximately 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 single, asymptomatic, well-circumscribed plaque following Blaschko's lines. The onset of the disease usually occurs in the first year of life. The color changes from flesh to yellow and brown. Over time, the lesion may thicken and become a wart.
Varicose capillary lymphangioma is a benign saccular enlargement of the cutaneous and subcutaneous lymph nodes. The condition is characterized by clusters of blisters that resemble frog eggs. The color depends on the content: the white, yellow 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 as a result of hemorrhage. Bubbles can change and take on a cute look. It is more often found in 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, less commonly, an erosion, ulcer or pustule followed by inguinal and/or femoral lymphadenopathy known as buboes.
Usually,syringomaare asymptomatic, small, soft or dense, flesh-colored or brown papules 1 - 3 mm in diameter. They are usually found in the periorbital areas and on the cheeks. However, syringomas can appear on the penis and buttocks. When located on the penis, syringomas can be confused with penile warts.
Schwannomas- These are neoplasms originating from Schwann cells. Penile schwannoma usually presents as a single, asymptomatic, slow-growing nodule on the dorsal aspect of the shaft of the penis.
Bowenoid papulosisis a precancerous focal intraepidermal dysplasia that usually appears as multiple red-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 to 3% of cases.
Usually,squamous cell carcinomathe penis manifests itself in the form of a nodule, ulcer or erythematous lesion. The rash may appear as a wart, leukoplakia or sclerosis. The most preferred site is the glans penis, followed by the foreskin and shaft of the penis.
Complications
Penile warts can be a cause of significant distress or concern to the patient and their sexual partner due to their cosmetic appearance and stickiness, stigmatization, concerns about future fertility and cancer risk, and their association with other diseases. other sexually transmitted diseases. It is estimated that 20 - 34% of affected patients have other 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 compared to 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 intercourse. Malignant transformation is rare except in immunocompromised individuals. Patients with penile warts are at increased risk of developing anogenital cancer, head and neck cancer as a result of co-infection with high-risk HPV.
prediction
If left untreated, genital warts may resolve on their own, remain unchanged, or increase in size and number. Approximately one-third of penile warts regress without treatment, and the average time until they disappear is approximately 9 months. With proper treatment, 35 to 100% of warts disappear within 3 to 16 weeks. Although the warts resolve, the HPV infection may remain, leading to recurrence. Relapse rates range from 25 to 67% within 6 months of treatment. In patients with subclinical infection, repeated infection (reinfection) after sexual intercourse and in the presence of immunodeficiency, a higher percentage of relapses occurs.
Treatment
Active treatment of penile warts is preferable to follow-up 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, eg itching, pain or bleeding). Penile warts that persist for more than 2 years are much less likely 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 with each other. Effectiveness varies depending on the treatment method. To date, no treatment has been proven to be consistently superior to other treatments. The choice of treatment should depend on the level of the doctor's skills, 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 the treatment must also be considered. In general, self-administered treatment is considered less effective than self-administered treatment.
The patient performs the treatment at home (as prescribed by the doctor)
Treatment methods used in the clinic
Methods used in the clinic include podophyllin, cryotherapy with liquid nitrogen, bichloroacetic acid or trichloroacetic acid, oral cimetidine, surgical excision, electrocautery, and carbon dioxide laser therapy.
Liquid Podophyllin 25%, derived from podophyllotoxin, works by stopping mitosis and causing tissue necrosis. The drug 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 removing warts reaches 62%. Because of reports of toxicity, including death, associated with podophyllin use, podofilox, which has a much better safety profile, is considered preferred.
Liquid nitrogen, the treatment of choice for penile warts, can be applied using a spray bottle or cotton-tipped applicator directly to and 2mm around the wart. Liquid nitrogen causes tissue damage and cell death by rapidly freezing to form 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 removing warts reaches 75%. Side effects include pain during treatment, erythema, desquamation, blistering, erosion, ulceration and dyspigmentation at the application site. A recent parallel randomized phase II trial in 16 Iranian men with genital warts showed that cryotherapy using Wartner's formulation containing 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 using Wartner's compound is less effective than cryotherapy using 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 the protein followed by cell destruction and thus removing the penile wart. A burning sensation may appear at the site of application. Relapses after the use of bichloroacetic or trichloroacetic acid occur as often as with other methods. Medicines can be used up to three times a week. The effectiveness of wart removal ranges from 64 to 88%.
Electrocautery, laser therapy, carbon dioxide laser, or surgical removal work by mechanically destroying the wart and may be used in cases where there is a large enough wart or a group of warts that is difficult to remove with conservative treatment methods. Mechanical treatment methods have the highest percentage of effectiveness, but their use has a higher risk of skin wounds. Local anesthesia applied to non-closed lesions 20 minutes before the procedure or a mixture of local anesthetics applied to closed lesions one hour before the procedure should be considered as measures 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 combinations 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 for immunocompromised patients with treatment-refractory 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 physiological hydration and probenecid.
Preventing
Genital warts can be prevented to a certain extent by delaying sexual activity and limiting the number of sexual partners. Latex condoms, when used consistently and correctly, reduce the transmission of HPV. Sexual partners with anogenital warts should be treated.
HPV vaccines are effective before sexual activity in the primary prevention of infection. This is because the vaccines do not provide protection against diseases caused by HPV vaccine types that an individual has 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 vaccines.
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, month 1 to 2 (usually 2), and month 6. Revaccination is indicated for men under 21 years of age and women under 26 years of age if they were not vaccinated at the target age. Vaccination is also recommended for men who are homosexual or immunocompetent under the age of 26, if they have not been vaccinated before. Vaccination reduces the likelihood of becoming infected with HPV and subsequently developing penile warts and penile cancer. Vaccinating both men and women is more helpful in reducing the risk of penile genital warts than vaccinating only men, since 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 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 the quality of his life. Although approximately one-third of penile warts resolve without treatment, active treatment is preferred to hasten wart resolution, reduce fear of infection, reduce emotional distress, improve cosmetic appearance, reduce social stigma associated withpenile lesions and to relieve symptoms.
Active treatment methods can be mechanical, chemical, immunomodulatory and antiviral and 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 the doctor's skill in this method, the patient's treatment preference and tolerance, as well as the number of warts and the severity of the disease. Comparative effectiveness, ease of use, side effects, cost and availability of the treatment must also be considered. HPV vaccines before sexual activity are effective in primary prevention of infection. The target age for vaccination is 11-12 years for both girls and boys.