Genital warts (condyloma acuminatum) are a sexually transmitted infection caused by the human papillomavirus (HPV) types 6 and 11. These are spread by skin to skin contact usually during sex. These present in clusters or separately and can be found in the genital or anal area. This activity describes the evaluation and management of genital warts and explains the role of the interprofessional team in improving care for patients with this condition.
Outline the etiology of genital warts.
Review the importance of biopsy in the evaluation of genital warts.
Explain the use of physically destructive therapies and topical agents in the management of genital warts.
Summarize the importance of collaboration and communication among the interprofessional team members to educate patients on the importance of the HPV vaccine which will enhance the delivery of care for patients with genital warts.
Genital warts (condyloma acuminatum) are the clinical manifestations of a sexually transmitted infection caused by some types of human papillomavirus (HPV).
Warts are a recognized symptom of genital HPV infections.
About 90% of those exposed who contract HPV will not develop genital warts.
Only about 10% who are infected may transmit the virus.
HPV types 6 and 11 cause genital warts. There are over 100 different known types of HPV viruses.
HPV is spread through direct skin-to-skin contact with an infected individual, usually during sex.
While some types of HPV cause cervical and anal cancer, these are not the same viral types that cause genital warts.
It is possible to be infected with different types of HPV at the same time.
HPV is transmitted primarily through penetrative sex. While HPV also can be transmitted via non-penetrative sexual activity, it is less common.
There is conflicting evidence about the effect of condoms on prevention.
Approximately three out of four unaffected partners of patients with warts develop them within eight months of contact.
Although 90% of HPV infections are cleared within two years of infection, it is possible for a latency period to occur, with the first occurrence or a recurrence happening months or even years later.
Latent HPV is transmissible, and if an individual has unprotected sex with an infected partner, there is a 70% chance they will become infected.
In individuals with a prior HPV infection, the appearance of new warts may be either from a new exposure or a recurrence.
Anal or genital warts may be transmitted during birth and may be an indicator of sexual abuse.
Genital warts may sometimes result from autoinoculation by warts elsewhere on the body, such as from the hands.
Genital HPV infections have an estimated prevalence of 10% to 20% with clinical manifestations in 1%. The incidence of HPV infection has been increasing. About 80% of those infected are between the ages of 17 and 33 years, with the peak age group being 20 to 24. It has been estimated that 2.9% of the US male population will have genital HPV DNA.
Although treatments can remove warts, they do not remove the HPV. Warts may sometimes spontaneously regress. Traditional theories postulate that the virus remains in the body for a lifetime. However, it is now believed that the virus may be either cleared or suppressed to levels below what polymerase chain reaction (PCR) tests can measure.
HPV infection appears to be the cause of most cases of anal cancer (about 90%) and virtually all cases of cervical cancer in women, with HPV type 16 accounting for about 50% of these. (Cervical cancer is the fourth most common cancer in women.) Some vulvar cancers have been linked to HPV infections (29% to 43%), while vaginal cancer is associated with HPV infections about 70% of the time (HPV Types 16 and 18).
In men, Bowen disease of the penis and about 35% to 40% of all penile cancers are associated with HPV infections.
Risk factors for HPV persistence include age, smoking, immunosuppression, and simultaneous infection with multiple HPV types.
Genital warts tare typically diagnosed visually with confirmatory biopsy generally unnecessary. These exophytic lesions form due to enlargement of the dermal papillae and are lined by hyperplastic squamous epithelium that shows koilocytes, which are squamous epithelial cells characterized by an acentric, hyperchromatic nucleus displaced by a large perinuclear vacuole.
History and Physical
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.
Treatment / Management
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.
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.
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.
Surgical removal under general anesthesia may be necessary for more extensive lesions, intra-anal warts, or in children.
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.
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.
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.
Interferon may also be used.
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
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.
Deterrence and Patient Education
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).
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.
Enhancing Healthcare Team Outcomes
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.
Lisboa C,Santo I,Azevedo J,Azevedo L,Pista A,Dias C,Cunha MJ, High Prevalence of Human Papillomavirus on Anal and Oral Samples from Men and Women with External Anogenital Warts: The HERCOLES Study. Acta dermato-venereologica. 2019 Feb 6; [PubMed PMID: 30723872]
Fichman Y,Levi A,Hodak E,Halachmi S,Mazor S,Wolf D,Caplan O,Lapidoth M, Efficacy of pulsed dye laser treatment for common warts is not influenced by the causative HPV type: a prospective study. Lasers in medical science. 2018 May; [PubMed PMID: 29218494]
Murray ML,Meadows J,Doré CJ,Copas AJ,Haddow LJ,Lacey C,Jit M,Soldan K,Bennett K,Tetlow M,Nathan M,Gilson R, Human papillomavirus infection: protocol for a randomised controlled trial of imiquimod cream (5%) versus podophyllotoxin cream (0.15%), in combination with quadrivalent human papillomavirus or control vaccination in the treatment and prevention of recurrence of anogenital warts (HIPvac trial). BMC medical research methodology. 2018 Nov 6; [PubMed PMID: 30400777]
Schöfer H,Tatti S,Lynde CW,Skerlev M,Hercogová J,Rotaru M,Ballesteros J,Calzavara-Pinton P, Sinecatechins and imiquimod as proactive sequential therapy of external genital and perianal warts in adults. International journal of STD [PubMed PMID: 28566057]