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 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-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% to 5% of sexually active young adult men have genital warts on physical examination. The maximum age of the disease is between 25 and 29 years.
Etiopathogenesis
HPV is a double-stranded DNA virus with a non-enveloped capsid that belongs to the Papillomavirus genus of the Papillomaviridae family and infects only humans. The virus has a circular genome of 8 kilobases in length, which encodes eight genes, including the genes for two structural encapsulating proteins, namely L1 and L2. The L1-containing virus-like particle 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 primarily transmitted through sexual contact and, less commonly, through oral sex, skin-to-skin contact, and fomites. In children, HPV infection can occur as a result of sexual abuse, vertical transmission, self-infection, infection by close household contact, and through fomites. HPV penetrates the cells of the basal layer of the epidermis through microtrauma to the skin or mucous membranes.
The incubation period of infection varies from 3 weeks to 8 months, with an average of 2 to 4 months. The disease is more common 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 a new partner and having sexual relations while living with them, not being circumcised and smoking. Other predisposing factors are humidity, 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 cause itching or pain. Genital warts are usually located on the frenulum, glans, 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.
Injuries can occur individually or in groups (clusters). They can be pedunculated or broad-based (sessile). Over time, the papules can merge into plaques. Warts can be filiform, exophytic, papillomatous, warty, hyperkeratotic, cerebriform, fungiform or cauliflower-shaped. The color can be flesh, pink, erythematous, brown, violet or hyperpigmented.
Diagnosis
The diagnosis is made clinically, usually based on history and examination. Dermatoscopy and in vivo confocal microscopy help improve diagnostic accuracy. Morphologically, warts can vary from finger-shaped and pineal to mosaic. Among the characteristics of the vascularization are glomerular, hairpin and punctate vessels. Papillomatosis is an integral 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 subclinical infected areas the sensitivity is considered low. Skin biopsy is rarely warranted but should be considered in the presence of atypical features (e. g. , atypical pigmentation, induration, attachment to underlying structures, hard consistency, ulceration, or bleeding), when the diagnosis is uncertain, or for warts that They are refractory to therapy. various treatments. Although some authors propose diagnosis by PCR 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
The differential diagnosis includes pearly penile papules, Fordyce granules, skin tags, condylomata planus 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 papulesThey present as asymptomatic, small, smooth, soft, yellowish, pearly white or flesh-colored papules, conical or dome-shaped, with a diameter of 1 to 4 mm. The lesions are usually uniform in size and shape and symmetrically distributed. Papules are usually located in single, double, or multiple rows in a circle around the crown and groove of the glans. The papules tend to be more noticeable on the dorsum 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 as smooth, discrete, creamy-yellow papules, asymptomatic, isolated or grouped, with a diameter of 1 to 2 mm. These papules are most noticeable on the shaft of the penis during erection or when the foreskin is pulled. Sometimes a dense, chalky or cheese-like material can be extracted from these granules.
skin tags, also known as skin tags, are soft, flesh-colored to dark brown, pedunculated or broad-based skin growths with a smooth outline. Sometimes they can be hyperkeratotic or have a warty appearance. Most skin tags measure between 2 and 5 mm in diameter, although occasionally they can be larger, especially in the groin. Skin tags 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.
Flat condylomas- They are skin lesions in secondary syphilis caused by the spirochete Treponema pallidum. Clinically, flat condylomas appear as wide, moist, grayish-white, velvety, flat or cauliflower-shaped papules or plaques. They usually develop in warm, moist areas of the genitals and perineum. Secondary syphilis is characterized by a symmetrical, diffuse, nonpruritic maculopapular rash on the trunk, palms of the hands, and soles of the feet. 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 annulareIt is a benign, self-limiting inflammatory disease of the dermis and subcutaneous tissue. The pathology is characterized by asymptomatic, firm, purplish-brown, erythematous or flesh-colored papules, generally arranged in a ring. As the condition progresses, central involution may be noted. A ring of papules often grows together to form a ring-shaped plaque. The granuloma is usually located on the extensor surfaces of the distal extremities, but can also be detected on the shaft and glans of the penis.
skin lichen planusIt is 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 glans. Approximately 25% of injuries occur on the genitals.
Epidermal nevusIt is a hamartoma that arises from the 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 onset of the disease usually occurs in the first year of life. The color varies from flesh to yellow and brown. Over time, the lesion may thicken and become warty.
Capillary varicose lymphangioma is a benign saccular dilation 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 whitish, yellow or light brown color is due to the color of the lymphatic fluid, and the reddish or bluish color is due to the presence of red blood cells in the lymphatic fluid as a result of hemorrhage. The blisters may undergo changes and take on a warty appearance. It is most commonly found on the extremities and less frequently in the genital area.
Lymphogranuloma venereumIt is a sexually transmitted disease caused by Chlamydia trachomatis. The disease is characterized by a transient painless genital papule and, less frequently, an erosion, ulcer or pustule followed by inguinal and/or femoral lymphadenopathy known as buboes.
