Genital warts may occur separately or in clusters. They may be found in the anal or genital area, including the penile shaft, scrotum, vagina, or labia majora. They also can be found on internal surfaces of the vagina and the anus.

They can be small (5 mm or less in diameter) or spread into large masses in the genital or anal area. Their color is variable but tends to be skin-colored or darker, and they may occasionally bleed.

Sometimes warts may cause itching, redness, or discomfort. An outbreak of genital warts may also cause psychological distress.

In most cases, the only identifiable symptoms of an HPV infection are warts.

The diagnosis of genital warts is usually made visually although a biopsy may be necessary for confirmation. Small warts may sometimes be confused with molluscum contagiosum. Genital warts typically rise above the skin surface, have parakeratosis, and demonstrate nuclear changes typical of HPV infections (nuclear enlargement with perinuclear clearing). Because genital warts are caused by low-risk HPV types, DNA tests should not be used for diagnosis or in low-risk HPV infections.

Some practitioners use an acetic acid solution to help identify small warts and affected skin areas, but this practice is controversial.  

A biopsy is recommended if there is uncertainty about the diagnosis or if the patient is immunocompromised.  Pigmented and ulcerated lesions should also be considered for biopsy.

Cystoscopy should be considered in patients where the glans is involved, the patient has lower urinary tract symptoms, or there are significant urethral symptoms.  In patients who have no symptoms, some experts have suggested waiting until any glans lesions have healed to avoid possible transfer of the HPV virus into the urethra.[7][8]

There is no cure for HPV. Removing visible warts does not reduce the transmission of the underlying HPV infection. About 80% of individuals with HPV will clear the infection spontaneously within 18 to 24 months.

Treatment varies depending on the number, size, and location of warts. Treatment can cause permanent depigmentation, itching, pain, and scarring.

Urethral meatus warts are best treated with surgery to minimize long-term complications.

The American Urological Association does not recommend treating sub-clinical (invisible) lesions.

Treatments are either ablative (vaporization, resection, coagulation, or excision) or involve the use of topical agents. Physically ablative treatments are more effective at wart removal, but in many cases, topical agents are preferred by patients as initial therapy, especially for smaller lesions.

Physical Removal or Destruction

Direct excision or physically destructive therapies are considered more effective on keratinized warts, especially if they are larger in size.[6]

• Simple surgical excision under local anesthesia is simple and direct but will leave a scar and requires a small surgical procedure.
• Liquid nitrogen cryosurgery ablation is inexpensive, considered safe for use during pregnancy, and does not usually cause much scarring but requires cryosurgical equipment and training.
• Electrocauterization is considered effective but causes scarring and requires some level of anesthesia.[6]
• Laser vaporization has minimal bleeding but may be somewhat less effective than other ablative techniques. It is relatively expensive and may cause a plume of virus-containing smoke.[9]
• Surgical removal under general anesthesia may be necessary for more extensive lesions, intra-anal warts, or in children. 

Topical Agents

Topical agents may be very effective and are less traumatic than surgical intervention.

• Podophyllotoxin solution 0.15% to 0.5% in a gel or cream can be applied to the affected area and is not washed off. Podofilox (an anti-mitotic drug) appears to be safer than podophyllin.[10]
• Imiquimod is a topical immune response cream applied to the affected area but may cause fungal infections and flu-like symptoms. Imiquimod is an immune enhancer and increases cytokines such as TNF-a)
• Sinecatechins is an ointment of catechins extracted from green tea that appears to have a higher clearance rate than podophyllotoxin and imiquimod while causing less local irritation, but clearance takes longer than with imiquimod.  Sinecatechins are available as a 15% ointment.  They work by reducing HPV gene products E6 and E7.[11]
• Skin erosion and pain are commonly reported with imiquimod and sinecatechins.
• Trichloroacetic acid is not as effective as cryosurgery and should be avoided on the vagina, cervix, or urinary meatus.[6]
• Interferon may also be used.

Discontinued

• A 5% 5-fluorouracil (5-FU) cream is no longer considered acceptable due to the side effects.
• Podophyllin, podofilox, and isotretinoin should be avoided during pregnancy.

• Condyloma lata or secondary syphilis
• Familial Benign Pemphigus
• Herpes simplex infection
• Benign nevi
• Vulvar neurofibromatosis

A high number of cases of genital warts fail to respond to treatment and often recur especially with repeated infections from sexual contact or with a long-incubation period of HPV. Mortality associated with the disease is due to the malignant transformation of the lesions. Morbidity associated with the disease is due to pruritus, bleeding, and the psychosocial burden of genital lesions.

Local complications with disfigurement are the most common complications of this disease. With untreated and advanced-stage disease, there is a risk of malignant transformation. This is the most feared complication. The current standard of care emphasizes treatment and primary prevention strategies to prevent this devastating outcome. 

Gardasil is a vaccine used to protect against human papillomavirus types 6, 11, 16, and 18. Types 16 and 18 cause an estimated 70% of cervical cancers, and 6 and 11 cause an estimated 90% of genital warts. The vaccine prevents the disease but is not therapeutic. The vaccine must be given before exposure to the virus type to be effective. The vaccine was approved by the United States Food and Drug Administration (FDA) in 2006 for use in children as early as nine years of age, primarily for its prophylactic activity against cervical cancer. Gardasil 9 was FDA approved in 2014 to protect against the four HPV strains covered by the first generation of Gardasil as well as five other HPV strains responsible for 20% of cervical cancers (HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58).[12]

Vaccines are preventative and should not be considered therapeutic. Quadrivalent or 9-valent vaccines are recommended and generally preferred over bivalent vaccines.

According to the Advisory Committee for Immunization Practices (ACIP), routine HPV vaccination is recommended for women 9 to 26 years of age, but it has shown high efficacy up to age 45.

The ACIP recommends routine male HPV quadrivalent vaccinations at age 11-12.  If not previously given or incomplete (the vaccines are a three-dose series), the vaccine should be given up to age 21.  From ages 22 to 26, the vaccine is considered optional.  In other words, the optimal age for male HPV vaccination is 11 to 12 years, but it may be given up to age 26 years. 

It remains to be seen if the more extensive use of vaccines can reduce the prevalence and penetration of HPV exposure, infections, and complications.

Genital warts are very common in clinical practice. Because of the risk of cancer, there is now a vaccine available to prevent these warts. Healthcare workers including nurse practitioners, physician assistants, and primary care physicians need to work in an interprofessional effort to educate patients about the importance of the HPV vaccine as it can prevent a variety of genital cancers. The ACIP recommends routine male HPV quadrivalent vaccinations at age 11-12.  If not previously given or incomplete (the vaccines are a three-dose series), the vaccine should be given up to age 21. From ages 22 to 26, the vaccine is considered optional. In other words, the optimal age for male HPV vaccination is 11 to 12 years, but it may be given up to age 26 years.