HPV Types: Can Other Strains Cause Warts? - Obstetrics and Gynecology

Dr. Huang Jianzhong reply Obstetrics and Gynecology

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Ans: The following is extracted from the Taiwan Society of Obstetrics and Gynecology newsletter.
The most accurate information regarding external genital warts in women indicates that approximately 90% are caused by infections with human papillomavirus (HPV) types 6 and 11.
These lesions are usually asymptomatic but may also present with symptoms such as itching, pain, bleeding, burning, and vaginal discharge.
The lesions can appear in colors such as flesh-colored, gray, pink, or brown, and may present as smooth, raised, or cauliflower-like papules, and even as extensive lesions.
Diagnosis is typically made visually, but differentiation from molluscum contagiosum, fibroepithelial polyps, vulvar papillomatosis, condylomata lata (secondary syphilis), vulvar carcinoma in situ, and adenocarcinoma may require biopsy, which can be difficult for younger patients to accept.
Genital warts are primarily transmitted through sexual contact.
In cases where genital warts occur in children, it is crucial to investigate potential sexual abuse, including a thorough examination for bruising, subcutaneous bleeding, abrasions, and injuries to the hymen and anus.
Vertical transmission may also occur through the birth canal or horizontal contact.
Treatment options include:
1.
Surgical excision: Local anesthesia can be used for the surgical removal of solitary lesions, particularly those with a broad base (>1 cm), large condylomata, or resistant tumors.
Pathological examination can confirm the diagnosis.
In adult studies, the clearance rate ranges from 36-100%, with recurrence rates between 8-65%, depending on the extent of the lesions.
Extensive lesions may require general anesthesia for surgery.
A disadvantage is the potential for scarring.
2.
Electrosurgery: This is the most commonly used method, where lesions are directly cauterized under local anesthesia.
In adult studies, the clearance rate is between 64-94%, with recurrence rates as high as 50%.
Multiple treatments may be necessary, and post-treatment pain can occur.
HPV DNA may aerosolize during treatment, necessitating the use of masks and protective equipment to prevent infection in the throat.
3.
Cryotherapy: Liquid nitrogen is applied directly to the lesions, causing cell death.
This method is cost-effective and most effective for small, keratinized lesions, but it may take several weeks to achieve clearance.
In adult studies, the clearance rate is between 54-88%, with recurrence rates of 21-40%.
Young children often cannot tolerate the pain associated with cryotherapy, and some reports suggest using topical anesthetics like lidocaine beforehand.
Side effects include pain, local skin irritation, and post-healing skin pigmentation changes.
4.
Laser therapy: Carbon dioxide lasers are effective for treating anal and genital warts.
However, this method can cause pain and scarring, is expensive, and requires skilled operation.
The clearance rate ranges from 40-100%, with recurrence rates varying widely from 4-77%.
Cytotoxic agents include:
1.
Trichloroacetic acid (TCA): A white liquid that is applied directly to lesions weekly, causing them to turn white and leading to protein coagulation, resulting in 80-90% cell death.
Care must be taken to avoid surrounding skin to prevent ulceration.
In adults, the clearance rate is 70-81%, with a recurrence rate of 36%.
2.
Podophyllotoxin: Derived from the root of a plant, podophyllin was the first drug used but has neurotoxic, myelotoxic, and hepatotoxic effects.
Podophyllotoxin (Wartec, Condylox) is a less toxic derivative that can be used in children.
Literature reports a clearance rate of 45-88% for genital warts in children, with a recurrence rate of 12-60%.
Side effects include burning sensations, and less commonly pain, skin breakdown, edema, itching, and bleeding.
3.
Cidofovir: An antiviral drug that inhibits DNA polymerase of several viruses, preventing viral replication.
It can be administered intravenously for cytomegalovirus-related optic neuritis or formulated as a topical cream or gel.
Reports indicate that 1-3% Cidofovir cream is effective for treating resistant non-genital warts and skin warts in children aged 6-14.
One report described successful treatment of a 3-year-old with penile warts using 1% Cidofovir cream, applied once daily for five days, followed by a two-week break and a repeat after 30 days, with no recurrence after one year.
Side effects include local irritation.
Immunomodulators include:
