Penile warts are the most common sexually transmitted disease in men and are caused by the human papillomavirus (HPV). Penile warts typically 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-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 adults have genital warts on physical examination. The peak age of the disease is 25-29 years.
Etiopathogenesis
HPV is a double-stranded DNA virus without a capsid belonging 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 structural encapsidating proteins, namely 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 contract several 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 contact, and fomites. In children, HPV infection can occur as a result of sexual abuse, vertical transmission, autoinfection, infection through close family contacts, 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 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, one sexual partner with multiple sexual partners, a history of sexually transmitted infections, early sexual activity, a shorter period of time between one meeting and another. new partner and have sexual intercourse while living with him, being uncircumcised and smoking. Other predisposing factors are humidity, maceration, trauma and epithelial defects in the penile region.
Histopathology
Histological examination reveals papillomatosis, focal parakeratosis, severe acanthosis, multiple vacuolated koilocytes, vascular distension, and large keratohyalin granules.
Clinical manifestations
Penile warts are generally asymptomatic and may occasionally cause itching or pain. Genital warts are usually located on the frenulum, glans, internal surface of the foreskin and coronal sulcus. At disease onset, penile warts typically appear as small, discrete, soft, smooth, pearly, dome-shaped papules.
Lesions can occur singly or in groups (clustered). They can be pedunculated or broad-based (sessile). Over time, the papules may coalesce into plaques. Warts can be filiform, exophytic, papillomatous, verrucous, hyperkeratotic, cerebriform, fungiform or cauliflower-shaped. The color may be flesh-colored, pink, erythematous, brown, purple, or hyperpigmented.
Diagnosis
The diagnosis is made clinically, usually on the basis of medical history and physical examination. In vivo dermoscopy and confocal microscopy help improve diagnostic accuracy. Morphologically, warts can range from finger-shaped, pineal to mosaic. Among the characteristics of the vascularization we can find glomerular, hairpin and punctate vessels. Papillomatosis is an integral feature of warts. Some authors suggest using the acetic acid test (whitening of the surface of warts when acetic acid is applied) to aid in 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, adhesion to underlying structures, hard consistency, ulceration, or bleeding), when the diagnosis is uncertain, or for refractory warts to various treatments. Although some authors propose PCR diagnostics to, among other things, determine the HPV type that determines the risk of malignancy, HPV typing is not recommended in routine practice.
Differential diagnosis
Differential diagnosis includes pearlescent penile papules, Fordyce granules, acrochordons, warts in syphilis, molluscum contagiosum, granuloma annulare, lichen planus, lichen planus, seborrheic keratosis, epidermal nevus, capillary varicose lymphangioma, lymphogranuloma venereum, scabies, syringoma, neuroma post-traumatic. , schwannoma, bowenoid papulosis and squamous cell carcinoma.
Pearly penile papulesPresent as asymptomatic, small, smooth, soft, yellowish, pearly white or flesh-colored papules, conical or dome-shaped with a diameter of 1 - 4 mm. The lesions are generally uniform in shape and size and symmetrically distributed. Typically, papules are found in single, double, or multiple rows in a circle around the crown and sulcus of the glans. The papules tend to be most evident on the dorsum of the crown and less evident towards the frenulum.
Fordyce granules- these are enlarged sebaceous glands. On the glans and shaft of the penis, Fordyce granules appear as smooth, asymptomatic, isolated or grouped, discrete, creamy yellow papules, with a diameter of 1 - 2 mm. These papules are most noticeable on the shaft of the penis during erection or when the foreskin is pulled. Sometimes a thick, chalky, or cheese-like material can be squeezed out of these granules.
Acrochordons, also known as 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 measure 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 often seen on the neck and intertriginous areas. When they appear in the penile area, they can mimic penile warts.
Sided warts- These are skin lesions in secondary syphilis caused by the spirochete Treponema pallidum. Clinically, condylomata lata appear as moist, grey-white, velvety, flat or cauliflower-like, large papules or plaques. They tend to develop in the 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 on the oral mucosa may occur, as may alopecia and generalized lymphadenopathy.
Granuloma annulareis a benign and self-limiting inflammatory disease of the dermis and subcutaneous tissue. The pathology is characterized by asymptomatic, consistent, brown-purple, erythematous or flesh-colored 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. The granuloma is usually located on the extensor surfaces of the distal extremities, but can also be found on the shaft and glans.
