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 to brown plaques on the glans and shaft of the penis.
To provide up-to-date information 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. " Search strategies 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. It is estimated that 0. 5 - 5% of sexually active young adult men have genital warts on physical examination. The peak age of this 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 and infects only humans. The virus has a circular genome 8 kilobases long, which encodes eight genes, including genes for two structural proteins that package it, namely L1 and L2. Virus-like particles containing L1 are 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 transmitted primarily 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 household contact, and through fomites. HPV penetrates the cells of the basal layer of the epidermis through microtraumas on the skin or mucous membranes.
The incubation period of infection ranges 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: immune deficiency, unprotected sexual intercourse, multiple sexual partners, sexual partners with multiple sexual partners, history of sexual infections, early sexual activity, a shorter period of time between meeting a new partner andhaving sexual intercourse living with him, not being circumcised and smoking. Other predisposing factors are moisture, maceration, trauma and epithelial defects in the penile area.
Histopathology
Histological examination revealed papillomatosis, focal parakeratosis, severe acanthosis, multivacuolar koilocytes, vascular distention and large keratohyalin granules.
Clinical manifestation
Penile warts are usually asymptomatic and can sometimes cause itching or 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, pearl-like dome-shaped papules.
Lesions may occur individually or in clusters (clusters). They can be stalked or broad-based (sessile). Over time, papules can coalesce into plaques. Warts may be filiform, exophytic, papillomatous, verrucous, hyperkeratotic, cerebriform, fungiform, or cauliflower-shaped. 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 pineal-shaped to mosaic. Among the features of vascularization one can find glomerular, hairpin and stem vessels. Papillomatosis is an important feature of warts. Some authors suggest using 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 subclinically infected areas the sensitivity is considered low. Skin biopsy is rarely necessary but should be considered in the presence of atypical features (eg, atypical pigmentation, induration, attachment to underlying structures, hard consistency, ulceration, or bleeding), when the diagnosis is uncertain, or for warts that are refractory to various treatments. Although some authors suggest PCR diagnostics to, among other things, determine the type of HPV that determines the risk of malignancy, HPV typing is not recommended in routine practice.
Differential diagnosis
Differential diagnoses include pearlescent penile papules, Fordyce granules, acrochordons, condyloma lata in syphilis, molluscum contagiosum, granuloma annulare, lichen planus, lichen planus, seborrheic keratosis, epidermal nevus, varicose capillary lymphangioma, lymphogranuloma venereum, lymphogranuloma venereum, lymphogranuloma posturema, symatogranuloma venereum. . , schwannoma, bowenoid papulosis and squamous cell carcinoma.
Pearly penile papulesPresent as asymptomatic, small, smooth, soft, yellowish, pearly white or flesh-colored, cone- or dome-shaped papules with a diameter of 1 - 4 mm. Lesions are usually uniform in size and shape and symmetrical in distribution. Typically, the papules are located in one, two or several rows in a circle around the crown and groove of the glans penis. Papules tend to be more prominent on the dorsum of the crown and less prominent toward the frenulum.
Fordyce details- this is an enlarged sebaceous gland. On the glans and penis, Fordyce granules appear as asymptomatic, isolated or clustered, discrete, creamy yellow, smooth papules with a diameter of 1 - 2 mm. These papules are more noticeable on the shaft of the penis during erection or when the foreskin is pulled. Sometimes a hard chalky or cheese-like substance can be squeezed out of these grains.
Acrochordons, also known as skintags ("skin tags"), are soft, flesh-colored to dark brown, stalked or broad skin growths with fine lines. Sometimes they may be hyperkeratotic or have the appearance of warts. Most acrochordons measure between 2 and 5 mm in diameter, although they can sometimes be larger, especially in the groin. Acrochordon can appear on almost any part of the body, but is most often seen on the neck and intertriginous area. When they appear in the penile area, they can mimic penile warts.
Condyloma lata- This is a skin lesion in secondary syphilis caused by the spirochete, Treponema pallidum. Clinically, condylomas lata appear as moist, gray-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. An erythematous or whitish rash on the oral mucosa may occur, as well as alopecia and generalized lymphadenopathy.
Granuloma annulareis a benign inflammatory disease that limits itself to the dermis and subcutaneous tissue. Pathology is characterized by asymptomatic, firm, brownish-purple, erythematous or flesh-colored papules, usually arranged in rings. As the condition progresses, central involution can be observed. Ring papules often grow together to form ring-shaped plaques. Granulomas are usually located on the extensor surface of the distal part, but can also be detected on the shaft and glans of the penis.
Lichen planus on the skinis a chronic inflammatory dermatosis that manifests as flat, polygonal, purple, itchy papules and plaques. Most often, the rash appears on the flexor surface of the hands, back, torso, legs, ankles and glans penis. About 25% of lesions occur on 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 that follows Blaschko's line. The onset of the disease usually occurs in the first year of life. Color varies from flesh to yellow and brown. Over time, the lesions may thicken and become warts.
Capillary varicose lymphangioma is a benign saccular enlargement of the skin and subcutaneous lymph nodes. This condition is characterized by clusters of blisters that resemble frog seeds. The color depends on the content: the whitish, 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 due to bleeding. The blisters may change and appear warty. Often found on the legs, less often in the genital area.