Generally,syringomasThey are asymptomatic, small, soft or dense papules, flesh-colored or brown, measuring between 1 and 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- They are neoplasms that originate from Schwann cells. Penile schwannoma usually presents as a single, asymptomatic, slowly growing nodule on the dorsal aspect of the penile shaft.
bowenoid papulosisIt is a precancerous focal intraepidermal dysplasia that usually appears as multiple reddish-brown papules or plaques in the anogenital area, particularly on the penis. The pathology is compatible with squamous cell carcinoma in situ. Progression to invasive squamous cell carcinoma occurs in 2 to 3% of cases.
Generally,squamous cell carcinomaThe penis manifests itself in the form of a nodule, ulcer or erythematous lesion. The rash may have a warty appearance, leukoplakia, or sclerosis. The most favored site is the glans, followed by the foreskin and the shaft of the penis.
Complications
Penile warts can be a cause of great concern or distress to the patient and their sexual partner due to their cosmetic appearance and contagiousness, stigmatization, concerns about future fertility and cancer risk, and their association with other sexually transmitted diseases. It is estimated that between 20 and 34% of affected patients have underlying 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 can bleed, cause urethral obstruction, and interfere with sexual 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 coinfection 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. About a third of penile warts return 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. Although the warts disappear, the HPV infection can remain and cause a recurrence. Relapse rates range from 25 to 67% within 6 months after treatment. Among patients with subclinical infection, recurrent infection (reinfection) after sexual relations and in the presence of immunodeficiencies, 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 fears of infecting a partner, relieves emotional stress, improves cosmetic appearance, reduces social stigma associated with lesions of the penis and relieves symptoms (e. g. , 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 for 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 the different treatment methods with each other. Efficacy 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 doctor's skill level, 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 the treatment must also be taken into account. In general, self-administered treatment is considered less effective than self-administered treatment.
The patient carries out 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, acts by arresting mitosis and causing tissue necrosis. The 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 applied to high-moisture areas of the skin. The effectiveness of wart removal reaches 62%. Due to reports of toxicity, including death, 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 using a spray bottle or cotton-tipped applicator directly onto the wart and 2mm around it. Liquid nitrogen causes tissue damage and cell death by freezing rapidly to form ice crystals. The minimum temperature necessary 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, peeling, blistering, erosion, ulceration and depigmentation at the application site. A recent parallel randomized phase II trial in 16 Iranian men with genital warts demonstrated that cryotherapy using the Wartner formulation containing a mixture of 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 with Wartner's composition 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 acts by coagulating proteins followed by cell destruction and consequently eliminating the penile wart. A burning sensation may occur at the application site. Relapses after the use of bichloroacetic or trichloroacetic acid occur as frequently as with other methods. The medications can be used up to three times a week. The effectiveness of wart removal ranges between 64 and 88%.
Electrocoagulation, laser therapy, carbon dioxide laser, or surgical excision work by mechanically destroying the wart and can be used in cases where there is a fairly large wart or a group of warts that is difficult to remove with treatment methods. conservatives. Mechanical treatment methods have the highest percentage of effectiveness, but their use has a higher risk of scarring the skin. Local anesthesia applied to nonoccluded lesions 20 minutes before the procedure or a local anesthetic mixture applied to occluded lesions one hour before the procedure should be considered measures that reduce discomfort and pain during the procedure. General anesthesia may be used to surgically remove 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 treatment includes topical, intralesional, or intravenous cidofovir, topical 5-fluorouracil, and topical ingenol mebutate.
Antiviral therapy with cidofovir may be considered for immunocompromised patients with warts refractory to treatment. 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 receive treatment.
HPV vaccines are effective before sexual activity in primary prevention of infection. This is because the vaccines do not provide protection against diseases caused by vaccinated HPV types that an individual acquired through prior 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 of girls and boys with the HPV vaccine.
The expected age for vaccination is 11 to 12 years for girls and boys. The vaccine can be administered from 9 years of age. Three doses of HPV vaccine should be administered at month 0, months 1 and 2 (usually 2), and month 6. Catch-up vaccination is indicated for men under 21 years of age and women under 26 years if they have not been vaccinated at the target age. Vaccination is also recommended for homosexual or immunocompetent men under 26 years of age, if they have not been previously vaccinated. Vaccination reduces the chance of becoming infected with HPV and subsequently developing warts and penile cancer. Vaccinating both men and women is more beneficial in reducing the risk of penile genital warts than vaccinating only men, since men can contract 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.
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 approximately one-third of penile warts resolve without treatment, active treatment is preferred to accelerate resolution of warts, reduce fear of infection, reduce emotional distress, improve cosmetic appearance, reduce social stigma associated with penile injuries and relieve symptoms.
Active treatment methods can be mechanical, chemical, immunomodulatory and antiviral and often combined. To date, no treatment has been proven to be superior to others. The choice of treatment method should depend on the doctor's level of competence in this method, the patient's preference and tolerability of the 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 the treatment must also be taken into account. HPV vaccines before sexual activity are effective in primary prevention of infection. The expected age for vaccination is 11 to 12 years for both girls and boys.