Lichen planus of the skinis a chronic inflammatory dermatosis that manifests itself 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. About 25% of lesions occur on the genitals.
Epidermal nevusit is a hamartoma that originates from the embryonic ectoderm and 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 contents: the whitish, yellow or light brown color is due to the color of the lymphatic fluid, while the reddish or bluish color is due to the presence of red blood cells in the lymphatic fluid following a hemorrhage. The blisters may undergo changes and take on a warty appearance. It is found more often on the extremities, less often in the genital area.
Venereal lymphogranulomais 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.
Generally,syringomasthey are asymptomatic, small, soft or dense, flesh-colored or brown papules, measuring 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 tumors originating from Schwann cells. Penile schwannoma usually presents as a single, asymptomatic, slow-growing nodule on the dorsal aspect of the penile shaft.
Bowenoid papulosisis a precancerous focal intraepidermal dysplasia that usually appears as multiple red-brown papules or plaques in the anogenital area, particularly in 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 appear warty, leukoplakia, or sclerosis. The most favored site is the glans, followed by the foreskin and the shaft of the penis.
Complications
Penile warts may be a cause of significant concern or distress to the patient and his or her sexual partner due to their cosmetic appearance and contagiousness, stigma, concerns about future fertility and cancer risk, and their association with other diseases sexually transmitted. 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 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 her 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 developing anogenital cancer, head cancer, and neck cancer due to 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 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 resolve, the HPV infection can persist, leading to recurrences. Recurrence rates range from 25 to 67% within 6 months of treatment. A higher percentage of relapses occurs among patients with subclinical infection, recurrent infection (reinfection) after sexual intercourse and in the presence of immunodeficiencies.
Treatment
Active treatment of penile warts is preferable to follow-up because it leads to faster resolution of lesions, reduces fear of infecting the partner, relieves emotional stress, improves aesthetic appearance, reduces social stigma associated with penile lesions penis and relieve symptoms (eg, itching, soreness, 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 between 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 skill level of the doctor, 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, costs and availability of the treatment should also be taken into consideration. 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 clinic
Methods used in the clinic include podophyllin, cryotherapy with liquid nitrogen, dichloroacetic acid 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 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 wart removal 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 the wart and 2mm around it. Liquid nitrogen causes tissue damage and cell death by rapidly freezing to form ice crystals. The minimum temperature necessary to destroy warts is -50°C, although some authors consider even -20°C effective.
The effectiveness of wart removal reaches 75%. Side effects include pain during treatment, erythema, scaling, blistering, erosion, ulceration, and dyspigmentation at the application site. A recent parallel phase II randomized 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 should be said that cryotherapy with Wartner's composition is less effective than cryotherapy with liquid nitrogen.
Dichloroacetic 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 proteins, followed by cell destruction and consequently removing the penile wart. A burning sensation may occur at the application site. Relapses after using bichloroacetic or trichloroacetic acid occur as frequently as with other methods. The drugs can be used up to three times a week. The effectiveness of wart removal varies from 64 to 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 large enough wart or a cluster of warts that is difficult to remove with conservative treatment methods . Mechanical treatment methods have the highest percentage of effectiveness, but their use carries a greater risk of scarring on 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 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 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 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, postinflammatory 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 the transmission of HPV. Sexual partners with anogenital warts should be treated.
HPV vaccines are effective before sexual activity in 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 Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices, 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 as early as 9 years of age. Three doses of HPV vaccine should be administered at month 0, month 1-2 (usually 2), and month 6. Catch-up vaccination is indicated for men under 21 years of age and women under 26 years of age years 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 previously been vaccinated. Vaccination reduces the chance of contracting HPV infection 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 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 a sexually transmitted disease caused by HPV. This pathology can have a negative psychosocial impact on the patient and negatively affect her quality of life. Although approximately one-third of penile warts resolve without treatment, active treatment is preferable to speed resolution of warts, reduce fear of infection, reduce emotional distress, improve cosmetic appearance, reduce social stigma associated with penile lesions penis and relieve symptoms.
Active treatment methods can be mechanical, chemical, immunomodulatory and antiviral, and often combined. So far no treatment has proven to be superior to the others. The choice of treatment method should depend on the doctor's level of expertise in this method, the patient's preferences and tolerability 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 the treatment should also be taken into consideration. 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.