Lymphogranuloma venereumis a sexually transmitted disease caused by Chlamydia trachomatis. The disease is characterized by painless, transient genital papules and, more rarely, erosions, ulcers or pustules followed by inguinal and/or femoral lymphadenopathy known as buboes.
Usually,syringomaare asymptomatic, small, soft or solid, flesh-colored or brown papules measuring 1 - 3 mm in diameter. They are usually found in the periorbital area and on the cheeks. However, syringomas can appear on the penis and buttocks. When located on the penis, a syringoma can be mistaken for a penile wart.
Schwannomas- This is a neoplasm that originates from Schwann cells. Penile schwannoma usually presents as a single, asymptomatic, slowly growing nodule on the dorsal aspect 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 the penis. This 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 nodules, ulcers or erythematous lesions. The rash may appear warty, 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 source of significant anxiety or distress for patients and their sexual partners because of their cosmetic appearance and their transmission, 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 sexually transmitted diseases. Patients often experience feelings of guilt, shame, inferiority complex 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 patients and negatively affect their quality of life. Large exophytic lesions can bleed, cause urethral obstruction, and interfere with sexual intercourse. Malignant transformation is rare except in immunocompromised individuals. Patients with penile warts are at higher risk of developing anogenital cancer, head cancer and neck cancer due to high-risk HPV coinfection.
Prediction
If no treatment is given, genital warts may heal on their own, remain unchanged, or increase in size and number. About one-third of penile warts regress without treatment, and the average time until they disappear is about 9 months. With proper treatment, 35 to 100% of warts disappear within 3 to 16 weeks. Even if the warts heal, the HPV infection may remain, leading to recurrence. Relapse rates range from 25 to 67% within 6 months of treatment. Among patients with subclinical infection, repeated infection (reinfection) after sexual intercourse and in the presence of immunodeficiency, a higher percentage of relapse occurs.
Treatment
Active treatment of penile warts is superior to follow-up because it leads to faster resolution of lesions, reduces fear of infecting a partner, relieves emotional stress, improves cosmetic appearance, reduces social stigma associated with penile lesions, and relieves symptoms (eg, itching-itching, pain or bleeding). Penile warts that persist for more than 2 years are less likely to resolve on their own, so active treatment should be offered first. Sexual partner counseling is mandatory. Screening for sexually transmitted diseases is also recommended.
Active treatment 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 one treatment has been shown to be consistently superior to another. The choice of treatment should depend on the skill level of the doctor, the patient's preference 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 taken into account. In general, self-administered treatments are considered less effective than self-administered treatments.
Patients carry out 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.
Podophyllin liquid 25%, derived from podophyllotoxin, works by stopping mitosis and causing tissue necrosis. This medicine 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 used on areas with high skin moisture. Wart removal effectiveness reaches 62%. Due to reports of toxicity, including death, associated with the use of podophyllin, podofilox, which has a better safety profile, is considered preferable.
Liquid nitrogen, the treatment of choice for penile warts, can be applied using a spray bottle or cotton-tipped applicator directly to and 2 mm 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.
Wart removal effectiveness reaches 75%. Side effects include pain during treatment, erythema, desquamation, blistering, erosion, ulceration and dyspigmentation at the application site. A recent phase II parallel randomized trial in 16 Iranian men with genital warts showed that cryotherapy using a Wartner formulation containing a mixture of 75% dimethyl ether and 25% propane was also effective. Further studies are needed to confirm or refute this conclusion. It must be said that cryotherapy using Wartner's composition 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 freezing the protein followed by the destruction of the cells and subsequently removes the penile wart. A burning sensation may occur at the application site. Relapse after using bichloroacetic or trichloroacetic acid occurs as often as with other methods. The drug can be used up to three times a week. Wart removal effectiveness 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 are relatively large warts or a group of warts that are difficult to remove with conservative treatment methods. Mechanical treatment methods have the highest percentage of effectiveness, but their use has a higher risk of scarring the skin. Local anesthesia applied to non-occluded lesions 20 minutes before the procedure or local anesthetic mixture applied to occluded lesions one hour before the procedure should be considered as measures to reduce discomfort and pain during the procedure. General anesthesia can be used to surgically remove large lesions.
Alternative Treatment
Patients who do not respond to first-line treatment 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 saline hydration and probenecid.
Prevention
Genital warts can be prevented to some extent by delaying sexual activity 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.
The HPV vaccine is effective before sexual activity in the primary prevention of infection. This is because the vaccine does not provide protection against the disease caused by the type of HPV vaccine acquired by the individual through previous sexual activity. The Immunization Practices Advisory Committee 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 the HPV vaccine.
The target age for vaccination is 11 - 12 years for girls and boys. The vaccine can be given as early as 9 years of age. Three doses of HPV vaccine should be given at month 0, months 1 to 2 (usually 2), and month 6. Catch-up vaccination is indicated for men under 21 years of age and women under 26 years of age if they have not been 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 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 genital warts than vaccinating men alone, as men can acquire 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 sexually transmitted diseases caused by HPV. This pathology can have a negative psychosocial impact on the patient and negatively affect his quality of life. Although about one-third of penile warts heal without treatment, active treatment is preferred to accelerate 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 often combined. So far, no one treatment has been proven to be superior to the others. The choice of treatment method should depend on the doctor's skill level in this method, the patient's preferences and tolerance of treatment, 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 taken into account. HPV vaccine before sexual activity is effective in primary prevention of infection. The target age for vaccination is 11 - 12 years for both girls and boys.