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.
In order 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". 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 males 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 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 genes for two encapsulating structural proteins, namely L1 and L2. The virus 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 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 the infection ranges from 3 weeks to 8 months, with an average of 2-4 months. The disease is more common in people with the following predisposing factors: immunodeficiency, unprotected sexual relations, multiple sexual partners, sexual partner with multiple sexual partners, history of sexually transmitted infections, early sexual activity, shorter time period between meeting a new partner and engaging in sexual relations living withwith him, not circumcision and smoking. Other predisposing factors are moisture, maceration, trauma and epithelial defects in the penile area.
Histopathology
Histological examination reveals papillomatosis, focal parakeratosis, severe acanthosis, multiple vacuolated koilocytes, vascular distension, and large keratohyaline granules.
Clinical manifestations
Penile warts are usually asymptomatic and can occasionally cause itching or pain. Genital warts are usually found 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 appear singly or in clusters (group). They can be on a peduncle or on a broad base (sessile). Over time, papules can coalesce into plaques. Warts can be filiform, exophytic, papillomatous, verrucous, hyperkeratotic, cerebriform, fungal, or cauliflower-shaped. The color can be flesh-colored, pink, erythematous, brown, purple, or hyperpigmented.
Diagnosis
The 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 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 (bleaching 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 for other types of penile warts and subclinically 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, attachment to underlying structures, firm 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 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, broad condylomas in syphilis, molluscum contagiosum, granuloma annulare, lichen planus, lichen planus, seborrheic keratosis, epidermal nevus, capillary granulation of varicose granules, capillary granule granuloma, ringoma, post-traumatic neuroma, schwannoma. , bowenoid papulosis and squamous cell carcinoma.
Pearly penile papulesThey appear as asymptomatic, small, smooth, soft, yellowish, pearly white 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 found in single, double or multiple rows in a circle around the crown and groove of the glans penis. The papules are 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 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 thick, chalky or cheese-like material can be squeezed out of these granules.
Acrochordons, also known as skintags ("skin tags"), are soft, flesh-colored to dark brown, pedunculated or broad-based growths with a smooth outline. They can sometimes be hyperkeratotic or warty. 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 commonly seen on the neck and intertriginous areas. 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, condyloma 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, alopecia and generalized lymphadenopathy may occur.
Granuloma annulareis a benign, self-limiting inflammatory disease of the dermis and subcutaneous tissue. The pathology is characterized by asymptomatic, solid, brown-purple, erythematous or fleshy papules, usually 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. Granuloma is usually found on the extensor surfaces of the distal extremities, but can also be found on the shaft and head of the penis.
Lichen planus of the skinis a chronic inflammatory dermatosis that manifests as flat, polygonal, purple papules and itchy plaques. Most often, the rash appears on the flexor surfaces of the hands, back, trunk, legs, ankles and glans. Approximately 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 following Blaschk'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 dilatation of skin and subcutaneous lymph nodes. The condition is characterized by clusters of blisters that resemble frog spawn. The color depends on the content: the whitish, yellow or light brown color is the result of the color of the lymph fluid, and the reddish or bluish color is the result of the presence of red blood cells in the lymph fluid as a result of bleeding. The blisters may change and take on a warty appearance. It is most often found on 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 a bubo.
usually,syringomasare asymptomatic, small, soft or dense, fleshy 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. When found on the penis, syringomas can be mistaken for penile warts.
Schwannomas- These are neoplasms originating from Schwann cells. Penile schwannoma usually presents as a single, asymptomatic, slow-growing nodule on the dorsal side 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 favorite place is the head of the penis, followed by the foreskin and shaft of the penis.
Complications
Penile warts can cause significant concern or distress for 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 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 a higher rate 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 the quality of his 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 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 disappear 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 though the warts go away, the HPV infection can remain, leading to recurrence. Relapse rates range from 25 to 67% within 6 months of treatment. In patients with subclinical infection, recurrent infection (reinfection) after sexual intercourse and with the presence of immunodeficiency, a higher percentage of recurrence occurs.
Treatment
Active treatment of penile warts is preferable to monitoring 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, 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 better than other treatments. The choice of treatment should depend on the skill level of the doctor, the patient's inclination and tolerance to treatment, as well as on 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 carries out the treatment at home (according to the doctor's recommendation)
Treatment methods used in the clinic
Methods used in the clinic include podophyllin, liquid nitrogen cryotherapy, bichloroacetic or trichloroacetic acid, oral cimetidine, surgical excision, electrocautery, and carbon dioxide laser therapy.
Liquid podophyllin 25%, derived from podophyllotoxin, works by arresting mitosis and causing tissue necrosis. The drug is applied directly to the nipple of the penis 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 with high skin moisture. Wart removal efficiency reaches 62%. Because of reports of toxicity, including death, associated with podophyllin use, podofilox, which has a much 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 the wart and 2mm around the wart. Liquid nitrogen causes tissue damage and cell death by rapid freezing and ice crystal formation. The minimum temperature required to destroy warts is -50°C, although some authors believe that -20°C is also effective.
Wart removal efficiency 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 a Wartner 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 composition is less effective than liquid nitrogen cryotherapy.
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 consequent removal of penile warts. A burning sensation may appear at the site of application. Relapses after the use of 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, laser carbon dioxide or surgical excision work by mechanical destruction of the wart and can be used in cases where there is a rather large wart or a cluster of warts that are difficult to remove with conservative treatment methods. Mechanical treatment methods have the highest percentage of efficiency, but their use has a higher risk of scarring the skin. Local anesthesia applied to non-occluded lesions 20 minutes before the procedure or a mixture of local anesthetics 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 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 ingenol mebutate.
Antiviral therapy with cidofovir may be considered for immunocompromised patients with treatment-resistant warts. Cidofovir is an acyclic nucleoside phosphonate that competitively inhibits viral DNA polymerase, thereby preventing viral replication.
Adverse effects of topical (intralesional) cidofovir include irritation, erosion, postinflammatory pigmentary changes, and superficial scarring at the application site. The main side effect of intravenous cidofovir is nephrotoxicity, which can be prevented by hydration 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, 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 vaccines do not provide protection against diseases caused by vaccine types of HPV 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 the HPV vaccine.
The target age for vaccination is 11 - 12 years for girls and boys. The vaccine can be administered already at the age of 9. Three doses of HPV vaccine should be given at month 0, month 1 to 2 (usually 2), and month 6. A booster vaccination is indicated for men younger than 21 years and women younger than 26 years if not vaccinated at the target age. Vaccination is also recommended for men who are gay or immunocompetent under the age of 26, if they have not been previously vaccinated. 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 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 desirable 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 treatment has been proven to be better than the others. The choice of treatment method should depend on the level of knowledge of the doctor in this method, the patient's preferences 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 treatment should also be considered. HPV vaccines before sexual activity are effective in the primary prevention of infection. The target age for vaccination is 11 - 12 years for both girls and boys.