1.
Imiquimod: The most commonly used immunomodulator, available as 5% Imiquimod cream (Aldara) and 3.75% Imiquimod cream (Zyclara), which induces cytokine production, particularly interferon, to clear warts.
In a study of 943 adult patients using 5% Imiquimod cream, the clearance rate was 47.8%, with recurrence rates of 8.8% at three months and 23% at six months.
In another study of 18 patients aged 9-18, the clearance rate was 88.9% after an average treatment duration of 5.8 months.
Although the FDA has not approved its use in children under 12, reports indicate it is safe and effective for younger children.
Common side effects include local itching, erythema, irritation, ulceration, and blistering.
2.
Catechins: The main components of green tea, including caffeine, amino acids, lignans, organic acids, proteins, chlorophyll, and polyphenols.
Sinecatechins, a catechin derivative, has been approved by the FDA for use in patients over 18.
In studies involving 1,004 patients using 15% ointment three times daily for up to 16 weeks, the clearance rate was 54.9%, with recurrence rates of 6-11%.
Although the cure rate is high, the need for multiple daily applications over a long duration is a drawback.
3.
Polyphenon E: An ointment derived from green tea with >85% catechin content, approved by the FDA for treating genital warts.
In a study of 125 men and 117 women treated with 15% or 10% Polyphenon E ointment for up to 12 weeks, the complete clearance rates were 61% for men and 56.8% for women with the 15% ointment, and 53.8% for men and 39.5% for women with the 10% ointment.
Recurrence rates after 12 weeks ranged from 10.3-11.8%.
Side effects occurred in 7.9% of patients, including hyperkeratosis, skin color changes, transient skin necrosis, allergic dermatitis, and pain.
4.
Cimetidine: An H2 receptor antagonist primarily used to treat peptic ulcers, it also acts as an immunomodulator, enhancing lymphocyte activity and suppressing cells.
It has been reported to treat skin fungi, herpes, Crohn's disease, and even recalcitrant warts.
The typical dosage is high, often 30 mg/kg divided into three doses daily for three months.
Reports indicate that four children aged 2-3 who failed other treatments for genital warts were successfully treated with oral Cimetidine, resulting in complete clearance.
Another report involving 16 children under 16 treated with oral Cimetidine for warts on the hands and feet showed complete clearance in 9 (56%) and good response (lesion disappearance >75%) in 5 (31%).
Side effects were mild and included diarrhea, nausea, abdominal pain, dry mouth, headache, and dizziness.
Prevention: Currently, there are two vaccines available to prevent HPV infection, both containing virus-like particles (VLPs) but no live virus.
The quadrivalent vaccine (types 6, 11, 16, 18, Gardasil) was approved by the FDA in 2006 for administration to females aged 9-26, while the bivalent vaccine (types 6, 18, Cervarix) was approved in 2009 for females aged 10-25.
Both require three doses, providing immunity for at least five years, and are most effective for those who have not yet engaged in sexual activity.
Both vaccines are effective in preventing high-grade cervical intraepithelial neoplasia, with the quadrivalent vaccine providing a 99% prevention rate for genital warts caused by HPV types 6 and 11, as well as preventing vaginal and vulvar cancers.
The quadrivalent vaccine was also approved for use in males aged 9-26 in 2009.
However, no studies have been designed to evaluate the bivalent vaccine's effectiveness in preventing genital warts.
Conclusion: Numerous studies indicate that no single method can completely cure genital warts, and the recurrence rate is high due to the variable latency period of HPV in the genital tract, the potential for reinfection at any time, and the multifocal nature of the lesions, making complete eradication challenging.
Some treatment modalities, such as cryotherapy, laser therapy, and electrosurgery, must be performed in a clinical setting.
In contrast, 0.5% podophyllotoxin gel or 5% imiquimod cream can be self-applied by patients.
Retrospective studies have shown that these two treatments are effective and tolerable for children.
Cidofovir is used after other treatment failures or in immunocompromised patients.
Ultimately, the best approach to treatment is prevention; if sexual activity cannot be avoided, vaccination, especially with the quadrivalent vaccine, should be considered at the onset of menstruation to potentially reduce the incidence of genital warts.

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Reply Date: 2017/07/27